Suppression of polymethyl methacrylate dust explosion by ultrafine water mist/additives.

PubMed

Gan, Bo; Li, Bei; Jiang, Haipeng; Bi, Mingshu; Gao, Wei

2018-06-05

The suppressions of ultrafine water mists containing additives (NaCl and NaHCO 3 ) on 100 nm, 5 μm, and 30 μm polymethyl methacrylate (PMMA) dust explosions were experimentally studied in a dust-explosion apparatus. High-speed photography showed that maximum vertical positions and flame propagation velocities were significantly decreased by suppression with ultrafine water mist/additives. Flame propagation velocities in 100 nm, 5 μm, and 30 μm dust explosions suppressed by the ultrafine pure water mist were reduced by 48.2%, 27.7%, and 15.3%, respectively. Maximum temperatures and temperature rising rates measured by a fine thermocouple in nano- and micro-PMMA dust explosions were also significantly decreased. It was proved that the addition of NaCl and NaHCO 3 improved the suppression effects of the ultrafine pure water mist. The improvement of explosion suppression by an 8% NaHCO 3 mist was superior to that of a 16% NaCl mist. The suppression mechanisms of ultrafine water mist/additives are further discussed by analyzing the physical and chemical effects. Copyright © 2018 Elsevier B.V. All rights reserved.

miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells.

PubMed

Li, Yingchao; Yan, Xiaoni; Ren, Li; Li, Yang

2018-01-19

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the metastasis of various cancers, including gastric cancer (GC). In this study, we explored the putative significance of miR-644a and its role in EMT-mediated metastasis of GC. We first detected the expression of miR-644a in a cohort of 107 GC tissues using quantitative RT-PCR. The expression of miR-644a was suppressed in GC tissues and was associated with a later clinical stage and tumor metastasis. Restoring the expression of miR-644a could significantly suppress the migration and invasion of HGC-27 and SGC-7901 cells, which might be correlated to its suppressive effect on the EMT process. We also found that carboxyl-terminal-binding protein 1 (CtBP1) was a putative target gene of miR-644a in GC and might be involved in the suppressive effect. Collectively, through targeting CtBP1-mediated suppression of the EMT process, miR-644a might suppress the tumor metastasis of GC cells.

Proflavine and Light in the Treatment of Experimental Herpetic Ocular Infections

PubMed Central

Lanier, Jeffrey D.; Whitcher, John P.; Dawson, Chandler R.; Oh, Jang O.

1974-01-01

The effect of purified proflavine and light exposure was assessed in rabbits whose eyes had been infected with one of two strains of herpesvirus. In comparing proflavine-light and placebo-light treatment, 0.1% proflavine administered twice daily for 5 days had a significant effect in suppressing herpetic eye disease, but 0.05% proflavine was less effective. In addition to being effective in infections with either virus strain, the 0.1% proflavine also suppressed intensity of corneal epithelial ulceration and stromal opacity in animals pretreated with subconjunctival corticosteroids to produce more severe disease. Proflavine or idoxuridine (IDU) alone or in combination showed no differences in suppressing herpetic ocular disease, but all were significantly more effective than placebo. Virus recovery rates were approximately the same from eyes treated with proflavine, IDU, or placebo, indicating that viral replication in the cornea and conjunctiva was not completely suppressed by either of the antiviral drugs alone or in combination. PMID:15825315

Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation

PubMed Central

Birdno, Merrill J.; Kuncel, Alexis M.; Dorval, Alan D.; Turner, Dennis A.; Gross, Robert E.

2012-01-01

Deep brain stimulation (DBS) provides dramatic tremor relief when delivered at high-stimulation frequencies (more than ∼100 Hz), but its mechanisms of action are not well-understood. Previous studies indicate that high-frequency stimulation is less effective when the stimulation train is temporally irregular. The purpose of this study was to determine the specific characteristics of temporally irregular stimulus trains that reduce their effectiveness: long pauses, bursts, or irregularity per se. We isolated these characteristics in stimulus trains and conducted intraoperative measurements of postural tremor in eight volunteers. Tremor varied significantly across stimulus conditions (P < 0.015), and stimulus trains with pauses were significantly less effective than stimulus trains without (P < 0.002). There were no significant differences in tremor between trains with or without bursts or between trains that were irregular or periodic. Thus the decreased effectiveness of temporally irregular DBS trains is due to long pauses in the stimulus trains, not the degree of temporal irregularity alone. We also conducted computer simulations of neuronal responses to the experimental stimulus trains using a biophysical model of the thalamic network. Trains that suppressed tremor in volunteers also suppressed fluctuations in thalamic transmembrane potential at the frequency associated with cerebellar burst-driver inputs. Clinical and computational findings indicate that DBS suppresses tremor by masking burst-driver inputs to the thalamus and that pauses in stimulation prevent such masking. Although stimulation of other anatomic targets may provide tremor suppression, we propose that the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus. PMID:21994263

The role of thought suppression in the relation between mindfulness meditation and alcohol use

PubMed Central

Bowen, Sarah; Witkiewitz, Katie; Dillworth, Tiara M.; Marlatt, G. Alan

2007-01-01

Previous studies have demonstrated that attempts to suppress thoughts about using substances may actually lead to increases in substance use. Vipassana, a mindfulness meditation practice, emphasizes acceptance, rather than suppression, of unwanted thoughts. Bowen and colleagues (2006) studied the effects of a Vipassana course on substance use and in an incarcerated population, showing significant reductions in substance use among the Vipassana group as compared to a treatment as usual control condition (Bowen, Witkiewitz, Dillworth, Chawla, Simpson, Ostafin, et al., 2006). The current study further examines the mediating effects of thought suppression in the relationship between participation in the course and subsequent alcohol use in an incarcerated population. Those who participated in the course reported significant decreases in avoidance of thoughts when compared to controls. The decrease in avoidance partially mediated effects of the course on post-release alcohol use and consequences. PMID:17300875

Thought Suppression, Impaired Regulation of Urges, and Addiction-Stroop Predict Affect-Modulated Cue-Reactivity among Alcohol Dependent Adults

PubMed Central

Garland, Eric L.; Carter, Kristin; Ropes, Katie; Howard, Matthew O.

2011-01-01

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention toward alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age = 39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state X trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. PMID:21967855

Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.

PubMed

Garland, Eric L; Carter, Kristin; Ropes, Katie; Howard, Matthew O

2012-01-01

Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. Copyright © 2011 Elsevier B.V. All rights reserved.

Fat suppression at 2D MR imaging of the hands: Dixon method versus CHESS technique and STIR sequence.

PubMed

Kirchgesner, Thomas; Perlepe, Vasiliki; Michoux, Nicolas; Larbi, Ahmed; Vande Berg, Bruno

2017-04-01

To compare the effectiveness of fat suppression and the signal-to-noise ratio (SNR) of the Dixon method with those of the CHESS (Chemical Shift-Selective) technique and STIR (Short Tau Inversion Recovery) sequence in hands of normal subjects at 2D MR imaging. 14 healthy volunteers (mean age of 29.4 years) consented to have both hands prospectively imaged with SE T1 Dixon, T1 CHESS, T2 Dixon, T2 CHESS and STIR sequences in a 1.5T MR scanner. Three radiologists scored the effectiveness of fat suppression in bone marrow (EFS BM ) and soft tissues (EFS ST ) in 20 joints per subject. One radiologist measured the SNR in 10 bones per subject. Statistical analysis used two-way ANOVA with random effects, paired t-test and observed agreement to assess differences in effectiveness of fat suppression, differences in SNR and inter-observer agreement. EFS BM was statistically significantly higher for T1 Dixon than for T1 CHESS and for T2 Dixon than for T2 CHESS (p<0.0001). EFS BM was significantly higher for T2 Dixon than for STIR in the coronal plane (p=0.0020). The SNR was significantly higher for T1 Dixon than for T1 CHESS and for T2 Dixon than for STIR (p<0.0001). The SNR was significantly lower for T2 Dixon than for T2 CHESS (p<0.0001). The Dixon method yields more effective fat suppression and higher SNR than the CHESS technique at 2D T1-weighted MR imaging of the hands. At T2-weighted MR imaging, fat suppression is more effective with the Dixon method while SNR is higher with the CHESS technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

PubMed

Wong, Shi-Bing; Cheng, Sin-Jhong; Hung, Wei-Chen; Lee, Wang-Tso; Min, Ming-Yuan

2015-01-01

Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

A Meta-Analysis of the Impact of Anaerobic Soil Disinfestation on Pest Suppression and Yield of Horticultural Crops

PubMed Central

Shrestha, Utsala; Augé, Robert M.; Butler, David M.

2016-01-01

Anaerobic soil disinfestation (ASD) is a proven but relatively new strategy to control soil borne pests of horticultural crops through anaerobic decomposition of organic soil amendments. The ASD technique has primarily been used to control soil borne pathogens; however, this technique has also shown potential to control plant parasitic nematodes and weeds. ASD can utilize a broad range of carbon (C) amendments and optimization may improve efficacy across environments. In this context, a meta-analysis using a random-effects model was conducted to determine effect sizes of the ASD effect on soil borne pathogens (533 studies), plant parasitic nematodes (91 studies), and weeds (88 studies) compared with unamended controls. Yield response to ASD was evaluated (123 studies) compared to unamended and fumigated controls. We also examined moderator variables for environmental conditions and amendments to explore the impact of these moderators on ASD effectiveness on pests and yield. Across all pathogen types with the exception of Sclerotinia spp., ASD studies show suppression of bacterial, oomycete and fungal pathogens (59 to 94%). Pathogen suppression was effective under all environmental conditions (50 to 94%) and amendment types (53 to 97%), except when amendments were applied at rates less than 0.3 kg m-2. The ASD effect ranged from 15 to 56% for nematode suppression and 32 to 81% for weed suppression, but these differences were not significant. Significant nematode moderators included study type, soil type, sampling depth, incubation period, and use of mixed amendments. Weed suppression due to ASD showed significant heterogeneity for all environmental conditions, confirming that these studies do not share a common effect size. Total crop yield was not reduced by ASD when compared to a fumigant control and yield was significantly higher (30%) compared to an unamended control, suggesting ASD as a feasible option to maintain yield without chemical soil fumigants. We conclude ASD is effective against soil borne pathogens and while not conclusive due to a limited number of studies, we expect the same for nematodes and weeds given observed effect sizes. Findings should assist researchers in exploring ASD efficacy in particular environmental conditions and allow for development of standard treatment protocols. PMID:27617017

[Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

PubMed

Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

2009-06-01

This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

Jew's mellow leaves (Corchorus olitorius) suppress elevation of postprandial blood glucose levels in rats and humans.

PubMed

Innami, Satoshi; Ishida, Hiroshi; Nakamura, Kahoru; Kondo, Mika; Tabata, Kimiko; Koguchi, Takashi; Shimizu, Jun; Furusho, Tadasu

2005-01-01

The study was performed to explore the suppressive effect of Jew's mellow leaves (JML) on postprandial blood glucose levels in rats and humans. A soluble dietary fiber (SDF) was extracted from the freeze-dried JML powder. An elevation of the postprandial blood glucose level in rats given 1% or 2% JML-SDF solution orally together with 20% glucose solution was significantly suppressed as compared with that observed in the control rats given only glucose solution. When seven healthy young male adults ingested 225 mL of JML mixed juice containing 15 g of freeze-dried powder with 75 g of glucose in the fasting state in the morning, the elevation of the postprandial blood glucose level was significantly suppressed as compared with the control subjects. The diffusion rate of glucose and the permeation rate of glucose in the cultured Caco-2 cells were both significantly reduced by the addition of appropriate amounts of JML-SDF when compared to the controls. These results indicate that the effective substance in JML for suppressing blood glucose elevation is a kind of mucilaginous SDF. The mechanism by which this suppression occurs may be largely attributable to the delayed absorption of glucose from the intestinal membrane in the upper digestive tract by viscous SDF.

The Hyperactivity of Efferent Auditory System in Patients with Schizophrenia: A Transient Evoked Otoacoustic Emissions Study

PubMed Central

Wahab, Suzaily; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Zakaria, Mohd. Normani

2016-01-01

Objective Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. Methods Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. Results We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). Conclusion The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients. PMID:26766950

Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner.

PubMed

Checker, Rahul; Sharma, Deepak; Sandur, Santosh K; Khan, Nazir M; Patwardhan, Raghavendra S; Kohli, Vineet; Sainis, Krishna B

2011-08-01

Recent investigations suggest that cellular redox status may play a key role in the regulation of several immune functions. Treatment of lymphocytes with vitamin K3 (menadione) resulted in a significant decrease in cellular GSH/GSSG ratio and concomitant increase in the ROS levels. It also suppressed Concanavalin A (Con A)-induced proliferation and cytokine production in lymphocytes and CD4 + T cells in vitro. Immunosuppressive effects of menadione were abrogated only by thiol containing antioxidants. Mass spectrometric analysis showed that menadione directly interacted with thiol antioxidant GSH. Menadione completely suppressed Con A-induced activation of ERK, JNK and NF-κB in lymphocytes. It also significantly decreased the homeostasis driven proliferation of syngeneic CD4 + T cells. Further, menadione significantly delayed graft-vs-host disease morbidity and mortality in mice. Menadione suppressed phytohemagglutinin-induced cytokine production in human peripheral blood mononuclear cells. These results reveal that cellular redox perturbation by menadione is responsible for significant suppression of lymphocyte responses.

Similarities between the irrelevant sound effect and the suffix effect.

PubMed

Hanley, J Richard; Bourgaize, Jake

2018-03-29

Although articulatory suppression abolishes the effect of irrelevant sound (ISE) on serial recall when sequences are presented visually, the effect persists with auditory presentation of list items. Two experiments were designed to test the claim that, when articulation is suppressed, the effect of irrelevant sound on the retention of auditory lists resembles a suffix effect. A suffix is a spoken word that immediately follows the final item in a list. Even though participants are told to ignore it, the suffix impairs serial recall of auditory lists. In Experiment 1, the irrelevant sound consisted of instrumental music. The music generated a significant ISE that was abolished by articulatory suppression. It therefore appears that, when articulation is suppressed, irrelevant sound must contain speech for it to have any effect on recall. This is consistent with what is known about the suffix effect. In Experiment 2, the effect of irrelevant sound under articulatory suppression was greater when the irrelevant sound was spoken by the same voice that presented the list items. This outcome is again consistent with the known characteristics of the suffix effect. It therefore appears that, when rehearsal is suppressed, irrelevant sound disrupts the acoustic-perceptual encoding of auditorily presented list items. There is no evidence that the persistence of the ISE under suppression is a result of interference to the representation of list items in a postcategorical phonological store.

Assessment of rock musician's efferent system functioning using contralateral suppression of otoacoustic emissions.

PubMed

Kumar, Prawin; Grover, Vibhu; Publius A, Sam; Sanju, Himanshu Kumar; Sinha, Sachchidanand

2016-12-01

Contralateral suppression of oto acoustic emission (OAE) is referred as activation of efferent system. Previous literature mentioned about the importance of contralateral suppression of OAEs as a tool to assess efferent system in different groups of population. There is dearth of literature to explore the efferent system function in experienced musicians exposed to rock music using TEOAEs and DPOAEs. Two groups of participant (14 rock musicians and 14 non-musicians) in the age range of 18-25 years were involved in the study. Contralateral suppression of TEOAEs and DPOAEs were measured using ILO (Version 6) in both groups. Descriptive statistics showed higher suppression of TEOAEs and DPOAEs in rock-musicians at most of the frequencies in comparison to non-musicians. For DPOAE measures, Mann Whitney U test results revealed significantly greater DPOAE suppression only at 1 kHz and 3 kHz in rock-musicians compared to non-musicians. For within group comparison, Kruskal Wallis test results revealed there were significant difference observed across most of the frequencies i.e. at 1 kHz, 3 kHz and 6 kHz. For TEOAE measures, Mann Whitney U test results revealed that only at 2 kHz, TEOAE suppression in rock-musician was significantly greater compared to non-musicians. Similarly, Kuskal Wallis test results revealed that within group there were no significant differences observed for most of the frequencies except 2 kHz. Based on the above finding, present study concludes that rock musicians are having better efferent system compared to non-musicians. No suppression effect at few frequencies probably indicates more vulnerability at those frequencies. Contralateral suppression of DPOAE shows more significant finding in comparison to contralateral suppression of TEOAEs in present study.

Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

NASA Technical Reports Server (NTRS)

Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

2003-01-01

Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

1-methylmalate from camu-camu (Myrciaria dubia) suppressed D-galactosamine-induced liver injury in rats.

PubMed

Akachi, Toshiyuki; Shiina, Yasuyuki; Kawaguchi, Takumi; Kawagishi, Hirokazu; Morita, Tatsuya; Sugiyama, Kimio

2010-01-01

To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.

The effects of high-intensity exercise on neural responses to images of food.

PubMed

Crabtree, Daniel R; Chambers, Edward S; Hardwick, Robert M; Blannin, Andrew K

2014-02-01

Acute bouts of high-intensity exercise modulate peripheral appetite regulating hormones to transiently suppress hunger. However, the effects of physical activity on central appetite regulation have yet to be fully investigated. We used functional magnetic resonance imaging (fMRI) to compare neural responses to visual food stimuli after intense exercise and rest. Fifteen lean healthy men [mean ± SD age: 22.5 ± 3.1 y; mean ± SD body mass index (in kg/m(2)): 24.2 ± 2.4] completed two 60-min trials-exercise (EX; running at ∼70% maximum aerobic capacity) and a resting control trial (REST)-in a counterbalanced order. After each trial, an fMRI assessment was completed in which images of high- and low-calorie foods were viewed. EX significantly suppressed subjective appetite responses while increasing thirst and core-body temperature. Furthermore, EX significantly suppressed ghrelin concentrations and significantly enhanced peptide YY release. Neural responses to images of high-calorie foods significantly increased dorsolateral prefrontal cortex activation and suppressed orbitofrontal cortex (OFC) and hippocampus activation after EX compared with REST. After EX, low-calorie food images increased insula and putamen activation and reduced OFC activation compared with REST. Furthermore, left pallidum activity was significantly elevated after EX when low-calorie images were viewed and was suppressed when high-calorie images were viewed, and these responses correlated significantly with thirst. Exercise increases neural responses in reward-related regions of the brain in response to images of low-calorie foods and suppresses activation during the viewing of high-calorie foods. These central responses are associated with exercise-induced changes in peripheral signals related to appetite-regulation and hydration status. This trial was registered at www.clinicaltrials.gov as NCT01926431.

Weight Suppression Predicts Maintenance and Onset of Bulimic Syndromes at 10-Year Follow-up

PubMed Central

Keel, Pamela K.; Heatherton, Todd F.

2010-01-01

Conflicting results have emerged regarding the prognostic significance of weight suppression for maintenance of bulimic symptoms. This study examined whether the magnitude of weight suppression would predict bulimic syndrome maintenance and onset in college-based samples of men (n=369) and women (n=968) at 10-year follow-up. Data come from a longitudinal study of body weight and disordered eating with high retention (80%). Among those with a bulimic syndrome at baseline, greater weight suppression significantly predicted maintenance of the syndrome, and, among those without a bulimic syndrome at baseline, greater weight suppression predicted onset of a bulimic syndrome at 10-year follow-up in multivariate models that included baseline body mass index, diet frequency, and weight perception. Future research should address mechanisms that could account for the effects of weight suppression over a long duration of follow-up. PMID:20455599

Electrocochleographic analysis of the suppression of tinnitus by electrical promontory stimulation.

PubMed

Watanabe, K; Okawara, D; Baba, S; Yagi, T

1997-01-01

To investigate the origin, and evaluate the mechanism by which tinnitus is suppressed we performed electrical promontory stimulation (EPS) in 56 patients with tinnitus, and measured the compound action potential (CAP) using electrocochleography before and after EPS. In the group of patients in whom tinnitus was suppressed, the CAP amplitudes increased significantly, whereas the latencies showed no remarkable change. In the group of patients in whom tinnitus was not suppressed, both the CAP amplitudes and latencies exhibited no significant change. These data indicate that the effect on the cochlear nerve plays an important role in the suppression of tinnitus by EPS. The CAP reflects the number of the auditory nerve fibers which discharge synchronously. It is speculated that an increase of the CAP amplitudes is caused by synchronizing discharges of the auditory nerve fibers, and that the mechanism by which EPS suppresses tinnitus may be related to synchronizing these discharges.

Comparison of Filters Dedicated to Speckle Suppression in SAR Images

NASA Astrophysics Data System (ADS)

Kupidura, P.

2016-06-01

This paper presents the results of research on the effectiveness of different filtering methods dedicated to speckle suppression in SAR images. The tests were performed on RadarSat-2 images and on an artificial image treated with simulated speckle noise. The research analysed the performance of particular filters related to the effectiveness of speckle suppression and to the ability to preserve image details and edges. Speckle is a phenomenon inherent to radar images - a deterministic noise connected with land cover type, but also causing significant changes in digital numbers of pixels. As a result, it may affect interpretation, classification and other processes concerning radar images. Speckle, resembling "salt and pepper" noise, has the form of a set of relatively small groups of pixels of values markedly different from values of other pixels representing the same type of land cover. Suppression of this noise may also cause suppression of small image details, therefore the ability to preserve the important parts of an image, was analysed as well. In the present study, selected filters were tested, and methods dedicated particularly to speckle noise suppression: Frost, Gamma-MAP, Lee, Lee-Sigma, Local Region, general filtering methods which might be effective in this respect: Mean, Median, in addition to morphological filters (alternate sequential filters with multiple structuring element and by reconstruction). The analysis presented in this paper compared the effectiveness of different filtering methods. It proved that some of the dedicated radar filters are efficient tools for speckle suppression, but also demonstrated a significant efficiency of the morphological approach, especially its ability to preserve image details.

Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex agnus-castus.

PubMed

Mesaik, M Ahmed; Murad, Shahnaz; Khan, Khalid Mohammed; Tareen, Rasool Bakhsh; Ahmed, Aqeel; Choudhary, Muhammad Iqbal

2009-11-01

Casticin (1), a flavonoid isolated from the aerial parts of Vitex agnus-castus, was found to be a potent immunomodulatory and cytotoxic compound. The activity was tested in vitro for chemiluminescence, chemotaxis, T-cell proliferation and cytotoxicity. Casticin (1) exhibited a significant inhibitory effect on monocyte oxidative burst in a dose dependent manner. It was found to have a significant suppressive effect on the chemotaxic action at higher concentrations on fMLP (10(-8) m) stimulated neutrophils. It also showed a potent suppressive effect on PHA stimulated T-cell (PMBC).

Glucocorticoid response elements and 11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression

PubMed Central

Liu, Yong; Mladinov, Domagoj; Pietrusz, Jennifer L.; Usa, Kristie; Liang, Mingyu

2009-01-01

Aims Hypertensive and other effects of excess glucocorticoids might be in part mediated by the suppression of endothelial nitric oxide synthase (eNOS) expression. We studied the transcriptional and biochemical mechanisms that mediate or modulate the suppression of eNOS expression by glucocorticoids. Methods and results We found that a mere three-fold increase in the concentration of the natural glucocorticoid cortisol (from 30 to 100 nmol/L) significantly decreased the expression level of eNOS in human endothelial cells. Deletion analysis of the eNOS promoter indicated that the segment within −119 bp upstream from the transcription start site was significantly involved in the effect of cortisol. Site-directed mutagenesis and chromatin immunoprecipitation analyses demonstrated the presence of a suppressive glucocorticoid response element (GRE) at −111 to −105 bp. 11β-hydroxysteroid dehydrogenases (11β-HSD) catalyse the interconversion of active and inactive glucocorticoids. The suppression of 11β-HSD2 using small interfering RNA markedly exacerbated the inhibition of eNOS by cortisol. The suppression of 11β-HSD1 abolished the inhibition of eNOS expression by cortisol. Conclusion We identified the first GRE in the eNOS promoter region and demonstrated that endogenous 11β-HSD1 and 11β-HSD2 play significant and distinct roles in modulating the effect of glucocorticoids on eNOS expression. PMID:18716005

Suppression Effect and Mechanism of Platinum and Nitrogen-Containing Silane on the Tracking and Erosion of Silicone Rubber for High-Voltage Insulation.

PubMed

Chen, Wan Juan; Zeng, Xingrong; Lai, Xuejun; Li, Hongqiang; Fang, Wei Zhen; Hou, Fei

2016-08-17

How to effectively improve the tracking and erosion resistance of silicone rubber (SR) was an urgent topic in the field of high-voltage insulation. In this work, the tracking and erosion resistance of SR was significantly improved by incorporating platinum (Pt) catalyst and nitrogen-containing silane (NS). The suppression effect and mechanism of Pt/NS on tracking and erosion were studied by inclined plane (IP) test, thermogravimetry (TG), thermogravimetry-Fourier transform infrared spectrometry, laser Raman spectroscopy, and scanning electron microscopy. It revealed that when 1.4 phr of NS and 6.7 ppm of Pt were added, the tracking resistance of SR was improved from 2.5 to 4.5 kV level in the IP test, and the eroded mass was significantly reduced. This might be attributed to the synergistic effect of Pt/NS on silicone chains. At a high temperature produced by arc discharge, Pt/NS would catalyze radical cross-linking, meanwhile suppressing oxidation and depolymerization of silicone chains. Hence, a tightly cross-linked network was formed and protected inner materials from arc ablation. Moreover, carbon deposit during pyrolysis was suppressed by Pt/NS, which served as the secondary mechanism of tracking suppression.

Suppressive effects of 3-bromopyruvate on the proliferation and the motility of hepatocellular carcinoma cells.

PubMed

Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

2016-01-01

The compound 3-bromopyruvate (3BP) is an analogue of pyruvate, which is the final product of glycolysis that enters the citric acid cycle. The present study aimed to investigate the suppressive effects of 3BP on the proliferation and motility of hepatocellular carcinoma (HCC) cells. HLF and PLC/PRF/5 cells were cultured with 3BP and subjected to an MTS assay. Apoptosis was analyzed by hematoxylin and eosin staining. Cell motility was analyzed using a scratch assay. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expression levels of cyclin D1 and matrix metalloproteinase (MMP)9. Proliferation of both cell lines was significantly suppressed by 3BP at 100 µM (P<0.05). The expression level of cyclin D1 was decreased after 3BP treatment at 100 µM in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with 3BP at 100 µM. These results revealed that 3BP suppressed cell proliferation, decreased the expression of cyclin D1, and induced apoptosis in HCC cells. 3BP significantly suppressed motility in both cell lines (P<0.05). The expression level of MMP9 was significantly decreased (P<0.05). 3BP suppressed the proliferation and motility of HCC cells by decreasing the expression of cyclin D1 and MMP9.

Suppressing effects of glucan on micronuclei induced by Co60 in mice.

PubMed

Chorvatovicová, D

1991-10-01

The effects of glucan on the frequency of micronuclei in polychromatic erythrocytes of A/Ph mouse bone marrow induced by Co60 irradiation were examined. Suppressing effect of three glucan derivatives was statistically significant (P less than 0.01) by intravenous application of glucan one hour after irradiation. The most expressive effect was obvious by K3 substituent (DS 0.89). Intraperitoneal application of glucan has to be done earlier than one hour after irradiation. The suppressive effects of glucans can be explained by their ability to trap OH radicals and so decrease the clastogenic effect of irradiation. The results may be useful for therapeutic application of glucan with radiation therapy.

Suppression of Bacterial Wilt and Fusarium Wilt by a Burkholderia nodosa Strain Isolated from Kalimantan Soils, Indonesia.

PubMed

Nion, Yanetri Asi; Toyota, Koki

2008-01-01

A trial was conducted to suppress bacterial wilt of tomato (BWT) caused by Ralstonia solanacearum using biocontrol agents (BCAs) isolated from soils in Kalimantan, Indonesia. Five isolates were selected from 270 isolates as better performing BCAs through screening four times using a pumice medium. The isolates selected were identified as Burkholderia nodosa, Burkholderia sacchari, Burkholderia pyrrocinia and Burkholderia terricola according to 16S rDNA sequences, fatty acid composition and carbon source utilization patterns. Among them, B. nodosa G5.2.rif1 had significant suppressive effects on Fusarium wilt of tomato (FWT) and spinach (FWS) as well as BWT. When B. nodosa G5.2rif1 was inoculated into a pumice medium in combination with sucrose, it showed even more stable disease suppression for BWT, but not for FWS. This suppression was considered to mainly occur through competition for nutrients. In two times greenhouse experiments for BWT using pots comparable in size to those used commercially, B. nodosa G5.2rif1 significantly suppressed the disease index by 33-79%, with no inhibitory effects on the growth, yield and quality of tomatoes.

The suppression effect in visuospatial and verbal working memory span tasks in patients with Alzheimer's disease: a 2-year follow-up study.

PubMed

Elosúa, M Rosa; Peinado, Matías; Contreras, María José; Reales, J Manuel; Montoro, Pedro R

2016-10-01

This study adapted a new task to assess visuospatial and verbal working memory impairments in patients with Alzheimer Disease (AD), including an executive strategy of information suppression. The aim was to examine the visuospatial and verbal difficulties, and additionally to explore the average sex differences, during a 2-year follow-up study. The results indicated that patients with AD showed a significantly lower performance, compared with healthy elderly controls, especially with the suppression of information required in this new task. However, suppression did not lead to a significantly greater decline in the performance of patients when compared with the control group.

Suppression of Host Photosynthesis by the Parasitic Plant Rhinanthus minor

PubMed Central

Cameron, Duncan D.; Geniez, Jean-Michelle; Seel, Wendy E.; Irving, Louis J.

2008-01-01

Background and Aims Parasitism is well understood to have wide-ranging deleterious effects on host performance in species thus far characterized. Photosynthetic performance reductions have been noted in the Striga–Zea mays association; however, no such information exists for facultative hemiparasitic plants and their hosts, nor are the effects of host species understood. Methods Chlorophyll fluorimetry was used to study the effects of parasitism by the hemiparasite Rhinanthus minor on the grass Phleum bertolinii and the forb Plantago lanceolata, and the effects of host species on the photosynthetic apparatus of R. minor. Key Results Parasitism by Rhinanthus led to a significant decrease in the host, and total (host + parasite) biomass in Phleum; however, in Plantago, no significant repression of growth was noted. Maximum quantum yield (Fv/Fm) was reduced in parasitized Plantago, relative to control plants, but not in Phleum. Fv/Fm was significantly lower in R. minor parasitizing Phleum than Plantago, suggesting Phleum to be a superior host to Plantago for R. minor. Steady-state quantum yield (ΦPSII) was significantly depressed in parasitized Phleum, but only at low irradiances in Plantago. ΦPSII was very low for R. minor grown on Plantago, but not Phleum. Conclusions Shown here is the first evidence of the suppression of host photosynthesis by a facultative hemiparasitic plant, which has significant effects on total biomass production. Host identity is a significant factor in parasite success, with the forb Plantago lanceolata exhibiting apparent chemical as well as previously identified physical defences to parasitism. It is proposed that the electron transport rate (as denoted by ΦPSII) represents the limiting factor for biomass accumulation in this system, and that Plantago is able to suppress the growth of Rhinanthus by suppressing the electron transport rate. PMID:18211886

miR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xun; Yu, Honggang, E-mail: honggang_yuwh@163.com; Lu, Xinyao

2014-02-28

Highlights: • miR-22 was decreased in GC tissue samples and cell lines. • miR-22 suppressed GC cell growth and motility in vitro. • CD151 was a direct target of miR-22. • miR-22 suppressed GC cell growth and motility by inhibiting CD151. - Abstract: Gastric cancer (GC) is the second common cause of cancer-related death worldwide. microRNAs (miRNAs) play important roles in the carcinogenesis of GC. Here, we found that miR-22 was significantly decreased in GC tissue samples and cell lines. Ectopic overexpression of miR-22 remarkably suppressed cell proliferation and colony formation of GC cells. Moreover, overexpression of miR-22 significantly suppressedmore » migration and invasion of GC cells. CD151 was found to be a target of miR-22. Furthermore, overexpression of CD151 significantly attenuated the tumor suppressive effect of miR-22. Taken together, miR-22 might suppress GC cells growth and motility partially by inhibiting CD151.« less

Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Ping; Fu, Shilong; Cao, Zhifei

Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressivemore » ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice. • Oroxin B effectively exerts anti-lymphoma without obvious toxicity. • Oroxin B promotes tumor-suppressive DDIT3 and inhibits tumorigenic GRP78.« less

Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut.

PubMed

Shimoda, Hiroshi; Tanaka, Junji; Kikuchi, Mitsunori; Fukuda, Toshiyuji; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2008-06-25

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4), while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.

Suppressive effects of retinoids, carotenoids and antioxidant vitamins on heterocyclic amine-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002).

PubMed

Okai, Y; Higashi-Okai, K; Nakamura, S; Yano, Y; Otani, S

1996-06-12

Effects of retinoids, carotenoids and antioxidant vitamins were studied by mutagen-induced umu C gene expression system in Salmonella typhimurium (TA 1535/pSK 1002). Retinol (vitamin A), retinol acetate and retinoic acid showed remarkable inhibitory activities, whereas retinol palmitate exhibited significant but weak activity for umu C gene expression in tester bacteria induced by 3-amino-3,4-dimethyl-5H-pyrido[4.3-b]indol (Trp-P-1) in the presence of hepatic metabolizing enzymes (S9 mixture). Carotenoids having provitamin A activity (beta-carotene and canthaxanthin) exhibited moderate suppressive effects on the same experimental system. The ranks of suppressive activities were retinol > retinol acetate > retinoic acid > canthaxanthin > beta-carotene > retinol palmitate and their doses for inhibition by 50% (ID50) were estimated to be 1.2 x 10(-7), 3.0 x 10(-7), 5.4 x 10(-7), 1.5 x 10(-6), 4.0 x 10(-5) and 6.0 x 10(-5) M, respectively. However, they did not cause significant inhibition on umu C gene expression induced by direct-acting mutagen (adriamycin or mitomycin C) in the absence of S9 mixture. Inhibition of umu gene expression appears to be due to inhibition of P450-mediated metabolic activation of the heterocyclic amine Trp-P-1. Ascorbic acid (vitamin C) showed weak but significant suppressive activity at high-dose concentrations (3 x 10(-6) - 10(-4)M). However, alpha-tocopherol did not exhibit significant suppression at all dose concentrations. The significance of the experimental results is discussed from the viewpoint of the chemoprevention against genotoxicity associated with carcinogenesis.

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

PubMed Central

Malpass, Gloria E.; Arimilli, Subhashini; Prasad, G. L.; Howlett, Allyn C.

2015-01-01

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. PMID:24927667

Perillyl alcohol suppresses antigen-induced immune responses in the lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imamura, Mitsuru; Sasaki, Oh; Okunishi, Katsuhide

Highlights: •Perillyl alcohol (POH) is an isoprenoid which inhibits the mevalonate pathway. •We examined whether POH suppresses immune responses with a mouse model of asthma. •POH treatment during sensitization suppressed Ag-induced priming of CD4{sup +} T cells. •POH suppressed airway eosinophila and cytokine production in thoracic lymph nodes. -- Abstract: Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes,more » its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4{sup +} T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects.« less

Effect of afferent feedback and central motor commands on soleus H-reflex suppression during arm cycling.

PubMed

Hundza, S R; de Ruiter, Geoff C; Klimstra, M; Zehr, E Paul

2012-12-01

Suppression of soleus H-reflex amplitude in stationary legs is seen during rhythmic arm cycling. We examined the influence of various arm-cycling parameters on this interlimb reflex modulation to determine the origin of the effect. We previously showed the suppression to be graded with the frequency of arm cycling but not largely influenced by changes in peripheral input associated with crank length. Here, we more explicitly explored the contribution of afferent feedback related to arm movement on the soleus H-reflex suppression. We explored the influence of load and rate of muscle stretch by manipulating crank-load and arm-muscle vibration during arm cycling. Furthermore, internally driven ("Active") and externally driven ("Passive") arm cycling was compared. Soleus H-reflexes were evoked with tibial nerve stimulation during stationary control and rhythmic arm-cycling conditions, including: 1) six different loads; 2) with and without vibration to arm muscles; and 3) Active and Passive conditions. No significant differences were seen in the level of suppression between the different crank loads or between conditions with and without arm-muscle vibration. Furthermore, in contrast to the clear effect seen during active cycling, passive arm cycling did not significantly suppress the soleus H-reflex amplitude. Current results, in conjunction with previous findings, suggest that the afferent feedback examined in these studies is not the primary source responsible for soleus H-reflex suppression. Instead, it appears that central motor commands (supraspinal or spinal in origin) associated with frequency of arm cycling are relatively more dominant sources.

Preventive effect of dietary astaxanthin on UVA-induced skin photoaging in hairless mice.

PubMed

Komatsu, Toshiyuki; Sasaki, Suguru; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

2017-01-01

Astaxanthin, a carotenoid found mainly in seafood, has potential clinical applications due to its antioxidant activity. In this study, we evaluated the effect of dietary astaxanthin derived from Haematococcus pluvialis on skin photoaging in UVA-irradiated hairless mice by assessing various parameters of photoaging. After chronic ultraviolet A (UVA) exposure, a significant increase in transepidermal water loss (TEWL) and wrinkle formation in the dorsal skin caused by UVA was observed, and dietary astaxanthin significantly suppressed these photoaging features. We found that the mRNA expression of lympho-epithelial Kazal-type-related inhibitor, steroid sulfatase, and aquaporin 3 in the epidermis was significantly increased by UVA irradiation for 70 days, and dietary astaxanthin significantly suppressed these increases in mRNA expression to be comparable to control levels. In the dermis, the mRNA expression of matrix metalloprotease 13 was increased by UVA irradiation and significantly suppressed by dietary astaxanthin. In addition, HPLC-PDA analysis confirmed that dietary astaxanthin reached not only the dermis but also the epidermis. Our results indicate that dietary astaxanthin accumulates in the skin and appears to prevent the effects of UVA irradiation on filaggrin metabolism and desquamation in the epidermis and the extracellular matrix in the dermis.

Preventive effect of dietary astaxanthin on UVA-induced skin photoaging in hairless mice

PubMed Central

Komatsu, Toshiyuki; Sasaki, Suguru; Manabe, Yuki; Hirata, Takashi

2017-01-01

Astaxanthin, a carotenoid found mainly in seafood, has potential clinical applications due to its antioxidant activity. In this study, we evaluated the effect of dietary astaxanthin derived from Haematococcus pluvialis on skin photoaging in UVA-irradiated hairless mice by assessing various parameters of photoaging. After chronic ultraviolet A (UVA) exposure, a significant increase in transepidermal water loss (TEWL) and wrinkle formation in the dorsal skin caused by UVA was observed, and dietary astaxanthin significantly suppressed these photoaging features. We found that the mRNA expression of lympho-epithelial Kazal-type-related inhibitor, steroid sulfatase, and aquaporin 3 in the epidermis was significantly increased by UVA irradiation for 70 days, and dietary astaxanthin significantly suppressed these increases in mRNA expression to be comparable to control levels. In the dermis, the mRNA expression of matrix metalloprotease 13 was increased by UVA irradiation and significantly suppressed by dietary astaxanthin. In addition, HPLC-PDA analysis confirmed that dietary astaxanthin reached not only the dermis but also the epidermis. Our results indicate that dietary astaxanthin accumulates in the skin and appears to prevent the effects of UVA irradiation on filaggrin metabolism and desquamation in the epidermis and the extracellular matrix in the dermis. PMID:28170435

Moderating effects of three coping strategies and self-esteem on perceived discrimination and depressive symptoms: A minority stress model for Asian international students.

PubMed

Wei, Meifen; Ku, Tsun-Yao; Russell, Daniel W; Mallinckrodt, Brent; Liao, Kelly Yu-Hsin

2008-10-01

This study examined 3 coping strategies (reflective, suppressive, and reactive), along with self-esteem, as moderators of the relation between perceived discrimination and depressive symptoms. International students (N = 354) from China, India, Korea, Taiwan, and Hong Kong provided data via an online survey. The role of perceived general stress was statistically controlled. Hierarchical regression analyses indicated a significant direct effect of perceived discrimination, a significant 2-way interaction of perceived discrimination and suppressive coping, and a significant 3-way interaction of perceived discrimination, reactive coping, and self-esteem in predicting depressive symptoms. An increased tendency to use suppressive coping appeared to strengthen the association between perceived discrimination and depressive symptoms. In contrast, the association between perceived discrimination and depressive symptoms was not significant when reactive coping was infrequently used, but only for students with relatively high self-esteem. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

The effects of fire suppression on Bachman's sparrows in upland pine forests of eastern Texas

Treesearch

Richard N. Conner; Clifford E. Shackelford; Richard R. Schaefer; Daniel Saenz

2005-01-01

We studied the effects of 8 years of fire suppression on shrub-level vegetation, Bachman's Sparrows (Aimophila aestivalis), and selected forest bird species between 1995 and 2003in eastern Texas. Woody shrub-level vegetation between ground level and 3 m above the ground, measured using a leaf area index, increased significantly in all sites !n...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Meichun; Department of Physiology, Hubei University of Medicine, Shiyan; Li, Jianjie

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca{sup 2+} increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca{sup 2+} increase were largely inhibited by using LaCl{sub 3}more » to block the Ca{sup 2+} release-activated Ca{sup 2+} channels (CRACs). Furthermore, PD significantly inhibited Ca{sup 2+} entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca{sup 2+} influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca{sup 2+} mobilization mainly through inhibiting Ca{sup 2+} entry via CRACs, thus exerting a protective effect against PCA. -- Highlights: ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca{sup 2+} entry through CRAC channels in mast cells.« less

Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice.

PubMed Central

Matsumoto, T; Ogata, M; Koga, K; Shigematsu, A

1994-01-01

To investigate the effect of peripheral and central benzodiazepine receptor ligands on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) activity in mouse macrophages, three types of ligands, 4'-chlorodiazepam (pure peripheral), midazolam (mixed), and clonazepam (pure central), were compared. Midazolam and 4'-chlorodiazepam significantly suppressed LPS (1-microgram/ml)-induced TNF activity in thioglycolate-elicited mouse macrophages. In every concentration examined (0.001 to 100 microM), 4'-chlorodiazepam was the most effective agent, clonazepam was the least effective agent, and midazolam had an effect intermediate between those of the other two ligands. The peripheral benzodiazepine receptor ligands had a dose-dependent suppressive effect, and the 50% inhibitory concentrations were 0.01 microM for 4'-chlorodiazepam and 5 microM for midazolam. Concomitant use of PK 11195 (10 microM), an antagonist of the peripheral benzodiazepine receptor, reversed this suppressive effect with 4'-chlorodiazepam (10 microM) or midazolam (10 microM). PK 11195 showed this antagonistic effect in a dose-dependent manner. Intravenous 4'-chlorodiazepam (5 mg/kg of body weight) significantly suppressed LPS (100-micrograms)-induced TNF activity of sera (2 h postchallenge with LPS) from thioglycolate-treated mice. The present findings suggest that the peripheral benzodiazepine receptor plays an important role in modulating LPS-induced TNF activity in mouse macrophages. PMID:8031051

Comparison of buprenorphine and methadone effects on opiate self-administration in primates.

PubMed

Mello, N K; Bree, M P; Mendelson, J H

1983-05-01

The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

Modulation of TNF Release by Choline Requires α7 Subunit Nicotinic Acetylcholine Receptor-Mediated Signaling

PubMed Central

Parrish, William R; Rosas-Ballina, Mauricio; Gallowitsch-Puerta, Margot; Ochani, Mahendar; Ochani, Kanta; Yang, Li-Hong; Hudson, LaQueta; Lin, Xinchun; Patel, Nirav; Johnson, Sarah M; Chavan, Sangeeta; Goldstein, Richard S; Czura, Christopher J; Miller, Edmund J; Al-Abed, Yousef; Tracey, Kevin J; Pavlov, Valentin A

2008-01-01

The α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR) is an essential component in the vagus nerve-based cholinergic anti-inflammatory pathway that regulates the levels of TNF, high mobility group box 1 (HMGB1), and other cytokines during inflammation. Choline is an essential nutrient, a cell membrane constituent, a precursor in the biosynthesis of acetylcholine, and a selective natural α7nAChR agonist. Here, we studied the anti-inflammatory potential of choline in murine endotoxemia and sepsis, and the role of the α7nAChR in mediating the suppressive effect of choline on TNF release. Choline (0.1–50 mM) dose-dependently suppressed TNF release from endotoxin-activated RAW macrophage-like cells, and this effect was associated with significant inhibition of NF-κB activation. Choline (50 mg/kg, intraperitoneally [i.p.]) treatment prior to endotoxin administration in mice significantly reduced systemic TNF levels. In contrast to its TNF suppressive effect in wild type mice, choline (50 mg/kg, i.p.) failed to inhibit systemic TNF levels in α7nAChR knockout mice during endotoxemia. Choline also failed to suppress TNF release from endotoxin-activated peritoneal macrophages isolated from α7nAChR knockout mice. Choline treatment prior to endotoxin resulted in a significantly improved survival rate as compared with saline-treated endotoxemic controls. Choline also suppressed HMGB1 release in vitro and in vivo, and choline treatment initiated 24 h after cecal ligation and puncture (CLP)-induced polymicrobial sepsis significantly improved survival in mice. In addition, choline suppressed TNF release from endotoxin-activated human whole blood and macrophages. Collectively, these data characterize the anti-inflammatory efficacy of choline and demonstrate that the modulation of TNF release by choline requires α7nAChR-mediated signaling. PMID:18584048

Chestnut astringent skin extract, an alpha-amylase inhibitor, retards carbohydrate absorption in rats and humans.

PubMed

Tsujita, Takahiro; Takaku, Takeshi; Suzuki, Tsuneo

2008-02-01

Inhibitors of carbohydrate-hydrolyzing enzyme play an important role to control postprandial blood glucose levels. In this paper, we investigated the effect of an ethanol extract from chestnut astringent skin (CAS) on alpha-amylase. Chestnut astringent skin extract strongly inhibited human and porcine pancreatic alpha-amylase. We also investigated the effect of CAS extract on carbohydrate absorption in rats and humans. Oral administration of CAS extract to normal rats fed corn starch (2 g/kg body weight), significantly suppressed the increase of blood glucose levels after starch loading in a dose-dependent manner. The effective dose of CAS extract required to achieve 20 and 40% suppression of the rise in blood glucose level was estimated to be 40 and 155 mg/kg body weight, respectively. Chestnut astringent skin extract also suppressed the rise in plasma insulin level and the fall in plasma non-esterified fatty acid level. In the type 2 diabetic rat model, CAS extract significantly suppressed the rise in blood glucose level after starch loading in a dose-dependent manner. Chestnut astringent skin extract also suppressed the rise in plasma glucose level after boiled rice loading in a dose-dependent manner in humans. The amount of CAS extract required to achieve 11 and 23% suppression in the rise in plasma glucose level was 300 and 600 mg/person, respectively. These results suggest that CAS extract retards absorption of carbohydrate and reduces post-prandial hyperglycemia.

Valerian Inhibits Rat Hepatocarcinogenesis by Activating GABA(A) Receptor-Mediated Signaling

PubMed Central

Kakehashi, Anna; Kato, Ayumi; Ishii, Naomi; Wei, Min; Morimura, Keiichirou; Fukushima, Shoji; Wanibuchi, Hideki

2014-01-01

Valerian is widely used as a traditional medicine to improve the quality of sleep due to interaction of several active components with the γ-aminobutyric acid (GABA) A receptor (GABA(A)R) system. Recently, activation of GABA signaling in stem cells has been reported to suppress cell cycle progression in vivo. Furthermore, possible inhibitory effects of GABA(A)R agonists on hepatocarcinogenesis have been reported. The present study was performed to investigate modulating effects of Valerian on hepatocarcinogenesis using a medium-term rat liver bioassay. Male F344 rats were treated with one of the most powerful Valerian species (Valeriana sitchensis) at doses of 0, 50, 500 and 5000 ppm in their drinking water after initiation of hepatocarcinogenesis with diethylnitrosamine (DEN). Formation of glutathione S-transferase placental form positive (GST-P+) foci was significantly inhibited by Valerian at all applied doses compared with DEN initiation control rats. Generation of 8-hydroxy-2′-deoxyguanosine in the rat liver was significantly suppressed by all doses of Valerian, likely due to suppression of Nrf2, CYP7A1 and induction of catalase expression. Cell proliferation was significantly inhibited, while apoptosis was induced in areas of GST-P+ foci of Valerian groups associated with suppression of c-myc, Mafb, cyclin D1 and induction of p21Waf1/Cip1, p53 and Bax mRNA expression. Interestingly, expression of the GABA(A)R alpha 1 subunit was observed in GST-P+ foci of DEN control rats, with significant elevation associated with Valerian treatment. These results indicate that Valerian exhibits inhibitory effects on rat hepatocarcinogenesis by inhibiting oxidative DNA damage, suppressing cell proliferation and inducing apoptosis in GST-P+ foci by activating GABA(A)R-mediated signaling. PMID:25419570

Emotion suppression affects cardiovascular responses to initial and subsequent laboratory stressors.

PubMed

Quartana, Phillip J; Burns, John W

2010-09-01

The study of anger suppression and risk for cardiovascular disease has relied predominately on inspection of correlations between trait anger-in and cardiovascular risk factors and disease. This approach tells us little about whether inhibitory processes have anything to do with outcomes, and cannot speak to whether suppression of anger per se affects cardiovascular parameters. Drawing on the broader emotion regulation literature, we examined the effects of experimentally induced anger and general negative emotion in the context of expressive and experiential suppression on cardiovascular responses to initial and subsequent laboratory stressors. Of all participants, 201 healthy participants were randomly assigned to one of six conditions formed by crossing emotion (anxiety, anger) and suppression (experiential, expressive, control) conditions. Participants completed a mental arithmetic task with anxiety or anger induction under their respective suppression manipulation instructions, and subsequently were exposed to a cold pressor task. Systolic blood pressure (SBP), diastolic blood pressure, and heart rate values were obtained for each experimental epoch. More robust SBP responses to the initial stressor were evidenced for those in the expressive versus the control condition. In response to the subsequent stressor, those in the experiential suppression condition showed the most pronounced SBP responses, suggesting pronounced delayed effects of this type of suppression. Effects of suppression on SBP reactivity were indistinguishable across anxiety and anger conditions. Effortful suppression of negative emotion has immediate and delayed consequences for stress-induced cardiovascular reactivity. Theoretical and clinical significance of these findings are discussed.

Pharmaceuticals suppress algal growth and microbial respiration and alter bacterial communities in stream biofilms.

PubMed

Rosi-Marshall, Emma J; Kincaid, Dustin W; Bechtold, Heather A; Royer, Todd V; Rojas, Miguel; Kelly, John J

2013-04-01

Pharmaceutical and personal care products are ubiquitous in surface waters but their effects on aquatic biofilms and associated ecosystem properties are not well understood. We measured in situ responses of stream biofilms to six common pharmaceutical compounds (caffeine, cimetidine, ciprofloxacin, diphenhydramine, metformin, ranitidine, and a mixture of each) by deploying pharmaceutical-diffusing substrates in streams in Indiana, Maryland, and New York. Results were consistent across seasons and geographic locations. On average, algal biomass was suppressed by 22%, 4%, 22%, and 18% relative to controls by caffeine, ciprofloxacin, diphenhydramine, and the mixed treatment, respectively. Biofilm respiration was significantly suppressed by caffeine (53%), cimetidine (51%), ciprofloxacin (91%), diphenhydramine (63%), and the mixed treatment (40%). In autumn in New York, photosynthesis was also significantly suppressed by diphenhydramine (99%) and the mixed treatment (88%). Pyrosequencing of 16S rRNA genes was used to examine the effects of caffeine and diphenhydramine on biofilm bacterial community composition at the three sites. Relative to the controls, diphenhydramine exposure significantly altered bacterial community composition and resulted in significant relative increases in Pseudomonas sp. and decreases in Flavobacterium sp. in all three streams. These ubiquitous pharmaceuticals, alone or in combination, influenced stream biofilms, which could have consequences for higher trophic levels and important ecosystem processes.

IL-1β directly suppress ghrelin mRNA expression in ghrelin-producing cells.

PubMed

Bando, Mika; Iwakura, Hiroshi; Ueda, Yoko; Ariyasu, Hiroyuki; Inaba, Hidefumi; Furukawa, Yasushi; Furuta, Hiroto; Nishi, Masahiro; Akamizu, Takashi

2017-05-15

In animal models, ghrelin production is suppressed by LPS administration. To elucidate the detailed molecular mechanisms involved in the phenomenon, we investigated the effects of LPS and LPS-inducible cytokines, including TNF-α, IL-1β, and IL-6, on the expression of ghrelin in the ghrelin-producing cell line MGN3-1. These cells expressed IL-1R, and IL-1β significantly suppressed ghrelin mRNA levels. The suppressive effects of IL-1β were attenuated by knockdown of IKKβ, suggesting the involvement of the NF-κB pathway. These results suggested that IL-1β is a major regulator of ghrelin expression during inflammatory processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive Difficulties in Struggling Comprehenders and their Relation to Reading Comprehension: A Comparison of Group Selection and Regression-Based Models

PubMed Central

Barnes, Marcia A.; Stuebing, Karla; Fletcher, Jack M.; Barth, Amy; Francis, David

2016-01-01

Difficulties suppressing previously encountered, but currently irrelevant information from working memory characterize less skilled comprehenders in studies in which they are matched to skilled comprehenders on word decoding and nonverbal IQ. These “extreme” group designs are associated with several methodological issues. When sample size permits, regression approaches permit a more accurate estimation of effects. Using data for students in grades 6 to 12 (n = 766), regression techniques assessed the significance and size of the relation of suppression to reading comprehension across the distribution of comprehension skill. After accounting for decoding efficiency and nonverbal IQ, suppression, measured by performance on a verbal proactive interference task, accounted for a small amount of significant unique variance in comprehension (less than 1%). A comparison of suppression in less skilled comprehenders matched to more skilled comprehenders (48 per group) on age, word reading efficiency and nonverbal IQ did not show significant group differences in suppression. The implications of the findings for theories of reading comprehension and for informing comprehension assessment and intervention are discussed. PMID:27175222

Effects of Flavonoids on Rumen Fermentation Activity, Methane Production, and Microbial Population

PubMed Central

Abdullah, Norhani; Oskoueian, Armin

2013-01-01

This research was carried out to evaluate the effects of flavone, myricetin, naringin, catechin, rutin, quercetin, and kaempferol at the concentration of 4.5% of the substrate (dry matter basis) on the rumen microbial activity in vitro. Mixture of guinea grass and concentrate (60 : 40) was used as the substrate. The results showed that all the flavonoids except naringin and quercetin significantly (P < 0.05) decreased the dry matter degradability. The gas production significantly (P < 0.05) decreased by flavone, myricetin, and kaempferol, whereas naringin, rutin, and quercetin significantly (P < 0.05) increased the gas production. The flavonoids suppressed methane production significantly (P < 0.05). The total VFA concentration significantly (P < 0.05) decreased in the presence of flavone, myricetin, and kaempferol. All flavonoids except naringin and quercetin significantly (P < 0.05) reduced the carboxymethyl cellulase, filter paperase, xylanase, and β-glucosidase activities, purine content, and the efficiency of microbial protein synthesis. Flavone, myricetin, catechin, rutin, and kaempferol significantly (P < 0.05) reduced the population of rumen microbes. Total populations of protozoa and methanogens were significantly (P < 0.05) suppressed by naringin and quercetin. The results of this research demonstrated that naringin and quercetin at the concentration of 4.5% of the substrate (dry matter basis) were potential metabolites to suppress methane production without any negative effects on rumen microbial fermentation. PMID:24175289

Involvement of phenazines and lipopeptides in interactions between Pseudomonas species and Sclerotium rolfsii, causal agent of stem rot disease on groundnut.

PubMed

Le, C N; Kruijt, M; Raaijmakers, J M

2012-02-01

To determine the role of phenazines (PHZ) and lipopeptide surfactants (LPs) produced by Pseudomonas in suppression of stem rot disease of groundnut, caused by the fungal pathogen Sclerotium rolfsii. In vitro assays showed that PHZ-producing Pseudomonas chlororaphis strain Phz24 significantly inhibited hyphal growth of S. rolfsii and suppressed stem rot disease of groundnut under field conditions. Biosynthesis and regulatory mutants of Phz24 deficient in PHZ production were less effective in pathogen suppression. Pseudomonas strains SS101, SBW25 and 267, producing viscosin or putisolvin-like LPs, only marginally inhibited hyphal growth of S. rolfsii and did not suppress stem rot disease. In contrast, Pseudomonas strain SH-C52, producing the chlorinated LP thanamycin, inhibited hyphal growth of S. rolfsii and significantly reduced stem rot disease of groundnut in nethouse and field experiments, whereas its thanamycin-deficient mutant was less effective. Phenazines and specific lipopeptides play an important role in suppression of stem rot disease of groundnut by root-colonizing Pseudomonas strains. Pseudomonas strains Phz24 and SH-C52 showed significant control of stem rot disease. Treatment of seeds or soil with these strains provides a promising supplementary strategy to control stem rot disease of groundnut. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Combined transdermal testosterone gel and the progestin nestorone suppresses serum gonadotropins in men.

PubMed

Mahabadi, Vahid; Amory, John K; Swerdloff, Ronald S; Bremner, William J; Page, Stephanie T; Sitruk-Ware, Regine; Christensen, Peter D; Kumar, Narender; Tsong, Yun-Yen; Blithe, Diana; Wang, Christina

2009-07-01

Testosterone (T) plus progestin combinations are the most promising hormonal male contraceptives. Nestorone (NES), a progestin without estrogenic or androgenic activity, when combined with T may be an excellent candidate for male contraception. Our objective was to determine the effect of transdermal NES gel alone or with T gel on gonadotropin suppression. The randomized, unblinded clinical trial was conducted at two academic medical centers. A total of 140 healthy male volunteers participated. One hundred subjects were randomized initially (20 per group) to apply NES gel 2 or 4 mg, T gel 10 g, or T gel 10 g plus NES gel 2 or 4 mg daily for 20 d. Because only about half of the subjects in T plus NES 4 mg group suppressed serum gonadotropins to 0.5 IU/liter or less (suboptimal suppression), two additional groups of 20 men were randomized to apply daily T gel 10 g plus NES gel 6 or 8 mg. Suppression of serum LH and FSH concentrations to 0.5 IU/liter or less after treatment was the main outcome variable. A total of 119 subjects were compliant with gel applications with few study-related adverse events. NES alone reduced gonadotropins significantly but less than T gel alone. Combined T gel 10g plus NES gel 6 or 8 mg suppressed both serum gonadotropins to 0.5 IU/liter or less in significantly more men than either gel alone. Transdermal NES gel alone had gonadotropin suppression activity. Combined transdermal NES (6 or 8 mg) plus T gel demonstrated safe and effective suppression of gonadotropins, justifying a longer-term study of this combination for suppression of spermatogenesis.

Prediction of the Seizure Suppression Effect by Electrical Stimulation via a Computational Modeling Approach.

PubMed

Ahn, Sora; Jo, Sumin; Jun, Sang Beom; Lee, Hyang Woon; Lee, Seungjun

2017-01-01

In this paper, we identified factors that can affect seizure suppression via electrical stimulation by an integrative study based on experimental and computational approach. Preferentially, we analyzed the characteristics of seizure-like events (SLEs) using our previous in vitro experimental data. The results were analyzed in two groups classified according to the size of the effective region, in which the SLE was able to be completely suppressed by local stimulation. However, no significant differences were found between these two groups in terms of signal features or propagation characteristics (i.e., propagation delays, frequency spectrum, and phase synchrony). Thus, we further investigated important factors using a computational model that was capable of evaluating specific influences on effective region size. In the proposed model, signal transmission between neurons was based on two different mechanisms: synaptic transmission and the electrical field effect. We were able to induce SLEs having similar characteristics with differentially weighted adjustments for the two transmission methods in various noise environments. Although the SLEs had similar characteristics, their suppression effects differed. First of all, the suppression effect occurred only locally where directly received the stimulation effect in the high noise environment, but it occurred in the entire network in the low noise environment. Interestingly, in the same noise environment, the suppression effect was different depending on SLE propagation mechanism; only a local suppression effect was observed when the influence of the electrical field transmission was very weak, whereas a global effect was observed with a stronger electrical field effect. These results indicate that neuronal activities synchronized by a strong electrical field effect respond more sensitively to partial changes in the entire network. In addition, the proposed model was able to predict that stimulation of a seizure focus region is more effective for suppression. In conclusion, we confirmed the possibility of a computational model as a simulation tool to analyze the efficacy of deep brain stimulation (DBS) and investigated the key factors that determine the size of an effective region in seizure suppression via electrical stimulation.

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase.

PubMed

Pandey, Puspa R; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Liu, Wen; Kobayashi, Aya; Xing, Fei; Fukuda, Koji; Hirota, Shigeru; Sugai, Tamotsu; Wakabayashi, Go; Koeda, Keisuke; Kashiwaba, Masahiro; Suzuki, Kazuyuki; Chiba, Toshimi; Endo, Masaki; Fujioka, Tomoaki; Tanji, Susumu; Mo, Yin-Yuan; Cao, Deliang; Wilber, Andrew C; Watabe, Kounosuke

2011-11-01

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24(-)/CD44(+)/ESA(+)) that were isolated from both ER+ and ER- breast cancer cell lines was examined. The authors found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, the results of this study indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol.

Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase

PubMed Central

Pandey, Puspa R.; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K.; Liu, Wen; Kobayashi, Aya; Xing, Fei; Fukuda, Koji; Hirota, Shigeru; Sugai, Tamotsu; Wakabayashi, Go; Koeda, Keisuke; Kashiwaba, Masahiro; Suzuki, Kazuyuki; Chiba, Toshimi; Endo, Masaki; Fujioka, Tomoaki; Tanji, Susumu; Mo, Yin-Yuan; Cao, Deliang; Wilber, Andrew C.; Watabe, Kounosuke

2012-01-01

Resveratrol is a natural polyphenolic compound and has been shown to exhibit cardio-protective as well as anti-neoplastic effects on various types of cancers. However, the exact mechanism of its anti-tumor effect is not clearly defined. Resveratrol has been shown to have strong hypolipidemic effect on normal adipocytes and as hyper-lipogenesis is a hallmark of cancer cell physiology, we examined the effect of resveratrol on lipid synthesis in cancer stem-like cells (CD24−/CD44+/ESA+) that were isolated from both ER+ and ER− breast cancer cell lines. We found that resveratrol significantly reduced the cell viability and mammosphere formation followed by inducing apoptosis in cancer stem-like cells. This inhibitory effect of resveratrol is accompanied by a significant reduction in lipid synthesis which is caused by the down-regulation of the fatty acid synthase (FAS) gene followed by up-regulation of pro-apoptotic genes, DAPK2 and BNIP3. The activation of apoptotic pathway in the cancer stem-like cells was suppressed by TOFA and by Fumonisin B1, suggesting that resveratrol-induced apoptosis is indeed through the modulation of FAS-mediated cell survival signaling. Importantly, resveratrol was able to significantly suppress the growth of cancer stem-like cells in an animal model of xenograft without showing apparental toxicity. Taken together, our results indicate that resveratrol is capable of inducing apoptosis in the cancer stem-like cells through suppression of lipogenesis by modulating FAS expression, which highlights a novel mechanism of anti-tumor effect of resveratrol. PMID:21188630

Intragastric nutrient infusion reduces motivation for food in male and female rats.

PubMed

Maske, Calyn B; Loney, Gregory C; Lilly, Nicole; Terrill, Sarah J; Williams, Diana L

2018-03-13

The idea that gut-derived satiation signals influence food reward has recently gained traction, but this hypothesis is largely based on studies focused on neural circuitry, not the peripherally released signals. Here, we directly tested the hypothesis that intragastric (IG) nutrient infusion can suppress motivation for food. In a series of experiments, IG sucrose infusion (15 kcal) significantly and reliably reduced operant responding for a sucrose reward on a progressive ratio (PR) schedule. Moreover, food deprivation for 24 h before the test session did not prevent the suppressive effect of nutrients. The suppressive effect of IG sucrose on fixed ratio 5 (FR5) operant responding was also assessed as a comparison. The effect of IG nutrients to reduce motivation was not limited to sucrose; IG Ensure infusion (9.3 kcal) also significantly reduced PR operant responding for sucrose pellets. To verify that these effects are not secondary to the osmotic challenge of concentrated nutrients, we tested IG infusion of non-caloric saline solutions equiosmolar to 40% sucrose or Ensure, and found no effect. Finally, we focused on glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) as candidate mediators for the effect of IG nutrients. Pretreatment with Exendin-9, a GLP-1R antagonist, delivered IP, significantly attenuated the ability of IG nutrients to suppress PR responding and breakpoint in males, but not females, whereas pretreatment with Devazepide, a CCKA receptor antagonist, failed to do so in both sexes. Together, these data support the idea that nutrient-induced satiation signals influence food reward, and may implicate GLP-1 in this process.

Suppression and interpersonal harmony: a cross-cultural comparison between Chinese and European Americans.

PubMed

Wei, Meifen; Su, Jenny C; Carrera, Stephanie; Lin, Shu-Ping; Yi, Fei

2013-10-01

Based on Markus and Kitayama's (1991) theory, this study was conducted to examine whether the association between emotional suppression and interpersonal harmony would be moderated by cultural group (i.e., Chinese and European Americans) and an Asian cultural value (i.e., emotional self-control). A total of 451 college students (205 Chinese and 246 European Americans) participated in this study. As expected, results indicated that the association between emotional suppression and interpersonal harmony was significantly positive for Chinese but not significant for European Americans. Similarly, when emotional self-control was examined as a moderator, the results still confirmed our hypotheses. That is, the association between emotional suppression and interpersonal harmony was significantly positive for those with stronger endorsement of emotional self-control but not for those with weaker endorsement of emotional self-control. Furthermore, we examined whether the above results could be replicated when forbearance (a construct similar to suppression) and distress disclosure (a construct opposite to suppression) were examined. The results showed the same pattern for forbearance and distress disclosure when cultural group or emotional self-control served as the moderator. The convergence of findings increased the robustness of our results. Finally, our data suggest that individuals from Eastern, interdependent cultures (e.g., Chinese) tend to value emotional suppression to preserve interpersonal harmony; individuals from Western, independent cultures may or may not necessarily suppress their emotions for this purpose. A comprehensive understanding of the different meanings of a specific strategy (i.e., emotional suppression) in different cultural contexts is important to promote effective cross-cultural counseling.

RNAi trigger fragment truncation attenuates soybean FAD2-1 transcript suppression and yields intermediate oil phenotypes.

PubMed

Wagner, Nicholas; Mroczka, Andrew; Roberts, Peter D; Schreckengost, William; Voelker, Toni

2011-09-01

Suppression of the microsomal ω6 oleate desaturase during the seed development of soybean (Glycine max) with the 420-bp soybean FAD2-1A intron as RNAi trigger shifts the conventional fatty acid composition of soybean oil from 20% oleic and 60% polyunsaturates to one containing greater than 80% oleic acid and less than 10% polyunsaturates. To determine whether RNAi could be attenuated by reducing the trigger fragment length, transgenic plants were generated to express successively shorter 5' or 3' deletion derivatives of the FAD2-1A intron. We observed a gradual reduction in transcript suppression with shorter trigger fragments. Fatty acid composition was less affected with shorter triggers, and triggers less than 60 bp had no phenotypic effect. No trigger sequences conferring significantly higher or lower suppression efficiencies were found, and the primary determinant of suppression effect was sequence length. The observed relationship of transcript suppression with the induced fatty acid phenotype indicates that RNAi is a saturation process and not a step change between suppressed and nonsuppressed states and intermediate suppression states can be achieved. © 2010 Monsanto. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.

Glycolipids from spinach suppress LPS-induced vascular inflammation through eNOS and NK-κB signaling.

PubMed

Ishii, Masakazu; Nakahara, Tatsuo; Araho, Daisuke; Murakami, Juri; Nishimura, Masahiro

2017-07-01

Glycolipids are the major constituent of the thylakoid membrane of higher plants and have a variety of biological and pharmacological activities. However, anti-inflammatory effects of glycolipids on vascular endothelial cells have not been elucidated. Here, we investigated the effect of glycolipids extracted from spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and evaluated the underlying molecular mechanisms. Treatment with glycolipids from spinach had no cytotoxic effects on cultured human umbilical vein endothelial cells (HUVECs) and significantly blocked the expression of LPS-induced interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in them. Glycolipids treatment also effectively suppressed monocyte adhesion to HUVECs. Treatment with glycolipids inhibited LPS-induced NF-κB phosphorylation and nuclear translocation. In addition, glycolipids treatment significantly promoted endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with a NOS inhibitor attenuated glycolipids-induced suppression of NF-κB activation and adhesion molecule expression, and abolished the glycolipids-mediated suppression of monocyte adhesion to HUVECs. These results indicate that glycolipids suppress LPS-induced vascular inflammation through attenuation of the NF-κB pathway by increasing NO production in endothelial cells. These findings suggest that glycolipids from spinach may have a potential therapeutic use for inflammatory vascular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tetrandrine suppresses lung cancer growth and induces apoptosis, potentially via the VEGF/HIF-1α/ICAM-1 signaling pathway

PubMed Central

Chen, Zhuo; Zhao, Liang; Zhao, Feng; Yang, Guanghai; Wang, Jian Jun

2018-01-01

The present study investigated the effect of tetrandrine on lung cancer cell growth and apoptosis, and its possible underlying molecular mechanism. A549 human lung cancer cells were incubated with between 2.5 and 10 µM tetrandrine for 12, 24 and 48 h, following which the effect of tetrandrine on cell viability and apoptosis were assessed using an MTT assay and flow cytometry. ELISA and western blotting were used to analyze VEGF activity, and the expression of poly (ADP-ribose) polymerase (PARP), phosphorylated protein kinase B (Akt), Bcl-2-associated X protein (Bax), hypoxia inducible factor (HIF)-1α and inter-cellular adhesion molecule-1 (ICAM-1). Tetrandrine effectively suppressed the growth of and induced apoptosis in A549 lung cancer cells. The expression of PARP, Bax, intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) was significantly upregulated, and the phosphorylation of Akt and expression of HIF-1α was significantly suppressed in A549 lung cancer cells. Therefore, tetrandrine may suppress cell viability and induce apoptosis via the VEGF/HIF-1α/ICAM-1 signaling pathway. PMID:29849794

Effects of 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic discs in male rats.

PubMed

Kimball, F A; Frielink, R D; Porteus, S E

1978-01-01

Silicone rubber discs containing 15(S)-15-methyl prostaglandin F2 alpha ester (15-Me-PGF2 alpha) in the matrix were implanted in the left side of the scrotums of Sprague-Dawley rats. The effect of 1% and 2% drug concentration was examined for 10, 20, or 28 days and compared with the effects of Silastic discs containing no prostaglandin. The discs containing prostaglandin reduced mean testicular and accessory gland weights. Histologically the testes and epididymides showed decreased or absent spermatogenic elements and hypertrophy of the interstitial cell masses in comparison with other cells. Implanted prostaglandin significantly depressed serum testosterone, luteinizing hormone, and follicle-stimulating hormone (FSH) concentrations when 15-Me-PGF2 alpha plasma concentrations exceeded 2 ng/ml. Hormone concentrations returned to control values as drug concentrations declined. FSH concentrations significantly exceeded control values 10 and 20 days after implantation, when prostaglandin concentration was nondetectable. The acute suppression of all three hormones suggest that 15-Me-PGF2 alpha either may act directly on the tests to suppress testosterone production or may suppress testosterone production or may suppress gonadotropin secretion, resulting in depressed testosterone output.

The effect of periodic wavy profile on suppressing window multipactor under arbitrary electromagnetic mode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, C., E-mail: chang@slac.stanford.edu; Key Laboratory of Physical Electronics and Devices of the Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi 710049; Liu, Y. S.

2015-01-05

The three-dimensional periodic ripple profile with each unit of rotational symmetric surface is proposed to suppress multipactor for arbitrary electromagnetic mode with any polarization. The field distribution and multipactor electron dynamics on the wavy surface are studied to illustrate the multipactor inhibition mechanism. High power microwave experiment was conducted to demonstrate the effect of wavy surface on significantly improving the window power capacity.

AZD8055 Exerts Antitumor Effects on Colon Cancer Cells by Inhibiting mTOR and Cell-cycle Progression.

PubMed

Chen, Yun; Lee, Cheng-Hung; Tseng, Bor-Yuan; Tsai, Ya-Hui; Tsai, Huang-Wen; Yao, Chao-Ling; Tseng, Sheng-Hong

2018-03-01

AZD8055 is an inhibitor of mammalian target of rapamycin (mTOR) that can suppress both mTOR complex 1 (mTORC1) and mTORC2. This study investigated the antitumor effects of AZD8055 on colon cancer. The effects of AZD8055 on proliferation, apoptosis, and cell cycle of colon cancer cells, and tumor growth in a mouse colon cancer model were studied. AZD8055 significantly inhibited proliferation and induced apoptosis of colon cancer cells (p<0.05). The phosphorylation of both AKT and S6 kinase 1 (S6K1) was suppressed by AZD8055. AZD8055 also induced G 0 /G 1 cell-cycle arrest, reduced cyclin D1 and increased p27 expression, and suppressed the levels of phospho-cyclin-dependent kinase 2 and phospho-retinoblastoma. Compared to the control, oral administration of AZD8055 significantly suppressed tumor growth in mice (p<0.05). AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The regulation of induced depression during a frustrating situation: benefits of expressive suppression in Chinese individuals.

PubMed

Yuan, Jiajin; Liu, Yingying; Ding, Nanxiang; Yang, Jiemin

2014-01-01

Studies from European-American cultures consistently reported that expressive suppression was associated with worse emotional consequence (e.g. depression) in comparison with acceptance. However, this conclusion may not apply to Chinese, as suppressing emotional displays to maintain relational harmony is culturally valued in East Asian countries. Thus, the present study examined the effects of suppression and acceptance on the depressive mood induced by a frustrating task in a Chinese sample. Sixty-four subjects were randomly assigned to one of three instructions: suppression, acceptance or no-regulation during a frustrating arithmetic task. The experience of depressive emotion and skin conductance response (SCR) were recorded during pre-frustration baseline, frustration induction and post-frustration recovery phases, respectively. Compared with the control and acceptance instructions, suppression instruction was associated with decreased depressive experiences and smaller SCR activity during frustration. There were no significant differences between acceptance and control groups in both subjective depression and SCR activity during frustration. Moreover, the suppression group showed a better emotional recovery after the frustrating task, in comparison with the acceptance and control groups. Correlation analyses verified that SCR reactivity was a reliable index of experienced depression during the frustration. Expressive suppression is effective in reducing depressive experiences and depression-related physiological activity (SCR) when Chinese people are involved. By contrast, the acceptance of depressive emotion in Chinese people does not produce a similar regulation effect. These findings suggest that cultural context should be considered in understanding the emotional consequences of suppression and acceptance strategies.

Change in ocean subsurface environment to suppress tropical cyclone intensification under global warming.

PubMed

Huang, Ping; Lin, I-I; Chou, Chia; Huang, Rong-Hui

2015-05-18

Tropical cyclones (TCs) are hazardous natural disasters. Because TC intensification is significantly controlled by atmosphere and ocean environments, changes in these environments may cause changes in TC intensity. Changes in surface and subsurface ocean conditions can both influence a TC's intensification. Regarding global warming, minimal exploration of the subsurface ocean has been undertaken. Here we investigate future subsurface ocean environment changes projected by 22 state-of-the-art climate models and suggest a suppressive effect of subsurface oceans on the intensification of future TCs. Under global warming, the subsurface vertical temperature profile can be sharpened in important TC regions, which may contribute to a stronger ocean coupling (cooling) effect during the intensification of future TCs. Regarding a TC, future subsurface ocean environments may be more suppressive than the existing subsurface ocean environments. This suppressive effect is not spatially uniform and may be weak in certain local areas.

Change in ocean subsurface environment to suppress tropical cyclone intensification under global warming

PubMed Central

Huang, Ping; Lin, I. -I; Chou, Chia; Huang, Rong-Hui

2015-01-01

Tropical cyclones (TCs) are hazardous natural disasters. Because TC intensification is significantly controlled by atmosphere and ocean environments, changes in these environments may cause changes in TC intensity. Changes in surface and subsurface ocean conditions can both influence a TC's intensification. Regarding global warming, minimal exploration of the subsurface ocean has been undertaken. Here we investigate future subsurface ocean environment changes projected by 22 state-of-the-art climate models and suggest a suppressive effect of subsurface oceans on the intensification of future TCs. Under global warming, the subsurface vertical temperature profile can be sharpened in important TC regions, which may contribute to a stronger ocean coupling (cooling) effect during the intensification of future TCs. Regarding a TC, future subsurface ocean environments may be more suppressive than the existing subsurface ocean environments. This suppressive effect is not spatially uniform and may be weak in certain local areas. PMID:25982028

White Light Generation in Human Saliva

NASA Astrophysics Data System (ADS)

Santhosh, C.; Dharmadhikari, A. K.; Dharmadhikari, J. A.; Alti, K.; Mathur, D.

2011-07-01

Interaction of intense, femto-second pulses of infrared light (800 nm) with water generates white light supercontinuum due to nonlinear optical effects. This supercontinuum was found to be suppressed by the addition of alpha amylase, a major protein in the human saliva. We have studied the suppression of supper continuum by human saliva, collected from healthy subjects with and without smoking habits. Suppression of the blue-sided components was observed significantly in non-smokers saliva than chain smokers.

The effects of psychoeducation on thought-action fusion, thought suppression, and responsibility.

PubMed

Marino-Carper, Teresa; Negy, Charles; Burns, Gillian; Lunt, Rachael A

2010-09-01

The current study examined the effects of a psychoeducational intervention designed to target thought-action fusion (TAF) on TAF, thought suppression, and responsibility cognitions. 139 undergraduate students (25 male; 114 female) who were relatively high in TAF with respect to their peers served as participants. Immediately following intervention, individuals who had received psychoeducation regarding TAF reported significantly lower morality TAF scores than individuals who had received psychoeducation regarding thoughts in general and individuals in the control group. At the two-week follow-up assessment, the likelihood TAF scores of those who had received psychoeducation regarding TAF were significantly lower than those of the control group. In addition, the group that received psychoeducation regarding TAF was the only group that did not experience a significant increase in thought suppression from baseline to post-intervention, and was also the only group to experience an increase in both frequency of and belief in low-responsibility thoughts from baseline to follow-up. Implications are discussed. (c) 2010 Elsevier Ltd. All rights reserved.

Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

PubMed

Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

2016-08-25

Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. © 2016 by The American Society of Hematology.

Anger suppression, interdependent self-construal, and depression among Asian American and European American college students.

PubMed

Cheung, Rebecca Y M; Park, Irene J K

2010-10-01

The present study tested a theoretical model of emotion regulation (Yap, Sheeber, & Allen, 2007) in a sample of Asian American and European American college students (N = 365). Specifically, the mediating role of anger suppression in the effect of temperament and family processes on depressive symptoms was tested across race and levels of interdependent self-construal (a culturally based self orientation emphasizing connectedness with others). Next, the moderation of the suppression-depression relation was tested by race and interdependent self-construal. Results indicated that the hypothesized model fit well across Asian American and European American students, as well as those with high versus low levels of interdependent self-construal. Anger suppression was a significant mediator of the hypothesized indirect effects on depressive symptoms. Moreover, race and interdependent self-construal moderated the suppression-depression link, such that Asian American status and a stronger interdependent self-construal attenuated the relation between anger suppression and depressive symptoms. Understanding both universal and culture-specific aspects of emotion regulation in the development of depressive symptoms will be essential for sound theory, future research, and effective prevention and intervention efforts across diverse populations. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Suppression of streptozotocin-induced type-1 diabetes in mice by radon inhalation.

PubMed

Nishiyama, Y; Kataoka, T; Teraoka, J; Sakoda, A; Tanaka, H; Ishimori, Y; Mitsunobu, F; Taguchi, T; Yamaoka, K

2013-01-01

We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia; however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas.

Weed suppression greatly increased by plant diversity in intensively managed grasslands: A continental-scale experiment.

PubMed

Connolly, John; Sebastià, Maria-Teresa; Kirwan, Laura; Finn, John Anthony; Llurba, Rosa; Suter, Matthias; Collins, Rosemary P; Porqueddu, Claudio; Helgadóttir, Áslaug; Baadshaug, Ole H; Bélanger, Gilles; Black, Alistair; Brophy, Caroline; Čop, Jure; Dalmannsdóttir, Sigridur; Delgado, Ignacio; Elgersma, Anjo; Fothergill, Michael; Frankow-Lindberg, Bodil E; Ghesquiere, An; Golinski, Piotr; Grieu, Philippe; Gustavsson, Anne-Maj; Höglind, Mats; Huguenin-Elie, Olivier; Jørgensen, Marit; Kadziuliene, Zydre; Lunnan, Tor; Nykanen-Kurki, Paivi; Ribas, Angela; Taube, Friedhelm; Thumm, Ulrich; De Vliegher, Alex; Lüscher, Andreas

2018-03-01

Grassland diversity can support sustainable intensification of grassland production through increased yields, reduced inputs and limited weed invasion. We report the effects of diversity on weed suppression from 3 years of a 31-site continental-scale field experiment.At each site, 15 grassland communities comprising four monocultures and 11 four-species mixtures based on a wide range of species' proportions were sown at two densities and managed by cutting. Forage species were selected according to two crossed functional traits, "method of nitrogen acquisition" and "pattern of temporal development".Across sites, years and sown densities, annual weed biomass in mixtures and monocultures was 0.5 and 2.0 t  DM ha -1 (7% and 33% of total biomass respectively). Over 95% of mixtures had weed biomass lower than the average of monocultures, and in two-thirds of cases, lower than in the most suppressive monoculture (transgressive suppression). Suppression was significantly transgressive for 58% of site-years. Transgressive suppression by mixtures was maintained across years, independent of site productivity.Based on models, average weed biomass in mixture over the whole experiment was 52% less (95% confidence interval: 30%-75%) than in the most suppressive monoculture. Transgressive suppression of weed biomass was significant at each year across all mixtures and for each mixture.Weed biomass was consistently low across all mixtures and years and was in some cases significantly but not largely different from that in the equiproportional mixture. The average variability (standard deviation) of annual weed biomass within a site was much lower for mixtures (0.42) than for monocultures (1.77). Synthesis and applications . Weed invasion can be diminished through a combination of forage species selected for complementarity and persistence traits in systems designed to reduce reliance on fertiliser nitrogen. In this study, effects of diversity on weed suppression were consistently strong across mixtures varying widely in species' proportions and over time. The level of weed biomass did not vary greatly across mixtures varying widely in proportions of sown species. These diversity benefits in intensively managed grasslands are relevant for the sustainable intensification of agriculture and, importantly, are achievable through practical farm-scale actions.

Astaxanthin reduces isoflurane-induced neuroapoptosis via the PI3K/Akt pathway.

PubMed

Wang, Chun-Mei; Cai, Xiao-Lan; Wen, Qing-Ping

2016-05-01

Astaxanthin is an oxygen-containing derivative of carotenoids that effectively suppresses reactive oxygen and has nutritional and medicinal value. The mechanisms underlying the effects of astaxanthin on isoflurane‑induced neuroapoptosis remain to be fully understood. The present study was conducted to evaluate the protective effect of astaxanthin to reduce isoflurane‑induced neuroapoptosis and to investigate the underlying mechanisms. The results demonstrated that isoflurane induced brain damage, increased caspase‑3 activity and suppressed the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway in an in vivo model. However, treatment with astaxanthin significantly inhibited brain damage, suppressed caspase‑3 activity and upregulated the PI3K/Akt pathway in the isoflurane‑induced rats. Furthermore, isoflurane suppressed cell growth, induced cell apoptosis, enhanced caspase‑3 activity and downregulated the PI3K/Akt pathway in organotypic hippocampal slice culture. Administration of astaxanthin significantly promoted cell growth, reduced cell apoptosis and caspase‑3 activity, and upregulated the PI3K/Akt pathway and isoflurane‑induced neuroapoptosis. The present study demonstrated that downregulation of the PI3K/Akt pathway reduced the effect of astaxanthin to protect against isoflurane‑induced neuroapoptosis in the in vitro model. The results of the current study suggested that the protective effect of astaxanthin reduces the isoflurane-induced neuroapoptosis via activation of the PI3K/Akt signaling pathway.

Fat suppression at three-dimensional T1-weighted MR imaging of the hands: Dixon method versus CHESS technique.

PubMed

Kirchgesner, T; Perlepe, V; Michoux, N; Larbi, A; Vande Berg, B

2018-01-01

To compare the effectiveness of fat suppression and the image quality of the Dixon method with those of the chemical shift-selective (CHESS) technique in hands of normal subjects at non-enhanced three-dimensional (3D) T1-weighted MR imaging. Both hands of 14 healthy volunteers were imaged with 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon, 3D FSPGR T1-weighted CHESS and 3D T1-weighted fast spin echo (FSE) CHESS sequences in a 1.5T MR scanner. Three radiologists scored the effectiveness of fat suppression in bone marrow (EFS BM ) and soft tissues (EFS ST ) in 20 joints per subject. One radiologist measured the signal-to-noise ratio (SNR) in 10 bones per subject. Statistical analysis used two-way ANOVA with random effects (P<0.0083), paired t-test (P<0.05) and observed agreement to assess differences in effectiveness of fat suppression, differences in SNR and interobserver agreement. EFS BM was statistically significantly higher for the 3D FSPGR T1-weighted Dixon than for the 3D FSPGR T1-weighted CHESS sequence and the 3D FSE T1-weighted CHESS sequence (P<0.0001). EFS ST was statistically significantly higher for the 3D FSPGR T1-weighted Dixon than for the 3D FSPGR T1-weighted CHESS sequence (P<0.0011) and for the 3D FSE T1-weighted CHESS sequence in the axial plane (P=0.0028). Mean SNR was statistically significantly higher for 3D FSPGR T1-weighted Dixon sequence than for 3D FSPGR T1-weighted CHESS and 3D FSE T1-weighted CHESS sequences (P<0.0001). The Dixon method yields more effective fat suppression and higher SNR than the CHESS technique at 3D T1-weighted MR imaging of the hands. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Immunomodulatory effect of Parsley (Petroselinum crispum) essential oil on immune cells: mitogen-activated splenocytes and peritoneal macrophages.

PubMed

Yousofi, Alireza; Daneshmandi, Saeed; Soleimani, Neda; Bagheri, Kambiz; Karimi, Mohammad Hossein

2012-04-01

Parsley (Petroselinum crispum) has been traditionally used for the treatment of allergy, autoimmune and chronic inflammatory disorders. The present study aims to investigate the suppressive effects of parsley essential oil on mouse splenocytes and macrophages cells. Parsley essential oil was harvested. It was treated on splenocytes and phytohemagglutinin (PHA) (5 μg/mL) and lipopolysaccharide (LPS) (10 μg/mL) activated splenocytes in different concentrations (0.01-100 μg/mL); then, proliferation was assayed by methyl tetrazolium (MTT) method. Treatment was also performed on the macrophages and LPS-stimulated macrophages (10 μg/ml) and the nitrite levels were measured using the diazotization method based on the Griess reaction and MTT assay for evaluation of the viability of the macrophages. Proliferation of splenocytes in all the treated groups was suppressed. In PHA-stimulated splenocytes, the suppression was seen in all the examined concentrations (0.01-100 μg/mL), while in the unstimulated and LPS-stimulated groups suppression was relatively dose dependent and in high concentration (10 and100 μg/mL).The viability of the macrophages in all groups was the same and in the unstimulated groups; NO suppression was significant in all the concentrations but in LPS-stimulated groups, it was significant in the three higher concentrations (1, 10, and100 μg/mL). The results of this study indicate that parsley essential oil may be able to suppress the cellular and humoral immune response. It can also suppress both NO production and the functions of macrophages as the main innate immune cells. These results may suggest that parsley essential oil is a proper suppressant for different applications.

Aging and the depth of binocular rivalry suppression.

PubMed

Norman, J Farley; Norman, Hideko F; Pattison, Kristina; Taylor, M Jett; Goforth, Katherine E

2007-09-01

Two experiments were designed to examine the effect of aging on the strength of binocular rivalry suppression. To produce rivalry, orthogonally oriented sine-wave luminance gratings were presented dichoptically. The observers were then required either to discriminate the spatial location of a probe spot presented to the dominant or suppressed eye's view or to detect the presence or absence of the probe. The observers in the younger and older age groups exhibited typical rivalry suppression for both tasks (i.e., the probe was more difficult to detect or discriminate when presented to the suppressed eye), but the magnitude of the suppression was significantly larger in the older observers. This increased suppression that accompanies aging can be explained by a reduction in the inhibition produced by the binocular matching circuitry of S. R. Lehky and R. Blake's (1991) model. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Hyperglycemia Suppresses Calcium Phosphate-Induced Aneurysm Formation Through Inhibition of Macrophage Activation.

PubMed

Tanaka, Teruyoshi; Takei, Yuichiro; Yamanouchi, Dai

2016-03-28

The aim of this study was to elucidate aspects of diabetes mellitus-induced suppression of aneurysm. We hypothesized that high glucose suppresses aneurysm by inhibiting macrophage activation via activation of Nr1h2 (also known as liver X receptor β), recently characterized as a glucose-sensing nuclear receptor. Calcium phosphate (CaPO4)-induced aneurysm formation was significantly suppressed in the arterial wall in type 1 and 2 diabetic mice. A murine macrophage cell line, RAW264.7, was treated with tumor necrosis factor α (TNF-α) plus CaPO4 and showed a significant increase in matrix metalloproteinase 9 (Mmp9) mRNA and secreted protein expression compared with TNF-α alone. Elevated Mmp9 expression was significantly suppressed by hyperglycemic conditions (15.5 mmol/L glucose) compared with normoglycemic conditions (5.5 mmol/L glucose) or normoglycemic conditions with high osmotic pressure (5.5 mmol/L glucose +10.0 mmol/L mannitol). Nr1h2 mRNA and protein expression were suppressed by treatment with TNF-α plus CaPO4 but were restored by hyperglycemic conditions. Activation of Nr1h2 by the antagonist GW3965 during stimulation with TNF-α plus CaPO4 mimicked hyperglycemic conditions and inhibited Mmp9 upregulation, whereas the deactivation of Nr1h2 by small interfering RNA (siRNA) under hyperglycemic conditions canceled the suppressive effect and restored Mmp9 expression induced by TNF-α plus CaPO4. Moreover, Nr1h2 activation with GW3965 significantly suppressed CaPO4-induced aneurysm in mice compared with vehicle-injected control mice. Our results show that hyperglycemia suppresses macrophage activation and aneurysmal degeneration through the activation of Nr1h2. Although further validation of the underlying pathway is necessary, targeting Nr1h2 is a potential therapeutic approach to treating aneurysm. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice.

PubMed

Kubo, Hisako; Hoshi, Masato; Mouri, Akihiro; Tashita, Chieko; Yamamoto, Yasuko; Nabeshima, Toshitaka; Saito, Kuniaki

2017-01-01

Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO -/- mice and KMO +/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80 + cells in KMO -/- mice was suppressed compared with those in KMO +/+ mice. KMO -/- mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO -/- mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Targeting acceptance in the management of food craving: The mediating roles of eating styles and thought suppression.

PubMed

Coffino, Jaime A; Heiss, Sydney; Hormes, Julia M

2018-04-01

Food craving is now widely considered to be a cognitively motivated state. Acceptance-based treatments are effective in reducing the adverse impact of food cravings on consumption, via a hypothesized decrease in experiential avoidance. The mechanisms that drive the success of acceptance-based management of craving remain to be empirically tested. This study examined the role of eating styles and thought suppression as mediators in the relationship between experiential avoidance and craving. Participants (n = 298, 51.5% female) completed the Food Craving Acceptance and Awareness Questionnaire (FAAQ), the Dutch Eating Behavior Questionnaire (DEBQ), the White Bear Suppression Inventory (WBSI; a measure of thought suppression), and the reduced version of the Food Craving Questionnaire- Trait (FCQ-T-r). Scores on the FAAQ were inversely associated with scores on the FCQ-T-r, DEBQ, and WBSI; FCQ-T-r scores were positively correlated with scores on the DEBQ and WBSI (all p < 0.001). The total indirect effect of acceptance on craving through the hypothesized mediators was significantly different from zero. Controlling for eating styles and thought suppression, acceptance remained a significant predictor of craving. Results thus provide initial evidence that eating styles and thought suppression mediate the relationship between food-specific experiential avoidance and food craving. Findings lay the foundation for future study of the proximal antecedents of food cravings and lend preliminary support for targeting thought suppression and eating styles in acceptance-based approaches to the management of craving. Copyright © 2018 Elsevier Ltd. All rights reserved.

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA.

PubMed

Stiles, David K; Zhang, Zhiming; Ge, Pei; Nelson, Brian; Grondin, Richard; Ai, Yi; Hardy, Peter; Nelson, Peter T; Guzaev, Andrei P; Butt, Mark T; Charisse, Klaus; Kosovrasti, Verbena; Tchangov, Lubomir; Meys, Michael; Maier, Martin; Nechev, Lubomir; Manoharan, Muthiah; Kaemmerer, William F; Gwost, Douglas; Stewart, Gregory R; Gash, Don M; Sah, Dinah W Y

2012-01-01

Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt). Silencing of Htt with RNA interference using direct CNS delivery in rodent models of Huntington's disease has been shown to reduce pathology and promote neuronal recovery. A key translational step for this approach is extension to the larger non-human primate brain, achieving sufficient distribution of small interfering RNA targeting Htt (siHtt) and levels of Htt suppression that may have therapeutic benefit. We evaluated the potential for convection enhanced delivery (CED) of siHtt to provide widespread and robust suppression of Htt in nonhuman primates. siHtt was infused continuously for 7 or 28 days into the nonhuman primate putamen to analyze effects of infusion rate and drug concentration on the volume of effective suppression. Distribution of radiolabeled siHtt and Htt suppression were quantified by autoradiography and PCR, respectively, in tissue punches. Histopathology was evaluated and Htt suppression was also visualized in animals treated for 28 days. Seven days of CED led to widespread distribution of siHtt and significant Htt silencing throughout the nonhuman primate striatum in an infusion rate and dose dependent manner. Htt suppression at therapeutic dose levels was well tolerated by the brain. A model developed from these results predicts that continuous CED of siHtt can achieve significant coverage of the striatum of Huntington's disease patients. These findings suggest that this approach may provide an important therapeutic strategy for treating Huntington's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme.

PubMed

Bain, J; Rachlis, V; Robert, E; Khait, Z

1980-04-01

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

ROCK activity affects IL-1-induced signaling possibly through MKK4 and p38 MAPK in Caco-2 cells.

PubMed

Banerjee, Sayantan; McGee, Dennis W

2016-09-01

Elevated levels of interleukin-1 (IL-1) accompany inflammatory bowel disease. IL-1-stimulated intestinal epithelial cells can secrete potent chemokines like CXCL8 to exacerbate inflammation. Previously, we found that inhibiting the Rho-associated kinase (ROCK) could inhibit IL-1- or TNF-α-induced CXCL8 secretion by the Caco-2 colonic epithelial cell line. This ROCK inhibition did not affect IκBα phosphorylation and degradation, but suppressed the phosphorylation of c-Jun N-terminal kinase (JNK). Therefore, ROCK must play an important role in epithelial cell CXCL8 responses through an effect on the JNK signaling pathway. Here, we extend these studies by showing that inhibiting ROCK suppressed the IL-1-induced phosphorylation of MKK4, a known activator of JNK, but not MKK7. Yet, ROCK inhibition had no significant effect on the IL-1-induced phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2. Inhibiting ROCK also suppressed the phosphorylation of p38 MAPK after IL-1 stimulation, but this inhibition had no significant effect on the stability of CXCL8 messenger RNA (mRNA) after IL-1 stimulation. These results suggest that ROCK may be important in IL-1-induced signaling through MKK4 to JNK and the activation of p38 MAPK. Finally, inhibiting ROCK in IL-1 and TNF-α co-stimulated Caco-2 cells also resulted in a significant suppression of CXCL8 secretion and mRNA levels suggesting that inhibiting ROCK may be a mechanism to inhibit the overall response of epithelial cells to both cytokines. These studies indicate a novel signaling event, which could provide a target for suppressing intestinal epithelial cells (IEC) chemokine responses involved in mucosal inflammation.

RNA interference suppression of MUC1 reduces the growth rate and metastatic phenotype of human pancreatic cancer cells.

PubMed

Tsutsumida, Hideaki; Swanson, Benjamin J; Singh, Pankaj K; Caffrey, Thomas C; Kitajima, Shinichi; Goto, Masamichi; Yonezawa, Suguru; Hollingsworth, Michael A

2006-05-15

MUC1 is a highly glycosylated, type I transmembrane protein expressed by normal ductal epithelial cells of the pancreas, breast, lung, and gastrointestinal tract, and overexpressed in many cases of adenocarcinoma. We down-regulated MUC1 expression by RNA interference and investigated the effects on malignant and metastatic potential of a human pancreatic cancer cell line, S2-013. MUC1-suppressed clones, S2-013.MTII.C1 and S2-013.MTII.C2, were established by targeting a sequence 3,151 bp from the initiation codon and characterized in vitro for proliferation, invasion, and adhesion. We evaluated the effects of MUC1 suppression in vivo on tumor growth and metastatic properties following implantation into the cecum or pancreas of athymic mice. MUC1-suppressed clones showed significantly decreased proliferation in vitro and in vivo. Global gene expression was evaluated by oligonucleotide microarray analysis. Surprisingly, genes predicted to increase doubling times (cyclin B1 and cyclin D3) were overexpressed in MUC1-suppressed clones. There were alterations in expression of several genes that may affect the malignant properties of pancreatic cancer. Adhesion of MUC1-suppressed cells in vitro to type IV collagen and fibronectin was slightly increased, and adhesion was slightly decreased to type I collagen and laminin. Results of implantation to cecum and pancreas showed significant reduction of metastasis to lymph nodes, lung, or peritoneal sites compared with S2-013.gfp-neo control cells. These results support the hypothesis that MUC1 contributes significantly to growth and metastasis, and that down-regulation of MUC1 protein expression decreases the metastatic potential of pancreatic adenocarcinoma.

Adenosine A(2B) receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells.

PubMed

Kaji, Wakako; Tanaka, Satomi; Tsukimoto, Mitsutoshi; Kojima, Shuji

2014-04-01

Regulatory T cells (Treg) play a role in suppression of immune response, including anti-tumor immunity. We have recently reported that treatment of naïve CD4 T cells with adenosine A(2B) receptor antagonist PSB603 under Treg-skewing conditions inhibits expression of Foxp3, a marker of differentiation to Treg, without blocking IL-2 production or CD25 expression, which are activation markers, in CD4 T cells. We hypothesized that PSB603 suppresses cancer growth and metastasis by inhibiting induction of Treg, thereby facilitating anti-tumor immunity. In this study, we first examined the effect of PSB603 on tumor growth in B16 melanoma-bearing C57BL/6 mice. Administration of PSB603 significantly suppressed the increase of tumor volume as well as the increase of Treg population in these mice. The populations of CD4 and CD8 T cells were higher and splenic lymphocyte-mediated cytotoxicity towards B16 melanoma was significantly increased in PSB603-treated mice. We confirmed that PSB603 did not reduce the viability of B16 melanoma cells in vitro. Moreover, we also examined the effect of PSB603 on tumor metastasis in pulmonary metastasis model mice intravenously injected with B16 melanoma cells. The metastasis was also suppressed in PSB603-treated mice, in which the population of Treg was significantly lower. Overall, our results suggest that A(2B) receptor antagonist PSB603 enhances anti-tumor immunity by inhibiting differentiation to Treg, resulting in a delay of tumor growth and a suppression of metastasis.

Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice.

PubMed

Hata, Ryu-Ichiro; Izukuri, Kazuhito; Kato, Yasumasa; Sasaki, Soichiro; Mukaida, Naofumi; Maehata, Yojiro; Miyamoto, Chihiro; Akasaka, Tetsu; Yang, Xiaoyan; Nagashima, Yoji; Takeda, Kazuyoshi; Kiyono, Tohru; Taniguchi, Masaru

2015-03-13

Cancer progression involves carcinogenesis, an increase in tumour size, and metastasis. Here, we investigated the effect of overexpressed CXC chemokine ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice was significantly lower compared with that for isogenic wild type C57BL/6 (Wt) mice. When tumour cells were injected into these mice, the size of the tumours that developed and the number of metastatic nodules in the lungs of the animals were always significantly lower in the Tg mice than in the Wt ones. Injection of anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis, suggesting that NK cell activity played an important role during CXCL14-mediated suppression of tumour growth and metastasis. The importance of NK cells on the metastasis was also supported when CXCL14 was expressed in B16 melanoma cells. Further, the survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention.

Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

PubMed

Andersen-Nissen, Erica; Chang, Joanne T; Thomas, Katherine K; Adams, Devin; Celum, Connie; Sanchez, Jorge; Coombs, Robert W; McElrath, M Juliana; Baeten, Jared M

2016-12-01

Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

The effects of spectral tuning of evening ambient light on melatonin suppression, alertness and sleep.

PubMed

Rahman, Shadab A; St Hilaire, Melissa A; Lockley, Steven W

2017-08-01

We compared the effects of bedroom-intensity light from a standard fluorescent and a blue- (i.e., short-wavelength) depleted LED source on melatonin suppression, alertness, and sleep. Sixteen healthy participants (8 females) completed a 4-day inpatient study. Participants were exposed to blue-depleted circadian-sensitive (C-LED) light and a standard fluorescent light (FL, 4100K) of equal illuminance (50lx) for 8h prior to a fixed bedtime on two separate days in a within-subject, randomized, cross-over design. Each light exposure day was preceded by a dim light (<3lx) control at the same time 24h earlier. Compared to the FL condition, control-adjusted melatonin suppression was significantly reduced. Although subjective sleepiness was not different between the two light conditions, auditory reaction times were significantly slower under C-LED conditions compared to FL 30min prior to bedtime. EEG-based correlates of alertness corroborated the reduced alertness under C-LED conditions as shown by significantly increased EEG spectral power in the delta-theta (0.5-8.0Hz) bands under C-LED as compared to FL exposure. There was no significant difference in total sleep time (TST), sleep efficiency (SE%), and slow-wave activity (SWA) between the two conditions. Unlike melatonin suppression and alertness, a significant order effect was observed on all three sleep variables, however. Individuals who received C-LED first and then FL had increased TST, SE% and SWA averaged across both nights compared to individuals who received FL first and then C-LED. These data show that the spectral characteristics of light can be fine-tuned to attenuate non-visual responses to light in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of interleukin-1 secretion by immunosuppressive drugs, alone and in combination.

PubMed

Reisman, L; Lin, W G; Martinelli, G P

1995-03-01

This study evaluates the ability of the immunosuppressive drugs dexamethasone, cyclosporine, FK506 and rapamycin, alone and in combination to suppress interleukin-1 beta (IL-1 beta) secretion in vitro by THP-1 cells when stimulated by lipopolysaccharide. All four drugs, when added to cell culture medium at therapeutic concentrations, significantly decrease secretion of the monokine to well below control levels. However, only dexamethasone completely suppresses IL-1 beta secretion in a dose-dependent fashion. Cyclosporine, FK506 and rapamycin only partially suppress secretion of IL-1 beta at concentrations within their therapeutic ranges and increasing concentrations of the drugs do not result in further suppression of secretion. Likewise, the combination of any two of these three drugs does not provide any additional suppressive effect. Dexamethasone, however, when added in increasing concentrations in combination with any of the other drugs, results in further suppression of IL-1 secretion in a dose-dependent fashion. These data suggest that cyclosporine, FK506 and rapamycin all share a common effect on the production of IL-1 beta, different from that of dexamethasone.

Impacts of suppression on emotional responses and performance outcomes: an experience-sampling study in younger and older workers.

PubMed

Yeung, Dannii Y; Fung, Helene H

2012-11-01

Past studies have demonstrated that older adults used less emotional suppression to regulate their emotions than did younger adults, but the effectiveness of using this emotion regulatory strategy on psychosocial well-being across age remains largely unexplored. The present study adopted an experience-sampling method to examine whether the impacts of momentary employment of emotional suppression on momentary positive and negative emotions and job performance would be different by age. Eighty-seven Chinese insurance workers, aged between 18 and 61 years, participated in a 5-day sampling study. Their affective responses at work, momentary task performance, and sales productivity were recorded. Results showed that older workers' greater use of suppression at work was associated with lower intensity of negative emotions, whereas such association was not found among younger workers. Moreover, greater use of suppression over the sampling period was significantly predictive of sales productivity of older workers, but such a positive association was not shown in younger workers. These findings reveal that the use of suppression at work may be more effective for older workers than for younger workers.

Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin.

PubMed

Simcha, I; Geiger, B; Yehuda-Levenberg, S; Salomon, D; Ben-Ze'ev, A

1996-04-01

Plakoglobin is a major component of the submembranal plaque of adherens junctions and desmosomes in mammalian cells. It is closely related to the Drosophila segment polarity gene armadillo which has a role in the transduction of transmembrane signals that regulate cell fate. Like its close homologue beta-catenin, plakoglobin can associate with the product of the tumor suppressor gene APC that is linked to human colon cancer. We have studied the effect of plakoglobin overexpression, and the cooperation between plakoglobin and N-cadherin, on the morphology and tumorigenic ability of cells either lacking, or expressing cadherin and alpha- and beta-catenin. Overexpression of plakoglobin in SV40-transformed 3T3 (SVT2) cells suppressed the tumorigenicity of the cells in syngeneic mice. Transfection with N-cadherin conferred an epithelial phenotype on the cell culture, but had no significant effect on the tumorigenicity of the cells. Cotransfection of plakoglobin and N-cadherin into SVT2 cells, however, was considerably more effective in tumor suppression than plakoglobin overexpression alone. Finally, transfection of plakoglobin into a human renal carcinoma cell line that expresses neither cadherins nor plakoglobin, or alpha-and beta-catenin, resulted in a dose-dependent suppression of tumor formation by these cells in nude mice. Plakoglobin, in these cells, did not exhibit junctional localization and was diffusely distributed in the cytoplasm, with a significant amount of the protein also localized in the nucleus. The results suggest that plakoglobin can efficiently suppress the tumorigenicity of cells in the presence of, or independently of the cadherin-catenin complex.

The Regulation of Induced Depression during a Frustrating Situation: Benefits of Expressive Suppression in Chinese Individuals

PubMed Central

Ding, Nanxiang; Yang, Jiemin

2014-01-01

Background Studies from European-American cultures consistently reported that expressive suppression was associated with worse emotional consequence (e.g. depression) in comparison with acceptance. However, this conclusion may not apply to Chinese, as suppressing emotional displays to maintain relational harmony is culturally valued in East Asian countries. Thus, the present study examined the effects of suppression and acceptance on the depressive mood induced by a frustrating task in a Chinese sample. Method Sixty-four subjects were randomly assigned to one of three instructions: suppression, acceptance or no-regulation during a frustrating arithmetic task. The experience of depressive emotion and skin conductance response (SCR) were recorded during pre-frustration baseline, frustration induction and post-frustration recovery phases, respectively. Results Compared with the control and acceptance instructions, suppression instruction was associated with decreased depressive experiences and smaller SCR activity during frustration. There were no significant differences between acceptance and control groups in both subjective depression and SCR activity during frustration. Moreover, the suppression group showed a better emotional recovery after the frustrating task, in comparison with the acceptance and control groups. Correlation analyses verified that SCR reactivity was a reliable index of experienced depression during the frustration. Conclusions Expressive suppression is effective in reducing depressive experiences and depression-related physiological activity (SCR) when Chinese people are involved. By contrast, the acceptance of depressive emotion in Chinese people does not produce a similar regulation effect. These findings suggest that cultural context should be considered in understanding the emotional consequences of suppression and acceptance strategies. PMID:24827934

Effects of isoflurane, sevoflurane and methoxyflurane on the electroencephalogram of the chicken.

PubMed

McIlhone, Amanda E; Beausoleil, Ngaio J; Johnson, Craig B; Mellor, David J

2014-11-01

Anaesthetics have differing effects on mammalian electroencephalogram (EEG) but little is known about the effects on avian EEG. This study explored how inhalant anaesthetics affect chicken EEG. Experimental study. Twelve female Hyline Brown chickens aged 6-11 weeks. Each chicken was anaesthetized with isoflurane, sevoflurane, and methoxyflurane. For each, anaesthesia was adjusted to 1, 1.5 and 2 times Minimum Anaesthetic Concentration (MAC). Total Power (Ptot), Median Frequency (F50), Spectral Edge Frequency (F95) and Burst Suppression Ratio (BSR) were calculated at each volume concentration. BSR data were analyzed using doubly repeated measures anova. Neither isoflurane nor sevoflurane could be included in analysis of F50, F95 and Ptot because of extensive burst suppression; Methoxyflurane data were analyzed using RM anova. There was a significant interaction between anaesthetic and concentration on BSR [F(4,22) = 10.65, p < 0.0001]. For both isoflurane and sevoflurane, BSR increased with concentration. Isoflurane caused less suppression than sevoflurane at 1.5 MAC and at final 1 MAC while methoxyflurane caused virtually no burst suppression. Methoxyflurane concentration had a significant effect on F50 [F(2,20) = 3.83, p = 0.04], F95 [F(2,20) = 4.03, p = 0.03] and Ptot [F(2,20) = 5.22, p = 0.02]. Decreasing methoxyflurane from 2 to 1 MAC increased F50 and F95. Ptot increased when concentration decreased from 1.5 to 1 MAC and tended to be higher at 1 MAC than at 2 MAC. Isoflurane and sevoflurane suppressed chicken EEG in a dose-dependent manner. Higher concentrations of methoxyflurane caused an increasing degree of synchronization of EEG. Isoflurane and sevoflurane suppressed EEG activity to a greater extent than did methoxyflurane at equivalent MAC multiples. Isoflurane caused less suppression than sevoflurane at intermediate concentrations. These results indicate the similarity between avian and mammalian EEG responses to inhalant anaesthetics and reinforce the difference between MAC and anaesthetic effects on brain activity in birds. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation.

PubMed

Ikedo, Taichi; Minami, Manabu; Kataoka, Hiroharu; Hayashi, Kosuke; Nagata, Manabu; Fujikawa, Risako; Higuchi, Sei; Yasui, Mika; Aoki, Tomohiro; Fukuda, Miyuki; Yokode, Masayuki; Miyamoto, Susumu

2017-06-19

Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide-treated RAW264.7 macrophages. In the anagliptin-treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP-1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide-stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP-1, and IL-6 (interleukin 6) independent of GLP-1 (glucagon-like peptide 1), the key mediator in the antidiabetic effects of DPP-4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal-regulated kinase 5), which mediates the anti-inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP-1 and IL-6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. A DPP-4 inhibitor, anagliptin, prevents the growth of IAs via its anti-inflammatory effects on macrophages. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Ma, Shuai

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressionsmore » of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.« less

Dreaming and personality: Wake-dream continuity, thought suppression, and the Big Five Inventory.

PubMed

Malinowski, Josie E

2015-12-15

Studies have found relationships between dream content and personality traits, but there are still many traits that have been underexplored or have had questionable conclusions drawn about them. Experimental work has found a 'rebound' effect in dreams when thoughts are suppressed prior to sleep, but the effect of trait thought suppression on dream content has not yet been researched. In the present study participants (N=106) reported their Most Recent Dream, answered questions about the content of the dream, and completed questionnaires measuring trait thought suppression and the 'Big Five' personality traits. Of these, 83 were suitably recent for analyses. A significant positive correlation was found between trait thought suppression and participants' ratings of dreaming of waking-life emotions, and high suppressors reported dreaming more of their waking-life emotions than low suppressors did. The results may lend support to the compensation theory of dreams, and/or the ironic process theory of mental control. Copyright © 2015 Elsevier Inc. All rights reserved.

Thought suppression predicts task switching deficits in patients with frontal lobe epilepsy.

PubMed

Gul, Amara; Ahmad, Hira

2015-04-01

To examine the relationship between task switching and thought suppression in connection with frontal lobe epilepsy (FLE). This experimental study included 30 patients with FLE admitted to the Services and Jinnah Hospital, Lahore, Pakistan between February and November 2013, and 30 healthy individuals from the local community. Participants performed a task switching experiment where they switched between emotion and age categorizations among faces. In addition, they completed a thought suppression questionnaire. There were 3 important results: (i) Patients with FLE showed weaker task switching abilities than healthy individuals. This result is attributed toward executive dysfunctions in patients with FLE. (ii) Contrary to the control group, patients with FLE showed larger switch cost for the age than the emotion categorization. This result can be seen in the context of social cognition deficits and poor inhibitory control in patients with FLE. In addition, larger switch costs reflected a binding effect with facial emotion as compared to age. The integration might represent emotion as an intrusive facial dimension that interrupted task switching performance. (iii) Patients with FLE had more recurrent suppression of thoughts than controls. Thought suppression was a significant predictor for switch costs. High scores on thought suppression were correlated with task switching deficits. The results suggest that thought suppression causes significant cognitive decline.

Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study.

PubMed

Li, Jinrong; Hess, Robert F; Chan, Lily Y L; Deng, Daming; Yang, Xiao; Chen, Xiang; Yu, Minbin; Thompson, Benjamin

2013-08-01

The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. Case-control study (aims 1-3) and cohort study (aim 4). Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. Interocular suppression assessed using dichoptic motion coherence thresholds. Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression using the dichoptic motion coherence threshold technique may provide useful information for the management and treatment of anisometropic amblyopia. Proprietary or commercial disclosure may be found after the references. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination.

PubMed

Zhou, Jieru; Cai, Wei; Jin, Min; Xu, Jingwei; Wang, Yanan; Xiao, Yichuan; Hao, Li; Wang, Bei; Zhang, Yanyun; Han, Jie; Huang, Rui

2015-09-02

Microglia are intrinsic immune cells in the central nervous system (CNS). The under controlled microglia activation plays important roles in inflammatory demyelination diseases, such as multiple sclerosis (MS). However, the means to modulate microglia activation as a therapeutic modality and the underlying mechanisms remain elusive. Here we show that administration of 18β-glycyrrhetinic acid (GRA), by using both preventive and therapeutic treatment protocols, significantly suppresses disease severity of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The treatment effect of GRA on EAE is attributed to its regulatory effect on microglia. GRA-modulated microglia significantly decreased pro-inflammatory profile in the CNS through suppression of MAPK signal pathway. The ameliorated CNS pro-inflammatory profile prevented the recruitment of encephalitogenic T cells into the CNS, which alleviated inflammation-induced demyelination. In addition, GRA treatment promoted remyelination in the CNS of EAE mice. The induced remyelination can be mediated by the overcome of inflammation-induced blockade of brain-derived neurotrophic factor expression in microglia, as well as enhancing oligodendrocyte precursor cell proliferation. Collectively, our results demonstrate that GRA-modulated microglia suppresses EAE through inhibiting microglia activation-mediated CNS inflammation, and promoting neuroprotective effect of microglia, which represents a potential therapeutic strategy for MS and maybe other neuroinflammatory diseases associated with microglia activation.

Intracochlear electrical stimulation suppresses apoptotic signaling in rat spiral ganglion neurons after deafening in vivo.

PubMed

Kopelovich, Jonathan C; Cagaanan, Alain P; Miller, Charles A; Abbas, Paul J; Green, Steven H

2013-11-01

To establish the intracellular consequences of electrical stimulation to spiral ganglion neurons after deafferentation. Here we use a rat model to determine the effect of both low and high pulse rate acute electrical stimulation on activation of the proapoptotic transcription factor Jun in deafferented spiral ganglion neurons in vivo. Experimental animal study. Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology. A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32, n = 24) or P60 (n = 22) for 4 hours of stimulation (monopolar, biphasic pulses, amplitude twice electrically evoked auditory brainstem response [eABR] threshold) at either 100 or 5000 Hz. Jun phosphorylation was assayed by immunofluorescence to quantitatively assess the effect of electrical stimulation on proapoptotic signaling. Jun phosphorylation was reliably suppressed by 100 Hz stimuli in deafened cochleae of P32 but not P60 rats. This effect was not significant in the basal cochlear turns. Stimulation frequency may be consequential: 100 Hz was significantly more effective than was 5 kHz stimulation in suppressing phospho-Jun. Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only 4 hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.

Effective Suppression of Methane Emission by 2-Bromoethanesulfonate during Rice Cultivation.

PubMed

Waghmode, Tatoba R; Haque, Md Mozammel; Kim, Sang Yoon; Kim, Pil Joo

2015-01-01

2-bromoethanesulfonate (BES) is a structural analogue of coenzyme M (Co-M) and potent inhibitor of methanogenesis. Several studies confirmed, BES can inhibit CH4 prodcution in rice soil, but the suppressing effectiveness of BES application on CH4 emission under rice cultivation has not been studied. In this pot experiment, different levels of BES (0, 20, 40 and 80 mg kg-1) were applied to study its effect on CH4 emission and plant growth during rice cultivation. Application of BES effectively suppressed CH4 emission when compared with control soil during rice cultivation. The CH4 emission rates were significantly (P<0.001) decreased by BES application possibly due to significant (P<0.001) reduction of methnaogenic biomarkers like Co-M concentration and mcrA gene copy number (i.e. methanogenic abunadance). BES significantly (P<0.001) reduced methanogen activity, while it did not affect soil dehydrogenase activity during rice cultivation. A rice plant growth and yield parameters were not affected by BES application. The maximum CH4 reduction (49% reduction over control) was found at 80 mg kg-1 BES application during rice cultivation. It is, therefore, concluded that BES could be a suitable soil amendment for reducing CH4 emission without affecting rice plant growth and productivity during rice cultivation.

Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer

PubMed Central

Gai, Wen-Tao; Yu, Da-Peng; Wang, Xin-Sheng; Wang, Pei-Tao

2016-01-01

Ursolic acid is a type of pentacyclic triterpene compound with multiple pharmacological activities including cancer resistance, protection from liver injury, antisepsis, anti-inflammation and antiviral activity. The present study aimed to investigate the anticancer effect of ursolic acid. Ursolic acid activates cell apoptosis and its pro-apoptotic mechanism remains to be fully elucidated. Cell Counting kit-8 assays, flow cytometric analysis and analysis of caspase-3 and caspase-9 activity were used to estimate the anticancer effect of ursolic acid on DU145 prostate cancer cells. The protein expression of cytochrome c, rho-associated protein kinase (ROCK), phosphatase and tensin homolog (PTEN) and cofilin-1 were examined using western blot analysis. In the present study, ursolic acid significantly suppressed cell growth and induced apoptosis, as well as increasing caspase-3 and caspase-9 activities of DU145 cells. Furthermore, cytoplasmic and mitochondrial cytochrome c protein expression was significantly activated and suppressed, respectively, by ursolic acid. Ursolic acid significantly suppressed the ROCK/PTEN signaling pathway and inhibited cofilin-1 protein expression in DU145 cells. The results of the present study indicate that the anticancer effect of ursolic acid activates cell apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. PMID:27698874

Polyethylene mulch modifies greenhouse microclimate and reduces infection of phytophthora infestans in tomato and Pseudoperonospora cubensis in cucumber.

PubMed

Shtienberg, D; Elad, Y; Bornstein, M; Ziv, G; Grava, A; Cohen, S

2010-01-01

The individual and joint effects of covering the soil with polyethylene mulch before planting and fungicides commonly used by organic growers on tomato late blight (caused by Phytophthora infestans) were studied in three experiments conducted from 2002 to 2005. Application of fungicides resulted in inconsistent and insufficient late blight suppression (control efficacy +/- standard error of 34.5 +/- 14.3%) but the polyethylene mulch resulted in consistent, effective, and highly significant suppression (control efficacy of 83.6 +/- 5.5%) of the disease. The combined effect of the two measures was additive. In a second set of three experiments carried out between 2004 and 2006, it was found that the type of polyethylene mulch used (bicolor aluminized, clear, or black) did not affect the efficacy of late blight suppression (control efficacy of 60.1 to 95.8%) and the differences in the effects among the different polyethylene mulches used were insignificant. Next, the ability of the mulch to suppress cucumber downy mildew (caused by Pseudoperonospora cubensis) was studied in four experiments carried out between 2006 and 2008. The mulch effectively suppressed cucumber downy mildew but the effect was less substantial (control efficacy of 34.9 +/- 4.8%) than that achieved for tomato late blight. The disease-suppressing effect of mulch appeared to come from a reduction in leaf wetness duration, because mulching led to reductions in both the frequency of nights when dew formed and the number of dew hours per night when it formed. Mulching also reduced relative humidity in the canopy, which may have reduced sporulation.

Effects of combined radiofrequency field exposure on amyloid-beta–induced cytotoxicity in HT22 mouse hippocampal neurones

PubMed Central

Lee, Jong-Sun; Kim, Jeong-Yub; Kim, Hee-Jin; Kim, Jeong Cheol; Lee, Jae-Seon; Kim, Nam; Park, Myung-Jin

2016-01-01

Alzheimer's disease (AD) is the most common progressive and irreversible neurodegenerative disease and it is caused by neuronal death in the brain. Recent studies have shown that non-ionizing radiofrequency (RF) radiation has some beneficial cognitive effects in animal models of AD. In this study, we examined the effect of combined RF radiation on amyloid-beta (Aβ)–induced cytotoxicity in HT22 rat hippocampal neurons. Treatment with Aβ suppressed HT22 cell proliferation in a concentration-dependent manner. RF exposure did not affect cell proliferation, and also had a marginal effect on Aβ-induced suppression of growth in HT22 cells. Cell cycle analysis showed that Aβ decreased the G1 fraction and increased the subG1 fraction, indicating increased apoptosis. Accordingly, Aβ increased the annexin V/propidium iodide (PI)–positive cell fraction and the degradation of poly (ADP ribose) polymerase and caspase-3 in HT22 cells. However, RF alone and the combination of Aβ and RF did not affect these events significantly. Aβ increased reactive oxygen species (ROS) generation, thereby suppressing cell proliferation. This was abrogated by N-acetylcysteine (NAC) treatment, indicating that Aβ-induced ROS generation is the main cause of suppression of proliferation. NAC also restored Aβ-induced annexin V/PI–positive cell populations. However, RF did not have a significant impact on these events. Finally, Aβ stimulated the ataxia telangiectasia and Rad3-related protein/checkpoint kinase 1 DNA single-strand breakage pathway, and enhanced beta-site amyloid precursor protein expression; RF had no effect on them. Taken together, our results demonstrate that RF exposure did not significantly affect the Aβ-induced decrease of cell proliferation, increase of ROS production, or induction of cell death in these cells. PMID:27325640

Research on improvement of power quality of Micro - grid based on SVG pulse load

NASA Astrophysics Data System (ADS)

Lv, Chuang; Xie, Pu

2017-05-01

Pulse load will make the micro-grid public bus power to produce a high peak pulse due to its cyclical pulsation characteristics,, and make the micro-grid voltage fluctuations, frequency fluctuations, voltage and current distortion, power factor reduction and other adverse effects. In order to suppress the adverse effects of the pulse load on the microgrid and improve the power quality of the microgrid, this paper established the SVG simulation model in Matlab / Simulink environment, the superiority of SVG is verified by comparing the improvement of power quality before and after adding the SVG to microgrid system. The results show that the SVG model can suppress the adverse effects effectively of the pulse load on the microgrid, which is of great value and significance to the reactive power compensation and harmonic suppression of the microgrid.

Suppression (but Not Reappraisal) Impairs Subsequent Error Detection: An ERP Study of Emotion Regulation's Resource-Depleting Effect

PubMed Central

Wang, Yan; Yang, Lixia; Wang, Yan

2014-01-01

Past event-related potentials (ERPs) research shows that, after exerting effortful emotion inhibition, the neural correlates of performance monitoring (e.g. error-related negativity) were weakened. An undetermined issue is whether all forms of emotion regulation uniformly impair later performance monitoring. The present study compared the cognitive consequences of two emotion regulation strategies, namely suppression and reappraisal. Participants were instructed to suppress their emotions while watching a sad movie, or to adopt a neutral and objective attitude toward the movie, or to just watch the movie carefully. Then after a mood scale, all participants completed an ostensibly unrelated Stroop task, during which ERPs (i.e. error-related negativity (ERN), post-error positivity (Pe) and N450) were obtained. Reappraisal group successfully decreased their sad emotion, relative to the other two groups. Compared with participants in the control group and the reappraisal group, those who suppressed their emotions during the sad movie showed reduced ERN after error commission. Participants in the suppression group also made more errors in incongruent Stroop trials than the other two groups. There were no significant main effects or interactions of group for reaction time, Pe and N450. Results suggest that reappraisal is both more effective and less resource-depleting than suppression. PMID:24777113

Suppression (but not reappraisal) impairs subsequent error detection: an ERP study of emotion regulation's resource-depleting effect.

PubMed

Wang, Yan; Yang, Lixia; Wang, Yan

2014-01-01

Past event-related potentials (ERPs) research shows that, after exerting effortful emotion inhibition, the neural correlates of performance monitoring (e.g. error-related negativity) were weakened. An undetermined issue is whether all forms of emotion regulation uniformly impair later performance monitoring. The present study compared the cognitive consequences of two emotion regulation strategies, namely suppression and reappraisal. Participants were instructed to suppress their emotions while watching a sad movie, or to adopt a neutral and objective attitude toward the movie, or to just watch the movie carefully. Then after a mood scale, all participants completed an ostensibly unrelated Stroop task, during which ERPs (i.e. error-related negativity (ERN), post-error positivity (Pe) and N450) were obtained. Reappraisal group successfully decreased their sad emotion, relative to the other two groups. Compared with participants in the control group and the reappraisal group, those who suppressed their emotions during the sad movie showed reduced ERN after error commission. Participants in the suppression group also made more errors in incongruent Stroop trials than the other two groups. There were no significant main effects or interactions of group for reaction time, Pe and N450. Results suggest that reappraisal is both more effective and less resource-depleting than suppression.

Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

PubMed

Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

2017-01-01

The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

Regional Extent of Peripheral Suppression in Amblyopia.

PubMed

Babu, Raiju J; Clavagnier, Simon; Bobier, William R; Thompson, Benjamin; Hess, Robert F

2017-04-01

Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

Improved optical properties of InAs quantum dots for intermediate band solar cells by suppression of misfit strain relaxation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, H.; School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, Arizona 85287-6106; Prioli, R.

The properties of InAs quantum dots (QDs) have been studied for application in intermediate band solar cells. It is found that suppression of plastic relaxation in the QDs has a significant effect on the optoelectronic properties. Partial capping plus annealing is shown to be effective in controlling the height of the QDs and in suppressing plastic relaxation. A force balancing model is used to explain the relationship between plastic relaxation and QD height. A strong luminescence has been observed from strained QDs, indicating the presence of localized states in the desired energy range. No luminescence has been observed from plasticallymore » relaxed QDs.« less

Transient Suppression of TGFβ Receptor Signaling Facilitates Human Islet Transplantation

PubMed Central

Fischbach, Shane; Song, Zewen; Gaffar, Iljana; Zimmerman, Ray; Wiersch, John; Prasadan, Krishna; Shiota, Chiyo; Guo, Ping; Ramachandran, Sabarinathan; Witkowski, Piotr

2016-01-01

Although islet transplantation is an effective treatment for severe diabetes, its broad application is greatly limited due to a shortage of donor islets. Suppression of TGFβ receptor signaling in β-cells has been shown to increase β-cell proliferation in mice, but has not been rigorously examined in humans. Here, treatment of human islets with a TGFβ receptor I inhibitor, SB-431542 (SB), significantly improved C-peptide secretion by β-cells, and significantly increased β-cell number by increasing β-cell proliferation. In addition, SB increased cell-cycle activators and decreased cell-cycle suppressors in human β-cells. Transplantation of SB-treated human islets into diabetic immune-deficient mice resulted in significant improvement in blood glucose control, significantly higher serum and graft insulin content, and significantly greater increases in β-cell proliferation in the graft, compared with controls. Thus, our data suggest that transient suppression of TGFβ receptor signaling may improve the outcome of human islet transplantation, seemingly through increasing β-cell number and function. PMID:26872091

Suppression of miR-19b enhanced the cytotoxic effects of mTOR inhibitors in human neuroblastoma cells.

PubMed

Chen, Yun; Tsai, Ya-Hui; Tseng, Bor-Jiun; Pan, Hsin-Yen; Tseng, Sheng-Hong

2016-11-01

Mammalian target of rapamycin (mTOR) inhibitors exert significant antitumor effects on several cancer cell types. In this study, we investigated the effects of mTOR inhibitors, in particular the regulation of the microRNA, in neuroblastoma cells. AZD8055 (a new mTOR inhibitor)- or rapamycin-induced cytotoxic effects on neuroblastoma cells were studied. Western blotting was used to investigate the expression of various proteins in the mTOR pathway. MicroRNA precursors and antagomirs were transfected into cells to manipulate the expression of target microRNA. AZD8055 exerted stronger cytotoxic effects than rapamycin in neuroblastoma cells (p<0.03). In addition, AZD8055 suppressed the mTOR pathway and increased the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in the neuroblastoma cells. AZD8055 significantly decreased miR-19b expression (p<0.005); in contrast, rapamycin increased miR-19b expression (p<0.05). Transfection of miR-19b antagomir into the neuroblastoma cells mimicked the effects of AZD8055 treatment, whereas miR-19b overexpression reversed the effects of AZD8055. Combination of miR-19b knockdown and rapamycin treatment significantly improved the sensitivity of neuroblastoma cells to rapamycin (p<0.02). Suppression of miR-19b may enhance the cytotoxic effects of mTOR inhibitors in neuroblastoma cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Deficient Suppression of Default Mode Regions during Working Memory in Individuals with Early Psychosis and at Clinical High-Risk for Psychosis

PubMed Central

Fryer, Susanna L.; Woods, Scott W.; Kiehl, Kent A.; Calhoun, Vince D.; Pearlson, Godfrey D.; Roach, Brian J.; Ford, Judith M.; Srihari, Vinod H.; McGlashan, Thomas H.; Mathalon, Daniel H.

2013-01-01

Background: The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) performance in youth at clinical high-risk (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls (HC). We hypothesized that the DMN would show load-dependent suppression during WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate pattern. Methods: fMRI data were collected from CHR (n = 32), ESZ (n = 22), and HC (n = 54) participants, ages 12–30. DMN regions were defined via seed-based connectivity analysis of resting-state fMRI data from an independent HC sample. Load-dependent deactivations of these DMN regions in response to WM probes were interrogated. Results: Healthy controls showed linear load-dependent increases in DMN deactivation. Significant Group-by-Load interactions were observed in DMN regions including medial prefrontal and lateral posterior parietal cortices. Group-by-Load effects in posterior DMN nodes resulted from less suppression at higher WM loads in ESZ relative to HC, with CHR differing from neither group. In medial prefrontal cortex, suppression of activity at higher WM loads was significantly diminished in both CHR and ESZ groups, relative to HC. In addition, investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that ESZ activated right DLPFC significantly more than HC, with CHR differing from neither group. Conclusion: While HC showed WM load-dependent modulation of DMN suppression, CHR individuals had deficient higher-load DMN suppression that was similar to, but less pronounced than, the distributed suppression deficits evident in ESZ patients. These results suggest that DMN dysregulation associated with schizophrenia predates psychosis onset. PMID:24032017

Deficient Suppression of Default Mode Regions during Working Memory in Individuals with Early Psychosis and at Clinical High-Risk for Psychosis.

PubMed

Fryer, Susanna L; Woods, Scott W; Kiehl, Kent A; Calhoun, Vince D; Pearlson, Godfrey D; Roach, Brian J; Ford, Judith M; Srihari, Vinod H; McGlashan, Thomas H; Mathalon, Daniel H

2013-01-01

The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) performance in youth at clinical high-risk (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls (HC). We hypothesized that the DMN would show load-dependent suppression during WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate pattern. fMRI data were collected from CHR (n = 32), ESZ (n = 22), and HC (n = 54) participants, ages 12-30. DMN regions were defined via seed-based connectivity analysis of resting-state fMRI data from an independent HC sample. Load-dependent deactivations of these DMN regions in response to WM probes were interrogated. Healthy controls showed linear load-dependent increases in DMN deactivation. Significant Group-by-Load interactions were observed in DMN regions including medial prefrontal and lateral posterior parietal cortices. Group-by-Load effects in posterior DMN nodes resulted from less suppression at higher WM loads in ESZ relative to HC, with CHR differing from neither group. In medial prefrontal cortex, suppression of activity at higher WM loads was significantly diminished in both CHR and ESZ groups, relative to HC. In addition, investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that ESZ activated right DLPFC significantly more than HC, with CHR differing from neither group. While HC showed WM load-dependent modulation of DMN suppression, CHR individuals had deficient higher-load DMN suppression that was similar to, but less pronounced than, the distributed suppression deficits evident in ESZ patients. These results suggest that DMN dysregulation associated with schizophrenia predates psychosis onset.

Electron attachment to molecules in a cluster environment: suppression and enhancement effects

NASA Astrophysics Data System (ADS)

Fabrikant, Ilya I.

2018-05-01

Cluster environments can strongly influence dissociative electron attachment (DEA) processes. These effects are important in many applications, particularly for surface chemistry, radiation damage, and atmospheric physics. We review several mechanisms for DEA suppression and enhancement due to cluster environments, particularly due to microhydration. Long-range electron-molecule and electron-cluster interactions play often a significant role in these effects and can be analysed by using theoretical models. Nevertheless many observations remain unexplained due to complexity of the physics and chemistry of interaction of DEA fragments with the cluster environment.

A sample preparation method for recovering suppressed analyte ions in MALDI TOF MS.

PubMed

Lou, Xianwen; de Waal, Bas F M; Milroy, Lech-Gustav; van Dongen, Joost L J

2015-05-01

In matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS), analyte signals can be substantially suppressed by other compounds in the sample. In this technical note, we describe a modified thin-layer sample preparation method that significantly reduces the analyte suppression effect (ASE). In our method, analytes are deposited on top of the surface of matrix preloaded on the MALDI plate. To prevent embedding of analyte into the matrix crystals, the sample solution were prepared without matrix and efforts were taken not to re-dissolve the preloaded matrix. The results with model mixtures of peptides, synthetic polymers and lipids show that detection of analyte ions, which were completely suppressed using the conventional dried-droplet method, could be effectively recovered by using our method. Our findings suggest that the incorporation of analytes in the matrix crystals has an important contributory effect on ASE. By reducing ASE, our method should be useful for the direct MALDI MS analysis of multicomponent mixtures. Copyright © 2015 John Wiley & Sons, Ltd.

Serotonin signaling is crucial in the induction of PUVA-induced systemic suppression of delayed type hypersensitivity but not local apoptosis or inflammation of the skin

PubMed Central

Wolf, Peter; Byrne, Scott N.; Limon-Flores, Alberto Y.; Hoefler, Gerald; Ullrich, Stephen E.

2016-01-01

Psoralen and UVA (PUVA) has immunosuppressive and proapoptotic effects, which are thought to be responsible alone or in combination for its therapeutic efficacy. However, the molecular mechanism by which PUVA mediates its effects are not well understood. Activation of the serotonin (5-hydroxytryptamine, 5-HT) pathway has been suggested to be involved in the modulation of T cell responses and found to mediate UVB-induced immune suppression. In particular, the activation of the 5-HT2A receptor has been proposed as one mechanism responsible for UV-induced immune suppression. We therefore hypothesized that 5-HT may play a role in PUVA-induced effects. The model of systemic suppression of delayed-type hypersensitivity (DTH) to Candida albicans was used to study immune function after exposure of C3H and KITW-Sh/W-Sh mice to a minimal inflammatory dose of topical PUVA. The intraperitoneal injection of the 5-HT2 receptor antagonist ketanserin or cyproheptadine or an anti-5-HT antibody immediately before PUVA exposure entirely abrogated suppression of DTH but had no significant effect on inflammation, as measured by swelling and cellular infiltration of the skin, and apoptosis as determined by the number of sunburn cells in C3H mice. Importantly, the systemic injection of 5-HT recapitulated PUVA immune suppression of DTH but did not induce inflammation or apoptosis in the skin. KITW-Sh/W-Sh mice (exhibiting myelopoietic abnormalities, including lack of 5-HT-containing mast cells) were resistant to PUVA-induced suppression of DTH but not local skin swelling. Thus, this points towards a crucial role of 5-HT signaling in PUVA-induced immune suppression but not inflammation or apoptosis in situ in the skin. PMID:26914366

Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation.

PubMed

Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

2018-01-01

We examined the role of verbal mediation in planning performance of English-Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children's planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation.

Planning Abilities in Bilingual and Monolingual Children: Role of Verbal Mediation

PubMed Central

Gangopadhyay, Ishanti; McDonald, Margarethe; Ellis Weismer, Susan; Kaushanskaya, Margarita

2018-01-01

We examined the role of verbal mediation in planning performance of English–Spanish-speaking bilingual children and monolingual English-speaking children, between the ages of 9 and 12 years. To measure planning, children were administered the Tower of London (ToL) task. In a dual-task paradigm, children completed ToL problems under three conditions: with no secondary task (baseline), with articulatory suppression, and with non-verbal motor suppression. Analyses revealed generally shorter planning times for bilinguals than monolinguals but both groups performed similarly on number of moves and execution times. Additionally, bilingual children were more efficient at planning throughout the duration of the task while monolingual children showed significant gains with more practice. Children’s planning times under articulatory suppression were significantly shorter than under motor suppression as well as the baseline condition, and there was no difference in planning times between monolingual and bilingual children during articulatory suppression. These results demonstrate that bilingualism influences performance on a complex EF measure like planning, and that these effects are not related to verbal mediation. PMID:29593620

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malpass, Gloria E., E-mail: gloria.malpass@gmail.com; Arimilli, Subhashini, E-mail: sarimill@wakehealth.edu; Prasad, G.L., E-mail: prasadg@rjrt.com

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5more » h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes.« less

Conflicting short and long-term management goals: Fire effects in endangered golden-cheeked warbler (Setophaga chrysoparia) habitat

Treesearch

Christina M. Andruk; Norma L. Fowler

2015-01-01

Decades of fire suppression have significantly altered the vegetation structure and composition of savannas, woodlands, and forests. The presence of endangered species and other species of conservation concern in these fire-suppressed systems makes re-introducing fire more challenging. In oak-juniper woodlands of central Texas, we are presented with the challenge of re...

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

Impressive Suppression of Colon Cancer Growth by Triple Combination SN38/EF24/Melatonin: "Oncogenic" Versus "Onco-Suppressive" Reactive Oxygen Species.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Shibata, Sayaka; Nikolova, Biliana; Aoki, Ichio; Higashi, Tatsuya

2017-10-01

The study aimed to investigate the effect of multi-targeted combinations (SN38/EF24; SN38/EF24/melatonin) on the growth of colon cancer in experimental animals and their impact on the ratio "oncogenic"/"onco-suppressive" reactive oxygen species (ROS) - a crucial factor for triggering carcinogenesis, as well as for development of effective therapeutic strategies. The experiments were conducted on colon cancer-grafted mice - non-treated, SN38/EF24-treated and SN38/EF24/melatonin-treated within 22 days. The balance between different types of ROS was measured in vivo by nitroxide-enhanced magnetic resonance imaging (MRI), as well as on isolated tissue specimens by conventional analytical tests. Both combinations significantly suppressed the tumor growth. Impressive anticancer effect was observed in SN38/EF24/melatonin-treated mice - almost complete destruction of the tumor. Both types of ROS (superoxide and hydroperoxides) were elevated in cancer, but the MRI data suggest that the ratio between them tends towards superoxide. SN38/EF24 decreased the level of superoxide, but did not affect the level of hydroperoxides in the cancerous tissue, while SN38/EF24/melatonin decreased the level of superoxide below the control and increased significantly the level of hydroperoxides. The most important observations are that: (i) colon cancer was characterized by a vicious cycle, that ensures a permanent domination of "oncogenic" ROS (as superoxide) over "onco-suppressive" ROS (as hydrogen peroxide); (ii) the anticancer effect of the triple combination EF24/SN38/melatonin was accompanied by decreasing "oncogenic" and increasing "onco-suppressive" ROS; (iii) the ratio between both types of ROS could be a new onco-target for combined therapy; and (iv) nitroxide-enhanced MRI is a valuable tool for analyzing of this ratio. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

PubMed

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

The influence of extractable organic matter on vitrinite reflectance suppression: A survey of kerogen and coal types

USGS Publications Warehouse

Barker, C.E.; Lewan, M.D.; Pawlewicz, M.J.

2007-01-01

The vitrinite reflectance suppression literature shows that while bitumen impregnation of the vitrinite group is often invoked as a significant contributor to suppression, its existence is not often supported by petrological evidence. This study examines bitumen impregnation as a factor in vitrinite suppression by comparing the vitrinite reflectance of source rock and coal samples before and after solvent-extraction. Bitumen, often defined as organic matter soluble or extractable in certain organic solvents, should be removed by Soxhlet method solvent extraction using chloroform. Removing the extractable bitumen should restore the suppressed reflectance to its true higher value. However, the solvent extracted samples averaged 0.014% Rv less than that of the unextracted samples. We conclude from these results and from other published data that reflectance suppression by bitumen impregnation in the vitrinite maceral group, above the huminite stage of gelification, is seemingly a rare phenomenon and whose effect on suppressing vitrinite reflectance is typically negligible. ?? 2006.

Rosmarinus officinalis Extract Suppresses Propionibacterium acnes–Induced Inflammatory Responses

PubMed Central

Tsai, Tsung-Hsien; Chuang, Lu-Te; Lien, Tsung-Jung; Liing, Yau-Rong; Chen, Wei-Yu

2013-01-01

Abstract Propionibacterium acnes is a key pathogen involved in the progression of acne inflammation. The development of a new agent possessing antimicrobial and anti-inflammatory activity against P. acnes is therefore of interest. In this study, we investigated the inhibitory effect of rosemary (Rosmarinus officinalis) extract on P. acnes–induced inflammation in vitro and in vivo. The results showed that ethanolic rosemary extract (ERE) significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including interleukin (IL)-8, IL-1β, and tumor necrosis factor-α in P. acnes–stimulated monocytic THP-1 cells. In an in vivo mouse model, concomitant intradermal injection of ERE attenuated the P. acnes–induced ear swelling and granulomatous inflammation. Since ERE suppressed the P. acnes–induced nuclear factor kappa-B (NF-κB) activation and mRNA expression of Toll-like receptor (TLR) 2, the suppressive effect of ERE might be due, at least partially, to diminished NF-κB activation and TLR2-mediated signaling pathways. Furthermore, three major constituents of ERE, carnosol, carnosic acid, and rosmarinic acid, exerted different immumodulatory activities in vitro. In brief, rosmarinic acid significantly suppressed IL-8 production, while the other two compounds inhibited IL-1β production. Further study is needed to explore the role of bioactive compounds of rosemary in mitigation of P. acnes–induced inflammation. PMID:23514231

Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Can; Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006; Wang, Lili

Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCCmore » inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.« less

Lactoferrin inhibits melanogenesis by down-regulating MITF in melanoma cells and normal melanocytes.

PubMed

Ishii, Nanase; Ryu, Mizuyuki; Suzuki, Yasushi A

2017-02-01

The aim of this study was to evaluate the effect of bovine lactoferrin (bLf) on melanin-producing cells and to elucidate its mechanism of action. We tested the anti-melanogenic effect of bLf on a 3-dimensional cultured pigmentation skin model and confirmed a 20% reduction in pigmentation, suggesting that bLf was transdermally absorbed and it suppressed melanin production. Treatment of human melanoma cells with bLf resulted in a significant, dose-dependent suppression of melanin production. Apo-bLf and holo-bLf suppressed melanogenesis to the same degree as bLf. The key feature behind this anti-melanogenic effect of bLf was the down-regulation of the microphthalmia-associated transcription factor (MITF), leading to the suppression of tyrosinase activity. Treatment with bLf resulted in both decreased expression of MITF mRNA and enhanced degradation of MITF protein. However, the primary effector was enhanced phosphorylation of extracellular signal-regulated kinase (ERK), leading to the phosphorylation and degradation of MITF. Our finding that bLf suppresses melanin production in melanocytes indicates that bLf is a possible candidate for application as a skin-whitening agent.

Propofol pretreatment attenuates LPS-induced granulocyte-macrophage colony-stimulating factor production in cultured hepatocytes by suppressing MAPK/ERK activity and NF-{kappa}B translocation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jawan, Bruno; Kao, Y.-H.; Department of Biological Sciences, National Sun Yat-Sen University, 70 Lien-Hai Road, Kaohsiung 804, Taiwan

Propofol (PPF), a widely used intravenous anesthetic for induction and maintenance of anesthesia during surgeries, was found to possess suppressive effect on host immunity. This study aimed at investigating whether PPF plays a modulatory role in the lipopolysaccharide (LPS)-induced inflammatory cytokine expression in a cell line of rat hepatocytes. Morphological observation and viability assay showed that PPF exhibits no cytotoxicity at concentrations up to 300 {mu}M after 48 h incubation. Pretreatment with 100 {mu}M PPF for 24 h prior to LPS stimulation was performed to investigate the modulatory effect on LPS-induced inflammatory gene production. The results of semi-quantitative RT-PCR demonstratedmore » that PPF pretreatment significantly suppressed the LPS-induced toll-like receptor (TLR)-4, CD14, tumor necrosis factor (TNF)-{alpha}, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression. Western blotting analysis showed that PPF pretreatment potentiated the LPS-induced TLR-4 downregulation. Flow cytometrical analysis revealed that PPF pretreatment showed no modulatory effect on the LPS-upregulated CD14 expression on hepatocytes. In addition, PPF pretreatment attenuated the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and I{kappa}B{alpha}, as well as the nuclear translocation of NF-{kappa}B primed by LPS. Moreover, addition of PD98059, a MAPK kinase inhibitor, significantly suppressed the LPS-induced NF-{kappa}B nuclear translocation and GM-CSF production, suggesting that the PPF-attenuated GM-CSF production in hepatocytes may be attributed to its suppressive effect on MAPK/ERK signaling pathway. In conclusion, PPF as an anesthetic may clinically benefit those patients who are vulnerable to sepsis by alleviating sepsis-related inflammatory response in livers.« less

In vivo effects of meloxicam and aspirin on blood, gastric mucosal, and synovial fluid prostanoid synthesis in dogs.

PubMed

Jones, Christopher J; Streppa, Heather K; Harmon, Barry G; Budsberg, Steven C

2002-11-01

To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively. 12 male dogs with unilateral osteoarthritis of the stifle joint. Each dog was treated in a crossover design with aspirin or meloxicam for 21 days. Prostaglandin E2 (PGE2) concentrations were measured at days 0 (baseline), 7, and 21 of each treatment period in lipopolysaccharide (LPS)-stimulated blood, synovial fluid collected by arthrocentesis, and endoscopic gastric mucosal biopsy specimens. Thromboxane B2 (TXB2) was evaluated in blood on days 0, 7, and 21 of each treatment period. Aspirin administration significantly suppressed PGE2 concentrations in blood, gastric mucosa, synovial fluid, and suppressed TXB2 concentration in blood at days 7 and 21. Meloxicam administration significantly suppressed PGE2 concentrations in blood and synovial fluid at days 7 and 21, but had no effect on concentrations of TXB2 in blood or PGE2 in gastric mucosa. Suppression of LPS-stimulated PGE2 concentrations in blood and synovial fluid by aspirin and meloxicam administration is consistent with activity against the COX-2 isoenzyme. Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1. Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1. Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints.

Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

PubMed Central

Spiegel, Daniel P.; Hansen, Bruce C.; Byblow, Winston D.; Thompson, Benjamin

2012-01-01

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex. PMID:22563485

MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

PubMed

Wei, Li-Qiang; Liang, Hui-Tao; Qin, Dong-Chun; Jin, Hui-Fang; Zhao, Yong; She, Ming-Cong

2014-12-01

MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-Inflammatory Cytokine Expression in Liver of Diabetic ob/ob Mice.

PubMed

Ogura, Kasane; Ogura, Masahito; Shoji, Toshihiko; Sato, Yuichi; Tahara, Yumiko; Yamano, Gen; Sato, Hiroki; Sugizaki, Kazu; Fujita, Naotaka; Tatsuoka, Hisato; Usui, Ryota; Mukai, Eri; Fujimoto, Shimpei; Inagaki, Nobuya; Nagashima, Kazuaki

2016-11-23

Procyanidins, the main ingredient of apple polyphenols, are known to possess antioxidative and anti-inflammatory effects associated closely with the pathophysiology of insulin resistance and type 2 diabetes. We investigated the effects of orally administered apple procyanidins (APCs) on glucose metabolism using diabetic ob/ob mice. We found no difference in body weight or body composition between mice treated with APCs and untreated mice. A 4 week oral administration of APCs containing water [0.5% (w/v)] ameliorated glucose tolerance, insulin resistance, and hepatic gluconeogenesis in ob/ob mice. APCs also suppressed the increase in the level of the pancreatic β-cell. Insulin-stimulated Akt phosphorylation was significantly enhanced; pro-inflammatory cytokine expression levels were significantly decreased, and c-Jun N-terminal kinase phosphorylation was downregulated in the liver of those mice treated with APCs. In conclusion, APCs ameliorate insulin resistance by improving hepatic insulin signaling through suppression of hepatic inflammation in ob/ob mice, which may be a mechanism with possible beneficial health effects of APCs in disturbed glucose metabolism.

Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria.

PubMed

Staphorsius, Annemieke S; Kreukels, Baudewijntje P C; Cohen-Kettenis, Peggy T; Veltman, Dick J; Burke, Sarah M; Schagen, Sebastian E E; Wouters, Femke M; Delemarre-van de Waal, Henriëtte A; Bakker, Julie

2015-06-01

Adolescents with gender dysphoria (GD) may be treated with gonadotropin releasing hormone analogs (GnRHa) to suppress puberty and, thus, the development of (unwanted) secondary sex characteristics. Since adolescence marks an important period for the development of executive functioning (EF), we determined whether the performance on the Tower of London task (ToL), a commonly used EF task, was altered in adolescents with GD when treated with GnRHa. Furthermore, since GD has been proposed to result from an atypical sexual differentiation of the brain, we determined whether untreated adolescents with GD showed sex-atypical brain activations during ToL performance. We found no significant effect of GnRHa on ToL performance scores (reaction times and accuracy) when comparing GnRHa treated male-to-females (suppressed MFs, n=8) with untreated MFs (n=10) or when comparing GnRHa treated female-to-males (suppressed FMs, n=12) with untreated FMs (n=10). However, the suppressed MFs had significantly lower accuracy scores than the control groups and the untreated FMs. Region-of-interest (ROI) analyses showed significantly greater activation in control boys (n=21) than control girls (n=24) during high task load ToL items in the bilateral precuneus and a trend (p<0.1) for greater activation in the right DLPFC. In contrast, untreated adolescents with GD did not show significant sex differences in task load-related activation and had intermediate activation levels compared to the two control groups. GnRHa treated adolescents with GD showed sex differences in neural activation similar to their natal sex control groups. Furthermore, activation in the other ROIs (left DLPFC and bilateral RLPFC) was also significantly greater in GnRHa treated MFs compared to GnRHa treated FMs. These findings suggest that (1) GnRHa treatment had no effect on ToL performance in adolescents with GD, and (2) pubertal hormones may induce sex-atypical brain activations during EF in adolescents with GD. Copyright © 2015 Elsevier Ltd. All rights reserved.

A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice

PubMed Central

Kozy, Heather M.; Lum, Jeremy A.; Sweetwood, Rosemary; Chu, Mabel; Cunningham, Cameron R.; Salamon, Hugh; Lloyd, Clare M.; Coffman, Robert L.; Hessel, Edith M.

2015-01-01

Background CpG-containing oligodeoxynucleotides (CpG-ODN) are potent inhibitors of Th2-mediated allergic airway disease in sensitized mice challenged with allergen. A single treatment has transient effects but a limited series of treatments has potential to achieve clinically meaningful sustained inhibition of allergic airway disease. Objective To optimize the treatment regimen and determine the mechanisms of action in mice of an inhaled form of CpG-ODN being developed for human asthma treatment. Methods A limited series of weekly intranasal 1018 ISS (CpG-ODN; B-class) treatments were given to ragweed allergen-sensitized mice chronically exposed to allergen during and after the 1018 ISS treatment regimen. Treatment effects were evaluated by measuring effect on lung Th2 cytokines and eosinophilia as well as lung dendritic cell function and T cell responses. Results Twelve intranasal 1018 ISS treatments induced significant suppression of BAL eosinophilia and IL-4, IL-5, and IL-13 levels and suppression was maintained through 13 weekly ragweed exposures administered after treatment cessation. At least 5 treatments were required for lasting Th2 suppression. CpG-ODN induced moderate Th1 responses but Th2 suppression did not require IFN-γ. Th2 suppression was associated with induction of a regulatory T cell response. Conclusion A short series of CpG-ODN treatments results in sustained suppression of allergic lung inflammation induced by a clinically relevant allergen. PMID:24464743

Effects of hypnotic bromovalerylurea on microglial BV2 cells.

PubMed

Kawasaki, Shun; Abe, Naoki; Ohtake, Fumito; Islam, Afsana; Choudhury, Mohammed Emamussalehin; Utsunomiya, Ryo; Kikuchi, Satoshi; Nishihara, Tasuku; Kuwabara, Jun; Yano, Hajime; Watanabe, Yuji; Aibiki, Mayuki; Yorozuya, Toshihiro; Tanaka, Junya

2017-06-01

An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effect of fractionated extracts and isolated pure compounds of Spondias mombin (L. Anacardiaceae) leaves on novelty-induced rearing and grooming behaviours in mice.

PubMed

Ayoka, Abiodun O; Owolabi, Rotimi A; Bamitale, Samuel K; Akomolafe, Rufus O; Aladesanmi, Joseph A; Ukponmwan, Eghe O

2013-01-01

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in mice. Propranolol-induced increase in novelty-induced grooming was significantly reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone significantly increased the gallic acid derivative-induced suppression of novelty-induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl derivative and potentiated the inhibitory effect of quercetin derivative and gallic acid derivative significantly. This study suggested that adrenergic and dopaminergic neuro-transmissions are strongly involved in the neural mechanisms of the effect of the three pure isolates derivative, while opioid neuro-transmission is strongly linked with the neural mechanism of behavioural effect of coumaroyl derivative.

Effects of In and Ni Addition on Microstructure of Sn-58Bi Solder Joint

NASA Astrophysics Data System (ADS)

Mokhtari, Omid; Nishikawa, Hiroshi

2014-11-01

In this study, the effect of adding 0.5 wt.% and 1 wt.% In and Ni to Sn-58Bi solder on intermetallic compound (IMC) layers at the interface and the microstructure of the solder alloys were investigated during reflow and thermal aging by scanning electron microscopy and electron probe micro-analysis. The results showed that the addition of minor elements was not effective in suppressing the IMC growth during the reflow; however, the addition of 0.5 wt.% In and Ni was effective in suppressing the IMC layer growth during thermal aging. The thickening kinetics of the total IMC layer was analyzed by plotting the mean thickness versus the aging time on log-log coordinates, and the results showed the transition point from grain boundary diffusion control to a volume diffusion control mechanism. The results also showed that the minor addition of In can significantly suppress the coarsening of the Bi phase.

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

PubMed Central

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity. PMID:28659796

Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia.

PubMed

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

2017-01-01

Acute myeloid leukemia (AML) is an acute leukemia common in most adults; its prevalence intensifies with age. The overall survival of AML is very poor because of therapeutic resistance. Azelaic acid (AZA) is non-toxic, non-teratogenic, and non-mutagenic and its antitumor effect on various tumor cells is well established; Nonetheless, its therapeutic effects in AML cells are largely unknown. In this study, it was shown that AZA significantly inhibits the cell viability and induces apoptosis in AML cells in a dose-dependent manner. Additionally, AZA suppressed the expression of phosphorylated Akt, Jab1 and Trx, and this suppression was enhanced by treatment with Jab1 siRNA. Furthermore, AZA sensitized AML cells to Ara-c chemotherapy. The suppressive effect of AZA on tumor growth was examined in vivo by subcutaneously inoculated AML cells in a tumor model using nude mice. These findings indicate that AZA is useful as an effective ingredient in antineoplastic activity.

Reversal of infectious mononucleosis-associated suppressor T cell activity by D-mannose

PubMed Central

1983-01-01

Epstein-Barr virus-induced infectious mononucleosis (IM) is associated with the activation of suppressor T lymphocytes that profoundly inhibit immunoglobulin (Ig) production in vitro. We have examined the nature of signals operating in the interaction between IM suppressor T cells and their targets, and explored the possibility that a lectin-like receptor molecule and its specific sugar might provide specificity to this interaction. When D-mannose or some of its derivatives, including alpha- methyl-D-mannoside, mannose-6-phosphate, and mannan, were added to suppressed cultures containing IM T lymphocytes and pokeweed mitogen (PWM)-stimulated normal mononuclear cells, a significant enhancement of Ig production was observed. These sugars had little or no effect on Ig production by the PWM-stimulated responder cells alone and thus the enhanced Ig production could be attributed to the reversal of suppression in the co-cultures by these sugars. This was further confirmed by the observation that the sugars were effective only if present during the first 24 h of culture, a time when IM suppressor T cells exert their principal effect. The effect of sugars on Ig production by suppressed cultures was similar to that achieved by decreasing by about fourfold the number of IM T cells in culture. The effect of the sugars is unlikely to represent a form of nonspecific toxicity, since inhibited cultures become responders in the presence of the sugar. Furthermore, toxicity restricted to the suppressor T cells is unlikely, since preincubation of the T cells with the sugars did not reduce their subsequent ability to suppress in secondary indicator cultures. In addition, there was no correlation between the effect of the sugars on T cell proliferation and their effect on T cell-mediated suppression. The reversal of suppression by sugars was dose dependent and demonstrated stereo-specificity in that L-mannose was without effect while D-mannose reversed suppression. These data indicate that D- mannose and some of its derivatives consistently reverse suppression of Ig production by IM T cells and strongly suggest a role for saccharides as critical components in the cellular receptors involved in certain physiologic immune cell interactions. PMID:6225821

Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

PubMed Central

Kuroyanagi, Gen; Otsuka, Takanobu; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Nakakami, Akira; Mizutani, Jun; Kozawa, Osamu; Tokuda, Haruhiko

2014-01-01

It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation. PMID:25290095

Virulence-suppressing effects of linezolid on methicillin-resistant Staphylococcus aureus: possible contribution to early defervescence.

PubMed

Yoshizawa, Sadako; Tateda, Kazuhiro; Saga, Tomoo; Ishii, Yoshikazu; Yamaguchi, Keizo

2012-04-01

In the present study, immunomodulatory effects of linezolid (LZD) on methicillin-resistance Staphylococcus aureus (MRSA) infections were evaluated. We have retrospectively reviewed treatment effects of LZD on 52 patients with severe MRSA infections. Sixty-four percent of the febrile patients demonstrated significant defervescence within 3 days, despite the presence of positive culture results. We speculated that this finding might be due to early anti-inflammatory effects of LZD, and to investigate this further we initiated in vivo experiments using mice MRSA pneumonia models. Mice were treated with either LZD or vancomycin (VCM) immediately after intranasal administration of MRSA. Bacterial numbers and levels of inflammatory cytokines in the lungs were determined. Although the bacterial burden in the lungs was not apparently different between the two groups, LZD but not VCM treatment significantly reduced induction of inflammatory cytokines in the lungs (P < 0.05). To evaluate whether this anti-inflammatory response was due to suppression of virulence factor expression, filter-sterilized supernatants of MRSA incubated in broth overnight with sub-MICs of LZD were subcutaneously administered to mice. To clarify whether LZD possesses direct host-modulating activity, cytokine responses to the supernatants were examined in mice pretreated with LZD. Interestingly, MRSA solutions prepared in the presence of sub-MICs of LZD revealed significant suppression of interleukin 6 (IL-6) in a dose-dependent manner (P < 0.05), but pretreatment of mice with LZD revealed no changes in cytokines. These findings suggest that sub-MICs of LZD might suppress virulence factors of MRSA, which may be associated with a reduction in endogenous pyrogens. These data may explain at least in part early defervescence observed in LZD-treated individuals.

Emotional suppression and depressive symptoms in women newly diagnosed with early breast cancer.

PubMed

Li, Lingyan; Yang, Yanjie; He, Jincai; Yi, Jinyao; Wang, Yuping; Zhang, Jinqiang; Zhu, Xiongzhao

2015-10-24

Patients with breast cancer usually present varying levels of depressive symptoms. Emotional suppression, as a coping style, refers to an individual's ability to consciously control expression of negative emotions. Thus, emotional suppression is an important psychological factor related to depressive symptoms in patients with breast cancer. It has long been considered that compared to European and American women, Chinese women are more likely to ascribe to norms of negative emotion control for smooth social interaction. However, there is paucity of research focusing on emotional suppression among Chinese women with breast cancer. Thus the aims of the current study were (1) to investigate the incidence of depressive symptoms in women newly diagnosed with early breast cancer in Mainland China, and (2) to examine the relationships between emotional suppression and depressive symptoms in these patients. The Center for Epidemiological Studies Depression Scale (CES-D), the Beck Anxiety Inventory (BAI) and the Chinese version of the Courtauld Emotional Control Scale (CECS) were used to assess the level of depressive symptoms, anxiety symptoms and emotional suppression respectively in 247 women with early breast cancer and 362 healthy women. Analyses of variance were conducted to investigate group differences on depressive symptoms and emotional suppression. Bivariate correlations and Hierarchical regression analyses were performed to examine the effect of emotional suppression on depressive symptoms in participants after controlling the impact of group membership and anxiety level. (1) The incidence rates of clinical and severe depressive symptoms in patients were 36.4 and 36.0 % respectively. (2) Patients scored significantly higher than healthy women on CECS. (3) The scores on CECS were significantly associated with the total CES-D scores in all participants; Anger suppression significantly predicted the total CES-D scores. The majority of women newly diagnosed with early breast cancer reported clinical or severe depressive symptoms. As well, these patients presented a controlled emotion coping style. Emotional suppression was associated with the level of depressive symptoms in women newly diagnosed with breast cancer. Anger suppression might play a unique role in the depressive symptoms among women newly diagnosed with breast cancer.

On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans.

PubMed

Carpentier, André C; Frisch, Frédérique; Cyr, Denis; Généreux, Philippe; Patterson, Bruce W; Giguère, Robert; Baillargeon, Jean-Patrice

2005-11-01

During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by approximately 60 and approximately 70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.

Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria.

PubMed

Costa, Rosalia; Dunsford, Michael; Skagerberg, Elin; Holt, Victoria; Carmichael, Polly; Colizzi, Marco

2015-11-01

Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001). Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents. © 2015 International Society for Sexual Medicine.

Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

PubMed

Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

2009-04-01

Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH < 4 and the median gastric pH were evaluated for 15 consecutive days by a Bravo capsule fixed to the stomach. On day 1, there was no significant difference between the acid-suppressing effects of the two drugs (ranitidine vs rabeprazole: not significant). Although rabeprazole sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P < 0.05), the effect of ranitidine hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

First pulse effect self-suppression picosecond regenerative amplifier (Conference Presentation)

NASA Astrophysics Data System (ADS)

Fan, Haitao; Chang, Liang; Zhang, Yi; Yao, Siyi; Lu, Wei; Yang, Xiaohong

2017-03-01

First pulse effect, commonly seen in nanosecond cavity-dumped lasers and picosecond regenerative amplifiers, not only leads to degradation of processing quality, but also acts as potential threat to optical switching elements. Several methods have been developed to suppress that effect, including electronic controls, polarization controls, and diffraction controls. We present a new way for first pulse self-suppression without any additional components. By carefully arranging the cavity mirror of a regenerative amplifier, we realized `parasitic lasing like' radiation. When the regenerative amplifier works in `operation ready' status, the parasitic lasing occurs and prevents the gain crystal from saturation. When the regenerative amplifier starts working and amplifying pulses, the first pulse in a pulse train will not get much more gain and energy than pulses following it. As parasitic lasing disappears at the same time, the average output power of the amplifier does not significantly reduce. This cost effective method does not require any additional component. In addition, as it is not polarization dependent, this method is widely suitable for different kinds of regenerative amplifiers. It's the easiest and cheapest way to suppress first pulse effect, to the best of our knowledge.

The Temporal Dynamics of Two Response-Focused Forms of Emotion Regulation: Experiential, Expressive, and Autonomic Consequences

PubMed Central

Dan-Glauser, Elise S.; Gross, James J.

2011-01-01

This study examines the early affective consequences of two close forms of suppression. Participants (N=37) were shown negative, positive, and neutral pictures and cued either to attend to the pictures, or to perform expressive or physiological suppression (i.e. reduce body reactions). Continuous measures of experience, expressivity, and autonomic responses showed that both suppression strategies produced rapid response modulation. Common effects of the two strategies included a transient increase in negative feeling, a durable decrease in positive feeling, and a decrease in expressivity, cardiovascular activity, and oxygenation. The two strategies were significantly different only in response to positive stimuli, with physiological suppression showing a larger decrease in experience intensity and blood pressure. These results suggest a strong overlap between the two suppression strategies in terms of their early impact on emotional responses. PMID:21361967

Inoculation with arbuscular mycorrhizal fungi suppresses initiation of haustoria in the root hemiparasite Pedicularis tricolor.

PubMed

Li, Ai-Rong; Smith, Sally E; Smith, F Andrew; Guan, Kai-Yun

2012-05-01

Plant parasitism and arbuscular mycorrhizal (AM) associations have many parallels and share a number of regulatory pathways. Despite a rapid increase in investigations addressing the roles of AM fungi in regulating interactions between parasitic plants and their hosts, few studies have tested the effect of AM fungi on the initiation and differentiation of haustoria, the parasite-specific structures exclusively responsible for host attachment and nutrient transfer. In this study, we tested the influence of AM fungi on haustorium formation in a root hemiparasitic plant. Using a facultative root hemiparasitic species (Pedicularis tricolor) with the potential to form AM associations, the effects of inoculation were tested with two AM fungal species, Glomus mosseae and Glomus intraradices, on haustorium initiation in P. tricolor grown alone or with Hordeum vulgare 'Fleet' (barley) as the host plant. This study consisted of two greenhouse pot experiments. Both AM fungal species dramatically suppressed intraspecific haustorium initiation in P. tricolor at a very low colonization level. The suppression over-rode inductive effects of the parasite's host plant on haustoria production and caused significant growth depression of P. tricolor. AM fungi had strong and direct suppressive effects on haustorium formation in the root hemiparasite. The significant role of AM fungi in haustorium initiation of parasitic plants was demonstrated for the first time. This study provides new clues for the regulation of haustorium formation and a route to development of new biocontrol strategies in management of parasitic weeds.

A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

PubMed

Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

2017-01-01

Turmeric ( Curcuma longa ) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

Herbal Compound Songyou Yin and Moderate Swimming Suppress Growth and Metastasis of Liver Cancer by Enhancing Immune Function.

PubMed

Zhang, Quan-Bao; Meng, Xiang-Ting; Jia, Qing-An; Bu, Yang; Ren, Zheng-Gang; Zhang, Bo-Heng; Tang, Zhao-You

2016-09-01

Objective Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity. © The Author(s) 2015.

Suppressive Effect of the n-Hexane Extract of Litsea japonica Fruit Flesh on Monosodium-Iodoacetate-Induced Osteoarthritis in Rats.

PubMed

Kim, Seung-Hyung; Choi, Hye-Jin; Yang, Won-Kyung; Lee, Ji-Eun; Cho, Ju-Hyun; Park, In-Jae; Park, Sunyoung; Park, Bo-Kyung; Jin, Mirim

2017-01-01

We examined the antiosteoarthritic effect of the n-hexane extract of Litsea japonica fruit flesh (LJF-HE) in a rat model of monosodium-iodoacetate- (MIA-) induced osteoarthritis. LJF-HE significantly reduced the difference in weight-bearing capabilities of the hind paws between healthy and MIA-treated rats. Histological examination of the knee joints indicated that LJF-HE suppressed cartilage and bone destruction. Additionally, there were decreases in the expression of matrix metalloproteinase-2 and metalloproteinase-9 and cyclooxygenase-2 in the joints. The serum levels of deoxypyridinoline (DPD) and osteocalcin, which are markers of bone metabolism, also decreased. Furthermore, LJF-HE significantly suppressed infiltration of inflammatory cells into the synovium and inhibited the expression of proinflammatory cytokines such as tumor necrosis factor- (TNF-) α , interleukin- (IL-) 1, and IL-6 in the joints and serum. The serum levels of leukotriene B4 and lipoxygenase were also significantly lowered by LJF-HE. Finally, LJF-HE inhibited the production of nitric oxide, prostaglandin E2, IL-6, and TNF- α in lipopolysaccharide-activated macrophages, which might be associated with inhibited phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Our data suggest that LJF-HE has an anti-inflammatory effect and may have potential as an antiosteoarthritic agent.

Attention-based long-lasting sensitization and suppression of colors.

PubMed

Tseng, Chia-Huei; Vidnyanszky, Zoltan; Papathomas, Thomas; Sperling, George

2010-02-22

In contrast to the short-duration and quick reversibility of attention, a long-term sensitization to color based on protracted attention in a visual search task was reported by Tseng, Gobell, and Sperling (2004). When subjects were trained for a few hours to search for a red object among colored distracters, sensitivity to red was increased for weeks. This sensitization was quantified using ambiguous motion displays containing isoluminant red-green and texture-contrast gratings, in which the perceived motion-direction depended both on the attended color and on the relative red-green saturation. Such long-term effects could result from either sensitization of the attended color, or suppression of unattended colors, or a combination of the two. Here we unconfound these effects by eliminating one of the paired colors of the motion display from the search task. The other paired color in the motion display can then be either a target or a distracter in the search task. Thereby, we separately measure the effect of attention on sensitizing the target color or suppressing distracter colors. The results indicate that only sensitization of the target color in the search task is statistically significant for the present experimental conditions. We conclude that selective attention to a color in our visual search task caused long-term sensitization to the attended color but not significant long-term suppression of the unattended color. Copyright 2009 Elsevier Ltd. All rights reserved.

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

PubMed

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Fat-suppressed MR images of both hands obtained using CHESS can be improved by rice pads.

PubMed

Moriya, Susumu; Miki, Yukio; Kamishima, Tamotsu; Kanagaki, Mitsunori; Yokobayashi, Tsuneo; Ishikawa, Mitsunori

2012-09-01

When chemical shift selective (CHESS) imaging is used with magnetic resonance imaging (MRI) for simultaneous imaging of both hands for the evaluation of rheumatoid arthritis, the fat suppression effect is poor. We investigated whether these fat-suppressed images using CHESS could be improved with the use of rice pads. T1-weighted images were obtained with CHESS and the same imaging parameters were used with and without rice pads on the coronal plane of both hands in 10 healthy volunteers. Patients were placed in a prone position with both hands extended overhead. The fat-suppression effect was classified into four categories and scored for both sets of images, and visual assessments were made by one radiologist and one radiologic technologist. The evaluation score was 1.1 for the images made without rice pads, and 3.2 for the images made with rice pads. The fat suppression effect was thus significantly better in the images made using rice pads (P<0.0001). Lingering fat signals disappeared almost completely in images of both hands using CHESS with rice pads, and it was confirmed that the images were improved and had good fat suppression. More accurate evaluation of inflammatory sites that occur in rheumatoid arthritis may thus be possible, promising better diagnostic accuracy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of suppression and acceptance of sadness on the urge for non-suicidal self-injury and self-punishment.

PubMed

Svaldi, Jennifer; Dorn, Christina; Matthies, Swantje; Philipsen, Alexandra

2012-12-30

The present study wanted to test the course of the urge for non-suicidal self-injury (UNSSI) and the urge for self-punishment (USP) when suppressing or accepting upcoming emotions in response to a sadness-inducing film clip in female participants with borderline personality disorder (BPD). Thirty-six women with BPD were allocated either to a condition in which they were asked to engage in expressive suppression or acceptance while watching a sadness-inducing film clip. Ratings of UNSSI, USP, and positive and negative emotions were assessed prior to the clip (baseline), immediately after it (t1) and after a 5min waiting period (t2), during which participants viewed landscape pictures. Additionally, physiological measures were obtained. Main results revealed a significant increase in UNSSI from baseline to t2 in the acceptance, but not in the suppression group. Furthermore, USP scores significantly increased from baseline to t2 in the acceptance, but not in the suppression condition. However, there was no differential impact on the sympathetic and parasympathetic branch depending on strategy. The results are in line with recent literature showing that expressive suppression in BPD may also have an adaptive function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Reappraisal and suppression mediate the contribution of regulatory focus to anxiety in healthy adults.

PubMed

Llewellyn, Nicole; Dolcos, Sanda; Iordan, Alexandru D; Rudolph, Karen D; Dolcos, Florin

2013-08-01

Theory and research link regulatory focus (RF) in the form of promotion and prevention goal orientation with internalizing symptoms (e.g., anxiety), but the relevant mechanisms are not well understood. This study investigated the role of two emotion regulation (ER) strategies (cognitive reappraisal and expressive suppression) as possible mediators. Path analysis using data from 179 healthy young participants (110 women, 69 men) revealed that stronger promotion orientation was significantly associated with less anxiety, and that the use of reappraisal and suppression partially mediated this association. Prevention was associated with more suppression but was not directly associated with anxiety. There were no gender differences in these effects. Collectively, these findings suggest that effective ER, through heightened use of reappraisal and dampened use of suppression, serves as a mechanism through which promotion confers protection against anxiety. This research provides empirical support to initiatives aimed at promoting healthy psychological adjustment and preventing anxiety, by optimizing ER strategies with respect to RF goal orientations. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Toward optimizing lighting as a countermeasure to sleep and circadian disruption in space flight.

PubMed

Fucci, Robert L; Gardner, James; Hanifin, John P; Jasser, Samar; Byrne, Brenda; Gerner, Edward; Rollag, Mark; Brainard, George C

2005-01-01

Light is being used as a pre-launch countermeasure to circadian and sleep disruption in astronauts. The effect of light on the circadian system is readily monitored by measurement of plasma melatonin. Our group has established an action spectrum for human melatonin regulation and determined the region of 446-477 nm to be the most potent for suppressing plasma melatonin. The aim of this study was to compare the efficacy of 460 and 555 nm for suppressing melatonin using a within-subjects design. Subjects (N=12) were exposed to equal photon densities (7.18 x 10(12) photons/cm2/s) at 460 and 555 nm. Melatonin suppression was significantly stronger at 460 nm (p<0.02). An extension to the action spectrum showed that 420 nm light at 16 and 32 microW/cm2 significantly suppressed melatonin (p<0.04 and p<0.002). These studies will help optimize lighting countermeasures to circadian and sleep disruption during spaceflight. c2005 Elsevier Ltd. All rights reserved.

Toward optimizing lighting as a countermeasure to sleep and circadian disruption in space flight

NASA Astrophysics Data System (ADS)

Fucci, Robert L.; Gardner, James; Hanifin, John P.; Jasser, Samar; Byrne, Brenda; Gerner, Edward; Rollag, Mark; Brainard, George C.

2005-05-01

Light is being used as a pre-launch countermeasure to circadian and sleep disruption in astronauts. The effect of light on the circadian system is readily monitored by measurement of plasma melatonin. Our group has established an action spectrum for human melatonin regulation and determined the region of 446-477 nm to be the most potent for suppressing plasma melatonin. The aim of this study was to compare the efficacy of 460 and 555 nm for suppressing melatonin using a within-subjects design. Subjects ( N=12) were exposed to equal photon densities ( 7.18×1012photons/cm2/s) at 460 and 555 nm. Melatonin suppression was significantly stronger at 460 nm ( p<0.02). An extension to the action spectrum showed that 420 nm light at 16 and 32μW/cm2 significantly suppressed melatonin ( p<0.04 and p<0.002). These studies will help optimize lighting countermeasures to circadian and sleep disruption during spaceflight.

The effect of levocabastine and furosemide pretreatment on hyperreactive response after nasal provocation with hypotonic aerosol in subjects with allergic rhinitis.

PubMed

Anzic, Srdjan Ante; Dzepina, Davor; Kalogjera, Livije

2007-11-01

Patients with allergic rhinitis demonstrate hyperreactive response in distilled water nasal provocation, shown by significant increase in nasal airway resistance (NAR). Antihistamines, including topical antihistamine, levocabastine, reduce response in non-specific nasal provocation tests. Furosemide is a diuretic which reduces hyperreactivity in lower airways, but the mode of its action is not yet fully understood. In this study, we hypothesized that either levocabastine or furosemide pre-treatment in allergic rhinitis patients reduced response to nasal challenge with non-isotonic aerosol. To test the hypothesis, we measured the effect of pre-treatment with levocabastine and furosemide in topical application on suppression of hyperreactive response to distilled water nasal inhalation. Nasal resistance was measured, prior to and after the provocation, by active anterior rhinomanometry in two randomized groups of patients, according to pre-treatment, either by levocabastine or furosemide, 20 patients in each group, respectively. Nasal airflow resistance and level of hyperreactive response considering nasal eosinophilia were tested. Significant increase in nasal resistance following provocation was found at baseline conditions (without pre-medication); pre-treatment with levocabastine and furosemide has suppressed such response. Patients with positive nasal eosinophilia showed a significantly higher increase in nasal resistance compared to those with negative smears. Furosemide has shown significantly better protective effect on nasal resistance increase in patients with positive eosinophils nasal smears. Levocabastine and furosemide pre-treatment suppress hyperreactive response to distilled water nasal provocation. Comparison of resistances (pre-treatment vs. without) showed more protective effect of furosemide, measured on both better and worse patent side of nose, in contrast to levocabastine group for which it was shown only on better patent side prior to provocation. Protection of furosemide was significantly more pronounced in patients with significant nasal eosinophilia.

Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model.

PubMed

Kim, Chulwon; Lee, Seok-Geun; Yang, Woong Mo; Arfuso, Frank; Um, Jae-Young; Kumar, Alan Prem; Bian, Jinsong; Sethi, Gautam; Ahn, Kwang Seok

2018-05-29

Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and human multiple myeloma xenograft tumors in athymic nu/nu mice model are mediated through the negative regulation of STAT3 and STAT5 pathways. Data from the in vitro studies indicated that FT could significantly inhibit cell viability, and induce apoptosis. Interestingly, FT also suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells, and this effect was found to be mediated via an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. Also, FT abrogated STAT3 and STAT5 DNA binding capacity and nuclear translocation. FT induced cell cycle arrest, downregulated the expression of STAT3-regulated anti-apoptotic, angiogenetic, and proliferative gene products; and this correlated with induction of caspase-3 activation and cleavage of PARP. Intraperitoneal administration of FT significantly suppressed the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade. Copyright © 2018 Elsevier B.V. All rights reserved.

Autophagy-mediated degradation of IAPs and c-FLIP L potentiates apoptosis induced by combination of TRAIL and Chal-24

DOE PAGES

Xu, Jennings; Xu, Xiuling; Shi, Shaoqing; ...

2015-11-02

Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. In this paper, we report that combination of the recently identified novel chalcone derivative, chalcone-24 (Chal-24), and TNF-related apoptosis-inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal-24 treatment significantly enhanced TRAIL-induced activation of caspase-8 and caspase-3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan-caspase inhibitor z-VAD-fmk. Chal-24 and TRAIL combination suppressed expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (c-FLIPL) and cellular inhibitor of apoptosis proteins (c-IAPs), and ectopic expression of c-FLIPL andmore » c-IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal-24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by Chal-24 and TRAIL combination, which was associated with attenuation of c-FLIPL and c-IAPs degradation. In conclusion, these results suggest that Chal-24 potentiates the anticancer activity of TRAIL through autophagy-mediated degradation of c-FLIPL and c-IAPs, and that combination of Chal-24 and TRAIL could be an effective approach in improving chemotherapy efficacy.« less

MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway.

PubMed

Wei, Chunyan; Zhang, Xi; He, Sai; Liu, Bianli; Han, Hongfang; Sun, Xuejun

2017-12-30

MicroRNAs are emerging as critical regulators in various fundamental biological processes, including tumor progression. MicroRNA-219-5p (miR-219-5p) has been suggested as a novel tumor suppressing miRNA for many types of human cancers. However, the expression and functional significance of miR-219-5p in epithelial ovarian cancer remain poorly understood. In this study, we sought to explore the potential functions of miR-219-5p in epithelial ovarian cancer. Herein, we found that miR-219-5p levels were significantly decreased in epithelial ovarian cancer tissues and cell lines. Further experiments showed that overexpression of miR-219-5p inhibited epithelial ovarian cancer cell proliferation, migration, and invasion, and suppressed the Wnt/β-catenin signaling pathway. By contrast, suppression of miR-219-5p exhibited the opposite effects. Twist was identified as a downstream target of miR-219-5p, and its expression was directly regulated by miR-219-5p. Restoration of Twist expression in miR-219-5p-overexpresing cells significantly reversed the antitumor effects of miR-219-5p. Taken together, our results revealed a tumor suppressive role for miR-219-5p in epithelial ovarian cancer that includes suppression of cell proliferation, migration, and invasion through downregulation of the Twist/Wnt/β-catenin signaling pathway. Our study suggests that miR-219-5p may have potential applications in the diagnosis and treatment of epithelial ovarian cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Fisetin inhibits the generation of inflammatory mediators in interleukin-1β-induced human lung epithelial cells by suppressing the NF-κB and ERK1/2 pathways.

PubMed

Peng, Hui-Ling; Huang, Wen-Chung; Cheng, Shu-Chen; Liou, Chian-Jiun

2018-07-01

Fisetin, a flavone that can be isolated from fruits and vegetables, has anti-tumor and anti-oxidative properties and ameliorates airway hyperresponsiveness in asthmatic mice. This study investigated whether fisetin can suppress the expression of inflammatory mediators and intercellular adhesion molecule 1 (ICAM-1) in A549 human lung epithelial cells that were stimulated with interleukin-1β (IL-1β) to induce inflammatory responses. A549 cells were treated with fisetin (3-30 μM) and then with IL-1β. Fisetin significantly inhibited COX-2 expression and reduced prostaglandin E 2 production, and it suppressed the levels of IL-8, CCL5, monocyte chemotactic protein 1, tumor necrosis factor α, and IL-6. Fisetin also significantly attenuated the expression of chemokine and inflammatory cytokine genes and decreased the expression of ICAM-1, which mediates THP-1 monocyte adhesion to inflammatory A549 cells. Fisetin decreased the translocation of nuclear transcription factor kappa-B (NF-κB) subunit p65 into the nucleus and inhibited the phosphorylation of proteins in the ERK1/2 pathway. Co-treatment of IL-1β-stimulated A549 cells with ERK1/2 inhibitors plus fisetin reduced ICAM-1 expression. Furthermore, fisetin significantly increased the effects of the protective antioxidant pathway by promoting the expression of nuclear factor erythroid-2-related factor-2 and heme oxygenase 1. Taken together, these data suggest that fisetin has anti-inflammatory effects and that it suppresses the expression of chemokines, inflammatory cytokines, and ICAM-1 by suppressing the NF-κB and ERK1/2 signaling pathways in IL-1β-stimulated human lung epithelial A549 cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes.

PubMed

Birzniece, Vita; Ho, Ken K Y

2015-10-01

Tamoxifen, a selective estrogen receptor modulator, suppresses GH secretion in women but not in men. It increases testosterone levels in men. As GH and testosterone stimulate fat metabolism, the metabolic consequences of tamoxifen may be greater in women than in men. To determine whether tamoxifen suppresses fat oxidation (Fox) to a greater degree in women than in men. An open-label study of ten healthy postmenopausal women and ten healthy men receiving 2-week treatment with tamoxifen (20  mg/day). GH response to arginine stimulation, serum levels of IGF1, testosterone and LH (men only), sex hormone binding globulin (SHBG) and whole body basal and postprandial Fox. In women, tamoxifen significantly reduced the mean GH response to arginine stimulation (Δ -87%, P<0.05) and circulating IGF1 levels (Δ -23.5±5.4%, P<0.01). Tamoxifen reduced postprandial Fox in women (Δ -34.6±10.3%; P<0.05). In men, tamoxifen did not affect the GH response to arginine stimulation but significantly reduced mean IGF1 levels (Δ -24.8±6.1%, P<0.01). Tamoxifen increased mean testosterone levels (Δ 52±14.2%; P<0.01). Fox was not significantly affected by tamoxifen in men. Tamoxifen attenuated the GH response to stimulation and reduced postprandial Fox in women but not in men. We conclude that at a therapeutic dose, the suppressive effect of tamoxifen on fat metabolism is gender-dependent. Higher testosterone levels may mitigate the suppression of GH secretion and Fox during tamoxifen treatment in men. © 2015 European Society of Endocrinology.

Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

PubMed

Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

2009-11-10

Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon LPS induced suppression of defensive rage. The results demonstrate that LPS suppresses defensive rage by acting through peripheral TNF-alpha in periphery and that central effects of LPS suppression of defensive rage are mediated through PGE(2) and 5-HT(1A) receptors in the medial hypothalamus.

Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis.

PubMed

Nadesalingam, Ajantha; Chen, Jacky H K; Farahvash, Armin; Khan, Meraj A

2018-01-01

Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus ), and bacteria ( Pseudomonas aeruginosa and Staphylococcus aureus ). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12), and P. aeruginosa . Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H 2 O 2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent NETosis. Although hypertonic saline partially suppresses ionomycin-induced NETosis, it enhances A23187-induced NETosis, and it does not alter S. aureus -induced NETosis. Overall, this study determined that hypertonic saline suppresses NOX2-dependent NETosis induced by several agonists; in contrast, it has variable effects on neutrophil death induced by NOX2-independent NETosis agonists. These findings are important in understanding the regulation of NETosis and apoptosis in neutrophils.

Garlic oil suppressed the hematological disorders induced by chemotherapy and radiotherapy in tumor-bearing mice.

PubMed

Zeng, Tao; Li, Yang; Zhang, Cui-Li; Yu, Li-Hua; Zhu, Zhen-Ping; Zhao, Xiu-Lan; Xie, Ke-Qin

2013-06-01

Although the anticancer effects of garlic and its products have been demonstrated by a variety of studies; however, few studies were conducted to investigate the effects of garlic on the adverse effects of chemo/radiotherapy. In order to clarify the above question and make a more comprehensive understanding of the anticancer effects of garlic, tumor xenograft mice model was established by subcutaneous injection of H22 tumor cells, and was used for the investigation of effects of garlic oil (GO) on the chemo/radiotherapy. In the chemotherapy test, tumor-bearing mice were treated with cyclophosphamide (CTX) or CTX plus GO (25 or 50 mg/kg bw) for 14 d, while the mice received a single 5 Gy total body radiation or radiation plus GO (25 or 50 mg/kg bw) in radiotherapy test. The results showed that GO did not increase the tumor inhibitory rate of CTX/radiation, which indicated that GO could not enhance the chemo/radiosensitivity of cancer cells. However, the decrease of the peripheral total white blood cells (WBCs) count induced by CTX/radiation was significantly suppressed by GO cotreatment. Furthermore, GO cotreatment significantly inhibited the decrease of the DNA contents and the micronuclei ratio of the bone marrow. Lastly, the reduction of the endogenous spleen colonies induced by CTX/radiation was significantly suppressed by GO cotreatment. These findings support the idea that GO consumption may benefit for the cancer patients receiving chemotherapy or radiotherapy. © 2013 Institute of Food Technologists®

An integrated genomic approach identifies persistent tumor suppressive effects of transforming growth factor-β in human breast cancer

PubMed Central

2014-01-01

Introduction Transforming growth factor-βs (TGF-βs) play a dual role in breast cancer, with context-dependent tumor-suppressive or pro-oncogenic effects. TGF-β antagonists are showing promise in early-phase clinical oncology trials to neutralize the pro-oncogenic effects. However, there is currently no way to determine whether the tumor-suppressive effects of TGF-β are still active in human breast tumors at the time of surgery and treatment, a situation that could lead to adverse therapeutic responses. Methods Using a breast cancer progression model that exemplifies the dual role of TGF-β, promoter-wide chromatin immunoprecipitation and transcriptomic approaches were applied to identify a core set of TGF-β-regulated genes that specifically reflect only the tumor-suppressor arm of the pathway. The clinical significance of this signature and the underlying biology were investigated using bioinformatic analyses in clinical breast cancer datasets, and knockdown validation approaches in tumor xenografts. Results TGF-β-driven tumor suppression was highly dependent on Smad3, and Smad3 target genes that were specifically enriched for involvement in tumor suppression were identified. Patterns of Smad3 binding reflected the preexisting active chromatin landscape, and target genes were frequently regulated in opposite directions in vitro and in vivo, highlighting the strong contextuality of TGF-β action. An in vivo-weighted TGF-β/Smad3 tumor-suppressor signature was associated with good outcome in estrogen receptor-positive breast cancer cohorts. TGF-β/Smad3 effects on cell proliferation, differentiation and ephrin signaling contributed to the observed tumor suppression. Conclusions Tumor-suppressive effects of TGF-β persist in some breast cancer patients at the time of surgery and affect clinical outcome. Carefully tailored in vitro/in vivo genomic approaches can identify such patients for exclusion from treatment with TGF-β antagonists. PMID:24890385

Suppression of Botrytis cinerea on necrotic grapevine tissues by early-season applications of natural products and biological control agents.

PubMed

Calvo-Garrido, Carlos; Viñas, Inmaculada; Elmer, Philip A G; Usall, Josep; Teixidó, Neus

2014-04-01

Necrotic tissues within grape (Vitis vinifera) bunches represent an important source of Botrytis cinerea inoculum for Botrytis bunch rot (BBR) at harvest in vineyards. This research quantified the incidence of B. cinerea on necrotic floral and fruit tissues and the efficacy of biologically based treatments for suppression of B. cinerea secondary inoculum within developing bunches. At veraison (2009 and 2010), samples of aborted flowers, aborted fruits and calyptras were collected, and the incidence and sporulation of B. cinerea were determined. Aborted fruits presented significantly higher incidence in untreated samples. Early-season applications of Candida sake plus Fungicover®, Fungicover alone or Ulocladium oudemansii significantly reduced B. cinerea incidence on aborted flowers and calyptras by 46-85%. Chitosan treatment significantly reduced B. cinerea incidence on calyptras. None of the treatments reduced B. cinerea incidence on aborted fruits. Treatments significantly reduced sporulation severity by 48% or more. Treatments were effective at reducing B. cinerea secondary inoculum on necrotic tissues, in spite of the variable control on aborted fruits. This is the first report to quantify B. cinerea on several tissues of bunch trash and to describe the effective suppression of saprophytic B. cinerea inoculum by biologically based treatments. © 2013 Society of Chemical Industry.

Caffeine Suppresses the Activation of Hepatic Stellate Cells cAMP-Independently by Antagonizing Adenosine Receptors.

PubMed

Yamaguchi, Momoka; Saito, Shin-Ya; Nishiyama, Ryota; Nakamura, Misuzu; Todoroki, Kenichiro; Toyo'oka, Toshimasa; Ishikawa, Tomohisa

2017-01-01

During liver injury, hepatic stellate cells (HSCs) are activated by various cytokines and transdifferentiated into myofibroblast-like activated HSCs, which produce collagen, a major source of liver fibrosis. Therefore, the suppression of HSC activation is regarded as a therapeutic target for liver fibrosis. Several epidemiological reports have revealed that caffeine intake decreases the risk of liver disease. In this study, therefore, we investigated the effect of caffeine on the activation of primary HSCs isolated from mice. Caffeine suppressed the activation of HSC in a concentration-dependent manner. BAPTA-AM, an intracellular Ca 2+ chelator, had no effect on the caffeine-induced suppression of HSC activation. None of the isoform-selective inhibitors of phosphodiesterase1 to 5 affected changes in the morphology of HSC during activation, whereas CGS-15943, an adenosine receptor antagonist, inhibited them. Caffeine had no effect on intracellular cAMP level or on the phosphorylation of extracellular signal-regulated kinase (ERK)1/2. In contrast, caffeine significantly decreased the phosphorylation of Akt1. These results suggest that caffeine inhibits HSC activation by antagonizing adenosine receptors, leading to Akt1 signaling activation.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals

PubMed Central

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-an; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-01-01

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients. PMID:29022906

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.

PubMed

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-An; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-10-12

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.

Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats.

PubMed

Setoue, Minoru; Ohuchi, Seiya; Morita, Tatsuya; Sugiyama, Kimio

2008-07-01

Rats were fed 25% casein (25C) diets differing in choline levels (0-0.5%) with and without 0.5% guanidinoacetic acid (GAA) or 0.75% L-methionine for 7 d to determine the effects of dietary choline level on experimental hyperhomocysteinemia. The effects of dietary choline (0.30%) and betaine (0.34%) on GAA- and methionine-induced hyperhomocysteinemia were also compared. Dietary choline suppressed hyperhomocysteinemia induced by GAA, but not by methionine, in a dose-dependent manner. GAA-induced enhancement of the plasma homocysteine concentration was suppressed by choline and betaine to the same degree, but the effects of these compounds were relatively small on methionine-induced hyperhomocysteinemia. Dietary supplementation with choline and betaine significantly increased the hepatic betaine concentration in rats fed a GAA diet, but not in rats fed a methionine diet. These results indicate that choline and betaine are effective at relatively low levels in reducing plasma homocysteine, especially under the condition of betaine deficiency without a loading of homocysteine precursor.

Factors contributing to the resistivity of a higher casein diet against choline deficiency-induced hyperhomocysteinemia in rats.

PubMed

Liu, Yi-qun; Liu, Ying; Morita, Tatsuya; Mori, Makoto; Sugiyama, Kimio

2012-01-01

The mechanism by which feeding a higher casein diet results in resistance to choline deprivation-induced hyperhomocysteinemia was investigated in rats. Plasma homocysteine concentration was significantly lower in rats fed a 30% casein diet (30C) than in rats fed a 10% casein diet (10C). Choline deprivation did not enhance plasma homocysteine concentration in rats fed 30C, while it significantly enhanced plasma homocysteine concentration in rats fed 10C. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 10C was significantly suppressed by methionine supplementation in a dose-dependent manner in the range of 0.1 to 0.3%, but the suppressive effect of methionine became smaller with an increase in supplementation level in the range of 0.3 to 0.5%. At a 0.5% supplementation level, methionine did not exhibit any suppressive effect on choline deprivation-induced hyperhomocysteinemia. The higher plasma homocysteine concentration in rats fed choline-deprived 10C+0.5% methionine was significantly decreased by concurrent supplementation with 0.32% glycine+0.94% serine to the level of rats fed 10C. Raising dietary total amino acid level by adding 3.61% branched-chain amino acids (BCAA)+4.5% acidic amino acids (AAA) to choline-deprived 10C+0.5% methionine+0.32% glycine+0.94% serine resulted in a further decrease in plasma homocysteine concentration to a level lower than the level in rats fed 10C. Choline deprivation-induced increases in hepatic S-adenosylhomocysteine and homocysteine concentrations were significantly suppressed by supplementation with glycine+serine and further suppressed by BCAA+AAA. Hepatic cystathionine β-synthase activity and its gene expression were significantly increased by BCAA+AAA. Hepatic triglyceride concentration changed in a manner similar to that of plasma homocysteine concentration. The results indicate that there are at least three factors contributing to the resistivity of rats fed a higher casein diet (30C) to choline deprivation-induced hyperhomocysteinemia, i.e., higher intake of methionine, higher intake of glycine and serine, and higher intake of other amino acids such as BCAA and AAA.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

PubMed Central

Choi, Jiho; Jeon, Changhoon; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin

2017-01-01

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg), but not α1-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor. PMID:29088102

Suppressive effects of fisetin on mice T lymphocytes in vitro and in vivo.

PubMed

Song, Bocui; Guan, Shuang; Lu, Jing; Chen, Zhibao; Huang, Guoren; Li, Gen; Xiong, Ying; Zhang, Shuang; Yue, Zhanpeng; Deng, Xuming

2013-11-01

Most of the immunosuppressive drugs have satisfactory therapeutic effects on organ transplantation and autoimmune disease. However, their clinical application is limited by side effects. Therefore, new and safe immunosuppressive drugs against acute and chronic rejections are eagerly awaited. Fisetin, a flavonoid present in various types of vegetables and fruits, has few side effects and low level of toxicity, which would be a desirable clinical feature. In the present study, we investigated the immunosuppressive effects and underlying mechanisms of fisetin against T-cell activation in vitro and in vivo. We measured the effect of fisetin on T-lymphocyte proliferation, T-cell subsets, cell cycle progression, cytokine production, and nuclear factor activation in vitro, as well as its influence on T cell-mediated delayed-type hypersensitivity reaction in vivo. In vitro, the results showed that fisetin significantly suppressed mouse splenocytes proliferation, Th1 and Th2 cytokine production, cell cycle and the ratio of CD4(+)/CD8(+) T cells. Furthermore, fisetin exerts an immunosuppressive effect in mouse T lymphocytes through the suppression of nuclear factor kappa B activation and nuclear factor of activated T cells signaling in a dose-dependent manner. In vivo, fisetin treatment also significantly inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reactions in mice. Fisetin had strong immunosuppressive activity in vitro and in vivo, suggesting a potential role for fisetin as an immunosuppressive agent. Copyright © 2013. Published by Elsevier Inc.

Control of edge localized modes by pedestal deposited impurity in the HL-2A tokamak

NASA Astrophysics Data System (ADS)

Zhang, Y. P.; Mazon, D.; Zou, X. L.; Zhong, W. L.; Gao, J. M.; Zhang, K.; Sun, P.; Dong, C. F.; Cui, Z. Y.; Liu, Yi; Shi, Z. B.; Yu, D. L.; Cheng, J.; Jiang, M.; Xu, J. Q.; Isobe, M.; Xiao, G. L.; Chen, W.; Song, S. D.; Bai, X. Y.; Zhang, P. F.; Yuan, G. L.; Ji, X. Q.; Li, Y. G.; Zhou, Y.; Delpech, L.; Ekedahl, A.; Giruzzi, G.; Hoang, T.; Peysson, Y.; Song, X. M.; Song, X. Y.; Li, X.; Ding, X. T.; Dong, J. Q.; Yang, Q. W.; Xu, M.; Duan, X. R.; Liu, Y.; the HL-2A Team

2018-04-01

Effect of the pedestal deposited impurity on the edge-localized mode (ELM) behaviour has been observed and intensively investigated in the HL-2A tokamak. Impurities have been externally seeded by a newly developed laser blow-off (LBO) system. Both mitigation and suppression of ELMs have been realized by LBO-seeded impurity. Measurements have shown that the LBO-seeded impurity particles are mainly deposited in the pedestal region. During the ELM mitigation phase, the pedestal density fluctuation is significantly increased, indicating that the ELM mitigation may be achieved by the enhancement of the pedestal transport. The transition from ELM mitigation to ELM suppression was triggered when the number of the LBO-seeded impurity exceeds a threshold value. During the ELM suppression phase, a harmonic coherent mode (HCM) is excited by the LBO-seeded impurity, and the pedestal density fluctuation is significantly decreased, the electron density is continuously increased, implying that HCM may reduce the pedestal turbulence, suppress ELMs, increase the pedestal pressure, thus extending the Peeling-Ballooning instability limit. It has been found that the occurance of the ELM mitigation and ELM suppression closely depends on the LBO laser spot diameter.

Cross-orientation masking in human color vision: application of a two-stage model to assess dichoptic and monocular sources of suppression.

PubMed

Kim, Yeon Jin; Gheiratmand, Mina; Mullen, Kathy T

2013-05-28

Cross-orientation masking (XOM) occurs when the detection of a test grating is masked by a superimposed grating at an orthogonal orientation, and is thought to reveal the suppressive effects mediating contrast normalization. Medina and Mullen (2009) reported that XOM was greater for chromatic than achromatic stimuli at equivalent spatial and temporal frequencies. Here we address whether the greater suppression found in binocular color vision originates from a monocular or interocular site, or both. We measure monocular and dichoptic masking functions for red-green color contrast and achromatic contrast at three different spatial frequencies (0.375, 0.75, and 1.5 cpd, 2 Hz). We fit these functions with a modified two-stage masking model (Meese & Baker, 2009) to extract the monocular and interocular weights of suppression. We find that the weight of monocular suppression is significantly higher for color than achromatic contrast, whereas dichoptic suppression is similar for both. These effects are invariant across spatial frequency. We then apply the model to the binocular masking data using the measured values of the monocular and interocular sources of suppression and show that these are sufficient to account for color binocular masking. We conclude that the greater strength of chromatic XOM has a monocular origin that transfers through to the binocular site.

The Effect of Aging and Attention on Visual Crowding and Surround Suppression of Perceived Contrast Threshold.

PubMed

Malavita, Menaka S; Vidyasagar, Trichur R; McKendrick, Allison M

2017-02-01

The purpose of this study was to study how, in midperipheral vision, aging affects visual processes that interfere with target detection (crowding and surround suppression) and to determine whether the performance on such tasks are related to visuospatial attention as measured by visual search. We investigated the effect of aging on crowding and suppression in detection of a target in peripheral vision, using different types of flanking stimuli. Both thresholds were also obtained while varying the position of the flanker (placed inside or outside of target, relative to fixation). Crowding thresholds were also estimated with spatial uncertainty (jitter). Additionally, we included a visual search task comprising Gabor stimuli to investigate whether performance is related to top-down attention. Twenty young adults (age, 18-32 years; mean age, 26.1 years; 10 males) and 19 older adults (age, 60-74 years; mean age, 70.3 years; 10 males) participated in the study. Older adults showed more surround suppression than the young (F[1,37] = 4.21; P < 0.05), but crowding was unaffected by age. In the younger group, the position of the flanker influenced the strength of crowding, but not the strength of suppression (F[1,39] = 4.11; P < 0.05). Crowding was not affected by spatial jitter of the stimuli. Neither crowding nor surround suppression was predicted by attentional efficiency measured in the visual search task. There was also no significant correlation between crowding and surround suppression. We show that aging does not affect visual crowding but does increase surround suppression of contrast, suggesting that crowding and surround suppression may be distinct visual phenomena. Furthermore, strengths of crowding and surround suppression did not correlate with each other nor could they be predicted by efficiency of visual search.

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ(9)-tetrahydrocannabinol in human CD4(+) T cells.

PubMed

Ngaotepprutaram, Thitirat; Kaplan, Barbara L F; Kaminski, Norbert E

2013-11-15

We have previously reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4(+) T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ(9)-THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ(9)-THC attenuated CD40L expression in human CD4(+) T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ(9)-THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ(9)-THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ(9)-THC suppresses human T cell function. © 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Keqing; Wang, Biao; Liu, Jiajia

Highlights: • In this paper, α-FeOOH/rGO hybrids had been prepared by a facile hydrothermal method. • The addition of the α-FeOOH/rGO hybrids showed a significant effect on the thermal stability and smoke suppression properties of PS composites. • Graphene can be employed to improve the smoke suppression properties of polymer and further extended the application of graphene. - Abstract: In this work, α-FeOOH/rGO hybrids were firstly prepared by a facile hydrothermal method. X-ray diffraction and transmission electron microscopy results indicated that α-FeOOH nanoparticles were dispersed uniformly on the surface of graphene nanosheets. Subsequently, the α-FeOOH/rGO hybrids were incorporated into polystyrenemore » (PS) matrix for the improvement of the thermal stability and smoke suppression properties. It was found that the thermal stability of PS nanocomposite was obviously enhanced upon the introduction of 2.0 wt% α-FeOOH/rGO hybrids. Furthermore, the addition of α-FeOOH/rGO hybrids could improve the smoke suppression properties of PS nanocomposites, as evidenced by the dramatical reduction of carbon monoxide production rate, total smoke release and total smoke production. The total flammable gaseous products from the PS nanocomposites were decreased which further led to the inhibition of smoke. Such a significant improvement in thermal stability and smoke suppression properties was mainly attributed to the physical barrier effect of graphene nanosheets and the catalytic carbonization function of α-FeOOH nanoparticles.« less

Improved background suppression in ¹H MAS NMR using composite pulses.

PubMed

Odedra, Smita; Wimperis, Stephen

2012-08-01

A well known feature of ¹H MAS NMR spectroscopy, particularly of solids where the concentration of ¹H nuclei is low, is the presence in the spectrum of a significant broad "background" signal arising from ¹H nuclei that are outside the MAS rotor and radiofrequency coil, probably located on the surfaces of the static components of the probehead. A popular method of suppressing this unwanted signal is the "depth pulse" method, consisting of a 90° pulse followed by one or two 180° pulses that are phase cycled according to the "Exorcycle" scheme, which removes signal associated with imperfect 180° pulses. Consequently, only spins in the centre of the radiofrequency coil contribute to the ¹H MAS spectrum, while those experiencing a low B₁ field outside the coil are suppressed. Although very effective at removing background signal from the spectrum, one drawback with this approach is that significant loss of the desired signal from the sample also occurs. Here we investigate the ¹H background suppression problem and, in particular, the use of novel antisymmetric passband composite pulses to replace the simple pulses in a depth pulse experiment. We show that it is possible to improve the intensity of the ¹H signals of interest while still maintaining effective background suppression. We expect that these results will be relevant to ¹H MAS NMR studies of, for example, nominally perdeuterated biological samples or nominally anhydrous inorganic materials. Copyright © 2012 Elsevier Inc. All rights reserved.

Improved background suppression in 1H MAS NMR using composite pulses

NASA Astrophysics Data System (ADS)

Odedra, Smita; Wimperis, Stephen

2012-08-01

A well known feature of 1H MAS NMR spectroscopy, particularly of solids where the concentration of 1H nuclei is low, is the presence in the spectrum of a significant broad "background" signal arising from 1H nuclei that are outside the MAS rotor and radiofrequency coil, probably located on the surfaces of the static components of the probehead. A popular method of suppressing this unwanted signal is the "depth pulse" method, consisting of a 90° pulse followed by one or two 180° pulses that are phase cycled according to the "Exorcycle" scheme, which removes signal associated with imperfect 180° pulses. Consequently, only spins in the centre of the radiofrequency coil contribute to the 1H MAS spectrum, while those experiencing a low B1 field outside the coil are suppressed. Although very effective at removing background signal from the spectrum, one drawback with this approach is that significant loss of the desired signal from the sample also occurs. Here we investigate the 1H background suppression problem and, in particular, the use of novel antisymmetric passband composite pulses to replace the simple pulses in a depth pulse experiment. We show that it is possible to improve the intensity of the 1H signals of interest while still maintaining effective background suppression. We expect that these results will be relevant to 1H MAS NMR studies of, for example, nominally perdeuterated biological samples or nominally anhydrous inorganic materials.

Effects of burn with and without Escherichia coli infection in rats on intestinal vs. splenic T-cell responses.

PubMed

Ravindranath, T; Al-Ghoul, W; Namak, S; Fazal, N; Durazo-Arvizu, R; Choudhry, M; Sayeed, M M

2001-12-01

To evaluate the effect of burn injury with and without an Escherichia coliseptic complication on T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses in intestinal Peyer's patch and splenic T cells. Prospective, randomized, sham-controlled animal study. University medical center research laboratory. Adult male Sprague-Dawley rats. Rats were subjected to a 30% total body surface area, full skin thickness burn. Infection in rats was induced via intraperitoneal inoculation of E. coli, 10(9) colony forming units/kg, with or without a prior burn. Rat Peyer's patch and splenic T lymphocytes were isolated by using a nylon wool cell purification protocol. T-cell proliferation, interleukin-2 production, and Ca(2+) signaling responses were measured after stimulation of cells with the mitogen, concanavalin A. T-cell proliferation was determined by measuring incorporation of (3)H-thymidine into T-cell cultures. Interleukin-2 production by T-cell cultures was measured by using enzyme-linked immunosorbent assay. Intracellular T-cell Ca2(+ )concentration, [Ca(2+)](i), was measured by the use of Ca(2+)-specific fluorescent label, fura-2, and its fluorometric quantification. [Ca(2+)](i) was also evaluated by the use of digital video imaging of fura-2 loaded individual T cells. T-cell proliferation and interleukin-2 production were suppressed substantially in both Peyer's patch and splenic T cells 3 days after either the initial burn alone or burn followed by the E. coli inoculation at 24 hrs after the initial burn. There seemed to be no demonstrable additive effects of E. coli infection on the effects produced by burn injury alone. The T-cell proliferation and interleukin-2 production suppressions with burn or burn-plus-infection insults were correlated with attenuated Ca(2+) signaling. E. coli infection alone suppressed T-cell proliferation in Peyer's patch but not in splenic T cells at 2 days postbacterial inoculation; E. coli infection had no effect on Peyer's patch or splenic T cells at 1 day postinjury. On the other hand, burn injury alone caused a substantial T-cell proliferative suppression at 2 days postburn in both Peyer's patch and splenic cells and a significant suppression in T-cell proliferation on day 1 postburn in Peyer's patch but not in the spleen. An initial burn injury suppressed T-cell proliferation at a level that it would not be further affected by a subsequent infection even if the infection by itself has the potential of suppressing T-cell proliferation. An earlier onset of T-cell suppression in Peyer's patch cells than in the spleen with burn could be attributable to an initial hypoperfusion-related intestinal mucosal tissue injury. Overall, our study supports the concept that burn injury per se can significantly suppress T-cell mediated immunity and that the intestine is an early tissue site of such suppression.

Alpha-band rhythm suppression during memory recall reflecting memory performance.

PubMed

Yokosawa, Koichi; Kimura, Keisuke; Chitose, Ryota; Momiki, Takuya; Kuriki, Shinya

2016-08-01

Alpha-band rhythm is thought to be involved in memory processes, similarly to other spontaneous brain rhythms. Ten right-handed healthy volunteers participated in our proposed sequential short-term memory task that provides a serial position effect in accuracy rate. We recorded alpha-band rhythms by magnetoencephalography during performance of the task and observed that the amplitude of the rhythm was suppressed dramatically in the memory recall period. The suppressed region was estimated to be in the occipital lobe, suggesting that alpha-band rhythm is suppressed by activation of the occipital attentional network. Additionally, the alpha-band suppression reflected accuracy rate, that is, the amplitude was suppressed more when recalling items with higher accuracy rate. The sensors with a significant correlation between alpha-band amplitude and accuracy rate were located widely from the frontal to occipital regions mainly in the right hemisphere. The results suggests that alpha-band rhythm is involved in memory recall and can be index of memory performance.

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

PubMed Central

Lew, Kim H.; Ludwig, Elizabeth A.; Milad, Mark A.; Donovan, Kathleen; Middleton, Elliott; Ferry, James J.; Jusko, William J.

2014-01-01

The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response. PMID:8222483

Penfluridol suppresses glioblastoma tumor growth by Akt-mediated inhibition of GLI1

PubMed Central

Ranjan, Alok; Srivastava, Sanjay K.

2017-01-01

Glioblastoma (GBM) is the most common brain tumor with poor survival rate. Our results show that penfluridol, an antipsychotic drug significantly reduced the survival of ten adult and pediatric glioblastoma cell lines with IC50 ranging 2–5 μM after 72 hours of treatment and induced apoptosis. Penfluridol treatment suppressed the phosphorylation of Akt at Ser473 and reduced the expression of GLI1, OCT4, Nanog and Sox2 in several glioblastoma cell lines in a concentration-dependent manner. Inhibiting Akt with LY294002 and siRNA, or inhibiting GLI1 using GANT61, cyclopamine, siRNA and CRISPR/Cas9 resulted in enhanced cell growth suppressive effects of penfluridol. On the other hand, overexpression of GLI1 significantly attenuated the effects of penfluridol. Our results further demonstrated that penfluridol treatment inhibited the growth of U87MG tumors by 65% and 72% in subcutaneous and intracranial in vivo glioblastoma tumor models respectively. Immunohistochemical and western blot analysis of tumors revealed reduced pAkt (Ser 473), GLI1, OCT4 and increase in caspase-3 cleavage and TUNEL staining, confirming in vitro findings. Taken together, our results indicate that overall glioblastoma tumor growth suppression by penfluridol was associated with Akt-mediated inhibition of GLI1. PMID:28380428

Suppression Effects of Betaine-Enriched Spinach on Hyperhomocysteinemia Induced by Guanidinoacetic Acid and Choline Deficiency in Rats

PubMed Central

Liu, Yi-Qun; Jia, Zheng; Han, Feng; Inakuma, Takahiro; Miyashita, Tatsuya; Sugiyama, Kimio; Sun, Li-Cui; Xiang, Xue-Song; Huang, Zhen-Wu

2014-01-01

Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA) addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25C) was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S) was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine β-synthase (CBS) in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation. PMID:25250392

Suppression effects of betaine-enriched spinach on hyperhomocysteinemia induced by guanidinoacetic acid and choline deficiency in rats.

PubMed

Liu, Yi-Qun; Jia, Zheng; Han, Feng; Inakuma, Takahiro; Miyashita, Tatsuya; Sugiyama, Kimio; Sun, Li-Cui; Xiang, Xue-Song; Huang, Zhen-Wu

2014-01-01

Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA) addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25 C) was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S) was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine β-synthase (CBS) in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.

Interferon-gamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1995-01-01

Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and perhaps to contribute to the anemia of chronic disease. In this study we demonstrated that the concentration of INF gamma required to suppress murine burst forming unit-erythroid (BFU-E) growth was significantly less than that required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma acted at the most primitive step in erythroid progenitor cell differentiation and proliferation, as inhibition was maximal when added at the time of BFU-E culture initiation. Inhibition was progressively less if INF gamma addition was delayed after culture initiation. The effects of INF gamma on BFU-E did not require the presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF alpha, or GM-CSF. This applied whether INF gamma was added to culture with individual antibodies or with a combination of all three antibodies. INF gamma was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as their effects were not neutralized by a monoclonal anti-INF gamma antibody. In contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous addition of anti-INF gamma. We have previously shown that the addition of TNF alpha does not suppress BFU-E growth in cultures from marrow depleted of macrophages. Suppression did occur, however, if a small concentration of INF gamma that does not inhibit and increasing concentration of TNF alpha were added to culture, suggesting a synergistic effect between INF-gamma and TNF alpha. These observations suggest that INF gamma is a potent direct inhibitor of erythroid colony growth in vitro. It exerts its negative regulatory effect primarily on the earliest stages of erythroid progenitor cell differentiation and proliferation, as much higher doses are required to suppress late erythroid cell development. INF gamma is also involved in GM-CSF-induced inhibition of BFU-E colony growth.

Activation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals.

PubMed

Liang, Shuwei; Chen, Zhuojia; Jiang, Guanmin; Zhou, Yan; Liu, Qiao; Su, Qiao; Wei, Weidong; Du, Jun; Wang, Hongsheng

2017-02-01

Triple-negative breast cancer (TNBC) is characterized by high vascularity and frequent metastasis. Here, we found that activation of G protein-coupled estrogen receptor (GPER) by its specific agonist G-1 can significantly inhibit interleukin 6 (IL-6) and vascular endothelial growth factor A (VEGF-A). TNBC tissue microarrays from 100 TNBC patients revealed GPER is negatively associated with IL-6 levels and higher grade and stage. Activation of GPER or anti-IL-6 antibody can inhibit both in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and migration of TNBC cells. While recombinant IL-6 supplementary can significantly reverse the inhibitory effects of G-1, suggesting the essential role of IL-6 in G-1 induced suppression of angiogenesis and invasiveness of TNBC cells. G-1 treatment decreased the phosphorylation, nuclear localization, transcriptional activities of NF-κB and suppressed its binding with IL-6 promoter. BAY11-7028, the inhibitor of NF-κB, can mimic the effect of G-1 to suppression of IL-6 and VEGF-A. While over expression of p65 can attenuate the inhibitory effects of G-1 on IL-6 and VEGF expression. The suppression of IL-6 by G-1 can further inhibit HIF-1α and STAT3 signals in TNBC cells by inhibition their expression, phosphorylation and/or nuclear localization. Moreover, G-1 also inhibited the in vivo NF-κB/IL-6 signals and angiogenesis and metastasis of MDA-MB-231 xenograft tumors. In conclusion, our study demonstrated that activation of GPER can suppress migration and angiogenesis of TNBC via inhibition of NF-κB/IL-6 signals, therefore it maybe act as an important target for TNBC treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Suppression of Poxvirus Replication by Resveratrol.

PubMed

Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

2017-01-01

Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

Kefiran suppresses antigen-induced mast cell activation.

PubMed

Furuno, Tadahide; Nakanishi, Mamoru

2012-01-01

Kefir is a traditional fermented milk beverage produced by kefir grains in the Caucasian countries. Kefiran produced by Lactobacillus kefiranofaciens in kefir grains is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. Here we investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca(2+) mobilization, degranulation, and tumor necrosis factor-α production in bone marrow-derived mast cells (BMMCs) in a dose-dependent manner. The phosphorylation of Akt, glycogen synthase kinase 3β, and extracellular signal-regulated kinases (ERKs) after antigen stimulation was also suppressed by pretreatment of BMMCs with kefiran. These findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran.

The effect of 6-methylthiohexyl isothiocyanate isolated from Wasabia japonica (wasabi) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-buatnone-induced lung tumorigenesis in mice.

PubMed

Yano, T; Yajima, S; Virgona, N; Yano, Y; Otani, S; Kumagai, H; Sakurai, H; Kishimoto, M; Ichikawa, T

2000-07-31

The present study was undertaken to estimate the effect of 6-methylthiohexyl isothiocyanate (6MHITC) isolated from Wasabia japonica (wasabi) pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice. Pretreatment with 6MHITC for 4 consecutive days at a daily dose of 5 micromol significantly inhibited NNK-induced O(6)-methylguanine formation in lungs at 4 h after the injection. In conjugation with this inhibitory effect, 6MHITC suppressed the increase in proliferating nuclear cell antigen level as well as ornithine decarboxylase activity at a promotion stage of NNK-induced lung tumorigenesis. Finally, this treatment of 6MHITC suppressed the NNK-induced lung tumorigenesis in mice. These results suggest that 6MHITC inhibits the development of lung tumors in mice treated with NNK, due to the suppression of initiation stage.

[Effect of previous experience in reacting to a danger signal on "open field" behavior in the rat].

PubMed

Poltyreva, T E; Petrov, E S

1983-01-01

Modification of rats behaviour in an "hopen field" test was investigated, induced by an acoustic stimulus, previously subjected to conditioning in a shuttle chamber in experiments with possibility and impossibility of avoidance from electrical shock. It has been established that presentation of a stimulus having the meaning of a danger signal, in a new situation, significantly suppresses investigating behaviour of rats, whereas the stimulus which had not been subjected to conditioning exerts no marked effect on behaviour. The greatest suppression was observed in rats with "learned helplessness". This fact suggests that the degree of suppression of the behaviour in an open field in response to a danger signal, depends on the animal's previous experience in reacting to this signal.

A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa

PubMed Central

Gi, Mia; Jeong, Junhui; Lee, Keehoon; Lee, Kang-Mu; Toyofuku, Masanori; Yong, Dong Eun

2014-01-01

Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 μM DTPA. Supplementation with Zn2+ or Mn2+ ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection. PMID:25246397

18β-Glycyrrhetinic acid suppresses TNF-α induced matrix metalloproteinase-9 and vascular endothelial growth factor by suppressing the Akt-dependent NF-κB pathway.

PubMed

Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Dilshara, Matharage Gayani; Park, Sang Rul; Choi, Yung Hyun; Hyun, Jin-Won; Chang, Weon-Young; Kim, Gi-Young

2014-08-01

Little is known about the molecular mechanism through which 18β-glycyrrhetinic acid (GA) inhibits metastasis and invasion of cancer cells. Therefore, this study aimed to investigate the effects of GA on the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in various types of cancer cells. We found that treatment with GA reduces tumor necrosis factor-α (TNF-α)-induced Matrigel invasion with few cytotoxic effects. Our findings also showed that MMP-9 and VEGF expression increases in response to TNF-α; however, GA reverses their expression. In addition, GA inhibited inhibitory factor kappa B degradation, sustained nuclear factor-kappa B (NF-κB) subunits, p65 and p50, in the cytosol compartments, and consequently suppressed the TNF-α-induced DNA-binding activity and luciferase activity of NF-κB. Specific NF-κB inhibitors, pyrrolidine dithiocarbamate, MG132, and PS-1145, also attenuated TNF-α-mediated MMP-9 and VEGF expression as well as activity by suppressing their regulatory genes. Furthermore, phosphorylation of TNF-α-induced phosphatidyl-inositol 3 kinase (PI3K)/Akt was significantly downregulated in the presence of GA accompanying with the inhibition of NF-κB activity, and as presumed, the specific PI3K/Akt inhibitor LY294002 significantly decreased MMP-9 and VEGF expression as well as activity. These results suggest that GA operates as a potential anti-invasive agent by downregulating MMP-9 and VEGF via inhibition of PI3K/Akt-dependent NF-κB activity. Taken together, GA might be an effective anti-invasive agent by suppressing PI3K/Akt-mediated NF-κB activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of bitter melon (Momordica charantia L.) on the gut microbiota in high fat diet and low dose streptozocin-induced rats.

PubMed

Zhu, Ying; Bai, Juan; Zhang, Yi; Xiao, Xiang; Dong, Ying

2016-09-01

The effects on gut microbiota of type 2 diabetic rats fed a bitter melon formulation (BLSP, a lyophilized superfine powder) were investigated. BLSP treatment significantly reduced fasting blood glucose levels (p < 0.05) and serum insulin levels (p < 0.05) of the diabetic rats. The gut microbiota of treated and control rats were profiled by PCR amplification and pyrosequencing of 16S rRNA genes (V3-V9 region). BLSP significantly reduced the ratio of Firmicutes to Bacteroidetes in diabetic rats, while the relative abundances of Ruminococcaceae, Bacteroides and Ruminococcus were significantly lowered in BLSP-treated rats compared to diabetic rats. Additionally, BLSP significantly suppressed the activation of MAPK (JNK and p38). The results indicate that BLSP can significantly modify the proportions of particular gut microbiota in diabetic rats without disturbing the normal population diversity. By suppressing the activation of MAPK signaling pathway, a BLSP containing diet may ameliorate type 2 diabetes.

New therapy with ASC-J9® to suppress the prostatitis via altering the cytokine CCL2 signals

PubMed Central

Lin, Shin-Jen; Chou, Fu-Ju; Lin, Chang-Yi; Chang, Hong-Chiang; Yeh, Shuyuan; Chang, Chawnshang

2016-01-01

Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects. PMID:27564257

New therapy with ASC-J9® to suppress the prostatitis via altering the cytokine CCL2 signals.

PubMed

Lin, Shin-Jen; Chou, Fu-Ju; Lin, Chang-Yi; Chang, Hong-Chiang; Yeh, Shuyuan; Chang, Chawnshang

2016-10-11

Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects.

Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and biofilm production in Legionella species.

PubMed

Kimura, Soichiro; Tateda, Kazuhiro; Ishii, Yoshikazu; Horikawa, Manabu; Miyairi, Shinichi; Gotoh, Naomasa; Ishiguro, Masaji; Yamaguchi, Keizo

2009-06-01

Bacteria commonly communicate with each other by a cell-to-cell signalling mechanism known as quorum sensing (QS). Recent studies have shown that the Las QS autoinducer N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12)-HSL) of Pseudomonas aeruginosa performs a variety of functions not only in intraspecies communication, but also in interspecies and interkingdom interactions. In this study, we report the effects of Pseudomonas 3-oxo-C(12)-HSL on the growth and suppression of virulence factors in other bacterial species that frequently co-exist with Ps. aeruginosa in nature. It was found that 3-oxo-C(12)-HSL, but not its analogues, suppressed the growth of Legionella pneumophila in a dose-dependent manner. However, 3-oxo-C(12)-HSL did not exhibit a growth-suppressive effect on Serratia marcescens, Proteus mirabilis, Escherichia coli, Alcaligenes faecalis and Stenotrophomonas maltophilia. A concentration of 50 microM 3-oxo-C(12)-HSL completely inhibited the growth of L. pneumophila. Additionally, a significant suppression of biofilm formation was demonstrated in L. pneumophila exposed to 3-oxo-C(12)-HSL. Our results suggest that the Pseudomonas QS autoinducer 3-oxo-C(12)-HSL exerts both bacteriostatic and virulence factor-suppressive activities on L. pneumophila alone.

MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Kui; Fan, Wendong; Wang, Xing

Highlights: Black-Right-Pointing-Pointer Laminar shear stress upregulates miR-101 expression in vascular endothelial cells. Black-Right-Pointing-Pointer miR-101 represses mTOR expression through a specific 3 Prime UTR binding site. Black-Right-Pointing-Pointer Overexpression of miR-101 inhibits G1/S transition and endothelial cell proliferation. Black-Right-Pointing-Pointer Blockade of miR-101 attenuates the suppressive effect of laminar flow on mTOR expression. -- Abstract: Shear stress associated with blood flow plays an important role in regulating gene expression and cell function in endothelial cells (ECs). MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that negatively regulate the expression of target genes by binding to the mRNA 3 Prime -untranslated region (3 Primemore » UTR) at the posttranscriptional level involved in diverse cellular processes. This study demonstrates that microRNA-101 in response to laminar shear stress (LSS) is involved in the flow regulation of gene expression in ECs. qRT-PCR analysis showed that miR-101 expression was significantly upregulated in human umbilical vein endothelial cells (HUVECs) exposed to 12 dyn/cm{sup 2} laminar shear stress for 12 h. We found that transfection of miR-101 significantly decreased the luciferase activity of plasmid reporter containing the 3 Prime UTR of mammalian target of rapamycin (mTOR) gene. Western analysis revealed that the protein level of mTOR was significantly reduced in ECs transfected with miR-101. Furthermore, miR-101 overexpression induced cell cycle arrest at the G1/S transition and suppressed endothelial cell proliferation. Finally, transfection of miR-101 inhibitors attenuated the suppressive effects of LSS on mTOR expression, which identified the efficacy of loss-of-function of miR-101 in laminar flow-treated ECs. In conclusion, we have demonstrated that upregulation of miR-101 in response to LSS contributes to the suppressive effects of LSS on mTOR expression and EC proliferation. These studies advance our understanding of the posttranscriptional mechanisms by which shear stress modulates endothelial homeostasis.« less

Effects of peptide fractions with different isoelectric points from wheat gluten hydrolysates on lipid oxidation in pork meat patties.

PubMed

Park, Eun Young; Imazu, Hiroko; Matsumura, Yasuki; Nakamura, Yasushi; Sato, Kenji

2012-08-01

Wheat gluten hydrolysate (WGH) was fractionated on the basis of the amphoteric nature of sample peptides by preparative isoelectric focusing (autofocusing). Cooked pork patties were stored at 4 and 20 °C in the dark. WGH and autofocusing fractions suppressed the oxidation of lipids in the patties. The acidic (pI < 3.0) and basic (pI > 9.0) autofocusing fractions suppressed lipid oxidation in the cooked patties to a greater extent than other fractions and WGH. Each autofocusing fraction was evaluated by 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical scavenging activities, β-carotene bleaching, oxygen radical absorbance capacity, and Fe(2+) chelating assays; however, none of the in vitro assays predicted the suppressive effect of WGH on lipid oxidation in the cooked patties. These findings suggest that the microdistribution of peptides in food systems and their interaction with food matrix compounds play a significant role in the suppression of lipid oxidation in meat patties rather than radical scavenging activity.

Various background pattern-effect on saccadic suppression.

PubMed

Mitrani, L; Radil-Weiss, T; Yakimoff, N; Mateeff, S; Bozkov, V

1975-09-01

It has been proved that the saccadic suppression is a phenomenon closely related to the presence of contours and structures in the visual field. Experiments were performed to clarify whether the structured background influences the pattern of attention distribution (making the stimulus detection more difficult) or whether the elevation of visual threshold is due to the "masking' effect of the moving background image over the retina. Two types of backgrounds were used therefore: those with symbolic meaning in the processing of which "psychological' mechanisms are presumably involved like picture reproductions of famous painters and photographs of nudes, and those lacking semantic significance like computer figures composed of randomly distributed black and white squares with different grain expressed as the entropy of the pattern. The results show that saccadic suppression is primarily a consequence of peripheral mechanisms, probably of lateral inhibition in the visual field occurring in the presence of moving edges over the retina. Psychological factors have to be excluded as being fundamental for saccadic suppression.

mu-Opioid receptor-independent fashion of the suppression of sodium currents by mu-opioid analgesics in thalamic neurons.

PubMed

Hashimoto, Keisuke; Amano, Taku; Kasakura, Akiko; Uhl, George R; Sora, Ichiro; Sakai, Norio; Kuzumaki, Naoko; Suzuki, Tsutomu; Narita, Minoru

2009-03-27

Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone, which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons.

The tomato plastidic fructokinase SlFRK3 plays a role in xylem development.

PubMed

Stein, Ofer; Damari-Weissler, Hila; Secchi, Francesca; Rachmilevitch, Shimon; German, Marcelo A; Yeselson, Yelena; Amir, Rachel; Schaffer, Arthur; Holbrook, N Michele; Aloni, Roni; Zwieniecki, Maciej A; Granot, David

2016-03-01

Plants have two kinds of fructokinases (FRKs) that catalyze the key step of fructose phosphorylation, cytosolic and plastidic. The major cytosolic tomato FRK, SlFRK2, is essential for the development of xylem vessels. In order to study the role of SlFRK3, which encodes the only plastidic FRK, we generated transgenic tomato (Solanum lycopersicon) plants with RNAi suppression of SlFRK3 as well as plants expressing beta-glucoronidase (GUS) under the SlFRK3 promoter. GUS staining indicated SlFRK3 expression in vascular tissues of the leaves and stems, including cambium, differentiating xylem, young xylem fibers and phloem companion cells. Suppression of SlFRK3 reduced the stem xylem area, stem and root water conductance, and whole-plant transpiration, with minor effects on plant development. However, suppression of SlFRK3 accompanied by partial suppression of SlFRK2 induced significant growth-inhibition effects, including the wilting of mature leaves. Grafting experiments revealed that these growth effects are imposed primarily by the leaves, whose petioles had unlignified, thin-walled xylem fibers with collapsed parenchyma cells around the vessels. A cross between the SlFRK2-antisense and SlFRK3-RNAi lines exhibited similar wilting and anatomical effects, confirming that these effects are the result of the combined suppression of SlFRK3 and SlFRK2. These results demonstrate a role of the plastidic SlFRK3 in xylem development and hydraulic conductance. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Non-transmissible Sendai virus vector encoding c-myc suppressor FBP-interacting repressor for cancer therapy

PubMed Central

Matsushita, Kazuyuki; Shimada, Hideaki; Ueda, Yasuji; Inoue, Makoto; Hasegawa, Mamoru; Tomonaga, Takeshi; Matsubara, Hisahiro; Nomura, Fumio

2014-01-01

AIM: To investigate a novel therapeutic strategy to target and suppress c-myc in human cancers using far up stream element (FUSE)-binding protein-interacting repressor (FIR). METHODS: Endogenous c-Myc suppression and apoptosis induction by a transient FIR-expressing vector was examined in vivo via a HA-tagged FIR (HA-FIR) expression vector. A fusion gene-deficient, non-transmissible, Sendai virus (SeV) vector encoding FIR cDNA, SeV/dF/FIR, was prepared. SeV/dF/FIR was examined for its gene transduction efficiency, viral dose dependency of antitumor effect and apoptosis induction in HeLa (cervical squamous cell carcinoma) cells and SW480 (colon adenocarcinoma) cells. Antitumor efficacy in a mouse xenograft model was also examined. The molecular mechanism of the anti-tumor effect and c-Myc suppression by SeV/dF/FIR was examined using Spliceostatin A (SSA), a SAP155 inhibitor, or SAP155 siRNA which induce c-Myc by increasing FIR∆exon2 in HeLa cells. RESULTS: FIR was found to repress c-myc transcription and in turn the overexpression of FIR drove apoptosis through c-myc suppression. Thus, FIR expressing vectors are potentially applicable for cancer therapy. FIR is alternatively spliced by SAP155 in cancer cells lacking the transcriptional repression domain within exon 2 (FIR∆exon2), counteracting FIR for c-Myc protein expression. Furthermore, FIR forms a complex with SAP155 and inhibits mutual well-established functions. Thus, both the valuable effects and side effects of exogenous FIR stimuli should be tested for future clinical application. SeV/dF/FIR, a cytoplasmic RNA virus, was successfully prepared and showed highly efficient gene transduction in in vivo experiments. Furthermore, in nude mouse tumor xenograft models, SeV/dF/FIR displayed high antitumor efficiency against human cancer cells. SeV/dF/FIR suppressed SSA-activated c-Myc. SAP155 siRNA, potentially produces FIR∆exon2, and led to c-Myc overexpression with phosphorylation at Ser62. HA-FIR suppressed endogenous c-Myc expression and induced apoptosis in HeLa and SW480 cells. A c-myc transcriptional suppressor FIR expressing SeV/dF/FIR showed high gene transduction efficiency with significant antitumor effects and apoptosis induction in HeLa and SW480 cells. CONCLUSION: SeV/dF/FIR showed strong tumor growth suppression with no significant side effects in an animal xenograft model, thus SeV/dF/FIR is potentially applicable for future clinical cancer treatment. PMID:24764668

Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis.

PubMed

Zhao, Linjie; Huang, Shuang; Mei, Shenglin; Yang, Zhengnan; Xu, Lian; Zhou, Nianxin; Yang, Qilian; Shen, Qiuhong; Wang, Wei; Le, Xiaobing; Lau, Wayne Bond; Lau, Bonnie; Wang, Xin; Yi, Tao; Zhao, Xia; Wei, Yuquan; Warner, Margaret; Gustafsson, Jan-Åke; Zhou, Shengtao

2018-04-17

Metastases constitute the greatest causes of deaths from cancer. However, no effective therapeutic options currently exist for cancer patients with metastasis. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor-suppressive activities in many cancers. To investigate whether modulation of ERβ could serve as a therapeutic strategy for cancer metastasis, we examined whether the selective ERβ agonist LY500307 could suppress lung metastasis of triple-negative breast cancer (TNBC) and melanoma. Mechanistically, while we observed that LY500307 potently induced cell death of cancer cells metastasized to lung in vivo, it does not mediate apoptosis of cancer cells in vitro, indicating that the cell death-inducing effects of LY500307 might be mediated by the tumor microenvironment. Pathological examination combined with flow cytometry assays indicated that LY500307 treatment induced significant infiltration of neutrophils in the metastatic niche. Functional experiments demonstrated that LY500307-treated cancer cells show chemotactic effects for neutrophils and that in vivo neutrophil depletion by Ly6G antibody administration could reverse the effects of LY500307-mediated metastasis suppression. RNA sequencing analysis showed that LY500307 could induce up-regulation of IL-1β in TNBC and melanoma cells, which further triggered antitumor neutrophil chemotaxis. However, the therapeutic effects of LY500307 treatment for suppression of lung metastasis was attenuated in IL1B -/- murine models, due to failure to induce antitumor neutrophil infiltration in the metastatic niche. Collectively, our study demonstrated that pharmacological activation of ERβ could augment innate immunity to suppress cancer metastatic colonization to lung, thus providing alternative therapeutic options for cancer patients with metastasis.

Financial Incentives for Linkage to Care and Viral Suppression Among HIV-Positive Patients: A Randomized Clinical Trial (HPTN 065).

PubMed

El-Sadr, Wafaa M; Donnell, Deborah; Beauchamp, Geetha; Hall, H Irene; Torian, Lucia V; Zingman, Barry; Lum, Garret; Kharfen, Michael; Elion, Richard; Leider, Jason; Gordin, Fred M; Elharrar, Vanessa; Burns, David; Zerbe, Allison; Gamble, Theresa; Branson, Bernard

2017-08-01

Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits. To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (<400 copies/mL), assessed at each calendar quarter. Outcomes assessed through laboratory test results reported to the National HIV Surveillance System. A total of 1061 coupons were dispensed for linkage to care at 18 financial incentive test sites and 39 359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not previously consistently virally suppressed, the proportion virally suppressed was 4.9% higher (95% CI, 1.4%-8.5%; P = .007) at financial incentive sites. In addition, continuity in care was 8.7% higher (95% CI, 4.2%-13.2%; P < .001) at financial incentive sites. Financial incentives, as used in this study (HPTN 065), significantly increased viral suppression and regular clinic attendance among HIV-positive patients in care. No effect was noted on linkage to care. Financial incentives offer promise for improving adherence to treatment and viral suppression among HIV-positive patients. clinicaltrials.gov Identifier: NCT01152918.

Persimmon-Tannin, an α-Amylase Inhibitor, Retards Carbohydrate Absorption in Rats.

PubMed

Tsujita, Takahiro

2016-01-01

Inhibitors of carbohydrate-hydrolyzing enzymes play an important role in controlling postprandial blood glucose levels. Thus the effect of persimmon tannin on pancreatic α-amylase and intestinal α-glucosidase has been investigated. Persimmon tannin inhibits pancreatic α-amylase and intestinal α-glucosidase in a concentration-dependent manner with the 50% inhibition concentration (IC50) for amylase, maltase and sucrase being 1.7 μg/mL, 632 μg/mL and 308 μg/mL, respectively. The effect of persimmon-tannin extract on carbohydrate absorption in rats has also been investigated. Oral administration of persimmon tannin to normal rats fed cornstarch (2 g/kg body weight) significantly suppressed the increase in blood glucose levels and the area under the curve (AUC) after starch loading in a dose-dependent manner. The effective dose of persimmon tannin required to achieve 50% suppression of the rise in blood glucose level was estimated to be 300 mg/kg body weight. Administration of persimmon tannin to rats fed maltose or sucrose delayed the increase of blood glucose level and slightly suppressed AUC, but not significantly. These results suggest that persimmon tannin retards absorption of carbohydrate and reduces post-prandial hyperglycemia mainly through inhibition of α-amylase.

Phenytoin attenuates the hyper-exciting neurotransmission in cultured embryonic cortical neurons.

PubMed

Chou, Ming-Yi; Lee, Chun-Yao; Liou, Horng-Huei; Pan, Chien-Yuan

2014-08-01

Phenytoin is an effective anti-epileptic drug that inhibits Na(+) channel activities; however, how phenytoin modulates synaptic transmission to soothe epileptic symptoms is not clear. To characterize the effects of phenytoin regulation on neurotransmission, we studied the electrophysical properties of cultured embryonic cortical neurons. Phenytoin inhibited the inward Na(+) current in a dose-dependent manner with an IC50 of 16.8 μM, and at 100 μM, the inhibitory effect of phenytoin on the Na(+) current was proportional to the frequency applied. In cultured neurons, phenytoin significantly decreased the action potential firing rate and the peak potential. To study the effect of phenytoin in neurotransmission, we measured the Ca(2+) responses from stimulated target neurons and their neighboring neurons. Phenytoin significantly suppressed the Ca(2+) responses evoked by strong stimulations in the target and neighboring neurons, and exerted a decreased inhibitory effect under moderate stimulation. Picrotoxin, a GABAA receptor antagonist, enhanced the recorded spontaneous excitatory postsynaptic current activities. After picrotoxin-induced enhancement, phenytoin had a more pronounced effect on the suppression of the spontaneous hyper-exciting excitatory postsynaptic current (>100 pA), but it only mildly inhibited the general excitatory postsynaptic current. Our results demonstrate that phenytoin suppresses the efficacy of neurotransmission especially for the high-frequency stimulation by reducing the Na(+) channel activity and can potentially alleviate epileptiform activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia.

PubMed

Lee, Fei-Peng; Shih, Chwen-Ming; Shen, Hsin-Yi; Chen, Chien-Ming; Chen, Chi-Ming; Ko, Wun-Chang

2010-06-10

In recent in vitro reports, the IC(50) value of ayanin (quercetin-3,7,4'-O-trimethylether) was 2.2microM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was >19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30-100micromol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100micromol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100micromol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG(2a) level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma.

Alleviation of response suppression to conditioned aversive stimuli by lesions of the dorsal noradrenergic bundle.

PubMed

Tsaltas, E; Gray, J A; Fillenz, M

1984-08-01

Rats with neurotoxic lesions of the dorsal ascending noradrenergic bundle (DB) were compared with sham-operated (SH) controls on the acquisition, steady state and extinction of response suppression maintained by a classical (conditioned suppression) or an instrumental (discriminated punishment) contingency. DB lesions interfered neither with the acquisition of the reference response of sucrose-rewarded barpressing nor with unconditioned responding to the overhead flashing light subsequently used as a signal of shock. The acquisition of discriminated response suppression was also unaffected by the lesion under both types of contingency. However, once discriminated suppression had stabilized, both the conditioned and the discriminative stimulus used were significantly less effective in maintaining suppression in DB animals than in SH controls provided that low intensity footshock (0.2 mA) was used as the unconditioned stimulus (UCS). Upon increase of UCS intensity (to 0.5 mA) normal suppression was observed in the DB group under both contingencies. Extinction of the classical contingency reinstated the difference between DB and SH performance: DB lesion resulted in significantly faster extinction of fear. In contrast, extinction of the discriminated punishment contingency was unaffected by the lesion, although generalized response suppression dissipated faster in the DB than in the SH animals trained under this condition. Our results offer no support for the reinforcement hypothesis of DB function (normal acquisition of barpressing and of discriminated suppression of barpressing); mixed support (greater initial generalization of suppression in DB animals) and contradiction (more rapid extinction of conditioned suppression in DB animals) for the attentional hypothesis; and weak support (reduced suppression and more rapid extinction of suppression in DB animals, but only within limited experimental parameters) for the anxiety hypothesis of DB function. Hence none of the extant theories of DB function offer a ready explanation of the pattern of results presented here. A simple interpretation which conforms with the sparsity of positive behavioural findings in the literature on DB lesions is that forebrain noradrenaline contributes to the detection and utilization of conditioned stimuli; but that this contribution is critical only for the detection of stimuli with low associative strength.

Mesenchymal stem cells do not suppress lymphoblastic leukemic cell line proliferation.

PubMed

Mousavi Niri, Neda; Jaberipour, Mansooreh; Razmkhah, Mahboobeh; Ghaderi, Abbas; Habibagahi, Mojtaba

2009-12-01

Several studies have demonstrated the immunosuppresive effects of mesenchymal stem cells (MSCs) in allogeneic or mitogenic interactions. Cell-cell contact inhibition and secretion of suppressive soluble factors have been suggested in this regard. To investigate if adipose derived MSCs could inhibit Jurkat lymphoblastic leukemia T cell proliferation during coculture. Adherent cells with the ability of cellular growth were isolated from normal adipose tissues. Initial characterization of growing cells by flow cytometry suggested their mesenchymal stem cell characteristics. Cells were maintained in culture and used during third to fifth culture passages. Jurkat or allogeneic peripheral blood mononuclear cells (PBMCs) were labeled with carboxy fluorescein diacetate succinimidyl ester and cocultured with increasing doses of MSCs or MSC culture supernatant. Proliferation of PBMCs or Jurkat cells under these conditions was assessed by flow cytometry after 2 and 3 days of coculture, respectively. Results showed the expression of CD105, CD166 and CD44, and the absence of CD45, CD34 and CD14 on the surface of MSC like cells. Moreover, initial differentiation studies showed the potential of cell differentiation into hepatocytes. Comparison of Jurkat cell proliferation in the presence and absence of MSCs showed no significant difference, with 70% of cells displaying signs of at least one cell division. Similarly, the highest concentration of MSC culture supernatant (50% vol/vol) had no significant effect on Jurkat cell proliferation (p>0.6). The same MSC lots significantly suppressed the allogeneic PHA activated PBMCs under similar culture conditions. Using Jurkat cells as a model of leukemia T cells, our results indicated an uncertainty about the suppressive effect of MSCs and their inhibitory metabolites on tumor or leukemia cell proliferation. Additional systematic studies with MSCs of different sources are needed to fully characterize the immunological properties of MSCs before planning clinical applications.

Tributyltin induces distinct effects on cortical and trabecular bone in female C57Bl/6J mice.

PubMed

Watt, James; Baker, Amelia H; Meeks, Brett; Pajevic, Paola D; Morgan, Elise F; Gerstenfeld, Louis C; Schlezinger, Jennifer J

2018-09-01

The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma (PPARγ), and liver X receptors (LXR) all have been shown to regulate bone homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual RXRα/β and PPARγ agonist. TBT induces RXR, PPARγ, and LXR-mediated gene transcription and suppresses osteoblast differentiation in vitro. Bone marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice were more sensitive to suppression of osteogenesis by TBT than those derived from male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10 mg/kg TBT for 10 weeks resulted in femurs with a smaller cross-sectional area and thinner cortex. Surprisingly, TBT induced significant increases in trabecular thickness, number, and bone volume fraction. TBT treatment did not change the Rankl:Opg RNA ratio in whole bone, and histological analyses showed that osteoclasts in the trabecular space were minimally reduced. In contrast, expression of cardiotrophin-1, an osteoblastogenic cytokine secreted by osteoclasts, increased. In primary bone marrow macrophage cultures, TBT marginally inhibited the number of osteoclasts that differentiated, in spite of significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk and resorptive activity. TBT induced expression of RXR- and LXR-dependent genes in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist, but not an LXR antagonist, significantly inhibited TBTs ability to suppress osteoclast differentiation. These results suggest that TBT has distinct effects on cortical versus trabecular bone, likely resulting from independent effects on osteoblast and osteoclast differentiation that are mediated through RXR. © 2018 Wiley Periodicals, Inc.

Pseudolaric acid B attenuates atherosclerosis progression and inflammation by suppressing PPARγ-mediated NF-κB activation.

PubMed

Li, Tan; Wang, Wei; Li, Yu-Xiu; Li, Xiao; Ji, Wen-Jie; Ma, Yong-Qiang; Chen, Hong; Zhao, Ji-Hong; Zhou, Xin

2018-06-01

Atherosclerosis is a progressive disease of large arteries characterized with chronic inflammation and aberrant immune response. Pseudolaric acid B (PB) has been found to exert multiple effects by inhibiting inflammatory response. However, there is no comprehensive assessment of the effects of PB on atherosclerosis using relevant in vivo and in vitro models. Male ApoE -/- mice were treated with PB orally with a high fat diet (HFD) to clarify its anti-atherosclerotic activities. RAW264.7 macrophage line, a well-accepted cell model of atherosclerosis, was used to investigate anti-inflammatory effects and molecular mechanisms of PB. PB significantly attenuated atherosclerotic lesions by modulating plasma lipid profiles as well as inhibiting inflammatory responses in macrophages of atherosclerotic mice. Meanwhile, PB markedly suppressed the expression of pro-inflammatory cytokines, and regulated cholesterol efflux related genes in oxidative low density lipoprotein (ox-LDL)-loaded macrophages. The cellular uptake of Dil-labeled ox-LDL was significantly inhibited by PB either. Moreover, the ability of PB to suppress nuclear factor kappa B (NF-κB) and activate peroxisome proliferator-activated receptor gamma (PPARγ) was confirmed using luciferase reporter assays. Conversely, the selective PPARγ antagonist GW9662 reversed the influence of PB in macrophages. Together, these findings indicate that PB exerts its protective effects on atherosclerosis by inhibiting macrophage-mediated inflammatory response and cellular ox-LDL uptake, and promoting cholesterol efflux by suppressing NF-κB activation PPARγ-dependently. Therefore, PB may be a promising agent for inflammatory and atherosclerotic diseases. Copyright © 2018. Published by Elsevier B.V.

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex.

PubMed

Di Lazzaro, V; Pilato, F; Dileone, M; Profice, P; Oliviero, A; Mazzone, P; Insola, A; Ranieri, F; Meglio, M; Tonali, P A; Rothwell, J C

2008-08-15

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.

PubMed

Liu, Ya-Wei; Chiu, Yung-Tsung; Fu, Shu-Ling; Huang, Yi-Tsau

2015-08-01

Hepatic fibrosis is a dynamic process which ultimately leads to cirrhosis in almost patients with chronic hepatic injury. However, progressive fibrosis is a reversible scarring response. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic fibrosis. Osthole is an active component majorly contained in the fruit of Cnidium monnieri (L.) Cusson. This present study investigated the therapeutic effects of osthole on rat liver fibrosis and HSC activation. We established the thioacetamide (TAA)-model of Sprague-Dawley (SD) rats to induce hepatic fibrosis. Rats were divided into three groups: control, TAA, and TAA + osthole (10 mg/kg). In vivo, osthole significantly reduced liver injury by diminishing levels of plasma AST and ALT, improving histological architecture, decreasing collagen and α-SMA accumulation, and improving hepatic fibrosis scores. Additionally, osthole reduced the expression of fibrosis-related genes significantly. Osthole also suppressed the production of fibrosis-related cytokines and chemokines. Moreover, nuclear translocation of p65 was significantly suppressed in osthole-treated liver. Osthole also ameliorated TAA-induced injury through reducing cellular oxidation. Osthole showed inhibitory effects in inflammation-related genes and chemokines production as well. In vitro, we assessed osthole effects in activated HSCs (HSC-T6 and LX-2). Osthole attenuated TGF-β1-induced migration and invasion in HSCs. Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly. Besides, osthole alleviated TGF-β1- or ET-1-induced HSCs contractility. Our study demonstrated that osthole improved TAA-caused liver injury, fibrogenesis and inflammation in rats. In addition, osthole suppressed HSCs activation in vitro significantly.

Identification of sequence motifs significantly associated with antisense activity.

PubMed

McQuisten, Kyle A; Peek, Andrew S

2007-06-07

Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic mediators to speed the process along like the RNA Induced Silencing Complex (RISC) in RNAi. The independence of motif position and antisense activity also allows us to bypass consideration of this feature in the modelling process, promoting model efficiency and reducing the chance of overfitting when predicting antisense activity. The increase in SVR correlation with significant features compared to nearest-neighbour features indicates that thermodynamics alone is likely not the only factor in determining antisense efficiency.

An analysis of suppressing migratory effect on human urinary bladder cancer cell line by silencing of snail-1.

PubMed

Salehi, Shima; Mansoori, Behzad; Mohammadi, Ali; Davoudian, Sadaf; Musavi Shenas, Seyed Mohammad Hossein; Shajari, Neda; Majidi, Jafar; Baradaran, Behzad

2017-12-01

Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. The significant silencing of snail-1 reached 60pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tributyltin engages multiple nuclear receptor pathways and suppresses osteogenesis in bone marrow multipotent stromal cells.

PubMed

Baker, Amelia H; Watt, James; Huang, Cassie K; Gerstenfeld, Louis C; Schlezinger, Jennifer J

2015-06-15

Organotins are members of the environmental obesogen class of contaminants because they activate peroxisome proliferator-activated receptor γ (PPARγ), the essential regulator of adipogenesis. Exposure to thiazolidinediones (PPARγ ligands used to treat type 2 diabetes) is associated with increased fractures. Diminished bone quality likely results from PPARγ's role in promoting adipogenesis while suppressing osteogenesis of bone marrow multipotent mesenchymal stromal cells (BM-MSC). We hypothesized that tributyltin (TBT) would be a potent modifier of BM-MSC differentiation and a negative regulator of bone formation. Organotins interact with both PPARγ and retinoid X receptors (RXR), suggesting that they activate multiple nuclear receptor pathways. To investigate the role of RXR in the actions of TBT, the effects of PPARγ (rosiglitazone) and RXR (bexarotene, LG100268) agonists were compared to the effects of TBT in BMS2 cells and primary mouse BM-MSC cultures. In BMS2 cells, TBT induced the expression of Fabp4, Abca1, and Tgm2 in an RXR-dependent manner. All agonists suppressed osteogenesis in primary mouse BM-MSC cultures, based on decreased alkaline phosphatase activity, mineralization, and expression of osteoblast-related genes. While rosiglitazone and TBT strongly activated adipogenesis, based on lipid accumulation and expression of adipocyte-related genes, the RXR agonists did not. Extending these analyses to other RXR heterodimers showed that TBT and the RXR agonists activated the liver X receptor pathway, whereas rosiglitazone did not. Application of either a PPARγ antagonist (T0070907) or an RXR antagonist (HX531) significantly reduced rosiglitazone-induced suppression of bone nodule formation. Only the RXR antagonist significantly reduced LG100268- and TBT-induced bone suppression. The RXR antagonist also inhibited LG100268- and TBT-induced expression of Abca1, an LXR target gene, in primary BM-MSC cultures. These results provide novel evidence that TBT activates multiple nuclear receptor pathways in BM-MSCs, activation of RXR is sufficient to suppress osteogenesis, and TBT suppresses osteogenesis largely through its direct interaction with RXR.

Wing rock suppression using forebody vortex control

NASA Technical Reports Server (NTRS)

Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

1991-01-01

Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

Testing Lunar Permanently Shadowed Regions for Water Ice: LEND Results from LRO

NASA Technical Reports Server (NTRS)

Sanin, A. B.; Mitrofanov, I. G.; Litvak, M. L.; Malakhov, A.; Boynton, W. V.; Chin, G.; Droege, G.; Evans, L. G.; Garvin, J.; Golovin, D. V.;

T-cell proliferative responses following sepsis in neonatal rats.

PubMed

Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M

2003-01-01

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis. Copyright 2003 S. Karger AG, Basel

Ghrelin protects against depleted uranium-induced apoptosis of MC3T3-E1 cells through oxidative stress-mediated p38-mitogen-activated protein kinase pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Yuhui; Liu, Cong; Huang, Jiawei

Depleted uranium (DU) mainly accumulates in the bone over the long term. Osteoblast cells are responsible for the formation of bone, and they are sensitive to DU damage. However, studies investigating methods of reducing DU damage in osteoblasts are rarely reported. Ghrelin is a stomach hormone that stimulates growth hormones released from the hypothalamic–pituitary axis, and it is believed to play an important physiological role in bone metabolism. This study evaluates the impact of ghrelin on DU-induced apoptosis of the osteoblast MC3T3-E1 and investigates its underlying mechanisms. The results show that ghrelin relieved the intracellular oxidative stress induced by DU,more » eliminated reactive oxygen species (ROS) and reduced lipid peroxidation by increasing intracellular GSH levels; in addition, ghrelin effectively suppressed apoptosis, enhanced mitochondrial membrane potential, and inhibited cytochrome c release and caspase-3 activation after DU exposure. Moreover, ghrelin significantly reduced the expression of DU-induced phosphorylated p38-mitogen-activated protein kinase (MAPK). A specific inhibitor (SB203580) or specific siRNA of p38-MAPK could significantly suppress DU-induced apoptosis and related signals, whereas ROS production was not affected. In addition, ghrelin receptor inhibition could reduce the anti-apoptosis effect of ghrelin on DU and reverse the effect of ghrelin on intracellular ROS and p38-MAPK after DU exposure. These results suggest that ghrelin can suppress DU-induced apoptosis of MC3T3-E1 cells, reduce DU-induced oxidative stress by interacting with its receptor, and inhibit downstream p38-MAPK activation, thereby suppressing the mitochondrial-dependent apoptosis pathway. - Highlights: • Ghrelin suppressed DU-induced apoptosis of MC3T3-E1 cells. • Ghrelin inhibited DU-induced oxidative stress and further p38-MAPK activation. • Ghrelin further suppressed mitochondrial-dependent apoptosis pathway. • The anti-oxidation effect of ghrelin was regulated through its receptor. • Ghrelin has the potential for use in drug therapies for DU poisoning.« less

Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice.

PubMed

Lee, Sooyeon; Park, Jong-Min; Jeong, Migyeong; Han, Young-Min; Go, Eun Jin; Ko, Weon Jin; Cho, Joo Young; Kwon, Chang Il; Hahm, Ki Baik

2016-01-01

Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. C57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. KRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

The Calcineurin-NFAT Axis Controls Allograft Immunity in Myeloid-Derived Suppressor Cells through Reprogramming T Cell Differentiation

PubMed Central

Wang, Xiao; Bi, Yujing; Xue, Lixiang; Liao, Jiongbo; Chen, Xi; Lu, Yun; Zhang, Zhengguo; Wang, Jian; Liu, Huanrong; Yang, Hui

2014-01-01

While cyclosporine (CsA) inhibits calcineurin and is highly effective in prolonging rejection for transplantation patients, the immunological mechanisms remain unknown. Herein, the role of calcineurin signaling was investigated in a mouse allogeneic skin transplantation model. The calcineurin inhibitor CsA significantly ameliorated allograft rejection. In CsA-treated allograft recipient mice, CD11b+ Gr1+ myeloid-derived suppressor cells (MDSCs) were functional suppressive immune modulators that resulted in fewer gamma interferon (IFN-γ)-producing CD8+ T cells and CD4+ T cells (TH1 T helper cells) and more interleukin 4 (IL-4)-producing CD4+ T cells (TH2) and prolonged allogeneic skin graft survival. Importantly, the expression of NFATc1 is significantly diminished in the CsA-induced MDSCs. Blocking NFAT (nuclear factor of activated T cells) with VIVIT phenocopied the CsA effects in MDSCs and increased the suppressive activities and recruitment of CD11b+ Gr1+ MDSCs in allograft recipient mice. Mechanistically, CsA treatment enhanced the expression of indoleamine 2,3-dioxygenase (IDO) and the suppressive activities of MDSCs in allograft recipients. Inhibition of IDO nearly completely recovered the increased MDSC suppressive activities and the effects on T cell differentiation. The results of this study indicate that MDSCs are an essential component in controlling allograft survival following CsA or VIVIT treatment, validating the calcineurin-NFAT-IDO signaling axis as a potential therapeutic target in transplantation. PMID:25452304

Sailuotong Prevents Hydrogen Peroxide (H₂O₂)-Induced Injury in EA.hy926 Cells.

PubMed

Seto, Sai Wang; Chang, Dennis; Ko, Wai Man; Zhou, Xian; Kiat, Hosen; Bensoussan, Alan; Lee, Simon M Y; Hoi, Maggie P M; Steiner, Genevieve Z; Liu, Jianxun

2017-01-05

Sailuotong (SLT) is a standardised three-herb formulation consisting of Panax ginseng , Ginkgo biloba , and Crocus sativus designed for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H₂O₂)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1-50 µg/mL) significantly suppressed the H₂O₂-induced cell death and abolished the H₂O₂-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H₂O₂ (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1-50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H₂O₂-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H₂O₂-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed.

Greatly Suppressed Shuttle Effect for Improved Lithium Sulfur Battery Performance through Short Chain Intermediates.

PubMed

Xu, Na; Qian, Tao; Liu, Xuejun; Liu, Jie; Chen, Yu; Yan, Chenglin

2017-01-11

The high solubility of long-chain lithium polysulfides and their infamous shuttle effect in lithium sulfur battery lead to rapid capacity fading along with low Coulombic efficiency. To address above issues, we propose a new strategy to suppress the shuttle effect for greatly enhanced lithium sulfur battery performance mainly through the formation of short-chain intermediates during discharging, which allows significant improvements including high capacity retention of 1022 mAh/g with 87% retention for 450 cycles. Without LiNO 3 -containing electrolytes, the excellent Coulombic efficiency of ∼99.5% for more than 500 cycles is obtained, suggesting the greatly suppressed shuttle effect. In situ UV/vis analysis of electrolyte during cycling reveals that the short-chain Li 2 S 2 and Li 2 S 3 polysulfides are detected as main intermediates, which are theoretically verified by density functional theory (DFT) calculations. Our strategy may open up a new avenue for practical application of lithium sulfur battery.

Suppressing the morning rise in cortisol impairs free recall.

PubMed

Rimmele, Ulrike; Meier, Flurina; Lange, Tanja; Born, Jan

2010-04-01

Elevated glucocorticoid levels impair memory retrieval. We investigated whether retrieval under naturally elevated glucocorticoid levels, i.e., during the morning rise in cortisol can be improved by suppressing cortisol. In a crossover study 16 men retrieved emotional and neutral texts and pictures (learned 3 d earlier) 30 min after morning awakening, following administration of the cortisol synthesis inhibitor metyrapone or placebo. Unexpectedly, the metyrapone-induced cortisol suppression significantly impaired free recall of both materials. Recognition remained unaffected. Thus, not only high, but also very low glucocorticoid levels impair retrieval, with the latter effect possibly reflecting insufficient occupation of hippocampal/amygdalar mineralocorticoid receptors (MRs).

Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4.

PubMed

Streitová, Denisa; Weiterová, Lenka; Hofer, Michal; Holá, Jirina; Horváth, Viktor; Kozubík, Alois; Znojil, Vladimír

2007-09-01

Adenosine has been observed to suppress the growth of MOLT-4 human leukemia cells in vitro. Changes in the cell cycle, especially increased percentage of cells in S phase, prolonged generation time, and induction of apoptosis at higher adenosine concentrations have been found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, reversed partially but significantly the adenosine-induced growth suppression. It follows from these results that the action of adenosine on the MOLT-4 cells comprises its cellular uptake and intracellular operation. These findings present new data on anticancer efficacy of adenosine.

The Biodistribution and Immune Suppressive Effects of Breast Cancer-Derived Exosomes.

PubMed

Wen, Shu Wen; Sceneay, Jaclyn; Lima, Luize Goncalves; Wong, Christina S F; Becker, Melanie; Krumeich, Sophie; Lobb, Richard J; Castillo, Vanessa; Wong, Ke Ni; Ellis, Sarah; Parker, Belinda S; Möller, Andreas

2016-12-01

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45 + bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR. ©2016 American Association for Cancer Research.

Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities.

PubMed

Yoshiji, Hitoshi; Kuriyama, Shigeki; Noguchi, Ryuichi; Yoshii, Junichi; Ikenaka, Yasuhide; Yanase, Koji; Namisaki, Tadashi; Kitade, Mitsuteru; Yamazaki, Masaharu; Akahane, Takemi; Asada, Kiyoshi; Tsujimoto, Tatsuhito; Uemura, Masahito; Fukui, Hiroshi

2006-01-01

Recent studies have revealed that angiogenesis plays a pivotal role in carcinogenesis and tumor growth. We previously reported that the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exerted potent anti-angiogenic activities. The aim of our current study was to examine the combination effect of VK and ACE-I on hepatocarcinogenesis induced by diethyl-nitrosamine, and orthotopic hepatocellular carcinoma (HCC) growth in rats. When used individually, both VK and ACE-I at clinically comparable low doses exerted significant inhibitory effects on tumor development in the liver. A combination treatment of VK and ACE-I showed a more potent suppressive effect against hepatocarcinogenesis. Neovascularization increased during hepatocarcinogenesis, and VK and ACE-I significantly attenuated angiogenesis in the tumor. In orthotopic HCC transplantation, VK and ACE-I also showed marked suppressive effects against HCC development similar to those against hepatocarcinogenesis. In both experiments, the suppressive effects of VK and ACE-I against angiogenesis were similar in magnitude to their inhibitory effects against hepatocarcinogenesis and orthotopic HCC development. In the orthotopic model, VK and ACE-I treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. Since both VK and ACE-I are widely used in clinical practice without serious side effects, this combination therapy may be an effective new therapeutic strategy against hepatocarcinogenesis and HCC growth in the future.

Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin

PubMed Central

Kobayashi, Hideki; Ouchi, Noriyuki; Kihara, Shinji; Walsh, Kenneth; Kumada, Masahiro; Abe, Yuki; Funahashi, Tohru; Matsuzawa, Yuji

2015-01-01

Adiponectin is an adipocyte-derived, antiatherogenic protein that is present in serum as three isoforms. Total adiponectin levels are decreased in obese or diabetic humans or animal models. This study was designed to elucidate the relative isoform distribution of adiponectin in human disease states and identify the active form of adiponectin toward vascular endothelial cells. The percentage of high molecular weight form (HMW) per total adiponectin was significantly lower in patients with coronary artery disease than control subjects, whereas the hexamer form was similar and the trimer form was significantly higher. During weight reduction in obese subjects, the HMW form increased and the trimer and hexamer forms decreased. Recombinant adiponectin dose-dependently suppressed apoptosis and caspase-3 activity in human umbilical vein endothelial cells (HUVECs). Transduction with dominant-negative AMP-activated protein kinase (AMPK) abolished the suppressive effect of adiponectin on HUVECs. Gel filtration chromatography was used to separate the adiponectin isoforms, and the antiapoptotic effect toward HUVECs was only observed with the HMW form. These data suggest that HMW adiponectin specifically confers the vascular-protective activities of this adipocytokine. PMID:14752031

Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice

PubMed Central

Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori

2016-01-01

Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)–induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. PMID:27021217

Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels.

PubMed

Geisler, Jürgen; Helle, Hilgegunn; Ekse, Dagfinn; Duong, Nhat K; Evans, Dean B; Nordbø, Yngve; Aas, Turid; Lønning, Per E

2008-10-01

To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (E(1)), estradiol (E(2)), and estrone sulfate (E(1)S) in postmenopausal women undergoing primary treatment for locally advanced estrogen receptor/progesterone receptor-positive breast cancers. Breast cancer tissue samples were collected before and following 4 months of neoadjuvant therapy with letrozole (2.5 mg o.d.), and tissue estrogen levels measured using a highly sensitive RIA after high-pressure liquid chromatography purification. Letrozole suppressed pretreatment tumor levels of E(2), E(1), and E(1)S by 97.6%, 90.7%, and 90.1%, respectively. These data reveal that letrozole suppresses tissue estrogen levels significantly below what has previously been recorded with anastrozole (89.0%, 83.4%, and 72.9% suppression, respectively) using the same methods. To confirm the differential effect of letrozole and anastrozole on each plasma estrogen fraction, we re-analyzed plasma samples obtained from a previous intrapatient cross-over study comparing letrozole and anastrozole using an improved RIA (detection limits of 0.67, 1.14, and 0.55 pmol/L for E(2), E(1), and E(1)S, respectively). Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E(2) (average suppression by 95.2% versus 92.8%; P = 0.018), E(1) (98.8% suppression versus 96.3%; P = 0.003), and E(1)S (98.9% suppression versus 95.3%; P = 0.003). Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.

Reliability of measures of transient evoked otoacoustic emissions with contralateral suppression.

PubMed

Stuart, Andrew; Cobb, Kensi M

2015-01-01

The reliability of measures of transient evoked otoacoustic emissions (TEOAEs) with contralateral suppression was examined. The effect of test session (i.e., initial test; retest without probe removal; retest with probe removal; and retest 1-2 days post initial test), gender, and ear was examined in 14 young adult females and 14 young adult males. TEOAEs were obtained bilaterally with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL broadband noise suppressor. Absolute TEOAE suppression and a normalized index of TEOAE suppression (i.e., percentage of suppression) were examined. Reliability of these measures was assessed with repeated measures linear mixed model analysis of variance, a coefficient of reliability, and Bland-Altman analyses. There were no statistically significant (p>0.05) main effects of test, gender, and ear or interactions for both absolute dB and % TEOAE suppression values. Cronbach's α were greater than 0.90 across the four tests for both TEOAE measures. Mean test differences or bias (i.e., between the initial and subsequent tests) for absolute and % TEOAE suppression ranged from -0.05 to 0.11 dB and -1.5% to 1.1%, respectively. There was no proportional/systematic bias with the mean differences of the first and subsequent measurements. Data herein were consistent with the view that bilateral TEOAE suppression measures are reliable across test sessions of 1-2 days among females and males and may provide a method to monitor medial olivocochlear efferent reflex status over time. Copyright © 2015 Elsevier Inc. All rights reserved.

Short-term and long-term effect of diaphragm biofeedback training in gastroesophageal reflux disease: an open-label, pilot, randomized trial.

PubMed

Sun, X; Shang, W; Wang, Z; Liu, X; Fang, X; Ke, M

2016-10-01

This study investigated the effectiveness of diaphragm biofeedback training (DBT) for patients with gastroesophageal reflux disease (GERD). A total of 40 patients with GERD treated at the Peking Union Medical College Hospital between September 2004 and July 2006 were randomized to receive DBT and rabeprazole proton pump inhibitor (PPI) or rabeprazole alone. The DBT + rabeprazole group received DBT during the 8-week initial treatment; the rabeprazole group did not. During the 6-month follow up, all patients took acid suppression according to their reflux symptoms, and the patients in the DBT + rabeprazole group were required to continue DBT. The primary outcome (used for power analysis) was the amount of acid suppression used at 6 months. Secondary outcomes were reflux symptoms, health-related quality of life (HRQL), and esophageal motility differences after the 8-week treatment compared with baseline. Acid suppression usage significantly decreased in the DBT + rabeprazole group compared with the rabeprazole group at 6 months (P < 0.05). At 8 weeks, reflux symptoms and GERD-HRQL were significantly improved in both groups (P < 0.05), without difference between them. Crural diaphragm tension (CDT) and gastroesophageal junction pressure (GEJP) significantly increased in the DBT + rabeprazole group (P < 0.05), but without change in lower esophageal sphincter (LES) pressure. There was no significant change in CDT, GEJP, and LES pressure compared with baseline in the rabeprazole group. In conclusion, long-term DBT could reduce acid suppression usage by enhancing the anti-reflux barrier, providing a non-pharmacological maintenance therapy and reducing medical costs for patients with GERD. © 2015 International Society for Diseases of the Esophagus.

Osthole pretreatment alleviates TNBS-induced colitis in mice via both cAMP/PKA-dependent and independent pathways.

PubMed

Sun, Wu; Cai, Yun; Zhang, Xin-Xin; Chen, Hao; Lin, Yan-Die; Li, Hao

2017-08-01

Osthole, a natural coumarin found in traditional Chinese medicinal plants, has shown multiple biological activities. In the present study, we investigated the preventive effects of osthole on inflammatory bowel disease (IBD). Colitis was induced in mice by infusing TNBS into the colonic lumen. Before TNBS treatment, the mice received osthole (100 mg·kg -1 ·d -1 , ip) for 3 d. Pretreatment with osthole significantly ameliorated the clinical scores, colon length shortening, colonic histopathological changes and the expression of inflammatory mediators in TNBS-induced colitis. Pretreatment with osthole elevated serum cAMP levels; but treatment with the PKA inhibitor H89 (10 mg·kg -1 ·d -1 , ip) did not abolish the beneficial effects of osthole on TNBS-induced colitis. In mouse peritoneal macrophages, pretreatment with osthole (50 μmol/L) significantly attenuated the LPS-induced elevation of cytokines at the mRNA level; inhibition of PKA completely reversed the inhibitory effects of osthole on IL-1β, IL-6, COX2, and MCP-1 but not on TNFα. In Raw264.7 cells, the p38 inhibitor SB203580 markedly suppressed LPS-induced upregulation of the cytokines, whereas the PKA inhibitors H89 or KT5720 did not abolish the inhibitory effects of SB203580. Moreover, in LPS-stimulated mouse peritoneal macrophages, SB203580 strongly inhibited the restored expression of IL-1β, IL-6, COX2, and MCP-1, which was achieved by abolishing the suppressive effects of osthole with the PKA inhibitors. Western blot analysis showed that osthole significantly suppressed the phosphorylation of p38, which was induced by TNBS in mice or by LPS in Raw264.7 cells. Inhibition of PKA partially reversed the suppressive effects of osthole on p38 phosphorylation in LPS-stimulated cells. Collectively, our results suggest that osthole is effective in the prevention of TNBS-induced colitis by reducing the expression of inflammatory mediators and attenuating p38 phosphorylation via both cAMP/PKA-dependent and independent pathways, among which the cAMP/PKA-independent pathway plays a major role.

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.

1986-03-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S.more » aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.« less

Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease.

PubMed

Wan Nazaimoon, W M; Khalid, B A

1998-04-01

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.

Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.

PubMed

Kuenzel, Heike E; Steiger, Axel; Held, Katja; Antonijevic, Irina A; Frieboes, Ralf-Michael; Murck, Harald

2005-07-01

Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia. CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs. Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night. After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night. While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.

Immunomodulatory properties of titanium dioxide nanostructural materials.

PubMed

Latha, T Sree; Reddy, Madhava C; R Durbaka, Prasad V; Muthukonda, Shankar V; Lomada, Dakshayani

2017-01-01

Although titanium dioxide (TiO 2 ) nanostructural materials have been widely used in Biology and Medicine, very little is known about immunomodulation mechanism of these materials. Objectives of this study are to investigate in vitro immunomodulatory effects of TiO 2 . Immunosuppressant may lower immune responses and are helpful for the treatment of graft versus host diseases and autoimmune disorders. In this study, we used H 2 Ti 3 O 7 titanium dioxide nanotubes (TNT) nanotubes along with commercial TiO 2 nanoparticles (TNP) and TiO 2 fine particles (TFP). We investigated the in vitro immunomodulatory effects of TNP, TNT, and TFP using mixed lymphocyte reaction (MLR). Suppression was studied by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cytokine profile was measured by enzyme-linked immunosorbent assay (ELISA). The results from this study illustrated that the TiO 2 nanostructural materials strongly suppressed splenocytes proliferation in MLR. For TNP and TNT, at 50 μg/ml suppression of 20%-25% and 30%-35%, respectively, and for TFP at 100 μg/ml suppression was 25%-30% was observed. Suppression of splenocytes proliferation in the presence of TNP, TNT, and TFP demonstrated that these nanostructural materials probably block T-cell-mediated responses in vitro . Our ELISA results confirmed that significantly lower levels of Th1 type cytokines (interleukin-2, interferon-γ) in the 48 h MLR culture supernatants. Our data suggest that TiO 2 nanostructural materials suppress splenocytes proliferation by suppressing Th1 cytokines.

The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.

PubMed

Spencer, Juliet V

2007-02-01

Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.

Monoclonal Antibody and an Antibody-Toxin Conjugate to a Cell Surface Proteoglycan of Melanoma Cells Suppress in vivo Tumor Growth

NASA Astrophysics Data System (ADS)

Bumol, T. F.; Wang, Q. C.; Reisfeld, R. A.; Kaplan, N. O.

1983-01-01

A monoclonal antibody directed against a cell surface chondroitin sulfate proteoglycan of human melanoma cells, 9.2.27, and its diphtheria toxin A chain (DTA) conjugate were investigated for their effects on in vitro protein synthesis and in vivo tumor growth of human melanoma cells. The 9.2.27 IgG and its DTA conjugate display similar serological activities against melanoma target cells but only the conjugate can induce consistent in vitro inhibition of protein synthesis and toxicity in M21 melanoma cells. However, both 9.2.27 IgG and its DTA conjugate effect significant suppression of M21 tumor growth in vivo in an immunotherapy model of a rapidly growing tumor in athymic nu/nu mice, suggesting that other host mechanisms may mediate monoclonal antibody-induced tumor suppression.

Lufenuron suppresses the resistance of Formosan subterranean termites (Isoptera: Rhinotermitidae) to entomopathogenic bacteria.

PubMed

Wang, Cai; Henderson, Gregg; Gautam, Bal K

2013-08-01

Pesticides can negatively affect insect immunity. Although studies show that Formosan subterranean termites, Coptotermes formosanus Shiraki, are resistant to microbial infections, the effects of pesticides on disease resistance is not well studied. In this study, C. formosanus previously fed lufenuron was exposed to each of the three entomopathogenic bacteria, Pseudomonas aeruginosa (Schroeter) Migula, Serratia marcescens Bizio, and Bacillus thuringiensis Berliner subsp. israelensis. We found that termite mortality was significantly higher and synergistic in the combination of lufenuron and P. aeruginosa compared with treatment of lufenuron or P. aeruginosa alone. Other bacteria and lufenuron combinations were not quite as effective. Interestingly, only in treatments without lufenuron did termites show carcass-burying behavior. The results indicate that lufenuron, a chitin synthesis inhibitor, can suppress Formosan subterranean termite resistance to P. aeruginosa. Possible suppression mechanisms are discussed.

Suppressive effects of Calendula micrantha essential oil and gibberelic acid (PGR) on repro ductive potential of the Mediterranean fruit fly Ceratitis capitata Wied. (Diptera: Tephritidae).

PubMed

Hussein, Karam T

2005-08-01

The volatile oil of Calendula micrtantha plant was extracted and the components were identified by Gc/Ms. Adulticidal efficiency of the volatile oil and gibberelic acid "plant growth promoting hormone" as well as their mixture was assessed against the Mediterranean fruit fly Ceratitis capitata. The result showed that the two compounds capable have characteristic resembling to insect juvenile hormones and have suppressive effect on reproductive potential. They induced the significant disturbances in the ovarian protein fraction and the amino acids patterns.

Coherent triplet excitation suppresses the heading error of the avian compass

NASA Astrophysics Data System (ADS)

Katsoprinakis, G. E.; Dellis, A. T.; Kominis, I. K.

2010-08-01

Radical-ion pair reactions are currently understood to underlie the biochemical magnetic compass of migratory birds. It was recently shown that radical-ion pair reactions form a rich playground for the application of quantum-information-science concepts and effects. We will show here that the intricate interplay between the quantum Zeno effect and the coherent excitation of radical-ion pairs leads to an exquisite angular sensitivity of the reaction yields. This results in a significant and previously unanticipated suppression of the avian compass heading error, opening the way to quantum engineering precision biological sensors.

Infant Reflux in the Primary Care Setting: A Brief Educational Intervention and Management Changes.

PubMed

Harris, Brendan Ryan; Bennett, William E

2018-07-01

There has been a significant increase in prescription of acid suppression therapy to infants despite limited support for efficacy and safety. Prior studies have shown that educational interventions can improve clinician practices. Our aim is to implement an educational module with high-yield evidence to decrease the rate of prescribing these medications. Chart review of infants seen by residents after completing module was performed. Twelve clinic sessions before and after intervention were examined. 28 residents completed the intervention and required clinics. Before implementation, 1.8% of infants seen were prescribed acid suppression with none receiving proton pump inhibitors (PPIs). After completion, 0.8% of infants were prescribed acid suppression and 1 patient received PPI. This was not a significant change. The study was unsuccessful in effecting changes in provider prescribing practices. Although, this is not the outcome expected, it is encouraging to have a low initial rate of PPI therapy prescribed patients.

LOW-MASS SUPPRESSION OF THE SATELLITE LUMINOSITY FUNCTION DUE TO THE SUPERSONIC BARYON-COLD-DARK-MATTER RELATIVE VELOCITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bovy, Jo; Dvorkin, Cora

We study the effect of the supersonic baryon-cold-dark-matter (CDM) flow, which has recently been shown to have a large effect on structure formation during the dark ages 10 {approx}< z {approx}< 1000, on the abundance of luminous, low-mass satellite galaxies around galaxies like the Milky Way. As the supersonic baryon-CDM flow significantly suppresses both the number of halos formed and the amount of baryons accreted onto such halos of masses 10{sup 6} < M{sub halo}/M{sub Sun} < 10{sup 8} at z {approx}> 10, a large effect results on the stellar luminosity function before reionization. As halos of these masses aremore » believed to have very little star formation after reionization due to the effects of photoheating by the ultraviolet background, this effect persists to the present day. We calculate that the number of low-mass 10{sup 6} < M{sub halo}/M{sub Sun} < 5 Multiplication-Sign 10{sup 7} halos that host luminous satellite galaxies today is typically suppressed by 50%, with values ranging up to 90% in regions where the initial supersonic velocity is high. We show that this previously ignored cosmological effect resolves some of the tension between the observed and predicted number of low-mass satellites in the Milky Way, reducing the need for other mass-dependent star-formation suppression before reionization.« less

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Zebularine suppresses the apoptotic potential of 5-fluorouracil via cAMP/PKA/CREB pathway against human oral squamous cell carcinoma cells.

PubMed

Suzuki, Maiko; Shinohara, Fumiaki; Endo, Manabu; Sugazaki, Masaki; Echigo, Seishi; Rikiishi, Hidemi

2009-07-01

During tumorigenesis, tumor suppressor and tumor-related genes are commonly silenced by aberrant DNA methylation in their promoter regions, which is one of the important determinants of susceptibility to 5-fluorouracil (5-FU) in oral squamous cell carcinoma (OSCC) cells. Here, we examine the chemotherapeutic efficacy of epigenetic agents on 5-FU cytotoxicity. We investigated the effect of a DNA methyltransferase (DNMT) inhibitor, zebularine (Zeb), on the chemosensitivity of 5-FU and cisplatin (CDDP) by MTT and TUNEL methods, and compared the molecular mechanism of action with those of a GSK3beta inhibitor, LiCl, and an Hsp90 inhibitor, 17-AAG. A significant apoptotic effect by a combination of Zeb or 17-AAG was found in CDDP treatment; however, considerable suppression of 5-FU-induced apoptosis was observed after incubation with Zeb, 17-AAG, or LiCl. Zeb's suppressive effects were associated with activation of the cAMP/PKA/CREB pathway, differing from mechanisms of 17-AAG and LiCl. Suppression of 5-FU-induced apoptosis by Zeb was not associated with increased Bcl-2 and Bcl-xL expressions dependent on transcription factor CREB, and with the expression level of thymidylate synthase. In the present study, we identified a more detailed mechanism of action by which Zeb suppresses 5-FU-induced apoptosis. These results indicate that combination therapies have to be carefully investigated due to potential harmful effects in the clinical application of DNMT inhibitors.

Quinolone Resistance Reversion by Targeting the SOS Response

PubMed Central

Recacha, E.; Machuca, J.; Díaz de Alba, P.; Ramos-Güelfo, M.; Docobo-Pérez, F.; Pascual, A.

2017-01-01

ABSTRACT Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. PMID:29018116

The suppression of inflammatory macrophage-mediated cytotoxicity and proinflammatory cytokine production by transgenic expression of HLA-E.

PubMed

Maeda, Akira; Kawamura, Takuji; Ueno, Takehisa; Usui, Noriaki; Eguchi, Hiroshi; Miyagawa, Shuji

2013-12-01

Macrophages participate in xenogenic rejection and represent a major biological obstacle to successful xenotransplantation. The signal inhibitory regulatory protein α (SIRPα) receptor was reported to be a negative regulator of macrophage phagocytic activity via interaction with CD47, its ligand. Because a majority of human macrophages express the inhibitory receptor CD94/NKG2A, which binds specifically to the human leukocyte antigen (HLA)-E and contains immunoreceptor tyrosine-based inhibition motifs (ITIMs), the inhibitory function of HLA class I molecules, HLA-E, on macrophage-mediated cytolysis was examined. The suppressive effect against proinflammatory cytokine production by macrophages was also examined. Complementary DNA (cDNA) of HLA-E, and CD47 were prepared and transfected into swine endothelial cells (SEC). The expression of the modified genes was evaluated by flow cytometry and macrophage-mediated cytolysis was assessed using in vitro generated macrophages. Transgenic expression of HLA-E significantly suppressed the macrophage-mediated cytotoxicity. HLA-E transgenic expression demonstrated a significant suppression equivalent to CD47 transgenic expression. Furthermore, transgenic HLA-E suppressed the production of pro-inflammatory cytokines by inflammatory macrophages. These results indicate that generating transgenic HLA-E pigs might protect porcine grafts from, not only NK cytotoxicity, but also macrophage-mediated cytotoxicity. © 2013 Elsevier B.V. All rights reserved.

Effect of long-term farming strategies on soil microbiota and soil health

NASA Astrophysics Data System (ADS)

Sommermann, Loreen; Babin, Doreen; Sandmann, Martin; Smalla, Kornelia; Schellenberg, Ingo; Grosch, Rita; Geistlinger, Joerg

2017-04-01

Increasing food and energy demands have resulted in considerable intensification of farming practices, which brought about severe consequences for agricultural soils, e.g. loss of fertility, erosion and enrichment of soil-borne plant diseases. In order to maintain soil quality and health for the future, the development of more extensive and sustainable farming strategies is urgently needed. The soil microbiome is regarded as a key player in soil ecosystem functions, particularly the natural ability of soils to suppress plant pathogens (suppressiveness). Recent studies showed that soil microbial communities are influenced by agricultural management. To further analyze the effects of farming strategies on soil suppressiveness and plant performance, agricultural soils from three long-term field trials in Thyrow, Bernburg (both in Germany) and Therwil (Switzerland) were sampled and subjected to molecular profiling of soil bacteria and fungi using marker genes and high-throughput amplicon sequencing. Significant effects on bacterial as well as fungal community composition, including plant pathogenic and beneficial taxa, were observed among variants of tillage and crop rotation. The least effect on both communities had fertilization, with no significance between variants. Subsequently, the same soils were subjected to growth chamber pot experiments with lettuce as a model (Lactuca sativa). After a growth period of six weeks significant differences in lettuce shoot and soil microbial biomass were observed among soil samples of the different long-term trials. Furthermore, the lettuce rhizosphere exhibited diverse bacterial community compositions as observed by DGGE (denaturing gradient gel electrophoresis). Using group-specific PCR-DGGE fingerprints, bacterial responders to fertilization, soil management and crop rotation were identified among different taxonomic groups. Currently, bacterial and fungal amplicon sequencing of rhizosphere and bulk soil from these pot experiments is ongoing in order to provide further insights into taxa potentially indicative for agricultural management and soil health. Presently, we are testing the potential of the different soil microbiomes to suppress the lettuce pathogen Rhizoctonia solani.

Anger Suppression, Interdependent Self-Construal, and Depression among Asian American and European American College Students

PubMed Central

Cheung, Rebecca Y. M.; Park, Irene J. K.

2010-01-01

The present study tested a theoretical model of emotion regulation (Yap, Sheeber, & Allen, 2007) in a sample of Asian American and European American college students (N = 365). Specifically, the mediating role of anger suppression in the effect of temperament and family processes on depressive symptoms was tested across race and levels of interdependent self-construal (a culturally based self orientation emphasizing connectedness with others). Next, the moderation of the suppression—depression relation was tested by race and interdependent self-construal. Results indicated that the hypothesized model fit well across Asian American and European American students as well as those with high vs. low levels of interdependent self-construal. Anger suppression was a significant mediator of the hypothesized indirect effects on depressive symptoms. Moreover, race and interdependent self-construal moderated the suppression—depression link, such that Asian American status and a stronger interdependent self-construal attenuated the relation between anger suppression and depressive symptoms. Understanding both universal and culture-specific aspects of emotion regulation in the development of depressive symptoms will be essential for sound theory, future research, and effective prevention and intervention efforts across diverse populations. PMID:21058815

The multi-year effects of repeatedly growing cotton with moderate resistance to Meloidogyne incognita

PubMed Central

Kemerait, Robert C.

2009-01-01

Meloidogyne incognita causes more damage to cotton in the US than any other pathogen. The objective of this study was to document the cumulative effect of moderate resistance on M. incognita population density, root galling, and yield suppression in the southern United States on a moderately resistant cotton genotype grown continuously for three years. Cotton genotypes were Phytogen PH98-3196 (77% suppression of M. incognita), Acala NemX (85% suppression of M. incognita), and Delta and Pine Land DP458 B/R (susceptible standard, 0% suppression). Cotton was grown in fumigated and non-fumigated plots to measure yield loss. Each genotype and nematicide combination was planted in the same place for three years at two sites to document cumulative effects. In 2006, following three years of the different genotypes, all plots at one site were planted with susceptible cotton to document residual effects of planting resistant genotypes. Root galling and nematode population densities in the soil were significantly lower, and percentage yield suppression was numerically lower, when moderately resistant cotton was grown compared to the susceptible standard in both fields in all three years. Differences between susceptible and moderately resistant genotypes are established quickly (after only one season) and then either maintained at similar levels or slightly increased in subsequent years depending on initial nematode levels. However, when susceptible cotton was grown following three years of the moderately resistant genotypes, the nematode suppression provided by moderate resistance was undetectable by the end of the first season. Moderately resistant cotton genotypes are more beneficial than previously reported and should be pursued for nematode management. Rotation of moderately resistant and susceptible cotton could be used along with nematicides to manage root-knot nematodes in a continuous cotton cropping system and reduce selection pressure on the nematodes. PMID:22661787

Essential oils have different effects on human pathogenic and commensal bacteria in mixed faecal fermentations compared with pure cultures.

PubMed

Thapa, Dinesh; Louis, Petra; Losa, Riccardo; Zweifel, Béatrice; Wallace, R John

2015-02-01

A static batch culture system inoculated with human faeces was used to determine the influence of essential oil compounds (EOCs) on mixed faecal microbiota. Bacteria were quantified using quantitative PCR of 16S rRNA genes. Incubation for 24 h of diluted faeces from six individuals caused enrichment of Bifidobacterium spp., but proportions of other major groups were unaffected. Thymol and geraniol at 500 p.p.m. suppressed total bacteria, resulting in minimal fermentation. Thymol at 100 p.p.m. had no effect, nor did eugenol or nerolidol at 100 or 500 p.p.m. except for a slight suppression of Eubacterium hallii. Methyl isoeugenol at 100 or 500 p.p.m. suppressed the growth of total bacteria, accompanied by a large fall in the molar proportion of propionate formed. The relative abundance of Faecalibacterium prausnitzii was unaffected except with thymol at 500 p.p.m. The ability of EOCs to control numbers of the pathogen Clostridium difficile was investigated in a separate experiment, in which the faecal suspensions were amended by the addition of pure culture of C. difficile. Numbers of C. difficile were suppressed by thymol and methyl isoeugenol at 500 p.p.m. and to a lesser extent at 100 p.p.m. Eugenol and geraniol gave rather similar suppression of C. difficile numbers at both 100 and 500 p.p.m. Nerolidol had no significant effect. It was concluded from these and previous pure-culture experiments that thymol and geraniol at around 100 p.p.m. could be effective in suppressing pathogens in the small intestine, with no concern for beneficial commensal colonic bacteria in the distal gut. © 2015 The Authors.

Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells.

PubMed

Huang, Wen-Chung; Wu, Shu-Ju; Tu, Rong-Syuan; Lai, You-Rong; Liou, Chian-Jiun

2015-06-01

Phloretin, a flavonoid isolated from the apple tree, is reported to have anti-inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we evaluated the suppressive effects of phloretin on intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1β-stimulated human lung epithelial A549 cells. The cells were pretreated with various concentrations of phloretin (3-100 μM), followed by induced inflammation by IL-1β. Phloretin inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM-1 gene and protein expression and suppressed monocyte adhesion to inflammatory A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. In addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both MAPK inhibitors and phloretin in inflammatory A549 cells. However, phlorizin, a derivative of phloretin, did not suppress the inflammatory response in IL-1β-stimulated A549 cells. These results suggest that phloretin might have an anti-inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1 expression via blocked NF-κB and MAPK signaling pathways.

Electrochemically Reduced Water Protects Neural Cells from Oxidative Damage

PubMed Central

Hamasaki, Takeki; Kinjo, Tomoya; Nakamichi, Noboru; Teruya, Kiichiro; Kabayama, Shigeru

2014-01-01

Aging-related neurodegenerative disorders are closely associated with mitochondrial dysfunction and oxidative stresses and their incidence tends to increase with aging. Brain is the most vulnerable to reactive species generated by a higher rate of oxygen consumption and glucose utilization compared to other organs. Electrochemically reduced water (ERW) was demonstrated to scavenge reactive oxygen species (ROS) in several cell types. In the present study, the protective effect of ERW against hydrogen peroxide (H2O2) and nitric oxide (NO) was investigated in several rodent neuronal cell lines and primary cells. ERW was found to significantly suppress H2O2 (50–200 μM) induced PC12 and SFME cell deaths. ERW scavenged intracellular ROS and exhibited a protective effect against neuronal network damage caused by 200 μM H2O2 in N1E-115 cells. ERW significantly suppressed NO-induced cytotoxicity in PC12 cells despite the fact that it did not have the ability to scavenge intracellular NO. ERW significantly suppressed both glutamate induced Ca2+ influx and the resulting cytotoxicity in primary cells. These results collectively demonstrated for the first time that ERW protects several types of neuronal cells by scavenging ROS because of the presence of hydrogen and platinum nanoparticles dissolved in ERW. PMID:25383141

Suppressive effect of viscous dietary fiber on elevations of uric acid in serum and urine induced by dietary RNA in rats is associated with strength of viscosity.

PubMed

Koguchi, Takashi; Nakajima, Hisao; Koguchi, Hiromi; Wada, Masahiro; Yamamoto, Yuji; Innami, Satoshi; Maekawa, Akio; Tadokoro, Tadahiro

2003-10-01

This study was performed to clarify how dietary fiber (DF) with different viscosities would be associated with dietary RNA metabolism. Male Wistar strain rats, four weeks old, were fed diets containing a 3% (w/w) yeast RNA and a 5% (w/w) viscous DF for five days. Viscosity of DF samples used, in order of strength, were xanthan gum (XG) > guar gum (GG) > locust bean gum (LBG) > karaya gum (KG) > pectin (PE) = arabic gum (AG) > CM-cellulose (CMC) = inulin (IN). The serum uric acid concentration in the viscous DF groups significantly decreased as compared with that in the cellulose (CL) group. The urinary excretions of uric acid and allantoin in the respective groups given AG, GG, IN, KG, PE, and XG were significantly suppressed as compared with those in the CL group. The fecal RNA excretion was markedly increased in the IN, KG, PE, and XG groups in comparison to the CL group. The DF with high viscosity significantly suppressed RNA digestion by RNase A and decreased uptakes of 14C-labeled adenosine and adenosine 5'-monophosphate (5'-AMP) in rat jejunum. The results reveal that the suppressive effect of DF on elevation of serum uric acid concentration induced by dietary RNA in rats is associated with the strength of DF viscosity. The mechanism by which this is accomplished is suggested to be attributed to the inhibitions of digestion for dietary RNA and/or absorption of the hydrolyzed compounds.

Suppression of pyritic sulphur during flotation tests using the bacterium Thiobacillus ferrooxidans.

PubMed

Townsley, C C; Atkins, A S; Davis, A J

1987-07-01

Environmental concern about sulphur dioxide emissions has led to the examination of the possibility of removing pyritic sulphur from coal prior to combustion during froth flotation, a routine method for coal cleaning at the pit-head. The bacterium Thiobacillus ferrooxidans was effective in leaching 80% and 63% -53 mum pyrite at 2% and 6% pulp density in shake flasks in 240 and 340 h, respectively.The natural floatability of pyrite was significantly reduced in the Hallimond tube following 2.5 min of conditioning in membrane-filtered bacterial liquor prior to flotation. The suppression effect was greatly enhanced in the presence of Thiobacillus ferrooxidans. A bacterial suspension in pH 2.0 distilled water showed 85% suppression, whereas in spent growth liquor this value was 95%. The optimum bacterial density was 3.25 x 10(10) cells/g pyrite in 230-ml distilled water (2% pulp density) in the Hallimond tube. The degree of suppression by the cells was related to particle size but not to pH or temperature. The sulphur content of a synthetic coal/pyrite mixture was reduced from 10.9 to 2.1% by flotation after bacterial preconditioning. It is postulated that pyrite removal in coals which are cleaned by froth flotation could be significantly reduced using a bacterial preconditioning stage with a short residence time of 2.5 min.

Differential effects of suppressors on hazardous sound pressure levels generated by AR-15 rifles: Considerations for recreational shooters, law enforcement, and the military.

PubMed

Lobarinas, Edward; Scott, Ryan; Spankovich, Christopher; Le Prell, Colleen G

2016-01-01

Firearm discharges produce hazardous levels of impulse noise that can lead to permanent hearing loss. In the present study, we evaluated the effects of suppression, ammunition, and barrel length on AR-15 rifles. Sound levels were measured left/right of a user's head, and 1-m left of the muzzle, per MIL-STD-1474-D, under both unsuppressed and suppressed conditions. Nine commercially available AR-15 rifles and 14 suppressors were used. Suppressors significantly decreased peak dB SPL at the 1-m location and the left ear location. However, under most rifle/ammunition conditions, levels remained above 140 dB peak SPL near a user's right ear. In a subset of conditions, subsonic ammunition produced values near or below 140 dB peak SPL. Overall suppression ranged from 7-32 dB across conditions. These data indicate that (1) suppressors reduce discharge levels to 140 dB peak SPL or below in only a subset of AR-15 conditions, (2) shorter barrel length and use of muzzle brake devices can substantially increase exposure level for the user, and (3) there are significant left/right ear sound pressure differences under suppressed conditions as a function of the AR-15 direct impingement design that must be considered during sound measurements to fully evaluate overall efficacy.

Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.

PubMed

Russell, S H; Kim, M S; Small, C J; Abbott, C R; Morgan, D G; Taheri, S; Murphy, K G; Todd, J F; Ghatei, M A; Bloom, S R

2000-12-01

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Joeng, Ji-Hyun

2014-01-01

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension. PMID:25598663

Control of the immune response by DHEA and its metabolites.

PubMed

Loria, R M; Padgett, D A

1998-06-01

The 17 keto steroid, Dehydroepiandrosterone (5-androsten-3 beta-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpesvirus type 2, coxsackievirus B4-CVB4),bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have reported that androstenediol (5-androsten-3 beta-17 beta-diol, beta AED), which is derived from DHEA, is at least 100x more effective in up-regulating systemic resistance against CVB4-infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol beta AET) which is formed by 7 beta hydroxylation of beta AED, was more effective against CVB4-infection than its precursor beta AED. Neither steroid however has shown any significant direct antiviral effects. The in-vitro influences of DHEA, beta AED, and beta AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (Con A) or lipopolysaccharide (LPS) activated cultures in a dose dependent manner. beta AED had little influence on the activation response. However, beta AET potentiated the response to both mitogens significantly above control. The regulation of interleukin-2 and interleukin-3 secretion from Con A-activated lymphocytes was analogous to these observations. These functions were suppressed by DHEA, unaffected by beta AED, and potently increased by beta AET. Moreover, the classic immuno-suppressive effects of hydro-cortisone on Con A-induced lymphocyte proliferation, as well as IL-2 and IL-3 production were unaffected by co-cultured with DHEA and only minimally counteracted by beta AED. In contrast, beta AET significantly counteracted the effect of hydrocortisone when co-cultured together. These results show that while in-vivo, DHEA, beta AED, and beta AET each function in a similar manner. In-vitro, their effects are dramatically different from one another with only beta AET potentiating the cellular response by increasing lymphocyte activation and counteracting the immuno-suppressive activity of hydrocortisone.

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis

PubMed Central

Amiri, Mina; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-01-01

Background Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Objective This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone–binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. Results COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=−0.48; 95% CI −0.81 to −0.15), 6 months (WMD=−2.33; 95% CI −3.48 to −1.18), and 12 months (WMD=−4.70; 95% CI −4.98 to −4.42) and a decrease in LH levels after 3 months (WMD=−3.57; 95% CI −5.14 to −1.99), 6 months (WMD=−5.68; 95% CI −9.57 to −1.80), and 12 months (WMD=−11.60; 95% CI −17.60 to −5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=−0.93; 95% CI −1.79 to −0.08) and LH (WMD=−4.59; 95% CI −7.53 to −1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone–binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone–binding globulin levels. Conclusions COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. PMID:29695378

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

PubMed

Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-04-25

Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=-0.93; 95% CI -1.79 to -0.08) and LH (WMD=-4.59; 95% CI -7.53 to -1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone-binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone-binding globulin levels. COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. ©Mina Amiri, Fahimeh Ramezani Tehrani, Fatemeh Nahidi, Ali Kabir, Fereidoun Azizi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.04.2018.

Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

PubMed Central

Galindo, Danielle; Villanueva, Linda; Nguyen, Cathy; Patel, Milan; Borbridge, Lisa; Attar, Mayssa; Schiffman, Rhett M.; Hollander, David A.

2011-01-01

Abstract Purpose Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model. Methods At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)–dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC50) for COX isoenzymes. Results Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E2 and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E2 elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC50 for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC50 for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. Conclusions Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC-dextran leakage. The difference in inflammation suppression may be due to differences in tissue concentrations and/or greater COX-1 suppression by ketorolac 0.45%. PMID:21351868

Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes.

PubMed

Stinson, Lisa F; Ireland, Demelza J; Kemp, Matthew W; Payne, Matthew S; Stock, Sarah J; Newnham, John P; Keelan, Jeffrey A

2014-03-01

Intrauterine infection and inflammation are responsible for the majority of early (<32 weeks) spontaneous preterm births (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3-20  h). In human membranes, the IKKβ inhibitor TPCA-1 (7  μM) and p38 MAPK inhibitor SB239063 (20  μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10  mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10  μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.

Efflux inhibitor suppresses Streptococcus mutans virulence properties.

PubMed

Zeng, Huihui; Liu, Jia; Ling, Junqi

2017-04-01

It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The impact of caloric preloading on attempts at food and eating-related thought suppression in restrained and unrestrained eaters.

PubMed

O'Connell, Cara; Larkin, Kevin; Mizes, J Scott; Fremouw, William

2005-07-01

The current study examined the impact of dietary restraint and caloric preload on thought suppression in a sample of 64 college females classified as either restrained or unrestrained eaters. Participants engaged in a 60-min laboratory session. One half of the participants were preloaded with a high-calorie milkshake and all participants were randomly assigned to a food and eating-related thought suppression condition or a no suppression control condition. Food-related thoughts were assessed with a digital counter and verbal references to food were tracked with an audio recorder. Restrained participants instructed to suppress food-related thoughts demonstrated significantly more food and eating-related thoughts than unrestrained participants. Preloading was associated with an increase in the frequency of indirect mentions to food and eating. Although the hypothesized "rebound" effect did not occur for any study groups, these findings indicate that both restraint status and preloading impact food and eating-related thoughts. Copyright 2005 by Wiley Periodicals, Inc

Multi-walled carbon nanotubes suppress potassium channel activities in PC12 cells

NASA Astrophysics Data System (ADS)

Xu, Haifei; Bai, Juan; Meng, Jie; Hao, Wei; Xu, Haiyan; Cao, Ji-Min

2009-07-01

The advancement in nanotechnology has produced technological and conceptual breakthroughs but the effects nanomaterials have on organisms at the cellular level are poorly understood. Here we report that carboxyl-terminated multi-walled carbon nanotubes (MWCNTs) act as antagonists of three types of potassium channels as assessed by whole-cell patch clamp electrophysiology on undifferentiated pheochromocytoma (PC12) cells. Our results showed that carboxyl-terminated MWCNTs suppress the current densities of Ito, IK and IK1 in a time-dependent and irreversible manner. The suppressions were most distinct 24 h after incubation with MWCNTs. However, MWCNTs did not significantly change the expression levels of reactive oxygen species (ROS) or intracellular free calcium and also did not alter the mitochondrial membrane potential (ΔΨm) in PC12 cells. These results suggest that oxidative stress was not involved in the MWCNTs suppression of Ito, IK and IK1 current densities. Nonetheless, the suppression of potassium currents by MWCNTs will impact on electrical signaling of excitable cells such as neurons and muscles.

Studies on some feed additives and materials giving partial protection against the suppressive effect of ochratoxin A on egg production of laying hens.

PubMed

Stoev, Stoycho D

2010-06-01

The protective effects of various feed supplements against the harmful effect of ochratoxin A on egg production and sexual maturation of two-weeks old Plymouth Rock female chicks designed for laying hens were studied. A significant protective effect of the feed additives or materials: water extract of artichoke (WEA), sesame seed (SS), Roxazyme-G (RG) and l-beta phenylalanine (PHE) against the suppressive effect of ochratoxin A (OTA) on egg production of laying hens was found. A similar protection was also seen on the toxic effect of OTA on various internal organs of the same hens. A significant protection was found against the decrease of the weight or the quantity of eggs as well as against the delay of the beginning of the laying period of chicks, both of which were provoked by ochratoxin A. These protective effects were strongest in chicks treated with SS or WEA, but were slightest in chicks treated with l-beta PHE. Copyright 2009 Elsevier Ltd. All rights reserved.

Improved Chemical Control of Chagas Disease Vectors in the Dry Chaco Region

PubMed Central

CECERE, MARÍA CARLA; VAZQUEZ-PROKOPEC, GONZALO M.; CEBALLOS, LEONARDO A.; BORAGNO, SILVANA; ZÁRATE, JOAQUÍN E.; KITRON, URIEL; GÜRTLER, RICARDO E.

2013-01-01

The effectiveness of two doses of suspension concentrate (SC) pyrethroid insecticides in suppressing peridomestic populations of Triatoma infestans (Klug) was evaluated in 28 rural communities located in Santiago del Estero province, northwestern Argentina, including 388 houses and 1,516 identified sites. Four treatments were randomly assigned to peridomiciles within each community: 5% SC β-cypermethrin at standard (S, 50 mg active ingredient [AI]/m2) and double dose (2S), and 2.5% SC deltamethrin at standard (D, 25 mg [AI]/m2) and double dose (2D). Simultaneously, we assessed the effects of both pyrethroids applied at standard doses against domestic infestations. Bug infestation at the site level was assessed by timed manual collections with a dislodging agent at baseline, 13 and 21 mo postspraying (MPS). In domiciles, D and S nearly suppressed all T. infestans infestations up to 21 MPS. In peridomestic sites infested before interventions, multiple logistic regression analysis showed that site-level reinfestation at 13 MPS was significantly lower for treatment 2D (1%) than for other treatments, whereas 2S (6%), D (5%), and S (14%) did not differ significantly between them. The risk of reinfestation after spraying was significantly greater in goat or pig corrals than in other peridomestic ecotopes (in which treatments did not differ significantly), and in sites infested before interventions than in uninfested sites. The application of SC deltamethrin at double dose in goat or pig corrals may suppress T. infestans foci and achieve more sustained effects in the dry Chaco. PMID:23540129

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Nakanishi, Yasutomo; Nishikawa, Satoshi; Kayasuga, Ryoji; Kawada, Naoki; Kunishige, Akiko; Hashimoto, Yasuaki; Tanaka, Makoto; Sugitani, Masafumi; Kawabata, Kazuhito

2014-08-01

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity.

PubMed

Cameron, Ivan L; Markov, Marko S; Hardman, W Elaine

2014-01-01

This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice. The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice. Once the tumor grew to 100 mm(3), daily EMF treatments were started by placing the cage of mice within the EMF field. Treatment ranged from 10 to 20 milli-Tesla (mT) and was given for 3 to 80 minutes either once or twice a day for 12 days. Tumors were measured and volumes calculated each 3-4 days. Therapeutic EMF treatment significantly suppressed tumor growth in all 7 EMF treated groups. Exposure to 20mT for 10 minutes twice a day was the most effective tumor growth suppressor. The effect of EMF treatment on extent of tumor vascularization, necrosis and viable area was determined after euthanasia. The EMF reduced the vascular (CD31 immunohistochemically positive) volume fraction and increased the necrotic volume of the tumor. Treatment with 15 mT for 10 min/d gave the maximum anti-angiogenic effect. Lack of a significant correlation between tumor CD 31 positive area and tumor growth rate indicates a mechanism for suppression of tumor growth in addition to suppression of tumor vascularization. It is proposed that EMF therapy aimed at suppression of tumor growth and vascularization may prove a safe alternative for patients whether they are or are not candidates for conventional cancer therapy.

Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-κB/MMP‑9.

PubMed

Chen, Xin-Jun; Wu, Mian-Yun; Li, Deng-Hui; You, Jin

2016-09-01

The present study aimed to investigate the effect of apigenin on glioma cells and to explore its potential mechanism. U87 human glioma cells treated with apigenin were used in the current study. Cell Counting Kit‑8 solution and Annexin V-fluorescein isothiocyanate/propidium iodide Apoptosis Detection kit were used to analyze the effect of apigenin on U87 cell viability and apoptotic cell death. Reverse transcription‑quantitative polymerase chain reaction analysis was also used to determine microRNA‑16 (miR‑16) and MMP‑9 gene expression levels. Nuclear factor‑κB (NF‑κB) and B‑cell CLL/lymphoma 2 (BCL2) protein expression levels were determined using western blot analysis. An anti‑miR‑16 plasmid was constructed and transfected into U87 cells. The current study demonstrated that apigenin significantly decreased cell viability and induced apoptotic cell death of U87 cells in a dose‑dependent manner. Additionally, it was demonstrated that apigenin significantly increased miR‑16 levels, suppressed BCL2 protein expression and suppressed the NF‑κB/MMP9 signaling pathway in U87 cells. Furthermore, downregulation of miR‑16 using the anti‑miR‑16 plasmid reversed the effect of apigenin on cell viability, BCL2 protein expression and the NF‑κB/MMP‑9 pathway in U87 cells. The results of the present study suggested that apigenin inhibits glioma cell growth through promoting miR‑16 and suppression of BCL2 and NF-κB/MMP-9. In conclusion, the present study demonstrated the potential anticancer effects of apigenin on glioma cells.

Suppressive effects of formoterol and salmeterol on eotaxin-1 in bronchial epithelial cells.

PubMed

Chu, Yu-Te; Chang, Tai-Tsung; Jong, Yuh-Jyh; Kuo, Po-Lin; Lee, Hsi-Ming; Lee, Min-Sheng; Chang, Hui-Wen; Hung, Chih-Hsing

2010-03-01

Eotaxin-1 (CCL11), an eosinophil-specific C-C chemokine, is a potent chemoattractant for mobilization of eosinophils into airways after allergic stimulation. Eotaxin-1 recruits eosinophils into inflammatory sites, and may play a role in the pathogenesis of asthma. Formoterol and salmeterol are two inhaled long acting beta(2) adrenoceptor agonists (LABAs), widely used for the local treatment of asthma. However, little is known about their effects on the eotaxin-1 expression of bronchial epithelial cells. BEAS-2B cells were stimulated by adding IL-4 with or without 2 h pre-treatment of formoterol or salmeterol. The protein and mRNA expression of eotaxin-1 were measured by ELISA assay and real-time PCR, respectively. Effects of formoterol and salmeterol on nuclear and cytosolic pSTAT-6 expression were evaluated by Western blot and immunofluorescence study. Formoterol and salmeterol (10(-7)-10(-10) m) significantly down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. A specific beta(2) adrenoceptor antagonist (ICI 118,551) reversed their suppression of eotaxin-1 production. Forskolin, an cAMP activator, could also suppress the expression of eotaxin-1 by IL-4 in a dose dependent manner (10(-7)-10(-10 )m). The western blot and immunofluorescence studies demonstrated that formoterol 10(-7 )m suppressed the nuclear expression of pSTAT-6. Formoterol and salmeterol, two inhaled long-acting beta(2) agonists, down-regulated IL-4- induced eotaxin-1 expression in BEAS-2B cells. The effect was mediated via the beta(2) adrenoceptor, and cAMP. Formoterol significantly down-regulated pSTAT6 at higher concentration, and further turned off the IL-4 signaling pathway.

An alternative mechanism for radioprotection by dimethyl sulfoxide; possible facilitation of DNA double-strand break repair.

PubMed

Kashino, Genro; Liu, Yong; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Yuko; Ono, Koji; Tano, Keizo; Watanabe, Masami

2010-01-01

The radioprotective effects of dimethyl sulfoxide (DMSO) have been known for many years, and the suppression of hydroxyl (OH) radicals induced by ionizing radiation has been thought to be the main cause of this effect. However, the DMSO concentration used was very high, and might be toxic, in earlier studies. In the present study, we administered a lower, non-toxic concentration (0.5%, i.e., 64 mM) of DMSO before irradiation and examined its radioprotective effects. Colony formation assay and micronucleus assay showed significant radioprotective effects in CHO, but not in xrs5, which is defective in the repair function of DNA double-strand breaks. The levels of phosphorylated H2AX and the formation of 53BP1 foci 15 minutes after irradiation, which might reflect initial DNA double-strand breaks, in DMSO-treated CHO cells were similar to those in non-treated cells, suggesting that the radioprotective effects were not attributable to the suppression of general indirect action in the lower concentration of DMSO. On the other hand, 2 hours after irradiation, the average number of 53BP1 foci, which might reflect residual DNA double-strand breaks, was significantly decreased in DMSO-treated CHO cells compared to non-treated cells. The results indicated that low concentration of DMSO exerts radioprotective effects through the facilitation of DNA double-strand break repair rather than through the suppression of indirect action.

Legacy effects of anaerobic soil disinfestation on soil bacterial community composition and production of pathogen-suppressing volatiles

PubMed Central

van Agtmaal, Maaike; van Os, Gera J.; Hol, W.H. Gera; Hundscheid, Maria P.J.; Runia, Willemien T.; Hordijk, Cornelis A.; de Boer, Wietse

2015-01-01

There is increasing evidence that microbial volatiles (VOCs) play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial community composition would affect the production by soils of VOCs suppressing the plant-pathogenic oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we compared the composition of bacterial communities in sandy soils that had been exposed to anaerobic disinfestation (AD), a treatment used to kill harmful soil organisms, with the composition in untreated soils. Three months after the AD treatment had been finished, there was still a clear legacy effect of the former anaerobic stress on bacterial community composition with a strong increase in relative abundance of the phylum Bacteroidetes and a significant decrease of the phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi, and Chlorobi. This change in bacterial community composition coincided with loss of production of Pythium suppressing soil volatiles (VOCs) and of suppression of Pythium impacts on Hyacinth root development. One year later, the composition of the bacterial community in the AD soils was reflecting that of the untreated soils. In addition, both production of Pythium-suppressing VOCs and suppression of Pythium in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS analysis identified several VOCs, among which compounds known to be antifungal, that were produced in the untreated soils but not in the AD soils. These compounds were again produced 15 months after the AD treatment. Our data indicate that soils exposed to a drastic stress can temporarily lose pathogen suppressive characteristics and that both loss and return of these suppressive characteristics coincides with shifts in the soil bacterial community composition. Our data are supporting the suggested importance of microbial VOCs in the natural buffer of soils against diseases caused by soil-borne pathogens. PMID:26217330

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

PubMed

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Combined treatment with dipeptidyl peptidase-4 inhibitor (sitagliptin) and angiotensin-II type 1 receptor blocker (losartan) suppresses progression in a non-diabetic rat model of steatohepatitis.

PubMed

Okura, Yasushi; Namisaki, Tadashi; Moriya, Kei; Kitade, Mitsuteru; Takeda, Kosuke; Kaji, Kosuke; Noguchi, Ryuichi; Nishimura, Norihisa; Seki, Kenichiro; Kawaratani, Hideto; Takaya, Hiroaki; Sato, Shinya; Sawada, Yasuhiko; Shimozato, Naotaka; Furukawa, Masanori; Nakanishi, Keisuke; Saikawa, Soichiro; Kubo, Takuya; Asada, Kiyoshi; Yoshiji, Hitoshi

2017-11-01

Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of non-diabetic non-alcoholic steatohepatitis (NASH) in a rat model. To induce NASH, Fischer 344 rats were fed a choline-deficient L-amino acid-defined diet for 12 weeks. We elucidated the chemopreventive effects of sitagliptin + losartan, especially in conjunction with hepatic stellate cell (HSC) activation, angiogenesis, and oxidative stress, all known to play important roles in the progression of NASH. Sitagliptin + losartan suppressed choline-deficient L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. The combination treatment exerted a greater inhibitory effect than monotherapy. These inhibitory effects occurred almost concurrently with the suppression of HSC activation, neovascularization, and oxidative stress. In vitro studies showed that sitagliptin + losartan inhibited angiotensin II-induced proliferation and expression of transforming growth factor-β1 and α1 (I)-procollagen mRNA of activated HSC and in vitro angiogenesis, in parallel with the suppression observed in in vivo studies. The widely and safely used sitagliptin + losartan combination treatment in clinical practice could be an effective strategy against NASH. © 2016 The Japan Society of Hepatology.

Pirfenidone exerts a suppressive effect on CCL18 expression in U937-derived macrophages partly by inhibiting STAT6 phosphorylation.

PubMed

Saito, Yoshinobu; Azuma, Arata; Matsuda, Kuniko; Kamio, Koichiro; Abe, Shinji; Gemma, Akihiko

2016-10-27

CC chemokine ligand 18 (CCL18) is suggested to play a role in the development of pulmonary fibrosis. Macrophages are thought to be the main source of CCL18, and the effect of pirfenidone, an anti-fibrotic agent for idiopathic pulmonary fibrosis, on the expression of CCL18 in macrophages warrants investigation. The purpose of this study was to investigate the effect of pirfenidone on the expression of CCL18 in macrophages. U937 cells were differentiated into macrophages by phorbol myristate acetate and then stimulated with recombinant IL-4 to induce the production of CCL18. The cells were treated with pirfenidone, and the mRNA and protein levels for CCL18 were measured by a reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effects of pirfenidone on the IL-4 receptor (IL-4R) expression and STAT6 activation were investigated and on the JAK kinase activity were measured using the Z'-LYTE™ kinase assay. Pirfenidone significantly suppressed the expression of CCL18 when the cells were treated with concentrations of 50-250 μg/mL. Pirfenidone did not affect the expression of the IL-4R components. The selective STAT6 inhibitor AS1517499 suppressed CCL18 expression. Both AS1517499 and pirfenidone suppressed STAT6 phosphorylation (p < .05), although the effect of pirfenidone was less marked than that of AS1517499. The Z'-LYTE™ kinase assay showed a reduction in the activities of JAK1, JAK3 and TYK2 by pirfenidone. Pirfenidone suppresses CCL18 expression in macrophages and this effect is thought to be attributed partly to the inhibition of STAT6 phosphorylation.

Facing Complaining Customer and Suppressed Emotion at Worksite Related to Sleep Disturbance in Korea

PubMed Central

2016-01-01

This study aimed to investigate the effect of facing complaining customer and suppressed emotion at worksite on sleep disturbance among working population. We enrolled 13,066 paid workers (male = 6,839, female = 6,227, age < 65 years) in the 3rd Korean Working Condition Survey (2011). The odds ratio (OR) and 95% confidence intervals (CI) for sleep disturbance occurrence were calculated using multiple logistic regression models. Among workers in working environments where they always engage complaining customers had a significantly higher risk for sleep disturbance than rarely group (The OR [95% CI]; 5.46 [3.43–8.68] in male, 5.59 [3.30–9.46] in female workers). The OR (95% CI) for sleep disturbance was 1.78 (1.16–2.73) and 1.63 (1.02–2.63), for the male and female groups always suppressing their emotions at the workplace compared with those rarely group. Compared to those who both rarely engaged complaining customers and rarely suppressed their emotions at work, the OR (CI) for sleep disturbance was 9.66 (4.34–20.80) and 10.17 (4.46–22.07), for men and women always exposed to both factors. Sleep disturbance was affected by interactions of both emotional demands (engaging complaining customers and suppressing emotions at the workplace). The level of emotional demand, including engaging complaining customers and suppressing emotions at the workplace is significantly associated with sleep disturbance among Korean working population. PMID:27709845

Facing Complaining Customer and Suppressed Emotion at Worksite Related to Sleep Disturbance in Korea.

PubMed

Lim, Sung Shil; Lee, Wanhyung; Hong, Kwanyoung; Jeung, Dayee; Chang, Sei Jin; Yoon, Jin Ha

2016-11-01

This study aimed to investigate the effect of facing complaining customer and suppressed emotion at worksite on sleep disturbance among working population. We enrolled 13,066 paid workers (male = 6,839, female = 6,227, age < 65 years) in the 3rd Korean Working Condition Survey (2011). The odds ratio (OR) and 95% confidence intervals (CI) for sleep disturbance occurrence were calculated using multiple logistic regression models. Among workers in working environments where they always engage complaining customers had a significantly higher risk for sleep disturbance than rarely group (The OR [95% CI]; 5.46 [3.43-8.68] in male, 5.59 [3.30-9.46] in female workers). The OR (95% CI) for sleep disturbance was 1.78 (1.16-2.73) and 1.63 (1.02-2.63), for the male and female groups always suppressing their emotions at the workplace compared with those rarely group. Compared to those who both rarely engaged complaining customers and rarely suppressed their emotions at work, the OR (CI) for sleep disturbance was 9.66 (4.34-20.80) and 10.17 (4.46-22.07), for men and women always exposed to both factors. Sleep disturbance was affected by interactions of both emotional demands (engaging complaining customers and suppressing emotions at the workplace). The level of emotional demand, including engaging complaining customers and suppressing emotions at the workplace is significantly associated with sleep disturbance among Korean working population.

Tree species effects on pathogen-suppressive capacities of soil bacteria across two tropical dry forests in Costa Rica.

PubMed

Becklund, Kristen; Powers, Jennifer; Kinkel, Linda

2016-11-01

Antibiotic-producing bacteria in the genus Streptomyces can inhibit soil-borne plant pathogens, and have the potential to mediate the impacts of disease on plant communities. Little is known about how antibiotic production varies among soil communities in tropical forests, despite a long history of interest in the role of soil-borne pathogens in these ecosystems. Our objective was to determine how tree species and soils influence variation in antibiotic-mediated pathogen suppression among Streptomyces communities in two tropical dry forest sites (Santa Rosa and Palo Verde). We targeted tree species that co-occur in both sites and used a culture-based functional assay to quantify pathogen-suppressive capacities of Streptomyces communities beneath 50 focal trees. We also measured host-associated litter and soil element concentrations as potential mechanisms by which trees may influence soil microbes. Pathogen-suppressive capacities of Streptomyces communities varied within and among tree species, and inhibitory phenotypes were significantly related to soil and litter element concentrations. Average proportions of inhibitory Streptomyces in soils from the same tree species varied between 1.6 and 3.3-fold between sites. Densities and proportions of pathogen-suppressive bacteria were always higher in Santa Rosa than Palo Verde. Our results suggest that spatial heterogeneity in the potential for antibiotic-mediated disease suppression is shaped by tree species, site, and soil characteristics, which could have significant implications for understanding plant community composition and diversity in tropical dry forests.

Inadequate RAAS suppression is associated with excessive left ventricular mass and systo-diastolic dysfunction.

PubMed

Gregori, Mario; Tocci, Giuliano; Marra, Andrea; Pignatelli, Giulia; Santolamazza, Caterina; Befani, Alberto; Ciavarella, Giuseppino Massimo; Ferrucci, Andrea; Paneni, Francesco

2013-10-01

Inadequate suppression of renin-angiotensin-aldosterone system (RAAS) following postural maneuvers may have detrimental effects on cardiac structure and function. In this study, we aimed to appraise the clinical significance of this phenomenon by assessing its relation with inappropriate ventricular mass (ILVM), an adverse phenotype of LV remodeling and dysfunction. Both supine and upright plasma renin activity (PRA) and aldosterone concentrations (PAC) were measured in 115 young newly diagnosed hypertensive subjects. 24-h ambulatory blood pressure monitoring and echocardiographic evaluation including tissue Doppler imaging (TDI) were also performed. Patients were divided as follows: (1) normal PRA and PAC (N) (n = 63); (2) suppressible RAAS (SR) in supine position (n = 27); (3) not suppressible RAAS (NSR) (n = 25). ILVM was expressed as the observed/predicted LV mass ratio ×100 (%PLVM), while LV dysfunction (LVD) was identified by TDI-derived myocardial performance index (MPI). NSR showed a higher prevalence of ILVM than SR and N. As compared with N and SR, NSR patients had reduced indices of systolic and diastolic function. MPI of the LV as well as prevalence of LVD was also significantly higher in the NSR group. Regression models showed that lack of RAAS suppression was independently associated with ILVM and LVD. Prevalence of ILVM and LVD is higher in patients without clinostatic RAAS suppression. Our findings encourage the assessment of RAAS deregulation to better estimate individual cardiovascular risk in patients with arterial hypertension.

Differential suppression of upper airway motor activity during carbachol-induced, REM sleep-like atonia.

PubMed

Fenik, V; Davies, R O; Pack, A I; Kubin, L

1998-10-01

Microinjections of carbachol into the pontine tegmentum of decerebrate cats have been used to study the mechanisms underlying the suppression of postural and respiratory motoneuronal activity during the resulting rapid eye movement (REM) sleep-like atonia. During REM sleep, distinct respiratory muscles are differentially affected; e.g., the activity of the diaphragm shows little suppression, whereas the activity of some upper airway muscles is quite strong. To determine the pattern of the carbachol-induced changes in the activity of different groups of upper airway motoneurons, we simultaneously recorded the efferent activity of the recurrent laryngeal nerve (RL), pharyngeal branch of the vagus nerve (Phar), and genioglossal branch of the hypoglossal (XII) and phrenic (Phr) nerves in 12 decerebrate, paralyzed, vagotomized, and artificially ventilated cats. Pontine carbachol caused a stereotyped suppression of the spontaneous activity that was significantly larger in Phar expiratory (to 8.3% of control) and XII inspiratory motoneurons (to 15%) than in Phr inspiratory (to 87%), RL inspiratory (to 79%), or RL expiratory motoneurons (to 72%). The suppression in upper airway motor output was significantly greater than the depression caused by a level of hypocapnia that reduced Phr activity as much as carbachol. We conclude that pontine carbachol evokes a stereotyped pattern of suppression of upper airway motor activity. Because carbachol evokes a state having many neurophysiological characteristics similar to those of REM sleep, it is likely that pontine cholinoceptive neurons have similar effects on the activity of upper airway motoneurons during both states.

Non-water-suppressed 1 H FID-MRSI at 3T and 9.4T.

PubMed

Chang, Paul; Nassirpour, Sahar; Avdievitch, Nikolai; Henning, Anke

2018-08-01

This study investigates metabolite concentrations using metabolite-cycled 1 H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1 H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, ∼0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. We showed the first implementation of non-water-suppressed metabolite-cycled 1 H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed. Magn Reson Med 80:442-451, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Resonant conversions of QCD axions into hidden axions and suppressed isocurvature perturbations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitajima, Naoya; Takahashi, Fuminobu, E-mail: kitajima@tuhep.phys.tohoku.ac.jp, E-mail: fumi@tuhep.phys.tohoku.ac.jp

2015-01-01

We study in detail MSW-like resonant conversions of QCD axions into hidden axions, including cases where the adiabaticity condition is only marginally satisfied, and where anharmonic effects are non-negligible. When the resonant conversion is efficient, the QCD axion abundance is suppressed by the hidden and QCD axion mass ratio. We find that, when the resonant conversion is incomplete due to a weak violation of the adiabaticity, the CDM isocurvature perturbations can be significantly suppressed, while non-Gaussianity of the isocurvature perturbations generically remain unsuppressed. The isocurvature bounds on the inflation scale can therefore be relaxed by the partial resonant conversion ofmore » the QCD axions into hidden axions.« less

Multipion Bose-Einstein correlations in p p ,p -Pb, and Pb-Pb collisions at energies available at the CERN Large Hadron Collider

NASA Astrophysics Data System (ADS)

Adam, J.; Adamová, D.; Aggarwal, M. M.; Aglieri Rinella, G.; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Almaraz, J. R. M.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Antičić, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshäuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badalà, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Balasubramanian, S.; Baldisseri, A.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnaföldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Barth, K.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Batista Camejo, A.; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.; Behera, N. K.; Belikov, I.; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Belmont, R.; Belmont-Moreno, E.; Belyaev, V.; Benacek, P.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.; Bielčík, J.; Bielčíková, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Bjelogrlic, S.; Blair, J. T.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Bøggild, H.; Boldizsár, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossú, F.; Botta, E.; Bourjau, C.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Cai, X.; Caines, H.; Calero Diaz, L.; Caliva, A.; Calvo Villar, E.; Camerini, P.; Carena, F.; Carena, W.; Carnesecchi, F.; Castillo Castellanos, J.; Castro, A. J.; Casula, E. A. R.; Ceballos Sanchez, C.; Cerello, P.; Cerkala, J.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chauvin, A.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Chibante Barroso, V.; Chinellato, D. D.; Cho, S.; Chochula, P.; Choi, K.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Chung, S. U.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Conesa Balbastre, G.; Conesa Del Valle, Z.; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Corrales Morales, Y.; Cortés Maldonado, I.; Cortese, P.; Cosentino, M. R.; Costa, F.; Crochet, P.; Cruz Albino, R.; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danisch, M. C.; Danu, A.; Das, D.; Das, I.; Das, S.; Dash, A.; Dash, S.; de, S.; de Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; de Falco, A.; de Gruttola, D.; De Marco, N.; de Pasquale, S.; Deisting, A.; Deloff, A.; Dénes, E.; Deplano, C.; Dhankher, P.; di Bari, D.; di Mauro, A.; di Nezza, P.; Diaz Corchero, M. A.; Dietel, T.; Dillenseger, P.; Divià, R.; Djuvsland, Ø.; Dobrin, A.; Domenicis Gimenez, D.; Dönigus, B.; Dordic, O.; Drozhzhova, T.; Dubey, A. K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Endress, E.; Engel, H.; Epple, E.; Erazmus, B.; Erdemir, I.; Erhardt, F.; Espagnon, B.; Estienne, M.; Esumi, S.; Eum, J.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernández Téllez, A.; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Fleck, M. G.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Fusco Girard, M.; Gaardhøje, J. J.; Gagliardi, M.; Gago, A. M.; Gallio, M.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-Solis, E.; Gargiulo, C.; Gasik, P.; Gauger, E. F.; Germain, M.; Gheata, A.; Gheata, M.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-Dziadus, E.; Glässel, P.; Goméz Coral, D. M.; Gomez Ramirez, A.; Gonzalez, V.; González-Zamora, P.; Gorbunov, S.; Görlich, L.; Gotovac, S.; Grabski, V.; Grachov, O. A.; Graczykowski, L. K.; Graham, K. L.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Gronefeld, J. M.; Grosse-Oetringhaus, J. F.; Grossiord, J.-Y.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Haake, R.; Haaland, Ø.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hamon, J. C.; Harris, J. W.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Heckel, S. T.; Helstrup, H.; Herghelegiu, A.; Herrera Corral, G.; Hess, B. A.; Hetland, K. F.; Hillemanns, H.; Hippolyte, B.; Horak, D.; Hosokawa, R.; Hristov, P.; Huang, M.; Humanic, T. J.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Ilkaev, R.; Inaba, M.; Incani, E.; Ippolitov, M.; Irfan, M.; Ivanov, M.; Ivanov, V.; Izucheev, V.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jahnke, C.; Jakubowska, M. J.; Jang, H. J.; Janik, M. A.; Jayarathna, P. H. S. Y.; Jena, C.; Jena, S.; Jimenez Bustamante, R. T.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kamin, J.; Kang, J. H.; Kaplin, V.; Kar, S.; Karasu Uysal, A.; Karavichev, O.; Karavicheva, T.; Karayan, L.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keijdener, D. L. D.; Keil, M.; Mohisin Khan, M.; Khan, P.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Kileng, B.; Kim, D. W.; Kim, D. J.; Kim, D.; Kim, H.; Kim, J. S.; Kim, M.; Kim, S.; Kim, T.; Kirsch, S.; Kisel, I.; Kiselev, S.; Kisiel, A.; Kiss, G.; Klay, J. L.; Klein, C.; Klein, J.; Klein-Bösing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Kollegger, T.; Kolojvari, A.; Kondratiev, V.; Kondratyeva, N.; Kondratyuk, E.; Konevskikh, A.; Kopcik, M.; Kostarakis, P.; Kour, M.; Kouzinopoulos, C.; Kovalenko, O.; Kovalenko, V.; Kowalski, M.; Koyithatta Meethaleveedu, G.; Králik, I.; Kravčáková, A.; Kretz, M.; Krivda, M.; Krizek, F.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kučera, V.; Kuhn, C.; Kuijer, P. G.; Kumar, A.; Kumar, J.; Kumar, L.; Kumar, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kuryakin, A.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Ladron de Guevara, P.; Lagana Fernandes, C.; Lakomov, I.; Langoy, R.; Lara, C.; Lardeux, A.; Lattuca, A.; Laudi, E.; Lea, R.; Leardini, L.; Lee, G. R.; Lee, S.; Lehas, F.; Lemmon, R. C.; Lenti, V.; Leogrande, E.; León Monzón, I.; León Vargas, H.; Leoncino, M.; Lévai, P.; Li, S.; Li, X.; Lien, J.; Lietava, R.; Lindal, S.; Lindenstruth, V.; Lippmann, C.; Lisa, M. A.; Ljunggren, H. M.; Lodato, D. F.; Loenne, P. I.; Loginov, V.; Loizides, C.; Lopez, X.; López Torres, E.; Lowe, A.; Luettig, P.; Lunardon, M.; Luparello, G.; Lutz, T. H.; Maevskaya, A.; Mager, M.; Mahajan, S.; Mahmood, S. M.; Maire, A.; Majka, R. D.; Malaev, M.; Maldonado Cervantes, I.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V.; Manso, F.; Manzari, V.; Marchisone, M.; Mareš, J.; Margagliotti, G. V.; Margotti, A.; Margutti, J.; Marín, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martin Blanco, J.; Martinengo, P.; Martínez, M. I.; Martínez García, G.; Martinez Pedreira, M.; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazzoni, M. A.; McDonald, D.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Mercado Pérez, J.; Meres, M.; Miake, Y.; Mieskolainen, M. M.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Minervini, L. M.; Mischke, A.; Mishra, A. N.; Miśkowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, B.; Molñar, L.; Montaño Zetina, L.; Montes, E.; Moreira de Godoy, D. A.; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Mühlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Natal da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; Nedosekin, A.; Nellen, L.; Ng, F.; Nicassio, M.; Niculescu, M.; Niedziela, J.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S. K.; Ohlson, A.; Okatan, A.; Okubo, T.; Olah, L.; Oleniacz, J.; Oliveira da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Ozdemir, M.; Pachmayer, Y.; Pagano, P.; Paić, G.; Pal, S. K.; Pan, J.; Pandey, A. K.; Papikyan, V.; Pappalardo, G. S.; Pareek, P.; Park, W. J.; Parmar, S.; Passfeld, A.; Paticchio, V.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Pereira da Costa, H.; Peresunko, D.; Pérez Lara, C. E.; Perez Lezama, E.; Peskov, V.; Pestov, Y.; Petráček, V.; Petrov, V.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Piyarathna, D. B.; Płoskoń, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Porteboeuf-Houssais, S.; Porter, J.; Pospisil, J.; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I.; Puccio, M.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Räsänen, S. S.; Rascanu, B. T.; Rathee, D.; Read, K. F.; Redlich, K.; Reed, R. J.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reolon, A. R.; Reshetin, A.; Revol, J.-P.; Reygers, K.; Riabov, V.; Ricci, R. A.; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rocco, E.; Rodríguez Cahuantzi, M.; Rodriguez Manso, A.; Røed, K.; Rogochaya, E.; Rohr, D.; Röhrich, D.; Romita, R.; Ronchetti, F.; Ronflette, L.; Rosnet, P.; Rossi, A.; Roukoutakis, F.; Roy, A.; Roy, C.; Roy, P.; Rubio Montero, A. J.; Rui, R.; Russo, R.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Sadovsky, S.; Šafařík, K.; Sahlmuller, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Saleh, M. A.; Salzwedel, J.; Sambyal, S.; Samsonov, V.; Šándor, L.; Sandoval, A.; Sano, M.; Sarkar, D.; Sarma, P.; Scapparone, E.; Scarlassara, F.; Schiaua, C.; Schicker, R.; Schmidt, C.; Schmidt, H. R.; Schuchmann, S.; Schukraft, J.; Schulc, M.; Schuster, T.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Scott, R.; Šefčík, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I.; Senosi, K.; Senyukov, S.; Serradilla, E.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shadura, O.; Shahoyan, R.; Shahzad, M. I.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, M.; Sharma, N.; Shigaki, K.; Shtejer, K.; Sibiriak, Y.; Siddhanta, S.; Sielewicz, K. M.; Siemiarczuk, T.; Silvermyr, D.; Silvestre, C.; Simatovic, G.; Simonetti, G.; Singaraju, R.; Singh, R.; Singha, S.; Singhal, V.; Sinha, B. C.; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. W.; Søgaard, C.; Song, J.; Song, M.; Song, Z.; Soramel, F.; Sorensen, S.; de Souza, R. D.; Sozzi, F.; Spacek, M.; Spiriti, E.; Sputowska, I.; Spyropoulou-Stassinaki, M.; Stachel, J.; Stan, I.; Stankus, P.; Stefanek, G.; Stenlund, E.; Steyn, G.; Stiller, J. H.; Stocco, D.; Strmen, P.; Suaide, A. A. P.; Sugitate, T.; Suire, C.; Suleymanov, M.; Suljic, M.; Sultanov, R.; Šumbera, M.; Szabo, A.; Szanto de Toledo, A.; Szarka, I.; Szczepankiewicz, A.; Szymanski, M.; Tabassam, U.; Takahashi, J.; Tambave, G. J.; Tanaka, N.; Tangaro, M. A.; Tarhini, M.; Tariq, M.; Tarzila, M. G.; Tauro, A.; Tejeda Muñoz, G.; Telesca, A.; Terasaki, K.; Terrevoli, C.; Teyssier, B.; Thäder, J.; Thomas, D.; Tieulent, R.; Timmins, A. R.; Toia, A.; Trogolo, S.; Trombetta, G.; Trubnikov, V.; Trzaska, W. H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vajzer, M.; Vala, M.; Valencia Palomo, L.; Vallero, S.; van der Maarel, J.; van Hoorne, J. W.; van Leeuwen, M.; Vanat, T.; Vande Vyvre, P.; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vauthier, A.; Vechernin, V.; Veen, A. M.; Veldhoen, M.; Velure, A.; Venaruzzo, M.; Vercellin, E.; Vergara Limón, S.; Vernet, R.; Verweij, M.; Vickovic, L.; Viesti, G.; Viinikainen, J.; Vilakazi, Z.; Villalobos Baillie, O.; Villatoro Tello, A.; Vinogradov, A.; Vinogradov, L.; Vinogradov, Y.; Virgili, T.; Vislavicius, V.; Viyogi, Y. P.; Vodopyanov, A.; Völkl, M. A.; Voloshin, K.; Voloshin, S. A.; Volpe, G.; von Haller, B.; Vorobyev, I.; Vranic, D.; Vrláková, J.; Vulpescu, B.; Wagner, B.; Wagner, J.; Wang, H.; Wang, M.; Watanabe, D.; Watanabe, Y.; Weber, M.; Weber, S. G.; Weiser, D. F.; Wessels, J. P.; Westerhoff, U.; Whitehead, A. M.; Wiechula, J.; Wikne, J.; Wilk, G.; Wilkinson, J.; Williams, M. C. S.; Windelband, B.; Winn, M.; Yang, H.; Yang, P.; Yano, S.; Yasin, Z.; Yin, Z.; Yokoyama, H.; Yoo, I.-K.; Yoon, J. H.; Yurchenko, V.; Yushmanov, I.; Zaborowska, A.; Zaccolo, V.; Zaman, A.; Zampolli, C.; Zanoli, H. J. C.; Zaporozhets, S.; Zardoshti, N.; Zarochentsev, A.; Závada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zgura, I. S.; Zhalov, M.; Zhang, H.; Zhang, X.; Zhang, Y.; Zhang, C.; Zhang, Z.; Zhao, C.; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zichichi, A.; Zimmermann, A.; Zimmermann, M. B.; Zinovjev, G.; Zyzak, M.; Alice Collaboration

2016-05-01

Three- and four-pion Bose-Einstein correlations are presented in p p ,p -Pb, and Pb-Pb collisions at the LHC. We compare our measured four-pion correlations to the expectation derived from two- and three-pion measurements. Such a comparison provides a method to search for coherent pion emission. We also present mixed-charge correlations in order to demonstrate the effectiveness of several analysis procedures such as Coulomb corrections. Same-charge four-pion correlations in p p and p -Pb appear consistent with the expectations from three-pion measurements. However, the presence of non-negligible background correlations in both systems prevent a conclusive statement. In Pb-Pb collisions, we observe a significant suppression of three- and four-pion Bose-Einstein correlations compared to expectations from two-pion measurements. There appears to be no centrality dependence of the suppression within the 0%-50% centrality interval. The origin of the suppression is not clear. However, by postulating either coherent pion emission or large multibody Coulomb effects, the suppression may be explained.

Multipion Bose-Einstein correlations in p p , p -Pb, and Pb-Pb collisions at energies available at the CERN Large Hadron Collider

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam, J.; Adamová, D.; Aggarwal, M. M.

Three- and four-pion Bose-Einstein correlations are presented in pp,p-Pb, and Pb-Pb collisions at the LHC. We compare our measured four-pion correlations to the expectation derived from two- and three-pion measurements. Such a comparison provides a method to search for coherent pion emission. We also present mixed-charge correlations in order to demonstrate the effectiveness of several analysis procedures such as Coulomb corrections. Same-charge four-pion correlations in pp and p-Pb appear consistent with the expectations from three-pion measurements. However, the presence of non-negligible background correlations in both systems prevent a conclusive statement. In Pb-Pb collisions, we observe a significant suppression of three-more » and four-pion Bose-Einstein correlations compared to expectations from two-pion measurements. There appears to be no centrality dependence of the suppression within the 0%-50% centrality interval. The origin of the suppression is not clear. However, by postulating either coherent pion emission or large multibody Coulomb effects, the suppression may be explained.« less

Multipion Bose-Einstein correlations in p p , p -Pb, and Pb-Pb collisions at energies available at the CERN Large Hadron Collider

DOE PAGES

Adam, J.; Adamová, D.; Aggarwal, M. M.; ...

2016-05-18

Three- and four-pion Bose-Einstein correlations are presented in pp,p-Pb, and Pb-Pb collisions at the LHC. We compare our measured four-pion correlations to the expectation derived from two- and three-pion measurements. Such a comparison provides a method to search for coherent pion emission. We also present mixed-charge correlations in order to demonstrate the effectiveness of several analysis procedures such as Coulomb corrections. Same-charge four-pion correlations in pp and p-Pb appear consistent with the expectations from three-pion measurements. However, the presence of non-negligible background correlations in both systems prevent a conclusive statement. In Pb-Pb collisions, we observe a significant suppression of three-more » and four-pion Bose-Einstein correlations compared to expectations from two-pion measurements. There appears to be no centrality dependence of the suppression within the 0%-50% centrality interval. The origin of the suppression is not clear. However, by postulating either coherent pion emission or large multibody Coulomb effects, the suppression may be explained.« less

Hydrazinonicotinamide prolongs quantum dot circulation and reduces reticuloendothelial system clearance by suppressing opsonization and phagocyte engulfment

NASA Astrophysics Data System (ADS)

Jung, Kyung-Ho; Park, Jin Won; Paik, Jin-Young; Lee, Eun Jeong; Choe, Yearn Seong; Lee, Kyung-Han

2012-12-01

In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)—a bifunctional crosslinker widely used to 99mTc radiolabel protein and nanoparticles for imaging studies—on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding

PubMed Central

Siemian, Justin N.; Li, Jiuzhou; Zhang, Yanan; Li, Jun-Xu

2015-01-01

Rationale Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for justification of alternative pain therapies. Objective This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Methods Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic effects of drugs in complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. Results 2-BFI (3.2–17.8 mg/kg, i.p.), phenyzoline (17.8–100 mg/kg, i.p.), and acetaminophen (56–178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Conclusions Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen. PMID:26613734

Extracellular NAD+ Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny.

PubMed

Pustovit, K B; Ivanova, A D; Kuz'min, V S

2018-05-01

The effects of sympathetic cotransmitter NAD+ (10 μM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 μM) altered the configuration and significantly lengthened the action potentials. NAD + against the background of norepinephrine stimulation significantly decreased the duration of action potentials, in particular, at 25% repolarization. The effect of purine compounds NAD + , ATP, and adenosine on bioelectrical activity of the heart of newborn rats was studied under basal conditions (without norepinephrine stimulation). The effect of NAD + against the background of adrenergic stimulation was more pronounced than under basal conditions and was probably determined by suppression of I CaL , which can be the main mechanism of NAD + action on rat heart.

From Flexible and Stretchable Meta-Atom to Metamaterial: A Wearable Microwave Meta-Skin with Tunable Frequency Selective and Cloaking Effects

PubMed Central

Yang, Siming; Liu, Peng; Yang, Mingda; Wang, Qiugu; Song, Jiming; Dong, Liang

2016-01-01

This paper reports a flexible and stretchable metamaterial-based “skin” or meta-skin with tunable frequency selective and cloaking effects in microwave frequency regime. The meta-skin is composed of an array of liquid metallic split ring resonators (SRRs) embedded in a stretchable elastomer. When stretched, the meta-skin performs as a tunable frequency selective surface with a wide resonance frequency tuning range. When wrapped around a curved dielectric material, the meta-skin functions as a flexible “cloaking” surface to significantly suppress scattering from the surface of the dielectric material along different directions. We studied frequency responses of multilayer meta-skins to stretching in a planar direction and to changing the spacing between neighboring layers in vertical direction. We also investigated scattering suppression effect of the meta-skin coated on a finite-length dielectric rod in free space. This meta-skin technology will benefit many electromagnetic applications, such as frequency tuning, shielding, and scattering suppression. PMID:26902969

Suppression of murine preadipocyte differentiation and reduction of visceral fat accumulation by a Petasites japonicus ethanol extract in mice fed a high-fat diet.

PubMed

Watanabe, Takayuki; Hata, Keishi; Hiwatashi, Kazuyuki; Hori, Kazuyuki; Suzuki, Nao; Itoh, Hideaki

2010-01-01

We investigated in this study the anti-obesity effect of an extract of Petasites japonicus (a culinary vegetable from Eastern Asia) on a murine adipocyte cell line (3T3-L1) and on diet-induced obesity-prone mice. An ethanol extract of P. japonicus. (PJET) suppressed 3T3-L1 preadipocyte differentiation; however, a hot water extract of P. japonicus (PJHW) exhibited no effect on cell differentiation. PJET significantly attenuated three adipogenetic transcription factors, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein and sterol regulatory element-binding protein 1C, at the mRNA level and suppressed the gene expression of fatty acid synthetase. An experiment with diet-induced obesity-prone C57BL/6J mice showed that PJET lowered the body weight gain and visceral fat tissue accumulation, and ameliorated the plasma cholesterol concentration. These findings suggest that P. japonicus might be an effective food against obesity.

Do Not Pay Any Attention to the Umpires: Thought Suppression and Task-Relevant Focusing Strategies.

PubMed

Dugdale, Jeremy R; Eklund, Robert C

2002-09-01

Two studies grounded in ironic-cognitive-processing theory were conducted to determine (a) whether ironic errors may be associated with efforts to exert mental control that typically occur in sport settings and (b) whether these potential ironic effects could be negated through the use of a task-relevant cue word to refocus one's thoughts during suppression. Participants were asked to watch a videotape of a series of clips of Australian Rules Football players, coaches, and umpires. Study 1 revealed that participants were more aware of umpires when instructed not to pay attention to them. Contrary to expectations, however, ironic effects were not significantly magnified by the combination of high cognitive load and the instruction not to pay attention to the umpires. Results from Study 2 indicated that potential ironic effects could be negated when individuals were given a task-relevant cue word to focus on when suppressing unwanted or negative thoughts. Overall, support for ironic processing theory was found in Studies 1 and 2 in this investigation.

Pharmacological properties of traditional medicine (XXXII): protective effects of hangeshashinto and the combinations of its major constituents on gastric lesions in rats.

PubMed

Kawashima, Keiko; Fujimura, Yu; Makino, Toshiaki; Kano, Yoshihiro

2006-09-01

The protective effect of Hangeshashinto (HST) and its major constituents, baicalin (BA), berberine (BE), saponin fraction of ginseng (GS) and glycyrrhizin (GL) on rat gastric lesion induced by ethanol was examined to clarify its active ingredients and action mechanism. Oral treatment with HST at the doses of 125 and 250 mg/kg suppressed ethanol-induced gastric lesions. The mixture of BA, BE, GL and GS (4M), each of BE, GL and GS at the dosage corresponded to HST (125 mg/kg) also suppressed the ethanol-induced gastric lesion in rats, but BA did not. Treatment of ethanol augmented the activity of myeloperoxidase (MPO) in the stomach, which was significantly suppressed by the administration of HST, BE, GL and GS. These results suggest that the protective effect of HST on ethanol-induced gastric lesion was depended on BE, GL and GS, by, in part, the reduction of MPO activity in stomach.

Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.

PubMed

Sun, Peipei; Zhou, Xin; He, Yingzhi; Liu, Huimin; Wang, Yuxin; Chen, Yiran; Li, Meifang; He, Yanjie; Li, Guowei; Li, Yuhua

2018-03-18

Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated with poor prognosis in solid tumors and leukemia. However, EPS8 expression and the relationship between EPS8 and HDACi on BL remains obscure. Here, we hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by downregulating EPS8. We demonstrated that TSA reduced cell viability, induced apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway activity, particularly when combined with TSA. Conversely, overexpression of EPS8 rescued this phenomenon. Then we showed that the combination of TSA and Epirubicin had a more significant effect when compared with TSA or Epirubicin alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by suppressing Phospho-Erk1/2 pathway through downregulating EPS8. Copyright © 2018 Elsevier Inc. All rights reserved.

Expressive suppression and neural responsiveness to nonverbal affective cues.

PubMed

Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

2015-10-01

Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors' poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Expressive suppression and neural responsiveness to nonverbal affective cues

PubMed Central

Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl

2016-01-01

Optimal social functioning occasionally requires concealment of one’s emotions in order to meet one’s immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors’ restricted affective displays reportedly inhibit their interlocutors’ emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors’ restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target’s affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors’ poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID:26365712

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

PubMed Central

Dideriksen, Jakob L.; Laine, Christopher M.; Dosen, Strahinja; Muceli, Silvia; Rocon, Eduardo; Pons, José L.; Benito-Leon, Julian; Farina, Dario

2017-01-01

Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient. PMID:28420958

AgRP Neurons Can Increase Food Intake during Conditions of Appetite Suppression and Inhibit Anorexigenic Parabrachial Neurons.

PubMed

Essner, Rachel A; Smith, Alison G; Jamnik, Adam A; Ryba, Anna R; Trutner, Zoe D; Carter, Matthew E

2017-09-06

To maintain energy homeostasis, orexigenic (appetite-inducing) and anorexigenic (appetite suppressing) brain systems functionally interact to regulate food intake. Within the hypothalamus, neurons that express agouti-related protein (AgRP) sense orexigenic factors and orchestrate an increase in food-seeking behavior. In contrast, calcitonin gene-related peptide (CGRP)-expressing neurons in the parabrachial nucleus (PBN) suppress feeding. PBN CGRP neurons become active in response to anorexigenic hormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (CCK), secreted by the small intestine. Additionally, exogenous compounds, such as lithium chloride (LiCl), a salt that creates gastric discomfort, and lipopolysaccharide (LPS), a bacterial cell wall component that induces inflammation, exert appetite-suppressing effects and activate PBN CGRP neurons. The effects of increasing the homeostatic drive to eat on feeding behavior during appetite suppressing conditions are unknown. Here, we show in mice that food deprivation or optogenetic activation of AgRP neurons induces feeding to overcome the appetite suppressing effects of amylin, CCK, and LiCl, but not LPS. AgRP neuron photostimulation can also increase feeding during chemogenetic-mediated stimulation of PBN CGRP neurons. AgRP neuron stimulation reduces Fos expression in PBN CGRP neurons across all conditions. Finally, stimulation of projections from AgRP neurons to the PBN increases feeding following administration of amylin, CCK, and LiCl, but not LPS. These results demonstrate that AgRP neurons are sufficient to increase feeding during noninflammatory-based appetite suppression and to decrease activity in anorexigenic PBN CGRP neurons, thereby increasing food intake during homeostatic need. SIGNIFICANCE STATEMENT The motivation to eat depends on the relative balance of activity in distinct brain regions that induce or suppress appetite. An abnormal amount of activity in neurons that induce appetite can cause obesity, whereas an abnormal amount of activity in neurons that suppress appetite can cause malnutrition and a severe reduction in body weight. The purpose of this study was to determine whether a population of neurons known to induce appetite ("AgRP neurons") could induce food intake to overcome appetite-suppression following administration of various appetite-suppressing compounds. We found that stimulating AgRP neurons could overcome various forms of appetite suppression and decrease neural activity in a separate population of appetite-suppressing neurons, providing new insights into how the brain regulates food intake. Copyright © 2017 the authors 0270-6474/17/378678-10$15.00/0.

Sailuotong Prevents Hydrogen Peroxide (H2O2)-Induced Injury in EA.hy926 Cells

PubMed Central

Seto, Sai Wang; Chang, Dennis; Ko, Wai Man; Zhou, Xian; Kiat, Hosen; Bensoussan, Alan; Lee, Simon M. Y.; Hoi, Maggie P. M.; Steiner, Genevieve Z.; Liu, Jianxun

2017-01-01

Sailuotong (SLT) is a standardised three-herb formulation consisting of Panax ginseng, Ginkgo biloba, and Crocus sativus designed for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H2O2)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1–50 µg/mL) significantly suppressed the H2O2-induced cell death and abolished the H2O2-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H2O2 (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1–50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H2O2-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H2O2-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed. PMID:28067784

Coffee Ingestion Suppresses Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

PubMed

Kobayashi, Misato; Kurata, Takao; Hamana, Yoshiki; Hiramitsu, Masanori; Inoue, Takashi; Murai, Atsushi; Horio, Fumihiko

2017-01-01

Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic β-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic β-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents.

Chromatic induction from surrounding stimuli under perceptual suppression.

PubMed

Horiuchi, Koji; Kuriki, Ichiro; Tokunaga, Rumi; Matsumiya, Kazumichi; Shioiri, Satoshi

2014-11-01

The appearance of colors can be affected by their spatiotemporal context. The shift in color appearance according to the surrounding colors is called color induction or chromatic induction; in particular, the shift in opponent color of the surround is called chromatic contrast. To investigate whether chromatic induction occurs even when the chromatic surround is imperceptible, we measured chromatic induction during interocular suppression. A multicolor or uniform color field was presented as the surround stimulus, and a colored continuous flash suppression (CFS) stimulus was presented to the dominant eye of each subject. The subjects were asked to report the appearance of the test field only when the stationary surround stimulus is invisible by interocular suppression with CFS. The resulting shifts in color appearance due to chromatic induction were significant even under the conditions of interocular suppression for all surround stimuli. The magnitude of chromatic induction differed with the surround conditions, and this difference was preserved regardless of the viewing conditions. The chromatic induction effect was reduced by CFS, in proportion to the magnitude of chromatic induction under natural (i.e., no-CFS) viewing conditions. According to an analysis with linear model fitting, we revealed the presence of at least two kinds of subprocesses for chromatic induction that reside at higher and lower levels than the site of interocular suppression. One mechanism yields different degrees of chromatic induction based on the complexity of the surround, which is unaffected by interocular suppression, while the other mechanism changes its output with interocular suppression acting as a gain control. Our results imply that the total chromatic induction effect is achieved via a linear summation of outputs from mechanisms that reside at different levels of visual processing.

Suppression versus enhancement of heavy quarkonia in p A collisions

NASA Astrophysics Data System (ADS)

Kopeliovich, B. Z.; Schmidt, Iván; Siddikov, M.

2017-06-01

We describe the production of heavy quarkonia in p A collisions within the dipole approach by assuming the dominance of the perturbative color-singlet mechanism (CSM) in the pT-integrated cross section. Although accounting for a nonzero heavy Q -Q ¯ separation is a higher-twist correction that is usually neglected, we found it to be the dominant source of nuclear effects, significantly exceeding the effects of leading-twist gluon shadowing and energy loss. Moreover, this contribution turns out to be the most reliably predicted, relying on the precise measurements of the dipole cross section at the Hadron-Electron Ring Accelerator (HERA) at DESY. The nuclear suppression of quarkonia has been anticipated to become stronger with energy because the dipole cross section steeply rises. However, the measured nuclear effects remain essentially unchanged within the energy range from that of the BNL Relativistic Heavy Ion Collider (RHIC) to that of the Large Hadron Collider (LHC). A production mechanism is proposed that enhances the charmonium yield. Nuclear effects for the production of J /ψ , ψ (2 S ) , Υ (1 S ) , and Υ (2 S ) are calculated and are in agreement with data from RHIC and LHC. The dipole description offers a unique explanation for the observed significant nuclear suppression of the ψ (2 S ) -to-J /ψ ratio, which is related to the nontrivial features of the ψ (2 S ) wave function.

Extracorporeal low-energy shock-wave therapy exerts anti-inflammatory effects in a rat model of acute myocardial infarction.

PubMed

Abe, Yuzuru; Ito, Kenta; Hao, Kiyotaka; Shindo, Tomohiko; Ogata, Tsuyoshi; Kagaya, Yuta; Kurosawa, Ryo; Nishimiya, Kensuke; Satoh, Kimio; Miyata, Satoshi; Kawakami, Kazuyoshi; Shimokawa, Hiroaki

2014-01-01

It has been previously demonstrated that extracorporeal low-energy shock-wave (SW) therapy ameliorates left ventricular (LV) remodeling through enhanced angiogenesis after acute myocardial infarction (AMI) in pigs in vivo. However, it remains to be examined whether SW therapy also exerts anti-inflammatory effects on AMI. METHODS AND RESULTS: AMI was created by ligating the proximal left anterior descending coronary artery in rats. They were randomly assigned to 2 groups: with (SW group) or without (control group) SW therapy (0.1 mJ/mm(2), 200 shots, 1 Hz to the whole heart at 1, 3 and 5 days after AMI). Four weeks after AMI, SW therapy significantly ameliorated LV remodeling and fibrosis. Histological examinations showed that SW therapy significantly suppressed the infiltration of neutrophils and macrophages at days 3 and 6, in addition to enhanced capillary density in the border area. Molecular examinations demonstrated that SW therapy enhanced the expression of endothelial nitric oxide synthase and suppressed the infiltration of transforming growth factor-β1-positive cells early after AMI. SW therapy also upregulated anti-inflammatory cytokines and downregulated pro-inflammatory cytokines in general. These results suggest that low-energy SW therapy suppressed post-MI LV remodeling in rats in vivo, which was associated with anti-inflammatory effects in addition to its angiogenic effects, and demonstrated a novel aspect of the therapy for AMI.

Bidirectional Influences of Anxiety and Depression in Young Children

PubMed Central

Hopkins, Joyce; Gouze, Karen R.; Bryant, Fred B.

2014-01-01

Anxiety and depression tend to co-occur in children. Studies indicate that higher levels of anxiety are associated with subsequent higher levels of depression, while depression may inhibit subsequent anxiety. It is important to increase our understanding of the temporal sequencing of these disorders and, particularly, to determine if suppression effects account for the inhibitory association. In addition, further information about these relationships in young children is needed. Participants were a diverse (20.4 % Hispanic, 16.7 % African American; 49.1 % boys) community sample of 796 children with data available at ages 4, 5, and 6–7 years. Anxiety and depression symptoms were assessed using the Child Symptom Inventory and symptom count measures from the Diagnostic Interview Schedule for Children-Parent Scale-Young Child version. The results indicated: (a) anxiety and depression were relatively stable over time; (b) anxiety at age 4 and 5 was a significant positive predictor of subsequent depression; (c) while an inhibitory effect of depression on subsequent anxiety was found, that inhibitory effect was due to negative suppression, and higher levels of depression were actually associated with subsequent anxiety; (e) consistent with a significant suppression effect, when depression was included as a predictor, the association between anxiety at ages 4 and 5 and anxiety one year later increases in magnitude. Both anxiety and depression are associated with higher levels of one another in the subsequent year. Implications for prevention are discussed. PMID:24934567

Effect of surface roughness on droplet splashing

NASA Astrophysics Data System (ADS)

Hao, Jiguang

2017-12-01

It is well known that rough surfaces trigger prompt splashing and suppress corona splashing on droplet impact. Upon water droplet impact, we experimentally found that a slightly rough substrate triggers corona splashing which is suppressed to prompt splashing by both further increase and further decrease of surface roughness. The nonmonotonic effect of surface roughness on corona splashing weakens with decreasing droplet surface tension. The threshold velocities for prompt splashing and corona splashing are quantified under different conditions including surface roughness, droplet diameter, and droplet surface tension. It is determined that slight roughness significantly enhances both prompt splashing and corona splashing of a water droplet, whereas it weakly affects low-surface-tension droplet splashing. Consistent with previous studies, high roughness triggers prompt splashing and suppresses corona splashing. Further experiments on droplet spreading propose that the mechanism of slight roughness enhancing water droplet splashing is due to the decrease of the wetted area with increasing surface roughness.

Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.

PubMed

Mizuno, Tetsuya; Kuno, Reiko; Nitta, Atsumi; Nabeshima, Toshitaka; Zhang, Guiqin; Kawanokuchi, Jun; Wang, Jinyan; Jin, Shijie; Takeuchi, Hideyuki; Suzumura, Akio

2005-12-20

We examined the neuroprotective role of nicergoline in neuron-microglia or neuron-astrocytes co-cultures. Nicergoline, an ergoline derivative, significantly suppressed the neuronal cell death induced by co-culture with activated microglia or astrocytes stimulated with lipopolysaccharide (LPS) and interferon (IFN)-gamma. To elucidate the mechanism by which nicergoline exerts a neuroprotective effect, we examined the production of inflammatory mediators and neurotrophic factors in activated microglia and astrocytes following nicergoline treatment. In microglia stimulated with LPS and IFN-gamma, nicergoline suppressed the production of superoxide anions, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in a dose-dependent manner. In astrocytes, nicergoline also suppressed the production of proinflammatory cytokines and enhanced brain-derived neurotrophic factor (BDNF). Thus, nicergoline-mediated neuroprotection resulted primarily from the inhibition of inflammatory mediators and the upregulation of neurotrophic factors by glial cells.

Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.

PubMed

Yano, Michiko; Minegishi, Yoshihiko; Sugita, Satoshi; Ota, Noriyasu

2017-10-15

Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Allelopathic potential of leaf and seed of Mucuna bracteata DC. ex Kurz on Eleusine indica (L.) gaertn

NASA Astrophysics Data System (ADS)

Halimshah, Syamimi; Ismail B., S.; Ahmad, Wan Juliana Wan

2015-09-01

A study was conducted to determine the allelopathic potential of leaf and seed of Mucuna bracteata on the growth of E. indica through aqueous extract and debris (incorporated into the soil) experiment. Three concentrations of leaf and seed aqueous extract (16.7, 33.3 and 66.7 g/L) and debris (2.5, 5.0 and 10.0 g/500 g soil) of M. bracteata were used in the experiment. Complete randomized design (CRD) with three replications was applied in this experiment which was conducted twice. Results demonstrated that the leaf and seed extracts of M. bracteata exhibited higher suppression effect on the growth and germination of E. indica as the concentration increased. The leaf and seed extracts significantly reduced all measured parameters at all concentrations except for the shoot length and germination of E. indica by seed extract at 16.7 g/L which recorded insignificant reduction by 40.5% and 4% respectively. The leaf and seed debris significantly reduced the root length of E. indica at all treatments. Seed debris also showed significant reduction on the germination at all treatments and other seedling growth parameters (shoot length, fresh weight and dry weight) at 2.5 and 10.0 g/500 g soil. Meanwhile, the leaf debris demonstrated stimulation effect on the seedling growth parameters. As a whole, the leaf showed higher suppression effect in aqueous extract experiment while the seed recorded higher suppression effect in the debris experiment. Further studies need to be conducted to investigate the type of inhibition mechanism involved in both experiments.

Quantitative differences in the immunomodulatory effects of Rebif and Avonex in IFN-β 1a treated multiple sclerosis patients

PubMed Central

Christophi, George P.; Christophi, Jennifer A.; Gruber, Ross C.; Mihai, Cornelia; Mejico, Luis J.; Massa, Paul T.; Jubelt, Burk

2012-01-01

Interferon-β (IFN-β) is a current effective treatment for multiple sclerosis (MS) and exerts its therapeutic effects by down-modulating the systemic immune response and cytokine signaling. In clinical practice there are several formulations of interferon including a low dose of IFN-β 1a formulation of 30μg IM once weekly (Avonex) and a high dose formulation of 44 μg SC three times weekly (Rebif). Recent studies suggest that Rebif is more efficacious compared to Avonex in preventing relapses and decreasing MRI activity in relapsing remitting MS (RRMS) patients. This study examines whether there are quantitative gene expression changes in interferon-treated RRMS patients that can explain the difference in efficacy and side effects between Rebif and Avonex. Herein, RRMS patients were treated for three months with IFN-β 1a and the levels of plasma cytokines and gene expression in peripheral blood mononuclear cells were examined. Thirty-two normal subjects were compared to thirty-two RRMS patients, of which ten were treated with Rebif and ten with Avonex. Rebif and Avonex both significantly and equally suppressed plasma TNF-α and IL-6 levels. Rebif suppressed IL-13 significantly more than Avonex. Rebif also significantly suppressed the levels of the chemokines CCL17 and RANTES, the protease ADAM8, and COX-2 at a higher degree compared to Avonex. The STAT1-inducible genes IP-10 and caspase 1 were significantly increased with Rebif compared to Avonex. In conclusion, the higher dosed, more frequently administered IFN-β 1a Rebif when compared to IFN β-1a Avonex has more potent immunomodulatory effects. These quantitative results might relate to efficacy and side-effect profile of the two IFN-β 1a formulations and provide prospective practical clinical tools to monitor treatment and adjust dosage. PMID:21658727

Hydraulic architecture and photosynthetic capacity as constraints on release from suppression in Douglas-fir and western hemlock.

PubMed

Renninger, Heidi J; Meinzer, Frederick C; Gartner, Barbara L

2007-01-01

We compared hydraulic architecture, photosynthesis and growth in Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), a shade-intolerant species, and western hemlock (Tsuga heterophylla (Raf.) Sarg.), a shade-tolerant species, to study the temporal pattern of release from suppressive shade. In particular, we sought to determine whether hydraulic architecture or photosynthetic capacity is most important in constraining release. The study was conducted at two sites with mixed stands of 10- to 20-year-old Douglas-fir and western hemlock. At one site, the stand had been thinned allowing release of the understory trees, whereas at the other site, the stand remained unthinned. Douglas-fir had lower height growth (from 1998-2003) and lower relative height growth (height growth from 1998 to 2003/height in 1998) than western hemlock. However, relative height growth of released versus suppressed trees was higher in Douglas-fir (130%) than in western hemlock (65%), indicating that, although absolute height growth was less, Douglas-fir did release from suppression. Release seemed to be constrained initially by a limited photosynthetic capacity in both species. Five years after release, Douglas-fir trees had 14 times the leaf area and 1.5 times the leaf nitrogen concentration (N (area)) of suppressed trees. Needles of released western hemlock trees had about twice the maximum assimilation rate (A (max)) at ambient [CO(2)] as needles of suppressed trees and exhibited no photoinhibition at the highest irradiances. After release, trees increased in leaf area, leaf N concentration and overall photosynthetic capacity. Subsequently, hydraulic architecture appeared to constrain release in Douglas-fir and, to a lesser extent, in western hemlock. Released trees had significantly less negative foliar delta(13)C values than suppressed trees and showed a positive relationship between leaf area:sapwood area ratio (A (L)/A (S)) and delta(13)C, suggesting that trees with more leaf area for a given sapwood area experienced a stomatal limitation on carbon gain. Nonetheless, these changes had no significant effects on leaf specific conductivities of suppressed versus released trees of either species, but leaf specific root conductance was significantly lower in released Douglas-fir.

Inhibition of buckwheat starch digestion by the formation of starch/bile salt complexes: possibility of its occurrence in the intestine.

PubMed

Takahama, Umeo; Hirota, Sachiko

2011-06-08

During the digestion of starch in foods, starch is mixed with bile in the duodenum. Because fatty acids and some kinds of polyphenols could bind to starch, it was postulated that bile salts might also bind to starch. The purpose of this paper is to study the effects of bile and bile salts on starch/iodine complex formation and pancreatin-induced starch digestion. Bile suppressed starch/iodine complex formation and inhibited pancreatin-induced starch digestion slightly in control buckwheat starch, but did so significantly in buckwheat starch from which fatty acids and polyphenols had been extracted. Such significant suppression and inhibition by bile were also observed in a reagent soluble starch. The effects of cholate and taurocholate on the starch/iodine complex formation and the pancreatin-induced starch digestion were essentially the same as those of bile. Bile, cholate, and taurocholate suppressed amylose/iodine complex formation more significantly than amylopectin/iodine complex formation and inhibited pancreatin-induced amylose digestion more effectively than the digestion of amylopectin. It is concluded from the results that bile salts could bind to starch, especially amylose, the helical structures of which were not occupied by other molecules such as fatty acids and polyphenols, and that the binding resulted in the inhibition of starch digestion by pancreatin. The conclusion suggests that the function of bile salts can be discussed from the point of not only lipid digestion but also starch digestion.

Apatinib, a novel tyrosine kinase inhibitor, suppresses tumor growth in cervical cancer and synergizes with Paclitaxel.

PubMed

Qiu, Haifeng; Li, Jing; Liu, Qiuli; Tang, Mei; Wang, Yuan

2018-06-09

Apatinib is a novel tyrosine kinase inhibitor that targets VEGFR2 signal and exhibits potent anti-tumor effects in human cancers. In this study, we aim to investigate the efficacy of Apatinib in cervical cancer. The protein expression of VEGFR2 and its relationships with clinical parameters were investigated in a panel of cervical cancer patients. In vitro, a series of experiments were performed to detect the effects of Apatinib on the proliferation, apoptosis and cell cycle in cervical cancer cells. Both the immortalized cell lines and primary cultured tissues were used to investigate the synergy between Apatinib and chemotherapeutic drugs. The in vivo effects of Apatinib were validated in a nude mouse model. Compared to that in normal cervix, VEGFR2 protein was significantly upregulated in cervical cancer tissues (P<0.001); this was positively correlated with advanced tumor stage, lymph node metastasis, and a poor prognosis. In vitro, Apatinib markedly induced apoptosis and G1-phase arrest, suppressed cell growth, and decreased colony formation ability. We also found that primary cancer tissues with higher level of VEGFR2 were much more sensitive to Apatinib. Further, we proved that Apatinib significantly increased the sensitivity to Paclitaxel in cervical cancer cells and the mouse model. Collectively, we firstly report the anti-tumor efficacy of Apatinib in cervical cancer. Moreover, Apatinib synergized with Paclitaxel to achieve more significant suppression on tumor growth, proposing that Apatinib might be a potent drug for cervical cancer.

miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Hongling; Fang, Jin; Zhang, Jichen

2014-07-18

Highlights: • miR-182 and CHL1 expression patterns are negatively correlated. • CHL1 is a direct target of miR-182 in PTC cells. • miR-182 suppression inhibits PTC cell growth and invasion. • CHL1 is involved in miR-182-mediated cell behavior. - Abstract: In this study, we investigated the role and underlying mechanism of action of miR-182 in papillary thyroid carcinoma (PTC). Bioinformatics analysis revealed close homolog of LI (CHL1) as a potential target of miR-182. Upregulation of miR-182 was significantly correlated with CHL1 downregulation in human PTC tissues and cell lines. miR-182 suppressed the expression of CHL1 mRNA through direct targeting ofmore » the 3′-untranslated region (3′-UTR). Downregulation of miR-182 suppressed growth and invasion of PTC cells. Silencing of CHL1 counteracted the effects of miR-182 suppression, while its overexpression mimicked these effects. Our data collectively indicate that miR-182 in PTC promotes cell proliferation and invasion through direct suppression of CHL1, supporting the potential utility of miR-182 inhibition as a novel therapeutic strategy against PTC.« less

Sulforaphane suppresses lipopolysaccharide-induced cyclooxygenase-2 (COX-2) expression through the modulation of multiple targets in COX-2 gene promoter.

PubMed

Woo, Kyung Jin; Kwon, Taeg Kyu

2007-12-15

Sulforaphane is a natural, biologically active compound extracted from cruciferous vegetables such as broccoli and cabbage. It possesses potent anti-inflammation and anti-cancer properties. The mechanism by which sulforaphane suppresses COX-2 expression remains poorly understood. In the present report, we investigated the effect of sulforaphane on the expression of COX-2 in lipopolysaccharide (LPS)-activated Raw 264.7 cells. Sulforaphane significantly suppressed the LPS-induced COX-2 protein and mRNA expression in a dose-dependent manner. The ability of sulforaphane to suppress the expression of the COX-2 was investigated using luciferase reporters controlled by various cis-elements in COX-2 promoter region. Electrophoretic mobility shift assay (EMSA) verified that NF-kappaB, C/EBP, CREB and AP-1 were identified as responsible for the sulforaphane-mediated COX-2 down-regulation. In addition, we demonstrated the signal transduction pathway of mitogen-activated protein kinase (MAP kinase) in LPS-induced COX-2 expression. Taken together, these results demonstrate that sulforaphane effectively suppressed the LPS-induced COX-2 protein via modulation of multiple core promoter elements (NF-kappaB, C/EBP, CREB and AP-1) in the COX-2 transcriptional regulation. These results will provide new insights into the anti-inflammatory and anti-carcinogenic properties of sulforaphane.

Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity

NASA Astrophysics Data System (ADS)

Markovitz, Craig D.; Hogan, Patrick S.; Wesen, Kyle A.; Lim, Hubert H.

2015-04-01

Objective. The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach. We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results. All eight stimulated AC subregions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance. We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders.

Gamma oscillations distinguish mere exposure from other likability effects.

PubMed

Kongthong, Nutchakan; Minami, Tetsuto; Nakauchi, Shigeki

2014-02-01

Repeated exposure to neutral stimuli enhances liking for those, which is called mere exposure effect (MEE) (Zajonc, 1968). Its behavioral effects have been extensively investigated. However, the mechanism by which it is generated remains unclear. To elucidate the neural mechanism of the MEE, we recorded electroencephalograms while subjects indicated their preferences for face stimuli with and without MEE induction. According to behavioral data, participants were divided into two groups, one with, and one without MEE tendency. In participants with an MEE tendency, gamma activity (40-60 [Hz]) in the parieto-occipital area was significantly weaker for exposed faces than unexposed ones, indicating a repetition-suppression effect. Gamma activity from sites exhibiting peak repetition-suppression effects was significantly weaker in theoretically genuine MEE trials than non-MEE trials, indicating that emotion processing might influence the MEE. These results suggest that existing theories regarding mechanisms underlying the MEE, namely, fluency misattribution and apprehensiveness reduction might not be mutually exclusive. Moreover, gamma activity might be a potential indicator to distinguish the MEE from other likability effects, at least in the case of human face stimuli. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity

PubMed Central

Dilshara, Matharage Gayani; Kang, Chang-Hee; Choi, Yung Hyun; Kim, Gi-Young

2015-01-01

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-α-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-α-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-α significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-α-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-α-induced invasion of LNCaP cells. Compared to untreated controls, TNF-α-stimulated LNCaP cells showed a significant increase in nuclear factor-κB (NF-κB) luciferase activity. However, mangiferin treatment markedly decreased TNF-α-induced NF-κB luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-κB subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-κB-mediated MMP-9 expression. [BMB Reports 2015; 48(10): 559-564] PMID:25739392

Mangiferin inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 expression and cellular invasion by suppressing nuclear factor-κB activity.

PubMed

Dilshara, Matharage Gayani; Kang, Chang-Hee; Choi, Yung Hyun; Kim, Gi-Young

2015-10-01

We investigated the effects of mangiferin on the expression and activity of metalloproteinase (MMP)-9 and the invasion of tumor necrosis factor (TNF)-α-stimulated human LNCaP prostate carcinoma cells. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that mangiferin significantly reversed TNF-α-induced mRNA and protein expression of MMP-9 expression. Zymography data confirmed that stimulation of cells with TNF-α significantly increased MMP-9 activity. However, mangiferin substantially reduced the TNF-α-induced activity of MMP-9. Additionally, a matrigel invasion assay showed that mangiferin significantly reduced TNF-α-induced invasion of LNCaP cells. Compared to untreated controls, TNF-α-stimulated LNCaP cells showed a significant increase in nuclear factor-κB (NF-κB) luciferase activity. However, mangiferin treatment markedly decreased TNF-α-induced NF-κB luciferase activity. Furthermore, mangiferin suppressed nuclear translocation of the NF-κB subunits p65 and p50. Collectively, our results indicate that mangiferin is a potential anti-invasive agent that acts by suppressing NF-κB-mediated MMP-9 expression.

Comparative Microbiome Analysis of a Fusarium Wilt Suppressive Soil and a Fusarium Wilt Conducive Soil From the Châteaurenard Region

PubMed Central

Siegel-Hertz, Katarzyna; Edel-Hermann, Véronique; Chapelle, Emilie; Terrat, Sébastien; Raaijmakers, Jos M.; Steinberg, Christian

2018-01-01

Disease-suppressive soils are soils in which specific soil-borne plant pathogens cause only limited disease although the pathogen and susceptible host plants are both present. Suppressiveness is in most cases of microbial origin. We conducted a comparative metabarcoding analysis of the taxonomic diversity of fungal and bacterial communities from suppressive and non-suppressive (conducive) soils as regards Fusarium wilts sampled from the Châteaurenard region (France). Bioassays based on Fusarium wilt of flax confirmed that disease incidence was significantly lower in the suppressive soil than in the conducive soil. Furthermore, we succeeded in partly transferring Fusarium wilt-suppressiveness to the conducive soil by mixing 10% (w/w) of the suppressive soil into the conducive soil. Fungal diversity differed significantly between the suppressive and conducive soils. Among dominant fungal operational taxonomic units (OTUs) affiliated to known genera, 17 OTUs were detected exclusively in the suppressive soil. These OTUs were assigned to the Acremonium, Chaetomium, Cladosporium, Clonostachys, Fusarium, Ceratobasidium, Mortierella, Penicillium, Scytalidium, and Verticillium genera. Additionally, the relative abundance of specific members of the bacterial community was significantly higher in the suppressive and mixed soils than in the conducive soil. OTUs found more abundant in Fusarium wilt-suppressive soils were affiliated to the bacterial genera Adhaeribacter, Massilia, Microvirga, Rhizobium, Rhizobacter, Arthrobacter, Amycolatopsis, Rubrobacter, Paenibacillus, Stenotrophomonas, and Geobacter. Several of the fungal and bacterial genera detected exclusively or more abundantly in the Fusarium wilt-suppressive soil included genera known for their activity against F. oxysporum. Overall, this study supports the potential role of known fungal and bacterial genera in Fusarium wilt suppressive soils from Châteaurenard and pinpoints new bacterial and fungal genera for their putative role in Fusarium wilt suppressiveness. PMID:29670584

Comparative Microbiome Analysis of a Fusarium Wilt Suppressive Soil and a Fusarium Wilt Conducive Soil From the Châteaurenard Region.

PubMed

Siegel-Hertz, Katarzyna; Edel-Hermann, Véronique; Chapelle, Emilie; Terrat, Sébastien; Raaijmakers, Jos M; Steinberg, Christian

2018-01-01

Disease-suppressive soils are soils in which specific soil-borne plant pathogens cause only limited disease although the pathogen and susceptible host plants are both present. Suppressiveness is in most cases of microbial origin. We conducted a comparative metabarcoding analysis of the taxonomic diversity of fungal and bacterial communities from suppressive and non-suppressive (conducive) soils as regards Fusarium wilts sampled from the Châteaurenard region (France). Bioassays based on Fusarium wilt of flax confirmed that disease incidence was significantly lower in the suppressive soil than in the conducive soil. Furthermore, we succeeded in partly transferring Fusarium wilt-suppressiveness to the conducive soil by mixing 10% (w/w) of the suppressive soil into the conducive soil. Fungal diversity differed significantly between the suppressive and conducive soils. Among dominant fungal operational taxonomic units (OTUs) affiliated to known genera, 17 OTUs were detected exclusively in the suppressive soil. These OTUs were assigned to the Acremonium, Chaetomium, Cladosporium, Clonostachys, Fusarium, Ceratobasidium, Mortierella, Penicillium, Scytalidium , and Verticillium genera. Additionally, the relative abundance of specific members of the bacterial community was significantly higher in the suppressive and mixed soils than in the conducive soil. OTUs found more abundant in Fusarium wilt-suppressive soils were affiliated to the bacterial genera Adhaeribacter, Massilia, Microvirga, Rhizobium, Rhizobacter, Arthrobacter, Amycolatopsis, Rubrobacter, Paenibacillus, Stenotrophomonas , and Geobacter . Several of the fungal and bacterial genera detected exclusively or more abundantly in the Fusarium wilt-suppressive soil included genera known for their activity against F. oxysporum . Overall, this study supports the potential role of known fungal and bacterial genera in Fusarium wilt suppressive soils from Châteaurenard and pinpoints new bacterial and fungal genera for their putative role in Fusarium wilt suppressiveness.

Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Nonsusceptible Bacteria in Multispecies Biofilms

PubMed Central

Forbes, Sarah; Cowley, Nicola; Mistry, Hitesh; Amézquita, Alejandro

2017-01-01

ABSTRACT The current investigation aimed to generate data to inform the development of risk assessments of biocide usage. Stabilized domestic drain biofilm microcosms were exposed daily over 6 months to increasing concentrations (0.01% to 1%) of the biocide benzalkonium chloride (BAC) in a simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analyzed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing, and changes in biofilm composition were assessed by high-throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in levels of viable bacteria than exposure to BAC-s, while bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1% were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations, and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched populations of organisms with lower antimicrobial susceptibility, and the effects were subsequently suppressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products. IMPORTANCE Assessment of the risks of biocide use has been based mainly on the exposure of axenic cultures of bacteria to biocides in simple aqueous solutions. The current investigation aimed to assess the effects of formulation on the outcome of biocide exposure in multispecies biofilms. Formulation of the cationic biocide BAC significantly increased antimicrobial potency. Bacteria with lower antimicrobial susceptibility whose populations were enriched after low-level biocide exposure were more effectively suppressed by the biocide at in-use concentrations (1% [wt/vol]) in a formulation than in a simple aqueous solution. These observations underline the importance of simulating normal deployment conditions in considering the risks and benefits of biocide use. PMID:28115386

Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes.

PubMed

Inman, A O; Monteiro-Riviere, N A; Riviere, J E

2008-05-01

Jet propellant (JP)-8, the primary jet fuel used by the U.S. military, consists of hydrocarbon-rich kerosene base commercial jet fuel (Jet-A) plus additives DC1-4A, Stadis 450 and diethylene glycol monomethyl ether. Human epidermal keratinocytes (HEK) were exposed to JP-8, aliphatic hydrocarbon (HC) fuel S-8 and aliphatic HC pentadecane (penta), tetradecane (tetra), tridecane (tri) and undecane (un) for 5 min. Additional studies were conducted with signal transduction pathway blockers parthenolide (P; 3.0 microm), isohelenin (I; 3.0 microm), SB 203580 (SB; 13.3 microm), substance P (SP; 3.0 microm) and recombinant human IL-10 (rHIL-10; 10 ng ml(-1)). In the absence of inhibitors, JP-8 and to a lesser extent un and S-8, had the greatest toxic effect on cell viability and inflammation suggesting, as least in vitro, that synthetic S-8 fuel is less irritating than the currently used JP-8. Each inhibitor significantly (P < 0.05) decreased HEK viability. DMSO, the vehicle for P, I and SB, had a minimal effect on viability. Overall, IL-8 production was suppressed at least 30% after treatment with each inhibitor. Normalizing data relative to control indicate which inhibitors suppress HC-mediated IL-8 to control levels. P was the most effective inhibitor of IL-8 release; IL-8 was significantly decreased after exposure to un, tri, tetra and penta but significantly increased after JP-8 exposure compared with controls. Inhibitors were not effective in suppressing IL-8 release in JP-8 exposures to control levels. This study shows that inhibiting NF-kappa B, which appears to play a role in cytokine production in HC-exposed HEK in vitro, may reduce the inflammatory effect of HC in vivo. Copyright (c) 2007 John Wiley & Sons, Ltd.

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

PubMed

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Effect of dehydration on erythropoiesis in mice - Relevance to the 'anemia' of space flight

NASA Technical Reports Server (NTRS)

Dunn, C. D. R.

1978-01-01

Mice deprived of water for 24 h showed an increase in hematocrit and loss of body weight comparable to that seen in men during space flight. The increase in hematocrit was entirely due to a decrease in plasma volume and was associated with suppression of erythropoiesis, but with no significant change in the serum titer of a presumptive humoral regulator of erythropoiesis, Erythroid Stimulating Activity (ESA). Mice deprived of water for 24 h may be a useful model for the study of the early hematological effects of space flight. The suppression of erythropoiesis due to a relative erythrocytosis appears to be independent of ESA.

The entomopathogenic fungus Nomuraea rileyi impairs cellular immunity of its host Helicoverpa armigera.

PubMed

Zhong, Ke; Liu, Zhan-Chi; Wang, Jia-Lin; Liu, Xu-Sheng

2017-09-01

In this study, we investigated the effect of the entomopathogenic fungus Nomuraea rileyi on Helicoverpa armigera cellular immune responses. Nomuraea rileyi infection had no effect on total hemocyte count (THC), but impaired hemocyte-mediated phagocytosis, nodulation, and encapsulation responses. Nomuraea rileyi infection led to a significant reduction in hemocyte spreading. An in vitro assay revealed that plasma from N. rileyi infected H. armigera larvae suppressed the spreading ability of hemocytes from naïve larvae. We infer that N. rileyi suppresses the cellular immune response of its host, possibly by secreting exogenous, cytotoxic compounds into the host's hemolymph. © 2017 Wiley Periodicals, Inc.

Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ{sup 9}-tetrahydrocannabinol in human CD4{sup +} T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ngaotepprutaram, Thitirat; Center for Integrative Toxicology, Michigan State University; Kaplan, Barbara L.F.

We have previously reported that Δ{sup 9}-tetrahydrocannabinol (Δ{sup 9}-THC), the main psychoactive cannabinoid in marijuana, suppresses CD40 ligand (CD40L) expression by activated mouse CD4{sup +} T cells. CD40L is involved in pathogenesis of many autoimmune and inflammatory diseases. In the present study, we investigated the molecular mechanism of Δ{sup 9}-THC-mediated suppression of CD40L expression using peripheral blood human T cells. Pretreatment with Δ{sup 9}-THC attenuated CD40L expression in human CD4{sup +} T cells activated by anti-CD3/CD28 at both the protein and mRNA level, as determined by flow cytometry and quantitative real-time PCR, respectively. Electrophoretic mobility shift assays revealed that Δ{supmore » 9}-THC suppressed the DNA-binding activity of both NFAT and NFκB to their respective response elements within the CD40L promoter. An assessment of the effect of Δ{sup 9}-THC on proximal T cell-receptor (TCR) signaling induced by anti-CD3/CD28 showed significant impairment in the rise of intracellular calcium, but no significant effect on the phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β. Collectively, these findings identify perturbation of the calcium-NFAT and NFκB signaling cascade as a key mechanistic event by which Δ{sup 9}-THC suppresses human T cell function. - Highlights: • Δ{sup 9}-THC attenuated CD40L expression in activated human CD4+ T cells. • Δ{sup 9}-THC suppressed DNA-binding activity of NFAT and NFκB. • Δ{sup 9}-THC impaired elevation of intracellular Ca2+. • Δ{sup 9}-THC did not affect phosphorylation of ZAP70, PLCγ1/2, Akt, and GSK3β.« less

Impact of hormonal therapy on intermediate risk prostate cancer treated with combination brachytherapy and external beam irradiation.

PubMed

Stock, Richard G; Yalamanchi, Swati; Yamalachi, Swati; Hall, Simon J; Stone, Nelson N

2010-02-01

We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.

Combination of Aβ Suppression and Innate Immune Activation in the Brain Significantly Attenuates Amyloid Plaque Deposition.

PubMed

Verbeeck, Christophe; Carrano, Anna; Chakrabarty, Paramita; Jankowsky, Joanna L; Das, Pritam

2017-12-01

Anti-Aβ clinical trials are currently under way to determine whether preventing amyloid deposition will be beneficial in arresting progression of Alzheimer disease. Both clinical and preclinical studies suggest that antiamyloid strategies are only effective if started at early stages of the disease process in a primary prevention strategy. Because this approach will be difficult to deploy, strategies for secondary prevention aimed at later stages of disease are also needed. In this study, we asked whether combining innate immune activation in the brain with concurrent Aβ suppression could enhance plaque clearance and could improve pathologic outcomes in mice with moderate amyloid pathologic disorder. Starting at 5 months of age, tet-off amyloid precursor protein transgenic mice were treated with doxycycline (dox) to suppress further amyloid precursor protein/Aβ production, and at the same time mice were intracranially injected with adeno-associated virus 1 expressing murine IL-6 (AAV1-mIL-6). Three months later, mice treated with the combination of Aβ suppression and AAV1-mIL-6 showed significantly less plaque pathologic disorder than dox or AAV1-mIL-6 only groups. The combination of AAV1-mIL-6 + dox treatment lowered total plaque burden by >60% versus untreated controls. Treatment with either dox or AAV1-mIL-6 alone was less effective than the combination. Our results suggest a synergistic mechanism by which the up-regulation of mIL-6 was able to improve plaque clearance in the setting of Aβ suppression. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

Suppressive immunoregulatory effects of three antidepressants via inhibition of the nuclear factor-κB activation assessed using primary macrophages of carp (Cyprinus carpio)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Wenhui

Antidepressants, having been applied for the treatment of major depressive disorder and other conditions for decades, are among the most commonly detected human pharmaceuticals in the aquatic environment. This study evaluated the immunotoxicity of acute exposure to environmentally relevant concentrations of amitriptyline, fluoxetine and mianserin using an in vitro primary macrophage model isolated from red common carp (Cyprinus carpio), and also explored their potential mechanisms of action. A potential suppressive immunoregulatory effect of antidepressant exposure was suggested based on the observed suppressive effects on oxidative stress parameters, bactericidal activity, NO production, and NO synthase activity, as well as pro-inflammatory cytokinemore » gene expression, and a significant stimulatory effect on anti-inflammatory interleukin-10 and interferon cytokine gene expression and ATPase activities in macrophages after 6 h-exposure to three individual antidepressants and a combination thereof. Notably, we also found these effects were significantly associated with a corresponding decrease in nuclear factor-κB (NF-κB) activity after antidepressants exposure, and the NF-κB antagonist significantly restrained the effects of antidepressants on gene expression of cytokines, indicating that antidepressants could alter the response of various immune-associated components via the inhibition of NF-κB. Moreover, time-dependent lethal concentrations of three antidepressants on primary macrophages were firstly determined at mg/L levels, and the synergetic effects of antidepressant mixtures were suggested and in particular, for some parameters including total antioxidant capacity and cytokine genes expression, they could be significantly affected by antidepressants exposure at concentrations as low as 10 ng/L, which together thereby revealed the potential risk of antidepressants to aquatic life. - Highlights: • Three different antidepressants all have immunoregulatory effects on macrophages. • Pro-inflammatory cytokine gene expression was inhibited by drug exposure. • Anti-inflammatory cytokine gene expression was induced by drug exposure. • NF-κB pathway was involved in the effects of antidepressants. • Synergetic effects occurred at environmentally relevant concentration of 10 ng/L.« less

Suppression of laser phase noise in direct-detection optical OFDM transmission using phase-conjugated pilots

NASA Astrophysics Data System (ADS)

Zhang, Lu; Ming, Yi; Li, Jin

2017-11-01

Due to the unique phase noise (PN) characteristics in direct-detection optical OFDM (DDO-OFDM) systems, the design of PN compensator is considered as a difficult task. In this paper, a laser PN suppression scheme with low complexity for DDO-OFDM based on coherent superposition of data carrying subcarriers and their phase conjugates is proposed. Through theoretical derivation, the obvious PN suppression is observed. The effectiveness of this technique is demonstrated by simulation of a 4-QAM DDO-OFDM system over 1000 km transmission length at different laser line-width and subcarrier frequency spacing. The results show that the proposed scheme can significantly suppress both varied phase rotation term (PTR) and inter-carrier interference (ICI), and the laser line-width can be relaxed with up to 9 dB OSNR saving or even breakthrough of performance floor.

Antiperoxidation activity of triterpenoids from rhizome of Anemone raddeana.

PubMed

Chen, Xin; Lu, Jincai; He, Wenfei; Chi, Haidong; Yamashita, Koichi; Manabe, Masanobu; Kodama, Hiroyuki

2009-03-01

Four triterpenoid compounds hederacolchiside E (1), hederasaponin B (2), raddeanoside 20 (3) and raddeanoside 21 (4) were isolated from ethanol extracts of rhizome of Anemone raddeana Regel. The effects of these triterpenoids on superoxide generation, tyrosyl phosphorylation of proteins and translocation of cytosolic compounds, such as p47(phox), p67(phox) and Rac to the cell membrane in human neutrophils was investigated. The superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was slightly suppressed by hederasaponin B, raddeanoside 20 and raddeanoside 21 in a concentration dependent manner. The superoxide generation induced by arachidonic acid (AA) was suppressed by hederasaponin B and raddeanoside 21 significantly. fMLP- and AA-induced tyrosyl phosphorylation and translocation of the cytosolic proteins: p47(phox), p67(phox), and Rac to the cell membrane were suppressed in parallel with the suppression of stimulus-induced superoxide generation.

Usefulness of IDEAL T2 imaging for homogeneous fat suppression and reducing susceptibility artefacts in brachial plexus MRI at 3.0 T.

PubMed

Tagliafico, Alberto; Bignotti, Bianca; Tagliafico, Giulio; Martinoli, Carlo

2016-01-01

To quantitatively and qualitatively compare fat-suppressed MR imaging quality using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with that using frequency-selective fat-suppressed (FSFS) T2 images of the brachial plexus at 3.0 T. Prospective MR image analysis was performed in 40 volunteers and 40 patients at a single centre. Oblique-sagittal and coronal IDEAL fat-suppressed T2 images and FSFS T2 images were compared. Visual assessment was performed by two independent musculoskeletal radiologists with respect to: (1) susceptibility artefacts around the neck, (2) homogeneity of fat suppression, (3) image sharpness and (4) tissue resolution contrast of pathologies. The signal-to-noise ratios (SNR) for each image sequence were assessed. Compared to FSFS sequences, IDEAL fat-suppressed T2 images significantly reduced artefacts around the brachial plexus and significantly improved homogeneous fat suppression (p < 0.05). IDEAL significantly improved sharpness and lesion-to-tissue contrast (p < 0.05). The mean SNRs were significantly improved on T2-weighted IDEAL images (p < 0.05). IDEAL technique improved image quality by reducing artefacts around the brachial plexus while maintaining a high SNR and provided superior homogeneous fat suppression than FSFS sequences.

Minocycline Suppresses Interleukine-6, Its Receptor System and Signaling Pathways and Impairs Migration, Invasion and Adhesion Capacity of Ovarian Cancer Cells: In Vitro and In Vivo Studies

PubMed Central

Ataie-Kachoie, Parvin; Morris, David L.; Pourgholami, Mohammad H.

2013-01-01

Interleukin (IL)-6 has been shown to be a major contributing factor in growth and progression of ovarian cancer. The cytokine exerts pro-tumorigenic activity through activation of several signaling pathways in particular signal transducer and activator of transcription (STAT3) and extracellular signal-regulated kinase (ERK)1/2. Hence, targeting IL-6 is becoming increasingly attractive as a treatment option in ovarian cancer. Here, we investigated the effects of minocycline on IL-6 and its signaling pathways in ovarian cancer. In vitro, minocycline was found to significantly suppress both constitutive and IL-1β or 4-hydroxyestradiol (4-OH-E2)-stimulated IL-6 expression in human ovarian cancer cells; OVCAR-3, SKOV-3 and CAOV-3. Moreover, minocycline down-regulated two major components of IL-6 receptor system (IL-6Rα and gp130) and blocked the activation of STAT3 and ERK1/2 pathways leading to suppression of the downstream product MCL-1. In female nude mice bearing intraperitoneal OVCAR-3 tumors, acute administration (4 and 24 h) of minocycline (30 mg/kg) led to suppression of IL-6. Even single dose of minocycline was effective at significantly lowering plasma and tumor IL-6 levels. In line with this, tumoral expression of p-STAT3, p-ERK1/2 and MCL-1 were decreased in minocycline-treated mice. Evaluation of the functional implication of minocycline on metastatic activity revealed the capacity of minocycline to inhibit cellular migration, invasion and adhesion associated with down-regulation of matrix metalloproteinases (MMP)-2 and 9. Thus, the data suggest a potential role for minocycline in suppressing IL-6 expression and activity. These effects may prove to be an important attribute to the upcoming clinical trials of minocycline in ovarian cancer. PMID:23593315

Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice.

PubMed

Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori

2016-06-01

Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Effect of propofol on androgen receptor activity in prostate cancer cells.

PubMed

Tatsumi, Kenichiro; Hirotsu, Akiko; Daijo, Hiroki; Matsuyama, Tomonori; Terada, Naoki; Tanaka, Tomoharu

2017-08-15

Androgen receptor is a nuclear receptor and transcription factor activated by androgenic hormones. Androgen receptor activity plays a pivotal role in the development and progression of prostate cancer. Although accumulating evidence suggests that general anesthetics, including opioids, affect cancer cell growth and impact patient prognosis, the effect of those drugs on androgen receptor in prostate cancer is not clear. The purpose of this study was to investigate the effect of the general anesthetic propofol on androgen receptor activity in prostate cancer cells. An androgen-dependent human prostate cancer cell line (LNCaP) was stimulated with dihydrotestosterone (DHT) and exposed to propofol. The induction of androgen receptor target genes was investigated using real-time reverse transcription polymerase chain reaction, and androgen receptor protein levels and localization patterns were analyzed using immunoblotting and immunofluorescence assays. The effect of propofol on the proliferation of LNCaP cells was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Propofol significantly inhibited DHT-induced expression of androgen receptor target genes in a dose- and time-dependent manner, and immunoblotting and immunofluorescence assays indicated that propofol suppressed nuclear levels of androgen receptor proteins. Exposure to propofol for 24h suppressed the proliferation of LNCaP cells, whereas 4h of exposure did not exert significant effects. Together, our results indicate that propofol suppresses nuclear androgen receptor protein levels, and inhibits androgen receptor transcriptional activity and proliferation in LNCaP cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Sub-toxic concentrations of nano-ZnO and nano-TiO2 suppress neurite outgrowth in differentiated PC12 cells.

PubMed

Irie, Tomohiko; Kawakami, Tsuyoshi; Sato, Kaoru; Usami, Makoto

2017-01-01

Nanomaterials have been extensively used in our daily life, and may also induce health effects and toxicity. Nanomaterials can translocate from the outside to internal organs, including the brain. For example, both nano-ZnO and nano-TiO 2 translocate into the brain via the olfactory pathway in rodents, possibly leading to toxic effects on the brain. Although the effects of nano-ZnO and nano-TiO 2 on neuronal viability or neuronal excitability have been studied, no work has focused on how these nanomaterials affect neuronal differentiation and development. In this study, we investigated the effects of nano-ZnO and nano-TiO 2 on neurite outgrowth of PC12 cells, a useful model system for neuronal differentiation. Surprisingly, the number, length, and branching of differentiated PC12 neurites were significantly suppressed by the 7-day exposure to nano-ZnO (in the range of 1.0 × 10 -4 to 1.0 × 10 -1 µg/mL), at which the cell viability was not affected. The number and length were also significantly inhibited by the 7-day exposure to nano-TiO 2 (1.0 × 10 -3 to 1.0 µg/mL), which did not have cytotoxic effects. These results demonstrate that the neurite outgrowth in differentiated PC12 cells was suppressed by sub-cytotoxic concentrations of nano-ZnO or nano-TiO 2 .

Light at Night and Measures of Alertness and Performance: Implications for Shift Workers.

PubMed

Figueiro, Mariana G; Sahin, Levent; Wood, Brittany; Plitnick, Barbara

2016-01-01

Rotating-shift workers, particularly those working at night, are likely to experience sleepiness, decreased productivity, and impaired safety while on the job. Light at night has been shown to have acute alerting effects, reduce sleepiness, and improve performance. However, light at night can also suppress melatonin and induce circadian disruption, both of which have been linked to increased health risks. Previous studies have shown that long-wavelength (red) light exposure increases objective and subjective measures of alertness at night, without suppressing nocturnal melatonin. This study investigated whether exposure to red light at night would not only increase measures of alertness but also improve performance. It was hypothesized that exposure to both red (630 nm) and white (2,568 K) lights would improve performance but that only white light would significantly affect melatonin levels. Seventeen individuals participated in a 3-week, within-subjects, nighttime laboratory study. Compared to remaining in dim light, participants had significantly faster reaction times in the GO/NOGO test after exposure to both red light and white light. Compared to dim light exposure, power in the alpha and alpha-theta regions was significantly decreased after exposure to red light. Melatonin levels were significantly suppressed by white light only. Results show that not only can red light improve measures of alertness, but it can also improve certain types of performance at night without affecting melatonin levels. These findings could have significant practical applications for nurses; red light could help nurses working rotating shifts maintain nighttime alertness, without suppressing melatonin or changing their circadian phase. © The Author(s) 2015.

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

PubMed

Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

2008-08-21

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Suppression on your own terms: internally generated displays of craving suppression predict rebound effects.

PubMed

Sayers, W Michael; Sayette, Michael A

2013-09-01

Research on emotion suppression has shown a rebound effect, in which expression of the targeted emotion increases following a suppression attempt. In prior investigations, participants have been explicitly instructed to suppress their responses, which has drawn the act of suppression into metaconsciousness. Yet emerging research emphasizes the importance of nonconscious approaches to emotion regulation. This study is the first in which a craving rebound effect was evaluated without simultaneously raising awareness about suppression. We aimed to link spontaneously occurring attempts to suppress cigarette craving to increased smoking motivation assessed immediately thereafter. Smokers (n = 66) received a robust cued smoking-craving manipulation while their facial responses were videotaped and coded using the Facial Action Coding System. Following smoking-cue exposure, participants completed a behavioral choice task previously found to index smoking motivation. Participants evincing suppression-related facial expressions during cue exposure subsequently valued smoking more than did those not displaying these expressions, which suggests that internally generated suppression can exert powerful rebound effects.

77 FR 74381 - Protection of Stratospheric Ozone: Listing of Substitutes for Ozone Depleting Substances-Fire...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

... Protection of Stratospheric Ozone: Listing of Substitutes for Ozone Depleting Substances--Fire Suppression... a companion proposed rule issuing listings for three fire suppressants under EPA's Significant New... companion proposed rule issuing listings for three fire suppressants under EPA's Significant New...

The antihypertension drug doxazosin suppresses JAK/STATs phosphorylation and enhances the effects of IFN-α/γ-induced apoptosis.

PubMed

Park, Mi Sun; Kim, Boh-Ram; Kang, Sokbom; Kim, Dae-Yong; Rho, Seung Bae

2014-11-01

Doxazosin, a commonly prescribed treatment for patients with benign prostatic hyperplasia, serves as an α1-blocker of the adrenergic receptors. In this study, we calculated its effect on the ovarian carcinoma cells. Doxazosin induces dose-dependent growth suppression and is additively activated through IFN-α or IFN-γ stimulation. They both enhanced G1 phase arrest, as well as the activity of caspase-3, and the reduction of cyclin D1 and CDK4 protein levels. Doxazosin growth suppression was abolished either by the Janus family of tyrosine kinase (JAK) or the signal transducer and activator of transcription (STAT) inhibitor treatment. The activity of JAK/STAT was dependent on the level of doxazosin, suggesting a requirement of doxazosin for the activation of JAK/STAT. Furthermore, doxazosin plus IFN-α or doxazosin plus IFN-γ additively suppressed the activation of the JAK/STAT signals through phosphorylation of JAK and STAT, thus affecting the activation of subsequent downstream signaling components PI3K, mTOR, 70S6K, and PKCδ. In vivo study demonstrated that doxazosin significantly suppressed tumor growth in an ovarian cancer cell xenograft mouse model, inducing apoptotic cell death by up-regulating the expression of p53, whereas c-Myc expression was markedly reduced. Our data indicate that doxazosin can modulate the apoptotic effects of IFN-α- and IFN-γ through the JAK/STAT signaling pathways. Collectively, we indicate that this action may be a potent chemotherapeutic property against ovarian carcinoma.

Ascofuranone suppresses EGF-induced HIF-1α protein synthesis by inhibition of the Akt/mTOR/p70S6K pathway in MDA-MB-231 breast cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Yun-Jeong; Cho, Hyun-Ji; Magae, Junji

2013-12-15

Hypoxia-inducible factor (HIF)-1 plays an important role in tumor progression, angiogenesis and metastasis. In this study, we investigated the potential molecular mechanisms underlying the anti-angiogenic effect of ascofuranone, an isoprenoid antibiotic from Ascochyta viciae, in epidermal growth factor (EGF)-1 responsive human breast cancer cells. Ascofuranone significantly and selectively suppressed EGF-induced HIF-1α protein accumulation, whereas it did not affect the expression of HIF-1β. Furthermore, ascofuranone inhibited the transcriptional activation of vascular endothelial growth factor (VEGF) by reducing protein HIF-1α. Mechanistically, we found that the inhibitory effects of ascofuranone on HIF-1α protein expression are associated with the inhibition of synthesis HIF-1α throughmore » an EGF-dependent mechanism. In addition, ascofuranone suppressed EGF-induced phosphorylation of Akt/mTOR/p70S6 kinase, but the phosphorylation of ERK/JNK/p38 kinase was not affected by ascofuranone. These results suggest that ascofuranone suppresses EGF-induced HIF-1α protein translation through the inhibition of Akt/mTOR/p70S6 kinase signaling pathways and plays a novel role in the anti-angiogenic action. - Highlights: • Inhibitory effect of ascofuranone on HIF-1α expression is EGF-specific regulation. • Ascofuranone decreases HIF-1α protein synthesis through Akt/mTOR pathways. • Ascofuranone suppresses EGF-induced VEGF production and tumor angiogenesis.« less

Immunosuppressive Effects of Bryoria sp. (Lichen-Forming Fungus) Extracts via Inhibition of CD8+ T-Cell Proliferation and IL-2 Production in CD4+ T Cells.

PubMed

Hwang, Yun-Ho; Lee, Sung-Ju; Kang, Kyung-Yun; Hur, Jae-Seoun; Yee, Sung-Tae

2017-06-28

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of CD8 + T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of CD8 + T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and IFN-γ as the CD8 + T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain (IL-2Rα) on CD8 + T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, IFN-γ, and CD69 on CD8 + T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of IL-2Rα expression in CD8 + T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

A new prostaglandin E1 analogue (TFC-612) improves the reduction in motor nerve conduction velocity in spontaneously diabetic GK (Goto-Kakizaki) rats.

PubMed

Suzuki, K; Saito, N; Sakata, Y; Toyota, T; Goto, Y

1990-11-01

A new prostaglandin E1 analogue, TFC-612, was given orally to 2 month-old spontaneously diabetic GK (Goto-Kakizaki) rats for 3 months to ascertain its effects on reduced motor nerve conduction velocity (MCV). A high dose of this compound (0.3 mg/kg body weight) significantly restored MCV after 2 and 3 months of administration, although the low dose (0.03 mg/kg body weight) did not. In addition, 1 month administration of TFC-612 significantly improved the reduced MCV in aged (5 month-old) GK rats only in the high dose group (0.3 mg/kg body weight), but not in the low dose group (0.03 mg/kg body weight). Although TFC-612 significantly suppressed sorbitol accumulation in the sciatic nerves of GK rats in a dose dependent manner after 3 months administration, this suppression was not observed after either 2 months administration to 2 month-old GK rats or after 1 month administration to 5 month-old GK rats. Fasting blood glucose levels of all GK rats remained high throughout the experiments, regardless of TFC-612 administration. TFC-612's improvement on reduced motor nerve conduction velocity was related partly to suppression of sorbitol accumulation, but other factors, including microcirculation, may contribute significantly to this effect. These results suggest that TFC-612 may be beneficial in the treatment of diabetic nerve impairment.

An entomopathogenic bacterium, Xenorhabdus nematophila, suppresses expression of antimicrobial peptides controlled by Toll and Imd pathways by blocking eicosanoid biosynthesis.

PubMed

Hwang, Jihyun; Park, Youngjin; Kim, Yonggyun; Hwang, Jihyun; Lee, Daeweon

2013-07-01

Immune-associated genes of the beet armyworm, Spodoptera exigua, were predicted from 454 pyrosequencing transcripts of hemocytes collected from fifth instar larvae challenged with bacteria. Out of 22,551 contigs and singletons, 36% of the transcripts had at least one significant hit (E-value cutoff of 1e-20) and used to predict immune-associated genes implicated in pattern recognition, prophenoloxidase activation, intracellular signaling, and antimicrobial peptides (AMPs). Immune signaling and AMP genes were further confirmed in their expression patterns in response to different types of microbial challenge. To discriminate the AMP expression signaling between Toll and Imd pathways, RNA interference was applied to specifically knockdown each signal pathway; the separate silencing treatments resulted in differential suppression of AMP genes. An entomopathogenic bacterium, Xenorhabdus nematophila, suppressed expression of most AMP genes controlled by Toll and Imd pathways, while challenge with heat-killed X. nematophila induced expression of all AMPs in experimental larvae. Benzylideneacetone (BZA), a metabolite of X. nematophila, suppressed the AMP gene inductions when it was co-injected with the heat-killed X. nematophila. However, arachidonic acid, a catalytic product of PLA2 , significantly reversed the inhibitory effect of BZA on the AMP gene expression. This study suggests that X. nematophila suppresses AMP production controlled by Toll and Imd pathways by inhibiting eicosanoid biosynthesis in S. exigua. © 2013 Wiley Periodicals, Inc.

Effects of NOx and SO2 on the secondary organic aerosol formation from photooxidation of α-pinene and limonene

NASA Astrophysics Data System (ADS)

Zhao, Defeng; Schmitt, Sebastian H.; Wang, Mingjin; Acir, Ismail-Hakki; Tillmann, Ralf; Tan, Zhaofeng; Novelli, Anna; Fuchs, Hendrik; Pullinen, Iida; Wegener, Robert; Rohrer, Franz; Wildt, Jürgen; Kiendler-Scharr, Astrid; Wahner, Andreas; Mentel, Thomas F.

2018-02-01

Anthropogenic emissions such as NOx and SO2 influence the biogenic secondary organic aerosol (SOA) formation, but detailed mechanisms and effects are still elusive. We studied the effects of NOx and SO2 on the SOA formation from the photooxidation of α-pinene and limonene at ambient relevant NOx and SO2 concentrations (NOx: < 1to 20 ppb, SO2: < 0.05 to 15 ppb). In these experiments, monoterpene oxidation was dominated by OH oxidation. We found that SO2 induced nucleation and enhanced SOA mass formation. NOx strongly suppressed not only new particle formation but also SOA mass yield. However, in the presence of SO2 which induced a high number concentration of particles after oxidation to H2SO4, the suppression of the mass yield of SOA by NOx was completely or partly compensated for. This indicates that the suppression of SOA yield by NOx was largely due to the suppressed new particle formation, leading to a lack of particle surface for the organics to condense on and thus a significant influence of vapor wall loss on SOA mass yield. By compensating for the suppressing effect on nucleation of NOx, SO2 also compensated for the suppressing effect on SOA yield. Aerosol mass spectrometer data show that increasing NOx enhanced nitrate formation. The majority of the nitrate was organic nitrate (57-77 %), even in low-NOx conditions (< ˜ 1 ppb). Organic nitrate contributed 7-26 % of total organics assuming a molecular weight of 200 g mol-1. SOA from α-pinene photooxidation at high NOx had a generally lower hydrogen to carbon ratio (H / C), compared to low NOx. The NOx dependence of the chemical composition can be attributed to the NOx dependence of the branching ratio of the RO2 loss reactions, leading to a lower fraction of organic hydroperoxides and higher fractions of organic nitrates at high NOx. While NOx suppressed new particle formation and SOA mass formation, SO2 can compensate for such effects, and the combining effect of SO2 and NOx may have an important influence on SOA formation affected by interactions of biogenic volatile organic compounds (VOCs) with anthropogenic emissions.

Anti-inflammatory and cytotoxic effects of methanol, ethanol, and water extracts of Angelicae Dahuricae Radix.

PubMed

Wang, Myeong-Hyeon; Jeong, Su-Hyeon; Guo, Huifang; Park, Jun-Beom

2016-01-01

Angelicae Dahuricae Radix has been used for the treatment of headaches, rhinitis, and colds in traditional medicine. Methanol, ethanol, and water extracts of Angelicae Dahuricae Radix were collected. A statistically significant reduction in the cellular viability of the mouse leukemic monocyte macrophage cell line was noted after treatment with water extracts of Angelicae Dahuricae Radix. Stimulation with lipopolysaccharides (LPS) for 24 h led to a robust increase in nitric oxide production, but Angelicae Dahuricae Radix at 400 μg/mL concentration significantly suppressed nitric oxide produced by the LPS-stimulated RAW 264.7 cells in 70% ethanol, absolute ethanol, 70% methanol, absolute methanol, and boiling water groups (P < 0.05). Pretreatment with absolute ethanol extract of Angelicae Dahuricae Radix suppressed the LPS-stimulated inducible nitric oxide synthase, interleukin-1β, and cycloxygenase-2 expression. Angelicae Dahuricae Radix showed significant cytotoxic effects on the human adenocarcinoma cell line and keratin-forming cell line. (J Oral Sci 58, 125-131, 2016).

Low trans structured fat from flaxseed oil improves plasma and hepatic lipid metabolism in apo E(-/-) mice.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Park, Yong-Bok; Lee, Ki-Teak; Park, Taesun; Choi, Myung-Sook

2009-07-01

The objective of this study was to explicate the effects of feeding low trans structured fat from flaxseed oil (LF) on plasma and hepatic lipid metabolism involved in apo E(-/-) mice. The animals were fed a commercial shortening (CS), commercial low trans fat (CL) and LF diet based on AIN-76 diet (10% fat) for 12 weeks. LF supplementation exerted a significant suppression in hepatic lipid accumulation with the concomitant decrease in liver weight. The LF significantly lowered plasma total cholesterol and free fatty acid whereas it significantly increased HDL-C concentration and the HDL-C/total-C ratio compared to the CS group. Reduction of hepatic lipid levels in the LF group was related with the suppression of hepatic enzyme activities for fatty acid and triglyceride synthesis, and cholesterol regulating enzyme activity compared to the CS and CL groups. Accordingly, low trans structured fat from flaxseed oil is highly effective for improving hyperlipidemia and hepatic lipid accumulation in apo E(-/-) mice.

Apple Procyanidins Suppress Amyloid β-Protein Aggregation

PubMed Central

Toda, Toshihiko; Sunagawa, Tadahiro; Kanda, Tomomasa; Tagashira, Motoyuki; Shirasawa, Takuji; Shimizu, Takahiko

2011-01-01

Procyanidins (PCs) are major components of the apple polyphenols (APs). We previously reported that treatment with PC extended the mean lifespan of Caenorhabditis elegans (Sunagawa et al., 2011). In order to estimate the neuroprotective effects of PC, we investigated the antiaggregative activity of PC on amyloid β-protein (Aβ) aggregation, which is a pathological hallmark of Alzheimer's disease. We herein report that PC significantly suppressed Aβ42 aggregation and dissociated Aβ42 aggregates in a dose-dependent manner, indicating that PC is a potent suppressor of Aβ aggregation. Furthermore, PC significantly inhibited Aβ42 neurotoxicity and stimulated proliferation in PC-12 cells. These results suggested that the PC and AP acted as neuroprotective factors against toxic Aβ aggregates. PMID:21826271

Isolation and Identification of Plant Growth Promoting Rhizobacteria from Cucumber Rhizosphere and Their Effect on Plant Growth Promotion and Disease Suppression

PubMed Central

Islam, Shaikhul; Akanda, Abdul M.; Prova, Ananya; Islam, Md. T.; Hossain, Md. M.

2016-01-01

Plant growth promoting rhizobacteria (PGPR) are the rhizosphere bacteria that may be utilized to augment plant growth and suppress plant diseases. The objectives of this study were to identify and characterize PGPR indigenous to cucumber rhizosphere in Bangladesh, and to evaluate their ability to suppress Phytophthora crown rot in cucumber. A total of 66 isolates were isolated, out of which 10 (PPB1, PPB2, PPB3, PPB4, PPB5, PPB8, PPB9, PPB10, PPB11, and PPB12) were selected based on their in vitro plant growth promoting attributes and antagonism of phytopathogens. Phylogenetic analysis of 16S rRNA sequences identified these isolates as new strains of Pseudomonas stutzeri, Bacillus subtilis, Stenotrophomonas maltophilia, and Bacillus amyloliquefaciens. The selected isolates produced high levels (26.78–51.28 μg mL-1) of indole-3-acetic acid, while significant acetylene reduction activities (1.79–4.9 μmole C2H4 mg-1 protein h-1) were observed in eight isolates. Cucumber plants grown from seeds that were treated with these PGPR strains displayed significantly higher levels of germination, seedling vigour, growth, and N content in root and shoot tissue compared to non-treated control plants. All selected isolates were able to successfully colonize the cucumber roots. Moreover, treating cucumber seeds with these isolates significantly suppressed Phytophthora crown rot caused by Phytophthora capsici, and characteristic morphological alterations in P. capsici hyphae that grew toward PGPR colonies were observed. Since these PGPR inoculants exhibited multiple traits beneficial to the host plants, they may be applied in the development of new, safe, and effective seed treatments as an alternative to chemical fungicides. PMID:26869996

Development and evaluation of the mallard duck as a model to investigate the immunotoxicity of environmental chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowles, J.R.

Studies were conducted to characterize the mallard duck (Anas platyrhyncos) as a model for evaluating the immunotoxic effects of environmental chemicals. A battery of immunotoxicity tests was validated for the mallard, including natural killer cell (NKC) activity, lymphocyte mitogenesis, antibody titers to sheep erythrocytes, peripheral differential leukocyte counts, macrophage phagocytosis and prostaglandin-E[sub 2] (PGE2) production. To investigate potential hormonal-immune axes, dexamethasone (DEX), methimazole, and thyroxine (T4) were used to study the influence of glucocorticoid excess, hypo-, and hyperthyroidism on immunity, respectively. Subsequently, the effects of polychlorinated biphenyls (PCBs, Aroclor 1254) on immune, endocrine, and hepatic cytochrome-P450 function were evaluated andmore » interpreted using results from the endocrine/immune studies. Results of these studies showed that antibody production was susceptible to suppression by DEX at doses which also caused significant changes in clinical plasma biochemistry values. NKC activity was enhanced by exposure to DEX in vivo, a phenomenon due to the inhibition of PGE2 production by adherent peripheral blood cells by DEX and mimicked in vitro with addition of indomethacin or DEX. Macrophage phagocytosis was significantly suppressed by DEX in vitro. Macrophage production of PGE2 ex vivo was suppressed in birds treated with DEX. In contrast to DEX, T4 or methimazole treatment elicited only slight physiologic changes in plasma albumin and cholesterol levels. No immune/thyroid axis was observed in mallards. Exposure to Aroclor 1254 induced significant hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase activities in addition to increasing total cytochrome P450 content, but did not affect immune function, plasma corticosterone, or clinical biochemistry values. Total triiodothyronine, but not T4, was dose-dependently suppressed by PCB treatment.« less

MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells.

PubMed

Zhang, W; Bai, W; Zhang, W

2014-08-01

Curcumin, a natural phytochemical, exhibits potent anticancer activities. Here, we sought to determine the molecular mechanisms underlying the cytotoxic effects of curcumin against human non-small cell lung cancer (NSCLC) cells. MTT assay and annexin-V/PI staining were used to analyze the effects of curcumin on the proliferation and apoptosis of A549 cells. The expression of microRNA-21 in curcumin-treated A549 cells was measured by quantitative real-time polymerase chain reaction assay. The protein level of phosphatase and tensin homolog (PTEN), a putative target of microRNA-21, was determined by Western blot analysis. Transfection of A549 cells with microRNA-21 mimic or PTEN small interfering RNA was performed to modulate the expression of microRNA-21 and PTEN under the treatment of curcumin. Curcumin at 20-40 μM inhibited cell proliferation and induced apoptosis in A549 cells. Curcumin treatment produced a dose-dependent and significant (P < 0.05) suppression of microRNA-21 expression, compared to untreated A549 cells. Moreover, the protein level of PTEN, a putative target of microRNA-21, was significantly elevated in curcumin-treated A549 cells, as determined by Western blot analysis. Transfection of A549 cells with microRNA-21 mimic or PTEN small interfering RNA significantly (P < 0.05) reversed the growth suppression and apoptosis induction by curcumin, compared to corresponding controls. Our data suggest a novel molecular mechanism in which inhibition of microRNA-21 and upregulation of PTEN mediate the anticancer activities of curcumin in NSCLC cells. Suppression of microRNA-21 may thus have therapeutic benefits against this malignancy.

Dynamics of Relaxation Processes of Spontaneous Otoacoustic Emissions

NASA Astrophysics Data System (ADS)

Murphy, William James

The dynamical response of spontaneous otoacoustic emissions (SOAEs) to suppression by ipsilateral pulsed external tones of different frequencies and levels is investigated in nine female subjects under normal conditions and in four female subjects during periods when aspirin is being administered. A simple Van der Pol limit-cycle oscillator driven by an external tone is used as an interpretive model. Typical results for both the onset of, and recovery from suppression yield 1/r_1 (where -r_1 is the negative linear component of the damping function) in the range of 2-25 msec. In accordance with the predictions of the model: (a) the relaxation time for the onset of suppression increases with the amount of suppression induced by the external tone, (b) the values of r _1 and the amplitudes of the unsuppressed emissions exhibit an inverse correlation, (c) the values inferred for r_1 are not significantly dependent on the frequency of the pulsed suppressor tone and (d) the inferred r_1 values are not significantly dependent upon the amount of suppression. In investigations involving subjects under aspirin administration, the changes in the relaxation time constants indicate that the main effect of aspirin administration is to reduce the negative damping parameter r_1. The salicylate is apparently not metabolized in some subjects whose emissions are negligibly affected by aspirin administration. A modification of the single-oscillator model is used to describe pulsed suppression data obtained from a primary SOAE (2545 Hz) which is suppressed by a neighboring secondary emission (2895 Hz). The response of the SOAE amplitude during pulsed suppression is modeled by a pair of Van der Pol limit-cycle oscillators with the primary oscillator linearly coupled to the displacement of the secondary higher-frequency one. The relaxation time constants for the onset of, and recovery from, suppression are 4.5 and 4.8 msec, respectively, for the primary SOAE and 7.5 and 10.5 msec for the secondary one. Aspirin administration reduces the magnitude of the overshoot by reducing the level of the higher frequency SOAE and thereby eliminating the suppression of the lower frequency one.

Parallel Regulation of Memory and Emotion Supports the Suppression of Intrusive Memories

PubMed Central

Anderson, Michael C.

2017-01-01

Intrusive memories often take the form of distressing images that emerge into a person's awareness, unbidden. A fundamental goal of clinical neuroscience is to understand the mechanisms allowing people to control these memory intrusions and reduce their emotional impact. Mnemonic control engages a right frontoparietal network that interrupts episodic retrieval by modulating hippocampal activity; less is known, however, about how this mechanism contributes to affect regulation. Here we report evidence in humans (males and females) that stopping episodic retrieval to suppress an unpleasant image triggers parallel inhibition of mnemonic and emotional content. Using fMRI, we found that regulation of both mnemonic and emotional content was driven by a shared frontoparietal inhibitory network and was predicted by a common profile of medial temporal lobe downregulation involving the anterior hippocampus and the amygdala. Critically, effective connectivity analysis confirmed that reduced amygdala activity was not merely an indirect consequence of hippocampal suppression; rather, both the hippocampus and the amygdala were targeted by a top-down inhibitory control signal originating from the dorsolateral prefrontal cortex. This negative coupling was greater when unwanted memories intruded into awareness and needed to be purged. Together, these findings support the broad principle that retrieval suppression is achieved by regulating hippocampal processes in tandem with domain-specific brain regions involved in reinstating specific content, in an activity-dependent fashion. SIGNIFICANCE STATEMENT Upsetting events sometimes trigger intrusive images that cause distress and that may contribute to psychiatric disorders. People often respond to intrusions by suppressing their retrieval, excluding them from awareness. Here we examined whether suppressing aversive images might also alter emotional responses to them, and the mechanisms underlying such changes. We found that the better people were at suppressing intrusions, the more it reduced their emotional responses to suppressed images. These dual effects on memory and emotion originated from a common right prefrontal cortical mechanism that downregulated the hippocampus and amygdala in parallel. Thus, suppressing intrusions affected emotional content. Importantly, participants who did not suppress intrusions well showed increased negative affect, suggesting that suppression deficits render people vulnerable to psychiatric disorders. PMID:28559378

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis

PubMed Central

Kim, Ji H.; Gupta, Subash C.; Park, Byoungduck; Yadav, Vivek R.; Aggarwal, Bharat B.

2012-01-01

Scope The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Methods and results Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Conclusion Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. PMID:22147524

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

PubMed

Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

2012-03-01

The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Can sleep quality and wellbeing be improved by changing the indoor lighting in the homes of healthy, elderly citizens?

PubMed Central

Sander, Birgit; Markvart, Jakob; Kessel, Line; Argyraki, Aikaterini; Johnsen, Kjeld

2015-01-01

The study investigated the effect of bright blue-enriched versus blue-suppressed indoor light on sleep and wellbeing of healthy participants over 65 years. Twenty-nine participants in 20 private houses in a uniform settlement in Copenhagen were exposed to two light epochs of 3 weeks with blue-enriched (280 lux) and 3 weeks blue-suppressed (240 lux) indoor light or vice versa from 8 to 13 pm in a randomized cross-over design. The first light epoch was in October, the second in November and the two light epochs were separated by one week. Participants were examined at baseline and at the end of each light epoch. The experimental indoor light was well tolerated by the majority of the participants. Sleep duration was 7.44 (95% CI 7.14–7.74) hours during blue-enriched conditions and 7.31 (95% CI 7.01–7.62) hours during blue-suppressed conditions (p = 0.289). Neither rest hours, chromatic pupillometry, nor saliva melatonin profile showed significant changes between blue-enriched and blue-suppressed epochs. Baseline Pittsburgh Sleep Quality Index (PSQI) was significantly worse in females; 7.62 (95% CI 5.13–10.0) versus 4.06 (95% CI 2.64–5.49) in males, p = 0.009. For females, PSQI improved significantly during blue-enriched light exposure (p = 0.007); no significant changes were found for males. The subjective grading of indoor light quality doubled from participants habitual indoor light to the bright experimental light, while it was stable between light epochs, although there were clear differences between blue-enriched and blue-suppressed electrical light conditions imposed. Even though the study was carried out in the late autumn at northern latitude, the only significant difference in Actiwatch-measured total blue light exposure was from 8 to 9 am, because contributions from blue-enriched, bright indoor light were superseded by contributions from daylight. PMID:26181467

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosomemore » protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.« less

Suppressing effects of glucan on micronuclei induced by cyclophosphamide in mice.

PubMed

Chorvatovicová, D; Navarová, J

1992-07-01

The effect of pretreatment with carboxymethylglucan (CMG) on the frequency of micronuclei induced by cyclophosphamide administration in mice was evaluated. Two doses of CMG (50 mg/kg body weight) injected either intraperitoneally 24 h or intravenously 1 h prior to two cyclophosphamide administrations (80 mg/kg) significantly decreased the frequency of micronucleated PCE in bone marrow. Of two evaluated derivatives of carboxymethylglucan, the K3 derivative was most efficient. The results show that it is possible to achieve a suppressive effect of soluble carboxymethylglucan prepared from Saccharomyces cerevisiae against cyclophosphamide mutagenicity. The notion may be useful for glucan's effects against pharmacocarcinogenesis. Therapeutic application of glucan with cyclophosphamide therapy may provide a remarkable decrease of the secondary tumour risk. The utilization of these results for human patients needs to be considered.

Isotope and fast ions turbulence suppression effects: Consequences for high-β ITER plasmas

NASA Astrophysics Data System (ADS)

Garcia, J.; Görler, T.; Jenko, F.

2018-05-01

The impact of isotope effects and fast ions on microturbulence is analyzed by means of non-linear gyrokinetic simulations for an ITER hybrid scenario at high beta obtained from previous integrated modelling simulations with simplified assumptions. Simulations show that ITER might work very close to threshold, and in these conditions, significant turbulence suppression is found from DD to DT plasmas. Electromagnetic effects are shown to play an important role in the onset of this isotope effect. Additionally, even external ExB flow shear, which is expected to be low in ITER, has a stronger impact on DT than on DD. The fast ions generated by fusion reactions can additionally reduce turbulence even more although the impact in ITER seems weaker than in present-day tokamaks.

Antiangiogenic effect of betaine on pathologic retinal neovascularization via suppression of reactive oxygen species mediated vascular endothelial growth factor signaling.

PubMed

Park, Sung Wook; Jun, Hyoung Oh; Kwon, Euna; Yun, Jun-Won; Kim, Jin Hyoung; Park, Young-Jun; Kang, Byeong-Cheol; Kim, Jeong Hun

2017-03-01

Reactive oxygen species (ROS) as well as vascular endothelial growth factor (VEGF) play important roles in pathologic retinal neovascularization. We investigated whether betaine inhibits pathologic retinal neovascularization in a mouse model of oxygen induced retinopathy (OIR). Betaine was intravitreally injected in OIR mice at postnatal day (P) 14. At P17, the neovascular tufts area in OIR retina was analyzed. Intravitreal injection of betaine (200μM) effectively reduced the neovascular tufts area in OIR retina (68.0±6.7% of the control eyes, P<0.05). Even in a high concentration (2mM), betaine never induced any retinal toxicity or cytotoxicity. Betaine significantly inhibited VEGF-induced proliferation, migration, and tube formation in human retinal microvascular endothelial cells (HRMECs). Betaine suppressed VEGF-induced VEGFR-2, Akt and ERK phosphorylation in HRMECs. In human brain astrocytes, betaine reduced tBH-induced ROS production, and subsequently attenuated tBH-induced VEGFA mRNA transcription via suppression of ROS. Our data suggest that betaine has an anti-angiogenic effect on pathologic retinal neovascularization via suppression of ROS mediated VEGF signaling. Betaine could be a potent anti-angiogenic agent to treat pathologic retinal neovascularization. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of tributyltin on early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes).

PubMed

Horie, Yoshifumi; Yamagishi, Takahiro; Shintaku, Yoko; Iguchi, Taisen; Tatarazako, Norihisa

2018-07-01

Tributyltin, an organotin compound, was used worldwide as an antifouling agent in aquatic environments and there has been much concern about the toxicological and ecotoxicological properties of organotin compounds. Even though it has been prohibited worldwide, tributyltin is still detected at low concentrations in aquatic environments. Here we investigated the effects of tributyltin on the early life-stage, reproduction, and gonadal sex differentiation in Japanese medaka (Oryzias latipes). In adults, exposure to tributyltin at 3.82 μg/L suppressed fecundity and fertility and increased mortality. At 10.48 μg/L all medaka died by the sixth day of exposure. Exposure to tributyltin during early life-stages induced no significant differences in mortality or embryonic development, but growth was suppressed in groups exposed to 0.13 and 0.68 μg/L. Furthermore, there was no abnormal gonadal development in Japanese medaka exposed to tributyltin. These results provide evidence of the negative effects of tributyltin on reproduction in a teleost fish. Tributyltin did not affect gonadal sex differentiation in Japanese medaka, but fecundity and fertility were suppressed, although it is not clear whether this suppression resulted from the endocrine-disrupting action of tributyltin or its toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Forward velocity effects on fan noise and the suppression characteristics of advanced inlets as measured in the NASA-Ames 40 by 80 foot wind tunnel

NASA Technical Reports Server (NTRS)

Moore, M. T.

1980-01-01

Forward velocity effects on the forward radiated fan noise and on the suppression characteristics of three advanced inlets relative to a baseline cylindrical inlet were measured in the NASA Ames Research Center 40 x 80 foot Wind Tunnel. A modified JT15D turbofan engine in a quiet nacelle was the source of fan noise; the advanced inlets were a Conventional Takeoff/Landing (CTOL) hybrid inlet, a Short Takeoff/Landing (STOL) hybrid inlet, and a treated deflector inlet. Also measured were the static to flight effects on the fan noise of canting the baseline inlet 4 deg downward to simulate typical wing mounted turbofan engines. The CTOL hybrid inlet suppressed the high tip speed fan noise as much as 18 PNdB on a 61 m (200 ft) sideline scaled to a CF6 size engine while the STOL hybrid inlet suppressed the low tip speed fan noise as much as 13 PNdB on a 61 m (200 ft) sideline scaled to a OCSEE size engine. The deflector inlet suppressed the high tip speed fan noise as much as 13 PNdB at 61 m (200 ft) overhead scaled to a CF6 size engine. No significant changes in fan noise suppression for the CTOL and STOL hybrid inlets occurred for forward velocity changes above 21 m/s (68 ft/s) or for angle of attack changes up to 15 deg. However, changes in both forward velocity and angle of attack changed the deflector inlet noise unpredictably due to the asymmetry of the inlet flow field into the fan.

Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT.

PubMed

Fujiwara, Yukio; Kiyota, Naoko; Hori, Masaharu; Matsushita, Sayaka; Iijima, Yoko; Aoki, Koh; Shibata, Daisuke; Takeya, Motohiro; Ikeda, Tsuyoshi; Nohara, Toshihiro; Nagai, Ryoji

2007-11-01

We recently identified esculeoside A, a new spirosolane-type glycoside, with a content in tomatoes that is 4-fold higher than that of lycopene. In the present study, we examined the effects of esculeoside A and esculeogenin A, a new aglycon of esculeoside A, on foam cell formation in vitro and atherogenesis in apoE-deficient mice. Esculeogenin A significantly inhibited the accumulation of cholesterol ester (CE) induced by acetylated low density lipoprotein (acetyl-LDL) in human monocyte-derived macrophages (HMDM) in a dose-dependent manner without inhibiting triglyceride accumulation, however, it did not inhibit the association of acetyl-LDL to the cells. Esculeogenin A also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-coenzymeA (CoA): cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that esculeogenin A suppresses the activity of both ACAT-1 and ACAT-2. Furthermore, esculeogenin A prevented the expression of ACAT-1 protein, whereas that of SR-A and SR-BI was not suppressed. Oral administration of esculeoside A to apoE-deficient mice significantly reduced the levels of serum cholesterol, triglycerides, LDL-cholesterol, and the areas of atherosclerotic lesions without any detectable side effects. Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis.

Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma.

PubMed

Mehta, Amit K; Singh, Bhanu P; Arora, Naveen; Gaur, Shailendra N

2010-07-01

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction and increased bronchial hyperreactivity (BHR). Therapeutic interventions reduce airway inflammation and relieve symptoms but associated with potential side effects that limit their usefulness. The present study was undertaken to assess the effect of choline on immune inflammation and BHR in asthma subjects. The patients of asthma (n=76) were recruited and treated with choline supplement (1500 mg twice) or standard pharmacotherapy for 6 months in two groups. The patients were evaluated by clinical, immunologic and biochemical parameters. The treatment with choline showed significant reduction in symptom/drug score and improvement in PC(20) FEV1 compared to baseline or standard pharmacotherapy (p<0.01). Choline therapy significantly reduced IL-4, IL-5 and TNF-alpha level as compared to baseline or standard pharmacotherapy after 6 months (p<0.01). Blood eosinophil count and total IgE levels were reduced in both the treatment groups. Cysteinyl leukotriene and leukotriene B4 were suppressed significantly by choline treatment (p<0.01). This was accompanied by decreased 8-isoprostanes, a biomarker for oxidative stress after choline treatment (p<0.01). Choline therapy modulates immune inflammation and suppresses oxidative stress in asthma patients. It can be used as an adjunct therapy for asthma patients. Copyright 2009 Elsevier GmbH. All rights reserved.

Effect of plasma nitriding on the structural stability and hydrogen absorption capability of Pd-coated Nb during thermal treatment

NASA Astrophysics Data System (ADS)

Ohtsu, Naofumi; Kozuka, Taro; Shibata, Yuga; Yamane, Misao

2017-11-01

Plasma nitriding was explored for improving the thermal stability of a composite hydrogen permeable membrane comprising a Pd coating on Nb substrate. A NbN intermediate layer was formed on the Nb substrate, and the progress of interdiffusion and deterioration of hydrogen absorption behavior after a thermal treatment at 573 and 773 K, respectively, were investigated. The intermediate layer significantly suppressed the interdiffusion between the coating and the substrate. Furthermore, an increase in the NbN concentration of the intermediate layer enhanced the suppression efficiency. However, the hydrogen permeability of the intermediate layer was significantly low, and hence, an increase in NbN concentration further decreased the hydrogen permeability. We concluded that the nitride layer with a high NbN content was unsuitable as an intermediate layer owing to its low hydrogen permeability, while the partial nitride layer with a low NbN content was inefficient in suppressing the interdiffusion.

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice.

PubMed

Cong, Min; Zhao, Weihua; Liu, Tianhui; Wang, Ping; Fan, Xu; Zhai, Qingling; Bao, Xiaoli; Zhang, Dong; You, Hong; Kisseleva, Tatiana; Brenner, David A; Jia, Jidong; Zhuang, Hui

2017-08-01

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation.

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice

PubMed Central

Cong, Min; Zhao, Weihua; Liu, Tianhui; Wang, Ping; Fan, Xu; Zhai, Qingling; Bao, Xiaoli; Zhang, Dong; You, Hong; Kisseleva, Tatiana; Brenner, David A.; Jia, Jidong; Zhuang, Hui

2017-01-01

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28–30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation. PMID:28627620

Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid.

PubMed

Liu, Hsien; Wang, Shih-Han; Chen, Shin-Cheh; Chen, Ching-Ying; Lo, Jo-Lin; Lin, Tsun-Mei

2016-11-25

CD4 + CD25 + regulatory T (Treg) cells suppress tumor immunity by inhibiting immune cells. Manipulation of Treg cells represents a new strategy for cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, inhibits the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed Treg-cell activity and activated inflammatory Th17 cells. However, the interaction between ZA and Treg cells remained unclear. This study investigated the immune modulation of Treg cells by ZA. Flow cytometry was used to analyze the phenotypic and immunosuppressive characteristics of Treg cells treated with ZA. Chemotactic migration was evaluated using transwell assays. Quantitative real-time PCR (qRT-PCR) was used to investigate the effect of ZA on the expression of suppressive molecules by Treg cells. Proliferation of isolated Treg cells in culture was inhibited by ZA, although ZA did not induce apoptosis. qRT-PCR and flow cytometry showed that ZA significantly downregulated the expression of CCR4, CTLA4, PD-1 and RANKL on Treg cells. Chemotactic migration and immunosuppressive functions were also significantly attenuated in Treg cells pretreated with ZA, and these effects were dose-dependent. Co-culture with Treg cells significantly increased the migration rate of breast cancer cells, while pretreatment of Treg cells with ZA attenuated this effect. Our findings demonstrated that ZA acted as an immune modulator by significantly inhibiting the expansion, migration, immunosuppressive function and pro-metastatic ability of Treg cells. Immunomodulation of Treg cells by ZA represents a new strategy for cancer therapy.

Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

PubMed

Blumstein, Gideon W; Parsa, Arya; Park, Anthony K; McDowell, Beverly L P; Arroyo-Mendoza, Melissa; Girguis, Marie; Adler-Moore, Jill P; Olson, Jon; Buckley, Nancy E

2014-01-01

Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5) C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10(4) C. albicans on day 2, followed by a higher challenge with 5×10(5) C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

PubMed

Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

2016-01-01

Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).

PubMed

Majdalawieh, Amin F; Carr, Ronald I

2010-04-01

Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.

Alleviative effects of s-allyl cysteine and s-ethyl cysteine on MCD diet-induced hepatotoxicity in mice.

PubMed

Lin, Chun-che; Yin, Mei-chin; Liu, Wen-hu

2008-11-01

Alleviative effects of s-allyl cysteine (SAC) and s-ethyl cysteine (SEC) upon methionine and choline deficient (MCD) diet-induced hepatotoxicity in mice were examined. SAC or SEC at 1g/L was added into drinking water for 7 weeks with MCD diet. MCD feeding significantly increased hepatic triglyceride and cholesterol levels, and elevated the activity of glucose-6-phosphate dehydrogenase (G6PDH), malic enzyme, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P < 0.05). However, the intake of SAC or SEC significantly decreased hepatic triglyceride accumulation, and reduced G6PDH and FAS activities (P < 0.05). MCD feeding significantly lowered serum and hepatic glutathione (GSH) levels, increased malondialdehyde (MDA) and oxidized glutathione (GSSG) formation, and suppressed the activity and mRNA expression of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (P < 0.05). The intake of SAC or SEC significantly increased serum and hepatic GSH levels, decreased MDA and GSSG formation, restored the activity and mRNA expression of GPX, SOD and catalase (P < 0.05). MCD feeding significantly enhanced the mRNA expression of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, matrix metalloproteinases-9 (MMP-9) and collagen-alpha1 (P < 0.05). The intake of SAC and SEC significantly blunted the mRNA expression of IL-1beta, IL-6, TNF-alpha, TGF-beta1 and collagen-alpha1 (P < 0.05). SEC was greater than SAC in suppressing IL-6 and TNF-alpha expression (P < 0.05), but SAC was greater than SEC in suppressing collagen-alpha1 and TGF-beta1 expression (P < 0.05). These data suggest that SAC and SEC are potent agents against MCD-induced hepatotoxicity.

Efficiency droop suppression of distance-engineered surface plasmon-coupled photoluminescence in GaN-based quantum well LEDs

NASA Astrophysics Data System (ADS)

Li, Yufeng; Wang, Shuai; Su, Xilin; Tang, Weihan; Li, Qiang; Guo, Maofeng; Zhang, Ye; Zhang, Minyan; Yun, Feng; Hou, Xun

2017-11-01

Ag coated microgroove with extreme large aspect-ratio of 500:1 was fabricated on p-GaN capping layer to investigate the coupling behavior between quantum wells and surface plasmon in highly spatial resolution. Significant photoluminescence enhancement was observed when the distance between Ag film and QWs was reduced from 220 nm to about 20 nm. A maximum enhancement ratio of 18-fold was achieved at the groove bottom where the surface plasmonic coupling was considered the strongest. Such enhancement ratio was found highly affected by the excitation power density. It also shows high correlation to the internal quantum efficiency as a function of coupling effect and a maximum Purcell Factor of 1.75 was estimated at maximum coupling effect, which matches number calculated independently from the time-resolved photoluminescence measurement. With such Purcell Factor, the efficiency was greatly enhanced and the droop was significantly suppressed.

(E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-κB signaling pathway.

PubMed

Li, Xiuxia; Peng, Fei; Xie, Caifeng; Wu, Wenshuang; Han, Xiaolei; Chen, Lijuan

2013-12-01

Our previous report has shown a natural pyranochalcones-derived compound, (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one (5b), that exerted protection against carrageenan-induced hind paw edema and adjuvant-induced arthritis. In this study, collagen-induced arthritis (CIA) model was used to further examine the anti-arthritic effects of 5b in vivo; the underlying molecular mechanisms of action were also investigated using a murine monocytic cell line, RAW264.7 cells. Here we showed that oral administration of 5b (20mg/kg) significantly suppressed the progression of arthritis. Improvement in disease severity was accompanied by inhibition of CD68-positive cells in knee joint and reduced pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in serum. In vitro, 5b suppressed expressions of iNOS, cyclooxygenase-2 (COX-2), TNF-α, IL-6 and IL-1β as well as productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated macrophages. This compound also significantly suppressed LPS-induced NF-κB activation, including phosphorylation of I-κB, degradation of I-κB, and nuclear translocation of p65 and p50. Treatment with 5b also blocked LPS-induced expression of TLR4 remarkably, suppressed degradation of IRAKs and phosphorylations of JNK and ERK, but had little effect to p38 kinase activation. These findings indicated that 5b might be a therapeutic agent for rheumatoid arthritis, and exerted an anti-inflammatory effect mainly through mediating TLR4, NF-κB and ERK/JNK signaling pathways in monocytes. © 2013.

I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties.

PubMed

Ma, Lingman; Qian, Lifen; Ying, Qidi; Zhang, Yan; Zhou, Changlin; Wu, Guanzhong

2017-01-15

Here, we investigated whether I 4 , which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE -/- mice were fed a Western diet and simultaneously administered I 4 , glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I 4 . The data indicated that I 4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I 4 , at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I 4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I 4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I 4 exerts potent inhibitory effects on atherosclerosis onset and development. Copyright © 2016. Published by Elsevier Ireland Ltd.

Perceived emotion suppression and culture: Effects on psychological well-being.

PubMed

Kwon, Heewon; Kim, Young-Hoon

2018-04-03

Whether the negative effects of emotion suppression on psychological well-being are applicable cross-culturally is a long-debated topic. The present study attempted to shed light on this debate, focusing on the effects of perceived emotion suppression and examining the psychological processes leading from perceived emotion suppression to lower psychological well-being. We used a scale manipulation to lead 196 American and 213 Chinese participants to perceive themselves as having suppressed their emotions to a greater or lesser extent and then measured their life satisfaction. As expected, both the American and Chinese participants reported lower life satisfaction in the high-suppression condition than in the low-suppression condition; this negative effect was mediated by positive affect and moderated by self-esteem. Specifically, perceived high emotion suppression decreased positive affect, which in turn led to lower well-being. This effect was observed only for those with low self-esteem, but the patterns and mechanisms were consistent cross-culturally. © 2018 International Union of Psychological Science.

Ecophysiological responses of two herbaceous species to prescribed burning, alone or in combination with overstory thinning.

PubMed

Huang, Jianjun; Boerner, Ralph E J; Rebbeck, Joanne

2007-05-01

The oak-rich deciduous forests of the central Appalachian Mountains of eastern North America have changed significantly since the onset of effective fire suppression early in the 20th century. Those changes have resulted in progressively decreasing light and nutrient supplies to herbaceous perennial understory species. Application of ecological restoration treatments such as reintroduction of frequent dormant-season fire and overstory thinning to pre-suppression density often increase light, soil temperature and moisture, and short-term nutrient availability to pre-suppression levels. To persist in this environment, perennial understory herbs must be able to acclimate phenotypically to the very different resource supply combinations present with and without fire suppression. As part of a larger study of the response of the long-lived herbaceous perennials Desmodium nudiflorum and Panicum boscii to ecosystem restoration treatments in Ohio mixed-oak forests, this study examined the ecophysiological effects of prescribed burning (B) and the combination of burning and thinning (T + B) in mixed-oak forests in southern Ohio. Control (C) plants had significantly lower maximum photosynthetic rate (A(max)) than those in the treated plots. The enhancement of A(max) averaged 26.7% and 52.7% in the B and T + B treatments, respectively. Plants from the T + B plots had higher quantum yield, stomatal conductance, and photosynthetic nutrient use efficiency than B and C plants. B plants had greater intrinsic water use efficiency (WUE) than plants in the C or T + B treatments. Light saturation point (LSP), light compensation point (LCP), and "dark" respiration (DR) did not differ among treatments. Photosynthetic parameters did vary significantly between the species, but no significant treatment × species interactions were detected. Our results support the hypothesis that prescribed burning, especially when combined with overstory thinning, in these perennial herbs can result in phenotypic acclimation characterized by enhanced photosynthetic performance.

Astragalus polysaccharide suppresses palmitate-induced apoptosis in human cardiac myocytes: the role of Nrf1 and antioxidant response

PubMed Central

Zhang, Ji; Gu, Jian-Yun; Chen, Zhi-Song; Xing, Kai-Chen; Sun, Bing

2015-01-01

Objective: Previous studies have shown that Astragalus polysaccharides (APS) can be used to ameliorate cardiotoxicity due to chemotherapy and improve the cardiac function. However, the mechanism by which APS mediate this effect is unclear. In the present study, the effects of APS, which suppressed ROS-mediated apoptosis through Nrf1 accumulation in human cardiac myocytes (HCMs), was investigated. Methods: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Nrf1 gene was overexpressed using a lentiviral expression vector in HCMs in vitro, in order to explore the mechanism by which the Nrf1 promoted cell growth. Results: CCK8 and Annexin V-PI double-labeling showed that PAL induced cell death in a concentration-dependent manner, and suppressed HCMs proliferation. The combination PAL with APS was significantly decreased the percentage of the early phase of apoptosis cells. ROS levels were increased in HCMs by exposure to PAL. APS treatment significantly inhibited generation of ROS in response to palmitate. Moreover, PAL administration significantly decreased the mRNA and proteins expression of Bcl-2 as well as increased the mRNA expression of BAX and the protein expression of caspase-3 and caspase-8 as compare to those of control group, but APS treatment could reverse PA-induced HCMs apoptosis. The levels of reactive oxygen species (ROS), which was an oxidative stress marker, was significantly increased in cardiomyocytes by exposure to PAL, but overexpressing Nrf1 could ameliorate ROS-induced cardiomyocyte toxicity and increase the expression of SOD1 and SOD2 in HCMs by overexpressing Nrf1. Conclusions: This study demonstrated that the PAL could induce HCMs apoptosis. However, APS could reverse PAL-induced cardiomyocyte toxicity, at least partially, through suppression ROS and Nrf1 accumulation in HCMs. PMID:26045757

Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13–Suppressed Elastin in Airway Fibroblasts in Asthma

PubMed Central

Slade, David; Church, Tony D.; Francisco, Dave; Heck, Karissa; Sigmon, R. Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L.; Que, Loretta; Sunday, Mary E.; Kraft, Monica

2016-01-01

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert’s resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13–induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13–induced suppression of ELN expression in airway fibroblasts. PMID:26074138

Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

PubMed

Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

2016-01-01

Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts.

Astragalus polysaccharide suppresses palmitate-induced apoptosis in human cardiac myocytes: the role of Nrf1 and antioxidant response.

PubMed

Zhang, Ji; Gu, Jian-Yun; Chen, Zhi-Song; Xing, Kai-Chen; Sun, Bing

2015-01-01

Previous studies have shown that Astragalus polysaccharides (APS) can be used to ameliorate cardiotoxicity due to chemotherapy and improve the cardiac function. However, the mechanism by which APS mediate this effect is unclear. In the present study, the effects of APS, which suppressed ROS-mediated apoptosis through Nrf1 accumulation in human cardiac myocytes (HCMs), was investigated. The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Nrf1 gene was overexpressed using a lentiviral expression vector in HCMs in vitro, in order to explore the mechanism by which the Nrf1 promoted cell growth. CCK8 and Annexin V-PI double-labeling showed that PAL induced cell death in a concentration-dependent manner, and suppressed HCMs proliferation. The combination PAL with APS was significantly decreased the percentage of the early phase of apoptosis cells. ROS levels were increased in HCMs by exposure to PAL. APS treatment significantly inhibited generation of ROS in response to palmitate. Moreover, PAL administration significantly decreased the mRNA and proteins expression of Bcl-2 as well as increased the mRNA expression of BAX and the protein expression of caspase-3 and caspase-8 as compare to those of control group, but APS treatment could reverse PA-induced HCMs apoptosis. The levels of reactive oxygen species (ROS), which was an oxidative stress marker, was significantly increased in cardiomyocytes by exposure to PAL, but overexpressing Nrf1 could ameliorate ROS-induced cardiomyocyte toxicity and increase the expression of SOD1 and SOD2 in HCMs by overexpressing Nrf1. This study demonstrated that the PAL could induce HCMs apoptosis. However, APS could reverse PAL-induced cardiomyocyte toxicity, at least partially, through suppression ROS and Nrf1 accumulation in HCMs.

Reversible beam heater for suppression of microbunching instability by transverse gradient undulators

NASA Astrophysics Data System (ADS)

Liu, Tao; Qin, Weilun; Wang, Dong; Huang, Zhirong

2017-08-01

The microbunching instability driven by beam collective effects in a linear accelerator of a free-electron laser (FEL) facility significantly degrades the electron beam quality and FEL performance. A conventional method to suppress this instability is to introduce an additional uncorrelated energy spread by laser-electron interaction, which has been successfully operated in the Linac Coherent Light Source and Fermi@Elettra, etc. Some other ideas are recently proposed to suppress the instability without increasing energy spread, which could benefit the seeded FEL schemes. In this paper, we propose a reversible electron beam heater using two transverse gradient undulators to suppress the microbunching instability. This scheme introduces both an energy spread increase and a transverse-to-longitudinal phase space coupling, which suppress the microbunching instabilities driven by both longitudinal space charge and coherent synchrotron radiation before and within the system. Finally the induced energy spread increase and emittance growth are reversed. Theoretical analysis and numerical simulations are presented to verify the feasibility of the scheme and indicate the capability to improve the seeded FEL radiation performance.

BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling

PubMed Central

Vin, Harina; Ojeda, Sandra S; Ching, Grace; Leung, Marco L; Chitsazzadeh, Vida; Dwyer, David W; Adelmann, Charles H; Restrepo, Monica; Richards, Kristen N; Stewart, Larissa R; Du, Lili; Ferguson, Scarlett B; Chakravarti, Deepavali; Ehrenreiter, Karin; Baccarini, Manuela; Ruggieri, Rosamaria; Curry, Jonathan L; Kim, Kevin B; Ciurea, Ana M; Duvic, Madeleine; Prieto, Victor G; Ullrich, Stephen E; Dalby, Kevin N; Flores, Elsa R; Tsai, Kenneth Y

2013-01-01

Vemurafenib and dabrafenib selectively inhibit the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase, resulting in high response rates and increased survival in melanoma. Approximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (cSCC) during therapy. The prevailing explanation for this is drug-induced paradoxical ERK activation, resulting in hyperproliferation. Here we show an unexpected and novel effect of vemurafenib/PLX4720 in suppressing apoptosis through the inhibition of multiple off-target kinases upstream of c-Jun N-terminal kinase (JNK), principally ZAK. JNK signaling is suppressed in multiple contexts, including in cSCC of vemurafenib-treated patients, as well as in mice. Expression of a mutant ZAK that cannot be inhibited reverses the suppression of JNK activation and apoptosis. Our results implicate suppression of JNK-dependent apoptosis as a significant, independent mechanism that cooperates with paradoxical ERK activation to induce cSCC, suggesting broad implications for understanding toxicities associated with BRAF inhibitors and for their use in combination therapies. DOI: http://dx.doi.org/10.7554/eLife.00969.001 PMID:24192036

Reversible beam heater for suppression of microbunching instability by transverse gradient undulators

DOE PAGES

Liu, Tao; Qin, Weilun; Wang, Dong; ...

2017-08-02

The microbunching instability driven by beam collective effects in a linear accelerator of a free-electron laser (FEL) facility significantly degrades the electron beam quality and FEL performance. A conventional method to suppress this instability is to introduce an additional uncorrelated energy spread by laser-electron interaction, which has been successfully operated in the Linac Coherent Light Source and Fermi@Elettra, etc. Some other ideas are recently proposed to suppress the instability without increasing energy spread, which could benefit the seeded FEL schemes. In this paper, we propose a reversible electron beam heater using two transverse gradient undulators to suppress the microbunching instability.more » This scheme introduces both an energy spread increase and a transverse-to-longitudinal phase space coupling, which suppress the microbunching instabilities driven by both longitudinal space charge and coherent synchrotron radiation before and within the system. Finally the induced energy spread increase and emittance growth are reversed. In conclusion, theoretical analysis and numerical simulations are presented to verify the feasibility of the scheme and indicate the capability to improve the seeded FEL radiation performance.« less

Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells.

PubMed

Shin, Hee Soon; Satsu, Hideo; Bae, Min-Jung; Totsuka, Mamoru; Shimizu, Makoto

2017-02-20

Chlorogenic acid (CHA) and caffeic acid (CA) are phenolic compounds found in coffee, which inhibit oxidative stress-induced interleukin (IL)-8 production in intestinal epithelial cells, thereby suppressing serious cellular injury and inflammatory intestinal diseases. Therefore, we investigated the anti-inflammatory mechanism of CHA and CA, both of which inhibited hydrogen peroxide (H₂O₂)-induced IL-8 transcriptional activity. They also significantly suppressed nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ) transcriptional activity, nuclear translocation of the p65 subunit, and phosphorylation of IκB kinase (IKK). Additionally, upstream of IKK, protein kinase D (PKD) was also suppressed. Finally, we found that they scavenged H₂O₂-induced reactive oxygen species (ROS) and the functional moiety responsible for the anti-inflammatory effects of CHA and CA was the catechol group. Therefore, we conclude that the presence of catechol groups in CHA and CA allows scavenging of intracellular ROS, thereby inhibiting H₂O₂-induced IL-8 production via suppression of PKD-NF-κB signaling in human intestinal epithelial cells.

Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats.

PubMed

Shen, Ling; Wang, David Q-H; Lo, Chunmin C; Arnold, Myrtha; Tso, Patrick; Woods, Stephen C; Liu, Min

2015-12-01

Ginsenoside Rb1 (Rb1) reduces food intake in both lean and high-fat diet induced-obese rats; however, the sites and/or mediation of the eating-suppressive effect of Rb1 have not previously been identified. We hypothesized that intraperitoneally (ip) administered Rb1 exerts its anorectic action by enhancing sensitivity to satiation signals, such as cholecystokinin (CCK), and/or that it acts through vagal afferent nerves that relay the satiating signaling to the hindbrain. To test these hypotheses, we gave ip bolus doses of Rb1 (2.5-10.0mg/kg) and CCK-8 (0.125-4.0μg/kg) alone or in combination and assessed food intake in rats. Low doses of Rb1 (2.5mg/kg) or CCK-8 (0.125μg/kg) alone had no effect on food intake whereas higher doses did. When these subthreshold doses of Rb1 and CCK-8 were co-administered, the combination significantly reduced food intake relative to saline controls, and this effect was attenuated by lorglumide, a selective CCK1-receptor antagonist. Interestingly, lorglumide blocked food intake induced by an effective dose of CCK-8 alone, but not by Rb1 alone, suggesting that Rb1's anorectic effect is independent of the CCK1 receptor. To determine whether peripherally administered Rb1 suppresses feeding via abdominal vagal nerves, we evaluated the effect of ip Rb1 injection in subdiaphragmatic vagal deafferentation (SDA) and control rats. Rb1's effect on food intake was significantly attenuated in SDA rats, compared with that in SHAM controls. These data indicate that the vagal afferent system is the major pathway conveying peripherally administered Rb1's satiation signal. Copyright © 2015 Elsevier Inc. All rights reserved.

Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro.

PubMed

Yamane, Hitomi; Ihara, Setsunosuke; Kuroda, Masaaki; Nishikawa, Akio

2011-08-01

Larval-to-adult myogenic conversion occurs in the dorsal muscle but not in the tail muscle during Xenopus laevis metamorphosis. To know the mechanism for tail-specific suppression of adult myogenesis, response character was compared between adult myogenic cells (Ad-cells) and larval tail myogenic cells (La-cells) to a Sonic hedgehog (Shh) inhibitor, notochord (Nc) cells, and spinal cord (SC) cells in vitro. Cyclopamine, an Shh inhibitor, suppressed the differentiation of cultured Ad (but not La) cells, suggesting the significance of Shh signaling in promoting adult myogenesis. To test the possibility that Shh-producing axial elements (notochord and spinal cord) regulate adult myogenesis, Ad-cells or La-cells were co-cultured with Nc or SC cells. The results showed that differentiation of Ad-cells were strongly inhibited by Nc cells but promoted by SC cells. If Ad-cells were "separately" co-cultured with Nc cells without direct cell-cell interactions, adult differentiation was not inhibited but rather promoted, suggesting that Nc cells have two roles, one is a short-range suppression and another is a long-range promotion for adult myogenesis. Immunohistochemical analysis showed both notochord and spinal cord express the N-terminal Shh fragment throughout metamorphosis. The "spinal cord-promotion" and long-range effect by Nc cells on adult myogenesis is thus involved in Shh signaling, while the signaling concerning the short-range "Nc suppression" will be determined by future studies. Interestingly, these effects, "Nc suppression" and "SC promotion" were not observed for La-cells. Situation where the spinal cord/notochord cross-sectional ratio is quite larger in tadpole trunk than in the tail seems to contribute to trunk-specific promotion and tail-specific suppression of adult myogenesis during Xenopus metamorphosis.

Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques

PubMed Central

Del Prete, Gregory Q.; Shoemaker, Rebecca; Oswald, Kelli; Lara, Abigail; Trubey, Charles M.; Fast, Randy; Schneider, Douglas K.; Kiser, Rebecca; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Freemire, Brandi; Keele, Brandon F.; Estes, Jacob D.; Quiñones, Octavio A.; Smedley, Jeremy; Macallister, Rhonda; Sanchez, Rosa I.; Wai, John S.; Tan, Christopher M.; Alvord, W. Gregory; Hazuda, Daria J.; Piatak, Michael

2014-01-01

Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool. Ex vivo SAHA treatment of CD4+ T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration. In vivo virologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression for in vivo assessments of AIDS virus functional cure/eradication approaches. PMID:25182644

Effect-site half-time for burst suppression is longer than for hypnosis during anaesthesia with sevoflurane.

PubMed

Kennedy, R R; Minto, C; Seethepalli, A

2008-01-01

The relationship between measures of drug effect such as bispectral index (BIS) and end-tidal (ET) levels of anaesthetic agents is described by the 'effect site equilibrium half-time', t(1/2)(ke0). There are limited data available on sevoflurane t(1/2)(ke0) during routine anaesthesia and surgery. Preliminary observations suggested t(1/2)(ke0) for the degree of hypnosis as estimated by BIS is different from that for burst suppression of the electroencephalograph, occurring at 'deep' levels of anaesthesia. This study aimed to determine and compare t(1/2)(ke0) for these two 'effects'. Large changes in ET sevoflurane were produced in 13 subjects during surgery. ET sevoflurane, BIS, and burst suppression ratio (BSR) were recorded every 10 s. Data were divided into epochs with BIS>30 (BIS) or with BSR>10% (burst suppression). Using a non-parametric modelling technique, t(1/2)(ke0) was determined for each epoch. There were 36 'BIS' and 20 burst suppression zones. Mean (sd) t(1/2)(ke0) for BIS was 3.48 (1.12) min and for BSR 9.9 (6.4) min. In all subjects, t(1/2)(ke0) BIS

Movement suppression time-out for undesirable behavior in psychotic and severely developmentally delayed children.

PubMed

Rolider, A; Van Houten, R

1985-01-01

The effects of a movement suppression time-out, which involved punishing any movement or verbalization while a client is in the time-out area, were evaluated in four experiments. The first experiment examined the effects of a DRO procedure and movement suppression plus DRO in suppressing self-injurious behavior in a psychotic child in three different situations. In Experiment 2, the results of the previous experiment were replicated with two dangerous behaviors in a second psychotic child. In a third experiment, movement suppression plus DRO was compared with contingent restraint in reducing inappropriate poking behavior in two settings. The movement suppression procedure eliminated poking whereas contingent restraint had little effect. In the final experiment, movement suppression time-out alone was compared with exclusionary time-out alone and simple corner time-out alone. Self-stimulation occurred at high levels during the exclusionary and simple corner time-out procedures. Self-stimulation was either suppressed or reduced during movement suppression time-out. The movement suppression time-out procedure produced a larger reduction in the target behavior in all three children. The effectiveness of the movement suppression procedure was explained in terms of the suppression of self-stimulation while the time-out procedure was being applied.

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.

PubMed

Francis, Prudence A; Pagani, Olivia; Fleming, Gini F; Walley, Barbara A; Colleoni, Marco; Láng, István; Gómez, Henry L; Tondini, Carlo; Ciruelos, Eva; Burstein, Harold J; Bonnefoi, Hervé R; Bellet, Meritxell; Martino, Silvana; Geyer, Charles E; Goetz, Matthew P; Stearns, Vered; Pinotti, Graziella; Puglisi, Fabio; Spazzapan, Simon; Climent, Miguel A; Pavesi, Lorenzo; Ruhstaller, Thomas; Davidson, Nancy E; Coleman, Robert; Debled, Marc; Buchholz, Stefan; Ingle, James N; Winer, Eric P; Maibach, Rudolf; Rabaglio-Poretti, Manuela; Ruepp, Barbara; Di Leo, Angelo; Coates, Alan S; Gelber, Richard D; Goldhirsch, Aron; Regan, Meredith M

2018-06-04

Background In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. Methods Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. Results In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. Conclusions Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).

Efficacy of Four Nematicides Against the Reproduction and Development of Pinewood Nematode, Bursaphelenchus xylophilus

PubMed Central

Bi, Zhenzhen; Gong, Yanting; Huang, Xiaojuan; Yu, Hongshi; Bai, Liqun; Hu, Jiafu

2015-01-01

To understand the efficacy of emamectin benzoate, avermectin, milbemectin, and thiacloprid on the reproduction and development of Bursaphelenchus xylophilus, seven parameters, namely population growth, fecundity, egg hatchability, larval lethality, percent larval development, body size, and sexual ratio, were investigated using sublethal (LC20) doses of these compounds in the laboratory. Emamectin benzoate treatment led to a significant suppression in population size, brood size, and percent larval development with 411, 3.50, and 49.63%, respectively, compared to 20850, 24.33, and 61.43% for the negative control. The embryonic and larval lethality increased obviously from 12.47% and 13.70% to 51.37% and 75.30%, respectively. In addition, the body length was also significantly reduced for both males and females in the emamectin benzoate treatment. Avermectin and milbemectin were also effective in suppressing population growth by increasing larval lethality and reducing larval development, although they did not affect either brood size or embryonic lethality. Body length for both male and female worms was increased by avermectin. Thiacloprid caused no adverse reproductive effects, although it suppressed larval development. Sexual ratio was not affected by any of these four nematicides. Our results indicate that emamectin benzoate, milbemectin, and avermectin are effective against the reproduction of B. xylophilus. We think these three nematicides can be useful for the control of pine wilt disease. PMID:26170474

Efficacy of Four Nematicides Against the Reproduction and Development of Pinewood Nematode, Bursaphelenchus xylophilus.

PubMed

Bi, Zhenzhen; Gong, Yanting; Huang, Xiaojuan; Yu, Hongshi; Bai, Liqun; Hu, Jiafu

2015-06-01

To understand the efficacy of emamectin benzoate, avermectin, milbemectin, and thiacloprid on the reproduction and development of Bursaphelenchus xylophilus, seven parameters, namely population growth, fecundity, egg hatchability, larval lethality, percent larval development, body size, and sexual ratio, were investigated using sublethal (LC20) doses of these compounds in the laboratory. Emamectin benzoate treatment led to a significant suppression in population size, brood size, and percent larval development with 411, 3.50, and 49.63%, respectively, compared to 20850, 24.33, and 61.43% for the negative control. The embryonic and larval lethality increased obviously from 12.47% and 13.70% to 51.37% and 75.30%, respectively. In addition, the body length was also significantly reduced for both males and females in the emamectin benzoate treatment. Avermectin and milbemectin were also effective in suppressing population growth by increasing larval lethality and reducing larval development, although they did not affect either brood size or embryonic lethality. Body length for both male and female worms was increased by avermectin. Thiacloprid caused no adverse reproductive effects, although it suppressed larval development. Sexual ratio was not affected by any of these four nematicides. Our results indicate that emamectin benzoate, milbemectin, and avermectin are effective against the reproduction of B. xylophilus. We think these three nematicides can be useful for the control of pine wilt disease.

Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

NASA Astrophysics Data System (ADS)

Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

2016-01-01

Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis

PubMed Central

Shang, Runze; Zhou, Liang; Wang, Xing; Duan, Juanli; Ruan, Bai; Gao, Yuan; Dai, Bin; Qu, Shibin; Liu, Wei; Ding, Rui; Wang, Lin; Wang, Desheng; Dou, Kefeng

2016-01-01

MicroRNA-150 (miR-150) is frequently dysregulated in cancer and is involved in carcinogenesis and cancer progression. In this study, we found that miR-150 was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent noncancerous tissues. Low levels of miR-150 were significantly associated with worse clinicopathological characteristics and a poor prognosis for patients with HCC. miR-150 overexpression inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Further experiments indicated that Grb2-associated binding protein 1 (GAB1) was a direct target of miR-150 in HCC cells. In addition, GAB1 expression was increased in HCC tissues and inversely correlated with miR-150 levels. Knockdown of GAB1 mimicked the tumor-suppressive effects of miR-150 overexpression on HCC cells, whereas restoration of GAB1 expression partially abolished the inhibitory effects. Moreover, miR-150 overexpression decreased GAB1 expression, subsequently downregulated phospho-ERK1/2 and suppressed epithelial-mesenchymal-transition (EMT). These effects caused by miR-150 overexpression were alleviated by exogenous GAB1 expression. Taken together, this study demonstrates that miR-150 may be useful as a prognostic marker and that the identified miR-150-GAB1-ERK axis is a potential therapeutic target for HCC. PMID:26871477

Effect of the cross sectional aspect ratio on the flow past a twisted cylinder

NASA Astrophysics Data System (ADS)

Jung, Jae Hwan; Yoon, Hyun Sik

2013-11-01

The cross-flow around twisted cylinders of cross sectional aspect ratio (A/B) from 1 to 2.25 is investigated at a subcritical Reynolds number (Re) of 3000 using large eddy simulation (LES). The flow past a corresponding smooth and wavy cylinder is also calculated for comparison and validation against experimental data. The effect of twisted surface assessed in terms of the mean drag and root-mean-square (RMS) value of fluctuating lift. The shear layer of the twisted cylinder covering the recirculation region is more elongated than those of the smooth and the wavy cylinder. Successively, vortex shedding of the twisted cylinder is considerably suppressed, compared with those of the smooth and the wavy cylinder. The maximum drag reduction of up to 13% compared with a smooth cylinder is obtained at a certain cross sectional aspect ratio. The fluctuating lift coefficient of the twisted cylinder is also significantly suppressed. We found that the cross sectional cross sectional aspect ratio (A/B) plays an essential role in determining the vortical structures behind the twisted cylinder which has a significant effect on the reduction of the fluctuating lift and suppression of flow-induced vibration. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP (No. 2011-0030013).

Dietary lactosucrose suppresses influenza A (H1N1) virus infection in mice

PubMed Central

KISHINO, Eriko; TAKEMURA, Naho; MASAKI, Hisaharu; ITO, Tetsuya; NAKAZAWA, Masatoshi

2015-01-01

This study examined the effects of lactosucrose (4G-β-D-galactosylsucrose) on influenza A virus infections in mice. First, the effects of lactosucrose on fermentation in the cecum and on immune function were investigated. In female BALB/c mice, lactosucrose supplementation for 6 weeks promoted cecal fermentation and increased both secretory IgA (SIgA) levels in feces and total IgA and IgG2a concentrations in serum. Both the percentage of CD4+ T cells in Peyer’s patches and the cytotoxic activity of splenic natural killer (NK) cells increased significantly in response to lactosucrose. Next, we examined the effects of lactosucrose on low-dose influenza A virus infection in mice. After 2 weeks of dietary supplementation with lactosucrose, the mice were infected with low-dose influenza A virus. At 7 days post infection, a comparison with control mice showed that weight loss was suppressed, as were viral titers in the lungs. In the spleens of lactosucrose-fed mice, there was an increase in the percentage of NK cells. Lastly, mice fed lactosucrose were challenged with a lethal dose of influenza A virus. The survival rate of these mice was significantly higher than that of mice fed a control diet. These results suggested that lactosucrose supplementation suppresses influenza A virus infection by augmenting innate immune responses and enhancing cellular and mucosal immunity. PMID:26594606

Effect of hypoxia on metabolic rate, core body temperature, and c-fos expression in the naked mole rat.

PubMed

Nathaniel, Thomas I; Otukonyong, Effiong; Abdellatif, Ahmed; Soyinka, Julius O

2012-10-01

Recent investigations of hypoxia physiology in the naked mole rat have opened up an interesting line of research into the basic physiological and genomic alterations that accompany hypoxia survival. The extent to which such findings connect the effect of hypoxia to metabolic rate (O₂ consumption), core body temperature (Tb), and transcripts encoding the immediate early gene product (such as c-fos) under a constant ambient temperature (Ta) is not well known. We investigated this issue in the current study. Our first sets of experiments measured Tb and metabolic rates during exposure of naked mole rats to hypoxia over a constant Ta. Hypoxia significantly decreased metabolic rates in the naked mole rat. Although core Tb also decreased during hypoxia, the effect of hypoxia in suppressing core Tb was not significant. The second series of experiments revealed that c-fos protein and mRNA expression in the hippocampus neurons (CA1) increased in naked mole rats that were repeatedly exposed to 3% O₂ for 60 min per day for 5 days when compared to normoxia. Our findings provide evidence for the up-regulation of c-fos and suppression of metabolic rate in hypoxia tolerating naked mole rats under constant ambient temperature. Metabolic suppression and c-fos upregulation constitute part of the physiological complex associated with adaptation to hypoxia. Published by Elsevier Ltd.

Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer.

PubMed

Zang, Mingde; Hu, Lei; Zhang, Baogui; Zhu, Zhenglun; Li, Jianfang; Zhu, Zhenggang; Yan, Min; Liu, Bingya

2017-08-26

Gastric cancer is a great threat to the health of the people worldwide and lacks effective therapeutic regimens. Luteolin is one of Chinese herbs and presents in many fruits and green plants. In our previous study, we observed that luteolin inhibited cell migration and promoted cell apoptosis in gastric cancer. In the present study, luteolin significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) through decreasing cell migration and proliferation of HUVECs in a dose-dependent manner. Vasculogenic mimicry (VM) tubes formed by gastric cancer cells were also inhibited with luteolin treatment. To explore how luteolin inhibited tubes formation, ELISA assay for VEGF was performed. Both of the VEGF secretion from Hs-746T cells and HUVECs were significantly decreased subsequent to luteolin treatment. In addition, cell migration was increased with the interaction between gastric cancer cells and HUVECs in co-culture assays. However, the promoting effects were abolished subsequent to luteolin treatment. Furthermore, luteolin inhibited VEGF secretion through suppressing Notch1 expression in gastric cancer. Overexpression of Notch1 in gastric cancer cells partially rescued the effects on cell migration, proliferation, HUVECs tube formation, and VM formation induced by luteolin treatment. In conclusion, luteolin inhibits angiogenesis and VM formation in gastric cancer through suppressing VEGF secretion dependent on Notch1 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Statistical analysis of hail characteristics in the hail-protected western part of Croatia using data from hail suppression stations

NASA Astrophysics Data System (ADS)

Počakal, Damir; Štalec, Janez

In the continental part of Croatia, operational hail suppression has been conducted for more than 30 years. The current protected area is 25,177 km 2 and has about 492 hail suppression stations which are managed with eight weather radar centres. This paper present a statistical analysis of parameters connected with hail occurrence on hail suppression stations in the western part of protected area in 1981-2000 period. This analysis compares data of two periods with different intensity of hail suppression activity and is made as a part of a project for assessment of hail suppression efficiency in Croatia. Because of disruption in hail suppression system during the independence war in Croatia (1991-1995), lack of rockets and other objective circumstances, it is considered that in the 1991-2000 period, hail suppression system could not act properly. Because of that, a comparison of hail suppression data for two periods was made. The first period (1981-1990), which is characterised with full application of hail suppression technology is compared with the second period (1991-2000). The protected area is divided into quadrants (9×9 km), such that every quadrant has at least one hail suppression station and intercomparison is more precise. Discriminant analysis was performed for the yearly values of each quadrant. These values included number of cases with solid precipitation, hail damage, heavy hail damage, number of active hail suppression stations, number of days with solid precipitation, solid precipitation damage, heavy solid precipitation damage and the number and duration of air traffic control bans. The discriminant analysis shows that there is a significant difference between the two periods. Average values of observed periods on isolated discriminant function 1 are for the first period (1981-1990) -0.36 and for the second period +0.23 standard deviation of all observations. The analysis for all eight variables shows statistically substantial differences in the number of hail suppression stations (which have a positive correlation) and in the number of cases with air traffic control ban, which have, like all other variables, a negative correlation. Results of statistical analysis for two periods show positive influence of hail suppression system. The discriminant analysis made for three periods shows that these three periods can not be compared because of the short time period, the difference in hail suppression technology, working conditions and possible differences in meteorological conditions. Therefore, neither the effectiveness nor ineffectiveness of hail suppression operations nor their efficiency can be statistically proven. For an exact assessment of hail suppression effectiveness, it is necessary to develop a project, which would take into consideration all the parameters used in such previous projects around the world—a hailpad polygon.

Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam.

PubMed

Kilts, C D; Commissaris, R L; Cordon, J J; Rech, R H

1982-01-01

This study examined the effects of various drug treatments (IP injections) proposed to modify central 5-hydroxytryptamine (5-HT) activity on a conditioned suppression of drinking behavior in water-deprived rats. The subjects were trained to drink their daily water requirement during a 10-min session. Intermittent tone periods of 7 s were then introduced, the last 5 s of which the drinking tube was electrified. The animals gradually suppressed tube contacts during the tone to a low constant level within 2 weeks of training. Diazepam increased punished responding dramatically. The 5-HT antagonists methysergide (1 - 18 mg/kg), cyproheptadine (1 - 18 mg/kg), metergoline (0.25 - 2.0 mg/kg) and cinanserin (10 - mg/kg) failed to induce large, reliable increases in punished responding. When a low dose of diazepam was combined with 5-HT antagonists, only one treatment, methysergide at 3 mg/kg, potentiated the anticonflict activity of diazepam. Acute or chronic treatment with PCPA increased behavior suppressed by punishment, but this effect was weak, brief, and poorly related to the depletion of brain 5-HT. LSD (0.3 - 100 microgram/kg) administered 1, 10, or 30 min before the test was ineffective in overcoming suppression by punishment. Mescaline (6 - 30 mg/kg) had no significant effect on punished responding. 5-HTP (18 mg/kg) decreased the number of shocks accepted, but not after pretreating with carbidopa. Pretreatment with carbidopa plus 5-HTP potentiated the anticonflict effect of diazepam. The 5-HT agonist mCPP (0.25 - 2.0 mg/kg) enhanced suppression due to punishment, but only in doses that interfered with unpunished responding. The 5-HT-releasing agent fenfluramine (0.25 - 1.0 mg/kg) did not affect this behavior. Amitriptyline pretreatment in a dose not affecting unpunished behavior (5.6 mg/kg) potentiated the diazepam-induced increase in punished responding. These results are difficult to reconcile with the proposal that suppression of behavior consequent to punishment is related to brain 5-HT activity.

Complex-enhanced chaotic signals with time-delay signature suppression based on vertical-cavity surface-emitting lasers subject to chaotic optical injection

NASA Astrophysics Data System (ADS)

Chen, Jianjun; Duan, Yingni; Zhong, Zhuqiang

2018-06-01

A chaotic system is constructed on the basis of vertical-cavity surface-emitting lasers (VCSELs), where a slave VCSEL subject to chaotic optical injection (COI) from a master VCSEL with the external feedback. The complex degree (CD) and time-delay signature (TDS) of chaotic signals generated by this chaotic system are investigated numerically via permutation entropy (PE) and self-correlation function (SF) methods, respectively. The results show that, compared with master VCSEL subject to optical feedback, complex-enhanced chaotic signals with TDS suppression can be achieved for S-VCSEL subject to COI. Meanwhile, the influences of several controllable parameters on the evolution maps of CD of chaotic signals are carefully considered. It is shown that the CD of chaotic signals for S-VCSEL is always higher than that for M-VCSEL due to the CIO effect. The TDS of chaotic signals can be significantly suppressed by choosing the reasonable parameters in this system. Furthermore, TDS suppression and high CD chaos can be obtained simultaneously in the specific parameter ranges. The results confirm that this chaotic system may effectively improve the security of a chaos-based communication scheme.

Complex-enhanced chaotic signals with time-delay signature suppression based on vertical-cavity surface-emitting lasers subject to chaotic optical injection

NASA Astrophysics Data System (ADS)

Chen, Jianjun; Duan, Yingni; Zhong, Zhuqiang

2018-03-01

A chaotic system is constructed on the basis of vertical-cavity surface-emitting lasers (VCSELs), where a slave VCSEL subject to chaotic optical injection (COI) from a master VCSEL with the external feedback. The complex degree (CD) and time-delay signature (TDS) of chaotic signals generated by this chaotic system are investigated numerically via permutation entropy (PE) and self-correlation function (SF) methods, respectively. The results show that, compared with master VCSEL subject to optical feedback, complex-enhanced chaotic signals with TDS suppression can be achieved for S-VCSEL subject to COI. Meanwhile, the influences of several controllable parameters on the evolution maps of CD of chaotic signals are carefully considered. It is shown that the CD of chaotic signals for S-VCSEL is always higher than that for M-VCSEL due to the CIO effect. The TDS of chaotic signals can be significantly suppressed by choosing the reasonable parameters in this system. Furthermore, TDS suppression and high CD chaos can be obtained simultaneously in the specific parameter ranges. The results confirm that this chaotic system may effectively improve the security of a chaos-based communication scheme.

Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts.

PubMed

Tanaka, Ryo; Umemura, Masanari; Narikawa, Masatoshi; Fujita, Takayuki; Yokoyama, Utako; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi; Ishikawa, Yoshihiro

2018-05-01

Mechanical stresses play important roles in the process of constructing and modifying heart structure. It has been well established that stretch force acting on cardiac fibroblasts induces fibrosis. However, the effects of compressive force, that is, hydrostatic pressure (HP), have not been well elucidated. We thus evaluated the effects of HP using a pressure-loading apparatus in human cardiac fibroblasts (HCFs) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCFs. HP then greatly inhibited glycogen synthase kinase 3 (GSK-3)α, which acts downstream of the PI3K/Akt pathway. Similarly, HP suppressed mRNA transcription of inflammatory cytokine-6, collagen I and III, and matrix metalloproteinase 1, compared with an atmospheric pressure condition. Furthermore, HP inhibited collagen matrix production in a three-dimensional HCF culture. Taken together, high HP suppressed the differentiation of fibroblasts into the myofibroblast phenotype. HP under certain conditions suppressed cardiac fibrosis via Akt/GSK-3 signaling in HCFs. These results might help to elucidate the pathology of some types of heart disease. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats.

PubMed

Sugiura, Takahiro; Tsutsui, Hidenobu; Takaoka, Masanori; Kobuchi, Shuhei; Hayashi, Kentaro; Fujii, Toshihide; Matsumura, Yasuo

2008-03-01

Enhanced renal sympathetic nerve activity (RSNA) during ischemic period and the renal venous norepinephrine (NE) overflow after reperfusion play important roles in the development of ischemic/reperfusion (I/R)-induced acute renal failure (ARF) in rats. This study evaluated whether agmatine, which is known to reduce sympathetic nerve activity and NE overflow by electrical stimulation, would prevent the I/R-induced renal dysfunction. Ischemic ARF was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous (IV) injection of agmatine (100 and 300 micromol/kg) to ischemic ARF rats dose-dependently suppressed the enhanced RSNA and attenuated the I/R-induced renal dysfunction and histological damage. Intracerebroventricular (ICV) injection of agmatine (600 nmol/kg) to ischemic ARF rats suppressed the enhanced RSNA during the ischemic period and attenuated the I/R-induced renal injury. Furthermore, both IV and ICV injection of agmatine significantly suppressed the renal venous NE overflow after the reperfusion. These results indicate that agmatine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppression of the enhanced RSNA during ischemic period and NE overflow from renal sympathetic nerve endings.

Manual fire suppression methods on typical machinery space spray fires

NASA Astrophysics Data System (ADS)

Carhart, H. W.; Leonard, J. T.; Budnick, E. K.; Ouellette, R. J.; Shanley, J. H., Jr.

1990-07-01

A series of tests was conducted to evaluate the effectiveness of Aqueous Film Forming Foam (AFFF), potassium bicarbonate powder (PKP) and Halon 1211, alone and in various combinations, in extinguishing spray fires. The sprays were generated by JP-5 jet fuel issuing from an open sounding tube, and open petcock, a leaking flange or a slit pipe, and contacting an ignition source. The results indicate that typical fuel spray fires, such as those simulated in this series, are very severe. Flame heights ranged from 6.1 m (20 ft) for the split pipe to 15.2 m (50 ft) for the sounding tube scenario. These large flame geometries were accompanied by heat release rates of 6 MW to greater than 50 MW, and hazardous thermal radiation levels in the near field environment, up to 9.1 m (30 ft) away. Successful suppression of these fires requires both a significant reduction in flame radiation and delivery of a suppression agent to shielded areas. Of the nine suppression methods tested, the 95 gpm AFFF hand line and the hand line in conjunction with PKP were particularly effective in reducing the radiant flux.

Curdlan blocks the immune suppression by myeloid-derived suppressor cells and reduces tumor burden.

PubMed

Rui, Ke; Tian, Jie; Tang, Xinyi; Ma, Jie; Xu, Ping; Tian, Xinyu; Wang, Yungang; Xu, Huaxi; Lu, Liwei; Wang, Shengjun

2016-08-01

Tumor-elicited immunosuppression is one of the essential mechanisms for tumor evasion of immune surveillance. It is widely thought to be one of the main reasons for the failure of tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of cells that play an important role in tumor-induced immunosuppression. These cells expand in tumor-bearing individuals and suppress T cell responses via various mechanisms. Curdlan, the linear (1 → 3)-β-glucan from Agrobacterium, has been applied in the food industry and other sectors. The anti-tumor property of curdlan has been recognized for a long time although the underlying mechanism still needs to be explored. In this study, we investigated the effect of curdlan on MDSCs and found that curdlan could promote MDSCs to differentiate into a more mature state and then significantly reduce the suppressive function of MDSCs, decrease the MDSCs in vivo and down-regulate the suppression in tumor-bearing mice, thus leading to enhanced anti-tumor immune responses. We, therefore, increase the understanding of further mechanisms by which curdlan achieves anti-tumor effects.

Estradiol modulates the anorexic response to central glucagon-like peptide 1.

PubMed

Maske, Calyn B; Jackson, Christine M; Terrill, Sarah J; Eckel, Lisa A; Williams, Diana L

2017-07-01

Estrogens suppress feeding in part by enhancing the response to satiation signals. Glucagon-like peptide 1 (GLP-1) acts on receptor populations both peripherally and centrally to affect food intake. We hypothesized that modulation of the central GLP-1 system is one of the mechanisms underlying the effects of estrogens on feeding. We assessed the anorexic effect of 0, 1, and 10μg doses of GLP-1 administered into the lateral ventricle of bilaterally ovariectomized (OVX) female rats on a cyclic regimen of either 2μg β-estradiol-3-benzoate (EB) or oil vehicle 30min prior to dark onset on the day following hormone treatment. Central GLP-1 treatment significantly suppressed food intake in EB-treated rats at both doses compared to vehicle, whereas only the 10μg GLP-1 dose was effective in oil-treated rats. To follow up, we examined whether physiologic-dose cyclic estradiol treatment influences GLP-1-induced c-Fos in feeding-relevant brain areas of OVX females. GLP-1 significantly increased c-Fos expression in the area postrema (AP) and nucleus of the solitary tract (NTS), and the presence of estrogens may be required for this effect in the paraventricular nucleus of the hypothalamus (PVN). Together, these data suggest that modulation of the central GLP-1 system may be one of the mechanisms by which estrogens suppress food intake, and highlight the PVN as a region of interest for future investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Does ethnicity matter in male hormonal contraceptive efficacy?

PubMed Central

Ilani, Niloufar; Liu, Peter Y; Swerdloff, Ronald S; Wang, Christina

2011-01-01

The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis. Baseline differences in testicular histomorphology and testosterone metabolism between East Asian and Caucasian men have been reported, but whether this contributes significantly to varying degrees of sperm suppression in response to exogenous testosterone therapy is less known. Testosterone alone male hormonal contraceptive regimens are effective and applicable for East Asian men, and less so for Caucasians. Combinations of progestins with androgens are sufficient to optimize effectiveness of suppression and applicability to all ethnicities. New compounds such as steroidal or non-steroidal selective androgen receptor modulators with dual androgenic and progestational activities are potential compounds for further development as male hormonal contraceptive methods. At the present time, combined androgen and progestin contraceptive regimens appear to be effective, safe, reversible and convenient to use for all men with ethnic, cultural and environmental differences. Further refinements on the hormonal agent, methods of delivery, and dose optimization of the androgen relative to the progestin are necessary. This goal mandates further investment and large clinical trials in multiethnic populations to better define safety and efficacy. PMID:21317912

Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, which down-regulates type I collagen synthesis in human osteoblasts.

PubMed

Vermes, C; Roebuck, K A; Chandrasekaran, R; Dobai, J G; Jacobs, J J; Glant, T T

2000-09-01

Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen alpha1[I] and procollagen alpha1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor kappaB (NF-kappaB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-kappaB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen alpha1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

Surface plasmon resonances in liquid metal nanoparticles

NASA Astrophysics Data System (ADS)

Ershov, A. E.; Gerasimov, V. S.; Gavrilyuk, A. P.; Karpov, S. V.

2017-06-01

We have shown significant suppression of resonant properties of metallic nanoparticles at the surface plasmon frequency during the phase transition "solid-liquid" in the basic materials of nanoplasmonics (Ag, Au). Using experimental values of the optical constants of liquid and solid metals, we have calculated nanoparticle plasmonic absorption spectra. The effect was demonstrated for single particles, dimers and trimers, as well as for the large multiparticle colloidal aggregates. Experimental verification was performed for single Au nanoparticles heated to the melting temperature and above up to full suppression of the surface plasmon resonance. It is emphasized that this effect may underlie the nonlinear optical response of composite materials containing plasmonic nanoparticles and their aggregates.

Development of model-based control for Bridgman crystal growth

NASA Astrophysics Data System (ADS)

Sonda, Paul; Yeckel, Andrew; Daoutidis, Prodromos; Derby, Jeffrey. J.

2004-05-01

We study the feasibility of using crucible rotation with feedback control to suppress oscillatory flows in two prototypical vertical Bridgman crystal growth systems—a stabilizing configuration driven by a time-oscillatory furnace disturbance and a thermally destabilized configuration, which exhibits inherent time-varying flows. Proportional controllers are applied to the two systems, with volume-averaged flow speed chosen as the single controlled output and crucible rotation chosen as the manipulated input. Proportional control is able to significantly suppress oscillations in the stabilizing configuration. For the destabilized case, control is effective for small-amplitude flows but is generally ineffective, due to the exacerbating effect of crucible rotation on the time-dependent flows exhibited by this system.

Suppressive effects of carotenoids on the antigen-induced degranulation in RBL-2H3 rat basophilic leukemia cells.

PubMed

Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

2014-01-01

In this study, the anti-degranulation effects of fifteen carotenoids were evaluated using RBL-2H3 rat basophilic leukemia cell line as a mast cell model. Nine carotenoids, fucoxanthin, zeaxanthin, β-carotene, astaxanthin, 3-hydroxyechinenone, fucoxanthinol, lycopene, β-cryptoxanthin, and siphonaxanthin significantly suppressed antigen-induced mast cell degranulation. Under the same conditions, the cellular carotenoid contents were quantified using high performance liquid chromatography-photodiode array (HPLC-PDA). There was no correlation between the cellular carotenoid contents and their anti-degranulation activities. These results indicate that the differences in the anti-degranulation activities of carotenoids were not related to their uptake by the cells.

Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110

PubMed Central

Kuo, Y; Ren, S; Lao, U; Edgar, B A; Wang, T

2013-01-01

A network of heat-shock proteins mediates cellular protein homeostasis, and has a fundamental role in preventing aggregation-associated neurodegenerative diseases. In a Drosophila model of polyglutamine (polyQ) disease, the HSP40 family protein, DNAJ-1, is a superior suppressor of toxicity caused by the aggregation of polyQ containing proteins. Here, we demonstrate that one specific HSP110 protein, 70 kDa heat-shock cognate protein cb (HSC70cb), interacts physically and genetically with DNAJ-1 in vivo, and that HSC70cb is necessary for DNAJ-1 to suppress polyglutamine-induced cell death in Drosophila. Expression of HSC70cb together with DNAJ-1 significantly enhanced the suppressive effects of DNAJ-1 on polyQ-induced neurodegeneration, whereas expression of HSC70cb alone did not suppress neurodegeneration in Drosophila models of either general polyQ disease or Huntington's disease. Furthermore, expression of a human HSP40, DNAJB1, together with a human HSP110, APG-1, protected cells from polyQ-induced neural degeneration in flies, whereas expression of either component alone had little effect. Our data provide a functional link between HSP40 and HSP110 in suppressing the cytotoxicity of aggregation-prone proteins, and suggest that HSP40 and HSP110 function together in protein homeostasis control. PMID:24091676

PDE5 Inhibitors Enhance Celecoxib Killing in Multiple Tumor Types

PubMed Central

BOOTH, LAURENCE; ROBERTS, JANE L.; CRUICKSHANKS, NICHOLA; TAVALLAI, SEYEDMEHRAD; WEBB, TIMOTHY; SAMUEL, PETER; CONLEY, ADAM; BINION, BRITTANY; YOUNG, HAROLD F.; POKLEPOVIC, ANDREW; SPIEGEL, SARAH; DENT, PAUL

2015-01-01

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 activation was dependent on nitric oxide and ceramide signaling. CD95 signaling activated the JNK pathway and inhibition of JNK suppressed cell killing. The drug combination inactivated mTOR and increased the levels of autophagy and knock down of Beclin1 or ATG5 strongly suppressed killing by the drug combination. The drug combination caused an ER stress response; knock down of IRE1α/XBP1 enhanced killing whereas knock down of eIF2α/ATF4/CHOP suppressed killing. Sildenafil and celecoxib treatment suppressed the growth of mammary tumors in vivo. Collectively our data demonstrate that clinically achievable concentrations of celecoxib and sildenafil have the potential to be a new therapeutic approach for cancer. PMID:25303541

Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis.

PubMed

Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi; Ohshima, Yasuhiro; Tago, Fumitoshi; Masada, Ayako; Kojima, Shuji

2008-07-01

We previously reported attenuation of autoimmune disease by low-dose gamma-ray irradiation in MRL-lpr/lpr mice. Here, we studied the effect of low-dose gamma-ray irradiation on collagen-induced arthritis (CIA) in DBA/1J mice. Mice were immunized with type II collagen, and exposed to low-dose gamma-rays (0.5 Gy per week for 5 weeks). Paw swelling, redness, and bone degradation were suppressed by irradiation, which also delayed the onset of pathological change and reduced the severity of the arthritis. Production of tumor necrosis factor-alpha, interferon-gamma, and interleukin-6, which play important roles in the onset of CIA, was suppressed by the irradiation. The level of anti-type II collagen antibody, which is essential for the onset of CIA, was also lower in irradiated CIA mice. The population of plasma cells was increased in CIA mice, but irradiation blocked this increase. Since regulatory T cells are known to be involved in suppression of autoimmune disease, the population of CD4(+)CD25(+)Foxp3(+) regulatory T cells was measured. Intriguingly, a significant increase of these regulatory T cells was found in irradiated CIA mice. Overall, our data suggest that low-dose gamma-ray irradiation could attenuate CIA through suppression of pro-inflammatory cytokines and autoantibody production, and induction of regulatory T cells.

Quinolone Resistance Reversion by Targeting the SOS Response.

PubMed

Recacha, E; Machuca, J; Díaz de Alba, P; Ramos-Güelfo, M; Docobo-Pérez, F; Rodriguez-Beltrán, J; Blázquez, J; Pascual, A; Rodríguez-Martínez, J M

2017-10-10

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog 10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog 10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this question, we have generated E. coli mutants that exhibited a spectrum of SOS activity, ranging from a natural SOS response to a hypoinducible or constitutively suppressed response. We tested the effects of these mutations on quinolone resistance reversion under therapeutic concentrations in a set of isogenic strains carrying different combinations of chromosome- and plasmid-mediated quinolone resistance mechanisms with susceptible, low-level quinolone resistant, resistant, and highly resistant phenotypes. Our comprehensive analysis opens up a new strategy for reversing drug resistance by targeting the SOS response. Copyright © 2017 Recacha et al.

Statins suppress apolipoprotein CIII-induced vascular endothelial cell activation and monocyte adhesion.

PubMed

Zheng, Chunyu; Azcutia, Veronica; Aikawa, Elena; Figueiredo, Jose-Luiz; Croce, Kevin; Sonoki, Hiroyuki; Sacks, Frank M; Luscinskas, Francis W; Aikawa, Masanori

2013-02-01

Activation of vascular endothelial cells (ECs) contributes importantly to inflammation and atherogenesis. We previously reported that apolipoprotein CIII (apoCIII), found abundantly on circulating triglyceride-rich lipoproteins, enhances adhesion of human monocytes to ECs in vitro. Statins may exert lipid-independent anti-inflammatory effects. The present study examined whether statins suppress apoCIII-induced EC activation in vitro and in vivo. Physiologically relevant concentrations of purified human apoCIII enhanced attachment of the monocyte-like cell line THP-1 to human saphenous vein ECs (HSVECs) or human coronary artery ECs (HCAECs) under both static and laminar shear stress conditions. This process mainly depends on vascular cell adhesion molecule-1 (VCAM-1), as a blocking VCAM-1 antibody abolished apoCIII-induced monocyte adhesion. ApoCIII significantly increased VCAM-1 expression in HSVECs and HCAECs. Pre-treatment with statins suppressed apoCIII-induced VCAM-1 expression and monocyte adhesion, with two lipophilic statins (pitavastatin and atorvastatin) exhibiting inhibitory effects at lower concentration than those of hydrophilic pravastatin. Nuclear factor κB (NF-κB) mediated apoCIII-induced VCAM-1 expression, as demonstrated via loss-of-function experiments, and pitavastatin treatment suppressed NF-κB activation. Furthermore, in the aorta of hypercholesterolaemic Ldlr(-/-) mice, pitavastatin administration in vivo suppressed VCAM-1 mRNA and protein, induced by apoCIII bolus injection. Similarly, in a subcutaneous dorsal air pouch mouse model of leucocyte recruitment, apoCIII injection induced F4/80+ monocyte and macrophage accumulation, whereas pitavastatin administration reduced this effect. These findings further establish the direct role of apoCIII in atherogenesis and suggest that anti-inflammatory effects of statins could improve vascular disease in the population with elevated plasma apoCIII.

Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity.

PubMed

Hasegawa, Yasushi; Inoue, Tatsuro; Kawaminami, Satoshi; Fujita, Miho

2016-07-01

To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801. Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Determination of microcystin-LR in drinking water using UPLC tandem mass spectrometry-matrix effects and measurement.

PubMed

Li, Wei; Duan, Jinming; Niu, Chaoying; Qiang, Naichen; Mulcahy, Dennis

2011-10-01

A simple detection method using ultra-performance liquid chromatography electrospray ionisation tandem mass spectrometry (UPLC-ESI-MS-MS) coupled with the sample dilution method for determining trace microcystin-LR (MC-LR) in drinking water is presented. The limit of detection (LOD) was 0.04 µg/L and the limit of quantitation (LOQ) was 0.1 µg/L. Water matrix effects of ionic strength, dissolved organic carbon (DOC) and pH were examined. The results indicate that signal detection intensity for MC-LR was significantly suppressed as the ionic strength increased from ultrapure water condition, whereas it increased slightly with solution pH and DOC at low concentrations. However, addition of methanol (MeOH) into the sample was able to counter the signal suppression effects. In this study, dilution of the tap water sample by adding 4% MeOH (v/v) was observed to be adequate to compensate for the signal suppression. The recoveries of the samples fortified with MC-LR (0.2, 1, and 10 µg/L) for three different tap water samples ranged from 84.4% to 112.9%.

Contralateral suppression of transient otoacoustic emissions and sentence recognition in noise in young adults.

PubMed

Stuart, Andrew; Butler, Alyson K

2012-10-01

One purported role of the medial olivocochlear (MOC) efferent system is to reduce the effects of masking noise. MOC system functioning can be evaluated noninvasively in humans through contralateral suppression of otoacoustic emissions. It has been suggested that the strength of the MOC efferent activity should be positively associated with listening performance in noise. The objective of the study was to further explore this notion by examining contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) and sentence recognition in two noises with normal hearing young adults. A repeated measures multivariate quasi-experimental design was employed. Thirty-two normal hearing young adult females participated. Reception thresholds for sentences (RTSs) were determined monaurally and binaurally in quiet and in competing continuous and interrupted noises. Both noises had an identical power spectrum and differed only in their temporal continuity. "Release from masking" was computed by subtracting RTS signal-to-noise ratios in interrupted from continuous noise. TEOAEs were evoked with 80 dB peSPL click stimuli. To examine contralateral suppression, TEOAEs were evaluated with 60 dB peSPL click stimuli with and without a contralateral 65 dB SPL white noise suppressor. A binaural advantage was observed for RTSs in quiet and noise (p < .0001) while there was no difference between ears (p >.05). In noise, performance was superior in the interrupted noise (i.e., RTSs were lower vs. continuous noise; p < .0001). There were no statistically significant differences in TEOAE levels between ears (p >.05). There was also no significant difference in the amount of suppression between ears (p = .41). There were no significant correlations or predictive linear relations between the amount of TEOAE suppression and any indices of sentence recognition in noise (i.e., RTS signal-to-noise ratios and release from masking; p > .05). The findings are not consistent with the notion that increased medial olivocochlear efferent feedback, as assessed via contralateral suppression of TEOAEs, is associated with improved speech perception in continuous and interrupted noise. American Academy of Audiology.

4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Mingche

Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P = 0.027) and depleting Atg-5 in ES-2 cell lines significantly inducedmore » apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy. - Highlights: • Atg-5 is overexpressed in ovarian cancer and silencing Atg-5 induces apoptosis. • 4-AAQB suppresses autophagy and PI3K/Akt/mTOR pathway. • 4-AAQB + cisplatin synergistically suppresses ovarian cancer via autophagy.« less

Osthole induces apoptosis and suppresses proliferation via the PI3K/Akt pathway in intrahepatic cholangiocarcinoma.

PubMed

Zhu, Xingyang; Song, Xiaoling; Xie, Kun; Zhang, Xue; He, Wei; Liu, Fubao

2017-10-01

Osthole is a natural coumarin isolated from Umbelliferae plant monomers. Previous research has indicated that osthole exerts a wide variety of biological effects, acting as anti-seizure, anti-osteoporosis and anti-inflammation. However, the regulatory effect and related molecular mechanism of osthole in intrahepatic cholangiocarcinoma (ICC) remain unknown. In the present study, the authors found that osthole inhibited ICC cell lines in a dose- and time-dependent manner. Osthole also significantly induced mitochondrial-dependent apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, the levels of p-Akt and PI3K were significantly decreased, while total Akt protein levels were unchanged. Following transfection with wild-type-Akt and constitutively active (CA)-Akt plasmids, the effects of osthole were decreased. Osthole was also able to suppress tumor growth in vivo. Together, these data demonstrated that osthole induces mitochondrial-dependent apoptosis via the PI3K/Akt pathway, suggesting that osthole may represent a novel and effective agent for the treatment of ICC.

Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases.

PubMed

Keeling, Kim M; Bedwell, David M

2011-01-01

Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy. Copyright © 2011 John Wiley & Sons, Ltd.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

PubMed

Chen, Xin; Feng, Shu-xian; Guo, Ping-ping; He, Yu-xia; Liu, Yu-dong; Ye, De-sheng; Chen, Shi-ling

2016-04-01

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

PubMed

Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

2016-02-15

To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

Anger Suppression and Subsequent Pain Behaviors among Chronic Low Back Pain Patients: Moderating Effects of Anger Regulation Style

PubMed Central

Quartana, Phillip; Bruehl, Stephen

2013-01-01

Background Suppression of anger is linked to subsequent pain intensity among chronic low back patients, but it is not clear whether anger regulation style (trait anger-out, anger-in) moderates these effects or if aroused anger accounts for links between anger regulation style and pain. Method Chronic low back pain patients (N=58) were assigned to Suppression or No Suppression conditions for a task with harassing confederate and then underwent structured pain behavior procedures. Spielberger Anger Expression Inventory tapped trait anger-out (AOS) and anger-in (AIS). Results Regressions tested Emotion Regulation condition × AOS and AIS effects on outcomes. AOS was related to grimacing and sighing for Suppression condition patients. AIS was related negatively to guarding and bracing for Suppression condition patients. Anger report partly mediated effects for AOS and AIS. Conclusions Anger regulation style moderated effects of state anger suppression on subsequent pain behaviors, effects that were partly explained by aroused anger. PMID:21544702

Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling

PubMed Central

Loo, Jacky F.C.; Xia, Dajin; Gao, Sizhi P.; Ma, Zhongjun; Chen, Zhe

2016-01-01

The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate the therapeutic potential of physalin A, a bioactive withanolide derived from Physalis alkekengi var. francheti used in traditional Chinese medicine, was evaluated in human NSCLC cells. Its and determined whether it effect oninhibited both constitutive and induced STAT3 activity, through repressing the phosphorylation levels of JAK2 and JAK3, resulting in anti-proliferation and pro-apoptotic effects on NSCLC cells was also determined, and. theThe antitumor effects of physalin A were also validated usingin an in vivo mouse xenograft models of NSCLC cells. Physalin A had anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore, physalin A abrogated the nuclear translocation and transcriptional activity of STAT3, thereby decreasing the expression levels of STAT3, its target genes, such as Bcl-2 and XIAP. Knockdown of STAT3 expression by small interfering RNA (siRNA) significantly enhanced the pro-apoptotic effects of physalin A in NSCLC cells. Moreover, physalin A significantly suppressed tumor xenograft growth. Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate the development of a therapeutic strategy for treating NSCLC. PMID:26843613

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

2000-01-01

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans

PubMed Central

Sidani, Reem M.; Garcia, Anna E.; Antoun, Joseph; Isbell, James M.; Abumrad, Naji N.

2016-01-01

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These “isoglycemic clamps” enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion. PMID:27279247

Enhancing Sensitivity of Liquid Chromatography-Mass Spectrometry of Peptides and Proteins Using Supercharging Agents.

PubMed

Nshanian, Michael; Lakshmanan, Rajeswari; Chen, Hao; Ogorzalek Loo, Rachel R; Loo, Joseph A

2018-04-01

Trifluoroacetic acid (TFA) is often used as a mobile phase modifier to enhance reversed phase chromatographic performance. TFA adjusts solution pH and is an ion-pairing agent, but it is not typically suitable for electrospray ionization-mass spectrometry (ESI-MS) and liquid chromatography/MS (LC/MS) because of its significant signal suppression. Supercharging agents elevate peptide and protein charge states in ESI, increasing tandem MS (MS/MS) efficiency. Here, LC/MS protein supercharging was effected by adding agents to LC mobile phase solvents. Significantly, the ionization suppression generally observed with TFA was, for the most part, rescued by supercharging agents, with improved separation efficiency (higher number of theoretical plates) and lowered detection limits.

Emotional memory can be persistently weakened by suppressing cortisol during retrieval.

PubMed

Rimmele, Ulrike; Besedovsky, Luciana; Lange, Tanja; Born, Jan

2015-03-01

Cortisol's effects on memory follow an inverted U-shaped function such that memory retrieval is impaired with very low concentrations, presumably due to insufficient activation of high-affine mineralocorticoid receptors (MR), or with very high concentrations, due to predominant low-affine glucocorticoid receptor (GR) activation. Through corresponding changes in re-encoding, the retrieval effect of cortisol might translate into a persistent change of the retrieved memory. We tested whether partial suppression of morning cortisol synthesis by metyrapone, leading to intermediate, circadian nadir-like levels with presumed predominant MR activation, improves retrieval, particularly of emotional memory, and persistently changes the memory. In a randomized, placebo-controlled, double-blind, within-subject cross-over design, 18 men were orally administered metyrapone (1g) vs. placebo at 4:00 AM to suppress the morning cortisol rise. Retrieval of emotional and neutral texts and pictures (learned 3 days earlier) was assessed 4h after substance administration and a second time one week later. Metyrapone suppressed endogenous cortisol release to circadian nadir-equivalent levels at the time of retrieval testing. Contrary to our expectations, metyrapone significantly impaired free recall of emotional texts (p<.05), whereas retrieval of neutral texts or pictures remained unaffected. One week later, participants still showed lower memory for emotional texts in the metyrapone than placebo condition (p<.05). Our finding that suppressing morning cortisol to nadir-like concentrations not only impairs acute retrieval, but also persistently weakens emotional memories corroborates the concept that retrieval effects of cortisol produce persistent memory changes, possibly by affecting re-encoding. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats

PubMed Central

Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.

2012-01-01

Background Etomidate is a sedative–hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague–Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1–24 and measuring serum corticosterone concentrations every 30 min. Results The sedative–hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion terminationvaried(methoxycarbonyletomidate>carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable. PMID:21572317

NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation.

PubMed

Yoshinaga, Ayana; Kajiya, Natsuki; Oishi, Kazuki; Kamada, Yuko; Ikeda, Asami; Chigwechokha, Petros Kingstone; Kibe, Toshiro; Kishida, Michiko; Kishida, Shosei; Komatsu, Masaharu; Shiozaki, Kazuhiro

2016-07-05

Naringin, which is one of the flavonoids contained in citrus fruits, is well known to possess various healthy functions to humans. It has been reported that naringin suppresses cancer cell growth in vitro and in vivo, although the underlying mechanisms are not fully understood. Recently, the roles of glycoconjugates, such as gangliosides, in cancer cells have been focused because of their regulatory effects of malignant phenotypes. Here, to clarify the roles of naringin in the negative-regulation of cancer cell growth, the alteration of glycoconjugates induced by naringin exposure and its significance on cell signaling were investigated. Human cancer cells, HeLa and A549, were exposed to various concentrations of naringin. Naringin treatment induced the suppression of cell growth toward HeLa and A549 cells accompanied with an increase of apoptotic cells. In naringin-exposed cells, GM3 ganglioside was drastically increased compared to the GM3 content prior to the treatment. Furthermore, naringin inhibited NEU3 sialidase, a GM3 degrading glycosidase. Similarly, NEU3 inhibition activities were also detected by other flavanone, such as hesperidin and neohesperidin dihydrocalcone, but their aglycones showed less inhibitions. Naringin-treated cancer cells showed suppressed EGFR and ERK phosphorylation levels. These results suggest a novel mechanism of naringin in the suppression of cancer cell growth through the alteration of glycolipids. NEU3 inhibitory effect of naringin induced GM3 accumulation in HeLa and A549 cells, leading the attenuation of EGFR/ERK signaling accompanied with a decrease in cell growth. Copyright © 2016 Elsevier B.V. All rights reserved.

Delving into α-stable distribution in noise suppression for seizure detection from scalp EEG

NASA Astrophysics Data System (ADS)

Wang, Yueming; Qi, Yu; Wang, Yiwen; Lei, Zhen; Zheng, Xiaoxiang; Pan, Gang

2016-10-01

Objective. There is serious noise in EEG caused by eye blink and muscle activities. The noise exhibits similar morphologies to epileptic seizure signals, leading to relatively high false alarms in most existing seizure detection methods. The objective in this paper is to develop an effective noise suppression method in seizure detection and explore the reason why it works. Approach. Based on a state-space model containing a non-linear observation function and multiple features as the observations, this paper delves deeply into the effect of the α-stable distribution in the noise suppression for seizure detection from scalp EEG. Compared with the Gaussian distribution, the α-stable distribution is asymmetric and has relatively heavy tails. These properties make it more powerful in modeling impulsive noise in EEG, which usually can not be handled by the Gaussian distribution. Specially, we give a detailed analysis in the state estimation process to show the reason why the α-stable distribution can suppress the impulsive noise. Main results. To justify each component in our model, we compare our method with 4 different models with different settings on a collected 331-hour epileptic EEG data. To show the superiority of our method, we compare it with the existing approaches on both our 331-hour data and 892-hour public data. The results demonstrate that our method is most effective in both the detection rate and the false alarm. Significance. This is the first attempt to incorporate the α-stable distribution to a state-space model for noise suppression in seizure detection and achieves the state-of-the-art performance.

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

PubMed Central

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

2008-01-01

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

A mixed-methods pilot study of the acceptability and effectiveness of a brief meditation and mindfulness intervention for people with diabetes and coronary heart disease.

PubMed

Keyworth, Chris; Knopp, Jasmin; Roughley, Kate; Dickens, Chris; Bold, Stuart; Coventry, Peter

2014-01-01

Mindfulness-based interventions can successfully target negative perseverative cognitions such as worry and thought suppression, but their acceptability and effectiveness in people with long-term conditions is uncertain. We therefore pilot tested a six-week meditation and mindfulness intervention in people (n = 40) with diabetes mellitus and coronary heart disease. We used a sequential mixed-methods approach that measured change in worry and thought suppression and qualitatively explored acceptability, feasibility, and user experience with a focus group (n = 11) and in-depth interviews (n = 16). The intervention was highly acceptable, with 90% completing ≥5 sessions. Meditation and mindfulness skills led to improved sleep, greater relaxation, and more-accepting approaches to illness and illness experience. At the end of the six-week meditation course, worry, and thought suppression were significantly reduced. Positive impacts of mindfulness-based interventions on psychological health may relate to acquisition and development of meta-cognitive skills but this needs experimental confirmation.

Age and Gender Differences in Relationships Among Emotion Regulation, Mood, and Mental Health.

PubMed

Masumoto, Kouhei; Taishi, Nozomi; Shiozaki, Mariko

2016-01-01

Objective: We investigated the effects of age on mood and mental health-mediated emotion regulation, such as cognitive reappraisal and expressive suppression, and examined whether these relationships differ according to gender. Method: We recruited 936 Japanese participants. They comprised six age groups ranging from 20 to 70 years old, with 156 participants in each age group and equal numbers of men and women. Results: Structural equation model analysis showed that older participants were more likely to use cognitive reappraisal, further enhancing positive mood and reducing negative mood, whereas, age did not affect expressive suppression. Moreover, expressive suppression had a smaller impact on mood than cognitive reappraisal. A multi-group analysis showed significant gender differences. In men, cognitive reappraisal increased with age and influenced mood more positively than in women. Discussion: Our findings indicated gender differences in aging effects on emotion regulation. We discussed about these results from the cognitive process, motivation to emotion regulation, and cultural differences.

microRNA-598 inhibits cell proliferation and invasion of glioblastoma by directly targeting metastasis associated in colon cancer-1.

PubMed

Wang, Ning; Zhang, Yang; Liang, Huaxin

2018-02-14

The dysregulation of microRNAs (miRNAs) expression is closely related with tumorigenesis and tumour development in glioblastoma (GBM). In this study, we found that miRNA-598 (miR-598) expression was significantly downregulated in GBM tissues and cell lines. Restoring miR-598 expression inhibited cell proliferation and invasion in GBM. Moreover, we validated that metastasis associated in colon cancer-1 (MACC1) is a novel target of miR-598 in GBM. Recovered MACC1 expression reversed the inhibitory effects of miR-598 overexpression on GBM cells. In addition, miR-598 overexpression suppressed the Met/AKT pathway activation in GBM. Our results provided compelling evidence that miR-598 serves tumour suppressive roles in GBM and that its anti-oncogenic effects are mediated chiefly through the direct suppression of MACC1 expression and regulation of the Met/AKT signalling pathway. Therefore, miR-598 is a potential target in the treatment of GBM.

Roll tracking effects of G-vector tilt and various types of motion washout

NASA Technical Reports Server (NTRS)

Jex, H. R.; Magdaleno, R. E.; Junker, A. M.

1978-01-01

In a dogfight scenario, the task was to follow the target's roll angle while suppressing gust disturbances. All subjects adopted the same behavioral strategies in following the target while suppressing the gusts, and the MFP-fitted math model response was generally within one data symbol width. The results include the following: (1) comparisons of full roll motion (both with and without the spurious gravity tilt cue) with the static case. These motion cues help suppress disturbances with little net effect on the visual performance. Tilt cues were clearly used by the pilots but gave only small improvement in tracking errors. (2) The optimum washout (in terms of performance close to real world, similar behavioral parameters, significant motion attenuation (60 percent), and acceptable motion fidelity) was the combined attenuation and first-order washout. (3) Various trends in parameters across the motion conditions were apparent, and are discussed with respect to a comprehensive model for predicting adaptation to various roll motion cues.

A Mixed-Methods Pilot Study of the Acceptability and Effectiveness of a Brief Meditation and Mindfulness Intervention for People with Diabetes and Coronary Heart Disease

PubMed Central

Keyworth, Chris; Knopp, Jasmin; Roughley, Kate; Dickens, Chris; Bold, Stuart; Coventry, Peter

2014-01-01

Mindfulness-based interventions can successfully target negative perseverative cognitions such as worry and thought suppression, but their acceptability and effectiveness in people with long-term conditions is uncertain. We therefore pilot tested a six-week meditation and mindfulness intervention in people (n = 40) with diabetes mellitus and coronary heart disease. We used a sequential mixed-methods approach that measured change in worry and thought suppression and qualitatively explored acceptability, feasibility, and user experience with a focus group (n = 11) and in-depth interviews (n = 16). The intervention was highly acceptable, with 90% completing ≥5 sessions. Meditation and mindfulness skills led to improved sleep, greater relaxation, and more-accepting approaches to illness and illness experience. At the end of the six-week meditation course, worry, and thought suppression were significantly reduced. Positive impacts of mindfulness-based interventions on psychological health may relate to acquisition and development of meta-cognitive skills but this needs experimental confirmation. PMID:24754440

Ultrathin ZnS and ZnO Interfacial Passivation Layers for Atomic-Layer-Deposited HfO2 Films on InP Substrates.

PubMed

Kim, Seung Hyun; Joo, So Yeong; Jin, Hyun Soo; Kim, Woo-Byoung; Park, Tae Joo

2016-08-17

Ultrathin ZnS and ZnO films grown by atomic layer deposition (ALD) were employed as interfacial passivation layers (IPLs) for HfO2 films on InP substrates. The interfacial layer growth during the ALD of the HfO2 film was effectively suppressed by the IPLs, resulting in the decrease of electrical thickness, hysteresis, and interface state density. Compared with the ZnO IPL, the ZnS IPL was more effective in reducing the interface state density near the valence band edge. The leakage current density through the film was considerably lowered by the IPLs because the film crystallization was suppressed. Especially for the film with the ZnS IPL, the leakage current density in the low-voltage region was significantly lower than that observed for the film with the ZnO IPL, because the direct tunneling current was suppressed by the higher conduction band offset of ZnS with the InP substrate.

The edge of awareness: Mask spatial density, but not color, determines optimal temporal frequency for continuous flash suppression.

PubMed

Drewes, Jan; Zhu, Weina; Melcher, David

2018-01-01

The study of how visual processing functions in the absence of visual awareness has become a major research interest in the vision-science community. One of the main sources of evidence that stimuli that do not reach conscious awareness-and are thus "invisible"-are still processed to some degree by the visual system comes from studies using continuous flash suppression (CFS). Why and how CFS works may provide more general insight into how stimuli access awareness. As spatial and temporal properties of stimuli are major determinants of visual perception, we hypothesized that these properties of the CFS masks would be of significant importance to the achieved suppression depth. In previous studies however, the spatial and temporal properties of the masks themselves have received little study, and masking parameters vary widely across studies, making a metacomparison difficult. To investigate the factors that determine the effectiveness of CFS, we varied both the temporal frequency and the spatial density of Mondrian-style masks. We consistently found the longest suppression duration for a mask temporal frequency of around 6 Hz. In trials using masks with reduced spatial density, suppression was weaker and frequency tuning was less precise. In contrast, removing color reduced mask effectiveness but did not change the pattern of suppression strength as a function of frequency. Overall, this pattern of results stresses the importance of CFS mask parameters and is consistent with the idea that CFS works by disrupting the spatiotemporal mechanisms that underlie conscious access to visual input.

[Suppression of tinnitus by band noise masker--a study of 600 cases].

PubMed

Watanabe, K; Kamio, T; Ohkawara, D; Aoki, H; Baba, S; Yagi, T

1997-09-01

We performed Band Noise Masker (BNM) therapy for the suppression of tinnitus in 600 patients and measured the pitch, loudness and masking level of tinnitus and residual inhibition (RI). We examined the efficiency of BNM therapy. The purpose of this study was to investigate the mechanism of suppression of tinnitus by BNM. Tinnitus was suppressed in 394 patients (66%) after BNM therapy. In the group of patients in whom we suppressed tinnitus, the loudness of tinnitus was reduced from 7.7 +/- 5.7dBSL to 7.5 +/- 5.5dBSL (p < 0.05) and the pitch of tinnitus did not exhibit a marked change. In the group of patients in whom we did not suppress tinnitus, the loudness and pitch of tinnitus did not exhibit a marked change. The efficiency of BNM therapy was high in the cases of presbyacusis and low in the cases of sudden deafness. There was no significant relationship between RI and the efficiency of BNM therapy. We examined these data and discussed the mechanism of suppression of tinnitus by BNM therapy. In all cases, after BNM therapy, the auditory threshold did not become worse. In 4 cases tinnitus became worse temporarily. In conclusion, BNM therapy is an effective mode for tinnitus control, is easily performed in our outpatient clinic or at home, and has no serious complications.

Rice bran protein hydrolysates prevented interleukin-6- and high glucose-induced insulin resistance in HepG2 cells.

PubMed

Boonloh, Kampeebhorn; Kukongviriyapan, Upa; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Senggunprai, Laddawan; Prawan, Auemduan; Thawornchinsombut, Supawan; Kukongviriyapan, Veerapol

2015-02-01

Rice bran, which is a byproduct of rice milling process, contains various nutrients and biologically active compounds. Rice bran protein hydrolysates have various pharmacological activities such as antidiabetic and antidyslipidemic effects. However, there are limited studies about the mechanisms of rice bran protein hydrolysates (RBP) on insulin resistance and lipid metabolism. RBP used in this study were prepared from Thai Jasmine rice. When HepG2 cells were treated with IL-6, the IRS-1 expression and Akt phosphorylation were suppressed. This effect of IL-6 was prevented by RBP in association with inhibition of STAT3 phosphorylation and SOCS3 expression. RBP could increase the phospho-AMPK levels and inhibit IL-6- or high glucose-induced suppression of AMPK and Akt activation. High glucose-induced dysregulation of the expression of lipogenic genes, including SREBP-1c, FASN and CPT-1, was normalized by RBP treatment. Moreover, impaired glucose utilization in insulin resistant HepG2 cells was significantly alleviated by concurrent treatment with RBP. Our results suggested that RBP suppresses inflammatory cytokine signaling and activates AMPK, and thereby these effects may underlie the insulin sensitizing effect.

Bee venom suppresses testosterone-induced benign prostatic hyperplasia by regulating the inflammatory response and apoptosis.

PubMed

Chung, Kyung-Sook; An, Hyo-Jin; Cheon, Se-Yun; Kwon, Ki-Rok; Lee, Kwang-Ho

2015-12-01

Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH. © 2015 by the Society for Experimental Biology and Medicine.

Bee venom suppresses testosterone-induced benign prostatic hyperplasia by regulating the inflammatory response and apoptosis

PubMed Central

Chung, Kyung-Sook; An, Hyo-Jin; Cheon, Se-Yun; Kwon, Ki-Rok

2015-01-01

Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH. PMID:26085572

Equilibrium E × B Flows in Nonlinear Gyrofluid Flux-Tube Simulations

NASA Astrophysics Data System (ADS)

Beer, M. A.; Hammett, G. W.

2000-10-01

Comparisons of theory with experiment often indicate levels of sheared E × B flow large enough to significantly suppress turbulence, especially when local transport barriers are formed. We extend our previous simulations by including equilibrium scale sheared E × B flow directly, by introducing a coordinate transformation which shears the simulation domain with the equilibrium E × B flow, while preserving smooth statistical periodicity across the radial domain. This method was used linearly in our previous comparisons with JET [Beer, Budny, Challis, et al., EPS (1999)] and is now applied to nonlinear simulations. This method makes use of some tricks suggested for this problem by Dimits [Int. Conf. on Numerical Simulation of Plasmas (1994)] based on special properties of discrete Fourier transforms. A similar coordinate transformation was previously used successfully by Waltz, et al. [Phys. Plasmas 5, 1784 (1998)], and we confirm their finding that the turbulence is suppressed when the shearing rate, ω_E, is comparable to the maximum linear growth rate in the absence of sheared flow, γ_lin. This is often significantly different than the threshold for linear suppression. With this extension, our simulations are able to address transport barriers from a more rigorous footing. Of particular interest will be the investigation of the expansion or propagation of barriers, where E × B shear suppression is by definition at the marginal point. In addition, our formulation uses general magnetic geometry, so we can rigorously investigate various geometrical effects (e.g. hats, Δ', κ) on the threshold for suppression.

Control of pseudo-shock oscillation in scramjet inlet-isolator using periodical excitation

NASA Astrophysics Data System (ADS)

Su, Wei-Yi; Chen, Yun; Zhang, Feng-Rui; Tang, Piao-Ping

2018-02-01

To suppress the pressure oscillation, stabilize the shock train in the scramjet isolator and delay the hypersonic inlet unstart, flow control using periodic excitation was investigated with unsteady Reynolds averaged Navier-Stokes simulations. The results showed that by injecting air to manipulate the cowl reflected shock wave, the separation bubble induced by it was diminished and the pressure oscillations of the shock train were markedly suppressed. The power spectral density and standard deviation of wall pressure were significantly reduced. The simulations revealed that this active control method can raise the critical back pressure by 17.5% compared with the baseline, which would successfully delay the hypersonic inlet unstarts. The results demonstrated that this active control method is effective in suppressing pressure oscillation and delaying hypersonic inlet unstarts.

Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

PubMed

Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

2013-01-01

The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation.

PubMed

Frank, N; Hermida, P; Sanchez-Londoño, A; Singh, R; Gradil, C M; Uricchio, C K

2017-07-01

Octreotide is a somatostatin analog that suppresses insulin secretion. We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Twelve horses, N = 5, ID = 7. Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated. Mean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P < .001) effects were detected for glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant. Octreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats.

PubMed

Obiri, David D; Osafo, Newman; Ayande, Patrick G; Antwi, Aaron O

2014-03-28

Xylopia aethiopica is used in a decoction of the dried fruit to treat bronchitis, asthma, arthritis, rheumatism, headache, neuralgia and colic pain. The aim of the study is to evaluate the anti-arthritic effects of a 70% aqueous ethanol extract of the fruit of Xylopia aethiopica in a chronic inflammatory model. Adjuvant arthritis was induced in Sprague-Dawley rats by intraplantar injection of Complete Freund's adjuvant into the right hind paw. Foot volume was measured by water displacement plethysmometry. The oedema component of inflammation was evaluated as the percentage change in paw swelling and the total oedema induced calculated as area under the time course curves. In addition to X-ray radiography, histopathology of ankle joints supported by haematological analysis was used to assess the anti-arthritic action of the extract of Xylopia aethiopica (XAE). Xylopia aethiopica extract (100, 300 and 600 mg kg(-1)) modified the time course curve significantly reducing hind paw oedema in the ipsilateral paw at all dose levels when administered both prophylactically and therapeutically. In addition XAE significantly suppressed the systemic spread of the arthritis from the ipsilateral to the contralateral limbs. The radiological pictures of the joints particularly metatarsal, phalanges and the ankle joint space of rats in the XAE-treated group showed protective effect against adjuvant-induced arthritis while histopathology revealed significant reduction in mononuclear infiltration, pannus formation and bone erosion. The haematological analysis in the test animals revealed significant improvement relative to the CFA model group. Xylopia aethiopica XAE suppresses joint inflammation and destruction in arthritic rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

GABAergic Neural Activity Involved in Salicylate-Induced Auditory Cortex Gain Enhancement

PubMed Central

Lu, Jianzhong; Lobarinas, Edward; Deng, Anchun; Goodey, Ronald; Stolzberg, Daniel; Salvi, Richard J.; Sun, Wei

2011-01-01

Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate-induced hyperexcitability and “increased central gain”, we examined the effects of γ-aminobutyric acid (GABA) receptor agonists and antagonists on salicylate-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of salicylate significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of salicylate also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the salicylate-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the salicylate-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the salicylate-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by salicylate may arise from a salicylate-induced suppression GABAergic inhibition in the AC. PMID:21664433

The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women.

PubMed

Ma, Doy Yung; Chang, Wei Hung; Chi, Mei Hung; Tsai, Hsin Chun; Yang, Yen Kuang; Chen, Po See

2016-05-30

In this study, the role of brain derived neurotrophic factor (BDNF) in stress resilience was investigated. With a focus on healthy subjects, we explored whether plasma BDNF levels are correlated with the dexamethasone suppression test (DST) and subjectively perceived social support status. Moreover, we examined the possible interacting effect of DST status and perceived social support on BDNF levels. Seventy-two healthy volunteers, 44 females and 28 males, were recruited from the community and completed the perceived routine support subscale of Measurement of Support Function (PRS_MSF) questionnaire. Plasma BDNF levels and DST suppression rate with the low dose DST were measured. There was a significant positive correlation between BDNF and DST suppression rate in the female subjects. This was also true for the plasma BDNF levels and PRS_MSF in the female subjects. The positive correlation between BDNF and PRS_MSF was significant only in female subjects with low DST suppression rates. Plasma BDNF levels were associated with stress resilience in a sex-specific manner. Subjects' belief in social support might buffer the biological stress reactions. Differences in social perception and the biological stress response between men and women merits further investigation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma.

PubMed

Zhang, Qi; Li, Qiang; Xu, Tao; Jiang, Hui; Xu, Lin-Gen

2016-06-01

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.

Suppression of ovalbumin-induced airway inflammatory responses in a mouse model of asthma by Mimosa pudica extract.

PubMed

Yang, Eun Ju; Lee, Ji-Sook; Yun, Chi-Young; Ryang, Yong Suk; Kim, Jong-Bae; Kim, In Sik

2011-01-01

Asthma is an inflammatory airway disease. The pathogenic mechanisms of asthma include the infiltration of leukocytes and release of cytokines. Mimosa pudica (Mp) has been used traditionally for the treatment of insomnia, diarrhea and inflammatory diseases. Although Mp extract has various therapeutic properties, the effect of this extract on asthma has not yet been reported. This study investigated the suppressive effects of Mp extract on asthmatic responses both in vitro and in vivo. Mp extract was acquired from dried and powdered whole plants of M. pudica using 80% ethanol. BALB/c mice were used for the mouse model of asthma induced by ovalbumin. Mp extract significantly inhibited the HMC-1 cell migration induced by stem cell factor and blocked the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in EoL-1 cells. Leukocytosis, eosinophilia and mucus hypersecretion in asthmatic lung were significantly suppressed by Mp extract. The release of ovalbumin-specific IgE in bronchoalveolar lavage fluid and serum was also decreased. Mp extract treatment resulted in no liver cytotoxicity. The Mp extract has inhibitory properties on asthma and may be used as a potent therapeutic agent for allergic lung inflammation. Copyright © 2010 John Wiley & Sons, Ltd.

Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors

PubMed Central

Xiong, Wei; Cui, Tanxing; Cheng, Kejun; Yang, Fei; Chen, Shao-Rui; Willenbring, Dan; Guan, Yun; Pan, Hui-Lin; Ren, Ke; Xu, Yan

2012-01-01

Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction. PMID:22585736

Large-Scale Identification and Analysis of Suppressive Drug Interactions

PubMed Central

Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P.

2014-01-01

SUMMARY One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

Protective effect of red-stemmed type of Ipomoea aquatica Forsk against CCl4-induced oxidative damage in mice.

PubMed

Hirai, Shizuka; Ishibuchi, Toyohito; Watabe, Shinpei; Makita, Miki; Kishida, Chiaki; Takagaki, Michiko; Kurauchi, Nobuyuki; Egashira, Yukari

2011-01-01

Water spinach (Ipomoea aquatica Forsk; I. aquatica) of the green-stemmed type (green type) is widely consumed, but there also exists a red-stemmed variety (red type). In the present study, the antioxidant capacity of the red type was compared to that of the green type in carbon tetrachloride (CCl(4))-treated mice. CCl(4)-induced thiobarbituric acid reactive substrate (TBARS) formation in the liver was significantly suppressed in mice fed 5% red-type I. aquatica, while the green type showed no effect. Hydrophobic oxygen radical absorbance capacity (H-ORAC(FL)) in the red type showed a lower level than that in the green type; however, lipophilic ORAC (L-ORAC(FL)) and total-ORAC(FL) levels were significantly higher in the red type than in the green type. α-Tocopherol, anthocyanidin/proanthocyanidin, and β-carotene contents were all significantly higher in the red type than in the green type. These results suggest that the wild red-type I. aquatica contains certain lipophilic components that exert antioxidant capacities not only in vitro but also in vivo. Such effective components in the red type would be beneficial phytochemicals for suppressing several diseases related to oxidative stress.

Lycium barbarum polysaccharide protects human keratinocytes against UVB-induced photo-damage.

PubMed

Li, Huaping; Li, Zhenjie; Peng, Liqian; Jiang, Na; Liu, Qing; Zhang, Erting; Liang, Bihua; Li, Runxiang; Zhu, Huilan

2017-02-01

Ultraviolet B (UVB) irradiation plays a key role in skin damage, which induces oxidative and inflammatory damages, thereby causing photoaging or photocarcinogenesis. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses significant antioxidative and anti-inflammatory effects on multiple tissues. In the present study, the photoprotective effects and potential underlying molecular mechanisms of LBP against UVB-induced photo-damage were investigated in immortalized human keratinocytes (HaCaT cells). The data indicated that pretreatment with LBP significantly attenuated UVB-induced decrease in cell viability, increase in ROS production and DNA damage. LBP also significantly suppressed UVB-induced p38 MAPK activation, and subsequently reversed caspase-3 activation and MMP-9 expression. Notably, LBP was found to induce Nrf2 nuclear translocation and increase the expression of Nrf2-dependent ARE target genes. Furthermore, the protective effects of LBP were abolished by siRNA-mediated Nrf2 silencing. These results showed that the antioxidant LBP could partially protect against UVB irradiation-induced photo-damage through activation of Nrf2/ARE pathway, thereby scavenging ROS and reducing DNA damage, and subsequently suppressing UVB-induced p38 MAP pathway. Thus, LBP can be potentially used for skincare against oxidative damage from environmental insults.

Constitutively expressed COX-2 in osteoblasts positively regulates Akt signal transduction via suppression of PTEN activity.

PubMed

Li, Ching-Ju; Chang, Je-Ken; Wang, Gwo-Jaw; Ho, Mei-Ling

2011-02-01

Cyclooxygenase-2 (COX-2) is thought to be an inducible enzyme, but increasing reports indicate that COX-2 is constitutively expressed in several organs. The status of COX-2 expression in bone and its physiological role remains undefined. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, which commonly suppress COX-2 activity, were reported to suppress osteoblast proliferation via Akt/FOXO3a/p27(Kip1) signaling, suggesting that COX-2 may be the key factor of the suppressive effects of NSAIDs on proliferation. Although Akt activation correlates with PTEN deficiency and cell viability, the role of COX-2 on PTEN/Akt regulation remains unclear. In this study, we hypothesized that COX-2 may be constitutively expressed in osteoblasts and regulate PTEN/Akt-related proliferation. We examined the localization and co-expression of COX-2 and p-Akt in normal mouse femurs and in cultured mouse (mOBs) and human osteoblasts (hOBs). Our results showed that osteoblasts adjacent to the trabeculae, periosteum and endosteum in mouse femurs constitutively expressed COX-2, while COX-2 co-expressed with p-Akt in osteoblasts sitting adjacent to trabeculae in vivo, and in mOBs and hOBs in vitro. We further used COX-2 siRNA to test the role of COX-2 in Akt signaling in hOBs; COX-2 silencing significantly inhibited PTEN phosphorylation, enhanced PTEN activity, and suppressed p-Akt level and proliferation. However, replenishment of the COX-2 enzymatic product, PGE2, failed to reverse COX-2-dependent Akt phosphorylation. Furthermore, transfection with recombinant human COX-2 (rhCOX-2) significantly reversed COX-2 siRNA-suppressed PTEN phosphorylation, but this effect was reduced when the enzymatic activity of rhCOX-2 was blocked. This finding indicated that the effect of COX-2 on PTEN/Akt signaling is not related to PGE2 but still dependent on COX-2 enzymatic activity. Conversely, COX-1 silencing did not affect PTEN/Akt signaling. Our findings provide new insight into bone physiology; namely, that COX-2 is constitutively expressed in osteoblasts in the dynamic bone growth area, which facilitates osteoblast proliferation via PTEN/Akt/p27(Kip1) signaling. Copyright © 2010 Elsevier Inc. All rights reserved.

Effect of α-particle irradiation on a NdFeAs(O,F) thin film

NASA Astrophysics Data System (ADS)

Tarantini, C.; Iida, K.; Sumiya, N.; Chihara, M.; Hatano, T.; Ikuta, H.; Singh, R. K.; Newman, N.; Larbalestier, D. C.

2018-07-01

The effect of α-particle irradiation on a NdFeAs(O,F) thin film has been investigated to determine how the introduction of defects affects basic superconducting properties, including the critical temperature T c and the upper critical field H c2, and properties more of interest for applications, like the critical current density J c and the related pinning landscape. The irradiation-induced suppression of the film T c is significantly smaller than on a similarly damaged single crystal. Moreover H c2 behaves differently, depending on the field orientation: for H//c the H c2 slope monotonically increases with increasing disorder, whereas for H//ab it remains constant at low dose and it increases only when the sample is highly disordered. This suggests that a much higher damage level is necessary to drive the NdFeAs(O,F) thin film into the dirty limit. Despite the increase in the low temperature H c2, the effects on the J c(H//c) performances are moderate in the measured temperature and field ranges, with a shifting of the pinning force maximum from 4.5 to 6 T after an irradiation of 2 × 1015 cm-2. On the contrary, J c(H//ab) is always suppressed. The analysis demonstrates that irradiation does introduce point defects (PD) acting as pinning centres proportionally to the irradiation fluence but also suppresses the effectiveness of c-axis correlated pinning present in the pristine sample. We estimate that significant performance improvements may be possible at high field or at temperatures below 10 K. The suppression of the J c(H//ab) performance is not related to a decrease of the J c anisotropy as found in other superconductors. Instead it is due to the presence of PD that decrease the efficiency of the ab-plane intrinsic pinning typical of materials with a layered structure.

Zinc L-carnosine suppresses inflammatory responses in lipopolysaccharide-induced RAW 264.7 murine macrophages cell line via activation of Nrf2/HO-1 signaling pathway.

PubMed

Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

2017-10-01

Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer. In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages. We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay. Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine. Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

Chitin amendment increases soil suppressiveness toward plant pathogens and modulates the actinobacterial and oxalobacteraceal communities in an experimental agricultural field.

PubMed

Cretoiu, Mariana Silvia; Korthals, Gerard W; Visser, Johnny H M; van Elsas, Jan Dirk

2013-09-01

A long-term experiment on the effect of chitin addition to soil on the suppression of soilborne pathogens was set up and monitored for 8 years in an experimental field, Vredepeel, The Netherlands. Chitinous matter obtained from shrimps was added to soil top layers on two different occasions, and the suppressiveness of soil toward Verticillium dahliae, as well as plant-pathogenic nematodes, was assessed, in addition to analyses of the abundances and community structures of members of the soil microbiota. The data revealed that chitin amendment had raised the suppressiveness of soil, in particular toward Verticillium dahliae, 9 months after the (second) treatment, extending to 2 years following treatment. Moreover, major effects of the added chitin on the soil microbial communities were detected. First, shifts in both the abundances and structures of the chitin-treated soil microbial communities, both of total soil bacteria and fungi, were found. In addition, the abundances and structures of soil actinobacteria and the Oxalobacteraceae were affected by chitin. At the functional gene level, the abundance of specific (family-18 glycoside hydrolase) chitinase genes carried by the soil bacteria also revealed upshifts as a result of the added chitin. The effects of chitin noted for the Oxalobacteraceae were specifically related to significant upshifts in the abundances of the species Duganella violaceinigra and Massilia plicata. These effects of chitin persisted over the time of the experiment.

Sensory effect of acetaldehyde on the perception of 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine: Role of acetaldehyde in sensory interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coetzee, C.; Brand, J.; Jacobson, Daniel A.

Background and Aims-Wine aroma is influenced by complex interactions between various wine constituents. This study investigated the sensory interactive effects of Sauvignon Blanc impact compounds, 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine, with acetaldehyde that typically forms during the oxidation of wine. Methods and Results-Spiked model wines were subjected to sensory descriptive analysis using a trained sensory panel. Additionally, the concentration of each compound varied from below aroma threshold values to high values as reported for wine. Depending on the concentration, acetaldehyde enhanced fruity attributes at a lower concentration, whereas suppression occurred at a higher concentration. Acetaldehyde effectively suppressed the green pepper aroma attributemore » at certain concentration values, whereas 3-mercaptohexan-1-ol suppressed oxidised green apple associated with acetaldehyde. Changes in attributes used for aroma description also occurred because of change in concentration. Conclusions-Complex sensory interactions may occur between Sauvignon Blanc impact compounds and one of the main oxidation-derived compounds, acetaldehyde. Acetaldehyde can enhance or suppress pleasant fruity characters depending on the concentration. Significance of the Study-This study showed the potential positive effect of acetaldehyde on white wine aroma when present at a low concentration. Formation of this compound during winemaking and ageing should, however, be controlled because of negative sensory interactions occurring at a higher concentration. In conclusion, this study may also contribute to the sensory characterisation of Sauvignon Blanc wine undergoing oxidation.« less

Sensory effect of acetaldehyde on the perception of 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine: Role of acetaldehyde in sensory interactions

DOE PAGES

Coetzee, C.; Brand, J.; Jacobson, Daniel A.; ...

2016-01-28

Background and Aims-Wine aroma is influenced by complex interactions between various wine constituents. This study investigated the sensory interactive effects of Sauvignon Blanc impact compounds, 3-mercaptohexan-1-ol and 3-isobutyl-2-methoxypyrazine, with acetaldehyde that typically forms during the oxidation of wine. Methods and Results-Spiked model wines were subjected to sensory descriptive analysis using a trained sensory panel. Additionally, the concentration of each compound varied from below aroma threshold values to high values as reported for wine. Depending on the concentration, acetaldehyde enhanced fruity attributes at a lower concentration, whereas suppression occurred at a higher concentration. Acetaldehyde effectively suppressed the green pepper aroma attributemore » at certain concentration values, whereas 3-mercaptohexan-1-ol suppressed oxidised green apple associated with acetaldehyde. Changes in attributes used for aroma description also occurred because of change in concentration. Conclusions-Complex sensory interactions may occur between Sauvignon Blanc impact compounds and one of the main oxidation-derived compounds, acetaldehyde. Acetaldehyde can enhance or suppress pleasant fruity characters depending on the concentration. Significance of the Study-This study showed the potential positive effect of acetaldehyde on white wine aroma when present at a low concentration. Formation of this compound during winemaking and ageing should, however, be controlled because of negative sensory interactions occurring at a higher concentration. In conclusion, this study may also contribute to the sensory characterisation of Sauvignon Blanc wine undergoing oxidation.« less