Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

PubMed

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2014-12-01

Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cassava Brown Streak Virus (Potyviridae) Encodes a Putative Maf/HAM1 Pyrophosphatase Implicated in Reduction of Mutations and a P1 Proteinase That Suppresses RNA Silencing but Contains No HC-Pro ▿

PubMed Central

Mbanzibwa, Deusdedith R.; Tian, Yanping; Mukasa, Settumba B.; Valkonen, Jari P. T.

2009-01-01

The complete positive-sense single-stranded RNA genome of Cassava brown streak virus (CBSV; genus Ipomovirus; Potyviridae) was found to consist of 9,069 nucleotides and predicted to produce a polyprotein of 2,902 amino acids. It was lacking helper-component proteinase but contained a single P1 serine proteinase that strongly suppressed RNA silencing. Besides the exceptional structure of the 5′-proximal part of the genome, CBSV also contained a Maf/HAM1-like sequence (678 nucleotides, 226 amino acids) recombined between the replicase and coat protein domains in the 3′-proximal part of the genome, which is highly conserved in Potyviridae. HAM1 was flanked by consensus proteolytic cleavage sites for ipomovirus NIaPro cysteine proteinase. Homology of CBSV HAM1 with cellular Maf/HAM1 pyrophosphatases suggests that it may intercept noncanonical nucleoside triphosphates to reduce mutagenesis of viral RNA. PMID:19386713

Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses.

PubMed

de Torres Zabala, Marta; Bennett, Mark H; Truman, William H; Grant, Murray R

2009-08-01

The importance of phytohormone balance is increasingly recognized as central to the outcome of plant-pathogen interactions. Recently it has been demonstrated that abscisic acid signalling pathways are utilized by the bacterial phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we examined the dynamics, inter-relationship and impact of three key acidic phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial virulence factor, coronatine, during progression of P. syringae infection of Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to play important early roles in determining the outcome of the infection process. SA is required in order to mount a full innate immune responses, while bacterial effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible innate immune responses by down-regulating SA biosynthesis and SA-mediated defences. Mutant analyses indicated that endogenous ABA levels represent an important reservoir that is necessary for effector suppression of plant-inducible innate defence responses and SA synthesis prior to subsequent pathogen-induced increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal resistance is epistatically dominant over acquired resistance due to ABA deficiency, although ABA also contributes to symptom development. We conclude that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences. We predict that hormonal perturbations, either induced or as a result of environmental stress, have a marked impact on pathological outcomes, and we provide a mechanistic basis for understanding priming events in plant defence.

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.

Feeding by whiteflies suppresses downstream jasmonic acid signaling by eliciting salicylic acid signaling.

PubMed

Zhang, Peng-Jun; Li, Wei-Di; Huang, Fang; Zhang, Jin-Ming; Xu, Fang-Cheng; Lu, Yao-Bin

2013-05-01

Phloem-feeding whiteflies in the species complex Bemisia tabaci cause extensive crop damage worldwide. One of the reasons for their "success" is their ability to suppress the effectual jasmonic acid (JA) defenses of the host plant. However, little is understood about the mechanisms underlying whitefly suppression of JA-regulated defenses. Here, we showed that the expression of salicylic acid (SA)-responsive genes (EDS1 and PR1) in Arabidopsis thaliana was significantly enhanced during feeding by whitefly nymphs. Whereas upstream JA-responsive genes (LOX2 and OPR3) also were induced, the downstream JA-responsive gene (VSP1) was repressed, i.e., whiteflies only suppressed downstream JA signaling. Gene-expression analyses with various Arabidopsis mutants, including NahG, npr-1, ein2-1, and dde2-2, revealed that SA signaling plays a key role in the suppression of downstream JA defenses by whitefly feeding. Assays confirmed that SA activation enhanced whitefly performance by suppressing downstream JA defenses.

L-Carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria.

PubMed

Oyanagi, Eri; Yano, Hiromi; Kato, Yasuko; Fujita, Hirofumi; Utsumi, Kozo; Sasaki, Junzo

2008-10-01

Membrane permeability transition (MPT) of mitochondria has an important role in apoptosis of various cells. The classic type of MPT is characterized by increased Ca(2+) transport, membrane depolarization, swelling, and sensitivity to cyclosporin A. In this study, we investigated whether L-carnitine suppresses oleic acid-induced MPT using isolated mitochondria from rat liver. Oleic acid-induced MPT in isolated mitochondria, inhibited endogenous respiration, caused membrane depolarization, and increased large amplitude swelling, and cytochrome c (Cyt. c) release from mitochondria. L-Carnitine was indispensable to beta-oxidation of oleic acid in the mitochondria, and this reaction required ATP and coenzyme A (CoA). In the presence of ATP and CoA, L-carnitine stimulated oleic acid oxidation and suppressed the oleic acid-induced depolarization, swelling, and Cyt. c release. L-Carnitine also contributed to maintaining mitochondrial function, which was decreased by the generation of free fatty acids with the passage of time after isolation. These results suggest that L-carnitine acts to maintain mitochondrial function and suppresses oleic acid-mediated MPT through acceleration of beta-oxidation. Copyright (c) 2008 John Wiley & Sons, Ltd.

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

PubMed Central

ZHAO, BING; HU, MENGCAI

2013-01-01

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study.

PubMed

Kilduff, Claire E; Counter, Melanie J; Thomas, Gareth A; Harrison, Nicholas K; Hope-Gill, Benjamin D

2014-01-01

Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57).

Effect of acid suppression therapy on gastroesophageal reflux and cough in idiopathic pulmonary fibrosis: an intervention study

PubMed Central

2014-01-01

Background Chronic cough affects more than 70 percent of patients with Idiopathic Pulmonary Fibrosis and causes significant morbidity. Gastroesophageal reflux is the cause of some cases of chronic cough; and also has a postulated role in the aetiology of Idiopathic Pulmonary Fibrosis. A high prevalence of acid; and more recently non-acid, reflux has been observed in Idiopathic Pulmonary Fibrosis cohorts. Therefore, gastroesophageal reflux may be implicated in the pathogenesis of cough in Idiopathic Pulmonary Fibrosis. Methods Eighteen subjects with Idiopathic Pulmonary Fibrosis underwent 24-hour oesophageal impedance and cough count monitoring after the careful exclusion of causes of chronic cough other than gastroesophageal reflux. All 18 were then treated with high dose acid suppression therapies. Fourteen subjects underwent repeat 24-hour oesophageal impedance and cough count monitoring after eight weeks. Results Total reflux and acid reflux frequencies were within the normal range in the majority of this cohort. The frequencies of non-acid and proximal reflux events were above the normal range. Following high dose acid suppression therapy there was a significant decrease in the number of acid reflux events (p = 0.02), but an increase in the number of non-acid reflux events (p = 0.01). There was no change in cough frequency (p = 0.70). Conclusions This study confirms that non-acid reflux is prevalent; and that proximal oesophageal reflux occurs in the majority, of subjects with Idiopathic Pulmonary Fibrosis. It is the first study to investigate the effect of acid suppression therapy on gastroesophageal reflux and cough in patients with Idiopathic Pulmonary Fibrosis. The observation that cough frequency does not improve despite verifiable reductions in oesophageal acid exposure challenges the role of acid reflux in Idiopathic Pulmonary Fibrosis associated cough. The finding that non-acid reflux is increased following the use of acid suppression therapies cautions against the widespread use of acid suppression in patients with Idiopathic Pulmonary Fibrosis given the potential role for non-acid reflux in the pathogenesis of cough and Idiopathic Pulmonary Fibrosis itself. Study registration The study was registered with the Cardiff and Vale University Local Health Board Research and Development Committee (09/CMC/4619) and the South East Wales Ethics Committee (09/WSE04/57). PMID:24876887

Signal enhancement for gradient reverse-phase high-performance liquid chromatography-electrospray ionization mass spectrometry analysis with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol.

PubMed

Kuhlmann, F E; Apffel, A; Fischer, S M; Goldberg, G; Goodley, P C

1995-12-01

Trifluoroacetic acid (TFA) and other volatile strong acids, used as modifiers in reverse-phase high-performance liquid chromatography, cause signal suppression for basic compounds when analyzed by electrospray ionization mass spectrometry (ESI-MS). Evidence is presented that signal suppression is caused by strong ion pairing between the TFA anion and the protonated sample cation of basic sample molecules. The ion-pairing process "masks" the protonated sample cations from the ESI-MS electric fields by rendering them "neutral. " Weakly basic molecules are not suppressed by this process. The TFA signal suppression effect is independent from the well-known spray problem that electrospray has with highly aqueous solutions that contain TFA. This previously reported spray problem is caused by the high conductivity and surface tension of aqueous TFA solutions. A practical method to enhance the signal for most basic analytes in the presence of signal-suppressing volatile strong acids has been developed. The method employs postcolumn addition of a solution of 75% propionic acid and 25% isopropanol in a ratio 1:2 to the column flow. Signal enhancement is typically 10-50 times for peptides and other small basic molecules. Thus, peptide maps that use ESI-MS for detection can be performed at lower levels, with conventional columns, without the need to use capillary chromatography or reduced mass spectral resolution to achieve satisfactory sensitivity. The method may be used with similar results for heptafluorobutyric acid and hydrochloric acid. A mechanism for TFA signal suppression and signal enhancement by the foregoing method, is proposed.

Linoleic acid suppresses cholesterol efflux and ATP-binding cassette transporters in murine bone marrow-derived macrophages

USDA-ARS?s Scientific Manuscript database

Individuals with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD), possibly associated with elevated plasma free fatty acid concentrations. Paradoxically, evidence suggests that unsaturated, compared to saturated fatty acids, suppress macrophage chole...

Escherichia coli tatC mutations that suppress defective twin-arginine transporter signal peptides.

PubMed

Strauch, Eva-Maria; Georgiou, George

2007-11-23

In vitro studies have suggested that the TatBC complex serves as the receptor for signal peptides targeted for export via the twin-arginine translocation (Tat) pathway. Substitution of the hallmark twin-arginine dipeptide with two lysines abrogates export of physiological substrates in all organisms. We report the isolation and characterization of suppressor mutations that allow export of an ssTor(KK)-GFP-SsrA tripartite fusion. We identified two amino acid suppressor mutations in the first cytoplasmic loop of TatC. In addition, two other amino acids in the first cytoplasmic loop exhibit epistatic suppression. Surprisingly, we also identified a suppressor mutation predicted to lie within the second periplasmic loop of TatC, a region that is not expected to interact directly with the signal peptide. The suppressor mutations allowed export of the native Esherichia coli Tat substrate trimethylamine N-oxide reductase with a twin-lysine substitution in its signal sequence. The cytoplasmic suppressor mutations conferred SDS sensitivity and partial filamentation, indicating that Tat export of authentic substrates was impaired.

Near-cognate suppression of amber, opal and quadruplet codons competes with aminoacyl-tRNAPyl for genetic code expansion

PubMed Central

O’Donoghue, Patrick; Prat, Laure; Heinemann, Ilka U.; Ling, Jiqiang; Odoi, Keturah; Liu, Wenshe R.; Söll, Dieter

2012-01-01

Over 300 amino acids are found in proteins in nature, yet typically only 20 are genetically encoded. Reassigning stop codons and use of quadruplet codons emerged as the main avenues for genetically encoding non-canonical amino acids (NCAAs). Canonical aminoacyl-tRNAs with near-cognate anticodons also read these codons to some extent. This background suppression leads to ‘statistical protein’ that contains some natural amino acid(s) at a site intended for NCAA. We characterize near-cognate suppression of amber, opal and a quadruplet codon in common Escherichia coli laboratory strains and find that the PylRS/tRNAPyl orthogonal pair cannot completely outcompete contamination by natural amino acids. PMID:23036644

Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARalpha and T- and B-cell targeting

EPA Science Inventory

T-cell-dependent antibody responses (TDAR) are suppressed in female C57BL/6N mice exposed to ≥3.75 mg/kg of perfluorooctanoic acid (PFOA) for 15 days. To determine if suppression of humoral immunity by PFOA is peroxisome proliferator activated receptor alpha (PPARa)-dependent and...

Effects of rare sugar D-allulose on acid production and probiotic activities of dairy lactic acid bacteria.

PubMed

Kimoto-Nira, H; Moriya, N; Hayakawa, S; Kuramasu, K; Ohmori, H; Yamasaki, S; Ogawa, M

2017-07-01

It has recently been reported that the rare sugar d-allulose has beneficial effects, including the suppression of postprandial blood glucose elevation in humans, and can be substituted for sucrose as a low-calorie food ingredient. To examine the applications of d-allulose in the dairy industry, we investigated the effects of d-allulose on the acid production of 8 strains of yogurt starter (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus) and 4 strains of lactococci, including potential probiotic candidates derived from dairy products. Acid production by 2 L. delbrueckii ssp. bulgaricus yogurt starter strains in milk was suppressed by d-allulose, but this phenomenon was also observed in some strains with another sugar (xylose), a sugar alcohol (sorbitol), or both. In contrast, among the dairy probiotic candidates, Lactococcus lactis H61, which has beneficial effects for human skin when drunk as part of fermented milk, was the only strain that showed suppression of acid production in the presence of d-allulose. Strain H61 did not metabolize d-allulose. We did not observe suppression of acid production by strain H61 with the addition of xylose or sorbitol, and xylose and sorbitol were not metabolized by strain H61. The acid production of strain H61 after culture in a constituted medium (tryptone-yeast extract-glucose broth) was also suppressed with the addition of d-allulose, but growth efficiency and sugar fermentation style were not altered. Probiotic activities-such as the angiotensin-converting enzyme inhibitory activity of H61-fermented milk and the superoxide dismutase activity of H61 cells grown in tryptone-yeast extract-glucose broth-were not affected by d-allulose. d-Allulose may suppress acid production in certain lactic acid bacteria without altering their probiotic activity. It may be useful for developing new probiotic dairy products from probiotic strains such as Lactococcus lactis H61. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images.

PubMed

Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R

2016-01-01

When monkeys view two images in fixed sequence repeatedly over days and weeks, neurons in area TE of the inferotemporal cortex come to exhibit prediction suppression. The trailing image elicits only a weak response when presented following the leading image that preceded it during training. Induction of prediction suppression might depend either on the contiguity of the images, as determined by their co-occurrence and captured in the measure of joint probability P(A,B), or on their contingency, as determined by their correlation and as captured in the measures of conditional probability P(A|B) and P(B|A). To distinguish between these possibilities, we measured prediction suppression after imposing training regimens that held P(A,B) constant but varied P(A|B) and P(B|A). We found that reducing either P(A|B) or P(B|A) during training attenuated prediction suppression as measured during subsequent testing. We conclude that prediction suppression depends on contingency, as embodied in the predictive relations between the images, and not just on contiguity, as embodied in their co-occurrence. Copyright © 2016 the American Physiological Society.

Suppressing my memories by listening to yours: The effect of socially triggered context-based prediction error on memory.

PubMed

Vlasceanu, Madalina; Drach, Rae; Coman, Alin

2018-05-03

The mind is a prediction machine. In most situations, it has expectations as to what might happen. But when predictions are invalidated by experience (i.e., prediction errors), the memories that generate these predictions are suppressed. Here, we explore the effect of prediction error on listeners' memories following social interaction. We find that listening to a speaker recounting experiences similar to one's own triggers prediction errors on the part of the listener that lead to the suppression of her memories. This effect, we show, is sensitive to a perspective-taking manipulation, such that individuals who are instructed to take the perspective of the speaker experience memory suppression, whereas individuals who undergo a low-perspective-taking manipulation fail to show a mnemonic suppression effect. We discuss the relevance of these findings for our understanding of the bidirectional influences between cognition and social contexts, as well as for the real-world situations that involve memory-based predictions.

Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.

PubMed

Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro

2017-04-01

The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.

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.

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

Interactions between cranberries and fungi: the proposed function of organic acids in virulence suppression of fruit rot fungi

PubMed Central

Tadych, Mariusz; Vorsa, Nicholi; Wang, Yifei; Bergen, Marshall S.; Johnson-Cicalese, Jennifer; Polashock, James J.; White, James F.

2015-01-01

Cranberry fruit are a rich source of bioactive compounds that may function as constitutive or inducible barriers against rot-inducing fungi. The content and composition of these compounds change as the season progresses. Several necrotrophic fungi cause cranberry fruit rot disease complex. These fungi remain mostly asymptomatic until the fruit begins to mature in late August. Temporal fluctuations and quantitative differences in selected organic acid profiles between fruit of six cranberry genotypes during the growing season were observed. The concentration of benzoic acid in fruit increased while quinic acid decreased throughout fruit development. In general, more rot-resistant genotypes (RR) showed higher levels of benzoic acid early in fruit development and more gradual decline in quinic acid levels than that observed in the more rot-susceptible genotypes. We evaluated antifungal activities of selected cranberry constituents and found that most bioactive compounds either had no effects or stimulated growth or reactive oxygen species (ROS) secretion of four tested cranberry fruit rot fungi, while benzoic acid and quinic acid reduced growth and suppressed secretion of ROS by these fungi. We propose that variation in the levels of ROS suppressive compounds, such as benzoic and quinic acids, may influence virulence by the fruit rot fungi. Selection for crops that maintain high levels of virulence suppressive compounds could yield new disease resistant varieties. This could represent a new strategy for control of disease caused by necrotrophic pathogens that exhibit a latent or endophytic phase. PMID:26322038

Distinguishing among potential mechanisms of singleton suppression.

PubMed

Gaspelin, Nicholas; Luck, Steven J

2018-04-01

Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Acid-suppressing therapies and subsite-specific risk of stomach cancer.

PubMed

Wennerström, E Christina M; Simonsen, Jacob; Camargo, M Constanza; Rabkin, Charles S

2017-04-25

Associations of stomach cancer risk with histamine type-2 receptor antagonists (H 2 RA) and proton-pump inhibitors (PPI) are controversial. We hypothesised that proximal extension of Helicobacter pylori infection from acid suppression would disproportionately increase cancers at proximal subsites. A total of 1 563 860 individuals in the Danish Prescription Drug Registry first prescribed acid-suppressive drugs 1995-2011 were matched to unexposed population-based controls. Hazard ratios (HR) were calculated by Cox proportional hazard regression for stomach cancers diagnosed more than one year after first prescription. There were 703 stomach cancers among H 2 RA-exposed individuals and 1347 among PPI-exposed. Restricted to individuals with five or more prescriptions, subsite-specific HRs for H 2 RA and PPI were 4.1 and 6.4 for proximal subsites vs 8.0 and 10.3 for distal subsites, respectively. Moderate exposures to acid-suppressive drugs did not favour proximal tumour localisation. Given confounding by indication, these findings do not resolve potential contribution to gastric carcinogenesis overall.

Omega-3 Free Fatty Acids Suppress Macrophage Inflammasome Activation by Inhibiting NF-κB Activation and Enhancing Autophagy

PubMed Central

Williams-Bey, Yolanda; Boularan, Cedric; Vural, Ali; Huang, Ning-Na; Hwang, Il-Young; Shan-Shi, Chong; Kehrl, John H.

2014-01-01

The omega-3 (ω3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity. PMID:24911523

Improved NASA-ANOPP Noise Prediction Computer Code for Advanced Subsonic Propulsion Systems. Volume 2; Fan Suppression Model Development

NASA Technical Reports Server (NTRS)

Kontos, Karen B.; Kraft, Robert E.; Gliebe, Philip R.

1996-01-01

The Aircraft Noise Predication Program (ANOPP) is an industry-wide tool used to predict turbofan engine flyover noise in system noise optimization studies. Its goal is to provide the best currently available methods for source noise prediction. As part of a program to improve the Heidmann fan noise model, models for fan inlet and fan exhaust noise suppression estimation that are based on simple engine and acoustic geometry inputs have been developed. The models can be used to predict sound power level suppression and sound pressure level suppression at a position specified relative to the engine inlet.

Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

PubMed

Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

2017-01-01

Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

Lung disease severity in idiopathic pulmonary fibrosis is more strongly associated with impedance measures of bolus reflux than pH parameters of acid reflux alone.

PubMed

Gavini, S; Borges, L F; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2017-05-01

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF). Pathogenesis may be related to chronic micro-aspiration. We aimed to assess objective measures of GER on multichannel intraluminal impedance and pH study (MII-pH) and their relationship with pulmonary function testing (PFT) results, and to compare the performance of pH/acid reflux parameters vs corresponding MII/bolus parameters in predicting pulmonary dysfunction in IPF. This was a retrospective cohort study of IPF patients undergoing prelung transplant evaluation with MII-pH off acid suppression, and having received PFT within 3 months. Patients with prior fundoplication were excluded. Severe pulmonary dysfunction was defined using diffusion capacity of the lung for carbon monoxide (DLCO) ≤40%. Six pH/acid reflux parameters with corresponding MII/bolus reflux measures were specified a priori. Multivariate analyses were applied using forward stepwise logistic regression. Predictive value of each parameter for severe pulmonary dysfunction was calculated by area-under-the-receiver-operating-characteristic-curve or c-statistic. Forty-five subjects (67% M, age 59, 15 mild-moderate vs 30 severe) met criteria for inclusion. Patient demographics and clinical characteristics were similar between pulmonary dysfunction groups. Abnormal total reflux episodes and prolonged bolus clearance time were significantly associated with pulmonary dysfunction severity on univariate and multivariate analyses. No pH parameters were significant. The c-statistic of each pH parameter was lower than its MII counterpart in predicting pulmonary dysfunction. MII/bolus reflux, but not pH/acid reflux, was associated with pulmonary dysfunction in prelung transplant patients with IPF. MII-pH may be more valuable than pH testing alone in characterizing GER in IPF. © 2016 John Wiley & Sons Ltd.

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.

Caffeic acid, a phenolic phytochemical in coffee, directly inhibits Fyn kinase activity and UVB-induced COX-2 expression

PubMed Central

Kang, Nam Joo; Lee, Ki Won; Shin, Bong Jik; Jung, Sung Keun; Hwang, Mun Kyung; Bode, Ann M.; Heo, Yong-Seok; Dong, Zigang

2009-01-01

Caffeic acid (3,4-dihydroxycinnamic acid) is a well-known phenolic phytochemical present in many foods, including coffee. Recent studies suggested that caffeic acid exerts anticarcinogenic effects, but little is known about the underlying molecular mechanisms and specific target proteins. In this study, we found that Fyn, one of the members of the non-receptor protein tyrosine kinase family, was required for ultraviolet (UV) B-induced cyclooxygenase-2 (COX-2) expression, and caffeic acid suppressed UVB-induced skin carcinogenesis by directly inhibiting Fyn kinase activity. Caffeic acid more effectively suppressed UVB-induced COX-2 expression and subsequent prostaglandin E2 production in JB6 P+ mouse skin epidermal (JB6 P+) cells compared with chlorogenic acid (5-O-caffeoylquinic acid), an ester of caffeic acid with quinic acid. Data also revealed that caffeic acid more effectively induced the downregulation of COX-2 expression at the transcriptional level mediated through the inhibition of activator protein-1 (AP-1) and nuclear factor-κB transcription activity compared with chlorogenic acid. Fyn kinase activity was suppressed more effectively by caffeic acid than by chlorogenic acid, and downstream mitogen-activated protein kinases (MAPKs) were subsequently blocked. Pharmacological Fyn kinase inhibitor (3-(4-chlorophenyl)1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and leflunomide) data also revealed that Fyn is involved in UVB-induced COX-2 expression mediated through the phosphorylation of MAPKs in JB6 P+ cells. Pull-down assays revealed that caffeic acid directly bound with Fyn and non-competitively with adenosine triphosphate. In vivo data from mouse skin also supported the idea that caffeic acid suppressed UVB-induced COX-2 expression by blocking Fyn kinase activity. These results suggested that this compound could act as a potent chemopreventive agent against skin cancer. PMID:19073879

Dynamic transition of neuronal firing induced by abnormal astrocytic glutamate oscillation

NASA Astrophysics Data System (ADS)

Li, Jiajia; Tang, Jun; Ma, Jun; Du, Mengmeng; Wang, Rong; Wu, Ying

2016-08-01

The gliotransmitter glutamate released from astrocytes can modulate neuronal firing by activating neuronal N-methyl-D-aspartic acid (NMDA) receptors. This enables astrocytic glutamate(AG) to be involved in neuronal physiological and pathological functions. Based on empirical results and classical neuron-glial “tripartite synapse” model, we propose a practical model to describe extracellular AG oscillation, in which the fluctuation of AG depends on the threshold of calcium concentration, and the effect of AG degradation is considered as well. We predict the seizure-like discharges under the dysfunction of AG degradation duration. Consistent with our prediction, the suppression of AG uptake by astrocytic transporters, which operates by modulating the AG degradation process, can account for the emergence of epilepsy.

Amino Acid-Assisted Dehalogenation of Carbon Tetrachloride by Green Rust: Inhibition of Chloroform Production.

PubMed

Yin, Weizhao; Strobel, Bjarne W; B Hansen, Hans Christian

2017-03-21

Layered Fe II -Fe III hydroxides (green rusts, GRs) are promising reactants for reductive dechlorination of chlorinated solvents due to high reaction rates and the opportunity to inject reactive slurries of the compounds into contaminant plumes. However, it is necessary to develop strategies that reduce the formation of toxic byproducts such as chloroform (CF). In this study, carbon tetrachloride (CT) dehalogenation by the chloride form of GR (GR Cl ) was tested in the presence of glycine (GLY) and other selected amino acids. GLY, alanine (ALA), and serine (SER) all resulted in remarkable suppression of CF formation with only ∼10% of CF recovery while sarcosine (SAR) showed insignificant effects. For two nonamino acid buffers, TRIS had little effect while HEPES resulted in a 40 times lower rate constant compared to experiments in which no buffer was added. The Fe II complexing properties of the amino acids and buffers caused variable extents of GR Cl dissolution which was linearly correlated with CF suppression and dehalogenation rate. We hypothesize that the CF suppression seen for amino acids is caused by stabilization of carbene intermediates via the carbonyl group. Different effects on CF suppression and CT dehalogenation rate were expected because of the different structural and chemical properties of the amino acids.

Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline.

PubMed

Ayabe, Tatsuhiro; Ohya, Rena; Kondo, Keiji; Ano, Yasuhisa

2018-03-19

Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD). Body weight, epididymal fat weight, and plasma triglyceride levels were increased in HFD-fed mice, and significantly decreased in iso-α-acids supplemented HFD-fed mice. HFD feeding enhances the production of inflammatory cytokines and chemokines, such as TNF-α, which was significantly suppressed by iso-α-acids administration. HFD-induced neuroinflammation caused lipid peroxidation, neuronal loss, and atrophy in hippocampus, and those were not observed in iso-α-acids-treated mice. Furthermore, iso-α-acids intake significantly improved cognitive decline induced by HFD-feeding. Iso-α-acids are food derived components that suppressing both lipid accumulation and brain inflammation, thus iso-α-acids might be beneficial for the risk of dementia increased by obesity and lifestyle-related diseases.

DIBROMOACETIC ACID ATTENUATES A DIMETHYLDITHIOCARBAMATE-INDUCED SUPPRESSION OF THE RAT LH SURGE

EPA Science Inventory

DIBROMOACETIC ACID ATTENUATES A DITHIOCARBAMATE-INDUCED SUPPRESSION OF THE LH SURGE IN THE RAT. Jerome M. Goldman, Ashley S. Murr, Angela R. Buckelew, W. Keith McElroy and Janet M. Ferrell. Repro. Toxicol. Div., NHEERL, ORD, US EPA, RTP, NC

At elevated concentrations, the ...

Perfluorooctanoic Acid Exposure Suppresses T-independent Antibody Responses

EPA Science Inventory

Exposure to  3.75mg/kg of perfluoroocatnoic acid (PFOA) for 15d suppresses T-dependent antibody responses (TDAR), suggesting that T helper cells and/or B cells/plasma cells may be impacted. This study evaluated effects of PFOA exposure on the T cell-independent antibody response...

An analytical technique for predicting the characteristics of a flexible wing equipped with an active flutter-suppression system and comparison with wind-tunnel data

NASA Technical Reports Server (NTRS)

Abel, I.

1979-01-01

An analytical technique for predicting the performance of an active flutter-suppression system is presented. This technique is based on the use of an interpolating function to approximate the unsteady aerodynamics. The resulting equations are formulated in terms of linear, ordinary differential equations with constant coefficients. This technique is then applied to an aeroelastic model wing equipped with an active flutter-suppression system. Comparisons between wind-tunnel data and analysis are presented for the wing both with and without active flutter suppression. Results indicate that the wing flutter characteristics without flutter suppression can be predicted very well but that a more adequate model of wind-tunnel turbulence is required when the active flutter-suppression system is used.

Ferulic Acid Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals

PubMed Central

Lin, Tzu Yu; Lu, Cheng Wei; Huang, Shu-Kuei

2013-01-01

Abstract This study investigated the effects and possible mechanism of ferulic acid, a naturally occurring phenolic compound, on endogenous glutamate release in the nerve terminals of the cerebral cortex in rats. Results show that ferulic acid inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). The effect of ferulic acid on the evoked glutamate release was prevented by chelating the extracellular Ca2+ ions, but was insensitive to the glutamate transporter inhibitor DL-threo-beta-benzyl-oxyaspartate. Ferulic acid suppressed the depolarization-induced increase in a cytosolic-free Ca2+ concentration, but did not alter 4-AP–mediated depolarization. Furthermore, the effect of ferulic acid on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking ryanodine receptors or mitochondrial Na+/Ca2+ exchange. These results show that ferulic acid inhibits glutamate release from cortical synaptosomes in rats through the suppression of presynaptic voltage-dependent Ca2+ entry. PMID:23342970

Combined thallium-201 and dynamic iodine-123 iodophenylpentadecanoic acid single-photon emission computed tomography in patients after acute myocardial infarction with effective reperfusion.

PubMed

Richter, W S; Beckmann, S; Cordes, M; Schuppenhauer, T; Schartl, M; Munz, D L

2000-12-01

Considerable derangements of energy metabolism are to be expected during ischemia and reperfusion. In ischemic myocardium, the oxidative degradation of carbohydrates is shifted toward the anaerobic production of lactate and the oxidation of fatty acids is suppressed. The aim of this study was to examine the uptake and metabolism of iodine-123 (123I) iodophenylpentadecanoic acid (IPPA) in stunned myocardium. In 15 patients, SPECT with 201Tl and 123I IPPA as well as echocardiography with low-dose dobutamine stimulation were performed 12 +/- 5 days after myocardial infarction with reperfusion. Follow-up echocardiography was carried out 24 +/- 8 days later for documentation of functional improvement. Uptake of 201Tl and 123I IPPA were obtained in five left ventricular segments, and dynamic SPECT imaging was used for calculation of the fast and the slow components of the biexponential myocardial 123I IPPA clearance. Wall motion improved in 14 of 26 dysfunctional segments (54%). Stunned segments were characterized by a reduced 123I IPPA extraction, a shorter half-life of the fast, and a longer half-life of the slow clearance component. All parameters of the combined 201Tl/123I IPPA study predicted functional recovery with similar accuracies (area under the receiver operator characteristic curves between 0.68 and 0.76; p = NS). Analysis of 201Tl uptake alone could not predict functional recovery in this study. Stunned myocardium is characterized by a disturbance of fatty acid metabolism. For prediction of functional improvement, 123I IPPA imaging added significant diagnostic information.

Comparative Analysis of EPA/DHA-PL Forage and Liposomes in Orotic Acid-Induced Nonalcoholic Fatty Liver Rats and Their Related Mechanisms.

PubMed

Chang, Mengru; Zhang, Tiantian; Han, Xiuqing; Tang, Qingjuan; Yanagita, Teruyoshi; Xu, Jie; Xue, Changhu; Wang, Yuming

2018-02-14

Nonalcoholic fatty liver disease (NAFLD) has become one predictive factor of death from various illnesses. The present study was to comparatively investigate the effects of eicosapentaenoic acid-enriched and docosahexaenoic acid-enriched phospholipids forage (EPA-PL and DHA-PL) and liposomes (lipo-EPA and lipo-DHA) on NAFLD and demonstrate the possible protective mechanisms involved. The additive doses of EPA-PL and DHA-PL in all treatment groups were 1% of total diets, respectively. The results showed that Lipo-EPA could significantly improve hepatic function by down-regulating orotic acid-induced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels by 55.6% and 34.2%, respectively (p < 0.01). Moreover, lipo-EPA exhibited excellent inhibition on the mRNA expression of SREBP-1c and FAS at the values of 0.454 ± 0.09 (p < 0.01) and 0.523 ± 0.08 (p < 0.01), respectively, thus ameliorating OA-induced NAFLD. Meanwhile, lipo-EPA could significantly suppress the SREBP-2 and HMGR levels (31.4% and 66.7%, p < 0.05, respectively). In addition, EPA-PL and lipo-DHA could also significantly suppress hepatic lipid accumulation mainly by enhancement of hepatic lipolysis and cholesterol efflux. Furthermore, DHA-PL played a certain role in inhibiting hepatic lipogenesis and accelerating cholesterol efflux. The results obtained in this work might contribute to the understanding of the biological activities of EPA/DHA-PL and liposomes and further investigation on its potential application values for food supplements.

DISRUPTION IN RAT ESTROUS CYCLICITY BY THE DRINKING WATER DISINFECTANT BY-PRODUCT DIBROMOACETIC ACID: RELATIONSHIP TO A SUPPRESSION ON ESTRADIOL METABOLISM?

EPA Science Inventory

Disruption in Rat Estrous Cyclicity by the Drinking Water Disinfectant By-Product Dibromoacetic Acid: Relationship to A Suppression on Estradiol Metabolism?

Ashley S. Murr and Jerome M. Goldman, Endocrinology Branch, Reproductive Toxicology Division National Health and En...

Suppression of elongation and growth of tomato seedlings by auxin biosynthesis inhibitors and modeling of the growth and environmental response.

PubMed

Higashide, Tadahisa; Narukawa, Megumi; Shimada, Yukihisa; Soeno, Kazuo

2014-04-02

To develop a growth inhibitor, the effects of auxin inhibitors were investigated. Application of 30 μM L-α-aminooxy-β-phenylpropionic acid (AOPP) or (S)-methyl 2-((1,3-dioxoisoindolin-2-yl)oxy)-3-phenylpropanoate (KOK1101), decreased the endogenous IAA levels in tomato seedlings at 8 days after sowing. Then, 10-1200 μM AOPP or KOK1101 were sprayed on the leaves and stem of 2-3 leaf stage tomato plants grown under a range of environmental conditions. We predicted plant growth and environmental response using a model based on the observed suppression of leaf enlargement. Spraying AOPP or KOK1101 decreased stem length and leaf area. Concentration-dependent inhibitions and dose response curves were observed. Although the effects of the inhibitors on dry weight varied according to the environmental conditions, the net assimilation rate was not influenced by the inhibitors. Accordingly, the observed decrease in dry weight caused by the inhibitors may result from decreased leaf area. Validation of the model based on observed data independent of the dataset showed good correlations between the observed and predicted values of dry weight and leaf area index.

Use of acid-suppressive therapy before anti-reflux surgery in 2922 patients: a nationwide register-based study in Denmark.

PubMed

Lødrup, A; Pottegård, A; Hallas, J; Bytzer, P

2015-07-01

Guidelines recommend that patients with gastro-oesophageal reflux disease are adequately treated with acid-suppressive therapy before undergoing anti-reflux surgery. Little is known of the use of acid-suppressive drugs before anti-reflux surgery. To determine the use of proton pump inhibitors and H2 -receptor antagonists in the year before anti-reflux surgery. A nationwide retrospective study of all patients aged ≥18 undergoing first-time anti-reflux surgery in Denmark during 2000-2012 using data from three different sources: the Danish National Register of Patients, the Danish National Prescription Register, and the Danish Person Register. The study population thus included 2922 patients (median age: 48 years, 55.7% male). The annual proportion of patients redeeming ≥180 DDD of acid-suppressive therapy increased from 17.0% 5 years before anti-reflux surgery to 64.9% 1 year before. The probability for inadequate dosing 1 year before surgery (<180 DDD) was significantly increased for younger patients, patients operated in the period 2000-2003, patients who had not undergone pre-surgical manometry, pH- or impedance monitoring, and patients who had not redeemed prescriptions on NSAID or anti-platelet drugs. Compliance with medical therapy should be evaluated thoroughly before planning anti-reflux surgery, as a high proportion of patients receive inadequate dosing of acid-suppressive therapy prior to the operation. © 2015 John Wiley & Sons Ltd.

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.

Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

PubMed

Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

2017-08-01

Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

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

Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

PubMed Central

Lee, Chan-Ho; Yoon, Seong-Jin; Lee, Sun-Mee

2012-01-01

Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders. PMID:23168580

Influence of Plant Hormones on Ethylene Production in Apple, Tomato, and Avocado Slices during Maturation and Senescence

PubMed Central

Lieberman, Morris; Baker, James E.; Sloger, Marcia

1977-01-01

Ethylene production by tissue slices from preclimacteric, climacteric, and postclimacteric apples was significantly reduced by isopentenyl adenosine (IPA), and by mixtures of IPA and indoleacetic acid, and of IPA, indoleacetic acid, and gibberellic acid after 4 hours of incubation. Ethylene production by apple (Pyrus malus L.) slices in abscisic acid was increased in preclimacteric tissues, decreased in climacteric peak tissues, and little affected in postclimacteric tissues. Indoleacetic acid suppressed ethylene production in tissues from preclimacteric apples but stimulated ethylene production in late climacteric rise, climacteric, and postclimacteric tissue slices. Gibberellic acid had less influence in suppressing ethylene production in preclimacteric peak tissue, and little influenced the production in late climacteric rise, climacteric peak, and postclimacteric tissues. IPA also suppressed ethylene production in pre- and postclimacteric tissue of tomatoes (Lycopersicon esculentum) and avocados (Persea gratissima). If ethylene production in tissue slices of ripening fruits is an index of aging, then IPA would appear to retard aging in ripening fruit, just as other cytokinins appear to retard aging in senescent leaf tissue. PMID:16660062

Influence of Plant Hormones on Ethylene Production in Apple, Tomato, and Avocado Slices during Maturation and Senescence.

PubMed

Lieberman, M; Baker, J E; Sloger, M

1977-08-01

Ethylene production by tissue slices from preclimacteric, climacteric, and postclimacteric apples was significantly reduced by isopentenyl adenosine (IPA), and by mixtures of IPA and indoleacetic acid, and of IPA, indoleacetic acid, and gibberellic acid after 4 hours of incubation. Ethylene production by apple (Pyrus malus L.) slices in abscisic acid was increased in preclimacteric tissues, decreased in climacteric peak tissues, and little affected in postclimacteric tissues. Indoleacetic acid suppressed ethylene production in tissues from preclimacteric apples but stimulated ethylene production in late climacteric rise, climacteric, and postclimacteric tissue slices. Gibberellic acid had less influence in suppressing ethylene production in preclimacteric peak tissue, and little influenced the production in late climacteric rise, climacteric peak, and postclimacteric tissues. IPA also suppressed ethylene production in pre- and postclimacteric tissue of tomatoes (Lycopersicon esculentum) and avocados (Persea gratissima). If ethylene production in tissue slices of ripening fruits is an index of aging, then IPA would appear to retard aging in ripening fruit, just as other cytokinins appear to retard aging in senescent leaf tissue.

Bile acids modulate glucocorticoid metabolism and the hypothalamic–pituitary–adrenal axis in obstructive jaundice☆

PubMed Central

McNeilly, Alison D.; Macfarlane, David P.; O’Flaherty, Emmett; Livingstone, Dawn E.; Mitić, Tijana; McConnell, Kirsty M.; McKenzie, Scott M.; Davies, Eleanor; Reynolds, Rebecca M.; Thiesson, Helle C.; Skøtt, Ole; Walker, Brian R.; Andrew, Ruth

2010-01-01

Background & Aims Suppression of the hypothalamic–pituitary–adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5β-reductase. Methods The effect of bile acids on glucocorticoid metabolism was studied in vitro in hepatic subcellular fractions and hepatoma cells, allowing quantitation of the kinetics and transcript abundance of 5β-reductase. Metabolism was subsequently examined in vivo in rats following dietary manipulation or bile duct ligation. Finally, glucocorticoid metabolism was assessed in humans with obstructive jaundice. Results In rat hepatic cytosol, chenodeoxycholic acid competitively inhibited 5β-reductase (Ki 9.19 ± 0.40 μM) and reduced its transcript abundance (in H4iiE cells) and promoter activity (reporter system, HepG2 cells). In Wistar rats, dietary chenodeoxycholic acid (1% w/w chow) inhibited hepatic 5β-reductase activity, reduced urinary excretion of 3α,5β-tetrahydrocorticosterone and reduced adrenal weight. Conversely, a fat-free diet suppressed bile acid levels and increased hepatic 5β-reductase activity, supplementation of the fat-free diet with CDCA reduced 5β-reductase activity, and urinary 3α,5β-reduced corticosterone. Cholestasis in rats suppressed hepatic 5β-reductase activity and transcript abundance. In eight women with obstructive jaundice, relative urinary excretion of 3α,5β-tetrahydrocortisol was significantly lower than in healthy controls. Conclusion These data suggest a novel role for bile acids in inhibiting hepatic glucocorticoid clearance, of sufficient magnitude to suppress hypothalamic–pituitary–adrenal axis activity. Elevated hepatic bile acids may account for adrenal insufficiency in liver disease. PMID:20347173

Triacylglycerol mobilization is suppressed by brefeldin A in Chlamydomonas reinhardtii

PubMed Central

Kato, Naohiro; Dong, Trung; Bailey, Michael; Lum, Tony; Ingram, Drury

2013-01-01

Brefeldin A suppresses vesicle trafficking by inhibiting exchange of GDP for GTP in ADP-ribosylation factor. We report that brefeldin A suppresses mobilization of triacylglycerols in Chlamydomonas reinhardtii, a model organism of green microalgae. Analyses revealed that brefeldin A causes Chlamydomonas to form lipid droplets in which triacylglycerols accumulate in a dose-dependent manner. Pulse labeling experiment using fluorescent fatty acids suggested that brefeldin A inhibits the cells from degrading fatty acids. The experiment also revealed that the cells transiently form novel compartments that accumulate exogenously added fatty acids in the cytoplasm, designated fatty acid-induced microbodies (FAIMs). Brefeldin A up-regulates the formation of FAIMs, whereas nitrogen deprivation that up-regulates triacylglycerol synthesis in Chlamydomonas does not cause the cells to form FAIMs. These results underscore the role of the vesicle trafficking machinery in triacylglycerol metabolism in green microalgae. PMID:23872273

Ferulic acid exerts antitumor activity and inhibits metastasis in breast cancer cells by regulating epithelial to mesenchymal transition.

PubMed

Zhang, Xiang; Lin, Dan; Jiang, Rong; Li, Hongzhong; Wan, Jingyuan; Li, Hongyuan

2016-07-01

Metastasis, which frequently occurs in breast cancer, is the major cause of mortality; therefore, new treatment strategies are urgently needed. Ferulic acid, isolated from Ferula foetida, a perennial herb, has shown antineoplastic activity in various types of cancers, such as colon and lung cancer, and central nervous system tumors. However, its potential role in suppressing breast cancer metastasis has not been fully understood. In the present study, we evaluated the antitumor activity of ferulic acid in breast cancer cell line-based in vitro and in vivo models. We first showed that ferulic acid treatment resulted in decreased viability, increased apoptosis and suppression of metastatic potential in breast cancer cell line MDA-MB-231. Furthermore, it was demonstrated that the antitumor activity of ferulic acid and its role in suppressing metastasis were regulated by the reversal of epithelial-mesenchymal transition (EMT). Consistent with our findings in vitro, the antitumor potential of ferulic acid was also verified in an MDA-MB-231 xenograft mouse model where significantly decreased tumor volume, weight and increased apoptosis were observed. Taken together, these results indicate that ferulic acid may be used as an effective therapeutic agent against breast cancer.

Nocturnal Gastroesophageal Reflux Revisited by Impedance-pH Monitoring

PubMed Central

Blondeau, Kathleen; Mertens, Veerle; Tack, Jan; Sifrim, Daniel

2011-01-01

Background/Aims Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. Methods Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. Results Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. Conclusions Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux. PMID:21602991

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid.

PubMed

Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie J M; Caillaud, Marie-Cécile; Furzer, Oliver J; Ishaque, Naveed; Wirthmueller, Lennart; Fabro, Georgina; Shirasu, Ken; Jones, Jonathan D G

2014-10-01

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome.

α-Lipoic acid suppresses the development of DNFB-induced atopic dermatitis-like symptoms in NC/Nga mice.

PubMed

Kim, Gun-Dong; Kim, Tae-Ho; Jang, An-Hee; Ahn, Hyun-Jong; Park, Yong Seek; Park, Cheung-Seog

2011-02-01

Atopic dermatitis (AD) is a common skin disease that has complex pathogenic mechanisms. Under specific pathogen-free conditions, repeated epicutaneous treatment of 2-4-dinitrofluorobenzene (DNFB) evokes AD-like clinical symptoms in NC/Nga mice. α-Lipoic acid (α-LA; 1, 2-dithiolane-3-pentanoic acid) is a dietary component that is synthesized in bacteria, yeast, plants, and mammals. α-LA and its reduced form, dihydrolipoic acid, are powerful antioxidants that have many physiological functions, including free radical scavenging of reactive oxygen species, generation of cellular antioxidants, chelation of metal ions, and inflammatory suppression. In this study, we investigated whether α-LA suppresses AD-like skin lesions induced by repeated DNFB application in NC/Nga mice. α-LA significantly suppressed production of interferon (IFN)-γ and interleukin (IL)-4 by activated CD4(+) T cells. We found that the oral administration of α-LA reduced AD-like clinical symptoms and inhibited increases of epidermal thickness in DNFB-induced AD-like skin lesions of NC/Nga mice. Furthermore, total serum IgE levels were dramatically reduced by topical α-LA treatment. Our findings suggest that oral administration of α-LA suppresses the development of AD in DNFB-treated NC/Nga mice and reduces IFN-γ and IL-4 production from activated CD4(+) T cells as well as total serum IgE levels. © 2011 John Wiley & Sons A/S.

Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma.

PubMed

Kast, Richard E

2008-10-01

This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid (ATRA, also termed tretinoin) exerts an anti-viral effect against hepatitis C virus (HCV) in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-a activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-a responses in these cancers.

Prediction suppression and surprise enhancement in monkey inferotemporal cortex.

PubMed

Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R

2017-07-01

Exposing monkeys, over the course of days and weeks, to pairs of images presented in fixed sequence, so that each leading image becomes a predictor for the corresponding trailing image, affects neuronal visual responsiveness in area TE. At the end of the training period, neurons respond relatively weakly to a trailing image when it appears in a trained sequence and, thus, confirms prediction, whereas they respond relatively strongly to the same image when it appears in an untrained sequence and, thus, violates prediction. This effect could arise from prediction suppression (reduced firing in response to the occurrence of a probable event) or surprise enhancement (elevated firing in response to the omission of a probable event). To identify its cause, we compared firing under the prediction-confirming and prediction-violating conditions to firing under a prediction-neutral condition. The results provide strong evidence for prediction suppression and limited evidence for surprise enhancement. NEW & NOTEWORTHY In predictive coding models of the visual system, neurons carry signed prediction error signals. We show here that monkey inferotemporal neurons exhibit prediction-modulated firing, as posited by these models, but that the signal is unsigned. The response to a prediction-confirming image is suppressed, and the response to a prediction-violating image may be enhanced. These results are better explained by a model in which the visual system emphasizes unpredicted events than by a predictive coding model. Copyright © 2017 the American Physiological Society.

Effects of lauric acid on ruminal protozoal numbers and fermentation pattern and milk production in lactating dairy cows

USDA-ARS?s Scientific Manuscript database

The objectives of this study were to evaluate lauric acid (LA) as a practical agent to suppress ruminal protozoa (RP), and to assess the effects of RP suppression on fermentation patterns and milk production in dairy cows. In experiment 1, six Holstein cows fitted with ruminal cannulae were used in ...

MODERATING INFLUENCE OF THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID ON A DITHIOCARBAMATE-INDUCED SUPPRESSION OF THE LUTEINIZING HORMONE SURGE IN FEMALE RATS.

EPA Science Inventory

The disinfection by-product dibromoacetic acid (DBA) has been found in female rats to increase circulating concentrations of both estradiol (E2) and estrone (E1). This effect is apparently due, at least in part, to a suppression in hepatic catabolism. The present study investigat...

Identification of cis-suppression of human disease mutations by comparative genomics.

PubMed

Jordan, Daniel M; Frangakis, Stephan G; Golzio, Christelle; Cassa, Christopher A; Kurtzberg, Joanne; Davis, Erica E; Sunyaev, Shamil R; Katsanis, Nicholas

2015-08-13

Patterns of amino acid conservation have served as a tool for understanding protein evolution. The same principles have also found broad application in human genomics, driven by the need to interpret the pathogenic potential of variants in patients. Here we performed a systematic comparative genomics analysis of human disease-causing missense variants. We found that an appreciable fraction of disease-causing alleles are fixed in the genomes of other species, suggesting a role for genomic context. We developed a model of genetic interactions that predicts most of these to be simple pairwise compensations. Functional testing of this model on two known human disease genes revealed discrete cis amino acid residues that, although benign on their own, could rescue the human mutations in vivo. This approach was also applied to ab initio gene discovery to support the identification of a de novo disease driver in BTG2 that is subject to protective cis-modification in more than 50 species. Finally, on the basis of our data and models, we developed a computational tool to predict candidate residues subject to compensation. Taken together, our data highlight the importance of cis-genomic context as a contributor to protein evolution; they provide an insight into the complexity of allele effect on phenotype; and they are likely to assist methods for predicting allele pathogenicity.

A Diel Flux Balance Model Captures Interactions between Light and Dark Metabolism during Day-Night Cycles in C3 and Crassulacean Acid Metabolism Leaves.

PubMed

Cheung, C Y Maurice; Poolman, Mark G; Fell, David A; Ratcliffe, R George; Sweetlove, Lee J

2014-06-01

Although leaves have to accommodate markedly different metabolic flux patterns in the light and the dark, models of leaf metabolism based on flux-balance analysis (FBA) have so far been confined to consideration of the network under continuous light. An FBA framework is presented that solves the two phases of the diel cycle as a single optimization problem and, thus, provides a more representative model of leaf metabolism. The requirement to support continued export of sugar and amino acids from the leaf during the night and to meet overnight cellular maintenance costs forces the model to set aside stores of both carbon and nitrogen during the day. With only minimal constraints, the model successfully captures many of the known features of C 3 leaf metabolism, including the recently discovered role of citrate synthesis and accumulation in the night as a precursor for the provision of carbon skeletons for amino acid synthesis during the day. The diel FBA model can be applied to other temporal separations, such as that which occurs in Crassulacean acid metabolism (CAM) photosynthesis, allowing a system-level analysis of the energetics of CAM. The diel model predicts that there is no overall energetic advantage to CAM, despite the potential for suppression of photorespiration through CO 2 concentration. Moreover, any savings in enzyme machinery costs through suppression of photorespiration are likely to be offset by the higher flux demand of the CAM cycle. It is concluded that energetic or nitrogen use considerations are unlikely to be evolutionary drivers for CAM photosynthesis. © 2014 American Society of Plant Biologists. All Rights Reserved.

A Diel Flux Balance Model Captures Interactions between Light and Dark Metabolism during Day-Night Cycles in C3 and Crassulacean Acid Metabolism Leaves1[C][W][OPEN

PubMed Central

Cheung, C.Y. Maurice; Poolman, Mark G.; Fell, David. A.; Ratcliffe, R. George; Sweetlove, Lee J.

2014-01-01

Although leaves have to accommodate markedly different metabolic flux patterns in the light and the dark, models of leaf metabolism based on flux-balance analysis (FBA) have so far been confined to consideration of the network under continuous light. An FBA framework is presented that solves the two phases of the diel cycle as a single optimization problem and, thus, provides a more representative model of leaf metabolism. The requirement to support continued export of sugar and amino acids from the leaf during the night and to meet overnight cellular maintenance costs forces the model to set aside stores of both carbon and nitrogen during the day. With only minimal constraints, the model successfully captures many of the known features of C3 leaf metabolism, including the recently discovered role of citrate synthesis and accumulation in the night as a precursor for the provision of carbon skeletons for amino acid synthesis during the day. The diel FBA model can be applied to other temporal separations, such as that which occurs in Crassulacean acid metabolism (CAM) photosynthesis, allowing a system-level analysis of the energetics of CAM. The diel model predicts that there is no overall energetic advantage to CAM, despite the potential for suppression of photorespiration through CO2 concentration. Moreover, any savings in enzyme machinery costs through suppression of photorespiration are likely to be offset by the higher flux demand of the CAM cycle. It is concluded that energetic or nitrogen use considerations are unlikely to be evolutionary drivers for CAM photosynthesis. PMID:24596328

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 Central

Shin, Hee Soon; Satsu, Hideo; Bae, Min-Jung; Totsuka, Mamoru; Shimizu, Makoto

2017-01-01

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. PMID:28230729

The relation of weight suppression and BMI to bulimic symptoms.

PubMed

Butryn, Meghan L; Juarascio, Adrienne; Lowe, Michael R

2011-11-01

High levels of weight suppression have been associated with greater binge eating and weight gain as well as poorer treatment outcome in bulimia nervosa. This study examined the relationship between weight suppression and bulimia nervosa symptoms and explored how weight suppression might interact with body mass index (BMI) in accounting for level of symptomatology at presentation for treatment. Participants were 64 women with threshold or sub-threshold bulimia nervosa. A clinical interview assessed binge eating and purging. Weight suppression and the interaction between BMI and weight suppression predicted frequency of binge eating such that participants with low BMI and high weight suppression engaged in the most binge eating. High levels of weight suppression also predicted more frequent purging. Additional research is warranted to examine mediators of these relationships. Copyright © 2010 Wiley Periodicals, Inc.

Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis.

PubMed

Yang, Guang-Wei; Jiang, Jin-Song; Lu, Wei-Qin

2015-10-12

Most anti-angiogenic therapies currently being evaluated target the vascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here, we identified ferulic acid as a novel fibroblast growth factor receptor 1 (FGFR1) inhibitor and a novel agent with potential anti-angiogenic and anti-cancer activities. Ferulic acid demonstrated inhibition of endothelial cell proliferation, migration and tube formation in response to basic fibroblast growth factor 1 (FGF1). In ex vivo and in vivo angiogenesis assays, ferulic acid suppressed FGF1-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of ferulic acid on different molecular components and found that ferulic acid suppressed FGF1-triggered activation of FGFR1 and phosphatidyl inositol 3-kinase (PI3K)-protein kinase B (Akt) signaling. Moreover, ferulic acid directly inhibited proliferation and blocked the PI3K-Akt pathway in melanoma cell. In vivo, using a melanoma xenograft model, ferulic acid showed growth-inhibitory activity associated with inhibition of angiogenesis. Taken together, our results indicate that ferulic acid targets the FGFR1-mediated PI3K-Akt signaling pathway, leading to the suppression of melanoma growth and angiogenesis.

An analytical model of non-photorespiratory CO₂release in the light and dark in leaves of C₃species based on stoichiometric flux balance.

PubMed

Buckley, Thomas N; Adams, Mark A

2011-01-01

Leaf respiration continues in the light but at a reduced rate. This inhibition is highly variable, and the mechanisms are poorly known, partly due to the lack of a formal model that can generate testable hypotheses. We derived an analytical model for non-photorespiratory CO₂ release by solving steady-state supply/demand equations for ATP, NADH and NADPH, coupled to a widely used photosynthesis model. We used this model to evaluate causes for suppression of respiration by light. The model agrees with many observations, including highly variable suppression at saturating light, greater suppression in mature leaves, reduced assimilatory quotient (ratio of net CO₂ and O₂ exchange) concurrent with nitrate reduction and a Kok effect (discrete change in quantum yield at low light). The model predicts engagement of non-phosphorylating pathways at moderate to high light, or concurrent with processes that yield ATP and NADH, such as fatty acid or terpenoid synthesis. Suppression of respiration is governed largely by photosynthetic adenylate balance, although photorespiratory NADH may contribute at sub-saturating light. Key questions include the precise diel variation of anabolism and the ATP : 2e⁻ ratio for photophosphorylation. Our model can focus experimental research and is a step towards a fully process-based model of CO₂ exchange. © 2010 Blackwell Publishing Ltd.

Histone deacetylase inhibitor valproic acid promotes the induction of pluripotency in mouse fibroblasts by suppressing reprogramming-induced senescence stress

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

Zhai, Yingying; Chen, Xi; Yu, Dehai

2015-09-10

Histone deacetylase inhibitor valproic acid (VPA) has been used to increase the reprogramming efficiency of induced pluripotent stem cell (iPSC) from somatic cells, yet the specific molecular mechanisms underlying this effect is unknown. Here, we demonstrate that reprogramming with lentiviruses carrying the iPSC-inducing factors (Oct4-Sox2-Klf4-cMyc, OSKM) caused senescence in mouse fibroblasts, establishing a stress barrier for cell reprogramming. Administration of VPA protected cells from reprogramming-induced senescent stress. Using an in vitro pre-mature senescence model, we found that VPA treatment increased cell proliferation and inhibited apoptosis through the suppression of the p16/p21 pathway. In addition, VPA also inhibited the G2/M phasemore » blockage derived from the senescence stress. These findings highlight the role of VPA in breaking the cell senescence barrier required for the induction of pluripotency. - Highlights: • Histone deacetylase inhibitor valproic acid enhances iPSC induction. • Valproic acid suppresses reprogramming-induced senescence stress. • Valproic acid downregulates the p16/p21 pathway in reprogramming. • This study demonstrates a new mechanistic role of valproic acid in enhancing reprogramming.« less

Extracellular acidification by lactic acid suppresses glucose deprivation-induced cell death and autophagy in B16 melanoma cells.

PubMed

Matsuo, Taisuke; Sadzuka, Yasuyuki

2018-02-19

In solid tumors, cancer cells survive and proliferate under conditions of microenvironment stress such as poor nutrients and hypoxia due to inadequate vascularization. These stress conditions in turn activate autophagy, which is important for cancer cell survival. However, autophagy has a contrary effect of inducing cell death in cancer cells cultured in vitro under conditions of glucose deprivation. In this study, we hypothesized that supplementation of lactic acid serves as a means of cell survival under glucose-deprived conditions. At neutral pH, cell death of B16 murine melanoma cells by autophagy under glucose-deprived conditions was observed. However, supplementation of lactic acid suppressed cell death and autophagy in B16 melanoma cells when cultured in glucose-deprived conditions. Sodium lactate, which does not change extracellular pH, did not inhibit cell death, while HCl-adjusted acidic pH suppressed cell death under glucose-deprived conditions. These results suggested that an acidic pH is crucial for cell survival under glucose-deprived conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Rethinking the bile acid/gut microbiome axis in cancer

PubMed Central

Phelan, John P.; Reen, F. Jerry; Caparros-Martin, Jose A.; O'Connor, Rosemary; O'Gara, Fergal

2017-01-01

Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts. PMID:29383197

Acid suppression and surgical therapy for Barrett's oesophagus.

PubMed

de Jonge, Pieter J F; Spaander, Manon C; Bruno, Marco J; Kuipers, Ernst J

2015-02-01

Gastro-oesophageal reflux disease is a common medical problem in developed countries, and is a risk factor for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Both proton pump inhibitor therapy and antireflux surgery are effective at controlling endoscopic signs and symptoms of gastro-oesophageal reflux in patients with Barrett's oesophagus, but often fail to eliminate pathological oesophageal acid exposure. The current available studies strongly suggest that acid suppressive therapy, both pharmacological as well as surgical acid suppression, can reduce the risk the development and progression in patients with Barrett's oesophagus, but are not capable of complete prevention. No significant differences have been found between pharmacological and surgical therapy. For clinical practice, patients should be prescribed a proton pump inhibitor once daily as maintenance therapy, with the dose guided by symptoms. Antireflux surgery can be a good alternative to proton pump inhibitor therapy, but should be primarily offered to patients with symptomatic reflux, and not to asymptomatic patients with the rationale to protect against cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antagonism between abscisic acid and gibberellins is partially mediated by ascorbic acid during seed germination in rice.

PubMed

Ye, Nenghui; Zhang, Jianhua

2012-05-01

The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. In the associated study, we investigated the relationship among ABA, reactive oxygen species (ROS), ascorbic acid (ASC) and GA during rice seed germination. ROS production is reduced by ABA, which hence results in decreasing ASC accumulation during imbibition. GA accumulation was also suppressed by a reduced ROS and ASC level, whereas application of exogenous ASC can partially rescue seed germination from ABA treatment. Further results show that production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. These studies reveal a new role for ASC in mediating the antagonism between ABA and GA during seed germination in rice.

Acid suppressants for managing gastro-oesophageal reflux and gastro-oesophageal reflux disease in infants: a national survey.

PubMed

Bell, Jane C; Schneuer, Francisco J; Harrison, Christopher; Trevena, Lyndal; Hiscock, Harriet; Elshaug, Adam G; Nassar, Natasha

2018-02-22

To evaluate the diagnosis and management of reflux and gastro-oesophageal reflux disease (GORD) in infants aged <1 year presenting to general practitioners (GPs). A nationally representative, prospective, cross-sectional survey of GP activity in Australia, 2006-2016 (Bettering the Evaluation And Care of Health Study). Annually, a random sample of around 1000 GPs recorded details for 100 consecutive visits with consenting, unidentified patients. Diagnoses of reflux and GORD and their management including prescribing of acid-suppressant medicines (proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs)) and counselling, advice or education. Of all infants' visits, 512 (2.7%) included a diagnosis of reflux (n=413, 2.2%) or GORD (n=99, 0.5%). From 2006 to 2016, diagnostic rates decreased for reflux and increased for GORD. Prescribing of acid suppressants occurred in 43.6% visits for reflux and 48.5% visits for GORD, similar to rates of counselling, advice or education (reflux: 38.5%, GORD: 43.4% of visits). Prescribing of PPIs increased (statistically significant only for visits for reflux), while prescribing of H2RAs decreased. Overprescribing of acid suppressants to infants may be occurring. In infants, acid-suppressant medicines are no better than placebo and may have significant negative side effects; however, guidelines are inconsistent. Clear, concise and consistent guidance is needed. GPs and parents need to understand what is normal and limitations of medical therapy. We need a greater understanding of the influences on GP prescribing practices, of parents' knowledge and attitudes and of the pressures on parents of infants with these conditions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers.

PubMed

Morelli, G; Chen, H; Rossiter, G; Rege, B; Lu, Y

2011-04-01

Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients. To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg. Helicobacter pylori-negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty-four-hour intragastric pH was monitored on days -1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5. A total of 248 subjects (N=31/group) were enrolled in the study. On day 5, rabeprazole-ER groups provided mean durations of 18.5-20.2 h (77.0-84.1% of 24-h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24-h) and rabeprazole-DR 20 mg (15.2 h/63.2% of 24-h). A similar increase was observed on day 1. While percentage of daytime (8 am-10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night-time (10 pm-8 am) with intragastric pH >4.0 was higher with the rabeprazole-ER groups (57.0-72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole-DR 20 mg (34.0%). Rabeprazole-ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole-DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night-time; this was supported by the extended-release pharmacokinetic characteristics. © 2011 Blackwell Publishing Ltd.

Impact of persistent, frequent regurgitation on quality of life in heartburn responders treated with acid suppression: a multinational primary care study.

PubMed

Kahrilas, P J; Howden, C W; Wernersson, B; Denison, H; Nuevo, J; Gisbert, J P

2013-05-01

In gastro-oesophageal reflux disease (GERD), heartburn responds well to acid suppression, but regurgitation is a common cause of incomplete treatment response. To assess the prevalence and burden of persistent, frequent regurgitation in primary care patients with GERD treated with acid suppression. We analysed observational data from 134 sites across six European countries in patients diagnosed with GERD. Within 3 months of the index visit, symptoms were assessed using the Reflux Disease Questionnaire, and their impact on sleep and work productivity with the Quality of Life in Reflux and Dyspepsia questionnaire and the Work Productivity and Activity Impairment Questionnaire, respectively. Patients provided information on concomitant over-the-counter (OTC) GERD medication use. Persistent, frequent (3-7 days/week) regurgitation was reported by 13.2% (153/1156) of GERD patients with no heartburn on acid suppression; the prevalence was very similar for patients with up to 2 days/week of ongoing mild heartburn. Among patients without heartburn, sleep disturbance of any type was reported by 50.7-60.1% with persistent, frequent regurgitation, compared with 38.1-51.1% and 14.4-19.2% of those with less frequent or no regurgitation respectively. Persistent, frequent regurgitation was associated with increased use of OTC medication and more hours of work missed, whether mild, infrequent heartburn was present or not. Frequent regurgitation, which persisted in 12-13% of patients with no or infrequent, mild heartburn on acid suppression, negatively affected sleep and work productivity, and increased use of OTC medication. Persistent, frequent regurgitation is problematic for primary care patients with GERD. © 2013 Blackwell Publishing Ltd.

3-Aminoquinoline/p-coumaric acid as a MALDI matrix for glycopeptides, carbohydrates, and phosphopeptides.

PubMed

Fukuyama, Yuko; Funakoshi, Natsumi; Takeyama, Kohei; Hioki, Yusaku; Nishikaze, Takashi; Kaneshiro, Kaoru; Kawabata, Shin-Ichirou; Iwamoto, Shinichi; Tanaka, Koichi

2014-02-18

Glycosylation and phosphorylation are important post-translational modifications in biological processes and biomarker research. The difficulty in analyzing these modifications is mainly their low abundance and dissociation of labile regions such as sialic acids or phosphate groups. One solution in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is to improve matrices for glycopeptides, carbohydrates, and phosphopeptides by increasing the sensitivity and suppressing dissociation of the labile regions. Recently, a liquid matrix 3-aminoquinoline (3-AQ)/α-cyano-4-hydroxycinnamic acid (CHCA) (3-AQ/CHCA), introduced by Kolli et al. in 1996, has been reported to increase sensitivity for carbohydrates or phosphopeptides, but it has not been systematically evaluated for glycopeptides. In addition, 3-AQ/CHCA enhances the dissociation of labile regions. In contrast, a liquid matrix 1,1,3,3-tetramethylguanidium (TMG, G) salt of p-coumaric acid (CA) (G3CA) was reported to suppress dissociation of sulfate groups or sialic acids of carbohydrates. Here we introduce a liquid matrix 3-AQ/CA for glycopeptides, carbohydrates, and phosphopeptides. All of the analytes were detected as [M + H](+) or [M - H](-) with higher or comparable sensitivity using 3-AQ/CA compared with 3-AQ/CHCA or 2,5-dihydroxybenzoic acid (2,5-DHB). The sensitivity was increased 1- to 1000-fold using 3-AQ/CA. The dissociation of labile regions such as sialic acids or phosphate groups and the fragmentation of neutral carbohydrates were suppressed more using 3-AQ/CA than using 3-AQ/CHCA or 2,5-DHB. 3-AQ/CA was thus determined to be an effective MALDI matrix for high sensitivity and the suppression of dissociation of labile regions in glycosylation and phosphorylation analyses.

Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

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

Fang, Zhong-Ze; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian

Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showedmore » that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.« less

Activation of peroxisome proliferator-activated receptor-α (PPARα) in proximal intestine improves postprandial lipidemia in obese diabetic KK-Ay mice.

PubMed

Kimura, Rino; Takahashi, Nobuyuki; Goto, Tsuyoshi; Murota, Kaeko; Kawada, Teruo

2013-01-01

Postprandial lipidemia is a risk factor for cardiovascular diseases. Thus, the suppression of postprandial lipidemia is valuable for disease management. Peroxisome proliferator-activated receptor- (PPAR ) is a key regulator in the lipid metabolism of peripheral tissues such as the liver and skeletal muscle, whose activation enhances fatty acid oxidation and decreases circulating lipid level. Recently, we have shown that bezafibrate, an agonistic compound for PPAR , suppresses post-prandial lipidemia by enhancing fatty acid oxidation in intestinal epithelial cells under physiological conditions. However, it was not elucidated whether the effect of PPAR on postprandial lipidemia is also observed under obese conditions, which change lipid metabolisms in various tissues and cells. Here, we observed that bezafibrate enhanced fatty acid oxidation in intestinal epithelial cells of obese diabetic KK-Ay mice. Bezafibrate treatment increased the mRNA expression levels of fatty acid oxidation-related genes, which are targets of PPAR , and enhanced CO2 production from [14C]-palmitic acid. The bezafibrate-treated mice showed the suppression of increasing serum triacylglyceride level after the oral administration of olive oil. Moreover, the effects of bezafibrate on mRNA expression and fatty acid oxidation were shown in only the proximal intestinal epithelial cells. These findings indicate that PPAR activation suppresses postprandial lipidemia under obese conditions through the enhancement of fatty acid oxidation, and that only the proximal intestine con-tributes to the effects in mice, suggesting that intestinal PPAR can be a target for prevention of obese-induced postprandial lipidemia. © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Foam suppression in overloaded manure-based biogas reactors using antifoaming agents.

PubMed

Kougias, P G; Boe, K; Tsapekos, P; Angelidaki, I

2014-02-01

Foam control is an imperative need in biogas plants, as foaming is a major operational problem. In the present study, the effect of oils (rapeseed oil, oleic acid, and octanoic acid) and tributylphosphate on foam reduction and process performance in batch and continuous manure-based biogas reactors was investigated. The compounds were tested in dosages of 0.05%, 0.1% and 0.5% v/vfeed. The results showed that rapeseed oil was most efficient to suppress foam at the dosage of 0.05% and 0.1% v/vfeed, while octanoic acid was most efficient to suppress foam at dosage of 0.5% v/vfeed. Moreover, the addition of rapeseed oil also increased methane yield. In contrast, tributylphosphate, which was very efficient antifoam, was found to be inhibitory to the biogas process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Acid-suppressive efficacy of a reduced dosage of rabeprazole: comparison of 10 mg twice daily rabeprazole with 20 mg twice daily rabeprazole, 30 mg twice daily lansoprazole, and 20 mg twice daily omeprazole by 24-hr intragastric pH-metry.

PubMed

Shimatani, Tomohiko; Inoue, Masaki; Kuroiwa, Tomoko; Xu, Jing; Tazuma, Susumu; Horikawa, Yoko; Nakamura, Masuo

2005-07-01

Rabeprazole achieves more potent acid suppression than other proton pump inhibitors. Therefore it is administered at reduced as well as high dosages in eradication therapy for Helicobacter pylori; however, there is incomplete assessment of the efficacy of a reduced dosage of rabeprazole as might be employed in therapy. In this study, we evaluated acid-suppressive efficacy of a reduced dosage of rabeprazole on day 7 by 24-hr pH-metry in 10 healthy male cytochrome P-450 2C19 extensive metabolizers without Helicobacterpylori infection and compared the results with those of high dosages of rabeprazole, lansoprazole, and omeprazole. Median intragastric pH value, pH >3 holding time ratio (pH>3HT), pH>4HT, pH>5HT, pH>6HT, and pH>7HT for 24 hr with rabeprazole, 10 mg twice daily, were not significantly different from those of rabeprazole, 20 mg twice daily, lansoprazole, 30 mg twice daily, and omeprazole, 20 mg twice daily. In conclusion, for acid-suppressive efficacy, a reduced dosage of rabeprazole is comparable to high dosages of rabeprazole, lansoprazole, and omeprazole.

Astringent compounds suppress taste responses in gerbil.

PubMed

Schiffman, S S; Suggs, M S; Simon, S A

1992-11-06

Astringent tastes are generally considered those that induce long-lasting puckering and drying sensations on the tongue and membranes of the oral cavity. Electrophysiological recordings were made here from the whole chorda tympani nerve in gerbil to understand the interactive effect of astringent-tasting molecules with a broad spectrum of tastants including mono- and divalent salts, bitter compounds, acids, and sweeteners. The astringent tasting compounds were tannic acid (24 mM at pH's 2.9 and 5.5), aluminum ammonium sulfate (30 mM), aluminum potassium sulfate (10 mM) and gallic acid (30 mM). Hydrochloric acid (1 mM, pH 2.9) was also tested to control for acidity, since aqueous solutions of astringent-tasting compounds are acidic. Adaptation of the tongue to tannic acid (24 mM) at both pH 2.9 and 5.5 markedly inhibited responses elicited by salts, acids, sweeteners, and bitter-tasting compounds. The degree of the inhibition at these two pH values is about the same which suggests that tannic acid itself (as opposed to acidity) may produce this inhibition. Chorda tympani responses to sweeteners were completely suppressed by tannic acid; responses to KCl, NH4Cl, and urea were the least suppressed. The aluminum salts also inhibited the chorda tympani responses to all stimuli tested. Gallic acid, which is weakly astringent, had minimal effects on the chorda tympani responses to the test compounds. These data suggest that both tannic acid and the aluminum salts inhibit a variety of transport pathways and receptors in taste cells for a broad spectrum of tastants. The inhibition of some of these pathways may contribute to the astringent taste sensation.

Methionine and serine synergistically suppress hyperhomocysteinemia induced by choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein diet.

PubMed

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

2011-01-01

The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.

Weight Suppression Predicts Bulimic Symptoms at 20-year Follow-up: The Mediating Role of Drive for Thinness

PubMed Central

Bodell, Lindsay P.; Brown, Tiffany A.; Keel, Pamela K.

2016-01-01

Weight suppression predicts the onset and maintenance of bulimic syndromes. Despite this finding, no study has examined psychological mechanisms contributing to these associations using a longitudinal design. Given societal pressures to be thin and an actual history of higher weight, it is possible that greater weight suppression contributes to increased fear of gaining weight and preoccupation with being thin, which increase vulnerability to eating disorders. The present study investigated whether greater drive for thinness mediates associations between weight suppression and bulimic symptoms over long-term follow-up. Participants were women (n = 1190) and men (n = 509) who completed self-report surveys in college and 10- and 20- years later. Higher weight suppression at baseline predicted higher bulimic symptoms at 20-year follow-up (p < .001), while accounting for demographic variables and baseline bulimic symptoms, body mass index, and drive for thinness. Increased drive for thinness at 10-year follow-up mediated this effect. Findings highlight the long-lasting effect of weight suppression on bulimic symptoms and suggest that preoccupation with thinness may help maintain this association. Future studies would benefit from incorporating other hypothesized consequences of weight suppression, including biological factors, into risk models. PMID:27808544

Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model.

PubMed

Taher, Yousef A; Piavaux, Benoit J A; Gras, Reneé; van Esch, Betty C A M; Hofman, Gerard A; Bloksma, Nanne; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-01

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive effects on asthma manifestations and (2) whether tryptophan depletion or generation of its downstream metabolites is involved. Ovalbumin (OVA)-sensitized and OVA-challenged BALB/c mice that display increased airway responsiveness to methacholine, serum OVA-specific IgE levels, bronchoalveolar eosinophilia, and TH2 cytokine levels were used as a model of allergic asthma. Sensitized mice received subcutaneous optimal (1 mg) or suboptimal (100 microg) OVA immunotherapy. Inhibition of IDO by 1-methyl-DL-tryptophan during immunotherapy, but not during inhalation challenge, partially reversed the suppressive effects of immunotherapy on airway eosinophilia and TH2 cytokine levels, whereas airway hyperresponsiveness and serum OVA-specific IgE levels remained suppressed. Administration of tryptophan during immunotherapy failed to abrogate its beneficial effects toward allergic airway inflammation. Interestingly, administration of tryptophan or its metabolites, kynurenine, 3-hydroxykynurenine, and xanthurenic acid, but not 3-hydroxyanthranilinic acid, quinolinic acid, and kynurenic acid, during suboptimal immunotherapy potentiated the reduction of eosinophilia. These effects coincided with reduced TH2 cytokine levels in bronchoalveolar lavage fluid, but no effects on IgE levels were detected. During immunotherapy, the tryptophan metabolites kynurenine, 3-hydroxykynurenine, and xanthurenic acid generated through IDO contribute to tolerance induction regarding TH2-dependent allergic airway inflammation.

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.

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

PubMed

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2016-05-01

Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of β-endorphin and μ-opioid receptor and estradiol receptor β expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of μ-opioid receptor). These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Finite element based model predictive control for active vibration suppression of a one-link flexible manipulator.

PubMed

Dubay, Rickey; Hassan, Marwan; Li, Chunying; Charest, Meaghan

2014-09-01

This paper presents a unique approach for active vibration control of a one-link flexible manipulator. The method combines a finite element model of the manipulator and an advanced model predictive controller to suppress vibration at its tip. This hybrid methodology improves significantly over the standard application of a predictive controller for vibration control. The finite element model used in place of standard modelling in the control algorithm provides a more accurate prediction of dynamic behavior, resulting in enhanced control. Closed loop control experiments were performed using the flexible manipulator, instrumented with strain gauges and piezoelectric actuators. In all instances, experimental and simulation results demonstrate that the finite element based predictive controller provides improved active vibration suppression in comparison with using a standard predictive control strategy. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Tangeretin Inhibits IL-12 Expression and NF-κB Activation in Dendritic Cells and Attenuates Colitis in Mice.

PubMed

Eun, Su-Hyeon; Woo, Je-Te; Kim, Dong-Hyun

2017-04-01

In the preliminary study, tangeretin (5,6,7,8,4'-pentamethoxy flavone), a major constituent of the pericarp of Citrus sp., inhibited TNF- α , IL-12, and IL-23 expression and nuclear factor kappa-B activation in lipopolysaccharide-stimulated dendritic cells; however, it did not affect IL-10 expression. Furthermore, tangeretin (5, 10, and 20 µM) suppressed the activation and translocation of nuclear factor kappa-B (p65) into the nuclei in vitro by inhibiting the binding of lipopolysaccharide on dendritic cells. Oral administration of tangeretin (10 and 20 mg/kg) suppressed the inflammatory responses, such as nuclear factor kappa-B and mitogen-activated protein kinase activation and myeloperoxidase activity, in the colon of mice with 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Tangeretin increased 2,4,6-trinitrobenzene sulfonic acid-suppressed expression of tight junction proteins occludin, claudin-1, and ZO-1. Tangeretin also inhibited 2,4,6-trinitrobenzene sulfonic acid-induced differentiation of Th1 and Th17 cells as well as the expression of T-bet, ROR γ t, interferon- γ , IL-12, IL-17, and TNF- α . However, tangeretin increased 2,4,6-trinitrobenzene sulfonic acid-suppressed differentiation of regulatory T cells as well as the expression of Foxp3 and IL-10. These results suggest that oral administration of tangeretin may attenuate colitis by suppressing IL-12 and TNF- α expression and nuclear factor kappa-B activation through the inhibition of lipopolysaccharide binding on immune cells such as dendritic cells. Georg Thieme Verlag KG Stuttgart · New York.

Young adults' internet addiction: Prediction by the interaction of parental marital conflict and respiratory sinus arrhythmia.

PubMed

Zhang, Hui; Spinrad, Tracy L; Eisenberg, Nancy; Luo, Yun; Wang, Zhenhong

2017-10-01

The aim of the current study was to address the potential moderating roles of respiratory sinus arrhythmia (RSA; baseline and suppression) and participant sex in the relation between parents' marital conflict and young adults' internet addiction. Participants included 105 (65 men) Chinese young adults who reported on their internet addiction and their parents' marital conflict. Marital conflict interacted with RSA suppression to predict internet addiction. Specifically, high RSA suppression was associated with low internet addiction, regardless of parental marital conflict; however, for participants with low RSA suppression, a positive relation between marital conflict and internet addiction was found. Internet addiction also was predicted by a significant three-way interaction among baseline RSA, marital conflict, and participant sex. Specifically, for men, marital conflict positively predicted internet addiction under conditions of low (but not high) baseline RSA. For women, marital conflict positively predicted internet addiction under conditions of high (but not low) baseline RSA. Findings highlight the importance of simultaneous consideration of physiological factors, in conjunction with family factors, in the prediction of young adults' internet addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding to its immunodominant T-cell epitope.

PubMed

Hufnagl, Karin; Ghosh, Debajyoti; Wagner, Stefanie; Fiocchi, Alessandro; Dahdah, Lamia; Bianchini, Rodolfo; Braun, Nina; Steinborn, Ralf; Hofer, Martin; Blaschitz, Marion; Roth, Georg A; Hofstetter, Gerlinde; Roth-Walter, Franziska; Pacios, Luis F; Jensen-Jarolim, Erika

2018-01-25

The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of -7.8 kcal/mol was calculated for RA into Bos d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS displacement assay, but had no effect on serum IgE binding in tolerant or challenge-positive milk allergic children. Bioinformatic analysis revealed that RA binds to the immunodominant T-cell epitope region of Bos d 5. In accordance, Bos d 5 significantly suppressed the CD3+ CD4+ cell numbers, proliferative response and IL-10, IL-13 and IFN-γ secretion from stimulated human PBMCs only when complexed with RA. This phenomenon was neither associated with apoptosis of T-cells nor with the activation of Foxp3+ T-cells, but correlated likely with enhanced stability to lysosomal digestion due to a predicted overlap of Cathepsin S cleavage sites with the RA binding site. Taken together, proper loading of Bos d 5 with RA may suppress its immunogenicity and prevent its allergenicity.

The role of the mitochondrial pyruvate carrier in substrate regulation

PubMed Central

Vacanti, Nathaniel M.; Divakaruni, Ajit S.; Green, Courtney R.; Parker, Seth J.; Henry, Robert R.; Ciaraldi, Theodore P.; Murphy, Anne N.; Metallo, Christian M.

2014-01-01

SUMMARY Pyruvate lies at a central biochemical node connecting carbohydrate, amino acid, and fatty acid metabolism, and the regulation of pyruvate flux into mitochondria represents a critical step in intermediary metabolism impacting numerous diseases. To characterize changes in mitochondrial substrate utilization in the context of compromised mitochondrial pyruvate transport, we applied 13C metabolic flux analysis (MFA) to cells after transcriptional or pharmacological inhibition of the mitochondrial pyruvate carrier (MPC). Despite profound suppression of both glucose and pyruvate oxidation, cell growth, oxygen consumption, and tricarboxylic acid (TCA) metabolism were surprisingly maintained. Oxidative TCA flux was achieved through enhanced reliance on glutaminolysis through malic enzyme and pyruvate dehydrogenase (PDH) as well as fatty acid and branched chain amino acid oxidation. Thus, in contrast to inhibition of complex I or PDH, suppression of pyruvate transport induces a form of metabolic flexibility associated with use of lipids and amino acids as catabolic and anabolic fuels. PMID:25458843

Identification of cis-suppression of human disease mutations by comparative genomics

PubMed Central

Jordan, Daniel M.; Frangakis, Stephan G.; Golzio, Christelle; Cassa, Christopher A.; Kurtzberg, Joanne; Davis, Erica E.; Sunyaev, Shamil R.; Katsanis, Nicholas

2015-01-01

Patterns of amino acid conservation have served as a tool for understanding protein evolution1. The same principles have also found broad application in human genomics, driven by the need to interpret the pathogenic potential of variants in patients2. Here we performed a systematic comparative genomics analysis of human disease-causing missense variants. We found that an appreciable fraction of disease-causing alleles are fixed in the genomes of other species, suggesting a role for genomic context. We developed a model of genetic interactions that predicts most of these to be simple pairwise compensations. Functional testing of this model on two known human disease genes3,4 revealed discrete cis amino acid residues that, although benign on their own, could rescue the human mutations in vivo. This approach was also applied to ab initio gene discovery to support the identification of a de novo disease driver in BTG2 that is subject to protective cis-modification in more than 50 species. Finally, on the basis of our data and models, we developed a computational tool to predict candidate residues subject to compensation. Taken together, our data highlight the importance of cis-genomic context as a contributor to protein evolution; they provide an insight into the complexity of allele effect on phenotype; and they are likely to assist methods for predicting allele pathogenicity5,6. PMID:26123021

Promoter regions of potato vacuolar invertase gene in response to sugars and hormones.

PubMed

Ou, Yongbin; Song, Botao; Liu, Xun; Xie, Conghua; Li, Meng; Lin, Yuan; Zhang, Huiling; Liu, Jun

2013-08-01

Potato vacuolar acid invertase (StvacINV1) (β-fructofuranosidase; EC 3.2.1.26) has been confirmed to play an important role in cold-induced sweetening of potato tubers. However, the transcriptional regulation mechanisms of StvacINV1 are largely unknown. In this study, the 5'-flanking sequence of StvacINV1 was cloned and the cis-acting elements were predicted. Histochemical assay showed that the StvacINV1 promoter governed β-glucuronidase (GUS) expression in potato leaves, stems, roots and tubers. Quantitative analysis of GUS expression suggested that the activity of StvacINV1 promoter was suppressed by sucrose, glucose, fructose, and cold, while enhanced by indole-3-acetic acid (IAA), and gibberellic acid (GA3). Further deletion analysis clarified that the promoter regions from -118 to -551, -551 to -1021, and -1021 to -1521 were required for responding to sucrose/glucose, GA3, and IAA, respectively. These findings provide essential information regarding transcriptional regulation mechanisms of StvacINV1. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Current Pharmacological Management of Gastroesophageal Reflux Disease

PubMed Central

Wang, Yao-Kuang; Hsu, Wen-Hung; Wang, Sophie S. W.; Lu, Chien-Yu; Kuo, Fu-Chen; Su, Yu-Chung; Yang, Sheau-Fang; Chen, Chiao-Yun; Wu, Deng-Chyang

2013-01-01

Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment. PMID:23878534

Antiplatelet effects of protopine isolated from Corydalis tubers.

PubMed

Ko, F N; Wu, T S; Lu, S T; Wu, Y C; Huang, T F; Teng, C M

1989-10-15

Protopine inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, PAF, collagen and ionophore A23187. Although the platelet aggregation caused by thrombin was not inhibited by protopine (100 micrograms/ml), the release reaction was partially suppressed. In rabbit platelet-rich plasma, protopine also inhibited the platelet aggregation caused by ADP, arachidonic acid, PAF and collagen. The thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, ionophore A23187 and thrombin was suppressed by protopine. Protopine inhibited the intracellular calcium increase caused by arachidonic acid in quin-2/AM loaded rabbit platelets. In the presence of indomethacin, the intracellular calcium increase caused by collagen and PAF was completely suppressed by protopine, and the intracellular calcium increase caused by thrombin was partially inhibited. The phosphoinositides breakdown caused by collagen and PAF was inhibited by protopine, but that by thrombin was not affected significantly. Protopine did not cause the elevation of cyclic AMP level of platelets. It is concluded that the antiplatelet effects of protopine is due to inhibition on thromboxane formation and phosphoinositides breakdown and then lead to the decrease of intracellular calcium concentration.

Turbofan aft duct suppressor study

NASA Technical Reports Server (NTRS)

Syed, A. A.; Motsinger, R. E.; Fiske, G. H.; Joshi, M. C.; Kraft, R. E.

1983-01-01

Suppressions due to acoustic treatment in the annular exhaust duct of a model fan were theoretically predicted and compared with measured suppressions. The predictions are based on the modal analysis of sound propagation in a straight annular flow duct with segmented treatment. Modal distributions of the fan noise source (fan-stator interaction only) were measured using in-duct modal probes. The flow profiles were also measured in the vicinity of the modal probes. The acoustic impedance of the single degree of freedom treatment was measured in the presence of grazing flow. The measured values of mode distribution of the fan noise source, the flow velocity profile and the acoustic impedance of the treatment in the duct were used as input to the prediction program. The predicted suppressions, under the assumption of uniform flow in the duct, compared well with the suppressions measured in the duct for all test conditions. The interaction modes generated by the rotor-stator interaction spanned a cut-off ratio range from nearly 1 to 7.

The relation of weight suppression and body mass index to symptomatology and treatment response in anorexia nervosa

PubMed Central

Berner, Laura A.; Shaw, Jena A.; Witt, Ashley A.; Lowe, Michael R.

2013-01-01

Weight suppression, the difference between highest past weight and current weight, is a robust predictor of clinical characteristics of bulimia nervosa; however, the influence of weight suppression in anorexia nervosa (AN) has been little studied, and no study to date has investigated the ways in which the relevance of weight suppression in AN may depend upon an individual’s current body mass index (BMI). The present study investigated weight suppression, BMI, and their interaction as cross-sectional and prospective predictors of psychological symptoms and weight in AN. Women with AN completed depression (Beck Depression Inventory-II) and eating disorder symptomatology measures (Eating Disorder Examination Questionnaire and Eating Disorders Inventory-3) at residential treatment admission (N = 350) and discharge (N = 238). Weight suppression and BMI were weakly correlated (r = −.22). At admission, BMI was positively correlated with all symptom measures except Restraint and depression scores. Weight suppression was also independently positively correlated with all measures except Weight Concern and Body Dissatisfaction subscale scores. In analyses examining discharge scores (including admission values as covariates), the admission weight suppression X BMI interaction consistently predicted post-treatment psychopathology. Controlling for weight gain in treatment and age, higher admission weight suppression predicted lower discharge scores (less symptom endorsement) among those with lower BMIs; among those with higher BMIs, higher weight suppression predicted higher discharge scores. These results are the first to demonstrate that absolute and relative weight status are joint indicators of AN severity and prognosis. These findings may have major implications for conceptualization and treatment of AN. PMID:24016010

Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARa and T- and B-cell targeting

EPA Pesticide Factsheets

Dosing information, body weights during exposure and immune system endpoints. This dataset is associated with the following publication:DeWitt, J., W. Williams , J. Creech, and R. Luebke. Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARalpha and T- and B-cell targeting. JOURNAL OF IMMUNOTOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 13(1): 38-45, (2016).

Weight suppression predicts bulimic symptoms at 20-year follow-up: The mediating role of drive for thinness.

PubMed

Bodell, Lindsay P; Brown, Tiffany A; Keel, Pamela K

2017-01-01

Weight suppression predicts the onset and maintenance of bulimic syndromes. Despite this finding, no study has examined psychological mechanisms contributing to these associations using a longitudinal design. Given societal pressures to be thin and an actual history of higher weight, it is possible that greater weight suppression contributes to increased fear of gaining weight and preoccupation with being thin, which increase vulnerability to eating disorders. The present study investigated whether greater drive for thinness mediates associations between weight suppression and bulimic symptoms over long-term follow-up. Participants were women (n = 1,190) and men (n = 509) who completed self-report surveys in college and 10- and 20-years later. Higher weight suppression at baseline predicted higher bulimic symptoms at 20-year follow-up (p < .001), while accounting for demographic variables and baseline bulimic symptoms, body mass index, and drive for thinness. Increased drive for thinness at 10-year follow-up mediated this effect. Findings highlight the long-lasting effect of weight suppression on bulimic symptoms and suggest that preoccupation with thinness may help maintain this association. Future studies would benefit from incorporating other hypothesized consequences of weight suppression, including biological factors, into risk models. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

DOEpatents

Visek, W.J.

1963-04-23

This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion.

PubMed

Zhang, Ji; Fan, Jing; Venneti, Sriram; Cross, Justin R; Takagi, Toshimitsu; Bhinder, Bhavneet; Djaballah, Hakim; Kanai, Masayuki; Cheng, Emily H; Judkins, Alexander R; Pawel, Bruce; Baggs, Julie; Cherry, Sara; Rabinowitz, Joshua D; Thompson, Craig B

2014-10-23

Many cancer cells consume large quantities of glutamine to maintain TCA cycle anaplerosis and support cell survival. It was therefore surprising when RNAi screening revealed that suppression of citrate synthase (CS), the first TCA cycle enzyme, prevented glutamine-withdrawal-induced apoptosis. CS suppression reduced TCA cycle activity and diverted oxaloacetate, the substrate of CS, into production of the nonessential amino acids aspartate and asparagine. We found that asparagine was necessary and sufficient to suppress glutamine-withdrawal-induced apoptosis without restoring the levels of other nonessential amino acids or TCA cycle intermediates. In complete medium, tumor cells exhibiting high rates of glutamine consumption underwent rapid apoptosis when glutamine-dependent asparagine synthesis was suppressed, and expression of asparagine synthetase was statistically correlated with poor prognosis in human tumors. Coupled with the success of L-asparaginase as a therapy for childhood leukemia, the data suggest that intracellular asparagine is a critical suppressor of apoptosis in many human tumors.

Improved amber and opal suppressor tRNAs for incorporation of unnatural amino acids in vivo. Part 2: Evaluating suppression efficiency

PubMed Central

Rodriguez, Erik A.; Lester, Henry A.; Dougherty, Dennis A.

2007-01-01

The incorporation of unnatural amino acids into proteins is a valuable tool for addition of biophysical probes, bio-orthogonal functionalities, and photoreactive cross-linking agents, although these approaches often require quantities of protein that are difficult to access with chemically aminoacylated tRNAs. THG73 is an amber suppressor tRNA that has been used extensively, incorporating over 100 residues in 20 proteins. In vitro studies have shown that the Escherichia coli Asn amber suppressor (ENAS) suppresses better than THG73. However, we report here that ENAS suppresses with <26% of the efficiency of THG73 in Xenopus oocytes. We then tested the newly developed Tetrahymena thermophila Gln amber suppressor (TQAS) tRNA library, which contains mutations in the second to fourth positions of the acceptor stem. The acceptor stem mutations have no adverse effect on suppression efficiency and, in fact, can increase the suppression efficiency. Combining mutations causes an averaging of suppression efficiency, and increased suppression efficiency does not correlate with increased ΔG of the acceptor stem. We created a T. thermophila opal suppressor, TQOpS′, which shows ∼50% suppression efficiency relative to THG73. The TQAS tRNA library, composed of functional suppressor tRNAs, has been created and will allow for screening in eukaryotic cells, where rapid analysis of large libraries is not feasible. PMID:17698637

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

Suppression of Hydroxycinnamate Network Formation in Cell Walls of Rice Shoots Grown under Microgravity Conditions in Space

PubMed Central

Wakabayashi, Kazuyuki; Soga, Kouichi; Hoson, Takayuki; Kotake, Toshihisa; Yamazaki, Takashi; Higashibata, Akira; Ishioka, Noriaki; Shimazu, Toru; Fukui, Keiji; Osada, Ikuko; Kasahara, Haruo; Kamada, Motoshi

2015-01-01

Network structures created by hydroxycinnamate cross-links within the cell wall architecture of gramineous plants make the cell wall resistant to the gravitational force of the earth. In this study, the effects of microgravity on the formation of cell wall-bound hydroxycinnamates were examined using etiolated rice shoots simultaneously grown under artificial 1 g and microgravity conditions in the Cell Biology Experiment Facility on the International Space Station. Measurement of the mechanical properties of cell walls showed that shoot cell walls became stiff during the growth period and that microgravity suppressed this stiffening. Amounts of cell wall polysaccharides, cell wall-bound phenolic acids, and lignin in rice shoots increased as the shoot grew. Microgravity did not influence changes in the amounts of cell wall polysaccharides or phenolic acid monomers such as ferulic acid (FA) and p-coumaric acid, but it suppressed increases in diferulic acid (DFA) isomers and lignin. Activities of the enzymes phenylalanine ammonia-lyase (PAL) and cell wall-bound peroxidase (CW-PRX) in shoots also increased as the shoot grew. PAL activity in microgravity-grown shoots was almost comparable to that in artificial 1 g-grown shoots, while CW-PRX activity increased less in microgravity-grown shoots than in artificial 1 g-grown shoots. Furthermore, the increases in expression levels of some class III peroxidase genes were reduced under microgravity conditions. These results suggest that a microgravity environment modifies the expression levels of certain class III peroxidase genes in rice shoots, that the resultant reduction of CW-PRX activity may be involved in suppressing DFA formation and lignin polymerization, and that this suppression may cause a decrease in cross-linkages within the cell wall architecture. The reduction in intra-network structures may contribute to keeping the cell wall loose under microgravity conditions. PMID:26378793

Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells.

PubMed

Wu, Yan; Guo, Sun-Wei

2007-11-01

Over-production of cyclooxygenase-2 (COX-2) plays an important role in the positive feedback loop that leads to proliferation and inflammation in endometriosis. Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA suppresses IL-1beta-induced COX-2 expression in endometrial stromal cells. In vitro study using a recently established immortalized endometrial stromal cell line. The stromal cells were pretreated with TSA before stimulation with IL-1beta, and COX-2 gene and protein expression was measured by real-time quantitative RT-PCR and Western blot analysis, respectively. IL-1beta stimulated COX-2 expression in a concentration-dependent manner in endometrial stromal cells. The induced COX-2 gene and protein expression were suppressed by TSA pretreatment. TSA suppresses IL-1beta-induced COX-2 gene and protein expression in endometrial stromal cells. This finding, coupled with the findings that TSA and another HDACI, valproic acid, suppress proliferation and induce cell cycle arrest, suggests that HDACIs are a promising class of compound that has therapeutic potential for endometriosis.

Evaluation of the addition of organic acids in the feed and/or water for broilers and the subsequent recovery of salmonella typhimurium from litter and ceca

USDA-ARS?s Scientific Manuscript database

Broiler Salmonella challenge experiments were conducted evaluating efficacy of formic and propionic acid feed supplements to suppress environmental and cecal Salmonella prevalence. In experiment 1, treatments were: formic acid, propionic acid, or basal control with no added acids. Seeder chicks we...

CSF 5-HIAA and DST non-suppression--orthogonal biologic risk factors for suicide in male mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Anna-Lena; Nordström, Peter

2009-01-30

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims (n=6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims (n=5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.

Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

PubMed Central

Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

2015-01-01

Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

The N1-suppression effect for self-initiated sounds is independent of attention

PubMed Central

2013-01-01

Background If we initiate a sound by our own motor behavior, the N1 component of the auditory event-related brain potential (ERP) that the sound elicits is attenuated compared to the N1 elicited by the same sound when it is initiated externally. It has been suggested that this N1 suppression results from an internal predictive mechanism that is in the service of discriminating the sensory consequences of one’s own actions from other sensory input. As the N1-suppression effect is becoming a popular approach to investigate predictive processing in cognitive and social neuroscience, it is important to exclude an alternative interpretation not related to prediction. According to the attentional account, the N1 suppression is due to a difference in the allocation of attention between self- and externally-initiated sounds. To test this hypothesis, we manipulated the allocation of attention to the sounds in different blocks: Attention was directed either to the sounds, to the own motor acts or to visual stimuli. If attention causes the N1-suppression effect, then manipulating attention should affect the effect for self-initiated sounds. Results We found N1 suppression in all conditions. The N1 per se was affected by attention, but there was no interaction between attention and self-initiation effects. This implies that self-initiation N1 effects are not caused by attention. Conclusions The present results support the assumption that the N1-suppression effect for self-initiated sounds indicates the operation of an internal predictive mechanism. Furthermore, while attention had an influence on the N1a, N1b, and N1c components, the N1-suppression effect was confined to the N1b and N1c subcomponents suggesting that the major contribution to the auditory N1-suppression effect is circumscribed to late N1 components. PMID:23281832

Competition-strength-dependent ground suppression in figure-ground perception.

PubMed

Salvagio, Elizabeth; Cacciamani, Laura; Peterson, Mary A

2012-07-01

Figure-ground segregation is modeled as inhibitory competition between objects that might be perceived on opposite sides of borders. The winner is the figure; the loser is suppressed, and its location is perceived as shapeless ground. Evidence of ground suppression would support inhibitory competition models and would contribute to explaining why grounds are shapeless near borders shared with figures, yet such evidence is scarce. We manipulated whether competition from potential objects on the ground side of figures was high (i.e., portions of familiar objects were potentially present there) or low (novel objects were potentially present). We predicted that greater competition would produce more ground suppression. The results of two experiments in which suppression was assessed via judgments of the orientation of target bars confirmed this prediction; a third experiment showed that ground suppression is short-lived. Our findings support inhibitory competition models of figure assignment, in particular, and models of visual perception entailing feedback, in general.

Smiling on the Inside: The Social Benefits of Suppressing Positive Emotions in Outperformance Situations.

PubMed

Schall, Marina; Martiny, Sarah E; Goetz, Thomas; Hall, Nathan C

2016-05-01

Although expressing positive emotions is typically socially rewarded, in the present work, we predicted that people suppress positive emotions and thereby experience social benefits when outperformed others are present. We tested our predictions in three experimental studies with high school students. In Studies 1 and 2, we manipulated the type of social situation (outperformance vs. non-outperformance) and assessed suppression of positive emotions. In both studies, individuals reported suppressing positive emotions more in outperformance situations than in non-outperformance situations. In Study 3, we manipulated the social situation (outperformance vs. non-outperformance) as well as the videotaped person's expression of positive emotions (suppression vs. expression). The findings showed that when outperforming others, individuals were indeed evaluated more positively when they suppressed rather than expressed their positive emotions, and demonstrate the importance of the specific social situation with respect to the effects of suppression. © 2016 by the Society for Personality and Social Psychology, Inc.

The Promiscuous sumA Missense Suppressor from Salmonella enterica Has an Intriguing Mechanism of Action

PubMed Central

Cole, Ashley E.; Hani, Fatmah M.; Altman, Ronni; Meservy, Megan; Roth, John R.; Altman, Elliot

2017-01-01

While most missense suppressors have very narrow specificities and only suppress the allele against which they were isolated, the sumA missense suppressor from Salmonella enterica serovar Typhimurium is a promiscuous or broad-acting missense suppressor that suppresses numerous missense mutants. The sumA missense suppressor was identified as a glyV tRNA Gly3(GAU/C) missense suppressor that can recognize GAU or GAC aspartic acid codons and insert a glycine amino acid instead of aspartic acid. In addition to rescuing missense mutants caused by glycine to aspartic acid changes as expected, sumA could also rescue a number of other missense mutants as well by changing a neighboring (contacting) aspartic acid to glycine, which compensated for the other amino acid change. Thus the ability of sumA to rescue numerous missense mutants was due in part to the large number of glycine codons in genes that can be mutated to an aspartic acid codon and in part to the general tolerability and/or preference for glycine amino acids in proteins. Because the glyV tRNA Gly3(GAU/C) missense suppressor has also been extensively characterized in Escherichia coli as the mutA mutator, we demonstrated that all gain-of-function mutants isolated in a glyV tRNA Gly3(GAU/C) missense suppressor are transferable to a wild-type background and thus the increased mutation rates, which occur in glyV tRNA Gly3(GAU/C) missense suppressors, are not due to the suppression of these mutants. PMID:27974497

Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet

PubMed Central

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

Acidic polysaccharide extracts from Gastrodia Rhizomes suppress the atherosclerosis risk index through inhibition of the serum cholesterol composition in Sprague Dawley rats fed a high-fat diet.

PubMed

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels.

Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors.

PubMed

Kang, Jaeseung; Kim, Eunjoon

2015-01-01

Animals prenatally exposed to valproic acid (VPA), an antiepileptic agent, have been used as a model for autism spectrum disorders (ASDs). Previous studies have identified enhanced NMDA receptor (NMDAR) function in the brain of VPA rats, and demonstrated that pharmacological suppression of NMDAR function normalizes social deficits in these animals. However, whether repetitive behavior, another key feature of ASDs, can be rescued by NMDAR inhibition remains unknown. We report here that memantine, an NMDAR antagonist, administered to VPA mice rescues both social deficits and repetitive behaviors such as self-grooming and jumping. These results suggest that suppression of elevated NMDAR function in VPA animals normalizes repetitive behaviors in addition to social deficits.

Caffeic acid phenethyl ester suppresses monocyte adhesion to the endothelium by inhibiting NF-κB/NOX2-derived ROS signaling

PubMed Central

Nakahara, Risa; Makino, Junya; Kamiya, Tetsuro; Hara, Hirokazu; Adachi, Tetsuo

2016-01-01

Caffeic acid phenethyl ester (CAPE), one of the major polyphenols, exhibits anti-oxidative, anti-bacterial, and anti-cancer properties. Atherosclerosis is a chronic inflammatory disease, the progression of which is closely related to the accumulated adhesion of inflammatory monocytes/macrophages to the endothelium. We herein determined whether CAPE and its derivatives suppressed THP-1 cell adhesion to human umbilical vein endothelial cells (HUVEC). Of the four polyphenols tested, CAPE significantly suppressed the 12-O-tetradecanoylphorbol 13-acetate (TPA)-elicited expression of cluster for differentiation (CD) 11b, 14, and 36, and this was accompanied by the inhibition of THP-1 cell adhesion to HUVEC. CAPE also suppressed the activation of TPA-elicited nuclear factor-κB (NF-κB) and accumulation of NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS), but did not affect extracellular signal-regulated kinase (ERK) phosphorylation. Taken together, these results demonstrated that CAPE suppressed THP-1 cell adhesion to HUVEC through, at least in part, the NF-κB, NOX2, and ROS-derived signaling axis. PMID:27257341

Acid extrusion via blood–brain barrier causes brain alkalosis and seizures after neonatal asphyxia

PubMed Central

Helmy, Mohamed M.; Ruusuvuori, Eva; Watkins, Paul V.; Voipio, Juha; Kanold, Patrick O.; Kaila, Kai

2012-01-01

Birth asphyxia is often associated with a high seizure burden that is predictive of poor neurodevelopmental outcome. The mechanisms underlying birth asphyxia seizures are unknown. Using an animal model of birth asphyxia based on 6-day-old rat pups, we have recently shown that the seizure burden is linked to an increase in brain extracellular pH that consists of the recovery from the asphyxia-induced acidosis, and of a subsequent plateau level well above normal extracellular pH. In the present study, two-photon imaging of intracellular pH in neocortical neurons in vivo showed that pH changes also underwent a biphasic acid–alkaline response, resulting in an alkaline plateau level. The mean alkaline overshoot was strongly suppressed by a graded restoration of normocapnia after asphyxia. The parallel post-asphyxia increase in extra- and intracellular pH levels indicated a net loss of acid equivalents from brain tissue that was not attributable to a disruption of the blood–brain barrier, as demonstrated by a lack of increased sodium fluorescein extravasation into the brain, and by the electrophysiological characteristics of the blood–brain barrier. Indeed, electrode recordings of pH in the brain and trunk demonstrated a net efflux of acid equivalents from the brain across the blood–brain barrier, which was abolished by the Na/H exchange inhibitor, N-methyl-isobutyl amiloride. Pharmacological inhibition of Na/H exchange also suppressed the seizure activity associated with the brain-specific alkalosis. Our findings show that the post-asphyxia seizures are attributable to an enhanced Na/H exchange-dependent net extrusion of acid equivalents across the blood–brain barrier and to consequent brain alkalosis. These results suggest targeting of blood–brain barrier-mediated pH regulation as a novel approach in the prevention and therapy of neonatal seizures. PMID:23125183

Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A

PubMed Central

Hoshimoto, Aihiro; Suzuki, Yasuo; Katsuno, Tatsuro; Nakajima, Hiroshi; Saito, Yasushi

2002-01-01

Medium-chain triglyceride (MCT) is often administered to patients with Crohn's disease (CD) or short-bowel syndrome. However, little is known about the effects of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8 secretion by differentiated Caco-2 cells.We found for the first time that caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the transcriptional level when precultured together for 24 h. We also tried to clarify the mechanism of IL-8 gene inhibition by examining the activation of NF-κB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation.The result of dual-luciferase assay using Caco-2 cells transfected with IL-8 promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the activation of IL-8 promoter.Similar results were observed when cells were precultured with the well-known potent histone deacetylase inhibitor trichostatin A (TSA).We examined the state of H4 acetylation in IL-8 promoter using the technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4 acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These results suggest that the inhibition of IL-8 gene transcription induced by caprylic acid and TSA does not necessarily require the marked suppression of transcription factors, and the mechanism of inhibition of IL-8 gene transcription may be different between caprylic acid and TSA. PMID:12010777

Quantitative prediction of the bitterness suppression of elemental diets by various flavors using a taste sensor.

PubMed

Miyanaga, Yohko; Inoue, Naoko; Ohnishi, Ayako; Fujisawa, Emi; Yamaguchi, Maki; Uchida, Takahiro

2003-12-01

The purpose of the study was to develop a method for the quantitative prediction of the bitterness suppression of elemental diets by various flavors and to predict the optimum composition of such elemental diets for oral administration using a multichannel taste sensor. We examined the effects of varying the volume of water used for dilution and of adding varying quantities of five flavors (pineapple, apple, milky coffee, powdered green tea, and banana) on the bitterness of the elemental diet, Aminoreban EN. Gustatory sensation tests with human volunteers (n = 9) and measurements using the artificial taste sensor were performed on 50 g Aminoreban EN dissolved in various volumes (140), 180, 220, 260, 300, 420, 660, 1140, and 2100 ml) of water, and on 50 g Aminoreban EN dissolved in 180 ml of water with the addition of 3-9 g of various flavors for taste masking. In gustatory sensation tests, the relationship between the logarithmic values of the volumes of water used for dilution and the bitterness intensity scores awarded by the volunteers proved to be linear. The addition of flavors also reduced the bitterness of elemental diets in gustatory sensation tests; the magnitude of this effect was, in decreasing order, apple, pineapple, milky coffee, powdered green tea, and banana. With the artificial taste sensor, large changes of membrane potential in channel 1, caused by adsorption (CPA values, corresponding to a bitter aftertaste), were observed for Aminoreban EN but not for any of the flavors. There was a good correlation between the CPA values in channel 1 and the results of the human gustatory tests, indicating that the taste sensor is capable of evaluating not only the bitterness of Aminoreban EN itself but also the bitterness-suppressing effect of the five flavors, which contained many elements such as organic acids and flavor components, and the effect of dilution (by water) on this bitterness. Using regression analysis of data derived from the taste sensor and from human gustatory data for four representative points, we were able to predict the bitterness of 50 g Aminoreban EN solutions diluted with various volumes of water (14-300 ml), with or without the addition of a selected flavor. Even though this prediction method does not offer perfect simulation of human taste sensations, the artificial taste sensor may be useful for predicting the bitterness intensity of elemental diets containing various flavors in the absence of results from full gustatory sensation tests.

Methods for suppressing isomerization of olefin metathesis products

DOEpatents

Firth, Bruce E.; Kirk, Sharon E.

2015-10-27

A method for suppressing isomerization of an olefin metathesis product produced in a metathesis reaction includes adding an isomerization suppression agent that includes nitric acid to a mixture that includes the olefin metathesis product and residual metathesis catalyst from the metathesis reaction under conditions that are sufficient to passivate at least a portion of the residual metathesis catalyst. Methods of refining a natural oil are described.

Mannitol can mitigate negative effects of simulated acid mist and fluoranthene in juvenile Japanese red pine (P. densiflora Sieb. et Zucc.).

PubMed

Oguntimehin, Ilemobayo; Bandai, Sayuri; Sakugawa, Hiroshi

2013-03-01

The negative health effects of simulated acid mists and fluoranthene on juvenile Japanese red pine were investigated, and the methods of protection from these pollutants were examined. The needle gas exchange, chlorophyll fluorescence, chemical contents and visual damage to needles caused by acid mist applied alone or its conjunction with fluoranthene were investigated over 60 d and 20 d, respectively. Acid mist at pH 2 and 3 caused physiological and visual damage, which was enhanced by the addition of fluoranthene to the mist. However, fluoranthene and acid mist at pH 4 and 5 showed only minor effects. These findings indicate that acid mist may be more harmful to pine trees if it occurs in conjunction with polycyclic aromatic hydrocarbons. Moreover, suppression of the singular and additive effects of these compounds was achieved using mannitol, which may be widely applicable to suppression of reactive oxygen species-mediated plant damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Mitochondrial 2-Oxoglutarate Carrier Is Part of a Metabolic Pathway That Mediates Glucose- and Glutamine-stimulated Insulin Secretion*

PubMed Central

Odegaard, Matthew L.; Joseph, Jamie W.; Jensen, Mette V.; Lu, Danhong; Ilkayeva, Olga; Ronnebaum, Sarah M.; Becker, Thomas C.; Newgard, Christopher B.

2010-01-01

Glucose-stimulated insulin secretion from pancreatic islet β-cells is dependent in part on pyruvate cycling through the pyruvate/isocitrate pathway, which generates cytosolic α-ketoglutarate, also known as 2-oxoglutarate (2OG). Here, we have investigated if mitochondrial transport of 2OG through the 2-oxoglutarate carrier (OGC) participates in control of nutrient-stimulated insulin secretion. Suppression of OGC in clonal pancreatic β-cells (832/13 cells) and isolated rat islets by adenovirus-mediated delivery of small interfering RNA significantly decreased glucose-stimulated insulin secretion. OGC suppression also reduced insulin secretion in response to glutamine plus the glutamate dehydrogenase activator 2-amino-2-norbornane carboxylic acid. Nutrient-stimulated increases in glucose usage, glucose oxidation, glutamine oxidation, or ATP:ADP ratio were not affected by OGC knockdown, whereas suppression of OGC resulted in a significant decrease in the NADPH:NADP+ ratio during stimulation with glucose but not glutamine + 2-amino-2-norbornane carboxylic acid. Finally, OGC suppression reduced insulin secretion in response to a membrane-permeant 2OG analog, dimethyl-2OG. These data reveal that the OGC is part of a mechanism of fuel-stimulated insulin secretion that is common to glucose, amino acid, and organic acid secretagogues, involving flux through the pyruvate/isocitrate cycling pathway. Although the components of this pathway must remain intact for appropriate stimulus-secretion coupling, production of NADPH does not appear to be the universal second messenger signal generated by these reactions. PMID:20356834

Salicylic acid suppresses jasmonic acid signaling downstream of SCFCOI1-JAZ by targeting GCC promoter motifs via transcription factor ORA59.

PubMed

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C M; Pieterse, Corné M J

2013-02-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCF(COI1), which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCF(COI1)-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59.

Effects of five oleanolic acid triterpenoid saponins from the rhizome of Anemone raddeana on stimulus-induced superoxide generation, phosphorylation of proteins and translocation of cytosolic compounds to cell membrane in human neutrophils.

PubMed

Wei, Shihu; He, Wenfei; Lu, Jincai; Wang, Zhonghuan; Yamashita, Koichi; Yokoyama, Masanori; Kodama, Hiroyuki

2012-03-01

Five oleanolic acid triterpenoid saponins (OTS-1, 2, 3, 4 and 5) were isolated from the rhizome of Anemone raddeana. The effect of these triterpenoid saponins on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c using a dual-beam spectrophotometer. The phosphorylation of neutrophil proteins, and translocation of p67(phox), p47(phox) and Rac to plasma membrane were investigated using specific monoclonal antibodies. The five oleanolic acid triterpenoid saponins used in this experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration-dependent manner. OTS-1, 2 and 4 suppressed phorbol 12-myristate 13-acetate (PMA)- and arachidonic acid (AA)-induced superoxide generation in a concentration-dependent manner, but OTS-3 and 5 showed no effect. fMLP- and PMA-induced tyrosyl or serine/threonine phosphorylation, and fMLP-, PMA- and AA-induced translocation of p67(phox), p47(phox) and Rac to plasma membrane were in parallel with the suppression of the stimulus-induced superoxide generation. Copyright © 2011 Elsevier B.V. All rights reserved.

ω-3 Polyunsaturated fatty acids and their cytochrome P450-derived metabolites suppress colorectal tumor development in mice.

PubMed

Wang, Weicang; Yang, Jun; Nimiya, Yoshiki; Lee, Kin Sing Stephen; Sanidad, Katherine; Qi, Weipeng; Sukamtoh, Elvira; Park, Yeonhwa; Liu, Zhenhua; Zhang, Guodong

2017-10-01

Many studies have shown that dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risks of colorectal cancer; however, the underlying mechanisms are not well understood. Here we used a LC-MS/MS-based lipidomics to explore the role of eicosanoid signaling in the anti-colorectal cancer effects of ω-3 PUFAs. Our results showed that dietary feeding of ω-3 PUFAs-rich diets suppressed growth of MC38 colorectal tumor, and modulated profiles of fatty acids and eicosanoid metabolites in C57BL/6 mice. Notably, we found that dietary feeding of ω-3 PUFAs significantly increased levels of epoxydocosapentaenoic acids (EDPs, metabolites of ω-3 PUFA produced by cytochrome P450 enzymes) in plasma and tumor tissue of the treated mice. We further showed that systematic treatment with EDPs (dose=0.5 mg/kg per day) suppressed MC38 tumor growth in mice, with reduced expressions of pro-oncogenic genes such as C-myc, Axin2, and C-jun in tumor tissues. Together, these results support that formation of EDPs might contribute to the anti-colorectal cancer effects of ω-3 PUFAs. Copyright © 2017 Elsevier Inc. All rights reserved.

Arginine inactivates human herpesvirus 2 and inhibits genital herpesvirus infection.

PubMed

Ikeda, Keiko; Yamasaki, Hisashi; Minami, Sawako; Suzuki, Yukiko; Tsujimoto, Kazuko; Sekino, Yoshihisa; Irie, Hiroshi; Arakawa, Tsutomu; Koyama, A Hajime

2012-12-01

Arginine, among the amino acids, has demonstrated unique properties, including suppression of protein-protein interactions and virus inactivation. We investigated the effects of arginine on the infectivity of human herpesvirus 2 (HHV-2) and the potential application of arginine as a chemotherapeutic agent against genital herpes. Arginine directly inactivated HHV-2 and characterization of the inactivation demonstrated that 1 M arginine at pH 4.3 inactivated the virus more efficiently compared to 0.1 M citrate or 1 M sodium chloride, indicating that neither acidic pH nor ionic strength alone is sufficient for virus inactivation. The effect of arginine was rapid and concentration-dependent. Although virus inactivation was efficient at an acidic pH, arginine inactivated the virus even at a neutral pH, provided that a higher arginine concentration and prolonged incubation time were used. In addition, arginine suppressed the multiplication of HHV-2 under the conditions at which its effect on cell viability was insignificant. Pilot mouse model studies revealed a marked suppression of death by arginine when the mice were infected with HHV-2 through the vaginal route, followed by an intermittent application of acidic arginine by vaginal instillation.

Defense Response and Suppression of Phytophthora Blight Disease of Pepper by Water Extract from Spent Mushroom Substrate of Lentinula edodes

PubMed Central

Kang, Dae-Sun; Min, Kyong-Jin; Kwak, A-Min; Lee, Sang-Yeop; Kang, Hee-Wan

2017-01-01

The spent mushroom substrate (SMS) of Lentinula edodes that was derived from sawdust bag cultivation was used as materials for controlling Phytophthora blight disease of pepper. Water extract from SMS (WESMS) of L. edodes inhibited mycelial growth of Phytophthora capsici, suppressed Phytophthora blight disease of pepper seedlings by 65% and promoted growth of the plant over 30%. In high performance liquid chromatography (HPLC) analysis, oxalic acid was detected as the main organic acid compound in WESMS and inhibited the fungal mycelium at a minimum concentration of 200 mg/l. In quantitative real-time PCR, the transcriptional expression of CaBPR1 (PR protein 1), CaBGLU (β-1,3-glucanase), CaPR-4 (PR protein 4), and CaPR-10 (PR protein 10) were significantly enhanced on WESMS and DL-β-aminobutyric acid (BABA) treated pepper leaves. In addition, the salicylic acid content was also increased 4 to 6 folds in the WESMS and BABA treated pepper leaves compared to water treated leaf sample. These findings suggest that WESMS of L. edodes suppress Phytophthora blight disease of pepper through multiple effects including antifungal activity, plant growth promotion, and defense gene induction. PMID:28592945

Defense Response and Suppression of Phytophthora Blight Disease of Pepper by Water Extract from Spent Mushroom Substrate of Lentinula edodes.

PubMed

Kang, Dae-Sun; Min, Kyong-Jin; Kwak, A-Min; Lee, Sang-Yeop; Kang, Hee-Wan

2017-06-01

The spent mushroom substrate (SMS) of Lentinula edodes that was derived from sawdust bag cultivation was used as materials for controlling Phytophthora blight disease of pepper. Water extract from SMS (WESMS) of L. edodes inhibited mycelial growth of Phytophthora capsici , suppressed Phytophthora blight disease of pepper seedlings by 65% and promoted growth of the plant over 30%. In high performance liquid chromatography (HPLC) analysis, oxalic acid was detected as the main organic acid compound in WESMS and inhibited the fungal mycelium at a minimum concentration of 200 mg/l. In quantitative real-time PCR, the transcriptional expression of CaBPR1 (PR protein 1), CaBGLU (β-1,3-glucanase), CaPR-4 (PR protein 4), and CaPR-10 (PR protein 10) were significantly enhanced on WESMS and DL-β-aminobutyric acid (BABA) treated pepper leaves. In addition, the salicylic acid content was also increased 4 to 6 folds in the WESMS and BABA treated pepper leaves compared to water treated leaf sample. These findings suggest that WESMS of L. edodes suppress Phytophthora blight disease of pepper through multiple effects including antifungal activity, plant growth promotion, and defense gene induction.

Ascorbic acid and reactive oxygen species are involved in the inhibition of seed germination by abscisic acid in rice seeds

PubMed Central

Ye, Nenghui; Zhu, Guohui; Liu, Yinggao; Liu, Rui; Shi, Lu; Jia, Liguo; Zhang, Jianhua

2012-01-01

The antagonism between abscisic acid (ABA) and gibberellin (GA) plays a key role in controlling seed germination, but the mechanism of antagonism during this process is not known. The possible links among ABA, reactive oxygen species (ROS), ascorbic acid (ASC), and GA during rice seed germination were investigated. Unlike in non-seed tissues where ROS production is increased by ABA, ABA reduced ROS production in imbibed rice seeds, especially in the embryo region. Such reduced ROS also led to an inhibition of ASC production. GA accumulation was also suppressed by a reduced ROS and ASC level, which was indicated by the inhibited expression of GA biosynthesis genes, amylase genes, and enzyme activity. Application of exogenous ASC can partially rescue seed germination from ABA treatment. Production of ASC, which acts as a substrate in GA biosynthesis, was significantly inhibited by lycorine which thus suppressed the accumulation of GA. Consequently, expression of GA biosynthesis genes was suppressed by the low levels of ROS and ASC in ABA-treated seeds. It can be concluded that ABA regulates seed germination in multiple dimensions. ROS and ASC are involved in its inhibition of GA biosynthesis. PMID:22200664

Risk of fracture and pneumonia from acid suppressive drugs.

PubMed

Eom, Chun-Sick; Lee, Sang-Soo

2011-09-26

A recently published systematic review and meta-analysis, incorporating all relevant studies on the association of acid suppressive medications and pneumonia identified up to August 2009, revealed that for every 200 patients, treated with acid suppressive medication, one will develop pneumonia. They showed the overall risk of pneumonia was higher among people using proton pump inhibitors (PPIs) [adjusted odds ratio (OR) = 1.27, 95% CI: 1.11-1.46, I(2) = 90.5%] and Histamine-2 receptor antagonists (H2RAs) (adjusted OR = 1.22, 95% CI: 1.09-1.36, I(2) = 0.0%). In the randomized controlled trials, use of H2RAs was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI: 1.01-1.48, I(2) = 30.6%). Another meta-analysis of 11 studies published between 1997 and 2011 found that PPIs, which reduce stomach acid production, were associated with increased risk of fracture. The pooled OR for fracture was 1.29 (95% CI: 1.18-1.41) with use of PPIs and 1.10 (95% CI: 0.99-1.23) with use of H2RAs, when compared with non-use of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30, 95% CI: 1.15-1.48) and of hip fracture risk (adjusted OR = 1.34, 95% CI: 1.09-1.66), whereas long-term H2RA use was not significantly associated with fracture risk. Clinicians should carefully consider when deciding to prescribe acid-suppressive drugs, especially for patients who are already at risk for pneumonia and fracture. Since it is unnecessary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the only minimum effective dose of drug required to achieve the desired therapeutic goals.

Are Developmentally-Exposed C57BL/6 Mice Insensitive to Suppression of TDAR by PFOA?

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is an environmentally persistent fluorinated compound that is present in biological samples worldwide and associated with multisystem toxicity in laboratory animal models. Several studies have reported suppression of T-cell-dependent antibody respons...

FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri.

PubMed

Thomas, Carissa M; Saulnier, Delphine M A; Spinler, Jennifer K; Hemarajata, Peera; Gao, Chunxu; Jones, Sara E; Grimm, Ashley; Balderas, Miriam A; Burstein, Matthew D; Morra, Christina; Roeth, Daniel; Kalkum, Markus; Versalovic, James

2016-10-01

Bacterial-derived compounds from the intestinal microbiome modulate host mucosal immunity. Identification and mechanistic studies of these compounds provide insights into host-microbial mutualism. Specific Lactobacillus reuteri strains suppress production of the proinflammatory cytokine, tumor necrosis factor (TNF), and are protective in a mouse model of colitis. Human-derived L. reuteri strain ATCC PTA 6475 suppresses intestinal inflammation and produces 5,10-methenyltetrahydrofolic acid polyglutamates. Insertional mutagenesis identified the bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene as essential for 5,10-methenyltetrahydrofolic acid polyglutamate biosynthesis, as well as for suppression of TNF production by activated human monocytes, and for the anti-inflammatory effect of L. reuteri 6475 in a trinitrobenzene sulfonic acid-induced mouse model of acute colitis. In contrast, folC encodes the enzyme responsible for folate polyglutamylation but does not impact TNF suppression by L. reuteri. Comparative transcriptomics between wild-type and mutant L. reuteri strains revealed additional genes involved in immunomodulation, including previously identified hdc genes involved in histidine to histamine conversion. The folC2 mutant yielded diminished hdc gene cluster expression and diminished histamine production, suggesting a link between folate and histadine/histamine metabolism. The identification of genes and gene networks regulating production of bacterial-derived immunoregulatory molecules may lead to improved anti-inflammatory strategies for digestive diseases. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

A clinical hepatologist's predictions about non-absorbed carbohydrates for the early twenty-first century.

PubMed

Conn, H O

1997-01-01

To put these predictions into perspective, the primary indication for lactulose therapy in the treatment of HE and SHE is presented and discussed. Six secondary indications for lactulose therapy are also listed and briefly commented upon. A dozen predictions about the status of lactulose are presented and briefly discussed. A. Lactulose will be the treatment of choice for HE.B. TIPS will be the most common cause of HE.C. Lactulose will not be approved in Mexico. D. Lactulose plus anti-diarrheal drugs will be agents for treatment of HE. E. Lactulose will not be the treatment of choice for constipation. F. Lactulose will not be used for Salmonella or Shigella carrier states. G. Lactulose will be routinely administered prophylactically after TIPS. H. Lactulose will be administered prophylactically to cirrhotic patients with portal hypertension. I. Lactulose plus anti-diarrheal drugs will be used for a variety of diverse purposes: (i) Suppression of bacterial growth; (ii) prevention of bacteriuria; (iii) diminution of cholesterol saturation of bile; (iv) adjunct treatment of gallstones with ursodeoxycholic acid; (v) Prevention of colon carcinoma.

Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana.

PubMed

Prince, David C; Rallapalli, Ghanasyam; Xu, Deyang; Schoonbeek, Henk-Jan; Çevik, Volkan; Asai, Shuta; Kemen, Eric; Cruz-Mireles, Neftaly; Kemen, Ariane; Belhaj, Khaoula; Schornack, Sebastian; Kamoun, Sophien; Holub, Eric B; Halkier, Barbara A; Jones, Jonathan D G

2017-03-20

Plants are exposed to diverse pathogens and pests, yet most plants are resistant to most plant pathogens. Non-host resistance describes the ability of all members of a plant species to successfully prevent colonization by any given member of a pathogen species. White blister rust caused by Albugo species can overcome non-host resistance and enable secondary infection and reproduction of usually non-virulent pathogens, including the potato late blight pathogen Phytophthora infestans on Arabidopsis thaliana. However, the molecular basis of host defense suppression in this complex plant-microbe interaction is unclear. Here, we investigate specific defense mechanisms in Arabidopsis that are suppressed by Albugo infection. Gene expression profiling revealed that two species of Albugo upregulate genes associated with tryptophan-derived antimicrobial metabolites in Arabidopsis. Albugo laibachii-infected tissue has altered levels of these metabolites, with lower indol-3-yl methylglucosinolate and higher camalexin accumulation than uninfected tissue. We investigated the contribution of these Albugo-imposed phenotypes to suppression of non-host resistance to P. infestans. Absence of tryptophan-derived antimicrobial compounds enables P. infestans colonization of Arabidopsis, although to a lesser extent than Albugo-infected tissue. A. laibachii also suppresses a subset of genes regulated by salicylic acid; however, salicylic acid plays only a minor role in non-host resistance to P. infestans. Albugo sp. alter tryptophan-derived metabolites and suppress elements of the responses to salicylic acid in Arabidopsis. Albugo sp. imposed alterations in tryptophan-derived metabolites may play a role in Arabidopsis non-host resistance to P. infestans. Understanding the basis of non-host resistance to pathogens such as P. infestans could assist in development of strategies to elevate food security.

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Peter

2008-11-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

Characterization of a novel rice gene OsATX and modulation of its expression by components of the stress signalling pathways.

PubMed

Agrawal, Ganesh K; Rakwal, Randeep; Jwa, N-S; Agrawal, Vishwanath P

2002-09-01

In our search to identify gene(s) involved in the rice self-defense responses, we cloned a novel rice (Oryza sativa L. cv. Nipponbare) gene, OsATX, a single copy gene, from the JA treated rice seedling leaves cDNA library. This gene encodes a 69 amino acid polypeptide with a predicted molecular mass of 7649.7 and a pI of 5.6. OsATX was responsive to cutting (wounding by cutting the excised leaf), over its weak constitutive expression in the healthy leaves. The critical signalling molecules, jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and hydrogen peroxide, together with protein phosphatase inhibitors, effectively up-regulated the OsATX expression with time, over the excised leaf cut control, whereas ethylene had no affect. Furthermore, copper, a heavy metal, also up-regulated OsATX expression. Moreover, induced expression of OsATX mRNA was influenced by light signal(s), and showed a requirement for de novo synthesized protein factors. Additionally, co-application of either JA or ABA with SA drastically suppressed the induced OsATX mRNA level. Finally, the blast pathogen, Magnaporthe grisea, triggered OsATX mRNA accumulation. These results strongly suggest a function/role(s) for OsATX in defense/stress responses in rice.

Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease*

PubMed Central

Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

2017-01-01

Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p < 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex (p < 0.05) and a significant improvement in a novel object recognition test (p < 0.05), as compared with control-fed 5xFAD mice. The differences in iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia. PMID:28087694

Homologous RXLR effectors from Hyaloperonospora arabidopsidis and Phytophthora sojae suppress immunity in distantly related plants.

PubMed

Anderson, Ryan G; Casady, Megan S; Fee, Rachel A; Vaughan, Martha M; Deb, Devdutta; Fedkenheuer, Kevin; Huffaker, Alisa; Schmelz, Eric A; Tyler, Brett M; McDowell, John M

2012-12-01

Diverse pathogens secrete effector proteins into plant cells to manipulate host cellular processes. Oomycete pathogens contain large complements of predicted effector genes defined by an RXLR host cell entry motif. The genome of Hyaloperonospora arabidopsidis (Hpa, downy mildew of Arabidopsis) contains at least 134 candidate RXLR effector genes. Only a small subset of these genes is conserved in related oomycetes from the Phytophthora genus. Here, we describe a comparative functional characterization of the Hpa RXLR effector gene HaRxL96 and a homologous gene, PsAvh163, from the Glycine max (soybean) pathogen Phytophthora sojae. HaRxL96 and PsAvh163 are induced during the early stages of infection and carry a functional RXLR motif that is sufficient for protein uptake into plant cells. Both effectors can suppress immune responses in soybean. HaRxL96 suppresses immunity in Nicotiana benthamiana, whereas PsAvh163 induces an HR-like cell death response in Nicotiana that is dependent on RAR1 and Hsp90.1. Transgenic Arabidopsis plants expressing HaRxL96 or PsAvh163 exhibit elevated susceptibility to virulent and avirulent Hpa, as well as decreased callose deposition in response to non-pathogenic Pseudomonas syringae. Both effectors interfere with defense marker gene induction, but do not affect salicylic acid biosynthesis. Together, these experiments demonstrate that evolutionarily conserved effectors from different oomycete species can suppress immunity in plant species that are divergent from the source pathogen's host. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer

PubMed Central

Hutchins, G. D.; Perry, K.; Territo, W.; Chisholm, R.; Acton, A.; Glick-Wilson, B.; Considine, R. V.; Moberly, S.; DeGrado, T. R.

2015-01-01

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m−2·min−1) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. PMID:26732686

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

PubMed

Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

2016-03-15

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. Copyright © 2016 the American Physiological Society.

Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

An in vivo invertebrate evaluation system for identifying substances that suppress sucrose-induced postprandial hyperglycemia

PubMed Central

Matsumoto, Yasuhiko; Ishii, Masaki; Sekimizu, Kazuhisa

2016-01-01

Sucrose is a major sweetener added to various foods and beverages. Excessive intake of sucrose leads to increases in blood glucose levels, which can result in the development and exacerbation of lifestyle-related diseases such as obesity and diabetes. In this study, we established an in vivo evaluation system using silkworms to explore substances that suppress the increase in blood glucose levels caused by dietary intake of sucrose. Silkworm hemolymph glucose levels rapidly increased after intake of a sucrose-containing diet. Addition of acarbose or voglibose, α-glycosidase inhibitors clinically used for diabetic patients, suppressed the dietary sucrose-induced increase in the silkworm hemolymph glucose levels. Screening performed using the sucrose-induced postprandial hyperglycemic silkworm model allowed us to identify some lactic acid bacteria that inhibit the increase in silkworm hemolymph glucose levels caused by dietary intake of sucrose. The inhibitory effects of the Lactococcus lactis #Ll-1 bacterial strain were significantly greater than those of different strains of lactic acid bacteria. No effect of the Lactococcus lactis #Ll-1 strain was observed in silkworms fed a glucose diet. These results suggest that the sucrose diet-induced postprandial hyperglycemic silkworm is a useful model for evaluating chemicals and lactic acid bacteria that suppress increases in blood glucose levels. PMID:27194587

An in vivo invertebrate evaluation system for identifying substances that suppress sucrose-induced postprandial hyperglycemia.

PubMed

Matsumoto, Yasuhiko; Ishii, Masaki; Sekimizu, Kazuhisa

2016-05-19

Sucrose is a major sweetener added to various foods and beverages. Excessive intake of sucrose leads to increases in blood glucose levels, which can result in the development and exacerbation of lifestyle-related diseases such as obesity and diabetes. In this study, we established an in vivo evaluation system using silkworms to explore substances that suppress the increase in blood glucose levels caused by dietary intake of sucrose. Silkworm hemolymph glucose levels rapidly increased after intake of a sucrose-containing diet. Addition of acarbose or voglibose, α-glycosidase inhibitors clinically used for diabetic patients, suppressed the dietary sucrose-induced increase in the silkworm hemolymph glucose levels. Screening performed using the sucrose-induced postprandial hyperglycemic silkworm model allowed us to identify some lactic acid bacteria that inhibit the increase in silkworm hemolymph glucose levels caused by dietary intake of sucrose. The inhibitory effects of the Lactococcus lactis #Ll-1 bacterial strain were significantly greater than those of different strains of lactic acid bacteria. No effect of the Lactococcus lactis #Ll-1 strain was observed in silkworms fed a glucose diet. These results suggest that the sucrose diet-induced postprandial hyperglycemic silkworm is a useful model for evaluating chemicals and lactic acid bacteria that suppress increases in blood glucose levels.

Acidic conditions induce the suppression of CD86 and CD54 expression in THP-1 cells.

PubMed

Mitachi, Takafumi; Mezaki, Minori; Yamashita, Kunihiko; Itagaki, Hiroshi

2018-01-01

To evaluate the sensitization potential of chemicals in cosmetics, using non-animal methods, a number of in vitro safety tests have been designed. Current assays are based on the expression of cell surface markers, such as CD86 and CD54, which are associated with the activation of dendritic cells, in skin sensitization tests. However, these markers are influenced by culture conditions through activating danger signals. In this study, we investigated the relationship between extracellular pH and the expression of the skin sensitization test human cell line activation test (h-CLAT) markers CD86 and CD54. We measured expression levels after THP-1 cells were exposed to representative contact allergens, i.e., 2,4-dinitrochlorobenzene and imidazolidinyl urea, under acidic conditions. These conditions were set by exposure to hydrochloric acid, lactic acid, and citric acid. An acidic extracellular pH (6-7) suppressed the augmentation of CD86 and CD54 levels by the sensitizer. Additionally, when the CD86/CD54 expression levels were suppressed, a reduction in the intracellular pH was confirmed. Furthermore, we observed that Na + /H + exchanger 1 (NHE-1), a protein that contributes to the regulation of extracellular/intracellular pH, is involved in CD86 and CD54 expression. These findings suggest that the extracellular/intracellular pH has substantial effects on in vitro skin sensitization markers and should be considered in evaluations of the safety of mixtures and commercial products in the future.

Protective effect of agaro-oligosaccharides on gut dysbiosis and colon tumorigenesis in high-fat diet-fed mice.

PubMed

Higashimura, Yasuki; Naito, Yuji; Takagi, Tomohisa; Uchiyama, Kazuhiko; Mizushima, Katsura; Ushiroda, Chihiro; Ohnogi, Hiromu; Kudo, Yoko; Yasui, Madoka; Inui, Seina; Hisada, Takayoshi; Honda, Akira; Matsuzaki, Yasushi; Yoshikawa, Toshikazu

2016-03-15

High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis. Copyright © 2016 the American Physiological Society.

[New-generation proton pump inhibitors: progress in the treatment of peptic acid diseases?].

PubMed

de Korwin, Jean-Dominique; Ducrotté, Philippe; Vallot, Thierry

2004-06-19

EFFECTS AND INCONVENIENCIES OF THE OLDER PRODUCTS: The proton pump inhibitors (PPIs) are now universally considered the treatment of choice for management of gastric-acid-related diseases, mainly gastro-oesophageal reflux disease (GERD). These drugs share similar properties: general structure, acid-activation step, covalent binding to the proton pump of the gastric parietal cell via the production of covalent disulphide bonds, relatively stable inhibition of H+,K+-ATPase. However, the older PPIs (omeprazole, lansoprazole et pantoprazole) have notable limitations. These drugs exhibit substantial interpatient variability and may have significant interactions with other drugs. These first-generation PPIs also do not achieve a rapid and sustained suppression of gastric acid, leading to the development of new acid-pump antagonists. The new-generation PPIs, esomeprazole and rabeprazole, offer several pharmacokinetic advantages: lower oxidative hepatic metabolism rate via the CYP 2C19 reducing the activity variations due to genetic polymorphisms and decreasing the risk of significant drug-drug interactions (advantages mainly for rabeprazole), lower metabolic clearance of esomeprazole (S-enantiomer of omeprazole) increasing plasma concentrations and acid suppression of this new PPI, higher accumulation of rabeprazole in the parietal cell due to its higher pKa. Gastric pH studies and therapeutic trials have demonstrated significant advantages of esomeprazole and rabeprazole compared with the older PPIs, which omeprazole is the prototype: a greater inhibition of acid secretion, a more rapid onset of action to provide reflux symptoms relief over 24 hours with lower GERD-related cost for rabeprazole, a sustained acid suppression, cost-effectiveness advantages for esomeprazole in the healing and maintenance of erosive esophagitis compared with lansoprazole, reduced potential for clinically significant drug-drug interactions with rabeprazole compared with omeprazole and esomeprazole. Due to their properties, esomeprazole and rabeprazole are the best candidates for "on demand" treatment of GERD.

UDCA and CDCA alleviate 17α-ethinylestradiol-induced cholestasis through PKA-AMPK pathways in rats

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

Li, Xiaojiaoyang; Yuan, Zihang

Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model. Our results showed that, both CDCA and UDCA significantly inducedmore » time- and concentration-dependent reduction in AMPK phosphorylation in SCRHs. Despite having different effects on FXR activation, CDCA and UDCA both inhibited EE-induced AMPK activation, accompanied with the up-regulation of FXR and its downstream bile acid transporters. However, although DCA activates FXR and induces SHP, it was unable to alleviate EE-induced FXR suppression and further aggravated EE-induced cholestasis. We further demonstrated that both CDCA and UDCA, but not DCA, activated cyclic AMP dependent protein kinase (PKA) in SCRHs and the livers of male rats (8 weeks old) liver. Furthermore, PKA antagonist, H89, blocked the AMPK inhibition by CDCA and UDCA, and pharmacological and genetic activation of PKA suppressed EE-induced AMPK activation and its downstream effects. Collectively, these results suggest that CDCA and UDCA protect against estrogen-induced cholestatic injury via PKA signaling pathway and up-regulation of EE-suppressed FXR, which suggests a potential therapeutic target for ICP. - Highlights: • AMPK is involved in cholestatic liver injury with bile acid dysregulation. • CDCA and UDCA inhibit the phosphorylation of AMPK and alleviate estrogen-induced cholestasis. • PKA activation contributes to the CDCA- and UDCA-induced protective effects. • FXR up-regulation may be critical for improvement of cholestasis.« less

Weight Suppression Predicts Time to Remission from Bulimia Nervosa

ERIC Educational Resources Information Center

Lowe, Michael R.; Berner, Laura A.; Swanson, Sonja A.; Clark, Vicki L.; Eddy, Kamryn T.; Franko, Debra L.; Shaw, Jena A.; Ross, Stephanie; Herzog, David B.

2011-01-01

Objective: To investigate whether, at study entry, (a) weight suppression (WS), the difference between highest past adult weight and current weight, prospectively predicts time to first full remission from bulimia nervosa (BN) over a follow-up period of 8 years, and (b) weight change over time mediates the relationship between WS and time to first…

Responses of plant seedlings to hypergravity: cellular and molecular aspects

NASA Astrophysics Data System (ADS)

Hoson, T.; Yoshioka, R.; Soga, K.; Wakabayashi, K.; Takeba, G.

Hypergravity produced by centrifugation has been used to analyze the responses of plant seedlings to gravity stimulus. Elongation growth of stem organs is suppressed by hypergravity, which can be recognized as a way for plants to resist gravitational force. The mechanisms inducing growth suppression under hypergravity conditions were analyzed at cellular and molecular levels. When growth was suppressed by hypergravity, a decrease in the cell wall extensibility was brought about in various plants. Hypergravity also induced a cell wall thickening and an increase in the molecular mass of the certain hemicellulosic polysaccharides. Both a decrease in the activities hydrolyzing such polysaccharides and an increase in the apoplast pH were involved in such changes in the cell wall constituents. Thus, the cell wall metabolism is greatly modified under hypergravity conditions, which causes a decrease in the cell wall extensibility, thereby inhibiting elongation growth in stem organs. On the other hand, to identify genes involved in hypergravity-induced growth suppression, changes in gene expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by differential display method. Sixty-two genes were expressed differentially: expression levels of 39 genes increased, whereas those of 23 genes decreased under hypergravity conditions. The expression of these genes was further analyzed using RT-PCR. One of genes upregulated by hypergravity encoded hydroxymethylglutaryl-CoA reductase (HMGR), which catalyzes a reaction producing mevalonic acid, a key precursor of hormones such as gibberellic acid and abscisic acid. The expression of HMGR gene increased within several hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR activity, prevented hypergravity-induced growth suppression, suggesting that HMGR is involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In addition, hypergravity increased the expression levels of CCR1 and ERD15, which were shown to take part in the signaling pathway of environmental stimuli such as temperature and water. These cellular and molecular changes appear to be involved in a series of events leading to growth suppression of stem organs under hypergravity conditions.

Amiloride-Sensitive and Amiloride-Insensitive Responses to NaCl + Acid Mixtures in Hamster Chorda Tympani Nerve

PubMed Central

Hettinger, Thomas P.; Savoy, Lawrence D.; Frank, Marion E.

2012-01-01

Component signaling in taste mixtures containing both beneficial and dangerous chemicals depends on peripheral processing. Unidirectional mixture suppression of chorda tympani (CT) nerve responses to sucrose by quinine and acid is documented for golden hamsters (Mesocricetus auratus). To investigate mixtures of NaCl and acids, we recorded multifiber responses to 50 mM NaCl, 1 and 3 mM citric acid and acetic acid, 250 μM citric acid, 20 mM acetic acid, and all binary combinations of each acid with NaCl (with and without 30 μM amiloride added). By blocking epithelial Na+ channels, amiloride treatment separated amiloride-sensitive NaCl-specific responses from amiloride-insensitive electrolyte-generalist responses, which encompass all of the CT response to the acids as well as responses to NaCl. Like CT sucrose responses, the amiloride-sensitive NaCl responses were suppressed by as much as 50% by citric acid (P = 0.001). The amiloride-insensitive electrolyte-generalist responses to NaCl + acid mixtures approximated the sum of NaCl and acid component responses. Thus, although NaCl-specific responses to NaCl were weakened in NaCl–acid mixtures, electrolyte-generalist responses to acid and NaCl, which tastes KCl-like, were transmitted undiminished in intensity to the central nervous system. The 2 distinct CT pathways are consistent with known rodent behavioral discriminations. PMID:22451526

Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model.

PubMed

Koskimaki, Jacob E; Karagiannis, Emmanouil D; Tang, Benjamin C; Hammers, Hans; Watkins, D Neil; Pili, Roberto; Popel, Aleksander S

2010-02-01

Angiogenesis is the formation of neovasculature from a pre-existing vascular network. Progression of solid tumors including lung cancer is angiogenesis-dependent. We previously introduced a bioinformatics-based methodology to identify endogenous anti-angiogenic peptide sequences, and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays. One family of peptides with high activity is derived from the alpha-fibrils of type IV collagen. Based on the results from the in vitro screening, we have evaluated the ability of a 20 amino acid peptide derived from the alpha5 fibril of type IV collagen, pentastatin-1, to suppress vessel growth in an angioreactor-based directed in vivo angiogenesis assay (DIVAA). In addition, pentastatin-1 suppressed tumor growth with intraperitoneal peptide administration in a small cell lung cancer (SCLC) xenograft model in nude mice using the NCI-H82 human cancer cell line. Pentastatin-1 decreased the invasion of vessels into angioreactors in vivo in a dose dependent manner. The peptide also decreased the rate of tumor growth and microvascular density in vivo in a small cell lung cancer xenograft model. The peptide treatment significantly decreased the invasion of microvessels in angioreactors and the rate of tumor growth in the xenograft model, indicating potential treatment for angiogenesis-dependent disease, and for translational development as a therapeutic agent for lung cancer.

Clostridium difficile Infection in the Department of Defense (DOD): 2007-2013

DTIC Science & Technology

2015-02-01

Comorbidity Burden among CDI Patients............................................................. 14 Previous Antibiotic and Gastric Acid Inhibitor...23 Previous Antibiotic and Gastric Acid Inhibitor Use...risk factors for CDI have been antibiotic use, advanced age (i.e., 65 years of age or older), comorbidity, use of gastric acid suppressants, and

Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor {alpha}/retinoid X receptor

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

Belanger, Adam J.; Luo Zhengyu; Vincent, Karen A.

2007-12-21

In response to cellular hypoxia, cardiomyocytes adapt to consume less oxygen by shifting ATP production from mitochondrial fatty acid {beta}-oxidation to glycolysis. The transcriptional activation of glucose transporters and glycolytic enzymes by hypoxia is mediated by hypoxia-inducible factor 1 (HIF-1). In this study, we examined whether HIF-1 was involved in the suppression of mitochondrial fatty acid {beta}-oxidation in hypoxic cardiomyocytes. We showed that either hypoxia or adenovirus-mediated expression of a constitutively stable hybrid form (HIF-1{alpha}/VP16) suppressed mitochondrial fatty acid metabolism, as indicated by an accumulation of intracellular neutral lipid. Both treatments also reduced the mRNA levels of muscle carnitine palmitoyltransferasemore » I which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for {beta}-oxidation. Furthermore, adenovirus-mediated expression of HIF-1{alpha}/VP16 in cardiomyocytes under normoxic conditions also mimicked the reduction in the DNA binding activity of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})/retinoid X receptor (RXR), in the presence or absence of a PPAR{alpha} ligand. These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPAR{alpha}/RXR.« less

Broadband Noise Control Using Predictive Techniques

NASA Technical Reports Server (NTRS)

Eure, Kenneth W.; Juang, Jer-Nan

1997-01-01

Predictive controllers have found applications in a wide range of industrial processes. Two types of such controllers are generalized predictive control and deadbeat control. Recently, deadbeat control has been augmented to include an extended horizon. This modification, named deadbeat predictive control, retains the advantage of guaranteed stability and offers a novel way of control weighting. This paper presents an application of both predictive control techniques to vibration suppression of plate modes. Several system identification routines are presented. Both algorithms are outlined and shown to be useful in the suppression of plate vibrations. Experimental results are given and the algorithms are shown to be applicable to non- minimal phase systems.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

Inhibition of chaotic escape from a potential well by incommensurate escape-suppressing excitations.

PubMed

Chacón, R; Martínez, J A

2002-03-01

Theoretical results are presented concerning the reduction of chaotic escape from a potential well by means of a harmonic parametric excitation that satisfies an ultrasubharmonic resonance condition with the escape-inducing excitation. The possibility of incommensurate escape-suppressing excitations is demonstrated by studying rational approximations to the irrational escape-suppressing frequency. The analytical predictions for the suitable amplitudes and initial phases of the escape-suppressing excitation are tested against numerical simulations based on a high-resolution grid of initial conditions. These numerical results indicate that the reduction of escape is reliably achieved for small amplitudes and at, and only at, the predicted initial phases. For the case of irrational escape-suppressing frequencies, the effective escape-reducing initial phases are found to lie close to the accumulation points of the set of suitable initial phases that are associated with the complete series of convergents up to the convergent giving the chosen rational approximation.

A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers

PubMed Central

Putnam, Christopher D.; Srivatsan, Anjana; Nene, Rahul V.; Martinez, Sandra L.; Clotfelter, Sarah P.; Bell, Sara N.; Somach, Steven B.; E.S. de Souza, Jorge; Fonseca, André F.; de Souza, Sandro J.; Kolodner, Richard D.

2016-01-01

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes. PMID:27071721

Protective effects of glycyrrhizic acid against non-alcoholic fatty liver disease in mice.

PubMed

Sun, Xue; Duan, Xingping; Wang, Changyuan; Liu, Zhihao; Sun, Pengyuan; Huo, Xiaokui; Ma, Xiaodong; Sun, Huijun; Liu, Kexin; Meng, Qiang

2017-07-05

Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. The purpose of the present study is to investigate the protective effect of glycyrrhizic acid (GA), a natural triterpene glycoside, on NAFLD induced by a high-fat diet (HFD) in mice, and further to elucidate the mechanisms underlying GA protection. GA treatment significantly reduced the relative liver weight, serum ALT, AST activities, levels of serum lipid, blood glucose and insulin. GA suppressed lipid accumulation in liver. Further mechanism investigation indicated that GA reduced hepatic lipogenesis via downregulating SREBP-1c, FAS and SCD1 expression, increased fatty acids β-oxidation via an increase in PPARα, CPT1α and ACADS, and promoted triglyceride metabolism through inducing LPL activity. Furthermore, GA reduced gluconeogenesis through repressing PEPCK and G6Pase, and increased glycogen synthesis through an induction in gene expression of PDase and GSK3β. In addition, GA increased insulin sensitivity through upregulating phosphorylation of IRS-1 and IRS-2. In conclusion, GA produces protective effect against NAFLD, due to regulation of genes involved in lipid, glucose homeostasis and insulin sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

One-pot conversion of biomass-derived xylose and furfural into levulinate esters via acid catalysis.

PubMed

Hu, Xun; Jiang, Shengjuan; Wu, Liping; Wang, Shuai; Li, Chun-Zhu

2017-03-07

Direct conversion of biomass-derived xylose and furfural into levulinic acid, a platform molecule, via acid-catalysis has been accomplished for the first time in dimethoxymethane/methanol. Dimethoxymethane acted as an electrophile to transform furfural into 5-hydroxymethylfurfural (HMF). Methanol suppressed both the polymerisation of the sugars/furans and the Aldol condensation of levulinic acid/ester.

Optimization of Reversed-Phase Peptide Liquid Chromatography Ultraviolet Mass Spectrometry Analyses Using an Automated Blending Methodology

PubMed Central

Chakraborty, Asish B.; Berger, Scott J.

2005-01-01

The balance between chromatographic performance and mass spectrometric response has been evaluated using an automated series of experiments where separations are produced by the real-time automated blending of water with organic and acidic modifiers. In this work, the concentration effects of two acidic modifiers (formic acid and trifluoroacetic acid) were studied on the separation selectivity, ultraviolet, and mass spectrometry detector response, using a complex peptide mixture. Peptide retention selectivity differences were apparent between the two modifiers, and under the conditions studied, trifluoroacetic acid produced slightly narrower (more concentrated) peaks, but significantly higher electrospray mass spectrometry suppression. Trifluoroacetic acid suppression of electrospray signal and influence on peptide retention and selectivity was dominant when mixtures of the two modifiers were analyzed. Our experimental results indicate that in analyses where the analyzed components are roughly equimolar (e.g., a peptide map of a recombinant protein), the selectivity of peptide separations can be optimized by choice and concentration of acidic modifier, without compromising the ability to obtain effective sequence coverage of a protein. In some cases, these selectivity differences were explored further, and a rational basis for differentiating acidic modifier effects from the underlying peptide sequences is described. PMID:16522853

Asiatic acid ameliorates pulmonary fibrosis induced by bleomycin (BLM) via suppressing pro-fibrotic and inflammatory signaling pathways.

PubMed

Dong, Shu-Hong; Liu, Yan-Wei; Wei, Feng; Tan, Hui-Zhen; Han, Zhi-Dong

2017-05-01

Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice. Further, Asiatic acid down-regulates inflammatory cells infiltration in bronchoalveolar lavage fluid (BALF) and pro-inflammatory cytokines expression in lung tissue specimens induced by BLM. Also, Asiatic acid apparently suppressed transforming growth factor-beta 1 (TGF-β1) expression in tissues of lung, accompanied with Collagen I, Collagen III, α-SMA and matrix metalloproteinase (TIMP)-1 decreasing, as well as Smads and ERK1/2 inactivation. Of note, Asiatic acid reduces NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome. The findings indicated that Asiatic acid might be an effective candidate for pulmonary fibrosis and inflammation treatment. Copyright © 2017. Published by Elsevier Masson SAS.

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.

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

PubMed Central

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

Influence of Liver Triglycerides on Suppression of Glucose Production by Insulin in Men

PubMed Central

Szuszkiewicz-Garcia, Magdalene; Browning, Jeffrey D.; Baxter, Jeannie D.; Abate, Nicola; Malloy, Craig R.

2015-01-01

Context: The ability of insulin to suppress hepatic glucose production is impaired among subjects with increased intrahepatic triglycerides (IHTG). However, little is known about the roles of insulin on the supporting fluxes of glucose production among patients with fatty liver. Objective: To evaluate the effects of insulin on fluxes through the three potential sources of plasma glucose (glycerol, the citric acid cycle, and glycogen) among patients with fatty liver. Design, Settings, Participants, and Intervention: Nineteen men with a range of IHTG (∼0.5% to 23%) were studied after an overnight fast and during hyperinsulinemia using magnetic resonance spectroscopy and stable isotope tracers. Main Outcome Measures: IHTG, gluconeogenesis from glycerol, gluconeogenesis from the citric acid cycle, glycogenolysis, and 13C-labeled glucose produced from the citric acid cycle during hyperinsulinemia were measured. Results: Men with high IHTG had higher fluxes through all pathways contributing to glucose production during hyperinsulinemia, compared to men with low IHTG, but they had similar fluxes after the fast. Consequently, men with fatty liver had impaired insulin efficiency in suppressing total glucose production as well as fluxes through all three biochemical pathways contributing to glucose. The detection of glucose isotopomers with 13C arising from [U-13C3]propionate ingested during hyperinsulinemia demonstrated continuous gluconeogenesis from the citric acid cycle in all subjects. Conclusions: These findings challenge the concept that individual glucose production pathways are selectively dysregulated during hepatic insulin resistance. Overproduction of glucose during hyperinsulinemia in men with fatty liver results from inadequate suppression of all the supporting fluxes of glucose production in response to insulin. PMID:25250633

Salicylic Acid Suppresses Jasmonic Acid Signaling Downstream of SCFCOI1-JAZ by Targeting GCC Promoter Motifs via Transcription Factor ORA59[C][W][OA

PubMed Central

Van der Does, Dieuwertje; Leon-Reyes, Antonio; Koornneef, Annemart; Van Verk, Marcel C.; Rodenburg, Nicole; Pauwels, Laurens; Goossens, Alain; Körbes, Ana P.; Memelink, Johan; Ritsema, Tita; Van Wees, Saskia C.M.; Pieterse, Corné M.J.

2013-01-01

Antagonism between the defense hormones salicylic acid (SA) and jasmonic acid (JA) plays a central role in the modulation of the plant immune signaling network, but the molecular mechanisms underlying this phenomenon are largely unknown. Here, we demonstrate that suppression of the JA pathway by SA functions downstream of the E3 ubiquitin-ligase Skip-Cullin-F-box complex SCFCOI1, which targets JASMONATE ZIM-domain transcriptional repressor proteins (JAZs) for proteasome-mediated degradation. In addition, neither the stability nor the JA-induced degradation of JAZs was affected by SA. In silico promoter analysis of the SA/JA crosstalk transcriptome revealed that the 1-kb promoter regions of JA-responsive genes that are suppressed by SA are significantly enriched in the JA-responsive GCC-box motifs. Using GCC:GUS lines carrying four copies of the GCC-box fused to the β-glucuronidase reporter gene, we showed that the GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Using plants overexpressing the GCC-box binding APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors ERF1 or ORA59, we found that SA strongly reduces the accumulation of ORA59 but not that of ERF1. Collectively, these data indicate that the SA pathway inhibits JA signaling downstream of the SCFCOI1-JAZ complex by targeting GCC-box motifs in JA-responsive promoters via a negative effect on the transcriptional activator ORA59. PMID:23435661

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.

Report on the analysis of common beverages spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) using NMR and the PURGE solvent-suppression technique.

PubMed

Lesar, Casey T; Decatur, John; Lukasiewicz, Elaan; Champeil, Elise

2011-10-10

In forensic evidence, the identification and quantitation of gamma-hydroxybutyric acid (GHB) in "spiked" beverages is challenging. In this report, we present the analysis of common alcoholic beverages found in clubs and bars spiked with gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL). Our analysis of the spiked beverages consisted of using (1)H NMR with a water suppression method called Presaturation Utilizing Relaxation Gradients and Echoes (PURGE). The following beverages were analyzed: water, 10% ethanol in water, vodka-cranberry juice, rum and coke, gin and tonic, whisky and diet coke, white wine, red wine, and beer. The PURGE method allowed for the direct identification and quantitation of both compounds in all beverages except red and white wine where small interferences prevented accurate quantitation. The NMR method presented in this paper utilizes PURGE water suppression. Thanks to the use of a capillary internal standard, the method is fast, non-destructive, sensitive and requires no sample preparation which could disrupt the equilibrium between GHB and GBL. Published by Elsevier Ireland Ltd.

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

Synthesis and regulation of chlorogenic acid in potato: Rerouting phenylpropanoid flux in HQT-silenced lines.

PubMed

Payyavula, Raja S; Shakya, Roshani; Sengoda, Venkatesan G; Munyaneza, Joseph E; Swamy, Prashant; Navarre, Duroy A

2015-05-01

Chlorogenic acid (CGA) is the major phenolic sink in potato tubers and can constitute over 90% of total phenylpropanoids. The regulation of CGA biosynthesis in potato and the role of the CGA biosynthetic gene hydroxycinnamoyl CoA:quinate hydroxycinnamoyl transferase (HQT) was characterized. A sucrose induced accumulation of CGA correlated with the increased expression of phenylalanine ammonia-lyase (PAL) rather than HQT. Transient expression of the potato MYB transcription factor StAN1 (anthocyanin 1) in tobacco increased CGA. RNAi suppression of HQT resulted in over a 90% reduction in CGA and resulted in early flowering. The reduction in total phenolics and antioxidant capacity was less than the reduction in CGA, suggesting flux was rerouted into other phenylpropanoids. Network analysis showed distinct patterns in different organs, with anthocyanins and phenolic acids showing negative correlations in leaves and flowers and positive in tubers. Some flavonols increased in flowers, but not in leaves or tubers. Anthocyanins increased in flowers and showed a trend to increase in leaves, but not tubers. HQT suppression increased biosynthesis of caffeoyl polyamines, some of which are not previously reported in potato. Decreased PAL expression and enzyme activity was observed in HQT suppressed lines, suggesting the existence of a regulatory loop between CGA and PAL. Electrophysiology detected no effect of CGA suppression on potato psyllid feeding. Collectively, this research showed that CGA in potatoes is synthesized through HQT and HQT suppression altered phenotype and redirected phenylpropanoid flux. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Magnaporthe oryzae Induces the Expression of a MicroRNA to Suppress the Immune Response in Rice.

PubMed

Zhang, Xin; Bao, Yalin; Shan, Deqi; Wang, Zhihui; Song, Xiaoning; Wang, Zhaoyun; Wang, Jiansheng; He, Liqiang; Wu, Liang; Zhang, Zhengguang; Niu, Dongdong; Jin, Hailing; Zhao, Hongwei

2018-05-01

MicroRNAs play crucial roles in plant responses to pathogen infections. The rice blast disease, caused by the fungus Magnaporthe oryzae , is the most important disease of rice ( Oryza sativa ). To explore the microRNA species that participate in rice immunity against the rice blast disease, we compared the expression of small RNAs between mock- and M. oryzae -treated rice. We found that infection by M. oryzae strain Guy11 specifically induced the expression of rice miR319 and, consequently, suppressed its target gene TEOSINTE BRANCHED/CYCLOIDEA/PROLIFERATING CELL FACTOR1 ( OsTCP21 ), which encodes a transcription factor. Using transgenic rice that overexpresses miR319b (OE) or expresses OsTCP21 -Res (which is resistant to miR319-mediated silencing), we found that OsTCP21 is a positive regulator of the rice defense response against the blast disease. When wild-type and miR319b-OE rice were infected by Guy11, multiple jasmonic acid (JA) synthetic and signaling components were suppressed, indicating that Guy11 suppresses JA signaling through inducing miR319. In particular, we found that LIPOXYGENASE2 ( LOX2 ) and LOX5 were specifically suppressed by miR319 overexpression or by Guy11 infection. LOXs are the key enzymes of JA synthesis, which catalyze the conversion of α-linoleic acid to hydroperoxy-octadecadienoic acid. The application of α-linoleic acid rescued disease symptoms on the OsTCP21 -Res rice but not wild-type rice, supporting our hypothesis that OsLOX2 and OsLOX5 are the key JA synthesis genes hijacked by Guy11 to subvert host immunity and facilitate pathogenicity. We propose that induced expression of OsLOX2/5 may improve resistance to the rice blast disease. © 2018 American Society of Plant Biologists. All Rights Reserved.

Magnaporthe oryzae Induces the Expression of a MicroRNA to Suppress the Immune Response in Rice1[OPEN

PubMed Central

Zhang, Xin; Bao, Yalin; Shan, Deqi; Wang, Zhihui; Song, Xiaoning; Wang, Zhaoyun; Wang, Jiansheng; He, Liqiang; Wu, Liang; Zhang, Zhengguang; Niu, Dongdong

2018-01-01

MicroRNAs play crucial roles in plant responses to pathogen infections. The rice blast disease, caused by the fungus Magnaporthe oryzae, is the most important disease of rice (Oryza sativa). To explore the microRNA species that participate in rice immunity against the rice blast disease, we compared the expression of small RNAs between mock- and M. oryzae-treated rice. We found that infection by M. oryzae strain Guy11 specifically induced the expression of rice miR319 and, consequently, suppressed its target gene TEOSINTE BRANCHED/CYCLOIDEA/PROLIFERATING CELL FACTOR1 (OsTCP21), which encodes a transcription factor. Using transgenic rice that overexpresses miR319b (OE) or expresses OsTCP21-Res (which is resistant to miR319-mediated silencing), we found that OsTCP21 is a positive regulator of the rice defense response against the blast disease. When wild-type and miR319b-OE rice were infected by Guy11, multiple jasmonic acid (JA) synthetic and signaling components were suppressed, indicating that Guy11 suppresses JA signaling through inducing miR319. In particular, we found that LIPOXYGENASE2 (LOX2) and LOX5 were specifically suppressed by miR319 overexpression or by Guy11 infection. LOXs are the key enzymes of JA synthesis, which catalyze the conversion of α-linoleic acid to hydroperoxy-octadecadienoic acid. The application of α-linoleic acid rescued disease symptoms on the OsTCP21-Res rice but not wild-type rice, supporting our hypothesis that OsLOX2 and OsLOX5 are the key JA synthesis genes hijacked by Guy11 to subvert host immunity and facilitate pathogenicity. We propose that induced expression of OsLOX2/5 may improve resistance to the rice blast disease. PMID:29549093

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

PubMed

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress Staphylococcus aureus Production of Toxic Shock Syndrome Toxin 1▿

PubMed Central

McNamara, Peter J.; Syverson, Rae Ellen; Milligan-Myhre, Kathy; Frolova, Olga; Schroeder, Sarah; Kidder, Joshua; Hoang, Thanh; Proctor, Richard A.

2009-01-01

Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1. PMID:19223628

A Study on Electric Power Smoothing System for Lead-Acid Battery of Stand-Alone Natural Energy Power System Using EDLC

NASA Astrophysics Data System (ADS)

Jia, Yan; Shibata, Ryosuke; Yamamura, Naoki; Ishida, Muneaki

To resolve energy shortage and global warming problem, renewable natural resource and its power system has been gradually generalizing. However, the power fluctuation suppressing in short period and the balance control of consumption and supply in long period are two of main problems that need to be resolved urgently in natural energy power system. In Stand-alone Natural Energy Power System (SNEPS) with power energy storage devices, power fluctuation in short period is one of the main reasons that recharge cycle times increase and lead-acid battery early failure. Hence, to prolong the service life of lead-acid battery and improve power quality through suppressing the power fluctuation, we proposed a method of electric power smoothing for lead-acid battery of SNEPS using bi-directional Buck/Boost converter and Electric Double Layer Capacitor (EDLC) in this paper. According to the test data of existing SNEPS, a power fluctuation condition is selected and as an example to analyze the validity of the proposed method. The analysis of frequency characteristics indicates the power fluctuation is suppressed a desired range in the target frequency region. The experimental results of confirmed the feasibility of the proposed system and the results well satisfy the requirement of system design.

Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens.

PubMed

Afrose, Sadia; Hossain, Md Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada

2010-01-01

This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of (14)C from 1-(14)C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver.

Dietary Karaya Saponin and Rhodobacter capsulatus Exert Hypocholesterolemic Effects by Suppression of Hepatic Cholesterol Synthesis and Promotion of Bile Acid Synthesis in Laying Hens

PubMed Central

Afrose, Sadia; Hossain, Md. Sharoare; Salma, Ummay; Miah, Abdul Gaffar; Tsujii, Hirotada

2010-01-01

This study was conducted to elucidate the mechanism underlying the hypolipidemic action of karaya saponin or Rhodobacter (R.) capsulatus. A total of 40 laying hens (20-week-old) were assigned into four dietary treatment groups and fed a basal diet (as a control) or basal diets supplemented with either karaya saponin, R. capsulatus, or both for 60 days. The level of serum low-density-lipoprotein cholesterol and the levels of cholesterol and triglycerides in the serum, liver, and egg yolk were reduced by all the supplementations (P < .05). Liver bile acid concentration and fecal concentrations of cholesterol, triacylglycerol, and bile acid were simultaneously increased by the supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus (P < .05). The supplementation of karaya saponin, R. capsulatus, and the combination of karaya saponin and R. capsulatus suppressed the incorporation of 14C from 1-14C-palmitic acid into the fractions of total lipids, phospholipids, triacylglycerol, and cholesterol in the liver in vitro (P < .05). These findings suggest that the hypocholesterolemic effects of karaya saponin and R. capsulatus are caused by the suppression of the cholesterol synthesis and the promotion of cholesterol catabolism in the liver. PMID:21490913

Leucine deprivation inhibits proliferation and induces apoptosis of human breast cancer cells via fatty acid synthase

PubMed Central

Xiao, Fei; Wang, Chunxia; Yin, Hongkun; Yu, Junjie; Chen, Shanghai; Fang, Jing; Guo, Feifan

2016-01-01

Substantial studies on fatty acid synthase (FASN) have focused on its role in regulating lipid metabolism and researchers have a great interest in treating cancer with dietary manipulation of amino acids. In the current study, we found that leucine deprivation caused the FASN-dependent anticancer effect. Here we showed that leucine deprivation inhibited cell proliferation and induced apoptosis of MDA-MB-231 and MCF-7 breast cancer cells. In an in vivo tumor xenograft model, the leucine-free diet suppressed the growth of human breast cancer tumors and triggered widespread apoptosis of the cancer cells. Further study indicated that leucine deprivation decreased expression of lipogenic gene FASN in vitro and in vivo. Over-expression of FASN or supplementation of palmitic acid (the product of FASN action) blocked the effects of leucine deprivation on cell proliferation and apoptosis in vitro and in vivo. Moreover, leucine deprivation suppressed the FASN expression via regulating general control non-derepressible (GCN)2 and sterol regulatory element-binding protein 1C (SREBP1C). Taken together, our study represents proof of principle that anticancer effects can be obtained with strategies to deprive tumors of leucine via suppressing FASN expression, which provides important insights in prevention of breast cancer via metabolic intervention. PMID:27579768

Omega-3 Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid Enhance Dexamethasone Sensitivity in Multiple Myeloma Cells by the p53/miR-34a/Bcl-2 Axis.

PubMed

Dai, Xianping; Li, Mengshun; Geng, Feng

2017-07-01

Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells. Both luciferase reporter assay and Western blot showed that Bcl-2 is the direct target of miR-34a in MM cells. In addition, we observed that PUFAs induced p53 protein expression in MM cells under dexamethasone administration. Furthermore, suppressing p53 by its inhibitor, Pifithrin-α, regulated the miR-34a expression and modulated the sensitivity to dexamethasone in U266 cells. In summary, these results suggest that PUFAs enhance dexamethasone sensitivity to MM cells through the p53/miR-34a axis with a likely contribution of Bcl-2 suppression.

The role of lactic acid bacteria (Lactobacillus sp yel133) from beef in inhibiting of microbial contaminants on various fillers of starter culture

NASA Astrophysics Data System (ADS)

Yunilas; Mirwandhono, E.

2018-02-01

The role of Lactic Acid Bacteria (LAB) on the starter culture can be seen from the ability to grow and suppress the growth of microbial contaminants (fungi). The research aimed to investigate the role of LAB (Lactobacillus sp YEL133) in inhibiting microbial contaminants (fungi) on starter cultures of various fillers. The materials used in this research was Lactobacillus sp YEL133 from beef and various fillers (rice flour, corn starch and wheat flour). The research methods used completely randomized design (CRD) with 3 treatments and 4 replications. The treatments of this research was P1(rice flour), P2 (corn starch) and P3 (wheat flour) that inoculated with Lactobacillus sp YEL133. Parameters which is observed such as: growth of lactic acid bacteria, total microbes and total fungi as microbial contaminants. The results showed that the starter culture with a filler material of rice flour produce lactic acid bacteria and microbes were highly significant (P <0.01) for corn starch and wheat flour, as well as able to suppress the growth of microbial contaminants (fungi). The conclusion of the research is the use Lactobacillus sp YEL133 can suppress the growth of fungi on the starter culture using rice flour.

Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

PubMed

Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease.

PubMed

Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

2017-03-03

Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia ( p < 0.05) and in microglial phagocytosis in the brain. In Alzheimer's model 5xFAD mice, oral administration of iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex ( p < 0.05) and a significant improvement in a novel object recognition test ( p < 0.05), as compared with control-fed 5xFAD mice. The differences in iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Estrogen suppresses melatonin-enhanced hyperactivation of hamster spermatozoa

PubMed Central

FUJINOKI, Masakatsu; TAKEI, Gen L.

2015-01-01

Hamster sperm hyperactivation is enhanced by progesterone, and this progesterone-enhanced hyperactivation is suppressed by 17β-estradiol (17βE2) and γ-aminobutyric acid (GABA). Although it has been indicated that melatonin also enhances hyperactivation, it is unknown whether melatonin-enhanced hyperactivation is also suppressed by 17βE2 and GABA. In the present study, melatonin-enhanced hyperactivation was significantly suppressed by 17βE2 but not by GABA. Moreover, suppression of melatonin-enhanced hyperactivation by 17βE2 occurred through non-genomic regulation via the estrogen receptor (ER). These results suggest that enhancement of hyperactivation is regulated by melatonin and 17βE2 through non-genomic regulation. PMID:25959801

Nickel Inhibits Mitochondrial Fatty Acid Oxidation

PubMed Central

Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

2015-01-01

Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

Citric Acid and Quinine Share Perceived Chemosensory Features Making Oral Discrimination Difficult in C57BL/6J Mice

PubMed Central

Treesukosol, Yada; Mathes, Clare M.

2011-01-01

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical. PMID:21421543

Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice.

PubMed

Watanabe, Yasuharu; Nagai, Yoshinori; Honda, Hiroe; Okamoto, Naoki; Yamamoto, Seiji; Hamashima, Takeru; Ishii, Yoko; Tanaka, Miyako; Suganami, Takayoshi; Sasahara, Masakiyo; Miyake, Kensuke; Takatsu, Kiyoshi

2016-03-15

Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages. ILG suppressed inflammatory changes induced by the co-culture through inhibition of NF-κB activation. This effect was independent of either inhibition of inflammasome activation or activation of peroxisome proliferator-activated receptor-γ. Moreover, ILG suppressed TNF-α-induced activation of adipocytes, coincident with inhibition of IκBα phosphorylation. Additionally, TNF-α-mediated inhibition of Akt phosphorylation under insulin signaling was alleviated by ILG in adipocytes. ILG suppressed palmitic acid-induced activation of macrophages, with decreasing the level of phosphorylated Jnk expression. Intriguingly, ILG improved high fat diet-induced fibrosis in adipose tissue in vivo. Finally, ILG inhibited TLR4- or Mincle-stimulated expression of fibrosis-related genes in stromal vascular fraction from obese adipose tissue and macrophages in vitro. Thus, ILG can suppress adipose tissue inflammation by both inflammasome-dependent and -independent manners and attenuate adipose tissue fibrosis by targeting innate immune sensors.

Glycyrrhetinic acid inhibits contact hypersensitivity induced by trichophytin via dectin-1.

PubMed

Nakamura, Tomoya; Nishibu, Akiko; Yoshida, Naoki; Yasoshima, Mitsue; Anzawa, Kazushi; Watanabe, Yasuharu; Nagai, Yoshinori; Takatsu, Kiyoshi; Ogawa, Kazuo; Mochizuki, Takashi

2016-04-01

Trichophyton infection is highly prevalent and tends to be recurrent. Therefore, it is important to develop new therapeutic agents. Previously, we established a mouse model of Trichophyton-induced contact hypersensitivity (CHS) and demonstrated that dectin-1 was involved in inflammation induced by trichophytin, the Trichophyton antigen. Here, we used that model to investigate glycyrrhetinic acid (GA) from plants of the genus Glycyrrhiza as a potential anti-inflammatory agent against superficial mycoses. GA suppressed swelling and the expression of inflammatory cytokines, including macrophage inflammatory protein (MIP)-2, interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ mRNA. Anti-MIP-2 antibody suppressed trichophytin-induced inflammation, and antidectin-1 antibody suppressed zymosan-induced MIP-2 production in keratinocyte cells. These results suggest that MIP-2 is produced by dectin-1 activation and is involved in inflammation associated with CHS to trichophytin. GA also suppressed zymosan-induced MIP-2 and interleukin (IL)-8, production in mouse and human macrophages and keratinocytes. Furthermore, GA suppressed the phosphorylation of spleen tyrosine kinase (Syk) and inhibitor of nuclear factor-kappa B (IκBα) and the degradation of IκBα in zymosan-simulated RAW264.7 cells. The results of this study suggest that GA suppresses inflammation induced by trichophytin, partly by the downregulation of Syk phosphorylation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ethylene signaling renders the jasmonate response of Arabidopsis insensitive to future suppression by salicylic Acid.

PubMed

Leon-Reyes, Antonio; Du, Yujuan; Koornneef, Annemart; Proietti, Silvia; Körbes, Ana P; Memelink, Johan; Pieterse, Corné M J; Ritsema, Tita

2010-02-01

Cross-talk between jasmonate (JA), ethylene (ET), and Salicylic acid (SA) signaling is thought to operate as a mechanism to fine-tune induced defenses that are activated in response to multiple attackers. Here, 43 Arabidopsis genotypes impaired in hormone signaling or defense-related processes were screened for their ability to express SA-mediated suppression of JA-responsive gene expression. Mutant cev1, which displays constitutive expression of JA and ET responses, appeared to be insensitive to SA-mediated suppression of the JA-responsive marker genes PDF1.2 and VSP2. Accordingly, strong activation of JA and ET responses by the necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola prior to SA treatment counteracted the ability of SA to suppress the JA response. Pharmacological assays, mutant analysis, and studies with the ET-signaling inhibitor 1-methylcyclopropene revealed that ET signaling renders the JA response insensitive to subsequent suppression by SA. The APETALA2/ETHYLENE RESPONSE FACTOR transcription factor ORA59, which regulates JA/ET-responsive genes such as PDF1.2, emerged as a potential mediator in this process. Collectively, our results point to a model in which simultaneous induction of the JA and ET pathway renders the plant insensitive to future SA-mediated suppression of JA-dependent defenses, which may prioritize the JA/ET pathway over the SA pathway during multi-attacker interactions.

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression

PubMed Central

Brown, Joel S.; Cunningham, Jessica J.; Gatenby, Robert A.

2015-01-01

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed—a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler–Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the ‘cost’ (decreased fecundity) of suppression verses the ‘cost’ of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. PMID:26056365

Growth Suppression and Therapy Sensitization of Breast Cancer.

DTIC Science & Technology

1997-07-01

mutant jun. As shown in Figure 8, T47D breast cancer cells grown in the presence of 9- cis retinoic acid do become more sensitive to suppression by p53...SRI 1220. We have used the plasmid reactivation assay to demonstrate that repair of a cisplatin damaged plasmid is inhibited by 9- cis retinoic acid in...3 hr in vitro Sensitivity of T47D cells to 9- cis RA with 25 pM cisplatin) 120 --- 25- T47D 1220 M 100 - 11-gal O ,p53 "o 8.0 o. m 5 wR 80 T47D

Regulating sadness and fear from outside and within: mothers' emotion socialization and adolescents' parasympathetic regulation predict the development of internalizing difficulties.

PubMed

Hastings, Paul D; Klimes-Dougan, Bonnie; Kendziora, Kimberly T; Brand, Ann; Zahn-Waxler, Carolyn

2014-11-01

Multilevel models of developmental psychopathology implicate both characteristics of the individual and their rearing environment in the etiology of internalizing problems and disorders. Maladaptive regulation of fear and sadness, the core of anxiety and depression, arises from the conjoint influences of ineffective parasympathetic regulation of emotion and ineffective emotion socialization experiences. In 171 youths (84 female, M = 13.69 years, SD = 1.84), we measured changes of respiratory sinus arrhythmia (RSA) in response to sadness- and fear-inducing film clips and maternal supportive and punitive responses to youths' internalizing emotions. Youths and mothers reported on youths' internalizing problems and anxiety and depression symptoms concurrently and 2 years later at Time 2. Maternal supportive emotion socialization predicted fewer, and punitive socialization predicted more, mother-reported internalizing problems at Time 2 only for youths who showed RSA suppression to fear-inducing films. More RSA suppression to sadness-inducing films predicted more youth-reported internalizing problems at Time 2 in girls only. In addition, less supportive emotion socialization predicted more youth-reported depression symptoms at Time 2 only for girls who showed more RSA suppression to sadness. RSA suppression to sadness versus fear might reflect different patterns of atypical parasympathetic regulation of emotional arousal, both of which increase the risk for internalizing difficulties in youths, and especially girls, who lack maternal support for regulating emotions.

Suppressed anger, evaluative threat, and cardiovascular reactivity: a tripartite profile approach.

PubMed

Jorgensen, Randall S; Kolodziej, Monika E

2007-11-01

Despite decades of theory and research implicating suppressed anger in the development of cardiovascular disorders involving cardiovascular reactivity (CVR), to date the theoretical components of low anger expression, guilt feelings over agonistic reactions, and defensive strivings to avoid social disapproval have not been used conjointly to profile suppressed anger for the prediction of CVR. The purpose of this study, then, was to cluster analyze measures of anger expression, hostility guilt, and social defensiveness to create a suppressed anger profile (low anger expression, high hostility guilt, high social defensiveness) and a non-suppressed profile from a sample of college males. Social evaluative threat may be a potent stressor for people who defensively suppress anger expression. Thus, to examine the combined effects of suppressed anger and social evaluative threat, participants, prior to telling a story to a Thematic Apperception Card (TAT), were randomly assigned to either a high-threat (story will be compared to stories created by the mentally ill) or a low-threat condition (story used to study effects of talking on cardiovascular responses). Blood pressure (BP) and heart rate (HR) were monitored during a rest period and the subsequent TAT card period. As predicted, suppressed anger males in the high-threat condition showed the highest levels of diastolic BP and HR change from the rest period. The suppressed anger group's systolic BP reactivity was independent of threat manipulation. Research implications are discussed.

Repetition Suppression and Multi-Voxel Pattern Similarity Differentially Track Implicit and Explicit Visual Memory

PubMed Central

Chun, Marvin M.; Kuhl, Brice A.

2013-01-01

Repeated exposure to a visual stimulus is associated with corresponding reductions in neural activity, particularly within visual cortical areas. It has been argued that this phenomenon of repetition suppression is related to increases in processing fluency or implicit memory. However, repetition of a visual stimulus can also be considered in terms of the similarity of the pattern of neural activity elicited at each exposure—a measure that has recently been linked to explicit memory. Despite the popularity of each of these measures, direct comparisons between the two have been limited, and the extent to which they differentially (or similarly) relate to behavioral measures of memory has not been clearly established. In the present study, we compared repetition suppression and pattern similarity as predictors of both implicit and explicit memory. Using functional magnetic resonance imaging, we scanned 20 participants while they viewed and categorized repeated presentations of scenes. Repetition priming (facilitated categorization across repetitions) was used as a measure of implicit memory, and subsequent scene recognition was used as a measure of explicit memory. We found that repetition priming was predicted by repetition suppression in prefrontal, parietal, and occipitotemporal regions; however, repetition priming was not predicted by pattern similarity. In contrast, subsequent explicit memory was predicted by pattern similarity (across repetitions) in some of the same occipitotemporal regions that exhibited a relationship between priming and repetition suppression; however, explicit memory was not related to repetition suppression. This striking double dissociation indicates that repetition suppression and pattern similarity differentially track implicit and explicit learning. PMID:24027275

Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

DTIC Science & Technology

2009-02-01

2005) 15-lipoxygenase metabolites of γ-linolenic acid / eicosapentaenoic acid suppress growth and arachidonic acid metabolism in human prostatic...found primarily in fish oils, comprise the -3 family: Alpha linolenic acid (ALA or -96 LNA; 18:3-3), eicosapentaenoic acid (EPA; 20:5-3), and... eicosapentaenoic acid (EPA) also 122 serves as a substrate for 15-LO-1 and COX-2, but metabolism of EPA by these enzymes results in 123 the formation of

Mutations in Elongation Factor Ef-1α Affect the Frequency of Frameshifting and Amino Acid Misincorporation in Saccharomyces Cerevisiae

PubMed Central

Sandbaken, M. G.; Culbertson, M. R.

1988-01-01

A mutational analysis of the eukaryotic elongation factor EF-1α indicates that this protein functions to limit the frequency of errors during genetic code translation. We found that both amino acid misincorporation and reading frame errors are controlled by EF-1α. In order to examine the function of this protein, the TEF2 gene, which encodes EF-1α in Saccharomyces cerevisiae, was mutagenized in vitro with hydroxylamine. Sixteen independent TEF2 alleles were isolated by their ability to suppress frameshift mutations. DNA sequence analysis identified eight different sites in the EF-1α protein that elevate the frequency of mistranslation when mutated. These sites are located in two different regions of the protein. Amino acid substitutions located in or near the GTP-binding and hydrolysis domain of the protein cause suppression of frameshift and nonsense mutations. These mutations may effect mistranslation by altering the binding or hydrolysis of GTP. Amino acid substitutions located adjacent to a putative aminoacyl-tRNA binding region also suppress frameshift and nonsense mutations. These mutations may alter the binding of aminoacyl-tRNA by EF-1α. The identification of frameshift and nonsense suppressor mutations in EF-1α indicates a role for this protein in limiting amino acid misincorporation and reading frame errors. We suggest that these types of errors are controlled by a common mechanism or closely related mechanisms. PMID:3066688

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.

Effects of dietary supplementation of ferulic acid and gamma-oryzanol on integument color and suppression of oxidative stress in cultured red sea bream, Pagrus major.

PubMed

Maoka, Takashi; Tanimoto, Fumio; Sano, Mitsuhiko; Tsurukawa, Kanji; Tsuno, Takuo; Tsujiwaki, Satomi; Ishimaru, Katsuya; Takii, Kenji

2008-01-01

The effects of ferulic acid (FA) and gamma-oryzanol (OZ) supplementation on cultured red sea bream were examined. Commercial brown fish meal diets supplemented with FA (0.01-0.5%) or OZ (0.05-0.5%) were given to zero-year, cultured red sea bream for 98 days. After the experiment, the brightness of the integument color ("L" value) of FA- and OZ-administrated fish was higher than that of control fish. Furthermore, 2-Thiobarbituric acid reactive substances (TBARS) in the liver of FA- and OZ-administrated fish was lower than in control fish. These results indicate that FA and OZ suppressed not only dark-color pigmentation but also oxidative stress in cultured red sea bream.

Metabolic basis for the differential susceptibility of Gram-positive pathogens to fatty acid synthesis inhibitors

PubMed Central

Parsons, Joshua B.; Frank, Matthew W.; Subramanian, Chitra; Saenkham, Panatda; Rock, Charles O.

2011-01-01

The rationale for the pursuit of bacterial type 2 fatty acid synthesis (FASII) as a target for antibacterial drug discovery in Gram-positive organisms is being debated vigorously based on their ability to incorporate extracellular fatty acids. The regulation of FASII by extracellular fatty acids was examined in Staphylococcus aureus and Streptococcus pneumoniae, representing two important groups of pathogens. Both bacteria use the same enzymatic tool kit for the conversion of extracellular fatty acids to acyl-acyl carrier protein, elongation, and incorporation into phospholipids. Exogenous fatty acids completely replace the endogenous fatty acids in S. pneumoniae but support only 50% of phospholipid synthesis in S. aureus. Fatty acids overcame FASII inhibition in S. pneumoniae but not in S. aureus. Extracellular fatty acids strongly suppress malonyl-CoA levels in S. pneumoniae but not in S. aureus, showing a feedback regulatory system in S. pneumoniae that is absent in S. aureus. Fatty acids overcame either a biochemical or a genetic block at acetyl-CoA carboxylase (ACC) in S. aureus, confirming that regulation at the ACC step is the key difference between these two species. Bacteria that possess a stringent biochemical feedback inhibition of ACC and malonyl-CoA formation triggered by environmental fatty acids are able to circumvent FASII inhibition. However, if exogenous fatty acids do not suppress malonyl-CoA formation, FASII inhibitors remain effective in the presence of fatty acid supplements. PMID:21876172

Suppression of Striatal Prediction Errors by the Prefrontal Cortex in Placebo Hypoalgesia.

PubMed

Schenk, Lieven A; Sprenger, Christian; Onat, Selim; Colloca, Luana; Büchel, Christian

2017-10-04

Classical learning theories predict extinction after the discontinuation of reinforcement through prediction errors. However, placebo hypoalgesia, although mediated by associative learning, has been shown to be resistant to extinction. We tested the hypothesis that this is mediated by the suppression of prediction error processing through the prefrontal cortex (PFC). We compared pain modulation through treatment cues (placebo hypoalgesia, treatment context) with pain modulation through stimulus intensity cues (stimulus context) during functional magnetic resonance imaging in 48 male and female healthy volunteers. During acquisition, our data show that expectations are correctly learned and that this is associated with prediction error signals in the ventral striatum (VS) in both contexts. However, in the nonreinforced test phase, pain modulation and expectations of pain relief persisted to a larger degree in the treatment context, indicating that the expectations were not correctly updated in the treatment context. Consistently, we observed significantly stronger neural prediction error signals in the VS in the stimulus context compared with the treatment context. A connectivity analysis revealed negative coupling between the anterior PFC and the VS in the treatment context, suggesting that the PFC can suppress the expression of prediction errors in the VS. Consistent with this, a participant's conceptual views and beliefs about treatments influenced the pain modulation only in the treatment context. Our results indicate that in placebo hypoalgesia contextual treatment information engages prefrontal conceptual processes, which can suppress prediction error processing in the VS and lead to reduced updating of treatment expectancies, resulting in less extinction of placebo hypoalgesia. SIGNIFICANCE STATEMENT In aversive and appetitive reinforcement learning, learned effects show extinction when reinforcement is discontinued. This is thought to be mediated by prediction errors (i.e., the difference between expectations and outcome). Although reinforcement learning has been central in explaining placebo hypoalgesia, placebo hypoalgesic effects show little extinction and persist after the discontinuation of reinforcement. Our results support the idea that conceptual treatment beliefs bias the neural processing of expectations in a treatment context compared with a more stimulus-driven processing of expectations with stimulus intensity cues. We provide evidence that this is associated with the suppression of prediction error processing in the ventral striatum by the prefrontal cortex. This provides a neural basis for persisting effects in reinforcement learning and placebo hypoalgesia. Copyright © 2017 the authors 0270-6474/17/379715-09$15.00/0.

40 CFR 180.1178 - Formic acid; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... pesticide formic acid is exempted from the requirement of a tolerance in or on honey and honeycomb when used to control tracheal mites and suppress varroa mites in bee colonies, and applied in accordance with...

40 CFR 180.1178 - Formic acid; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... pesticide formic acid is exempted from the requirement of a tolerance in or on honey and honeycomb when used to control tracheal mites and suppress varroa mites in bee colonies, and applied in accordance with...

40 CFR 180.1178 - Formic acid; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... pesticide formic acid is exempted from the requirement of a tolerance in or on honey and honeycomb when used to control tracheal mites and suppress varroa mites in bee colonies, and applied in accordance with...

40 CFR 180.1178 - Formic acid; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... pesticide formic acid is exempted from the requirement of a tolerance in or on honey and honeycomb when used to control tracheal mites and suppress varroa mites in bee colonies, and applied in accordance with...

40 CFR 180.1178 - Formic acid; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... pesticide formic acid is exempted from the requirement of a tolerance in or on honey and honeycomb when used to control tracheal mites and suppress varroa mites in bee colonies, and applied in accordance with...

The PPARdelta agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition.

PubMed

Kino, T; Rice, K C; Chrousos, G P

2007-05-01

Interleukin-6 and downstream liver effectors acute phase reactants are implicated in the systemic inflammatory reaction. Peroxisome proliferator-activated receptor delta (PPARdelta), which binds to and is activated by a variety of fatty acids, was recently shown to have anti-inflammatory actions. We examined the ability of the synthetic PPARdelta agonist GW501516 to suppress interleukin-6-induced expression of acute phase proteins in human hepatoma HepG2 cells and rat primary hepatocytes. Results GW501516 dose-dependently suppressed interleukin-6-induced mRNA expression of the acute phase protein alpha1-antichymotrypsin in HepG2 cells. The compound also suppressed interleukin-6-induced mRNA expression of alpha2-acid glycoprotein, beta-fibrinogen and alpha2-macroglobulin in and the secretion of C-reactive protein by rat primary hepatocytes. Depletion of the PPARdelta receptor, but not of PPARalpha or gamma, attenuated the suppressive effect of GW501516 on interleukin-6-induced alpha1-antichymotrypsin mRNA expression, indicating that PPARdelta specifically mediated this effect. Since interleukin-6 stimulates the transcriptional activity of the alpha1-antichymotrypsin promoter by activating the signal transducer and activator of transcription (STAT) 3, we examined functional interaction of this transcription factor and PPARdelta on this promoter. Overexpression of PPARdelta enhanced the suppressive effect of GW501516 on STAT3-activated transcriptional activity of the alpha1-antichymotrypsin promoter, while GW501516 suppressed interleukin-6-induced binding of this transcription factor to this promoter. These findings indicate that agonist-activated PPARdelta interferes with interleukin-6-induced acute phase reaction in the liver by inhibiting the transcriptional activity of STAT3. PPARdelta agonists might be useful for the suppression of systemic inflammatory reactions in which IL-6 plays a central role.

Role for apyrases in polar auxin transport in Arabidopsis.

PubMed

Liu, Xing; Wu, Jian; Clark, Greg; Lundy, Stacey; Lim, Minhui; Arnold, David; Chan, Jing; Tang, Wenqiang; Muday, Gloria K; Gardner, Gary; Roux, Stanley J

2012-12-01

Recent evidence indicates that extracellular nucleotides regulate plant growth. Exogenous ATP has been shown to block auxin transport and gravitropic growth in primary roots of Arabidopsis (Arabidopsis thaliana). Cells limit the concentration of extracellular ATP in part through the activity of ectoapyrases (ectonucleoside triphosphate diphosphohydrolases), and two nearly identical Arabidopsis apyrases, APY1 and APY2, appear to share this function. These findings, plus the fact that suppression of APY1 and APY2 blocks growth in Arabidopsis, suggested that the expression of these apyrases could influence auxin transport. This report tests that hypothesis. The polar movement of [(3)H]indole-3-acetic acid in both hypocotyl sections and primary roots of Arabidopsis seedlings was measured. In both tissues, polar auxin transport was significantly reduced in apy2 null mutants when they were induced by estradiol to suppress the expression of APY1 by RNA interference. In the hypocotyl assays, the basal halves of APY-suppressed hypocotyls contained considerably lower free indole-3-acetic acid levels when compared with wild-type plants, and disrupted auxin transport in the APY-suppressed roots was reflected by their significant morphological abnormalities. When a green fluorescent protein fluorescence signal encoded by a DR5:green fluorescent protein construct was measured in primary roots whose apyrase expression was suppressed either genetically or chemically, the roots showed no signal asymmetry following gravistimulation, and both their growth and gravitropic curvature were inhibited. Chemicals that suppress apyrase activity also inhibit gravitropic curvature and, to a lesser extent, growth. Taken together, these results indicate that a critical step connecting apyrase suppression to growth suppression is the inhibition of polar auxin transport.

Suppressive and enhancing effects in early visual cortex during illusory shape perception: A comment on.

PubMed

Moors, Pieter

2015-01-01

In a recent functional magnetic resonance imaging study, Kok and de Lange (2014) observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

Optical frequency shot-noise suppression in electron beams: Three-dimensional analysis

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

Nause, A.; Dyunin, E.; Gover, A.

2010-05-15

A predicted effect of current shot-noise suppression at optical-frequencies in a drifting charged-particle-beam and the corresponding process of particles self-ordering are analyzed in a one-dimensional (1D) model and verified by three-dimensional numerical simulations. The analysis confirms the prediction of a 1D single mode Langmuir plasma wave model of longitudinal plasma oscillation in the beam, and it defines the regime of beam parameters in which this effect takes place. The suppression of relativistic beam shot noise can be utilized to enhance the coherence of free electron lasers and of any coherent radiation device using an electron beam.

NITRIC ACID RECPVERY FROM WASTE COLUTIONS

DOEpatents

Wilson, A.S.

1959-04-14

The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acids ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of rutheniuim.

Nitric acid recovery from waste solutions

DOEpatents

Wilson, A. S.

1959-04-14

The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acid, ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of ruthenium.

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.

Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation.

PubMed

Colomar, A; Guardiola, B; Llompart-Pou, J A; Ayestarán, I; Rodríguez-Pilar, J; Ferreruela, M; Raurich, J M

To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). A retrospective secondary analysis was carried out. The Intensive Care Unit of a University Hospital. Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. Lower respiratory tract infection episodes. Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Sphingolipid-Mediated Apoptosis and Tumor Suppression in Breast Carcinoma.

DTIC Science & Technology

1996-10-01

diacylglycerol and ceramide. The radioactive spots corresponding to phosphatidic acid and ceramide-phosphate, the phosphorylated products of diacylglycerol (DAG...threonine protein phosphatase (7). This phosphatase is inhibited by okadaic acid , and okadaic acid appears to inhibit the effects of ceramide on...Arg to Thr at amino acid 291 in the reactive site loop. In MCF-7 cells expressing this mutant, there was no significant inhibition of ceramide

Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep

PubMed Central

Rozance, Paul J.; Thorn, Stephanie R.; Friedman, Jacob E.; Hay, William W.

2012-01-01

Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion. PMID:22649066

Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids.

PubMed

Takeuchi, Koji; Nagahama, Kenji

2014-01-01

Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus.

Insulin activation of plasma non-esterified fatty acid uptake in metabolic syndrome

PubMed Central

Ramos-Roman, Maria A.; Lapidot, Smadar A.; Phair, Robert D.; Parks, Elizabeth J.

2012-01-01

Objectives Insulin control of fatty acid metabolism has long been deemed dominated by suppression of adipose lipolysis. This study’s goal was to test the hypothesis that this single role of insulin is insufficient to explain observed fatty acid dynamics. Methods and Results Fatty acid kinetics were measured during a meal-tolerance test and insulin sensitivity assessed by IVGTT in overweight human subjects (n=15, BMI 35.8 ± 7.1 kg/m2). Non-steady state tracer kinetic models were formulated and tested using ProcessDB© software. Suppression of adipose release alone could not account for NEFA concentration changes postprandially, but when combined with insulin activation of fatty acid uptake was consistent with the NEFA data. The observed insulin Km for NEFA uptake was inversely correlated with both insulin sensitivity of glucose uptake (IVGTT Si) (r=−0.626, P=0.01), and whole body fat oxidation after the meal (r=−0.538, P=0.05). Conclusions These results support insulin regulation of fatty acid turnover by both release and uptake mechanisms. Activation of fatty acid uptake is consistent with the human data, has mechanistic precedent in cell culture, and highlights a new potential target for therapies aimed at improving the control of fatty acid metabolism in insulin-resistant disease states. PMID:22723441

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.

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

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling.

PubMed

Lovelace, Erica S; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard P; Zink, Erika M; Kim, Young-Mo; Kyle, Jennifer E; Webb-Robertson, Bobbie-Jo M; Waters, Katrina M; Metz, Thomas O; Farin, Federico; Oberlies, Nicholas H; Polyak, Stephen J

2015-08-28

Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Anti-inflammatory effects arose with prolonged (i.e., 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, whereas silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

PubMed Central

Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Stephen J.

2016-01-01

Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed silymarin suppression of glycolytic, tricarboxylic acid (TCA) cycle, and amino acid metabolism. Anti-inflammatory effects arose with prolonged (i.e. 24 h) silymarin exposure, with suppression of multiple pro-inflammatory mRNAs and signaling pathways including nuclear factor kappa B (NF-κB) and forkhead box O (FOXO). Studies with murine knock out cells revealed that silymarin inhibition of both mTOR and NF-κB was partially AMPK dependent, while silymarin inhibition of mTOR required DDIT4. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Thus, natural products activate stress and repair responses that culminate in an anti-inflammatory cellular phenotype. Natural products like silymarin may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation. PMID:26186142

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.

18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

PubMed

Wang, Di; Zhang, Yongfeng; Wang, Chunyue; Jia, Dongxu; Cai, Guangsheng; Lu, Jiahui; Wang, Di; Zhang, Zhang-Jin

2016-09-01

The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

Hydrothermal Reactivity of Amines

NASA Astrophysics Data System (ADS)

Robinson, K.; Shock, E.; Hartnett, H. E.; Williams, L. B.; Gould, I.

2013-12-01

The reactivity of aqueous amines depends on temperature, pH, and redox state [1], all of which are highly variable in hydrothermal systems. Temperature and pH affect the ratio of protonated to unprotonated amines (R-NH2 + H+ = R-NH3+), which act as nucleophiles and electrophiles, respectively. We hypothesize that this dual nature can explain the pH dependence of reaction rates, and predict that rates will approach a maximum at pH = pKa where the ratio of protonated and unprotonated amines approaches one and the two compounds are poised to react with one another. Higher temperatures in hydrothermal systems allow for more rapid reaction rates, readily reversible reactions, and unique carbon-nitrogen chemistry in which water acts as a reagent in addition to being the solvent. In this study, aqueous benzylamine was used as a model compound to explore the reaction mechanisms, kinetics, and equilibria of amines under hydrothermal conditions. Experiments were carried out in anoxic silica glass tubes at 250°C (Psat) using phosphate-buffered solutions to observe changes in reaction rates and product distributions as a function of pH. The rate of decomposition of benzylamine was much faster at pH 4 than at pH 9, consistent with the prediction that benzylamine acts as both nucleophile and an electrophile, and our estimate that the pKa of benzylamine is ~5 at 250°C and Psat. Accordingly, dibenzylamine is the primary product of the reaction of two benzylamine molecules, and this reaction is readily reversible under hydrothermal conditions. Extremely acidic or basic pH can be used to suppress dibenzylamine production, which also suppresses the formation of all other major products, including toluene, benzyl alcohol, dibenzylimine, and tribenzylamine. This suggests that dibenzylamine is the lone primary product that then itself reacts as a precursor to produce the above compounds. Analog experiments performed with ring-substituted benzylamine derivatives and chiral methylbenzylamine suggest an SN2 mechanism for the formation of dibenzylamine. These results show the interdependence of pH and speciation with amine reaction rates. We predict the distribution of primary, secondary, tertiary, and quaternary amines in hydrothermal solutions can be used to solve for the pH of subsurface reaction zones in hydrothermal systems. [1] McCollom, T.M. (2013) The influence of minerals on decomposition of the n-alkyl-α-amino acid norvaline under hydrothermal conditions. Geochim. Cosmochim. Acta, 104, 330-357.

Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis.

PubMed

Kim, Hyemee; Banerjee, Nivedita; Ivanov, Ivan; Pfent, Catherine M; Prudhomme, Kalan R; Bisson, William H; Dashwood, Roderick H; Talcott, Stephen T; Mertens-Talcott, Susanne U

2016-09-01

Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and downregulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding of docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of anti-inflammatory mechanisms of mango (Mangifera Indica L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis

PubMed Central

Kim, Hyemee; Banerjee, Nivedita; Ivanov, Ivan; Pfent, Catherine M.; Prudhomme, Kalan R.; Bisson, William H.; Dashwood, Rodrick H.; Talcott, Stephen T.; Mertens-Talcott, Susanne U.

2016-01-01

Scope Tannin-rich fruits have been evaluated as alternative prevention strategies for colorectal cancer based on their anti-inflammatory properties. This study compared tannin-rich preparations from mango (rich in gallotannins) and pomegranate (rich in ellagitannins) in the dextran sodium sulfate-induced colitis model. Methods and results In rats, mango and pomegranate beverages decreased intestinal inflammation and the levels of pro-inflammatory cytokines in mucosa and serum. The mango beverage suppressed the ratio of phosphorylated/total protein expression of the IGF-1R-AKT/mTOR axis and down-regulated mRNA expression of Igf1, Insr, and pik3cv. Pomegranate decreased p70S6K and RPS6, as well as Rps6ka2, Map2k2, and Mapk1 mRNA. In silico modeling indicated a high binding-docked of gallic acid to the catalytic domain of IGF-1R, which may suppress the activity of the enzyme. Ellagic acid docked effectively into the catalytic domains of both IGF-1R and EGFR. In vitro assays with lipopolysaccharide-treated CCD-18Co cells using polyphenolic extracts from each beverage, as well as pure compounds, corroborated the predictions made in silico. Conclusion Mango polyphenols inhibited the IGF-1R- AKT/mTOR axis, and pomegranate polyphenols downregulate the mTOR downstream pathway through reductions in ERK1/2. These results suggest that extracts rich in gallo- and ellagitannins act on different molecular targets in the protection against ulcerative colitis. PMID:27028006

Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses: a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19.

PubMed

Shimatani, Tomohiko; Inoue, Masaki; Kuroiwa, Tomoko; Xu, Jing; Mieno, Hiroshi; Nakamura, Masuo; Tazuma, Susumu

2006-01-01

To improve clinical outcomes of the initial therapy for gastroesophageal reflux disease, intragastric pH should be above 4.0 for more than 20 hours a day (83.3%) and nocturnal gastric acid breakthrough, defined as 60 continuous minutes of intragastric pH below 4.0 at night, should be inhibited. A "step-down" therapy sometimes fails because of insufficient acid suppression. Therefore we compared the acid-suppressive effects of proton pump inhibitors. This was a prospective, randomized, open-label, 8-way crossover study. In 9 healthy Helicobacter pylori-negative cytochrome P450 (CYP) 2C19 homozygous extensive metabolizers, intragastric pH was measured for 24 hours on day 7 of treatment with rabeprazole, omeprazole, and lansoprazole orally administered once daily at reduced and standard doses. Compared with baseline data (7% [range, 5%-20%]), the median values of the 24-hour percent of time that intragastric pH was above 4.0 significantly increased but did not exceed 83.3% under any of the 7 regimens, which were as follows: 10 mg rabeprazole (51% [range, 28%-78%], P < .01), 20 mg rabeprazole (59% [range, 36%-83%], P < .01), 10 mg omeprazole (26% [range, 4%-33%], P < .05), 20 mg omeprazole (48% [range, 31%-73%], P < .01), 40 mg omeprazole (62% [range, 47%-87%], P < .01), 15 mg lansoprazole (34% [range, 5%-51%], P < .05), and 30 mg lansoprazole (56% [range, 20%-76%], P < .05). Significant differences were observed among 10, 20, and 40 mg omeprazole (10 mg versus 20 mg, P < .01; 10 mg versus 40 mg, P < .01; and 20 mg versus 40 mg, P < .05) and between 15 and 30 mg lansoprazole (P < .01), whereas no significant difference was observed between 10 and 20 mg rabeprazole. Nocturnal gastric acid breakthrough was observed under all regimens. Rabeprazole, omeprazole, and lansoprazole, given once daily at standard doses, cannot be expected to achieve ideal acid suppression for the initial therapy for gastroesophageal reflux disease in Helicobacter-negative CYP2C19 homozygous extensive metabolizers. Rabeprazole 10 mg may be appropriate for step-down therapy.

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

Kimura, Rino; Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp; Murota, Kaeko

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation ofmore » peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.« less

Suppression of acute and anticipatory nausea by peripherally restricted fatty acid amide hydrolase inhibitor in animal models: role of PPARα and CB1 receptors.

PubMed

Rock, Erin M; Moreno-Sanz, Guillermo; Limebeer, Cheryl L; Petrie, Gavin N; Angelini, Roberto; Piomelli, Daniele; Parker, Linda A

2017-11-01

Effective treatments of nausea are limited. In this study we evaluated the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937, to suppress acute and anticipatory nausea in rats and examined the pharmacological mechanism of this effect. We investigated the potential of URB937 (administered i.p.) to reduce the establishment of lithium chloride-induced conditioned gaping (model of acute nausea) and to reduce the expression of contextually-elicited conditioned gaping (model of anticipatory nausea) in rats. The role of CB 1 receptors, CB 2 receptors and PPARα in the anti-nausea effect of URB937 was examined. The potential of URB937 to suppress FAAH activity in tissue collected from the area postrema (AP), prefrontal cortex (PFC), liver and duodenum and to elevate levels of FAAH substrates - anandamide (AEA), N-oleoylethanolamide (OEO) and N-palmitoylethanolamide (PEA) - in the AP was also evaluated. URB937 reduced acute nausea by a PPARα-dependent mechanism and reduced anticipatory nausea by a CB 1 receptor-dependent mechanism. The PPARα agonist, GW7647, similarly attenuated acute nausea. URB937 reduced FAAH activity in the liver and the duodenum but not in the PFC. In addition, URB937 reduced FAAH activity and elevated levels of fatty-acid ethanolamides in the AP, a brain region that is not protected by the blood-brain barrier. The anti-nausea action of URB937 may occur in the AP and may involve PPARα to suppress acute nausea and CB 1 receptors to suppress anticipatory nausea. © 2017 The British Pharmacological Society.

Suppression of Cytochrome P450 Reductase (POR) Expression in Hepatoma Cells Replicates the Hepatic Lipidosis Observed in Hepatic POR-Null Mice

PubMed Central

Banerjee, Subhashis; Stolarczyk, Elzbieta I.; Zou, Ling

2011-01-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis. PMID:21368239

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.

PubMed

Porter, Todd D; Banerjee, Subhashis; Stolarczyk, Elzbieta I; Zou, Ling

2011-06-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis.

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.

Biogenesis of Fe/S proteins and pathogenicity: IscR plays a key role in allowing Erwinia chrysanthemi to adapt to hostile conditions.

PubMed

Rincon-Enriquez, Gabriel; Crété, Patrice; Barras, Frédéric; Py, Béatrice

2008-03-01

The Erwinia chrysanthemi genome is predicted to encode three systems, Nif, Isc and Suf, known to assist Fe/S cluster biogenesis and the CsdAE cysteine desulphurase. Single iscU, hscA and fdx mutants were found sensitive to paraquat and exhibited reduced virulence on both chicory leaves and Arabidopsis thaliana. Depletion of the whole Isc system led to a pleiotropic phenotype, including sensitivity to both paraquat and 2,2'-dipyridyl, auxotrophies for branched-chain amino acids, thiamine, nicotinic acid, and drastic alteration in virulence. IscR was able to suppress all of the phenotypes listed above in a sufC-dependent manner while depletion of the Isc system led to IscR-dependent activation of the suf operon. No virulence defects were found associated with csdA or nifS mutations. Surprisingly, we found that the sufC mutant was virulent against A. thaliana, whereas its virulence had been found altered in Saintpaulia. Collectively, these results lead us to propose that E. chrysanthemi possess the Fe/S biogenesis strategy suited to the physico-chemical conditions encountered in its host upon infection. In this view, the IscR regulator, which controls both Isc and Suf, is predicted to play a major role in the ability of E. chrysanthemi to colonize a wide array of different plants.

Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain.

PubMed

Elshorbagy, Amany K; Samocha-Bonet, Dorit; Jernerén, Fredrik; Turner, Cheryl; Refsum, Helga; Heilbronn, Leonie K

2018-06-13

Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes. We investigated amino acid changes during food overconsumption. Forty healthy men and women with a body mass index (mean ± SEM) of 25.6 ± 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients. Insulin sensitivity and body composition were assessed at baseline (day 0) and day 28. Fasting serum amino acids were measured at days 0, 3, and 28. Linear mixed-effects models evaluated the effect of time in the total group and separately in those with low and high body fat gain (below compared with at or above median fat gain, 1.95 kg). At days 0 and 28, insulin-induced suppression of serum amino acids during a hyperinsulinemic-euglycemic clamp test and, in a subset (n = 20), adipose tissue mRNA expression of selected amino acid metabolizing enzymes were assessed. Weight increased by 2.8 kg. High fat gainers gained 2.6 kg fat mass compared with 1.1 kg in low fat gainers. Valine and isoleucine increased at day 3 (+17% and +22%, respectively; P ≤ 0.002) and remained elevated at day 28, despite a decline in valine (P = 0.019) from day 3 values. Methionine, cystathionine, and taurine were unaffected. Serum total cysteine (tCys) transiently increased at day 3 (+11%; P = 0.022) only in high fat gainers (P-interaction = 0.043), in whom the cysteine catabolic enzyme cysteine dioxygenase (CDO1) was induced (+26%; P = 0.025) in adipose tissue (P-interaction = 0.045). Overconsumption did not alter adipose tissue mRNA expression of the BCAA-metabolizing enzymes branched-chain keto acid dehydrogenase E1α polypeptide (BCKDHA) or branched-chain amino transferase 1 (BCAT1). In the total population at day 0, insulin infusion decreased all serum amino acids (-11% to -47%; P < 0.01), except for homocysteine and tCys, which were unchanged, and glutathione, which was increased by 54%. At day 28, insulin increased tCys (+8%), and the insulin-induced suppression of taurine and phenylalanine observed at day 0, but not that of BCAAs, was significantly impaired. These findings highlight the role of nutrient oversupply in increasing fasting BCAA concentrations in healthy adults. The link between cysteine availability, CDO1 expression, and fat gain deserves investigation. This trial was registered at www.clinicaltrials.gov as NCT00562393.

Towards the elements of successful insect Ribonucleic acid interference (RNAi)

USDA-ARS?s Scientific Manuscript database

Ribonucleic acid interference (RNAi), the sequence-specific suppression of gene expression, offers great opportunities for insect science, especially to analyze gene function, manage pest populations, and reduce disease pathogens. The accumulating body of literature on insect RNAi has revealed that ...

Predicting Barrett's Esophagus in Families: An Esophagus Translational Research Network (BETRNet) Model Fitting Clinical Data to a Familial Paradigm.

PubMed

Sun, Xiangqing; Elston, Robert C; Barnholtz-Sloan, Jill S; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Tian, Ye D; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford D; Chandar, Apoorva; Warfe, James M; Brock, Wendy; Chak, Amitabh

2016-05-01

Barrett's esophagus is often asymptomatic and only a small portion of Barrett's esophagus patients are currently diagnosed and under surveillance. Therefore, it is important to develop risk prediction models to identify high-risk individuals with Barrett's esophagus. Familial aggregation of Barrett's esophagus and esophageal adenocarcinoma, and the increased risk of esophageal adenocarcinoma for individuals with a family history, raise the necessity of including genetic factors in the prediction model. Methods to determine risk prediction models using both risk covariates and ascertained family data are not well developed. We developed a Barrett's Esophagus Translational Research Network (BETRNet) risk prediction model from 787 singly ascertained Barrett's esophagus pedigrees and 92 multiplex Barrett's esophagus pedigrees, fitting a multivariate logistic model that incorporates family history and clinical risk factors. The eight risk factors, age, sex, education level, parental status, smoking, heartburn frequency, regurgitation frequency, and use of acid suppressant, were included in the model. The prediction accuracy was evaluated on the training dataset and an independent validation dataset of 643 multiplex Barrett's esophagus pedigrees. Our results indicate family information helps to predict Barrett's esophagus risk, and predicting in families improves both prediction calibration and discrimination accuracy. Our model can predict Barrett's esophagus risk for anyone with family members known to have, or not have, had Barrett's esophagus. It can predict risk for unrelated individuals without knowing any relatives' information. Our prediction model will shed light on effectively identifying high-risk individuals for Barrett's esophagus screening and surveillance, consequently allowing intervention at an early stage, and reducing mortality from esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 25(5); 727-35. ©2016 AACR. ©2016 American Association for Cancer Research.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed

Quecine, Maria Carolina; Kidarsa, Teresa A; Goebel, Neal C; Shaffer, Brenda T; Henkels, Marcella D; Zabriskie, T Mark; Loper, Joyce E

2015-12-11

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

An Interspecies Signaling System Mediated by Fusaric Acid Has Parallel Effects on Antifungal Metabolite Production by Pseudomonas protegens Strain Pf-5 and Antibiosis of Fusarium spp.

PubMed Central

Quecine, Maria Carolina; Kidarsa, Teresa A.; Goebel, Neal C.; Shaffer, Brenda T.; Henkels, Marcella D.; Zabriskie, T. Mark

2015-01-01

Pseudomonas protegens strain Pf-5 is a rhizosphere bacterium that suppresses soilborne plant diseases and produces at least seven different secondary metabolites with antifungal properties. We derived mutants of Pf-5 with single and multiple mutations in biosynthesis genes for seven antifungal metabolites: 2,4-diacetylphoroglucinol (DAPG), pyrrolnitrin, pyoluteorin, hydrogen cyanide, rhizoxin, orfamide A, and toxoflavin. These mutants were tested for inhibition of the pathogens Fusarium verticillioides and Fusarium oxysporum f. sp. pisi. Rhizoxin, pyrrolnitrin, and DAPG were found to be primarily responsible for fungal antagonism by Pf-5. Previously, other workers showed that the mycotoxin fusaric acid, which is produced by many Fusarium species, including F. verticillioides, inhibited the production of DAPG by Pseudomonas spp. In this study, amendment of culture media with fusaric acid decreased DAPG production, increased pyoluteorin production, and had no consistent influence on pyrrolnitrin or orfamide A production by Pf-5. Fusaric acid also altered the transcription of biosynthetic genes, indicating that the mycotoxin influenced antibiotic production by Pf-5 at the transcriptional level. Addition of fusaric acid to the culture medium reduced antibiosis of F. verticillioides by Pf-5 and derivative strains that produce DAPG but had no effect on antibiosis by Pf-5 derivatives that suppressed F. verticillioides due to pyrrolnitrin or rhizoxin production. Our results demonstrated the importance of three compounds, rhizoxin, pyrrolnitrin, and DAPG, in suppression of Fusarium spp. by Pf-5 and confirmed that an interspecies signaling system mediated by fusaric acid had parallel effects on antifungal metabolite production and antibiosis by the bacterial biological control organism. PMID:26655755

Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing

PubMed Central

Turk, Harmony F.; Monk, Jennifer M.; Fan, Yang-Yi; Callaway, Evelyn S.; Weeks, Brad

2013-01-01

Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling. PMID:23426968

Suppression of muscle wasting by the plant‐derived compound ursolic acid in a model of chronic kidney disease

PubMed Central

Yu, Rizhen; Chen, Ji‐an; Xu, Jing; Cao, Jin; Wang, Yanlin; Thomas, Sandhya S.

2016-01-01

Abstract Background Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF‐1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation. Methods Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone. Results Using cultured C2C12 myotubes to study muscle wasting, we found that exposure to glucocorticoids cause loss of cell proteins plus an increase in myostatin; both responses are significantly suppressed by ursolic acid. Results from promoter and ChIP assays demonstrated a mechanism involving ursolic acid blockade of myostatin promoter activity that is related to CEBP/δ expression. In mouse models of CKD‐induced or dexamethasone‐induced muscle wasting, we found that ursolic acid blocked the loss of muscle mass by stimulating protein synthesis and decreasing protein degradation. These beneficial responses included decreased expression of myostatin and inflammatory cytokines (e.g. TGF‐β, IL‐6 and TNFα), which are initiators of muscle‐specific ubiquitin‐E3 ligases (e.g. Atrogin‐1, MuRF‐1 and MUSA1). Conclusions Ursolic acid improves CKD‐induced muscle mass by suppressing the expression of myostatin and inflammatory cytokines via increasing protein synthesis and reducing proteolysis. PMID:27897418

The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.

PubMed

Ishizaka, Toshihiko; Okada, Sachie; Takemoto, Eri; Tokuyama, Emi; Tsuji, Eriko; Mukai, Junji; Uchida, Takahiro

2007-10-01

The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.

Differential Roles of Thought Suppression and Dispositional Mindfulness in Posttraumatic Stress Symptoms and Craving

PubMed Central

Garland, Eric; Roberts-Lewis, Amelia

2012-01-01

Exposure to traumatic events often results in severe distress which may elicit self-medication behaviors. Yet, some individuals exposed to trauma do not develop post-traumatic stress symptoms and comorbid addictive impulses. In the wake of traumatic events, psychological processes like thought suppression and mindfulness may modulate post-traumatic stress and craving for substances. We examined the differential roles of mindfulness and suppression in comorbid post-traumatic stress and craving in a sample of 125 persons with extensive trauma histories and psychiatric symptoms in residential treatment for substance dependence. Results indicated that thought suppression, rather than extent of trauma history, significantly predicted post-traumatic stress symptom severity while dispositional mindfulness significantly predicted both post-traumatic stress symptoms and craving. In multiple regression models, mindfulness and thought suppression combined explained nearly half of the variance in post-traumatic stress symptoms and one-quarter of the variance in substance craving. Moreover, multivariate path analysis indicated that prior traumatic experience was associated with greater thought suppression, which in turn was correlated with increased post-traumatic stress symptoms and drug craving, whereas dispositional mindfulness was associated with decreased suppression, post-traumatic stress, and craving. The maladaptive strategy of thought suppression appears to be linked with adverse psychological consequences of traumatic life events. In contrast, dispositional mindfulness appears to be a protective factor that buffers individuals from experiencing more severe post-traumatic stress symptoms and craving. PMID:22385734

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

PubMed

Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

2015-07-19

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Counteracting foaming caused by lipids or proteins in biogas reactors using rapeseed oil or oleic acid as antifoaming agents.

PubMed

Kougias, P G; Boe, K; Einarsdottir, E S; Angelidaki, I

2015-08-01

Foaming is one of the major operational problems in biogas plants, and dealing with foaming incidents is still based on empirical practices. Various types of antifoams are used arbitrarily to combat foaming in biogas plants, but without any scientific support this action can lead to serious deterioration of the methanogenic process. Many commercial antifoams are derivatives of fatty acids or oils. However, it is well known that lipids can induce foaming in manure based biogas plants. This study aimed to elucidate the effect of rapeseed oil and oleic acid on foam reduction and process performance in biogas reactors fed with protein or lipid rich substrates. The results showed that both antifoams efficiently suppressed foaming. Moreover rapeseed oil resulted in stimulation of the biogas production. Finally, it was reckoned that the chemical structure of lipids, and more specifically their carboxylic ends, is responsible for their foam promoting or foam counteracting behaviour. Thus, it was concluded that the fatty acids and oils could suppress foaming, while salt of fatty acids could generate foam. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding and inhibition of NFκB transactivation

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

Park, Mi Hee; Kang, Dong Woo; Jung, Yunjin

2013-12-06

Highlights: •We found CAFÉ, a natural product that suppresses expression and activity of PLD1. •CAPE decreased PLD1 expression by inhibiting NFκB transactivation. •CAPE rapidly inhibited PLD activity via its binding to a Cys837 of PLD1. •PLD1 downregulation by CAPE inhibited invasion and proliferation of glioma cells. -- Abstract: Upregulation of phospholipase D (PLD) is functionally linked with oncogenic signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active compound of propolis extract that exhibits anti-proliferative, anti-inflammatory, anti-oxidant, and antineoplastic properties. In this study, we demonstrated that CAPE suppressed the expression of PLD1 at the transcriptional level via inhibition ofmore » binding of NFκB to PLD1 promoter. Moreover, CAPE, but not its analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced downregulation of PLD1 suppressed invasion and proliferation of glioma cells. Taken together, the results of this study indicate that CAPE might contribute to anti-neoplastic effect by targeting PLD1.« less

Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury

DTIC Science & Technology

2015-10-01

study. Finally, we have established a DSMB and DSMB charter. 15. SUBJECT TERMS Trauma, hemorrhage, transfusion , fibrinolysis, immune suppression...injury parameters. 2. KEYWORDS: Trauma, hemorrhage, transfusion , fibrinolysis, immune suppression, pharmacokinetics, outcomes, adverse events. 3...impact on expenditures Nothing to Report Significant changes in use or care of human subjects, vertebrate animals , biohazards, and/or select agents

Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo

PubMed Central

Ñahui Palomino, Rogers A.; Zicari, Sonia; Vanpouille, Christophe; Vitali, Beatrice; Margolis, Leonid

2017-01-01

Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1) infection. We identified at least three factors that mediated this suppression: (i) Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl) to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM) diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii) Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii) Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink decreasing the number of free virions. In summary, we found that lactobacilli inhibit HIV-1 replication in human tissue ex vivo by multiple mechanisms. Further studies are needed to evaluate the potential of altering the spectra of vaginal microbiota as an effective strategy to enhance vaginal health. Human tissues ex vivo may serve as a test system for these strategies. PMID:28579980

Nickel inhibits mitochondrial fatty acid oxidation.

PubMed

Uppala, Radha; McKinney, Richard W; Brant, Kelly A; Fabisiak, James P; Goetzman, Eric S

2015-08-07

Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation-the pathway by which fatty acids are catabolized for energy-in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with l-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 h), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Partial replacement of dietary linoleic acid with long chain n-3 polyunsaturated fatty acids protects against dextran sulfate sodium-induced colitis in rats.

PubMed

Tyagi, Anupama; Kumar, Uday; Santosh, Vadakattu Sai; Reddy, Suryam; Mohammed, Saazida Bhanu; Ibrahim, Ahamed

2014-12-01

Imbalances in the dietary n-6 and n-3 polyunsaturated fatty acids have been implicated in the increased prevalence of inflammatory bowel disease. This study investigated the effects of substitution of linoleic acid with long chain n-3 polyunsaturated fatty acids and hence decreasing n-6:n-3 fatty acid ratio on inflammatory response in dextran sulfate sodium induced colitis. Male weanling Sprague Dawley rats were fed diets with n-6:n-3 fatty acid in the ratios of 215,50,10 or 5 for 3 months and colitis was induced by administration of dextran sulfate sodium in drinking water during last 11 days. Decreasing the dietary n-6:n-3 fatty acid ratio to 10 and 5 significantly attenuated the severity of colitis as evidenced by improvements in clinical symptoms, reversal of shortening of colon length, reduced severity of anemia, preservation of colonic architecture as well as reduced colonic mucosal myeloperoxidase activity. This protection was associated with suppression of colonic mucosal proinflammatory mediators such as TNFα, IL-1β and nitric oxide. These findings suggest that long chain n-3 polyunsaturated fatty acids at a level of 3.0 g/kg diet (n-6:n-3 ratio of 10) prevents dextran sulfate sodium induced colitis by suppressing the proinflammatory mediators. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of salicylic acid on Aspergillus flavus infection and aflatoxin B₁ accumulation in pistachio (Pistacia vera L.) fruit.

PubMed

Panahirad, Sima; Zaare-Nahandi, Fariborz; Mohammadi, Nilufar; Alizadeh-Salteh, Saeedeh; Safaie, Naser

2014-07-01

One of the most important saprophytic infections in fresh pistachio fruits after harvesting is Aspergillus flavus colonization, which significantly reduces fruit quality. Salicylic acid plays a crucial role in plant tissues and has a suppression effect on some fungi. The inhibitory effect of salicylic acid on the growth of A. flavus was assessed in vitro and in vivo. For this purpose, seven concentrations (0, 1, 3, 5, 7, 9 and 11 mmol L(-1)) of salicylic acid were used in both experiments. Also, aflatoxin B1 contents of the samples were analysed using immunoaffinity chromatography. The results obtained from in vitro experiments showed that salicylic acid significantly reduced Aspergillus growth at all concentrations, and at 9 mmol L(-1) growth was completely suppressed. In vivo evaluation showed relatively high levels of inhibition, though the intact treated fruits as compared with the injured treated fruits demonstrated higher inhibitory effects. Regarding the inhibitory effects of salicylic acid on the control of A. flavus contamination, its application on pistachio fruits after harvesting could be a promising approach to control the fungus infection and reduce aflatoxin production in treated fruits. © 2013 Society of Chemical Industry.

Expression proteomics study to determine metallodrug targets and optimal drug combinations.

PubMed

Lee, Ronald F S; Chernobrovkin, Alexey; Rutishauser, Dorothea; Allardyce, Claire S; Hacker, David; Johnsson, Kai; Zubarev, Roman A; Dyson, Paul J

2017-05-08

The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity. RAPTA-EA bearing a GST inhibiting ethacrynic acid moiety, causes upregulation of mainly oxidative stress related proteins. The approach used in this work could be applied to the prediction of effective drug combinations to test in cancer chemotherapy clinical trials.

Enhancing Perception of Contaminated Food through Acid-Mediated Modulation of Taste Neuron Responses

PubMed Central

Chen, Yan; Amrein, Hubert

2015-01-01

SUMMARY Background Natural foods not only contain nutrients, but also non-nutritious and potentially harmful chemicals. Thus, animals need to evaluate food content in order to make adequate feeding decisions. Results Here, we investigate the effects of acids on the taste neuron responses and on taste behavior of desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila melanogaster. Using Ca2+ imaging, we show that acids neither activate sweet nor bitter taste neurons in tarsal taste sensilla. However, they suppress responses to bitter compounds in bitter-sensing neurons. Moreover, acids reverse suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with these observations, behavioral analyses show that bitter compound-mediated inhibition on feeding behavior is alleviated by acids. To investigate the cellular mechanism by which acids modulate these effects, we silenced bitter sensing gustatory neurons. Surprisingly, this intervention had little effect on acid-mediated de-repression of sweet neuron or feeding responses to either sugar/bitter compound mixtures, or sugar/bitter compound/acid mixtures, suggesting two independent pathways by which bitter compounds are sensed. Conclusions Our investigations reveal that acids, when presented in dietary relevant concentrations, enhance the perception of sugar/bitter compound mixtures. Drosophila’s natural food sources - fruits and cohabitating yeast - are rich in sugars and acids, but are rapidly colonized by microorganisms, such as fungi, protozoan parasites and bacteria, many of which produce bitter compounds. We propose that acids present in most fruits counteract the inhibitory effects of these bitter compounds during feeding. PMID:25131671

Fumaric acid attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling.

PubMed

Roh, Kyung-Baeg; Jung, Eunsun; Park, Deokhoon; Lee, Jongsung

2013-08-01

Eotaxin-1 is a potent chemoattractant for eosinophils and a critical mediator during the development of eosinophilic inflammation. Fumaric acid is an intermediate product of the citric acid cycle, which is source of intracellular energy. Although fumaric acid ameliorates psoriasis and multiple sclerosis, its involvement in eotaxin-1-mediated effects has not been assessed. In this study, we investigated the effects of fumaric acid on eotaxin-1 expression in a mouse fibroblast cell line. We found that fumaric acid significantly inhibited tumor necrosis factor-α (TNF-α-induced eotaxin-1 expression. This fumaric acid effect was mediated through the inhibition of p38 mitogen-activated protein kinase (MAPK)-dependent nuclear factor (NF)-κB signaling. We also found that fumaric acid operates downstream of MEKK3 during TNF-α-induced NF-κB signaling, which upregulated eotaxin-1 expression. In addition, fumaric acid attenuated expression of CC-chemokine receptor 3 (CCR3), an eotaxin-1 receptor, and adhesion molecules that play important roles in eosinophil binding to induce allergic inflammation. Taken together, these findings indicate that inhibiting TNF-α-induced eotaxin-1 expression by fumaric acid occurs primarily through suppression of NF-κB signaling, which is mediated by inhibiting p38 MAPK and suggest that fumaric acid may be used as a complementary treatment option for eotaxin-1-mediated diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Regulation of mTOR by Nutrients

DTIC Science & Technology

2012-07-01

individual genes (as indicated by the Drosophila genome CG numbers) were starved of amino acids for 1 h followed by amino acid stimulation for 30 min...acid signals. Knockdown of Rag gene expression suppressed the stimulatory effect of amino acids on TORC1 in Drosophila melanogaster S2 cells...Each individual DNA fragment was amplified with this primer by PCR from Drosophila genomic DNA and the PCR products were purified using the High Pure

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

Wang Lei; Yang Jinmin

Little Higgs theory naturally predicts a light Higgs boson whose most important discovery channel at the LHC is the diphoton signal pp{yields}h{yields}{gamma}{gamma}. In this work, we perform a comparative study for this signal in some typical little Higgs models, namely, the littlest Higgs model, two littlest Higgs models with T-parity (named LHT-I and LHT-II), and the simplest little Higgs models. We find that compared with the standard model prediction, the diphoton signal rate is always suppressed and the suppression extent can be quite different for different models. The suppression is mild (< or approx. 10%) in the littlest Higgs modelmore » but can be quite severe ({approx_equal}90%) in other three models. This means that discovering the light Higgs boson predicted by the little Higgs theory through the diphoton channel at the LHC will be more difficult than discovering the standard model Higgs boson.« less

Effects of Data Anonymization by Cell Suppression on Descriptive Statistics and Predictive Modeling Performance

PubMed Central

Ohno-Machado, Lucila; Vinterbo, Staal; Dreiseitl, Stephan

2002-01-01

Protecting individual data in disclosed databases is essential. Data anonymization strategies can produce table ambiguation by suppression of selected cells. Using table ambiguation, different degrees of anonymization can be achieved, depending on the number of individuals that a particular case must become indistinguishable from. This number defines the level of anonymization. Anonymization by cell suppression does not necessarily prevent inferences from being made from the disclosed data. Preventing inferences may be important to preserve confidentiality. We show that anonymized data sets can preserve descriptive characteristics of the data, but might also be used for making inferences on particular individuals, which is a feature that may not be desirable. The degradation of predictive performance is directly proportional to the degree of anonymity. As an example, we report the effect of anonymization on the predictive performance of a model constructed to estimate the probability of disease given clinical findings.

Effects of data anonymization by cell suppression on descriptive statistics and predictive modeling performance.

PubMed Central

Ohno-Machado, L.; Vinterbo, S. A.; Dreiseitl, S.

2001-01-01

Protecting individual data in disclosed databases is essential. Data anonymization strategies can produce table ambiguation by suppression of selected cells. Using table ambiguation, different degrees of anonymization can be achieved, depending on the number of individuals that a particular case must become indistinguishable from. This number defines the level of anonymization. Anonymization by cell suppression does not necessarily prevent inferences from being made from the disclosed data. Preventing inferences may be important to preserve confidentiality. We show that anonymized data sets can preserve descriptive characteristics of the data, but might also be used for making inferences on particular individuals, which is a feature that may not be desirable. The degradation of predictive performance is directly proportional to the degree of anonymity. As an example, we report the effect of anonymization on the predictive performance of a model constructed to estimate the probability of disease given clinical findings. PMID:11825239

Climate dependency of tree growth suppressed by acid deposition effects on soils in Northwest Russia

USGS Publications Warehouse

Lawrence, G.B.; Lapenis, A.G.; Berggren, D.; Aparin, B.F.; Smith, K.T.; Shortle, W.C.; Bailey, S.W.; Varlyguin, D.L.; Babikov, B.

2005-01-01

Increased tree growth in temperate and boreal forests has been proposed as a direct consequence of a warming climate. Acid deposition effects on nutrient availability may influence the climate dependency of tree growth, however. This study presents an analysis of archived soil samples that has enabled changes in soil chemistry to be tracked with patterns of tree growth through the 20th century. Soil samples collected in 1926, 1964, and 2001, near St. Petersburg, Russia, showed that acid deposition was likely to have decreased root-available concentrations of Ca (an essential element) and increased root-available concentrations of Al (an inhibitor of Ca uptake). These soil changes coincided with decreased diameter growth and a suppression of climate-tree growth relationships in Norway spruce. Expected increases in tree growth from climate warming may be limited by decreased soil fertility in regions of northern and eastern Europe, and eastern North America, where Ca availability has been reduced by acidic deposition. ?? 2005 American Chemical Society.

Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway

PubMed Central

Xu, Linfeng; Lao, Yuanzhi; Zhao, Yanhui; Qin, Jian; Fu, Wenwei; Zhang, Yingjia; Xu, Hongxi

2015-01-01

Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 μM IC50 values against JAK2/JAK3 kinases and less than 1 μM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity. PMID:26090459

Effect of several electrolyzed waters on the skin permeation of lidocaine, benzoic Acid, and isosorbide mononitrate.

PubMed

Kitamura, Toshihiko; Todo, Hiroaki; Sugibayashi, Kenji

2009-02-01

The effects of several electrolyzed waters were evaluated on the permeation of model base, acid and non-ionized compounds, lidocaine (LC), benzoic acid (BA), and isosorbide mononitrate (ISMN), respectively, through excised hairless rat skin. Strong alkaline-electrolyzed reducing water (ERW) enhanced and suppressed the skin permeation of LC and BA, respectively, and it also increased the skin permeation of ISMN, a non-ionized compound. On the contrary, strong acidic electrolyzed oxidizing water (EOW) enhanced BA permeation, whereas suppressing LC permeation. Only a marginal effect was observed on the skin permeation of ISMN by EOW. These marked enhancing effects of ERW on the skin permeation of LC and ISMN were explained by pH partition hypothesis as well as a decrease in skin impedance. The present results strongly support that electrolyzed waters, ERW and EOW, can be used as a new vehicle in topical pharmaceuticals or cosmetics to modify the skin permeation of drugs without severe skin damage.

Climate dependency of tree growth suppressed by acid deposition effects on soils in northwest Russia.

PubMed

Lawrence, Gregory B; Lapenis, Andrei G; Berggren, Dan; Aparin, Boris F; Smith, Kevin T; Shortle, Walter C; Bailey, Scott W; Varlyguin, Dmitry L; Babikov, Boris

2005-04-01

Increased tree growth in temperate and boreal forests has been proposed as a direct consequence of a warming climate. Acid deposition effects on nutrient availability may influence the climate dependency of tree growth, however. This study presents an analysis of archived soil samples that has enabled changes in soil chemistry to be tracked with patterns of tree growth through the 20th century. Soil samples collected in 1926, 1964, and 2001, near St. Petersburg, Russia, showed that acid deposition was likely to have decreased root-available concentrations of Ca (an essential element) and increased root-available concentrations of Al (an inhibitor of Ca uptake). These soil changes coincided with decreased diameter growth and a suppression of climate-tree growth relationships in Norway spruce. Expected increases in tree growth from climate warming may be limited by decreased soil fertility in regions of northern and eastern Europe, and eastern North America, where Ca availability has been reduced by acidic deposition.

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

Punishment in human choice: direct or competitive suppression?

PubMed Central

Critchfield, Thomas S; Paletz, Elliott M; MacAleese, Kenneth R; Newland, M Christopher

2003-01-01

This investigation compared the predictions of two models describing the integration of reinforcement and punishment effects in operant choice. Deluty's (1976) competitive-suppression model (conceptually related to two-factor punishment theories) and de Villiers' (1980) direct-suppression model (conceptually related to one-factor punishment theories) have been tested previously in nonhumans but not at the individual level in humans. Mouse clicking by college students was maintained in a two-alternative concurrent schedule of variable-interval money reinforcement. Punishment consisted of variable-interval money losses. Experiment 1 verified that money loss was an effective punisher in this context. Experiment 2 consisted of qualitative model comparisons similar to those used in previous studies involving nonhumans. Following a no-punishment baseline, punishment was superimposed upon both response alternatives. Under schedule values for which the direct-suppression model, but not the competitive-suppression model, predicted distinct shifts from baseline performance, or vice versa, 12 of 14 individual-subject functions, generated by 7 subjects, supported the direct-suppression model. When the punishment models were converted to the form of the generalized matching law, least-squares linear regression fits for a direct-suppression model were superior to those of a competitive-suppression model for 6 of 7 subjects. In Experiment 3, a more thorough quantitative test of the modified models, fits for a direct-suppression model were superior in 11 of 13 cases. These results correspond well to those of investigations conducted with nonhumans and provide the first individual-subject evidence that a direct-suppression model, evaluated both qualitatively and quantitatively, describes human punishment better than a competitive-suppression model. We discuss implications for developing better punishment models and future investigations of punishment in human choice. PMID:13677606

Dynamics of convulsive seizure termination and postictal generalized EEG suppression

PubMed Central

Bauer, Prisca R.; Thijs, Roland D.; Lamberts, Robert J.; Velis, Demetrios N.; Visser, Gerhard H.; Tolner, Else A.; Sander, Josemir W.; Lopes da Silva, Fernando H.; Kalitzin, Stiliyan N.

2017-01-01

Abstract It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15–61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal generalized EEG suppression. PMID:28073789

Cellular mechanisms underlying the inhibitory effect of flufenamic acid on chloride secretion in human intestinal epithelial cells.

PubMed

Pongkorpsakol, Pawin; Yimnual, Chantapol; Chatsudthipong, Varanuj; Rukachaisirikul, Vatcharin; Muanprasat, Chatchai

2017-06-01

Intestinal Cl - secretion is involved in the pathogenesis of secretory diarrheas including cholera. We recently demonstrated that flufenamic acid (FFA) suppressed Vibrio cholerae El Tor variant-induced intestinal fluid secretion via mechanisms involving AMPK activation and NF-κB-suppression. The present study aimed to investigate the effect of FFA on transepithelial Cl - secretion in human intestinal epithelial (T84) cells. FFA inhibited cAMP-dependent Cl - secretion in T84 cell monolayers with IC 50 of ∼8 μM. Other fenamate drugs including tolfenamic acid, meclofenamic acid and mefenamic acid exhibited the same effect albeit with lower potency. FFA also inhibited activities of CFTR, a cAMP-activated apical Cl - channel, and KCNQ1/KCNE3, a cAMP-activated basolateral K + channel. Mechanisms of CFTR inhibition by FFA did not involve activation of its negative regulators. Interestingly, FFA inhibited Ca 2+ -dependent Cl - secretion with IC 50 of ∼10 μM. FFA inhibited activities of Ca 2+ -activated Cl - channels and K Ca 3.1, a Ca 2+ -activated basolateral K + channels, but had no effect on activities of Na + -K + -Cl - cotransporters and Na + -K + ATPases. These results indicate that FFA inhibits both cAMP and Ca 2+ -dependent Cl - secretion by suppressing activities of both apical Cl - channels and basolateral K + channels. FFA and other fenamate drugs may be useful in the treatment of secretory diarrheas. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Proboscis Conditioning Experiments with Honeybees, Apis Mellifera Caucasica, with Butyric Acid and DEET Mixture as Conditioned and Unconditioned Stimuli

PubMed Central

Abramson, Charles I.; Giray, Tugrul; Mixson, T. Andrew; Nolf, Sondra L.; Wells, Harrington; Kence, Aykut; Kence, Meral

2010-01-01

Three experiments are described investigating whether olfactory repellents DEET and butyric acid can support the classical conditioning of proboscis extension in the honeybee, Apis mellifera caucasica (Hymenoptera: Apidae). In the first experiment DEET and butyric acid readily led to standard acquisition and extinction effects, which are comparable to the use of cinnamon as a conditioned stimulus. These results demonstrate that the odor of DEET or butyric acid is not intrinsically repellent to honey bees. In a second experiment, with DEET and butyric acid mixed with sucrose as an unconditioned stimulus, proboscis conditioning was not established. After several trials, few animals responded to the unconditioned stimulus. These results demonstrate that these chemicals are gustatory repellents when in direct contact. In the last experiment a conditioned suppression paradigm was used. Exposing animals to butyric acid or DEET when the proboscis was extended by direct sucrose stimulation or by learning revealed that retraction of the proboscis was similar to another novel odor, lavender, and in all cases greatest when the animal was not permitted to feed. These results again demonstrate that DEET or butyric acid are not olfactory repellents, and in addition, conditioned suppression is influenced by feeding state of the bee. PMID:20879917

Proboscis conditioning experiments with honeybees, Apis mellifera caucasica, with butyric acid and DEET mixture as conditioned and unconditioned stimuli.

PubMed

Abramson, Charles I; Giray, Tugrul; Mixson, T Andrew; Nolf, Sondra L; Wells, Harrington; Kence, Aykut; Kence, Meral

2010-01-01

Three experiments are described investigating whether olfactory repellents DEET and butyric acid can support the classical conditioning of proboscis extension in the honeybee, Apis mellifera caucasica (Hymenoptera: Apidae). In the first experiment DEET and butyric acid readily led to standard acquisition and extinction effects, which are comparable to the use of cinnamon as a conditioned stimulus. These results demonstrate that the odor of DEET or butyric acid is not intrinsically repellent to honey bees. In a second experiment, with DEET and butyric acid mixed with sucrose as an unconditioned stimulus, proboscis conditioning was not established. After several trials, few animals responded to the unconditioned stimulus. These results demonstrate that these chemicals are gustatory repellents when in direct contact. In the last experiment a conditioned suppression paradigm was used. Exposing animals to butyric acid or DEET when the proboscis was extended by direct sucrose stimulation or by learning revealed that retraction of the proboscis was similar to another novel odor, lavender, and in all cases greatest when the animal was not permitted to feed. These results again demonstrate that DEET or butyric acid are not olfactory repellents, and in addition, conditioned suppression is influenced by feeding state of the bee.

Review article: pH, healing and symptom relief with rabeprazole treatment in acid-related disorders.

PubMed

Robinson, M

2004-11-01

Control of gastric acid secretion by antisecretory agents has been the cornerstone of therapy in the successful management of all acid-related disorders, including gastro-oesophageal reflux disease (GERD), and duodenal and gastric ulcer. Treatment efficacy has been strongly correlated with degree and duration of acid suppression within the 24-h period and with total duration of therapy. All proton pump inhibitors are highly effective for the healing of ulcers and erosive oesophagitis. All have closely similar mechanisms of action, yet important pharmacological differences exist, which can significantly impact certain aspects of their clinical efficacy. Rabeprazole's rapid activation over a wide pH range may be the explanation for its early onset of effective acid inhibition compared with other proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole. Like rabeprazole, esomeprazole is also a potent inhibitor of gastric acid at steady state, although it is thought that rabeprazole may provide enhanced first-day acid suppression compared with esomeprazole. First-day antisecretory efficacy should produce faster symptom relief, a hypothesis supported by clinical data. Moreover, drugs with pharmacological profiles that include both rapid onset and potent antisecretory effects should help control healthcare costs by reducing the need for otherwise commonly used twice-daily proton pump inhibitor administration.

Plasmodium falciparum: differing effects of non-esterified fatty acids and phospholipids on intraerythrocytic growth in serum-free medium.

PubMed

Asahi, Hiroko; Izumiyama, Shinji; Tolba, Mohammed Essa Marghany; Kwansa-Bentum, Bethel

2011-03-01

Different combinations of non-esterified fatty acids (NEFA) had variable effects on intraerythrocytic growth of Plasmodium falciparum. All stages of the parasite cultured in medium supplemented with cis-9-octadecenoic acid (C18:1-cis-9), hexadecanoic acid (C16:0), phospholipids (Pld) and bovine albumin free of NEFA were similar to those grown in complete growth medium. Three typical growth patterns indicating suppressed schizogony (SS), suppressed formation of merozoites (SMF), and inhibited invasion of merozoites (IMI) resulted from culture in other combinations of lipids. Unsaturated or saturated NEFA with longer or shorter carbon chains than C18:1-cis-9 or C16:0, higher degree of unsaturation, and trans-forms mainly resulted in SS and SMF effects. However, IMI or partial IMI was observed with tetradecanoic acid or octadecanoic acid enriched with C18:1-cis-9, and cis-9-hexadecenoic acid plus C16:0. Isoforms of C18:1-cis-9 also mainly resulted in partial IMI. SMF also occurred with C18:1-cis-9 plus C16:0 in the absence of Pld. Thus different NEFA exerted distinct roles in erythrocytic growth of the parasite by sustaining development at different stages. Copyright © 2010 Elsevier Inc. All rights reserved.

Phage display peptide libraries: deviations from randomness and correctives

PubMed Central

Ryvkin, Arie; Ashkenazy, Haim; Weiss-Ottolenghi, Yael; Piller, Chen; Pupko, Tal; Gershoni, Jonathan M

2018-01-01

Abstract Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library. In a previous study, we implemented next generation sequencing to evaluate a naïve library and discovered severe deviations from randomness in UAG codon over-representation as well as in high G phosphoramidite abundance causing amino acid distribution biases. In this study, we demonstrate that the UAG over-representation can be attributed to the burden imposed on the phage upon the assembly of the recombinant Protein 8 subunits. This was corrected by constructing the libraries using supE44-containing bacteria which suppress the UAG driven abortive termination. We also demonstrate that the overabundance of G stems from variant synthesis-efficiency and can be corrected using compensating oligonucleotide-mixtures calibrated by mass spectroscopy. Construction of libraries implementing these correctives results in markedly improved libraries that display random distribution of amino acids, thus ensuring that enriched peptides obtained in biopanning represent a genuine selection event, a fundamental assumption for phage display applications. PMID:29420788

An acoustic streaming instability in thermoacoustic devices utilizing jet pumps.

PubMed

Backhaus, S; Swift, G W

2003-03-01

Thermoacoustic-Stirling hybrid engines and feedback pulse tube refrigerators can utilize jet pumps to suppress streaming that would otherwise cause large heat leaks and reduced efficiency. It is desirable to use jet pumps to suppress streaming because they do not introduce moving parts such as bellows or membranes. In most cases, this form of streaming suppression works reliably. However, in some cases, the streaming suppression has been found to be unstable. Using a simple model of the acoustics in the regenerators and jet pumps of these devices, a stability criterion is derived that predicts when jet pumps can reliably suppress streaming.

A Clostridium Group IV Species Dominates and Suppresses a Mixed Culture Fermentation by Tolerance to Medium Chain Fatty Acids Products

PubMed Central

Andersen, Stephen J.; De Groof, Vicky; Khor, Way Cern; Roume, Hugo; Props, Ruben; Coma, Marta; Rabaey, Korneel

2017-01-01

A microbial community is engaged in a complex economy of cooperation and competition for carbon and energy. In engineered systems such as anaerobic digestion and fermentation, these relationships are exploited for conversion of a broad range of substrates into products, such as biogas, ethanol, and carboxylic acids. Medium chain fatty acids (MCFAs), for example, hexanoic acid, are valuable, energy dense microbial fermentation products, however, MCFA tend to exhibit microbial toxicity to a broad range of microorganisms at low concentrations. Here, we operated continuous mixed population MCFA fermentations on biorefinery thin stillage to investigate the community response associated with the production and toxicity of MCFA. In this study, an uncultured species from the Clostridium group IV (related to Clostridium sp. BS-1) became enriched in two independent reactors that produced hexanoic acid (up to 8.1 g L−1), octanoic acid (up to 3.2 g L−1), and trace concentrations of decanoic acid. Decanoic acid is reported here for the first time as a possible product of a Clostridium group IV species. Other significant species in the community, Lactobacillus spp. and Acetobacterium sp., generate intermediates in MCFA production, and their collapse in relative abundance resulted in an overall production decrease. A strong correlation was present between the community composition and both the hexanoic acid concentration (p = 0.026) and total volatile fatty acid concentration (p = 0.003). MCFA suppressed species related to Clostridium sp. CPB-6 and Lactobacillus spp. to a greater extent than others. The proportion of the species related to Clostridium sp. BS-1 over Clostridium sp. CPB-6 had a strong correlation with the concentration of octanoic acid (p = 0.003). The dominance of this species and the increase in MCFA resulted in an overall toxic effect on the mixed community, most significantly on the Lactobacillus spp., which resulted in a decrease in total hexanoic acid concentration to 32 ± 2% below the steady-state average. As opposed to the current view of MCFA toxicity broadly leading to production collapse, this study demonstrates that varied tolerance to MCFA within the community can lead to the dominance of some species and the suppression of others, which can result in a decreased productivity of the fermentation. PMID:28265558

Oral branched-chain amino acids decrease whole-body proteolysis

NASA Technical Reports Server (NTRS)

Ferrando, A. A.; Williams, B. D.; Stuart, C. A.; Lane, H. W.; Wolfe, R. R.

1995-01-01

BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

Periodic variation in bile acids controls circadian changes in uric acid via regulation of xanthine oxidase by the orphan nuclear receptor PPARα.

PubMed

Kanemitsu, Takumi; Tsurudome, Yuya; Kusunose, Naoki; Oda, Masayuki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

2017-12-29

Xanthine oxidase (XOD), also known as xanthine dehydrogenase, is a rate-limiting enzyme in purine nucleotide degradation, which produces uric acid. Uric acid concentrations in the blood and liver exhibit circadian oscillations in both humans and rodents; however, the underlying mechanisms remain unclear. Here, we demonstrate that XOD expression and enzymatic activity exhibit circadian oscillations in the mouse liver. We found that the orphan nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) transcriptionally activated the mouse XOD gene and that bile acids suppressed XOD transactivation. The synthesis of bile acids is known to be under the control of the circadian clock, and we observed that the time-dependent accumulation of bile acids in hepatic cells interfered with the recruitment of the co-transcriptional activator p300 to PPARα, thereby repressing XOD expression. This time-dependent suppression of PPARα-mediated transactivation by bile acids caused an oscillation in the hepatic expression of XOD, which, in turn, led to circadian alterations in uric acid production. Finally, we also demonstrated that the anti-hyperuricemic effect of the XOD inhibitor febuxostat was enhanced by administering it at the time of day before hepatic XOD activity increased. These results suggest an underlying mechanism for the circadian alterations in uric acid production and also underscore the importance of selecting an appropriate time of day for administering XOD inhibitors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback.

PubMed

Behroozmand, Roozbeh; Larson, Charles R

2011-06-06

The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment

PubMed Central

Prasad, Sahdeo; Yadav, Vivek R.; Sung, Bokyung; Gupta, Subash C.; Tyagi, Amit K.; Aggarwal, Bharat B.

2016-01-01

The development of chemoresistance in human pancreatic cancer is one reason for the poor survival rate for patients with this cancer. Because multiple gene products are linked with chemoresistance, we investigated the ability of ursolic acid (UA) to sensitize pancreatic cancer cells to gemcitabine, a standard drug used for the treatment of pancreatic cancer. These investigations were done in AsPC-1, MIA PaCa-2, and Panc-28 cells and in nude mice orthotopically implanted with Panc-28 cells. In vitro, UA inhibited proliferation, induced apoptosis, suppressed NF-κB activation and its regulated proliferative, metastatic, and angiogenic proteins. UA (20 μM) also enhanced gemcitabine (200 nM)-induced apoptosis and suppressed the expression of NF-κB-regulated proteins. In the nude mouse model, oral administration of UA (250 mg/kg) suppressed tumor growth and enhanced the effect of gemcitabine (25 mg/kg). Furthermore, the combination of UA and gemcitabine suppressed the metastasis of cancer cells to distant organs such as liver and spleen. Immunohistochemical analysis showed that biomarkers of proliferation (Ki-67) and microvessel density (CD31) were suppressed by the combination of UA and gemcitabine. UA inhibited the activation of NF-κB and STAT3 and the expression of tumorigenic proteins regulated by these inflammatory transcription factors in tumor tissue. Furthermore, the combination of two agents decreased the expression of miR-29a, closely linked with tumorigenesis, in the tumor tissue. UA was found to be bioavailable in animal serum and tumor tissue. These results suggest that UA can inhibit the growth of human pancreatic tumors and sensitize them to gemcitabine by suppressing inflammatory biomarkers linked to proliferation, invasion, angiogenesis, and metastasis. PMID:26909608

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

[Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells].

PubMed

Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Wang, Kunfu; Wang, Mingfu; Wang, Didi; Ge, Tangdong; Sun, Jie

2014-09-01

Three long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), are the most biologically active polyunsaturated fatty acids in the body. They are important in developing and maintaining the brain function, and in preventing and treating many diseases such as cardiovascular disease, inflammation and cancer. Although mammals can biosynthesize these long-chain polyunsaturated fatty acids, the efficiency is very low and dietary intake is needed to meet the requirement. In this study, a multiple-genes expression vector carrying mammalian A6/A5 fatty acid desaturases and multiple-genes expression vector carrying mammalian Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases coding genes was used to transfect HEK293T cells, then the overexpression of the target genes was detected. GC-MS analysis shows that the biosynthesis efficiency and level of DHA, EPA and ARA were significantly increased in cells transfected with the multiple-genes expression vector. Particularly, DHA level in these cells was 2.5 times higher than in the control cells. This study indicates mammal possess a certain mechanism for suppression of high level of biosynthesis of long chain polyunsaturated fatty acids, and the overexpression of Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases broke this suppression mechanism so that the level of DHA, EPA and ARA was significantly increased. This study also provides a basis for potential applications of this gene construct in transgenic animal to produce high level of these long-chain polyunsaturated fatty acid.

Supplementation of Ascorbic Acid in Weanling Horses Following Prolonged Transportation

PubMed Central

Ralston, Sarah; Stives, Michelle

2012-01-01

Simple Summary Horses normally synthesize adequate amounts of ascorbic acid (vitamin C) in their liver to meet their needs for the vitamin. However, prolonged stress results in low plasma concentrations and reduced immune function. Weanling horses were supplemented with ascorbic acid for 5 or 10 days or no ascorbic acid (4 per group) following 50+ hours of transportation. Supplementation caused increases in plasma concentrations but both supplemented groups had decreased plasma ascorbic acid for 1 to 3 weeks following cessation of supplementation, possibly due to suppressed synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. Abstract Though horses synthesize ascorbic acid in their liver in amounts that meet their needs under normal circumstances, prolonged stress results in low plasma concentrations due to enhanced utilization and renal excretion and can reduce immune function. It was hypothesized that plasma ascorbic acid could be maintained in weanling horses by oral supplementation following prolonged transportation. Weanlings were supplemented with no ascorbic acid (Tx 0: n = 4), 5 grams ascorbic acid twice daily for 5 days (Tx 1: n = 4) or for 10 days (Tx 2: n = 4) following >50 hours of transportation. Supplementation caused slight (P < 0.2) increases in plasma ascorbic acid concentrations. Both supplemented groups had decreased (P < 0.05) plasma concentrations for 1 to 3 weeks following cessation of supplementation, possibly due to increased renal excretion or suppressed hepatic synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided. PMID:26486916

Trajectories of Change in Emotion Regulation and Social Anxiety During Cognitive-Behavioral Therapy for Social Anxiety Disorder

PubMed Central

Goldin, Philippe R.; Lee, Ihno; Ziv, Michal; Jazaieri, Hooria; Heimberg, Richard G.; Gross, James J.

2014-01-01

Cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD) may decrease social anxiety by training emotion regulation skills. This randomized controlled trial of CBT for SAD examined changes in weekly frequency and success of cognitive reappraisal and expressive suppression, as well as weekly intensity of social anxiety among patients receiving 16 weekly sessions of individual CBT. We expected these variables to (1) differ from pre-to-post-CBT vs. Waitlist, (2) have differential trajectories during CBT, and (3) covary during CBT. We also expected that weekly changes in emotion regulation would predict (4) subsequent weekly changes in social anxiety, and (5) changes in social anxiety both during and post-CBT. Compared to Waitlist, CBT increased cognitive reappraisal frequency and success, decreased social anxiety, but had no impact on expressive suppression. During CBT, weekly cognitive reappraisal frequency and success increased, whereas weekly expressive suppression frequency and social anxiety decreased. Weekly decreases in social anxiety were associated with concurrent increases in reappraisal success and decreases in suppression frequency. Granger causality analysis showed that only reappraisal success increases predicted decreases in subsequent social anxiety during CBT. Reappraisal success increases pre-to-post-CBT predicted reductions in social anxiety symptom severity post-CBT. The trajectory of weekly changes in emotion regulation strategies may help clinicians understand whether CBT is effective and predict decreases in social anxiety. PMID:24632110

An integrated global chemomics and system biology approach to analyze the mechanisms of the traditional Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills for pulmonary diseases.

PubMed

Tao, Jin; Hou, Yuanyuan; Ma, Xiaoyao; Liu, Dan; Tong, Yongling; Zhou, Hong; Gao, Jie; Bai, Gang

2016-01-08

Traditional Chinese medicine (TCM) herbal formulae provide valuable therapeutic strategies. However, the active ingredients and mechanisms of action remain unclear for most of these formulae. Therefore, the identification of complex mechanisms is a major challenge in TCM research. This study used a network pharmacology approach to clarify the anti-inflammatory and cough suppressing mechanisms of the Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills (ChuanbeiPipa dropping pills, CBPP). The chemical constituents of CBPP were identified by high-quality ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and anti-inflammatory ingredients were selected and analyzed using the PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics websites to predict the target proteins and related pathways, respectively. Then, an RNA-sequencing (RNA-Seq) analysis was carried out to investigate the different expression of genes in the lung tissue of rats with chronic bronchitis. Six main constituents affected 19 predicted pathways, including ursolic acid and oleanolic acid from Eriobotrya japonica (Thunb.) Lindl. (Eri), peiminine from Fritillaria usuriensis Maxim. (Fri), platycodigenin and polygalacic acid from Platycodon grandiflorum (Jacq.) A. DC. (Pla) and guanosine from Pinellia ternata (Thunb.) Makino. (Pin). Expression of 34 genes was significantly decreased after CBPP treatment, affecting four therapeutic functions: immunoregulation, anti-inflammation, collagen formation and muscle contraction. The active components acted on the mitogen activated protein kinase (MAPK) pathway, transforming growth factor (TGF)-beta pathway, focal adhesion, tight junctions and the action cytoskeleton to exert anti-inflammatory effects, resolve phlegm, and relieve cough. This novel approach of global chemomics-integrated systems biology represents an effective and accurate strategy for the study of TCM with multiple components and multiple target mechanisms.

Amino acid-based zwitterionic polymers: antifouling properties and low cytotoxicity.

PubMed

Li, Wenchen; Liu, Qingsheng; Liu, Lingyun

2014-01-01

A group of five amino acid containing zwitterionic vinyl monomers, based on serine, lysine, ornithine, glutamic acid, and aspartic acid, respectively, were proposed and developed for potential antifouling applications. Their polymer brushes were grafted on gold chips by surface-initiated photoiniferter-mediated polymerization. We then compared their performance in resisting protein adsorption from full human serum and plasma. All five polymers can reduce protein adsorption by more than 90% compared to the unmodified gold. The ornithine-based and aspartic acid-based poly(methacrylamide) can most strongly resist protein adsorption from serum and plasma, compared to the other three. The ability of surfaces to suppress bacterial adhesion is another criterion in evaluating antifouling properties of materials. Our results show that the five polymer-grafted surfaces can significantly suppress Escherichia coli K12 adhesion to 99% compared to the bare gold surface. The zwitterionic structure of amino acids, with homogenously distributed and balanced positive and negative charges, is responsible for the outstanding antifouling properties. Considering multiple potential applications (e.g. medical devices and drug delivery) of the antifouling materials, we further systematically evaluated the cytotoxicity of both monomers and polymer nanogels for all five materials at various concentrations. Very low cytotoxicity was observed for all tested amino acid-based monomers and nanogels, which is comparable or even lower than the traditional and some newly developed antifouling materials, which might be related to the biomimetic nature of amino acids.

Detection of high concentrations of organic acids in fish emulsion and their role in pathogen or disease suppression.

PubMed

Abbasi, Pervaiz A; Lazarovits, George; Jabaji-Hare, Suha

2009-03-01

Fish emulsion (FE) added to a sandy-loam soil at 1 and 2% rates reduced the viability of Verticillium dahliae microsclerotia by 39 and 74% in 1 day, 87 and 98% in 3 days, and 95 and 99% in 6 days, respectively. The immediate kill of microsclerotia indicated that FE contains toxic substances. We found in FE high concentrations (400 mmol/liter) of organic acids, including some known toxicants. Glycolic, acetic, formic, n-butyric, and propionic acids were the major organic acids detected in FE at the proportions of 52.5, 26.9, 7.9, 7.2, and 4.7%, respectively. In solution assays, the viability of V. dahliae microsclerotia treated for 24 h in 1, 2, 5, and 10% FE (pH 3.6 to 3.0) or a mixture of organic acids (pH 4.1 to 3.9) equivalent to the proportions in FE was reduced by 74, 94, 97, and 99% or 81, 91, 98, and 99%, respectively. The viability of microsclerotia was increased when the treatment solutions were buffered to pH 6.0. The organic acids mixtures and formic (0.025%) and acetic (0.1%) acids were toxic to Pythium ultimum. A mixture of organic acids (1, 2, and 4%) provided immediate protection of cucumber seedlings from damping-off in P. ultimum-infested muck and sandy-loam soils but not in peat-based mix. FE (1 and 2%) provided immediate protection of cucumber seedlings from damping-off in an infested muck soil, and disease protection was consistent when planting was delayed for 7, 14, and 28 days after adding FE. FE (1, 2, and 4%) did not provide immediate protection of cucumber seedlings from damping-off in a P. ultimum-infested peat-based mix; however, disease suppression was evident when planting was delayed for 7, 14, and 21 days after adding FE. Real-time polymerase chain reaction analyses of the peat-based mix indicated that the P. ultimum populations in the FE-amended mix declined over time. This study suggests that these organic acids in FE played a major role in pathogen or disease suppression, depending on the soil and substrate.

Activation of farnesoid X receptor promotes triglycerides lowering by suppressing phospholipase A2 G12B expression.

PubMed

Liu, Qingli; Yang, Meng; Fu, Xuekun; Liu, Renzhong; Sun, Caijun; Pan, Haobo; Wong, Chi-Wai; Guan, Min

2016-11-15

As a novel mediator of hepatic very low-density lipoproteins (VLDL) secretion, phospholipase A2 G12B (PLA2G12B) is transcriptionally regulated by hepatocyte nuclear factor-4 alpha (HNF-4α). Farnesoid X receptor (FXR) plays a critical role in maintaining bile acids and triglycerides (TG) homeostasis. Here we report that FXR regulates serum TG level in part through PLA2G12B. Activation of FXR by chenodeoxycholic acid (CDCA) or GW4064 significantly decreased PLA2G12B expression in HepG2 cells. PLA2G12B expression was transcriptionally repressed due to an FXR-mediated up-regulation of small heterodimer partner (SHP) which functionally suppresses HNF-4α activity. We found that hepatic PLA2G12B expression was suppressed and serum TG level reduced in high fat diet mice treated with CDCA. Concurrently, CDCA treatment lowered hepatic VLDL-TG secretion. Our data demonstrate that activation of FXR promotes TG lowering, not only by decreasing de novo lipogenesis but also reducing hepatic secretion of TG-rich VLDL particles in part through suppressing PLA2G12B expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Jet Noise Modeling for Supersonic Business Jet Application

NASA Technical Reports Server (NTRS)

Stone, James R.; Krejsa, Eugene A.; Clark, Bruce J.

2004-01-01

This document describes the development of an improved predictive model for coannular jet noise, including noise suppression modifications applicable to small supersonic-cruise aircraft such as the Supersonic Business Jet (SBJ), for NASA Langley Research Center (LaRC). For such aircraft a wide range of propulsion and integration options are under consideration. Thus there is a need for very versatile design tools, including a noise prediction model. The approach used is similar to that used with great success by the Modern Technologies Corporation (MTC) in developing a noise prediction model for two-dimensional mixer ejector (2DME) nozzles under the High Speed Research Program and in developing a more recent model for coannular nozzles over a wide range of conditions. If highly suppressed configurations are ultimately required, the 2DME model is expected to provide reasonable prediction for these smaller scales, although this has not been demonstrated. It is considered likely that more modest suppression approaches, such as dual stream nozzles featuring chevron or chute suppressors, perhaps in conjunction with inverted velocity profiles (IVP), will be sufficient for the SBJ.

A simulation and optimisation procedure to model daily suppression resource transfers during a fire season in Colorado

Treesearch

Yu Wei; Erin J. Belval; Matthew P. Thompson; Dave E. Calkin; Crystal S. Stonesifer

2016-01-01

Sharing fire engines and crews between fire suppression dispatch zones may help improve the utilisation of fire suppression resources. Using the Resource Ordering and Status System, the Predictive Services’ Fire Potential Outlooks and the Rocky Mountain Region Preparedness Levels from 2010 to 2013, we tested a simulation and optimisation procedure to transfer crews and...

Evaluation of Suppressiveness of Soils Exhibiting Soil-Borne Disease Suppression after Long-Term Application of Organic Amendments by the Co-cultivation Method of Pathogenic Fusarium oxysporum and Indigenous Soil Microorganisms.

PubMed

Mitsuboshi, Masahiro; Kioka, Yuuzou; Noguchi, Katsunori; Asakawa, Susumu

2018-03-29

Preventive measures against soil-borne diseases need to be implemented before cultivation because very few countermeasures are available after the development of diseases. Some soils suppress soil-borne diseases despite the presence of a high population density of pathogens. If the suppressiveness of soil against soil-borne diseases may be predicted and diagnosed for crop fields, it may be possible to reduce the labor and cost associated with excessive disinfection practices. We herein evaluated the suppressiveness of soils in fields with the long-term application of organic amendments by examining the growth of pathogenic Fusarium oxysporum co-cultivated with indigenous soil microorganisms on agar plates. Soils treated with coffee residue compost or rapeseed meal showed suppressiveness against spinach wilt disease by F. oxysporum f. sp. spinaciae or spinach wilt and lettuce root rot diseases by F. oxysporum f. sp. spinaciae and F. oxysporum f. sp. lactucae, respectively, and the growth of pathogenic Fusarium spp. on agar plates was suppressed when co-cultured with microorganisms in a suspension from these soils before crop cultivation. These results indicate the potential of the growth degree of pathogenic F. oxysporum estimated by this method as a diagnostic indicator of the suppressiveness of soil associated with the inhabiting microorganisms. A correlation was found between the incidence of spinach wilt disease in spinach and the growth degree of F. oxysporum f. sp. spinaciae by this co-cultivation method, indicating that suppressiveness induced by organic amendment applications against F. oxysporum f. sp. spinaciae is evaluable by this method. The co-cultivation method may be useful for predicting and diagnosing suppressiveness against soil-borne diseases.

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.

Evaluation of Suppressiveness of Soils Exhibiting Soil-Borne Disease Suppression after Long-Term Application of Organic Amendments by the Co-cultivation Method of Pathogenic Fusarium oxysporum and Indigenous Soil Microorganisms

PubMed Central

Mitsuboshi, Masahiro; Kioka, Yuuzou; Noguchi, Katsunori; Asakawa, Susumu

2018-01-01

Preventive measures against soil-borne diseases need to be implemented before cultivation because very few countermeasures are available after the development of diseases. Some soils suppress soil-borne diseases despite the presence of a high population density of pathogens. If the suppressiveness of soil against soil-borne diseases may be predicted and diagnosed for crop fields, it may be possible to reduce the labor and cost associated with excessive disinfection practices. We herein evaluated the suppressiveness of soils in fields with the long-term application of organic amendments by examining the growth of pathogenic Fusarium oxysporum co-cultivated with indigenous soil microorganisms on agar plates. Soils treated with coffee residue compost or rapeseed meal showed suppressiveness against spinach wilt disease by F. oxysporum f. sp. spinaciae or spinach wilt and lettuce root rot diseases by F. oxysporum f. sp. spinaciae and F. oxysporum f. sp. lactucae, respectively, and the growth of pathogenic Fusarium spp. on agar plates was suppressed when co-cultured with microorganisms in a suspension from these soils before crop cultivation. These results indicate the potential of the growth degree of pathogenic F. oxysporum estimated by this method as a diagnostic indicator of the suppressiveness of soil associated with the inhabiting microorganisms. A correlation was found between the incidence of spinach wilt disease in spinach and the growth degree of F. oxysporum f. sp. spinaciae by this co-cultivation method, indicating that suppressiveness induced by organic amendment applications against F. oxysporum f. sp. spinaciae is evaluable by this method. The co-cultivation method may be useful for predicting and diagnosing suppressiveness against soil-borne diseases. PMID:29459498

Ceriporic acid B, an extracellular metabolite of Ceriporiopsis subvermispora, suppresses the depolymerization of cellulose by the Fenton reaction.

PubMed

Rahmawati, Noor; Ohashi, Yasunori; Watanabe, Takahito; Honda, Yoichi; Watanabe, Takashi

2005-01-01

The white rot fungus, Ceriporiopsis subvermispora, is able to degrade lignin in wood without intensive damage to cellulose. Since lignin biodegradation by white rot fungi proceeds by radical reactions, accompanied by the production of a large amount of Fe3+-reductant phenols and reductive radical species in the presence of iron ions, molecular oxygen, and H2O2, C. subvermispora has been proposed to possess a biological system which suppresses the production of a cellulolytic active oxygen species, *OH, by the Fenton reaction. In the present paper, we demonstrate that 1-nonadecene-2,3-dicarboxylic acid (ceriporic acid B), an extracellular metabolite of C. subvermispora, strongly inhibited *OH production and the depolymerization of cellulose by the Fenton reaction in the presence of iron ions, cellulose, H2O2, and a reductant for Fe3+, hydroquinone (HQ), at the physiological pH of the fungus.

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

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

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pHmore » 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic acid-capped gold nanoparticles inhibit EGF-modulated p300 stabilization. • Gallic acid-capped gold nanoparticles abrogate EGF-induced NFκB/c-Jun activation.« less

Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5’-Phosphate Production in E. coli

DOE PAGES

Oberhardt, Matthew A.; Zarecki, Raphy; Reshef, Leah; ...

2016-01-28

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous ‘replacer’ gene rescues lethality caused by inactivation of a ‘target’ gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predictedmore » target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5’-phosphate (the active form of Vitamin B 6), which we validate experimentally via multicopy suppression. Here, we perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.« less

A possible correlation between performance IQ, visuomotor adaptation ability and mu suppression.

PubMed

Anwar, Muhammad Nabeel; Navid, Muhammad Samran; Khan, Mushtaq; Kitajo, Keiichi

2015-04-07

Psychometric, anatomical and functional brain studies suggest that individuals differ in the way that they perceive and analyze information and strategically control and execute movements. Inter-individual differences are also observed in neural correlates of specific and general cognitive ability. As a result, some individuals perceive and adapt to environmental conditions and perform motor activities better than others. The aim of this study was to identify a common factor that predicts adaptation of a reaching movement to a visual perturbation and suppression of movement-related brain activity (mu rhythms). Twenty-eight participants participated in two different experiments designed to evaluate visuomotor adaptation and mu suppression ability. Performance intelligence quotient (IQ) was assessed using the revised Wechsler Adult Intelligence Scale. Performance IQ predicted adaptation index of visuomotor performance (r=0.43, p=0.02) and suppression of mu rhythms (r=-0.59; p<0.001). Participants with high performance IQ were faster at adapting to a visuomotor perturbation and better at suppressing mu activity than participants with low performance IQ. We found a possible link between performance IQ and mu suppression, and performance IQ and the initial rate of adaptation. Individuals with high performance IQ were better in suppressing mu rhythms and were quicker at associating motor command and required movement than individuals with low performance IQ. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancing perception of contaminated food through acid-mediated modulation of taste neuron responses.

PubMed

Chen, Yan; Amrein, Hubert

2014-09-08

Natural foods contain not only nutrients, but also nonnutritious and potentially harmful chemicals. Thus, animals need to evaluate food content in order to make adequate feeding decisions. Here, we investigate the effects of acids on the taste neuron responses and on taste behavior of desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila melanogaster. Using Ca2+ imaging, we show that acids activate neither sweet nor bitter taste neurons in tarsal taste sensilla. However, they suppress responses to bitter compounds in bitter-sensing neurons. Moreover, acids reverse suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with these observations, behavioral analyses show that bitter-compound-mediated inhibition on feeding behavior is alleviated by acids. To investigate the cellular mechanism by which acids modulate these effects, we silenced bitter-sensing gustatory neurons. Surprisingly, this intervention had little effect on acid-mediated derepression of sweet neuron or feeding responses to either sugar/bitter compound mixtures or sugar/bitter compound/acid mixtures, suggesting that there are two independent pathways by which bitter compounds are sensed. Our investigations reveal that acids, when presented in dietary relevant concentrations, enhance the perception of sugar/bitter compound mixtures. Drosophila's natural food sources-fruits and cohabitating yeast-are rich in sugars and acids but are rapidly colonized by microorganisms, such as fungi, protozoan parasites, and bacteria, many of which produce bitter compounds. We propose that the acids present in most fruits counteract the inhibitory effects of these bitter compounds during feeding. Copyright © 2014 Elsevier Ltd. All rights reserved.

The components of rice and watermelon root exudates and their effects on pathogenic fungus and watermelon defense.

PubMed

Ren, Lixuan; Huo, Hongwei; Zhang, Fang; Hao, Wenya; Xiao, Liang; Dong, Caixia; Xu, Guohua

2016-06-02

Watermelon (Citrullus lanatus) is susceptible to wilt disease caused by the fungus Fusarium oxysporum f. sp niveum (FON). Intercropping management of watermelon/aerobic rice (Oryza sativa) alleviates watermelon wilt disease, because some unidentified component(s) in rice root exudates suppress FON sporulation and spore germination. Here, we show that the phenolic acid p-coumaric acid is present in rice root exudates only, and it inhibits FON spore germination and sporulation. We found that exogenously applied p-coumaric acid up-regulated the expression of ClPR3 in roots, as well as increased chitinase activity in leaves. Furthermore, exogenously applied p-coumaric acid increased β-1,3-glucanase activity in watermelon roots. By contrast, we found that ferulic acid was secreted by watermelon roots, but not by rice roots, and that it stimulated spore germination and sporulation of FON. Exogenous application of ferulic acid down-regulated ClPR3 expression and inhibited chitinase activity in watermelon leaves. Salicylic acid was detected in both watermelon and rice root exudates, which stimulated FON spore germination at low concentrations and suppressed spore germination at high concentrations. Exogenously applied salicylic acid did not alter ClPR3 expression, but did increase chitinase and β-1,3-glucanase activities in watermelon leaves. Together, our results show that the root exudates of phenolic acids were different between rice and watermelon, which lead to their special ecological roles on pathogenic fungus and watermelon defense.

The components of rice and watermelon root exudates and their effects on pathogenic fungus and watermelon defense

PubMed Central

Ren, Lixuan; Huo, Hongwei; Zhang, Fang; Hao, Wenya; Xiao, Liang; Dong, Caixia; Xu, Guohua

2016-01-01

ABSTRACT Watermelon (Citrullus lanatus) is susceptible to wilt disease caused by the fungus Fusarium oxysporum f. sp niveum (FON). Intercropping management of watermelon/aerobic rice (Oryza sativa) alleviates watermelon wilt disease, because some unidentified component(s) in rice root exudates suppress FON sporulation and spore germination. Here, we show that the phenolic acid p-coumaric acid is present in rice root exudates only, and it inhibits FON spore germination and sporulation. We found that exogenously applied p-coumaric acid up-regulated the expression of ClPR3 in roots, as well as increased chitinase activity in leaves. Furthermore, exogenously applied p-coumaric acid increased β-1,3-glucanase activity in watermelon roots. By contrast, we found that ferulic acid was secreted by watermelon roots, but not by rice roots, and that it stimulated spore germination and sporulation of FON. Exogenous application of ferulic acid down-regulated ClPR3 expression and inhibited chitinase activity in watermelon leaves. Salicylic acid was detected in both watermelon and rice root exudates, which stimulated FON spore germination at low concentrations and suppressed spore germination at high concentrations. Exogenously applied salicylic acid did not alter ClPR3 expression, but did increase chitinase and β-1,3-glucanase activities in watermelon leaves. Together, our results show that the root exudates of phenolic acids were different between rice and watermelon, which lead to their special ecological roles on pathogenic fungus and watermelon defense. PMID:27217091

Resistin Regulates Fatty Acid Β Oxidation by Suppressing Expression of Peroxisome Proliferator Activator Receptor Gamma-Coactivator 1α (PGC-1α).

PubMed

He, Fang; Jin, Jie-Qiong; Qin, Qing-Qing; Zheng, Yong-Qin; Li, Ting-Ting; Zhang, Yun; He, Jun-Dong

2018-01-01

Abnormal fatty acid β oxidation has been associated with obesity and type 2 diabetes. Resistin is an adipokine that has been considered as a potential factor in obesity-mediated insulin resistance and type 2 diabetes. However, the effect of resistin on fatty acid β oxidation needs to be elucidated. We detected the effects of resistin on the expression of fatty acid oxidation (FAO) transcriptional regulatory genes, the fatty acid transport gene, and mitochondrial β-oxidation genes using real-time PCR. The rate of FAO was measured using 14C-palmitate. Immunofluorescence assay and western blot analysis were used to explore the underlying molecular mechanisms. Resistin leads to a reduction in expression of the FAO transcriptional regulatory genes ERRα and NOR1, the fatty acid transport gene CD36, and the mitochondrial β-oxidation genes CPT1, MCAD, and ACO. Importantly, treatment with resistin led to a reduction in the rate of cellular fatty acid oxidation. In addition, treatment with resistin reduced phosphorylation of acetyl CoA carboxylase (ACC) (inhibitory). Mechanistically, resistin inhibited the activation of CREB, resulting in suppression of PGC-1α. Importantly, overexpressing PGC-1α can rescue the inhibitory effects of resistin on fatty acid β oxidation. Activating the transcriptional activity of CREB using small molecular chemicals is a potential pharmacological strategy for preventing the inhibitory effects of resistin on fatty acid β oxidation. © 2018 The Author(s). Published by S. Karger AG, Basel.

Phosphite, an analog of phosphate, suppresses the coordinated expression of genes under phosphate starvation.

PubMed

Varadarajan, Deepa K; Karthikeyan, Athikkattuvalasu S; Matilda, Paino Durzo; Raghothama, Kashchandra G

2002-07-01

Phosphate (Pi) and its analog phosphite (Phi) are acquired by plants via Pi transporters. Although the uptake and mobility of Phi and Pi are similar, there is no evidence suggesting that plants can utilize Phi as a sole source of phosphorus. Phi is also known to interfere with many of the Pi starvation responses in plants and yeast (Saccharomyces cerevisiae). In this study, effects of Phi on plant growth and coordinated expression of genes induced by Pi starvation were analyzed. Phi suppressed many of the Pi starvation responses that are commonly observed in plants. Enhanced root growth and root to shoot ratio, a hallmark of Pi stress response, was strongly inhibited by Phi. The negative effects of Phi were not obvious in plants supplemented with Pi. The expression of Pi starvation-induced genes such as LePT1, LePT2, AtPT1, and AtPT2 (high-affinity Pi transporters); LePS2 (a novel acid phosphatase); LePS3 and TPSI1 (novel genes); and PAP1 (purple acid phosphatase) was suppressed by Phi in plants and cell cultures. Expression of luciferase reporter gene driven by the Pi starvation-induced AtPT2 promoter was also suppressed by Phi. These analyses showed that suppression of Pi starvation-induced genes is an early response to addition of Phi. These data also provide evidence that Phi interferes with gene expression at the level of transcription. Synchronized suppression of multiple Pi starvation-induced genes by Phi points to its action on the early molecular events, probably signal transduction, in Pi starvation response.

Suppression of DS1 Phosphatidic Acid Phosphatase Confirms Resistance to Ralstonia solanacearum in Nicotiana benthamiana

PubMed Central

Nakano, Masahito; Nishihara, Masahiro; Yoshioka, Hirofumi; Takahashi, Hirotaka; Sawasaki, Tatsuya; Ohnishi, Kouhei; Hikichi, Yasufumi; Kiba, Akinori

2013-01-01

Nicotiana benthamiana is susceptible to Ralstonia solanacearum. To analyze molecular mechanisms for disease susceptibility, we screened a gene-silenced plant showing resistance to R. solanacearum, designated as DS1 (Disease suppression 1). The deduced amino acid sequence of DS1 cDNA encoded a phosphatidic acid phosphatase (PAP) 2. DS1 expression was induced by infection with a virulent strain of R. solanacearum in an hrp-gene-dependent manner. DS1 rescued growth defects of the temperature-sensitive ∆lpp1∆dpp1∆pah1 mutant yeast. Recombinant DS1 protein showed Mg2+-independent PAP activity. DS1 plants showed reduced PAP activity and increased phosphatidic acid (PA) content. After inoculation with R. solanacearum, DS1 plants showed accelerated cell death, over-accumulation of reactive oxygen species (ROS), and hyper-induction of PR-4 expression. In contrast, DS1-overexpressing tobacco plants showed reduced PA content, greater susceptibility to R. solanacearum, and reduced ROS production and PR-4 expression. The DS1 phenotype was partially compromised in the plants in which both DS1 and NbCoi1 or DS1 and NbrbohB were silenced. These results show that DS1 PAP may affect plant immune responses related to ROS and JA cascades via regulation of PA levels. Suppression of DS1 function or DS1 expression could rapidly activate plant defenses to achieve effective resistance against Ralstonia solanacearum. PMID:24073238

Anticancer effects of garlic and garlic-derived compounds for breast cancer control.

PubMed

Tsubura, Airo; Lai, Yen-Chang; Kuwata, Maki; Uehara, Norihisa; Yoshizawa, Katsuhiko

2011-03-01

Garlic and garlic-derived compounds reduce the development of mammary cancer in animals and suppress the growth of human breast cancer cells in culture. Oil-soluble compounds derived from garlic, such as diallyl disulfide (DADS), are more effective than water-soluble compounds in suppressing breast cancer. Mechanisms of action include the activation of metabolizing enzymes that detoxify carcinogens, the suppression of DNA adduct formation, the inhibition of the production of reactive oxygen species, the regulation of cell-cycle arrest and the induction of apoptosis. Selenium-enriched garlic or organoselenium compounds provide more potent protection against mammary carcinogenesis in rats and greater inhibition of breast cancer cells in culture than natural garlic or the respective organosulfur analogues. DADS synergizes the effect of eicosapentaenoic acid, a breast cancer suppressor, and antagonizes the effect of linoleic acid, a breast cancer enhancer. Moreover, garlic extract reduces the side effects caused by anti-cancer agents. Thus, garlic and garlic-derived compounds are promising candidates for breast cancer control.

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.

Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK.

PubMed

Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun; Bode, Ann M; Lee, Hyo-Jeong; Heo, Yong-Seok; Boardman, Lisa; Limburg, Paul; Lee, Hyong Joo; Dong, Zigang

2011-06-01

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation.

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

PubMed

Richter, J E; Pandolfino, J E; Vela, M F; Kahrilas, P J; Lacy, B E; Ganz, R; Dengler, W; Oelschlager, B K; Peters, J; DeVault, K R; Fass, R; Gyawali, C P; Conklin, J; DeMeester, T

2013-01-01

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Effect of long-chain Fatty acids on the binding of triflupromazine to human serum albumin: a spectrophotometric study.

PubMed

Kitamura, Keisuke; Takegami, Shigehiko; Tanaka, Rumi; Omran, Ahmed Ahmed; Kitade, Tatsuya

2014-01-01

Human serum albumin (HSA) in the blood binds long-chain fatty acids (LCFAs), and the number of bound LCFAs varies from 1 to 7 depending on the physical condition of the body. In this study, the influence of LCFA-HSA binding on drug-HSA binding was studied using triflupromazine (TFZ), a psychotropic phenothiazine drug, in a buffer (0.1 M NaCl, pH 7.40, 37°C) by a second-derivative spectrophotometric method which can suppress the residual background signal effects of HSA observed in the absorption spectra. The examined LCFAs were caprylic acid (CPA), lauric acid (LRA), oleic acid (OLA), and linoleic acid (LNA), respectively. Using the derivative intensity change of TFZ induced by the addition of HSA containing LCFA, the binding mode of TFZ was predicted to be a partition-like nonspecific binding. The binding constant (K M(-1)) showed an increase according to the LCFA content in HSA for LRA, OLA, and LNA up to an LCFA/HSA molar ratio of 3-4. However, at higher ratios the K value decreased, i.e. for OLA and LNA, at an LCFA/HSA ratio of 6-7, the K value decreased to 40% of the value for HSA alone. In contrast, CPA, having the shortest chain length (8 carbons) among the studied LCFAs, induced a 20% decrease in the K value regardless of its content in HSA. Since the pharmacological activity of a drug is closely related to the unbound drug concentration in the blood, the results of the present study are pharmaco-kinetically, pharmacologically, and clinically very important.

Aqueous aerosol SOA formation: impact on aerosol physical properties.

PubMed

Woo, Joseph L; Kim, Derek D; Schwier, Allison N; Li, Ruizhi; McNeill, V Faye

2013-01-01

Organic chemistry in aerosol water has recently been recognized as a potentially important source of secondary organic aerosol (SOA) material. This SOA material may be surface-active, therefore potentially affecting aerosol heterogeneous activity, ice nucleation, and CCN activity. Aqueous aerosol chemistry has also been shown to be a potential source of light-absorbing products ("brown carbon"). We present results on the formation of secondary organic aerosol material in aerosol water and the associated changes in aerosol physical properties from GAMMA (Gas-Aerosol Model for Mechanism Analysis), a photochemical box model with coupled gas and detailed aqueous aerosol chemistry. The detailed aerosol composition output from GAMMA was coupled with two recently developed modules for predicting a) aerosol surface tension and b) the UV-Vis absorption spectrum of the aerosol, based on our previous laboratory observations. The simulation results suggest that the formation of oligomers and organic acids in bulk aerosol water is unlikely to perturb aerosol surface tension significantly. Isoprene-derived organosulfates are formed in high concentrations in acidic aerosols under low-NO(x) conditions, but more experimental data are needed before the potential impact of these species on aerosol surface tension may be evaluated. Adsorption of surfactants from the gas phase may further suppress aerosol surface tension. Light absorption by aqueous aerosol SOA material is driven by dark glyoxal chemistry and is highest under high-NO(x) conditions, at high relative humidity, in the early morning hours. The wavelength dependence of the predicted absorption spectra is comparable to field observations and the predicted mass absorption efficiencies suggest that aqueous aerosol chemistry can be a significant source of aerosol brown carbon under urban conditions.

Disruption of the vacuolar calcium-ATPases in Arabidopsis results in the activation of a salicylic acid-dependent programmed cell death pathway.

PubMed

Boursiac, Yann; Lee, Sang Min; Romanowsky, Shawn; Blank, Robert; Sladek, Chris; Chung, Woo Sik; Harper, Jeffrey F

2010-11-01

Calcium (Ca(2+)) signals regulate many aspects of plant development, including a programmed cell death pathway that protects plants from pathogens (hypersensitive response). Cytosolic Ca(2+) signals result from a combined action of Ca(2+) influx through channels and Ca(2+) efflux through pumps and cotransporters. Plants utilize calmodulin-activated Ca(2+) pumps (autoinhibited Ca(2+)-ATPase [ACA]) at the plasma membrane, endoplasmic reticulum, and vacuole. Here, we show that a double knockout mutation of the vacuolar Ca(2+) pumps ACA4 and ACA11 in Arabidopsis (Arabidopsis thaliana) results in a high frequency of hypersensitive response-like lesions. The appearance of macrolesions could be suppressed by growing plants with increased levels (greater than 15 mm) of various anions, providing a method for conditional suppression. By removing plants from a conditional suppression, lesion initials were found to originate primarily in leaf mesophyll cells, as detected by aniline blue staining. Initiation and spread of lesions could also be suppressed by disrupting the production or accumulation of salicylic acid (SA), as shown by combining aca4/11 mutations with a sid 2 (for salicylic acid induction-deficient2) mutation or expression of the SA degradation enzyme NahG. This indicates that the loss of the vacuolar Ca(2+) pumps by itself does not cause a catastrophic defect in ion homeostasis but rather potentiates the activation of a SA-dependent programmed cell death pathway. Together, these results provide evidence linking the activity of the vacuolar Ca(2+) pumps to the control of a SA-dependent programmed cell death pathway in plants.

Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.

PubMed

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2013-11-01

To elucidate the mechanism of rutin in blocking macrophage-mediated inflammation and high fat diet-induced obesity and fatty liver. Both in vitro and in vivo approaches were taken in evaluating the effects of rutin on palmitic acids-triggered inflammation in cultured macrophages, and on weight gain and development of fatty liver of mice fed a high fat diet. Palmitic acids increase mRNA levels of pro-inflammatory cytokines, and elevate the production of TNFα in cultured macrophages. Pre-exposure of rutin to cells greatly suppressed these elevations. The suppressed inflammation by rutin was correlated with a decrease in transcription of genes responsible for ER stress and production of reactive oxygen species. In vivo, rutin protects mice from high fat diet-induced obesity, fatty liver and insulin resistance. The protective effects were associated with lack of hypertrophy and crown-like structures in the white adipose tissue, decreased mRNA levels of marker genes for macrophages including F4/80, Cd11c and Cd68, and repressed transcription of genes involved in chronic inflammation such as Mcp1 and Tnfα in white adipose tissue. In addition, rutin increases the expression of genes responsible for energy expenditure in brown adipose tissue including Pgc1α and Dio2. Furthermore, rutin suppresses transcription of Srebp1c and Cd36 in the liver, leading to a blockade of fatty liver development. These results suggest that supplementation of rutin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

Synthesis of aminocarbonyl N-acylhydrazones by a three-component reaction of isocyanides, hydrazonoyl chlorides, and carboxylic acids.

PubMed

Giustiniano, Mariateresa; Meneghetti, Fiorella; Mercalli, Valentina; Varese, Monica; Giustiniano, Francesco; Novellino, Ettore; Tron, Gian Cesare

2014-10-17

A novel one-pot multicomponent synthesis of α-aminocarbonyl N-acylhydrazones starting from readily available hydrazonoyl chlorides, isocyanides, and carboxylic acids is reported. The strategy exploits the ability of the carboxylic acid as a third component to suppress all competing reactions between nitrile imines and isocyanides, channeling the course of the reaction toward the formation of this novel class of compounds.

Studies on Synthesis of Electrochemically Exfoliated Functionalized Graphene and Polylactic Acid/Ferric Phytate Functionalized Graphene Nanocomposites as New Fire Hazard Suppression Materials.

PubMed

Feng, Xiaming; Wang, Xin; Cai, Wei; Qiu, Shuilai; Hu, Yuan; Liew, Kim Meow

2016-09-28

Practical application of functionalized graphene in polymeric nanocomposites is hampered by the lack of cost-effective and eco-friendly methods for its production. Here, we reported a facile and green electrochemical approach for preparing ferric phytate functionalized graphene (f-GNS) by simultaneously utilizing biobased phytic acid as electrolyte and modifier for the first time. Due to the presence of phytic acid, electrochemical exfoliation leads to low oxidized graphene sheets (a C/O ratio of 14.8) that are tens of micrometers large. Successful functionalization of graphene was confirmed by the appearance of phosphorus and iron peaks in the X-ray photoelectron spectrum. Further, high-performance polylactic acid/f-GNS nanocomposites are readily fabricated by a convenient masterbatch strategy. Notably, inclusion of well-dispersed f-GNS resulted in dramatic suppression on fire hazards of polylactic acid in terms of reduced peak heat-release rate (decreased by 40%), low CO yield, and formation of a high graphitized protective char layer. Moreover, obviously improvements in crystallization rate and thermal conductivities of polylactic acid nanocomposites were observed, highlighting its promising potential in practical application. This novel strategy toward the simultaneous exfoliation and functionalization for graphene demonstrates a simple yet very effective approach for fabricating graphene-based flame retardants.

Effect of somatostatin on meal-induced gastric secretion in duodenal ulcer patients.

PubMed

Konturek, S J; Swierczek, J; Kwiecień, N; Mikoś, E; Oleksy, J; Wierzbicki, Z

1977-11-01

The effect of somatostatin, a growth hormone releasing-inhibiting hormone (GH-RIH) on basal and meal-, pentagastrin-, or histamine-stimulated gastric acid and pepsin secretion was studied in six duodenal ulcer patients. Intravenous GH-RIH infused in graded doses ranging from 0.62 to 5.0 microgram/kg/hr produced a dose-related inhibition of pentagastrin-induced acid secretion reaching about 15% of control level at the dose of 5.0 microgram/kg/hr. Acid inhibition was paralleled by a decrease in the pepsin output and accompanied by a dose-dependent reduction in serum growth hormone and insulin levels measured by radioimmunoassay. GH-RIH used in a single dose of 2.5 microgram/kg/hr produced about 85% inhibition of acid secretion induced by a meal (measured by intragastric titration) accompanied by a significant decrease in serum gastrin and insulin levels. The effect of GH-RIH on histamine-stimulated secretion was very modest and observed only after stopping the GH-RIH infusion. Thus GH-RIH suppressed acid and pepsin secretion induced by pentagastrin and a meal, and this effect was accompanied by a suppression of serum growth hormone and gastrin levels which may contribute to the inhibition of gastric secretion observed.

Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases

PubMed Central

Movsesyan, Nina; Platt, Frances M.

2017-01-01

In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters. PMID:29119141

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.

The Processing of Attended and Predicted Sounds in Time.

PubMed

Paris, Tim; Kim, Jeesun; Davis, Chris

2016-01-01

Neural responses to an attended event are typically enhanced relative to those from an unattended one (attention enhancement). Conversely, neural responses to a predicted event are typically reduced relative to those from an unpredicted one (prediction suppression). What remains to be established is what happens with attended and predicted events. To examine the interaction between attention and prediction, we combined two robust paradigms developed for studying attention and prediction effects on ERPs into an orthogonal design. Participants were presented with sounds in attended or unattended intervals with onsets that were either predicted by a moving visual cue or unpredicted (no cue was provided). We demonstrated an N1 enhancement effect for attended sounds and an N1 suppression effect for predicted sounds; furthermore, an interaction between these effects was found that emerged early in the N1 (50-95 msec), indicating that attention enhancement only occurred when the sound was unpredicted. This pattern of results can be explained by the precision of the predictive cue that reduces the need for attention selection in the attended and predicted condition.

Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness.

PubMed

Lee, Jisoo; Kim, Yoo-Sun; Lee, JaeHwan; Heo, Seung Chul; Lee, Kook Lae; Choi, Sang-Woon; Kim, Yuri

2016-07-21

Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133⁺CD44⁺ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.

Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1.

PubMed

Kim, Sung-Jo; Zhang, Zhongjian; Saha, Arjun; Sarkar, Chinmoy; Zhao, Zhenwen; Xu, Yan; Mukherjee, Anil B

2010-08-02

Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking Ppt1, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL. Published by Elsevier Ireland Ltd.

Walnut Phenolic Extract and Its Bioactive Compounds Suppress Colon Cancer Cell Growth by Regulating Colon Cancer Stemness

PubMed Central

Lee, Jisoo; Kim, Yoo-Sun; Lee, JaeHwan; Heo, Seung Chul; Lee, Kook Lae; Choi, Sang-Woon; Kim, Yuri

2016-01-01

Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133+CD44+ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133+CD44+ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs. PMID:27455311

Suppression of the lethal effect of acidic-phospholipid deficiency by defective formation of the major outer membrane lipoprotein in Escherichia coli.

PubMed Central

Asai, Y; Katayose, Y; Hikita, C; Ohta, A; Shibuya, I

1989-01-01

The Escherichia coli pgsA3 allele encoding a defective phosphatidylglycerophosphate synthase is lethal for all but certain strains. Genetic analysis of such strains has revealed that the lethal effect is fully suppressed by the lack of the major outer membrane lipoprotein that consumes phosphatidylglycerol for its maturation. Images PMID:2556377

Down-regulation of a chitin synthase a gene by RNA interference enhances pathogenicity of Beauveria bassiana ANU1 against Spodoptera exigua (HÜBNER).

PubMed

Lee, Jung-Bok; Kim, Hyun Soo; Park, Youngjin

2017-02-01

Chitin synthase (CHS) is an important enzymatic component, which is required for chitin formation in the cuticles and cuticular linings of other tissues in insects. CHSs have been divided into two classes, classes A and B, based on their amino acid sequence similarities and functions. Class A CHS (CHS-A) is specifically expressed in the epidermis and related ectodermal cells such as tracheal cells, while class B CHS (CHS-B) is expressed in gut epithelial cells that produce peritrophic matrices. In this study, we cloned the CHS-A gene from the beet armyworm, Spodoptera exigua (SeCHS-A). The SeCHS-A contains an open reading frame of 4,698 nucleotides, encoding a protein of 1,565 amino acids with a predicted molecular mass of approximately 177.8 kDa. The SeCHS-A mRNA was expressed in all developmental stages and specifically in the epidermis and tracheae tissue by quantitative real-time-PCR analysis. Expression of SeCHS-A gene was suppressed by feeding double-stranded RNA (dsCHS-A, 400 ng/larva) in the third instar larvae of S. exigua. Suppression of the SeCHS-A gene expression significantly increased 35% of mortality on pupation of S. exigua. Also, the third instar larvae fed with dsCHS-A significantly increased susceptibility to entomopathogenic fungi, Beauveria bassiana ANU1 at 3 days after treatment. These results suggest that the SeCHS-A gene plays an important role in development of S. exigua and RNA interference may apply to effective pest control with B. bassiana. © 2017 Wiley Periodicals, Inc.

Retinoid acid-induced microRNA-27b-3p impairs C2C12 myoblast proliferation and differentiation by suppressing α-dystrobrevin

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

Li, Nan; Tang, Yi; Liu, Bo

We previously reported that excess retinoic acid (RA) resulted in hypoplastic and derangement of myofilaments in embryonic tongue by inhibiting myogenic proliferation and differentiation through CamKIID pathway. Our further studies revealed that the expression of a series of miRNAs was altered by RA administration in embryonic tongue as well as in C2C12 cells. Thus, if excess RA impairs myogenic proliferation and differentiation through miRNAs is taken into account. In present study, miR-27b-3p was found up-regulated in RA-treated C2C12 cells as in embryonic tongue, and predicted to target the 3′UTR of α-dystrobrevin (DTNA). Luciferase reporter assays confirmed the direct interaction betweenmore » miR-27b-3p and the 3′UTR of DTNA. MiR-27b-3p mimics recapitulated the RA repression on DTNA expression, C2C12 proliferation and differentiation, while the miR-27b-3p inhibitor circumvented these defects resulting from excess RA. As expected, the effects of siDTNA on C2C12 were coincided with those by RA treatment or miR-27b-3p mimics. Therefore, these findings indicated that excess RA inhibited the myoblast proliferation and differentiation by up-regulating miR-27b-3p to target DTNA, which implied a new mechanism in myogenic hypoplasia. - Highlights: • A mechanism that RA results in tongue deformity by disrupting the myogenesis. • A non-muscle specific miR mediating the RA suppression on tongue myogenesis. • A target gene of non-muscle specific miR involved in RA induced tongue deformity.« less

Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.

PubMed

Yang, Jing; Sun, Lixin; Wang, Lu; Hassan, Hozeifa M; Wang, Xuan; Hylemon, Phillip B; Wang, Tao; Zhou, Huiping; Zhang, Luyong; Jiang, Zhenzhou

2017-01-01

Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo . The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro . The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

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

Wada, Isao; Otaka, Michiro; Jin, Mario

2006-10-20

Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared betweenmore » control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.« less

Food for thought: examining the relationship between food thought suppression and weight-related outcomes.

PubMed

Barnes, Rachel D; Tantleff-Dunn, Stacey

2010-08-01

The current study sought to extend previous eating behaviors and thought suppression literature by assessing the relationship between food thought suppression and weight-related outcomes. Three hundred and twelve overweight/obese community men and women completed self-report measures of thought suppression, weight history, and eating behaviors. Women were more likely than men to endorse food thought suppression, as were individuals who currently were dieting, when compared with those nondieters. Food thought suppression also predicted binge eating, food cravings, and other eating disordered symptoms. Results have implications for obesity and support further exploration of third wave interventions, such as Acceptance and Commitment Therapy and Mindfulness, in the treatment of obesity. 2010 Elsevier Ltd. All rights reserved.

Design and experimental validation of a flutter suppression controller for the active flexible wing

NASA Technical Reports Server (NTRS)

Waszak, Martin R.; Srinathkumar, S.

1992-01-01

The synthesis and experimental validation of an active flutter suppression controller for the Active Flexible Wing wind tunnel model is presented. The design is accomplished with traditional root locus and Nyquist methods using interactive computer graphics tools and extensive simulation based analysis. The design approach uses a fundamental understanding of the flutter mechanism to formulate a simple controller structure to meet stringent design specifications. Experimentally, the flutter suppression controller succeeded in simultaneous suppression of two flutter modes, significantly increasing the flutter dynamic pressure despite modeling errors in predicted flutter dynamic pressure and flutter frequency. The flutter suppression controller was also successfully operated in combination with another controller to perform flutter suppression during rapid rolling maneuvers.

Development of a Liner Design Methodology and Relevant Results of Acoustic Suppression in the Farfield for Mixer-Ejector Nozzles

NASA Technical Reports Server (NTRS)

Salikuddin, M.

2006-01-01

We have developed a process to predict noise field interior to the ejector and in the farfield for any liner design for a mixer-ejector of arbitrary scale factor. However, a number of assumptions, not verified for the current application, utilized in this process, introduce uncertainties in the final result, especially, on a quantitative basis. The normal impedance model for bulk with perforated facesheet is based on homogeneous foam materials of low resistivity. The impact of flow conditions for HSCT application as well as the impact of perforated facesheet on predicted impedance is not properly accounted. Based on the measured normal impedance for deeper bulk samples (i.e., 2.0 in.) the predicted reactance is much higher compared to the data at frequencies above 2 kHz for T-foam and 200 ppi SiC. The resistance is under predicted at lower frequencies (below 4 kHz) for these samples. Thus, the use of such predicted data in acoustic suppression is likely to introduce inaccuracies. It should be noted that the impedance prediction methods developed recently under liner technology program are not utilized in the studies described in this report due to the program closeout. Acoustic suppression prediction is based on the uniform flow and temperature conditions in a two-sided treated constant area rectangular duct. In addition, assumptions of equal energy per mode noise field and interaction of all frequencies with the treated surface for the entire ejector length may not be accurate. While, the use of acoustic transfer factor minimizes the inaccuracies associated with the prediction for a known test case, the assumption of the same factor for other liner designs and with different linear scale factor ejectors seems to be very optimistic. As illustrated in appendix D that the predicted noise suppression for LSM-1 is lower compared to the measured data is an indication of the above argument. However, the process seems to be more reliable when used for the same scale models for different liner designs as demonstrated for Gen. 1 mixer-ejectors.

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

PubMed

Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.

PubMed

Pasman, Wilrike J; Heimerikx, Jos; Rubingh, Carina M; van den Berg, Robin; O'Shea, Marianne; Gambelli, Luisa; Hendriks, Henk F J; Einerhand, Alexandra W C; Scott, Corey; Keizer, Hiskias G; Mennen, Louise I

2008-03-20

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 muM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day.CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake.

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells.

PubMed

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

2016-11-01

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

16(R)-hydroxyeicosatetraenoic acid, a novel cytochrome P450 product of arachidonic acid, suppresses activation of human polymorphonuclear leukocyte and reduces intracranial pressure in a rabbit model of thromboembolic stroke.

PubMed

Bednar, M M; Gross, C E; Russell, S R; Fuller, S P; Ahern, T P; Howard, D B; Falck, J R; Reddy, K M; Balazy, M

2000-12-01

Activated polymorphonuclear leukocytes (PMNs) have been suggested to contribute to the development of increased intracranial pressure (ICP). We recently demonstrated that human PMNs produce a novel cytochrome P450-derived arachidonic acid metabolite, 1 6(R)-hydroxyeicosatetraenoic acid [16(R)-HETE], that modulates their function. It was thus of interest to examine this novel mediator in an acute stroke model. 16-HETE was assessed initially in a variety of human PMN and platelet in vitro assays and subsequently in an established rabbit model of thromboembolic stroke. A total of 50 rabbits completed a randomized, blinded, four-arm study, receiving 16(R)-HETE, tissue plasminogen activator, both, or neither. Experiments were completed 7 hours after autologous clot embolization. The primary end point for efficacy was the suppression of increased ICP. In in vitro assays, 16(R)-HETE selectively inhibited human PMN adhesion and aggregation and leukotriene B4 synthesis. In the thromboembolic stroke model, animals that received 16(R)-HETE demonstrated significant suppression of increased ICP (7.7 +/- 1.2 to 13.1 +/- 2.7 mm Hg, baseline versus final 7-h time point, mean +/- standard error), compared with either the vehicle-treated group (7.7 +/- 0.9 to 15.8 +/- 2.6 mm Hg) or the tissue plasminogen activator-treated group (7.6 +/- 0.6 to 13.7 +/- 2.1 mm Hg). The group that received the combination of 16(R)-HETE plus tissue plasminogen activator demonstrated no significant change in ICP for the duration of the protocol (8.6 +/- 0.6 to 11.1 +/- 1.2 mm Hg). 16(R)-HETE suppresses the development of increased ICP in a rabbit model of thromboembolic stroke and may serve as a novel therapeutic strategy in ischemic and inflammatory pathophysiological states.

Suppression of Alfvénic modes through modification of the fast ion distribution

NASA Astrophysics Data System (ADS)

Fredrickson, Eric

2017-10-01

Experiments on NSTX-U have shown for the first time that small amounts of high pitch-angle, low ρL beam ions can strongly suppress the counter-propagating Global Alfvén Eigenmodes (GAE) [1]. GAE have been implicated in the redistribution of fast ions and modification of the electron power balance in previous experiments on NSTX. The ability to predict the stability of Alfvén modes, and development of methods to control them, is important for fusion reactors like ITER, which like NSTX, will be heated with a large population of non-thermal, super-Alfvénic ions (unlike the normal operation of conventional tokamaks). The suppression of the GAE by adding a small population of high-pitch resonant fast ions is qualitatively consistent with an analytic model of the Doppler-shifted ion-cyclotron resonance drive responsible for GAE instability [2]. The model predicts that fast ions with k⊥ρL <1.9 are stabilizing, which is in good agreement with the experimental observations. A quantitative analysis was done using the HYM stability code [3] of one of the nearly 100 identified examples of GAE suppression. The simulations find remarkable agreement with the observed mode numbers and frequencies of the unstable GAE prior to suppression. Adding the population of high pitch-angle, low ρL beam ions to the HYM fast ion distribution function predicts complete suppression of the GAE. TRANSP/NUBEAM calculations for the example analyzed with HYM suggest that the additional beam source increases the population of resonant fast ions with k⊥ρL <1.9 by roughly a factor of four. Work supported by U.S. DOE Contract DE-AC02-09CH11466.

Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

PubMed Central

2011-01-01

Background The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Conclusions Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds. PMID:21645406

Isoprene suppression of new particle formation: Potential mechanisms and implications

NASA Astrophysics Data System (ADS)

Lee, Shan-Hu; Uin, Janek; Guenther, Alex B.; de Gouw, Joost A.; Yu, Fangqun; Nadykto, Alex B.; Herb, Jason; Ng, Nga L.; Koss, Abigail; Brune, William H.; Baumann, Karsten; Kanawade, Vijay P.; Keutsch, Frank N.; Nenes, Athanasios; Olsen, Kevin; Goldstein, Allen; Ouyang, Qi

2016-12-01

Secondary aerosols formed from anthropogenic pollutants and natural emissions have substantial impacts on human health, air quality, and the Earth's climate. New particle formation (NPF) contributes up to 70% of the global production of cloud condensation nuclei (CCN), but the effects of biogenic volatile organic compounds (BVOCs) and their oxidation products on NPF processes in forests are poorly understood. Observations show that isoprene, the most abundant BVOC, suppresses NPF in forests. But the previously proposed chemical mechanism underlying this suppression process contradicts atmospheric observations. By reviewing observations made in other forests, it is clear that NPF rarely takes place during the summer when emissions of isoprene are high, even though there are sufficient concentrations of monoterpenes. But at present it is not clear how isoprene and its oxidation products may change the oxidation chemistry of terpenes and how NOx and other atmospheric key species affect NPF in forest environments. Future laboratory experiments with chemical speciation of gas phase nucleation precursors and clusters and chemical composition of particles smaller than 10 nm are required to understand the role of isoprene in NPF. Our results show that climate models can overpredict aerosol's first indirect effect when not considering the absence of NPF in the southeastern U.S. forests during the summer using the current nucleation algorithm that includes only sulfuric acid and total concentrations of low-volatility organic compounds. This highlights the importance of understanding NPF processes as function of temperature, relative humidity, and BVOC compositions to make valid predictions of NPF and CCN at a wide range of atmospheric conditions.

Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health

USDA-ARS?s Scientific Manuscript database

Dietary supplementation with fermentable fiber is thought to suppress metabolic syndrome via production of short-chain fatty acids (SCFA), which activate the free fatty acid receptors including GPR43. However, herein, we demonstrate that fermentable (inulin), but not insoluble (cellulose) fiber, mar...

Supression of humoral immunity by perfluorooctanic acid is independent of elevated serum corticosterone concentration in mice

EPA Science Inventory

The T-cell-dependent antibody response is suppressed in mice exposed to 3.75, 7.5, 15, and 30 mg PFOA (perfluorooctanoic acid)/kg body weight (bw). Reduced bw accompanied immunosuppression at 15 and 30 mg/kg. We investigated the hypothesis that the observed immunosuppression is s...

Doxorubicin-loaded microgels composed of cinnamic acid-gelatin conjugate and cinnamic acid-Pluronic F127 conjugate.

PubMed

Zhang, Hong; Kim, Jin-Chul

2016-01-01

Microgels were prepared by cinnamic acid-gelatin (type B) conjugate (CA-GelB) and cinnamic acid-Pluronic F127 conjugate (CA-Plur). (1)H NMR confirmed that CA was conjugated to gelatin and the gelatin to CA residue molar ratio was estimated to be 1:4.7 by a colorimetric method. CA-Plur of which the CA residue to Plur molar ratio was 1.2:1 was used as a thermo-sensitive polymer. The CA residues of CA-Plur/CA-GelB mixture were readily photo-dimerized to form microgels by UV irradiation. The isoelectric point of the microgel was found to be pH 5.8 and the hydrodynamic diameter decreased when the suspension temperature increased. The microgel could hardly retard the release of doxorubicin (DOX) at pH 3.0 and pH 5.0, but it could suppress and control the release at pH 7.4 possibly due to electrostatic attraction. Meanwhile, the release of DOX at pH 7.4 was less suppressed when the medium temperature was higher, possibly because of thermal thinning of Pluronic chain layer.

Tripartite Motif 24 (Trim24/Tif1α) Tumor Suppressor Protein Is a Novel Negative Regulator of Interferon (IFN)/Signal Transducers and Activators of Transcription (STAT) Signaling Pathway Acting through Retinoic Acid Receptor α (Rarα) Inhibition*

PubMed Central

Tisserand, Johan; Khetchoumian, Konstantin; Thibault, Christelle; Dembélé, Doulaye; Chambon, Pierre; Losson, Régine

2011-01-01

Recent genetic studies in mice have established that the nuclear receptor coregulator Trim24/Tif1α suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor α (Rara)-dependent transcription and cell proliferation. However, Rara targets regulated by Trim24 remain unknown. We report that the loss of Trim24 resulted in interferon (IFN)/STAT pathway overactivation soon after birth (week 5). Despite a transient attenuation of this pathway by the induction of several IFN/STAT pathway repressors later in the disease, this phenomenon became more pronounced in tumors. Remarkably, Rara haplodeficiency, which suppresses tumorigenesis in Trim24−/− mice, prevented IFN/STAT overactivation. Moreover, together with Rara, Trim24 bound to the retinoic acid-responsive element of the Stat1 promoter and repressed its retinoic acid-induced transcription. Altogether, these results identify Trim24 as a novel negative regulator of the IFN/STAT pathway and suggest that this repression through Rara inhibition may prevent liver cancer. PMID:21768647

Reduced Gut Acidity Induces an Obese-Like Phenotype in Drosophila melanogaster and in Mice

PubMed Central

Yen, Jui-Hung; Kuo, Ping-Chang; Yeh, Sheng-Rong; Lin, Hung-Yu; Fu, Tsai-Feng; Wu, Ming-Shiang; Wang, Horng-Dar; Wang, Pei-Yu

2015-01-01

In order to identify genes involved in stress and metabolic regulation, we carried out a Drosophila P-element-mediated mutagenesis screen for starvation resistance. We isolated a mutant, m2, that showed a 23% increase in survival time under starvation conditions. The P-element insertion was mapped to the region upstream of the vha16-1 gene, which encodes the c subunit of the vacuolar-type H+-ATPase. We found that vha16-1 is highly expressed in the fly midgut, and that m2 mutant flies are hypomorphic for vha16-1 and also exhibit reduced midgut acidity. This deficit is likely to induce altered metabolism and contribute to accelerated aging, since vha16-1 mutant flies are short-lived and display increases in body weight and lipid accumulation. Similar phenotypes were also induced by pharmacological treatment, through feeding normal flies and mice with a carbonic anhydrase inhibitor (acetazolamide) or proton pump inhibitor (PPI, lansoprazole) to suppress gut acid production. Our study may thus provide a useful model for investigating chronic acid suppression in patients. PMID:26436771

Induction of suppressor cells from peripheral blood T cells by 15-hydroperoxyeicosatetraenoic acid (15-HPETE).

PubMed

Gualde, N; Rigaud, M; Goodwin, J S

1985-11-01

15-hydroperoxyeicosetetraenoic acid (15-HPETE), a lipoxygenase metabolite of arachidonic acid, inhibited polyclonal IgG and IgM production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood mononuclear cells, whereas 15-hydroxyeicosetetraenoic acid (15-HETE) had little effect in this system. T cells preincubated for 18 hr with 15-HPETE caused substantial inhibition of IgG and IgM production of fresh, autologous B and T cells stimulated by PWM. The suppressive effect of the 15-HPETE-treated cells was lost if the cells were irradiated before the PWM culture, but not by treatment with mitomycin C. The suppressive effect was also lost if OKT8+ T cells were removed after, but not before, preincubation of the T cells with 15-HPETE. OKT8- T cells incubated with 15-HPETE for 18 hr showed a large increase in the percentage of cells staining with directly fluoresceinated Leu-2, another marker for suppressor cells. Thus, 15-HPETE induces functional and phenotypic suppressor cells from resting human peripheral blood T cells.

Mechanisms that improve referential access*

PubMed Central

Gernsbacher, Morton Ann

2015-01-01

Two mechanisms, suppression and enhancement, are proposed to improve referential access. Enhancement improves the accessibility of previously mentioned concepts by increasing or boosting their activation; suppression improves concepts’ accessibility by decreasing or dampening the activation of other concepts. Presumably, these mechanisms are triggered by the informational content of anaphors. Six experiments investigated this proposal by manipulating whether an anaphoric reference was made with a very explicit, repeated name anaphor or a less explicit pronoun. Subjects read sentences that introduced two participants in their first clauses, for example, “Ann predicted that Pam would lose the track race,” and the sentences referred to one of the two participants in their second clauses, “but Pam/she came in first very easily.” While subjects read each sentence, the activation level of the two participants was measured by a probe verification task. The first two experiments demonstrated that explicit, repeated name anaphors immediately trigger the enhancement of their own antecedents and immediately trigger the suppression of other (nonantecedent) participants. The third experiment demonstrated that less explicit, pronoun anaphors also trigger the suppression of other nonantecedents, but they do so less quickly—even when, as in the fourth experiment, the semantic information to identify their antecedents occurs prior to the pronouns (e.g., “Ann predicted that Pam would lose the track race. But after winning the race, she …”). The fifth experiment demonstrated that more explicit pronouns – pronouns that match the gender of only one participant—trigger suppression more powerfully. A final experiment demonstrated that it is not only rementioned participants who improve their referential access by triggering the suppression of other participants; newly introduced participants do so too (e.g., “Ann predicted that Pam would lose the track race, but Kim …”). Thus, both suppression and enhancement improve referential access, and the contribution of these two mechanisms is a function of explicitness. The role of these two mechanisms in mediating other referential access phenomena is also discussed. PMID:2752708

Validation of the model for ELM suppression with 3D magnetic fields using low torque ITER baseline scenario discharges in DIII-D

NASA Astrophysics Data System (ADS)

Moyer, R. A.; Paz-Soldan, C.; Nazikian, R.; Orlov, D. M.; Ferraro, N. M.; Grierson, B. A.; Knölker, M.; Lyons, B. C.; McKee, G. R.; Osborne, T. H.; Rhodes, T. L.; Meneghini, O.; Smith, S.; Evans, T. E.; Fenstermacher, M. E.; Groebner, R. J.; Hanson, J. M.; La Haye, R. J.; Luce, T. C.; Mordijck, S.; Solomon, W. M.; Turco, F.; Yan, Z.; Zeng, L.; DIII-D Team

2017-10-01

Experiments have been executed in the DIII-D tokamak to extend suppression of Edge Localized Modes (ELMs) with Resonant Magnetic Perturbations (RMPs) to ITER-relevant levels of beam torque. The results support the hypothesis for RMP ELM suppression based on transition from an ideal screened response to a tearing response at a resonant surface that prevents expansion of the pedestal to an unstable width [Snyder et al., Nucl. Fusion 51, 103016 (2011) and Wade et al., Nucl. Fusion 55, 023002 (2015)]. In ITER baseline plasmas with I/aB = 1.4 and pedestal ν * ˜ 0.15, ELMs are readily suppressed with co- I p neutral beam injection. However, reducing the beam torque from 5 Nm to ≤ 3.5 Nm results in loss of ELM suppression and a shift in the zero-crossing of the electron perpendicular rotation ω ⊥ e ˜ 0 deeper into the plasma. The change in radius of ω ⊥ e ˜ 0 is due primarily to changes to the electron diamagnetic rotation frequency ωe * . Linear plasma response modeling with the resistive MHD code m3d-c1 indicates that the tearing response location tracks the inward shift in ω ⊥ e ˜ 0. At pedestal ν * ˜ 1, ELM suppression is also lost when the beam torque is reduced, but the ω ⊥ e change is dominated by collapse of the toroidal rotation v T . The hypothesis predicts that it should be possible to obtain ELM suppression at reduced beam torque by also reducing the height and width of the ωe * profile. This prediction has been confirmed experimentally with RMP ELM suppression at 0 Nm of beam torque and plasma normalized pressure β N ˜ 0.7. This opens the possibility of accessing ELM suppression in low torque ITER baseline plasmas by establishing suppression at low beta and then increasing beta while relying on the strong RMP-island coupling to maintain suppression.

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

Oberhardt, Matthew A.; Zarecki, Raphy; Reshef, Leah

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous ‘replacer’ gene rescues lethality caused by inactivation of a ‘target’ gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predictedmore » target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5’-phosphate (the active form of Vitamin B 6), which we validate experimentally via multicopy suppression. Here, we perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.« less

Why did the white bear return? Obsessive-compulsive symptoms and attributions for unsuccessful thought suppression

PubMed Central

Magee, Joshua C.; Teachman, Bethany A.

2007-01-01

The current study examined the nature and consequences of attributions about unsuccessful thought suppression. Undergraduate students with either high (N=67) or low (N=59) levels of obsessive-compulsive symptoms rated attributions to explain their unsuccessful thought suppression attempts. We expected that self-blaming attributions and attributions ascribing importance to unwanted thoughts would predict more distress and greater recurrence of thoughts during time spent monitoring or suppressing unwanted thoughts. Further, we expected that these attributions would mediate the relationship between obsessive-compulsive symptom levels and the negative thought suppression outcomes (distress and thought recurrence). Structural equation models largely confirmed the hypotheses, suggesting that attributions may be an important factor in explaining the consequences of thought suppression. Implications are discussed for cognitive theories of obsessive-compulsive disorder and thought suppression. PMID:17825786

Emotional suppression and breast cancer: validation research on the Spanish Adaptation of the Courtauld Emotional Control Scale (CECS).

PubMed

Durá, Estrella; Andreu, Yolanda; Galdón, Maria José; Ibáñez, Elena; Pérez, Sandra; Ferrando, Maite; Murgui, Sergio; Martínez, Paula

2010-05-01

Emotional suppression has played an important role in the research on psychosocial factors related to cancer. It has been argued to be an important psychological factor predicting worse psychosocial adjustment in people with cancer and it may mediate health outcomes. The reference instrument in the research on emotional suppression is the Courtauld Emotional Control Scale (CECS). The present study analysed construct validity of a new Spanish adaptation of the CECS in a sample of 175 breast cancer patients. The results confirmed the proposal by Watson and Greer claiming that the CECS is composed of three subscales that measure different dimensions, but not independent, from emotional control. The present Spanish version of the CECS showed high internal consistency in each subseale as well as the total score. According to Derogatis (BSI-18) criteria, emotional suppression predicts clinically significant distress. In short, our results support the reliability, validity and utility of this Spanish adaptation of the CECS in clinical and research settings.

Administration of chlorogenic acid alleviates spinal cord injury via TLR4/NF‑κB and p38 signaling pathway anti‑inflammatory activity.

PubMed

Chen, Dayong; Pan, Dan; Tang, Shaolong; Tan, Zhihong; Zhang, Yanan; Fu, Yunfeng; Lü, Guohua; Huang, Qinghua

2018-01-01

Chlorogenic acid, as a secondary metabolite of plants, exhibits a variety of effects including free radical scavenging, antiseptic, anti‑inflammatory and anti‑viral, in addition to its ability to reduce blood glucose, protect the liver and act as an anti‑hyperlipidemic agent and cholagogue. The present study demonstrated that administration of chlorogenic acid alleviated spinal cord injury (SCI) via anti‑inflammatory activity mediated by nuclear factor (NF)‑κB and p38 signaling pathways. Wistar rats were used to structure a SCI model rat to explore the effects of administration of chlorogenic acid on SCI. The Basso, Beattie and Bresnahan test was executed for assessment of neuronal functional recovery and then spinal cord tissue wet/dry weight ratio was recorded. The present study demonstrated that chlorogenic acid increased SCI‑inhibition of BBB scores and decreased SCI‑induction of spinal cord wet/dry weight ratio in rats. In addition, chlorogenic acid suppressed SCI‑induced inflammatory activity, inducible nitric oxide synthase activity and cyclooxygenase‑2 protein expression in the SCI rat. Furthermore, chlorogenic acid suppressed Toll like receptor (TLR)‑4/myeloid differentiation primary response 88 (MyD88)/NF‑κB/IκB signaling pathways and downregulated p38 mitogen activated protein kinase protein expression in SCI rats. The findings suggest that administration of chlorogenic acid alleviates SCI via anti‑inflammatory activity mediated by TLR4/MyD88/NF‑κB and p38 signaling pathways.

Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats.

PubMed

Norazalina, S; Norhaizan, M E; Hairuszah, I; Norashareena, M S

2010-05-01

This study is carried out to determine the potential of phytic acid extracted from rice bran in the suppression of colon carcinogenesis induced by azoxymethane (AOM) in rats. Seventy-two male Sprague-Dawley rats were divided into 6 groups with 12 rats in each group. The intended rats for cancer treatment received two intraperitoneal injections of AOM in saline (15mg/kg bodyweight) over a 2-week period. The treatments of phytic acid were given in two concentrations: 0.2% (w/v) and 0.5% (w/v) during the post-initiation phase of carcinogenesis phase via drinking water. The colons of the animals were analyzed for detection and quantification of aberrant crypt foci (ACF) after 8 weeks of treatment. The finding showed treatment with 0.2% (w/v) extract phytic acid (EPA) gave the greatest reduction in the formation of ACF. In addition, phytic acid significantly suppressed the number of ACF in the distal, middle and proximal colon as compared to AOM alone (p<0.05). For the histological classification of ACF, treatment with 0.5% (w/v) commercial phytic acid (CPA) had the highest percentage (71%) of non-dysplastic ACF followed by treatment with 0.2% (w/v) EPA (61%). Administration of phytic acid also reduced the incidence and multiplicity of total tumors even though there were no significant differences between groups. In conclusion, this study found the potential value of phytic acid extracted from rice bran in reducing colon cancer risk in rats.

Antepartal insulin-like growth factor 1 and insulin-like growth factor binding protein 2 concentrations are indicative of ketosis in dairy cows.

PubMed

Piechotta, M; Mysegades, W; Ligges, U; Lilienthal, J; Hoeflich, A; Miyamoto, A; Bollwein, H

2015-05-01

A study involving a small number of cows found that the concentrations of insulin-like growth hormone 1 (IGF1) may be a useful predictor of metabolic disease. Further, IGF1 may provide also a pathophysiological link to metabolic diseases such as ketosis. The objective of the current study was to test whether the low antepartal total IGF1 or IGF1 binding protein (IGFBP) concentrations might predict ketosis under field conditions. Clinical examinations and blood sampling were performed antepartum (262-270 d after artificial insemination) on 377 pluriparous pregnant Holstein Friesian cows. The presence of postpartum diseases were recorded (ketosis, fatty liver, displacement of the abomasum, hypocalcemia, mastitis, retention of fetal membranes, and clinical metritis or endometritis), and the concentrations of IGF1, IGFBP2, IGFBP3, and nonesterified fatty acids were measured. Cows with postpartum clinical ketosis had lower IGF1 concentrations antepartum than healthy cows. The sensitivity of antepartal IGF1 as a marker for postpartum ketosis was 0.87, and the specificity was 0.43; a positive predictive value of 0.91 and a negative predictive value of 0.35 were calculated. The cows with ketosis and retained fetal membranes had lower IGFBP2 concentrations compared with the healthy cows. It can be speculated that lower IGF1 production in the liver during late pregnancy may increase growth hormone secretions and lipolysis, thereby increasing the risk of ketosis. Lower IGFBP2 concentrations may reflect the suppression of IGFBP2 levels through higher growth hormone secretion. In conclusion, compared with nonesterified fatty acids as a predictive parameter, IGF1 and IGFBP2 may represent earlier biomarkers of inadequate metabolic adaptation to the high energy demand required postpartum. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of L-cysteine and N-acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5-aminolevulinic acid and exposed to radiation.

PubMed

He, D; Behar, S; Roberts, J E; Lim, H W

1996-10-01

The effects of L-cysteine (LC) and N-acetylcysteine (NAC) on porphyrin accumulation in a human dermal microvascular endothelial cell line (HMEC-1) and a human epidermoid carcinoma cell line (A431) loaded with 5-aminolevulinic acid (ALA) and exposed to ultraviolet A (UVA) and blue light radiation were determined. Porphyrin accumulation was decreased in the presence of 0.1-7.5 mM LC (24.8%-31.4% suppression in HMEC-1 cell; 35.8%-48.9% suppression in A431 cells), and in the presence of 0.1-10.0 mM NAC (30.9%-58.0% suppression in HMEC-1 cells; 8.5%-45.3% in A431 cells). The suppression occurred in a LC or NAC dose-dependent fashion. The above was associated with partial reversal of suppression of ferrochelatase (FeC) activity in HMEC-1 cells and in A431 cells. As compared to FeC activity in cells treated with ALA and irradiation, enzyme activity was higher (by 31.9%-62.1%) in the presence of LC (1.0 mM or 5.0 mM) and in the presence of NAC (1.0 mM or 5.0 mM). These data indicate that LC and NAC have protective effects on porphyrin- and irradiation-induced diminution of FeC activity in HMEC-1 cells and A341 cells in vitro.

LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

PubMed

Choi, B K; Hercules, D M; Gusev, A I

2001-02-01

The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

Immunosuppressive compounds from a deep water marine sponge, Agelas flabelliformis.

PubMed

Gunasekera, S P; Cranick, S; Longley, R E

1989-01-01

Two immunosuppressive compounds, 4 alpha-methyl-5 alpha-cholest-8-en-3 beta-ol and 4,5-dibromo-2-pyrrolic acid were isolated from a deep water marine sponge, Agelas flabelliformis. Their structures were determined by comparison of their spectral data with those of samples isolated from other organisms. Both compounds were highly active in suppression of the response of murine splenocytes in the two-way mixed lymphocyte reaction (MLR) with little to no demonstrable cytotoxicity at lower doses. In addition, 4,5-dibromo-2-pyrrolic acid suppressed the proliferative response of splenocytes to suboptimal concentrations of the mitogen, concanavalin A (Con A). These results describe for the first time compounds isolated from the marine sponge A. flabelliformis that possess potent in vitro immunosuppressive activity.

Choice is good, but relevance is excellent: autonomy-enhancing and suppressing teacher behaviours predicting students' engagement in schoolwork.

PubMed

Assor, Avi; Kaplan, Haya; Roth, Guy

2002-06-01

This article examines two questions concerning teacher-behaviours that are characterised in Self-Determination Theory (Ryan & Deci, 2000) as autonomy-supportive or suppressive: (1) Can children differentiate among various types of autonomy-enhancing and suppressing teacher behaviours? (2) Which of those types of behaviour are particularly important in predicting feelings toward and engagement in schoolwork? It was hypothesised that teacher behaviours that help students to understand the relevance of schoolwork for their personal interests and goals are particularly important predictors of engagement in schoolwork. Israeli students in grades 3-5 (N = 498) and in grades 6-8 (N = 364) completed questionnaires assessing the variables of interest. Smallest Space Analyses indicated that both children and early adolescents can differentiate among three types of autonomy enhancing teacher behaviours - fostering relevance, allowing criticism, and providing choice - and three types of autonomy suppressing teacher behaviours - suppressing criticism, intruding, and forcing unmeaningful acts. Regression analyses supported the hypothesis concerning the importance of teacher behaviours that clarify the personal relevance of schoolwork. Among the autonomy-suppressing behaviours, 'Criticism-suppression' was the best predictor of feelings and engagement. The findings underscore the active and empathic nature of teachers' role in supporting students' autonomy, and suggest that autonomy-support is important not only for early adolescents but also for children. Discussion of potential determinants of the relative importance of various autonomy-affecting teacher actions suggests that provision of choice should not always be viewed as a major indicator of autonomy support.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

PubMed

Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

2013-07-15

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

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.

Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer

PubMed Central

Murray, Shannon; Witt, Kristina; Seitz, Christina; Wallerius, Majken; Xie, Hanjing; Ullén, Anders; Harmenberg, Ulrika; Lidbrink, Elisabet; Rolny, Charlotte; Andersson, John

2017-01-01

ABSTRACT Regulatory T cells (Treg) suppress anti-tumor immune responses and their infiltration in the tumor microenvironment is associated with inferior prognosis in cancer patients. Thus, in order to enhance anti-tumor immune responses, selective depletion of Treg is highly desired. We found that treatment with zoledronic acid (ZA) resulted in a selective decrease in the frequency of Treg that was associated with a significant increase in proliferation of T cells and natural killer (NK) cells in peripheral blood of patients with metastatic cancer. In vitro, genome-wide transcriptomic analysis revealed alterations in calcium signaling pathways in Treg following treatment with ZA. Furthermore, co-localization of the nuclear factor of activated T cells (NFAT) and forkhead box P3 (FOXP3) was significantly reduced in Treg upon ZA-treatment. Consequently, reduced expression levels of CD25, STAT5 and TGFβ were observed. Functionally, ZA-treated Treg had reduced capacity to suppress T and NK cell proliferation and anti-tumor responses compared with untreated Treg in vitro. Treatment with ZA to selectively inhibit essential signaling pathways in Treg resulting in reduced capacity to suppress effector T and NK cell responses represents a novel approach to inhibit Treg activity in patients with cancer. PMID:28920001

Upregulation of suppressor of cytokine signaling 3 in microglia by cinnamic acid.

PubMed

Chakrabarti, Sudipta; Jana, Malabendu; Roy, Avik; Pahan, Kalipada

2018-05-06

Neuroinflammation plays an important role in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Suppressor of cytokine signaling 3 (SOCS3) is an anti-inflammatory molecule that suppresses cytokine signaling and inflammatory gene expression in different cells including microglia. However, pathways through which SOCS3 could be upregulated are poorly described. Cinnamic acid is a metabolite of cinnamon, a natural compound that is being widely used all over the world as a spice or flavoring agent. This study delineates the importance of cinnamic acid for the upregulation of SOCS3 in microglia. Cinnamic acid upregulated the expression of SOCS3 mRNA and protein in mouse BV-2 microglial cells in dose- and time-dependent manner. Accordingly, cinnamic acid also increased the level of SOCS3 and suppressed the expression of inducible nitric oxide synthase and proinflammatory cytokines (TNFα, IL-1β and IL-6) in LPS-stimulated BV-2 microglial cells. Similar to BV-2 microglial cells, cinnamic acid also increased the expression of SOCS3 in primary mouse microglia and astrocytes. Presence of cAMP response element in the promoter of socs3 gene, activation of cAMP response element binding (CREB) by cinnamic acid, abrogation of cinnamic acid-mediated upregulation of SOCS3 by siRNA knockdown of CREB, and the recruitment of CREB to the socs3 gene promoter by cinnamic acid suggest that cinnamic acid increases the expression of SOCS3 by CREB. These studies suggest that cinnamic acid upregulates SOCS3 via CREB pathway, which may be of importance in neuroinflammatory and neurodegenerative disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of silicate and phosphate additives on the kinetics of the oxygen evolution reaction in valve-regulated lead/acid batteries

NASA Astrophysics Data System (ADS)

Vinod, M. P.; Vijayamohanan, K.; Joshi, S. N.

Effect of sodium silicate and phosphoric acid additives on the kinetics of oxygen evolution on PbO 2 electrodes in sulfuric acid has been studied in gelled and flooded electrolytes with relevance to valve-regulated lead/acid batteries. A comparison of the open-circuit potential versus time transients, with and without these additives, indicates that the additives suppress self-discharge of the electrodes. Tafel polarization studies also suggest that the addition of phosphoric acid attenuates the rate of oxygen evolution reaction. These findings have been supported with cyclic voltammetric data.

How Bacterial Pathogens Eat Host Lipids: Implications for the Development of Fatty Acid Synthesis Therapeutics*

PubMed Central

Yao, Jiangwei; Rock, Charles O.

2015-01-01

Bacterial type II fatty acid synthesis (FASII) is a target for the development of novel therapeutics. Bacteria incorporate extracellular fatty acids into membrane lipids, raising the question of whether pathogens use host fatty acids to bypass FASII and defeat FASII therapeutics. Some pathogens suppress FASII when exogenous fatty acids are present to bypass FASII therapeutics. FASII inhibition cannot be bypassed in many bacteria because essential fatty acids cannot be obtained from the host. FASII antibiotics may not be effective against all bacteria, but a broad spectrum of Gram-negative and -positive pathogens can be effectively treated with FASII inhibitors. PMID:25648887

The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

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

Xie, Fan; Li, Pengcheng; Gong, Jianhua

Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer)more » augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.« less

Involvement of the BLT2 receptor in the itch-associated scratching induced by 12-(S)-lipoxygenase products in ICR mice

PubMed Central

Kim, H J; Kim, D K; Kim, H; Koh, J Y; Kim, K M; Noh, M S; Lee, S; Kim, S; Park, S H; Kim, J J; Kim, S Y; Lee, C H

2008-01-01

Background and purpose: Recently, we reported that 12(S)-HPETE (12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid) induces scratching in ICR mice. We hypothesized that 12(S)-HPETE might act as an agonist of the low-affinity leukotriene B4 receptor BLT2. To confirm the involvement of the BLT2 receptor in 12(S)-HPETE-induced scratching, we studied the scratch response using the BLT2 receptor agonists compound A (4′-{[pentanoyl (phenyl) amino]methyl}-1,1′-biphenyl-2-carboxylic acid) and 12(S)-HETE (12(S)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid). Experimental approach: A video recording was used to determine whether the BLT2 receptor agonists caused itch-associated scratching in ICR mice. Selective antagonists and several chemicals were used. Key results: Both 12(S)-HETE and compound A dose dependently induced scratching in the ICR mice. The dose–response curve for compound A showed peaks at around 0.005–0.015 nmol per site. Compound A- and 12(S)-HETE-induced scratching was suppressed by capsaicin and naltrexon. We examined the suppressive effects of U75302 (6-[6-(3-hydroxy-1E,5Z-undecadienyl)-2-pyridinyl]-1,5-hexanediol, the BLT1 receptor antagonist) and LY255283 (1-[5-ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]-ethanone, the BLT2 receptor antagonist) on the BLT2 agonist-induced scratching. LY255283 suppressed compound A- and 12(S)-HETE-induced scratching, but U75302 did not. LY255283 required a higher dose to suppress the compound A-induced scratching than it did to suppress the 12(S)-HETE-induced scratching. One of the BLT2 receptor agonists, 12(R)-HETE (12(R)-hydroxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid), also induced scratching in the ICR mice. Conclusions and implications: Our present results corroborate the hypothesis that the BLT2 receptor is involved in 12(S)-lipoxygenase-product-induced scratching in ICR mice. We also confirmed that this animal model could be a valuable means of evaluating the effects of BLT2 receptor antagonists. PMID:18536755

Identification of ATP Citrate Lyase as a Positive Regulator of Glycolytic Function in Glioblastomas

PubMed Central

Beckner, Marie E.; Fellows-Mayle, Wendy; Zhang, Zhe; Agostino, Naomi R.; Kant, Jeffrey A.; Day, Billy W.; Pollack, Ian F.

2009-01-01

Glioblastomas, the most malignant type of glioma, are more glycolytic than normal brain tissue. Robust migration of glioblastoma cells has been previously demonstrated under glycolytic conditions and their pseudopodia contain increased glycolytic and decreased mitochondrial enzymes. Glycolysis is suppressed by metabolic acids, including citric acid which is excluded from mitochondria during hypoxia. We postulated that glioma cells maintain glycolysis by regulating metabolic acids, especially in their pseudopodia. The enzyme that breaks down cytosolic citric acid is ATP citrate lyase (ACLY). Our identification of increased ACLY in pseudopodia of U87 glioblastoma cells on 1D gels and immunoblots prompted investigation of ACLY gene expression in gliomas for survival data and correlation with expression of ENO1, that encodes enolase 1. Queries of the NIH’s REMBRANDT brain tumor database based on Affymetrix data indicated that decreased survival correlated with increased gene expression of ACLY in gliomas. Queries of gliomas and glioblastomas found an association of upregulated ACLY and ENO1 expression by chi square for all probe sets (reporters) combined and correlation for numbers of probe sets indicating shared upregulation of these genes. Real-time quantitative PCR confirmed correlation between ACLY and ENO1 in 21 glioblastomas (p < 0.001). Inhibition of ACLY with hydroxycitrate suppressed (p < 0.05) in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhanced the suppressive effects of a Met inhibitor on cell migration. In summary, gene expression data, proteomics and functional assays support ACLY as a positive regulator of glycolysis in glioblastomas. PMID:19795461

Cinnamic acid derivatives inhibit hepatitis C virus replication via the induction of oxidative stress.

PubMed

Amano, Ryota; Yamashita, Atsuya; Kasai, Hirotake; Hori, Tomoka; Miyasato, Sayoko; Saito, Setsu; Yokoe, Hiromasa; Takahashi, Kazunori; Tanaka, Tomohisa; Otoguro, Teruhime; Maekawa, Shinya; Enomoto, Nobuyuki; Tsubuki, Masayoshi; Moriishi, Kohji

2017-09-01

Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC 50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr 705 in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2. Compound 6 potently suppressed HCV replication, but it did not inhibit the JAK1/2-dependent phosphorylation of STAT3 Tyr 705  at the same concentration. Furthermore, a pan-JAK inhibitor tofacitinib potently impaired phosphorylation of STAT3 Tyr 705 , but it did not inhibit HCV replication in the replicon cells and HCV-infected cells at the same concentration, supporting the notion that the phosphorylated state of STAT3 Tyr 705 is not necessarily correlated with HCV replication. The production of reactive oxygen species (ROS) was induced by treatment with compound 6, whereas N-acetyl-cysteine restored HCV replication and impaired ROS production in the replicon cells treated with compound 6. These data suggest that compound 6 inhibits HCV replication via the induction of oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Antisense suppression of phospholipase D alpha retards abscisic acid- and ethylene-promoted senescence of postharvest Arabidopsis leaves.

PubMed Central

Fan, L; Zheng, S; Wang, X

1997-01-01

Membrane disruption has been proposed to be a key event in plant senescence, and phospholipase D (PLD; EC 3.1.4.4) has been thought to play an important role in membrane deterioration. We recently cloned and biochemically characterized three different PLDs from Arabidopsis. In this study, we investigated the role of the most prevalent phospholipid-hydrolyzing enzyme, PLD alpha, in membrane degradation and senescence in Arabidopsis. The expression of PLD alpha was suppressed by introducing a PLD alpha antisense cDNA fragment into Arabidopsis. When incubated with abscisic acid and ethylene, leaves detached from the PLD alpha-deficient transgenic plants showed a slower rate of senescence than did those from wild-type and transgenic control plants. The retardation of senescence was demonstrated by delayed leaf yellowing, lower ion leakage, greater photosynthetic activity, and higher content of chlorophyll and phospholipids in the PLD alpha antisense leaves than in those of the wild type. Treatment of detached leaves with abscisic acid and ethylene stimulated PLD alpha expression, as indicated by increases in PLD alpha mRNA, protein, and activity. In the absence of abscisic acid and ethylene, however, detached leaves from the PLD alpha-deficient and wild-type plants showed a similar rate of senescence. In addition, the suppression of PLD alpha did not alter natural plant growth and development. These data suggest that PLD alpha is an important mediator in phytohormone-promoted senescence in detached leaves but is not a direct promoter of natural senescence. The physiological relevance of these findings is discussed. PMID:9437863

Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

PubMed

Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

2017-07-01

The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

Plant, cell, and molecular mechanisms of abscisic-acid regulation of stomatal apertures. In vivo phosphorylation of phosphoenolpyruvate carboxylase in guard cells of Vicia faba L. is enhanced by fusicoccin and suppressed by abscisic acid

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

Du, Z.; Aghoram, K.; Outlaw, W.H. Jr.

Plants regulate water loss and CO{sub 2} gain by modulating the aperture sizes of stomata that penetrate the epidermis. Aperture size itself is increased by osmolyte accumulation and consequent turgor increase in the pair of guard cells that flank each stoma. Guard-cell phosphoenolpyruvate carboxylase, which catalyzes the regulated step leading to malate synthesis, is crucial for charge and pH maintenance during osmolyte accumulation. Regulation of this cytosolic enzyme by effectors is well documented, but additional regulation by posttranslational modification is predicted by the alteration of PEPC kinetics during stomatal opening. In this study, the authors have investigated whether this alterationmore » is associated with the phosphorylation status of this enzyme. Using sonicated epidermal peels (isolated guard cells) pre-loaded with {sub 32}PO{sub 4}, the authors induced stomatal opening and guard-cell malate accumulation by incubation with 5 {micro}M fusicoccin (FC). In corroboratory experiments, guard cells were incubated with 5 {micro}M fusicoccin (FC). In corroboratory experiments, guard cells were incubated with the FC antagonist, 10 {micro}M abscisic acid (ABA). The phosphorylation status of PEPC was assessed by immunoprecipitation, electrophoresis, immunoblotting, and autoradiography. PEPC was phosphorylated when stomata were stimulated to open, and phosphorylation was lessened by incubation with ABA.« less

Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1 alpha: implications for metabolic disease.

PubMed

Muoio, Deborah M; Koves, Timothy R

2007-10-01

Dyslipidemia and intramuscular accumulation of fatty acid metabolites are increasingly recognized as core features of obesity and type 2 diabetes. Emerging evidence suggests that normal physiological adaptations to a heavy lipid load depend on the coordinated actions of broad transcriptional regulators such as the peroxisome proliferator activated receptors (PPARs) and PPAR gamma coactivator 1 alpha (PGC1 alpha). The application of transcriptomics and targeted metabolic profiling tools based on mass spectrometry has led to our finding that lipid-induced insulin resistance is a condition in which upregulation of PPAR-targeted genes and high rates of beta-oxidation are not supported by a commensurate upregulation of tricarboxylic acid (TCA) cycle activity. In contrast, exercise training enhances mitochondrial performance, favoring tighter coupling between beta-oxidation and the TCA cycle, and concomitantly restores insulin sensitivity in animals fed a chronic high-fat diet. The exercise-activated transcriptional coactivator, PGC1 alpha, plays a key role in coordinating metabolic flux through these 2 intersecting metabolic pathways, and its suppression by overfeeding may contribute to diet-induced mitochondrial dysfunction. Our emerging model predicts that muscle insulin resistance arises from a mitochondrial disconnect between beta-oxidation and TCA cycle activity. Understanding of this "disconnect" and its molecular basis may lead to new therapeutic approaches to combatting metabolic disease.

Acid-Sensing Ion Channel Pharmacology, Past, Present, and Future ….

PubMed

Rash, Lachlan D

2017-01-01

pH is one of the most strictly controlled parameters in mammalian physiology. An extracellular pH of ~7.4 is crucial for normal physiological processes, and perturbations to this have profound effects on cell function. Acidic microenvironments occur in many physiological and pathological conditions, including inflammation, bone remodeling, ischemia, trauma, and intense synaptic activity. Cells exposed to these conditions respond in different ways, from tumor cells that thrive to neurons that are either suppressed or hyperactivated, often fatally. Acid-sensing ion channels (ASICs) are primary pH sensors in mammals and are expressed widely in neuronal and nonneuronal cells. There are six main subtypes of ASICs in rodents that can form homo- or heteromeric channels resulting in many potential combinations. ASICs are present and activated under all of the conditions mentioned earlier, suggesting that they play an important role in how cells respond to acidosis. Compared to many other ion channel families, ASICs were relatively recently discovered-1997-and there is a substantial lack of potent, subtype-selective ligands that can be used to elucidate their structural and functional properties. In this chapter I cover the history of ASIC channel pharmacology, which began before the proteins were even identified, and describe the current arsenal of tools available, their limitations, and take a glance into the future to predict from where new tools are likely to emerge. © 2017 Elsevier Inc. All rights reserved.

Dihydrosterculic acid from cottonseed oil suppresses desaturase activity and improves liver metabolomic profiles of high-fat-fed mice

USDA-ARS?s Scientific Manuscript database

Consuming a high polyunsaturated fatty acid (PUFA) diet has been shown to cause accumulation of PUFA in skeletal muscle. We have found that increasing the PUFA content in skeletal muscle of mice was associated with increased PPARd expression and activity and we sought to examine the effect of differ...

Immune activation and suppression by group B streptococcus in a murine model of urinary tract infection.

PubMed

Kline, Kimberly A; Schwartz, Drew J; Lewis, Warren G; Hultgren, Scott J; Lewis, Amanda L

2011-09-01

Group B streptococcus (GBS) is a common commensal of the gastrointestinal and vaginal mucosa and a leading cause of serious infections in newborns, the elderly, and immunocompromised populations. GBS also causes infections of the urinary tract. However, little is known about host responses to GBS urinary tract infection (UTI) or GBS virulence factors that participate in UTI. Here we describe a novel murine model of GBS UTI that may explain some features of GBS urinary tract association in the human host. We observed high titers and heightened histological signs of inflammation and leukocyte recruitment in the GBS-infected kidney. However, extensive inflammation and leukocyte recruitment were not observed in the bladder, suggesting that GBS may suppress bladder inflammation during cystitis. Acute GBS infection induced the localized expression of proinflammatory cytokines interleukin-1α (IL-1α), macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and IL-9, as well as IL-10, more commonly considered an anti-inflammatory cytokine. Using isogenic GBS strains with different capsule structures, we show that capsular sialic acid residues contribute to GBS urinary tract pathogenesis, while high levels of sialic acid O-acetylation attenuate GBS pathogenesis in the setting of UTI, particularly in direct competition experiments. In vitro studies demonstrated that GBS sialic acids participate in the suppression of murine polymorphonuclear leukocyte (PMN) bactericidal activities, in addition to reducing levels of IL-1α, tumor necrosis factor alpha, IL-1β, MIP-1α, and KC produced by PMNs. These studies define several basic molecular and cellular events characterizing GBS UTI in an animal model, showing that GBS participates simultaneously in the activation and suppression of host immune responses in the urinary tract.

Rodlike Supramolecular Nanoassemblies of Degradable Poly(Aspartic Acid) Derivatives and Hydroxyl-Rich Polycations for Effective Delivery of Versatile Tumor-Suppressive ncRNAs.

PubMed

Song, Hai-Qing; Pan, Wenting; Li, Rui-Quan; Yu, Bingran; Liu, Wenjuan; Yang, Ming; Xu, Fu-Jian

2018-03-01

The delivery of tumor-suppressive noncoding RNAs (ncRNAs) including short ncRNAs (i.e., miRNAs) and long ncRNAs (lncRNAs) is put forward to treat tumors. In this work, novel rodlike supramolecular nanoassemblies (CNC @CB[8] @ PGEA) of degradable poly(aspartic acid) (PAsp) derivatives-grafted cellulose nanocrystals (CNCs) and hydroxyl-rich polycations (ethanolamine-functionalized poly(glycidyl methacrylate), PGEA) are proposed via typical cucurbit[8]uril (CB[8])-based host-guest interactions for delivery of different ncRNAs to treat hepatocellular carcinoma (HCC). Spindly CNCs, one kind of natural polysaccharide nanoparticles, possess good biocompatibility and unique physico-chemical properties. PGEA with abundant hydroxyl groups is one promising gene carrier with low cytotoxicity. PAsp can benefit the disassembly and degradability of nanoassemblies within cells. CNC @ CB[8]@PGEA combines the different unique properties of CNC, PGEA, and PAsp. CNC @ CB[8] @ PGEA effectively complexes the expression constructs of miR-101 (plasmid pc3.0-miR-101) and lncRNA MEG3 (plasmid pc3.0-MEG3). CNC @ CB[8] @ PGEA produces much better transfection performances than PGEA-containing assembly units. In addition, the codelivery system of CNC @ CB[8] @ PGEA/(pc3.0-MEG3+pc3.0-miR-101) nanocomplexes demonstrates better efficacy in suppressing HCC than CNC @ CB[8] @ PGEA/pc3.0-MEG3 or CNC @ CB[8] @ PGEA/pc3.0-miR-101 nanocomplexes alone. Such rodlike supramolecular nanoassemblies will provide a promising means to produce efficient delivery vectors of versatile tumor-suppressive nucleic acids. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effect of cyclic phosphatidic acid on the proliferation and differentiation of mouse cerebellar granule precursor cells during cerebellar development.

PubMed

Konakazawa, Misa; Gotoh, Mari; Murakami-Murofushi, Kimiko; Hamano, Ayana; Miyamoto, Yasunori

2015-07-21

The proliferation and differentiation of cerebellar granule cell precursors (GCPs) are highly regulated spatiotemporally during development. We focused on cyclic phosphatidic acid (cPA) as a lipid mediator with a cyclic phosphate group as a regulatory factor of GCPs. While its structure is similar to that of lysophosphatidic acid (LPA), its function is very unique. cPA is known to be present in the cerebellum at high levels, but its function has not been fully elucidated. In this study, we examined the role of cPA on the proliferation and differentiation of GCPs. A cell cycle analysis of GCPs revealed that cPA reduced the number of phospho-histone H3 (Phh3)-positive cells and bromodeoxy uridine (BrdU)-incorporated cells and increased an index of the cell cycle exit. We next analyzed the effect of cPA on GCP differentiation using Tuj1 as a neuronal marker of final differentiation. The results show that cPA increased the number of Tuj1-positive cells. Further analysis of the proliferation of GCPs showed that cPA suppressed Sonic hedgehog (Shh)-dependent proliferation, but did not suppress insulin-like growth factor-1 (IGF-1)-dependent proliferation. P2Y5 (LPA6), an LPA receptor, is highly expressed in GCPs. The knockdown of P2Y5 suppressed the inhibitory effect of cPA on the proliferation of GCPs, suggesting that P2Y5 is a candidate receptor for cPA. Thus, cPA suppresses the Shh-dependent proliferation of GCPs and promotes the differentiation of GCPs through P2Y5. These results demonstrate that cPA plays a critical role in the development of GCPs. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Nitrate and Ammonium Induced Photosynthetic Suppression in N-Limited Selenastrum minutum.

PubMed

Elrifi, I R; Turpin, D H

1986-05-01

Nitrate-limited chemostat cultures of Selenastrum minutum Naeg. Collins (Chlorophyta) were used to determine the effects of nitrogen addition on photosynthesis, dark respiration, and dark carbon fixation. Addition of NO(3) (-) or NH(4) (+) induced a transient suppression of photosynthetic carbon fixation (70 and 40% respectively). Intracellular ribulose bisphosphate levels decreased during suppression and recovered in parallel with photosynthesis. Photosynthetic oxygen evolution was decreased by N-pulsing under saturating light (650 microeinsteins per square meter per second). Under subsaturating light intensities (<165 microeinsteins per square meter per second) NH(4) (+) addition resulted in O(2) consumption in the light which was alleviated by the presence of the tricarboxylic acid cycle inhibitor fluoroacetate. Addition of NO(3) (-) or NH(4) (+) resulted in a large stimulation of dark respiration (67 and 129%, respectively) and dark carbon fixation (360 and 2080%, respectively). The duration of N-induced perturbations was dependent on the concentration of added N. Inhibition of glutamine 2-oxoglutarate aminotransferase by azaserine alleviated all these effects. It is proposed that suppression of photosynthetic carbon fixation in response to N pulsing was the result of a competition for metabolites between the Calvin cycle and nitrogen assimilation. Carbon skeletons required for nitrogen assimilation would be derived from tricarboxylic acid cycle intermediates. To maintain tricarboxylic acid cycle activity triose phosphates would be exported from the chloroplast. This would decrease the rate of ribulose bisphosphate regeneration and consequently decrease net photosynthetic carbon accumulation. Stoichiometric calculations indicate that the Calvin cycle is one source of triose phosphates for N assimilation; however, during transient N resupply the major demand for triose phosphates must be met by starch or sucrose breakdown. The effects of N-pulsing on O(2) evolution, dark respiration, and dark C-fixation are shown to be consistent with this model.

Prediction errors in wildland fire situation analyses.

Treesearch

Geoffrey H. Donovan; Peter Noordijk

2005-01-01

Wildfires consume budgets and put the heat on fire managers to justify and control suppression costs. To determine the appropriate suppression strategy, land managers must conduct a wildland fire situation analysis (WFSA) when:A wildland fire is expected to or does escape initial attack,A wildland fire managed for resource benefits...

A Further Look at the Prediction of Weapons Effectiveness in Suppressive Fire

DTIC Science & Technology

1979-05-01

official Oeciertmirit Of the .,m’y politiOn. unless 11) designated by other authorized documents. . I tiny~ flggq rr- SECURITY CLASSIFICAT ION OF THIS PAGE...presents the results of an investigation originally designed to determine what aspects of the auditory signatures of passing projectiles are perceived as...suppression is based on a future risk, while reactive suppression is based on a current risk. Nay-or 2 0 implies that weapons designers need more

Reciprocal inhibition between miR-26a and NF-κB regulates obesity-related chronic inflammation in chondrocytes.

PubMed

Xie, Qingyun; Wei, Meng; Kang, Xia; Liu, Da; Quan, Yi; Pan, Xianming; Liu, Xiling; Liao, Dongfa; Liu, Jinbiao; Zhang, Bo

2015-04-25

Obesity is causally linked to osteoarthritis (OA), with the mechanism being not fully elucidated. miRNAs (miRs) are pivotal regulators of various diseases in multiple tissues, including inflammation in the chondrocytes. In the present study, we for the first time identified the expression of miR-26a in mouse chondrocytes. Decreased level of miR-26a was correlated to increased chronic inflammation in the chondrocytes and circulation in obese mouse model. Mechanistically, we demonstrated that miR-26a attenuated saturated free fatty acid-induced activation of NF-κB (p65) and production of proinflammatory cytokines in chondrocytes. Meanwhile, NF-κB (p65) also suppressed miR-26a production by directly binding to a predicted NF-κB binding element in the promoter region of miR-26a. Finally, we observed a negative correlation between NF-κB and miR-26a in human patients with osteoarthritis. Thus, we identified a reciprocal inhibition between miR-26a and NF-κB downstream of non-esterified fatty acid (NEFA) signalling in obesity-related chondrocytes. Our findings provide a potential mechanism linking obesity to cartilage inflammation. © 2015 Authors.

Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy

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

Feder, J.N.; Jan, L.Y.; Jan, Y.N.

The Drosophila hairy gene encodes a basic helix- loop-helix protein that functions in at least two steps during Drosophila development: (1) during embryogenesis, when it partakes in the establishment of segments, and (2) during the larval stage, when it functions negatively in determining the pattern of sensory bristles on the adult fly. In the rat, a structurally homologous gene (RHL) behaves as an immediate-early gene in its response to growth factors and can, like that in Drosophila, suppress neuronal differentiation events. Here, the authors report the genomic cloning of the human hairy gene homolog (HRY). The coding region of themore » gene is contained within four exons. The predicted amino acid sequence reveals only four amino acid differences between the human and rat genes. Analysis of the DNA sequence 5[prime] to the coding region reveals a putatitve untranslated exon. To increase the value of the HRY gene as a genetic marker and to assess its potential involvement in genetic disorders, they sublocalized the locus to chromosome 3q28-q29 by fluorescence in situ hybridization. 34 refs., 4 figs., 1 tab.« less

Ischaemic memory imaging using metabolic radiopharmaceuticals: overview of clinical settings and ongoing investigations.

PubMed

Yoshinaga, Keiichiro; Naya, Masanao; Shiga, Tohru; Suzuki, Eriko; Tamaki, Nagara

2014-02-01

"Ischaemic memory" is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). β-Methyl-p-[(123)I]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of (123)I-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with (18)F-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations.

Suppression of fat deposition in broiler chickens by (-)-hydroxycitric acid supplementation: A proteomics perspective

PubMed Central

Peng, Mengling; Han, Jing; Li, Longlong; Ma, Haitian

2016-01-01

(-)-Hydroxycitric acid (HCA) suppresses fatty acid synthesis in animals, but its biochemical mechanism in poultry is unclear. This study identified the key proteins associated with fat metabolism and elucidated the biochemical mechanism of (-)-HCA in broiler chickens. Four groups (n = 30 each) received a diet supplemented with 0, 1000, 2000 or 3000 mg/kg (-)-HCA for 4 weeks. Of the differentially expressed liver proteins, 40 and 26 were identified in the mitochondrial and cytoplasm respectively. Pyruvate dehydrogenase E1 components (PDHA1 and PDHB), dihydrolipoyl dehydrogenase (DLD), aconitase (ACO2), a-ketoglutarate dehydrogenase complex (DLST), enoyl-CoA hydratase (ECHS1) and phosphoglycerate kinase (PGK) were upregulated, while NADP-dependent malic enzyme (ME1) was downregulated. Biological network analysis showed that the identified proteins were involved in glycometabolism and lipid metabolism, whereas PDHA1, PDHB, ECHS1, and ME1 were identified in the canonical pathway by Ingenuity Pathway Analysis. The data indicated that (-)-HCA inhibited fatty acid synthesis by reducing the acetyl-CoA supply, via promotion of the tricarboxylic acid cycle (upregulation of PDHA1, PDHB, ACO2, and DLST expression) and inhibition of ME1 expression. Moreover, (-)-HCA promoted fatty acid beta-oxidation by upregulating ECHS1 expression. These results reflect a biochemically relevant mechanism of fat reduction by (-)-HCA in broiler chickens. PMID:27586962

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux.

PubMed

Krill, Joseph T; Naik, Rishi D; Higginbotham, Tina; Slaughter, James C; Holzman, Michael D; Francis, David O; Garrett, C Gaelyn; Vaezi, Michael F

2017-05-01

The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow-up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52-77 mo). The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31-4.17) and poor preoperative symptom response to acid-suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05-7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P < .01). The rate of symptom recurrence was lowest among patients with primary typical reflux symptoms who had a partial or full symptom response to AST (P < .01). The severity of acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with extraesophageal symptoms of GERD than in patients with typical GERD. Response to AST before surgery was associated with ARS effectiveness in patients with extraesophageal reflux symptoms. Caution should be exercised when advocating ARS for patients with extraesophageal symptoms that do not respond to AST. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Reliving emotional personal memories: affective biases linked to personality and sex-related differences.

PubMed

Denkova, Ekaterina; Dolcos, Sanda; Dolcos, Florin

2012-06-01

Although available evidence suggests that the emotional valence and recollective properties of autobiographical memories (AMs) may be influenced by personality- and sex-related differences, overall these relationships remain poorly understood. The present study investigated these issues by comparing the effect of general personality traits (extraversion and neuroticism) and specific traits linked to emotion regulation (ER) strategies (reappraisal and suppression) on the retrieval of emotional AMs and on the associated postretrieval emotional states, in men and women. First, extraversion predicted recollection of positive AMs in both men and women, whereas neuroticism predicted the proportion of negative AMs in men and the frequency of rehearsing negative AMs in women. Second, reappraisal predicted positive AMs in men, and suppression predicted negative AMs in women. Third, while reliving of positive memories had an overall indirect effect on postretrieval positive mood through extraversion, reliving of negative AMs had a direct effect on postretrieval negative mood, which was linked to inefficient engagement of suppression in women. Our findings suggest that personality traits associated with positive affect predict recollection of positive AMs and maintenance of a positive mood, whereas personality traits associated with negative affect, along with differential engagement of habitual ER strategies in men and women, predict sex-related differences in the recollection and experiencing of negative AMs. These findings provide insight into the factors that influence affective biases in reliving AMs, and into their possible link to sex-related differences in the susceptibility to affective disorders.

Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine

PubMed Central

Zylka, Mark J.; Sowa, Nathaniel A.; Taylor-Blake, Bonnie; Twomey, Margaret A.; Herrala, Annakaisa; Voikar, Vootele; Vihko, Pirkko

2008-01-01

SUMMARY Thiamine monophosphatase (TMPase, also known as Fluoride-Resistant Acid Phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of Prostatic Acid Phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent anti-nociceptive, anti-hyperalgesic and anti-allodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5’-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A1-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain. PMID:18940592

Response to glucose and lipid infusions in sepsis: a kinetic analysis

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

Shaw, J.H.; Wolfe, R.R.

The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U-/sup 14/C-glucose and 1,2, /sup 13/C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of themore » control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model.« less

Plantago lanceolata L. leaves prevent obesity in C57BL/6 J mice fed a high-fat diet.

PubMed

Yoshida, Taiji; Rikimaru, Kazuhiro; Sakai, Miho; Nishibe, Sansei; Fujikawa, Takahiko; Tamura, Yoshifumi

2013-01-01

The highly abundant and widely dispersed plant Plantago lanceolata L. (narrow leaf or English plantain) has been used for culinary and medicinal purposes since ancient times. Here, we investigated the anti-obesity effects of P. lanceolata leaf powder (shortly PL) when fed to male C57BL/6 J mice. Addition of PL to a high-fat diet did not affect food intake but significantly reduced food efficiency, suppressed body weight gain and visceral fat accumulation, and reduced serum free-fatty acid and glucose levels. PL-fed mice exhibited marked increases in HSL, Adrd3 and Cpt2 mRNA levels, and significant decreases in Fas transcripts in epididymal white adipose tissue (WAT). These findings suggest that dietary PL exerts anti-obesity effects by stimulating metabolism throughout visceral fat tissue by activating lipolysis, accelerating fatty acid β-oxidation and suppressing fatty acid synthase in WAT. To our knowledge, this is the first demonstration of anti-obesity substances derived from a Plantago species.

Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes.

PubMed

Kikugawa, Masaki; Ida, Tomoaki; Ihara, Hideshi; Sakamoto, Tatsuji

2017-08-01

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

Effects of abscisic acid and nitric oxide on trap formation and trapping of nematodes by the fungus Drechslerella stenobrocha AS6.1.

PubMed

Xu, Ling-Ling; Lai, Yi-Ling; Wang, Lin; Liu, Xing-Zhong

2011-02-01

The in vitro effects of abscisic acid (ABA) and nitric oxide (NO) on the nematode-trapping fungus Drechslerella stenobrocha AS6.1 were examined. The average number of traps (constricting rings) per colony and the percentage of nematodes (Caenorhabditis elegans) trapped were greatly increased by addition of ABA but greatly suppressed by addition of sodium nitroprusside (SNP, an NO donor) to corn meal agar. The suppressive effect of SNP was not negated by addition of an NO synthase competitive inhibitor (l-naphthylacetic acid, L-NNA) or an NO-specific scavenger [2-(4-carboxyphenyl)-4,4, 5,5-tetramethylimidazoline-1-oxyl-3-oxide, cPTIO]. When added without SNP, however, L-NNA and cPTIO caused moderate increases in trap number and trapping. The results indicate that the trap formation and nematode-trapping ability of D. stenobrocha were enhanced by ABA but decreased by exogenous NO. Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

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

Danno, Hirosuke; Ishii, Kiyo-aki; Nakagawa, Yoshimi

To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPAR{alpha} agonist and repressed by PPAR{alpha} antagonist. Luciferasemore » reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPAR{alpha}. Deletion studies identified the PPRE for PPAR{alpha} activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPAR{alpha} directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPAR{alpha} suggest that CREBH is involved in nutritional regulation.« less

Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date

PubMed Central

Sugano, Kentaro

2018-01-01

Potassium-competitive acid blocker (P-CAB) is a class of drug that competitively blocks the potassium-binding site of H+, K+-adenosine triphosphate (ATP)ase. Although the history of this class of drugs started over 30 years ago, clinical use of two P-CABs, revaprazan and vonoprazan, were only recently approved in Korea and Japan, respectively. Among them, vonoprazan has several advantages over conventional proton-pump inhibitors (PPIs), including rapid onset of action, long duration of acid suppression, fewer interindividual variations in terms of acid suppression, and minimum dietary influence on its action. These advantages of vonoprazan have been proved in clinical trials conducted for license approvals for several acid-related diseases. In this review article, current evidence of vonoprazan in the management of gastroesophageal reflux disease (GERD) will be summarized. Since the clinical trial data, as well as postmarketed clinical data, have consistently demonstrated superiority of vonoprazan over conventional PPIs in terms of achieving healing of mucosal breaks and maintaining the healing, it may provide an excellent, if not complete, option for fulfilling some of the unmet needs for current GERD therapy. The safety problem of vonoprazan is also discussed, as more pronounced hypergastrinemia inevitably ensues with its use. PMID:29383028

Ursolic acid and oleanolic acid suppress preneoplastic lesions induced by 1,2-dimethylhydrazine in rat colon.

PubMed

Furtado, Ricardo A; Rodrigues, Erlon P; Araújo, Felipe R R; Oliveira, Wendel L; Furtado, Michelle A; Castro, Márcio B; Cunha, Wilson R; Tavares, Denise C

2008-06-01

Ursolic acid (UA) and oleanolic acid (OA) are pentacyclic triterpenoid compounds found in plants used in the human diet and in medicinal herbs, in the form of aglycones or as the free acid. These compounds are known for their hepatoprotective, anti-inflammatory, antimicrobial, hypoglycemic, antimutagenic, antioxidant, and antifertility activities. In the present study, we evaluated the effects of UA and OA on the formation of 1,2-dimethyl-hydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon of the male Wistar rat. The animals received subcutaneous (sc) injections of DMH (40 mg/kg body weight) twice a week for two weeks to induce ACF. UA, OA and a mixture of UA and OA were administered to the rats five times a week for four weeks by gavage at doses of 25 mg/kg body weight/day each, during and after DMH treatment. All animals were sacrificed in week 5 for the evaluation of ACF. The results showed a significant reduction in the frequency of ACF in the group treated with the triterpenoid compounds plus DMH when compared to those treated with DMH alone, suggesting that UA and OA suppress the formation of ACF and have a protective effect against colon carcinogenesis.

Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.

PubMed

Ito, Kentaro; Bahry, Mohammad A; Hui, Yang; Furuse, Mitsuhiro; Chowdhury, Vishwajit S

2015-09-01

Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake. Copyright © 2015. Published by Elsevier Inc.

Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

PubMed Central

Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

2016-01-01

Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

Clinical Trial: High-Dose Acid Suppression for Chronic Cough: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Shaheen, Nicholas J.; Crockett, Seth D.; Bright, Stephanie D.; Madanick, Ryan D.; Buckmire, Robert; Couch, Marion; Dellon, Evan S.; Galanko, Joseph A.; Sharpless, Ginny; Morgan, Douglas R.; Spacek, Melissa B.; Heidt-Davis, Paris; Henke, David

2011-01-01

Summary Background Cough may be a manifestation of gastro-esophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. Aim To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were non-smokers without history of asthma, with chronic cough for > 8 weeks. All subjects underwent a baseline 24 hr pH/impedance study, methacholine challenge test (MCT), and laryngoscopy. Subjects were randomized to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores, and change in laryngeal findings. Results 40 subjects were randomized (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8, vs. 5.9 in placebo, p = 0.3), or Fisman Cough Severity/Frequency scores. The proportion of patients who improved by >1 standard deviation on the CQLQ was 27.8% (5/18) and 31.8% (7/22) in the placebo and PPI groups respectively. Conclusions In subjects with chronic cough and rare or no heartburn, high-dose PPI did not improve cough-related quality of life or symptoms in this randomized controlled trial. PMID:21083673

Disruption of the mitochondria-associated ER membrane (MAM) plays a central role in palmitic acid-induced insulin resistance.

PubMed

Shinjo, Satoko; Jiang, Shuying; Nameta, Masaaki; Suzuki, Tomohiro; Kanai, Mai; Nomura, Yuta; Goda, Nobuhito

2017-10-01

The mitochondria-associated ER membrane (MAM) is a specialized subdomain of ER that physically connects with mitochondria. Although disruption of inter-organellar crosstalk via the MAM impairs cellular homeostasis, its pathological significance in insulin resistance in type 2 diabetes mellitus remains unclear. Here, we reveal the importance of reduced MAM formation in the induction of fatty acid-evoked insulin resistance in hepatocytes. Palmitic acid (PA) repressed insulin-stimulated Akt phosphorylation in HepG2 cells within 12h. Treatment with an inhibitor of the ER stress response failed to restore PA-mediated suppression of Akt activation. Mitochondrial reactive oxygen species (ROS) production did not increase in PA-treated cells. Even short-term exposure (3h) to PA reduced the calcium flux from ER to mitochondria, followed by a significant decrease in MAM contact area, suggesting that PA suppressed the functional interaction between ER and mitochondria. Forced expression of mitofusin-2, a critical component of the MAM, partially restored MAM contact area and ameliorated the PA-elicited suppression of insulin sensitivity with Ser473 phosphorylation of Akt selectively improved. These results suggest that loss of proximity between ER and mitochondria, but not perturbation of homeostasis in the two organelles individually, plays crucial roles in PA-evoked Akt inactivation in hepatic insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp.

PubMed

Leib, Michael S; Duncan, Robert B; Ward, Daniel L

2007-01-01

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites

PubMed Central

Ahn, Jiyun; Chung, Woo-Jae; Jang, Young Jin; Seong, Ki-Seung; Moon, Jae-Hak; Ha, Tae Youl; Jung, Chang Hwa

2015-01-01

Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis. PMID:26317351

Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites.

PubMed

Kim, Yang-Ji; Lee, Da-Hye; Ahn, Jiyun; Chung, Woo-Jae; Jang, Young Jin; Seong, Ki-Seung; Moon, Jae-Hak; Ha, Tae Youl; Jung, Chang Hwa

2015-01-01

Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis.

Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals.

PubMed

Li, Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

2007-09-19

Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH* signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH* signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]* radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions.

Deer Bone Oil Extract Suppresses Lipopolysaccharide-Induced Inflammatory Responses in RAW264.7 Cells.

PubMed

Choi, Hyeon-Son; Im, Suji; Park, Yooheon; Hong, Ki-Bae; Suh, Hyung Joo

2016-01-01

The aim of this study was to investigate the effect of deer bone oil extract (DBOE) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. DBOE was fractionated by liquid-liquid extraction to obtain two fractions: methanol fraction (DBO-M) and hexane fraction (DBO-H). TLC showed that DBO-M had relatively more hydrophilic lipid complexes, including unsaturated fatty acids, than DBOE and DBO-H. The relative compositions of tetradecenoyl carnitine, α-linoleic acid, and palmitoleic acid increased in the DBO-M fraction by 61, 38, and 32%, respectively, compared with DBOE. The concentration of sugar moieties was 3-fold higher in the DBO-M fraction than DBOE and DBO-H. DBO-M significantly decreased LPS-induced nitric oxide (NO) production in RAW264.7 cells in a dose-dependent manner. This DBO-M-mediated decrease in NO production was due to downregulation of mRNA and protein levels of inducible nitric oxide synthase (iNOS). In addition, mRNA expression of pro-inflammatory mediators, such as cyclooxygenase (COX-2), interleukin (IL)-1β, and IL-12β, was suppressed by DBO-M. Our data showed that DBO-M, which has relatively higher sugar content than DBOE and DBO-H, could play an important role in suppressing inflammatory responses by controlling pro-inflammatory cytokines and mediators.

Genome-scale model guided design of Propionibacterium for enhanced propionic acid production.

PubMed

Navone, Laura; McCubbin, Tim; Gonzalez-Garcia, Ricardo A; Nielsen, Lars K; Marcellin, Esteban

2018-06-01

Production of propionic acid by fermentation of propionibacteria has gained increasing attention in the past few years. However, biomanufacturing of propionic acid cannot compete with the current oxo-petrochemical synthesis process due to its well-established infrastructure, low oil prices and the high downstream purification costs of microbial production. Strain improvement to increase propionic acid yield is the best alternative to reduce downstream purification costs. The recent generation of genome-scale models for a number of Propionibacterium species facilitates the rational design of metabolic engineering strategies and provides a new opportunity to explore the metabolic potential of the Wood-Werkman cycle. Previous strategies for strain improvement have individually targeted acid tolerance, rate of propionate production or minimisation of by-products. Here we used the P. freudenreichii subsp . shermanii and the pan- Propionibacterium genome-scale metabolic models (GEMs) to simultaneously target these combined issues. This was achieved by focussing on strategies which yield higher energies and directly suppress acetate formation. Using P. freudenreichii subsp . shermanii , two strategies were assessed. The first tested the ability to manipulate the redox balance to favour propionate production by over-expressing the first two enzymes of the pentose-phosphate pathway (PPP), Zwf (glucose-6-phosphate 1-dehydrogenase) and Pgl (6-phosphogluconolactonase). Results showed a 4-fold increase in propionate to acetate ratio during the exponential growth phase. Secondly, the ability to enhance the energy yield from propionate production by over-expressing an ATP-dependent phosphoenolpyruvate carboxykinase (PEPCK) and sodium-pumping methylmalonyl-CoA decarboxylase (MMD) was tested, which extended the exponential growth phase. Together, these strategies demonstrate that in silico design strategies are predictive and can be used to reduce by-product formation in Propionibacterium . We also describe the benefit of carbon dioxide to propionibacteria growth, substrate conversion and propionate yield.

Factor structure and clinical correlates of the Food Thought Suppression Inventory within treatment seeking obese women with binge eating disorder

PubMed Central

Barnes, Rachel D.; Sawaoka, Takuya; White, Marney A.; Masheb, Robin M.; Grilo, Carlos M.

2013-01-01

Prior research on the relations among eating behaviors and thought suppression is limited to a measure of general thought suppression, the White Bear Suppression Inventory. To address this limitation, researchers recently validated the Food Thought Suppression Inventory (FTSI). Analyses using this measure suggest that food thought suppression is distinct from and is more predictive of eating disorder psychopathology than is general thought suppression. The FTSI, however, has not yet been validated in clinical samples. The purpose of the current study is to examine the factor structure and clinical correlates of the FTSI within treatment seeking obese women with binge eating disorder (BED; N = 128). Analyses revealed a valid and reliable one-factor measure of food thought suppression that was related to higher levels of eating and general psychopathology. The findings provide evidence for the use of the FTSI with obese women with BED. Future research should examine the psychometric properties of the FTSI within larger and more diverse samples. PMID:23265399

Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

PubMed

Schindler, Andreas; Bartels, Andreas

2017-05-01

Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Coffee phenolic phytochemicals suppress colon cancer metastasis by targeting MEK and TOPK

PubMed Central

Kang, Nam Joo; Lee, Ki Won; Kim, Bo Hyun; Bode, Ann M.; Lee, Hyo-Jeong; Heo, Yong-Seok; Boardman, Lisa; Limburg, Paul; Lee, Hyong Joo; Dong, Zigang

2011-01-01

Epidemiological studies suggest that coffee consumption reduces the risk of cancers, including colon cancer, but the molecular mechanisms and target(s) underlying the chemopreventive effects of coffee and its active ingredient(s) remain unknown. Based on serving size or daily units, coffee contains larger amounts of phenolic phytochemicals than tea or red wine. Coffee or chlorogenic acid inhibited CT-26 colon cancer cell-induced lung metastasis by blocking phosphorylation of ERKs. Coffee or caffeic acid (CaA) strongly suppressed mitogen-activated MEK1 and TOPK activities and bound directly to either MEK1 or TOPK in an ATP-noncompetitive manner. Coffee or CaA, but not caffeine, inhibited ERKs phosphorylation, AP-1 and NF-κB transactivation and subsequently inhibited TPA-, EGF- and H-Ras-induced neoplastic transformation of JB6 P+ cells. Coffee consumption was also associated with a significant attenuation of ERKs phosphorylation in colon cancer patients. These results suggest that coffee and CaA target MEK1 and TOPK to suppress colon cancer metastasis and neoplastic cell transformation. PMID:21317303

Mapping Interactions between Myosin Relay and Converter Domains That Power Muscle Function*

PubMed Central

Kronert, William A.; Melkani, Girish C.; Melkani, Anju; Bernstein, Sanford I.

2014-01-01

Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile508, Asn509, and Asp511) in communicating with converter domain residue Arg759. We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle. PMID:24627474

Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

PubMed

Love, Ryan J; Jones, Kim S

2013-12-01

Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Measured and simulated performance of Compton-suppressed TIGRESS HPGe clover detectors

NASA Astrophysics Data System (ADS)

Schumaker, M. A.; Hackman, G.; Pearson, C. J.; Svensson, C. E.; Andreoiu, C.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Boston, A. J.; Chakrawarthy, R. S.; Churchman, R.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hyland, B.; Jones, B.; Maharaj, R.; Morton, A. C.; Phillips, A. A.; Sarazin, F.; Scraggs, H. C.; Smith, M. B.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.

2007-01-01

Tests of the performance of a 32-fold segmented HPGe clover detector coupled to a 20-fold segmented Compton-suppression shield, which form a prototype element of the TRIUMF-ISAC Gamma-Ray Escape-Suppressed Spectrometer (TIGRESS), have been made. Peak-to-total ratios and relative efficiencies have been measured for a variety of γ-ray energies. These measurements were used to validate a GEANT4 simulation of the TIGRESS detectors, which was then used to create a simulation of the full 12-detector array. Predictions of the expected performance of TIGRESS are presented. These predictions indicate that TIGRESS will be capable, for single 1 MeV γ rays, of absolute detection efficiencies of 17% and 9.4%, and peak-to-total ratios of 54% and 61% for the "high-efficiency" and "optimized peak-to-total" configurations of the array, respectively.

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Cantarovich, Marcelo; Lipman, Mark; Tchervenkov, Jean I; Paraskevas, Steven

2016-02-01

Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

PubMed

Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D

2017-04-01

Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Leucine-enriched essential amino acids attenuate inflammation in rat muscle and enhance muscle repair after eccentric contraction.

PubMed

Kato, Hiroyuki; Miura, Kyoko; Nakano, Sayako; Suzuki, Katsuya; Bannai, Makoto; Inoue, Yoshiko

2016-09-01

Eccentric exercise results in prolonged muscle damage that may lead to muscle dysfunction. Although inflammation is essential to recover from muscle damage, excessive inflammation may also induce secondary damage, and should thus be suppressed. In this study, we investigated the effect of leucine-enriched essential amino acids on muscle inflammation and recovery after eccentric contraction. These amino acids are known to stimulate muscle protein synthesis via mammalian target of rapamycin (mTOR), which, is also considered to alleviate inflammation. Five sets of 10 eccentric contractions were induced by electrical stimulation in the tibialis anterior muscle of male SpragueDawley rats (8-9 weeks old) under anesthesia. Animals received a 1 g/kg dose of a mixture containing 40 % leucine and 60 % other essential amino acids or distilled water once a day throughout the experiment. Muscle dysfunction was assessed based on isometric dorsiflexion torque, while inflammation was evaluated by histochemistry. Gene expression of inflammatory cytokines and myogenic regulatory factors was also measured. We found that leucine-enriched essential amino acids restored full muscle function within 14 days, at which point rats treated with distilled water had not fully recovered. Indeed, muscle function was stronger 3 days after eccentric contraction in rats treated with amino acids than in those treated with distilled water. The amino acid mix also alleviated expression of interleukin-6 and impeded infiltration of inflammatory cells into muscle, but did not suppress expression of myogenic regulatory factors. These results suggest that leucine-enriched amino acids accelerate recovery from muscle damage by preventing excessive inflammation.

Predictive Suppression of Cortical Excitability and Its Deficit in Schizophrenia

PubMed Central

Schroeder, Charles E.; Leitman, David I.

2013-01-01

Recent neuroscience advances suggest that when interacting with our environment, along with previous experience, we use contextual cues and regularities to form predictions that guide our perceptions and actions. The goal of such active “predictive sensing” is to selectively enhance the processing and representation of behaviorally relevant information in an efficient manner. Since a hallmark of schizophrenia is impaired information selection, we tested whether this deficiency stems from dysfunctional predictive sensing by measuring the degree to which neuronal activity predicts relevant events. In healthy subjects, we established that these mechanisms are engaged in an effort-dependent manner and that, based on a correspondence between human scalp and intracranial nonhuman primate recordings, their main role is a predictive suppression of excitability in task-irrelevant regions. In contrast, schizophrenia patients displayed a reduced alignment of neuronal activity to attended stimuli, which correlated with their behavioral performance deficits and clinical symptoms. These results support the relevance of predictive sensing for normal and aberrant brain function, and highlight the importance of neuronal mechanisms that mold internal ongoing neuronal activity to model key features of the external environment. PMID:23843536

Does adolescent alcohol and marijuana use predict suppressed growth in psychosocial maturity among male juvenile offenders?

PubMed

Chassin, Laurie; Dmitrieva, Julia; Modecki, Kathryn; Steinberg, Laurence; Cauffman, Elizabeth; Piquero, Alex R; Knight, George P; Losoya, Sandra H

2010-03-01

Multiple theories suggest mechanisms by which the use of alcohol and drugs during adolescence could dampen growth in psychosocial maturity. However, scant empirical evidence exists to support this proposition. The current study tested whether alcohol and marijuana use predicted suppressed growth in psychosocial maturity among a sample of male serious juvenile offenders (n = 1,170) who were followed from ages 15 to 21 years. Alcohol and marijuana use prospectively predicted lower maturity 6 months later. Moreover, boys with the greatest increases in marijuana use showed the smallest increases in psychosocial maturity. Finally, heterogeneity in the form of age-related alcohol and marijuana trajectories was related to growth in maturity, such that only boys who decreased their alcohol and marijuana use significantly increased in psychosocial maturity. Taken together, these findings suggest that patterns of elevated alcohol and marijuana use in adolescence may suppress age-typical growth in psychosocial maturity from adolescence to young adulthood, but that effects are not necessarily permanent, because decreasing use is associated with increases in maturity.

Predictors of expressive writing content and posttraumatic stress following a mass shooting.

PubMed

Reddy, Madhavi K; Seligowski, Antonia V; Rabenhorst, Mandy M; Orcutt, Holly K

2015-05-01

This study examined relations among experiential avoidance, state dissociation during writing, cognitive-emotional processing, and posttraumatic stress in the context of an expressive writing task among 58 undergraduate females who were students at a large midwestern university that had recently experienced a mass shooting. Experiential avoidance significantly predicted reported suppression during the writing task. Additionally, posttraumatic stress symptoms (PTSS) at the time of the writing task were significantly associated with state dissociation, suppression, and the use of positive emotion words during the writing. Finally, at the zero-order level, prospective PTSS were associated with state dissociation and suppression during the earlier writing task. However, in a full regression model, only experiential avoidance and PTSS at the time of the writing task significantly predicted prospective PTSS. Supplemental analyses suggest processes may operate differently across levels of exposure. Findings from the present study provide further support for the role of experiential avoidance, state dissociation during writing, and cognitive-emotional processing in predicting PTSS. Additionally, experiential avoidance may play an important role in how individuals use cognitive-emotional processing to narrate a traumatic event. (c) 2015 APA, all rights reserved).

Two Anatomically and Computationally Distinct Learning Signals Predict Changes to Stimulus-Outcome Associations in Hippocampus.

PubMed

Boorman, Erie D; Rajendran, Vani G; O'Reilly, Jill X; Behrens, Tim E

2016-03-16

Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in lateral orbitofrontal cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Dose-dependent effects of β-phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) on animal behavior.

PubMed

Tyurenkov, I N; Bagmetova, V V; Chernyshova, Yu V; Merkushenkova, O V

2014-12-01

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutam) in doses of 13-650 mg/kg suppressed depressive behavior of animals in the Porsolt test (i.e. produced antidepressant properties), reduced anxiety in the open-field, elevated plus maze, and Vogel conflict tests (i.e. produced anxiolytic effects). RGPU-135 in doses of 26-130 mg/kg exhibited more pronounced antidepressant action and in doses of 26 and 52 mg/kg had more pronounced anxiolytic effects. RGPU-135 in doses of 13-78 mg/kg increased locomotor and exploratory activity of animals in the open-field test. Activating effects of this agent decreased with increasing the dose. RGPU-135 in the subtoxic dose (650 mg/kg) suppressed locomotor activity of animals (produced sedative effect).

Activity in early visual areas predicts interindividual differences in binocular rivalry dynamics

PubMed Central

Yamashiro, Hiroyuki; Mano, Hiroaki; Umeda, Masahiro; Higuchi, Toshihiro; Saiki, Jun

2013-01-01

When dissimilar images are presented to the two eyes, binocular rivalry (BR) occurs, and perception alternates spontaneously between the images. Although neural correlates of the oscillating perception during BR have been found in multiple sites along the visual pathway, the source of BR dynamics is unclear. Psychophysical and modeling studies suggest that both low- and high-level cortical processes underlie BR dynamics. Previous neuroimaging studies have demonstrated the involvement of high-level regions by showing that frontal and parietal cortices responded time locked to spontaneous perceptual alternation in BR. However, a potential contribution of early visual areas to BR dynamics has been overlooked, because these areas also responded to the physical stimulus alternation mimicking BR. In the present study, instead of focusing on activity during perceptual switches, we highlighted brain activity during suppression periods to investigate a potential link between activity in human early visual areas and BR dynamics. We used a strong interocular suppression paradigm called continuous flash suppression to suppress and fluctuate the visibility of a probe stimulus and measured retinotopic responses to the onset of the invisible probe using functional MRI. There were ∼130-fold differences in the median suppression durations across 12 subjects. The individual differences in suppression durations could be predicted by the amplitudes of the retinotopic activity in extrastriate visual areas (V3 and V4v) evoked by the invisible probe. Weaker responses were associated with longer suppression durations. These results demonstrate that retinotopic representations in early visual areas play a role in the dynamics of perceptual alternations during BR. PMID:24353304

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

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

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulatedmore » with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic acid inhibited RANKL-induced osteoclastogenesis in bone marrow macrophages. • Betulinic acid decreased bone resorption by suppressing osteoclast activity. • Orally administered betulinic acid inhibited cancer-associated bone diseases in mice.« less

Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

PubMed

Akashi, Iwao; Kagami, Keisuke; Hirano, Toshihiko; Oka, Kitaro

2009-04-01

The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated. Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels. Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats. The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.

Effects of feeding lauric acid on ruminal protozoa numbers, fermentation, and digestion and on milk production in dairy cows

USDA-ARS?s Scientific Manuscript database

The objectives of this study were: (1) to determine the level of lauric acid (LA) addition to the diet necessary to effectively suppress ruminal protozoa (RP) to the extent observed when a single dose was given directly into the rumen; (2) to assess its effects on production and ruminal metabolism; ...

Ilaprazole for the treatment of gastro-esophageal reflux.

PubMed

Savarino, Edoardo; Ottonello, Andrea; Martinucci, Irene; Dulbecco, Pietro; Savarino, Vincenzo

2016-10-01

Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients. The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD. Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.

Nutrient-sensing nuclear receptors PPARα and FXR control liver energy balance.

PubMed

Preidis, Geoffrey A; Kim, Kang Ho; Moore, David D

2017-04-03

The nuclear receptors PPARα (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the fasted and fed state, respectively. PPARα activation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear receptors also regulate numerous other metabolic pathways relevant to liver energy balance. Here we review evidence that they function coordinately to control key nutrient pathways, including fatty acid oxidation and gluconeogenesis in the fasted state and lipogenesis and glycolysis in the fed state. We have also recently reported that these receptors have mutually antagonistic impacts on autophagy, which is induced by PPARα but suppressed by FXR. Secretion of multiple blood proteins is a major drain on liver energy and nutrient resources, and we present preliminary evidence that the liver secretome may be directly suppressed by PPARα, but induced by FXR. Finally, previous studies demonstrated a striking deficiency in bile acid levels in malnourished mice that is consistent with results in malnourished children. We present evidence that hepatic targets of PPARα and FXR are dysregulated in chronic undernutrition. We conclude that PPARα and FXR function coordinately to integrate liver energy balance.

Various causes behind the desorption hysteresis of carboxylic acids on mudstones.

PubMed

Rasamimanana, S; Lefèvre, G; Dagnelie, R V H

2017-02-01

Adsorption desorption is a key factor for leaching, migration and (bio)degradation of organic pollutants in soils and sediments. Desorption hysteresis of apolar organic compounds is known to be correlated with adsorption/diffusion into soil organic matter. This work focuses on the desorption hysteresis of polar organic compounds on a natural mudstone sample. Acetic, citric and ortho-phthalic acids displayed adsorption-desorption hysteresis on Callovo-Oxfordian mudstone. The non-reversible behaviours resulted from three different mechanisms. Adsorption and desorption kinetics were evaluated using 14C- and 3H-labelled tracers and an isotopic exchange method. The solid-liquid distribution ratio of acetate decreased using a NaN 3 bactericide, indicating a rapid bacterial consumption compared with negligible adsorption. The desorption hysteresis of phthalate was apparent and suppressed by the equilibration of renewal pore water with mudstone. This confirms the significant and reversible adsorption of phthalate. Finally, persistent desorption hysteresis was evidenced for citrate. In this case, a third mechanism should be considered, such as the incorporation of citrate in the solid or a chemical perturbation, leading to strong desorption resilience. The results highlighted the different pathways that polar organic pollutants might encounter in a similar environment. Data on phthalic acid is useful to predict the retarded transport of phthalate esters and amines degradation products in sediments. The behaviour of citric acid is representative of polydentate chelating agents used in ore and remediation industries. The impact of irreversible adsorption on solid/solution partitioning and transport deserves further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicogenomic analysis of the hepatic effects of perfluorooctanoic acid on rare minnows (Gobiocypris rarus)

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

Wei Yanhong; Graduate School of the Chinese Academy of Sciences, Beijing, 100080; Liu Yang

2008-02-01

Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant that has been detected in a variety of terrestrial and aquatic organisms. To assess the effects of PFOA in fish and predict its potential mode of action, a toxicogenomic approach was applied to hepatic gene expression profile analysis in male and female rare minnows (Gobiocypris rarus) using a custom cDNA microarray containing 1773 unique genes. Rare minnows were treated with continuous flow-through exposure to PFOA at concentrations of 3, 10, and 30 mg/L for 28 days. Based on the observed histopathological changes, the livers from fish exposed to 10 mg/L PFOA weremore » selected for further hepatic gene expression analysis. While 124 and 171 genes were significantly altered by PFOA in males and females, respectively, of which 43 genes were commonly regulated in both sexes. The affected genes are involved in multiple biological processes, including lipid metabolism and transport, hormone action, immune responses, and mitochondrial functions. PFOA exposure significantly suppressed genes involved in fatty acid biosynthesis and transport but induced genes associated with intracellular trafficking of cholesterol. Alterations in expression of genes associated with mitochondrial fatty acid {beta}-oxidation were only observed in female rare minnows. In addition, PFOA inhibited genes responsible for thyroid hormone biosynthesis and significantly induced estrogen-responsive genes. These findings implicate PFOA in endocrine disruption. This work contributes not only to the elucidation of the potential mode of toxicity of PFOA to aquatic organisms but also to the use of toxicogenomic approaches to address issues in environmental toxicology.« less

Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia.

PubMed

Richter, W S; Fischer, S; Ernst, N; Munz, D L

2001-07-01

Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.

Nutritional support for adaptation to radiation-induced suppression of mucosal immunity in the intestine of the rat.

PubMed

Harari, Y; Grossie, V B; Castro, G A

1996-06-01

Appropriate enteral nutrition provided immediately after injury or trauma to the gastrointestinal tract may limit or reverse damage to the mucosal barrier. In this regard, diets containing amino acids, such as arginine and glutamine, or fish oil have been identified as beneficial. This report assesses the role of amino acids as "essential nutrients" in the repair of intestinal mucosa damaged by gamma radiation. Rats were used experimentally to test the hypothesis that the recovery of the immune responses in the intestinal mucosa, which are suppressed by radiation, can be improved by feeding an elemental amino acid diet, referred to hereafter as the diet, immediately after irradiation. The objective was to assess the impact of the diet on the expression of type I hypersensitivity or anaphylaxis in the jejunal mucosa. The local expression of this immunological response, which involves several radiosensitive cell types, was studied in rats immunized by oral infection with the nematode parasite, Trichinella spiralis. Rats that recover from infection become immunized and their small intestine undergoes anaphylaxis when subsequently challenged with parasite-derived antigen. This hypersensitivity response is expressed, in part, as Cl- secretion and can be observed in vitro or in vivo. When challenge is provided by a secondary inoculum of infective T. spiralis larvae, Cl- secretion is accompanied by fluid secretion and by the rapid expulsion of the parasite from the intestine. Immunized rats maintained on a stock diet and exposed to 7 Gy of total-abdominal irradiation from a cobalt-60 gamma-ray source failed to express antigen-induced Cl- secretion fully for up to 14 days postirradiation, and rejection of the parasite was suppressed for at least 30 days postirradiation. The suppression of immune responsiveness is associated with the disappearance of intestinal mucosal mast cells, which normally trigger the anaphylactic response. When rats are maintained on the diet after irradiation, the capacity to reject the parasite remains suppressed. However, the ability to express anaphylaxis-mediated Cl- secretion returns by 3 days postirradiation. The quick, diet-supported recovery of antigen-induced Cl- secretion occurs despite the continued absence of mast cells. Although the recovery of anaphylaxis-mediated responses suppressed by irradiation is only partial, our experimental results underscore the potential for enhancing the recovery process through nutritional support.

Multipolar Electrostatic Energy Prediction for all 20 Natural Amino Acids Using Kriging Machine Learning.

PubMed

Fletcher, Timothy L; Popelier, Paul L A

2016-06-14

A machine learning method called kriging is applied to the set of all 20 naturally occurring amino acids. Kriging models are built that predict electrostatic multipole moments for all topological atoms in any amino acid based on molecular geometry only. These models then predict molecular electrostatic interaction energies. On the basis of 200 unseen test geometries for each amino acid, no amino acid shows a mean prediction error above 5.3 kJ mol(-1), while the lowest error observed is 2.8 kJ mol(-1). The mean error across the entire set is only 4.2 kJ mol(-1) (or 1 kcal mol(-1)). Charged systems are created by protonating or deprotonating selected amino acids, and these show no significant deviation in prediction error over their neutral counterparts. Similarly, the proposed methodology can also handle amino acids with aromatic side chains, without the need for modification. Thus, we present a generic method capable of accurately capturing multipolar polarizable electrostatics in amino acids.

A nonaqueous potentiometric titration study of the dissociation of t-butyl methacrylate-methacrylic acid copolymers.

PubMed

Nakatani, Kiyoharu; Yamashita, Jun; Sekine, Tomomi; Toriumi, Minoru; Itani, Toshiro

2003-05-01

The dissociation of t-butyl methacrylate-methacrylic acid copolymers in dimethyl sulfoxide was analyzed by a nonaqueous potentiometric titration technique. The negative logarithm of the dissociation constant of the monomer unit of a methacrylic acid (MAA) monotonously increased with the increasing degree of dissociation corresponding to the titrant/MAA amount ratio, and was highly influenced by the copolymerization ratio. The results are discussed in terms of the suppression of the dissociation of MAA by a neighboring charged methacrylate anion unit.

Pressure Suppresses Serotonin Release by Guinea Pig Striatal Synaptosomes

DTIC Science & Technology

1988-01-01

neurological syndrome. Brit J Pharmacol 1982; 76:447-452. 5. Wardley-Smith B, Meldrum BS. Effect of excitatory amino acid antagonists on !he high pressure...Res 1974; 1:,-28. *14. IBichard AR, Little HIJ. Drugs that increase Y-aminobutyric acid tr.ansmission prm ict PF..atnst * I the high pressure...Effects of high pressure of heliox on the striatal 5-HIAA and ascorbic acid rates in the rat. Cent Etud Rech Bio-Physiol Rep 84-08. 1984:35. 7

Successful Initial Development of Styrene Substitutes and Suppressants for Vinyl Ester Resin Formulations

DTIC Science & Technology

2003-08-01

into a separatory funnel. Distilled water was added to remove the acid from the ether phase. The layers were allowed to separate, and the water layer...The reaction mixtures were removed from the heat 2 hr after the last acrylic acid aliquot was added. The acrylated oils were purified via ether... remove inhibitor and any unreacted acid , the reaction mixture was ether extracted (25). The mixture was dissolved in diethyl ether and poured into a

Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

PubMed

Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

1987-12-01

Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

Branched-chain amino acid (BCAA) supplementation enhances adaptability to exercise training of mice with a muscle-specific defect in the control of BCAA catabolism.

PubMed

Xu, Minjun; Kitaura, Yasuyuki; Shindo, Daichi; Shimomura, Yoshiharu

2018-03-01

Branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BDK) suppresses the branched-chain amino acid (BCAA) catabolism by inactivation of the BCKDH complex. The muscle-specific BDK-deficient (BDK-mKO) mice showed accelerated BCAA oxidation in muscle and decreased endurance capacity after training (Xu et al. PLoS One. 12 (2017) e0180989). We here report that BCAA supplementation overcompensated endurance capacity in BDK-mKO mice after training.

Palmitic acid suppresses apolipoprotein M gene expression via the pathway of PPAR{sub β/δ} in HepG2 cells

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

Luo, Guanghua; Shi, Yuanping; Zhang, Jun

Highlights: • Palmitic acid significantly inhibited APOM gene expression in HepG2 cells. • Palmitic acid could obviously increase PPARB/D mRNA levels in HepG2 cells. • PPAR{sub β/δ} antagonist, GSK3787, had no effect on APOM expression. • GSK3787 could reverse the palmitic acid-induced down-regulation of APOM expression. • Palmitic acid induced suppression of APOM expression is mediated via the PPAR{sub β/δ} pathway. - Abstract: It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important formore » further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPAR{sub β/δ}) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPAR{sub β/δ} pathway.« less

Reversible temperature-dependent differences in brown adipose tissue respiration during torpor in a mammalian hibernator.

PubMed

McFarlane, Sarah V; Mathers, Katherine E; Staples, James F

2017-03-01

Although seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal and interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage. As predicted, maximal ETS enzyme activities of isolated BAT mitochondria did not differ between torpor and IBE. In contrast to this pattern, respiration rates of mitochondria isolated from torpid individuals were suppressed by ~60% compared with rates from IBE individuals when measured at 37°C. At 10°C, however, mitochondrial respiration rates tended to be greater in torpor than IBE. As a result, the temperature sensitivity (Q 10 ) of mitochondrial respiration was significantly lower in torpor (~1.4) than IBE (~2.4), perhaps facilitating energy savings during entrance into torpor and thermogenesis at low body temperatures. Despite the observed differences in isolated mitochondria, norepinephrine-stimulated respiration rates of isolated BAT adipocytes did not differ between torpor and IBE, perhaps because the adipocyte isolation requires lengthy incubation at 37°C, potentially reversing any changes that occur in torpor. Such changes may include remodeling of BAT mitochondrial membrane phospholipids, which could change in situ enzyme activities and temperature sensitivities. Copyright © 2017 the American Physiological Society.

Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy

PubMed Central

Voora, Deepak; Ortel, Thomas L.; Lucas, Joseph E.; Chi, Jen-Tsan; Becker, Richard C.; Ginsburg, Geoffrey S.

2012-01-01

Objectives To develop an integrated metric of non COX-1 dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. Background NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a variety of NCDPF assays are available, no standard exists and their reproducibility is not established. Methods We administered 325mg/day aspirin to two cohorts of volunteers (HV1, n = 52, and HV2, n = 96) and diabetics (DM, n = 74) and measured NCDPF using epinephrine, collagen, and ADP aggregometry and PFA100 (collagen/epi) before (Pre), after one dose (Post), and after several weeks (Final). COX-1 activity was assessed with arachidonic acid aggregometry (AAA). The primary outcome of the study, the platelet function score (PFS), was derived from a principal components analysis of NCDPF measures. Results The PFS strongly correlated with each measure of NCDPF in each cohort. After two or four weeks of daily aspirin the Final PFS strongly correlated (r > 0.7, p<0.0001) and was higher (p < 0.01) than the Post PFS. The magnitude and direction of the change in PFS (Final - Post) in an individual subject was moderately inversely proportional to the Post PFS in HV1 (r = −0.45), HV2 (r = −0.54), DM (r = −0.68), p<0.0001 for all. AAA remained suppressed during aspirin therapy. Conclusions The PFS summarizes multiple measures of NCDPF. Despite suppression of COX-1 activity, NCDPF during aspirin therapy is predictably dynamic: those with heightened NCDPF continue to decline whereas those with low/normal NCDPF return to pre-aspirin levels over time. PMID:22294277

Possible mechanisms of dose-dependent cough suppressive effect of Althaea officinalis rhamnogalacturonan in guinea pigs test system.

PubMed

Sutovská, M; Nosálová, G; Sutovský, J; Franová, S; Prisenznáková, L; Capek, P

2009-07-01

The rhamnogalacturonan, isolated from the roots of medicinal plant Althaea officinalis L., showed various biological effects on the citric acid-induced cough reflex and reactivity of airways smooth muscle in vitro and in vivo conditions. It possessed dose-dependent cough suppression effect comparable with opioid agonist codeine. However, reactivity of the airways smooth muscle, measured in vitro as well as in vivo conditions was not significantly affected by rhamnogalacturonan and thus bronchodilatory activity did not participate in the cough suppression effect of polysaccharide tested. Moreover, the cough suppression effect of the polymer was not significantly modified by pretreatment of K(+)(ATP) ion channels with selective antagonist and therefore activation of this type of ion channels is not involved in the mechanism of rhamnogalacturonan cough suppressive ability. On the contrary, pretreatment of animals with selective 5-HT(2) receptors antagonist significantly decreased rhamnogalacturonan antitussive efficacy. From this point of view it seems that the cough suppression effect of the polymer is associated with the serotonergic 5-HT(2) receptor's function.

Valproic acid exposure sequentially activates Wnt and mTOR pathways in rats.

PubMed

Qin, Liyan; Dai, Xufang; Yin, Yunhou

2016-09-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, limited verbal communication and repetitive behaviors. Recent studies have demonstrated that Wnt signaling and mTOR signaling play important roles in the pathogenesis of ASD. However, the relationship of these two signaling pathways in ASD remains unclear. We assessed this question using the valproic acid (VPA) rat model of autism. Our results demonstrated that VPA exposure activated mTOR signaling and suppressed autophagy in the prefrontal cortex, hippocampus and cerebellum of autistic model rats, characterized by enhanced phospho-mTOR and phospho-S6 and decreased Beclin1, Atg5, Atg10, LC3-II and autophagosome formation. Rapamycin treatment suppressed the effect of VPA on mTOR signaling and ameliorated the autistic-like behaviors of rats in our autism model. The administration of VPA also activated Wnt signaling through up-regulating beta-catenin and phospho-GSK3beta. Suppression of the Wnt pathway by sulindac relieved autistic-like behaviors and attenuated VPA-induced mTOR signaling activation in autistic model rats. Our results demonstrate that VPA exposure sequentially activates Wnt signaling and mTOR signaling in rats. Suppression of the Wnt signaling pathway relieves autistic-like behaviors partially by deactivating the mTOR signaling pathway in VPA-exposed rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA

PubMed Central

Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

2015-01-01

Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 108 dm3 mol−1 s−1 and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10–1000 μmol dm−3) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. PMID:25212600

Jasmonic acid-mediated defense suppresses brassinosteroid-mediated susceptibility to Rice black streaked dwarf virus infection in rice.

PubMed

He, Yuqing; Zhang, Hehong; Sun, Zongtao; Li, Junmin; Hong, Gaojie; Zhu, Qisong; Zhou, Xuebiao; MacFarlane, Stuart; Yan, Fei; Chen, Jianping

2017-04-01

Plant hormones play a vital role in plant immune responses. However, in contrast to the relative wealth of information on hormone-mediated immunity in dicot plants, little information is available on monocot-virus defense systems. We used a high-throughput-sequencing approach to compare the global gene expression of Rice black-streaked dwarf virus (RBSDV)-infected rice plants with that of healthy plants. Exogenous hormone applications and transgenic rice were used to test RBSDV infectivity and pathogenicity. Our results revealed that the jasmonic acid (JA) pathway was induced while the brassinosteroid (BR) pathway was suppressed in infected plants. Foliar application of methyl jasmonate (MeJA) or brassinazole (BRZ) resulted in a significant reduction in RBSDV incidence, while epibrassinolide (BL) treatment increased RBSDV infection. Infection studies using coi1-13 and Go mutants demonstrated JA-mediated resistance and BR-mediated susceptibility to RBSDV infection. A mixture of MeJA and BL treatment resulted in a significant reduction in RBSDV infection compared with a single BL treatment. MeJA application efficiently suppressed the expression of BR pathway genes, and this inhibition depended on the JA coreceptor OsCOI1. Collectively, our results reveal that JA-mediated defense can suppress the BR-mediated susceptibility to RBSDV infection. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol

PubMed Central

Plevkova, J.; Kollarik, M.; Poliacek, I.; Brozmanova, M.; Surdenikova, L.; Tatar, M.; Mori, N.

2013-01-01

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (−)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose. PMID:23640596

Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis

PubMed Central

Cheyuo, Cletus; Jacob, Asha

2012-01-01

Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin-mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID:22068604

[Circadian rhythms of acid production and alkalization in the stomach of healthy subjects and duodenal ulcer patients].

PubMed

Kolesnikova, I Iu; Beliaeva, G S; Leint'eva, V A; Smirnova, A A

2008-01-01

We studied 24-h rhythms of acid production and alkalization in 30 patients with duodenal ulcer (DU) and 30 healthy subjects using upper endoscopic examination and computer intragastric pH-metry. Gastric acid production was higher in DU patients and was more intensive in the daytime than at night. Healthy subjects had low and monotonous acid production. In DU decompensation of alkalization in the antral stomach and suppression of duodenogastric reflux is total. In healthy subjects antrum alkalization is more evident and intensive at night due to, among other causes, duodenogastric reflux.

Effect of Interferon, Polyacrylic Acid, and Polymethacrylic Acid on Tail Lesions in Mice Infected with Vaccinia Virus

PubMed Central

De Clercq, E.; De Somer, P.

1968-01-01

Intravenous inoculation of mice with vaccinia virus produced characteristic lesions of the tail surface which were suppressed by intraperitoneal administration of interferon and polyacrylic acid (PAA). Polymethacrylic acid (PMAA) stimulated the formation of vaccinia virus lesions. For full activity, both interferon and PAA must be given prior to infection. PAA was still significantly effective at small dose levels (3 mg/kg) and achieved protection for at least 4 weeks. Protection increased with increasing molecular weight of the polymer. The mode of action of PAA is discussed. PMID:5676405

Novel application of proton pump inhibitor for the prevention of colitis-induced colorectal carcinogenesis beyond acid suppression.

PubMed

Kim, Yoon Jae; Lee, Jeong Sang; Hong, Kyung Sook; Chung, Jun Won; Kim, Ju Hyun; Hahm, Ki Baik

2010-08-01

Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid-reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of beta-catenin-accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. 2010 AACR.

TRANSPARENT TESTA GLABRA1 Regulates the Accumulation of Seed Storage Reserves in Arabidopsis1[OPEN

PubMed Central

Chen, Mingxun; Zhang, Bin; Li, Chengxiang; Kulaveerasingam, Harikrishna; Chew, Fook Tim; Yu, Hao

2015-01-01

Seed storage reserves mainly consist of starch, triacylglycerols, and storage proteins. They not only provide energy for seed germination and seedling establishment, but also supply essential dietary nutrients for human beings and animals. So far, the regulatory networks that govern the accumulation of seed storage reserves in plants are still largely unknown. Here, we show that TRANSPARENT TESTA GLABRA1 (TTG1), which encodes a WD40 repeat transcription factor involved in many aspects of plant development, plays an important role in mediating the accumulation of seed storage reserves in Arabidopsis (Arabidopsis thaliana). The dry weight of ttg1-1 embryos significantly increases compared with that of wild-type embryos, which is accompanied by an increase in the contents of starch, total protein, and fatty acids in ttg1-1 seeds. FUSCA3 (FUS3), a master regulator of seed maturation, binds directly to the TTG1 genomic region and suppresses TTG1 expression in developing seeds. TTG1 negatively regulates the accumulation of seed storage proteins partially through transcriptional repression of 2S3, a gene encoding a 2S albumin precursor. TTG1 also indirectly suppresses the expression of genes involved in either seed development or synthesis/modification of fatty acids in developing seeds. In addition, we demonstrate that the maternal allele of the TTG1 gene suppresses the accumulation of storage proteins and fatty acids in seeds. Our results suggest that TTG1 is a direct target of FUS3 in the framework of the regulatory hierarchy controlling seed filling and regulates the accumulation of seed storage proteins and fatty acids during the seed maturation process. PMID:26152712

TRANSPARENT TESTA GLABRA1 Regulates the Accumulation of Seed Storage Reserves in Arabidopsis.

PubMed

Chen, Mingxun; Zhang, Bin; Li, Chengxiang; Kulaveerasingam, Harikrishna; Chew, Fook Tim; Yu, Hao

2015-09-01

Seed storage reserves mainly consist of starch, triacylglycerols, and storage proteins. They not only provide energy for seed germination and seedling establishment, but also supply essential dietary nutrients for human beings and animals. So far, the regulatory networks that govern the accumulation of seed storage reserves in plants are still largely unknown. Here, we show that TRANSPARENT TESTA GLABRA1 (TTG1), which encodes a WD40 repeat transcription factor involved in many aspects of plant development, plays an important role in mediating the accumulation of seed storage reserves in Arabidopsis (Arabidopsis thaliana). The dry weight of ttg1-1 embryos significantly increases compared with that of wild-type embryos, which is accompanied by an increase in the contents of starch, total protein, and fatty acids in ttg1-1 seeds. FUSCA3 (FUS3), a master regulator of seed maturation, binds directly to the TTG1 genomic region and suppresses TTG1 expression in developing seeds. TTG1 negatively regulates the accumulation of seed storage proteins partially through transcriptional repression of 2S3, a gene encoding a 2S albumin precursor. TTG1 also indirectly suppresses the expression of genes involved in either seed development or synthesis/modification of fatty acids in developing seeds. In addition, we demonstrate that the maternal allele of the TTG1 gene suppresses the accumulation of storage proteins and fatty acids in seeds. Our results suggest that TTG1 is a direct target of FUS3 in the framework of the regulatory hierarchy controlling seed filling and regulates the accumulation of seed storage proteins and fatty acids during the seed maturation process. © 2015 American Society of Plant Biologists. All Rights Reserved.

Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression.

PubMed

Wang, Bin; Ding, Yanping; Zhao, Xiaozheng; Han, Xuexiang; Yang, Na; Zhang, Yinlong; Zhao, Ying; Zhao, Xiao; Taleb, Mohammad; Miao, Qing Robert; Nie, Guangjun

2018-08-01

Nogo-B receptor (NgBR) plays fundamental roles in regulating angiogenesis, vascular development, and the epithelial-mesenchymal transition (EMT) of cancer cells. However, the therapeutic effect of NgBR blockade on tumor vasculature and malignancy is unknown, investigations on which requires an adequate delivery system for small interfering RNA against NgBR (NgBR siRNA). Here a surface charge switchable polymeric nanoparticle that was sensitive to the slightly acidic tumor microenvironment was developed for steady delivery of NgBR siRNA to tumor tissues. The nanoformulation was constructed by conjugating 2, 3-dimethylmaleic anhydride (DMMA) molecules to the surface amines of micelles formed by cationic co-polymer poly(lactic-co-glycolic acid) 2 -poly(ethylenimine) and subsequent absorption of NgBR siRNAs. The nanoparticles remained negatively charged in physiological condition and smartly converted to positive surface charge due to tumor-acidity-activated shedding of DMMA. The charge conversion facilitated cellular uptake of siRNAs and in turn efficiently depleted the expression of NgBR in tumor-bearing tissues. Silencing of NgBR suppressed endothelial cell migration and tubule formation, and reverted the EMT process of breast cancer cells. Delivery of the nanoformulation to mice bearing orthotopic breast carcinoma showed no effect on tumor growth, but led to remarkable decrease of distant metastasis by normalizing tumor vessels and suppressing the EMT of breast cancer cells. This study demonstrated that NgBR is a promising therapeutic target in abnormal tumor vasculature and aggressive cancer cells, and the tumor-responsive nanoparticle with the feature of charge transformation offers great potential for tumor-specific delivery of gene therapeutics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determination of community structure through deconvolution of PLFA-FAME signature of mixed population.

PubMed

Dey, Dipesh K; Guha, Saumyen

2007-02-15

Phospholipid fatty acids (PLFAs) as biomarkers are well established in the literature. A general method based on least square approximation (LSA) was developed for the estimation of community structure from the PLFA signature of a mixed population where biomarker PLFA signatures of the component species were known. Fatty acid methyl ester (FAME) standards were used as species analogs and mixture of the standards as representative of the mixed population. The PLFA/FAME signatures were analyzed by gas chromatographic separation, followed by detection in flame ionization detector (GC-FID). The PLFAs in the signature were quantified as relative weight percent of the total PLFA. The PLFA signatures were analyzed by the models to predict community structure of the mixture. The LSA model results were compared with the existing "functional group" approach. Both successfully predicted community structure of mixed population containing completely unrelated species with uncommon PLFAs. For slightest intersection in PLFA signatures of component species, the LSA model produced better results. This was mainly due to inability of the "functional group" approach to distinguish the relative amounts of the common PLFA coming from more than one species. The performance of the LSA model was influenced by errors in the chromatographic analyses. Suppression (or enhancement) of a component's PLFA signature in chromatographic analysis of the mixture, led to underestimation (or overestimation) of the component's proportion in the mixture by the model. In mixtures of closely related species with common PLFAs, the errors in the common components were adjusted across the species by the model.

Expression of Selected Ginkgo biloba Heat Shock Protein Genes After Cold Treatment Could Be Induced by Other Abiotic Stress

PubMed Central

Cao, Fuliang; Cheng, Hua; Cheng, Shuiyuan; Li, Linling; Xu, Feng; Yu, Wanwen; Yuan, Honghui

2012-01-01

Heat shock proteins (HSPs) play various stress-protective roles in plants. In this study, three HSP genes were isolated from a suppression subtractive hybridization (SSH) cDNA library of Ginkgo biloba leaves treated with cold stress. Based on the molecular weight, the three genes were designated GbHSP16.8, GbHSP17 and GbHSP70. The full length of the three genes were predicted to encode three polypeptide chains containing 149 amino acids (Aa), 152 Aa, and 657 Aa, and their corresponding molecular weights were predicted as follows: 16.67 kDa, 17.39 kDa, and 71.81 kDa respectively. The three genes exhibited distinctive expression patterns in different organs or development stages. GbHSP16.8 and GbHSP70 showed high expression levels in leaves and a low level in gynoecia, GbHSP17 showed a higher transcription in stamens and lower level in fruit. This result indicates that GbHSP16.8 and GbHSP70 may play important roles in Ginkgo leaf development and photosynthesis, and GbHSP17 may play a positive role in pollen maturation. All three GbHSPs were up-regulated under cold stress, whereas extreme heat stress only caused up-regulation of GbHSP70, UV-B treatment resulted in up-regulation of GbHSP16.8 and GbHSP17, wounding treatment resulted in up-regulation of GbHSP16.8 and GbHSP70, and abscisic acid (ABA) treatment caused up-regulation of GbHSP70 primarily. PMID:22754330

Effect of Soil pH Increase by Biochar on NO, N2O and N2 Production during Denitrification in Acid Soils

PubMed Central

Obia, Alfred; Cornelissen, Gerard; Mulder, Jan; Dörsch, Peter

2015-01-01

Biochar (BC) application to soil suppresses emission of nitrous- (N2O) and nitric oxide (NO), but the mechanisms are unclear. One of the most prominent features of BC is its alkalizing effect in soils, which may affect denitrification and its product stoichiometry directly or indirectly. We conducted laboratory experiments with anoxic slurries of acid Acrisols from Indonesia and Zambia and two contrasting BCs produced locally from rice husk and cacao shell. Dose-dependent responses of denitrification and gaseous products (NO, N2O and N2) were assessed by high-resolution gas kinetics and related to the alkalizing effect of the BCs. To delineate the pH effect from other BC effects, we removed part of the alkalinity by leaching the BCs with water and acid prior to incubation. Uncharred cacao shell and sodium hydroxide (NaOH) were also included in the study. The untreated BCs suppressed N2O and NO and increased N2 production during denitrification, irrespective of the effect on denitrification rate. The extent of N2O and NO suppression was dose-dependent and increased with the alkalizing effect of the two BC types, which was strongest for cacao shell BC. Acid leaching of BC, which decreased its alkalizing effect, reduced or eliminated the ability of BC to suppress N2O and NO net production. Just like untreated BCs, NaOH reduced net production of N2O and NO while increasing that of N2. This confirms the importance of altered soil pH for denitrification product stoichiometry. Addition of uncharred cacao shell stimulated denitrification strongly due to availability of labile carbon but only minor effects on the product stoichiometry of denitrification were found, in accordance with its modest effect on soil pH. Our study indicates that stimulation of denitrification was mainly due to increases in labile carbon whereas change in product stoichiometry was mainly due to a change in soil pH. PMID:26397367

Effect of Soil pH Increase by Biochar on NO, N2O and N2 Production during Denitrification in Acid Soils.

PubMed

Obia, Alfred; Cornelissen, Gerard; Mulder, Jan; Dörsch, Peter

2015-01-01

Biochar (BC) application to soil suppresses emission of nitrous- (N2O) and nitric oxide (NO), but the mechanisms are unclear. One of the most prominent features of BC is its alkalizing effect in soils, which may affect denitrification and its product stoichiometry directly or indirectly. We conducted laboratory experiments with anoxic slurries of acid Acrisols from Indonesia and Zambia and two contrasting BCs produced locally from rice husk and cacao shell. Dose-dependent responses of denitrification and gaseous products (NO, N2O and N2) were assessed by high-resolution gas kinetics and related to the alkalizing effect of the BCs. To delineate the pH effect from other BC effects, we removed part of the alkalinity by leaching the BCs with water and acid prior to incubation. Uncharred cacao shell and sodium hydroxide (NaOH) were also included in the study. The untreated BCs suppressed N2O and NO and increased N2 production during denitrification, irrespective of the effect on denitrification rate. The extent of N2O and NO suppression was dose-dependent and increased with the alkalizing effect of the two BC types, which was strongest for cacao shell BC. Acid leaching of BC, which decreased its alkalizing effect, reduced or eliminated the ability of BC to suppress N2O and NO net production. Just like untreated BCs, NaOH reduced net production of N2O and NO while increasing that of N2. This confirms the importance of altered soil pH for denitrification product stoichiometry. Addition of uncharred cacao shell stimulated denitrification strongly due to availability of labile carbon but only minor effects on the product stoichiometry of denitrification were found, in accordance with its modest effect on soil pH. Our study indicates that stimulation of denitrification was mainly due to increases in labile carbon whereas change in product stoichiometry was mainly due to a change in soil pH.

Indication of acid suppression therapy and predictors for the prophylactic use of protonpump inhibitors vs. histamine-2 receptor antagonists in a Malaysian tertiary hospital

PubMed Central

Oh, Ai L.; Tan, Andrew G.; Phan, Hui S.; Lee, Basil C.; Jumaat, Nafisah; Chew, Soo P.; Wong, Siok H.; Ting, Shee H.; Subramaniam, Theebaa

2015-01-01

Background: Proton-pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are common acid suppressants used in gastrointestinal disorders. The trend of usage in Malaysia has changed from predominantly H2RA to PPI from 2007 to 2008, 3.46 versus 2.87 and 2.99 versus 3.24 DDD (Defined Daily Dose)/1000 population/day respectively. This raises concerns as PPI overutilization amounts to higher cost expenditure and are associated with various untoward consequences such as Clostridium difficile-associated diarrhea, pneumonia, and osteoporosis. Objectives: To evaluate the indication of acid suppression therapy (AST) and to look for predictors associated with the prophylactic use of PPI as compared to H2RA. Methods: Data collection was conducted via a standardized surveillance form over a 2-month period in the general medical wards of Sarawak General Hospital. All patients who received at least one dose of PPI or H2RA in any dosage form were included in the study. Appropriateness of prophylaxis was determined using current available guidelines. Selected risk factors were analysed using simple logistic regression to look for predictors associated with the choice of PPI in prophylactic AST. Results: Out of 212 cases in the present cohort, about three quarters (75.5%, n=160) of acid suppressants were given as prophylaxis. Over half of these did not have appropriate indications for prophylactic AST (58.1%, n=93). Among all cases given prophylactic AST, 75.0% (n=120) of them were given PPI. Renal insufficiency was identified as the only predictor associated with the use of prophylactic PPI in preference to H2RA (OR=2.86, 95%CI 1.21:6.72, p=0.011). Conclusion: Inappropriate prophylactic AST is a major concern and may even be underestimated due to the lack of appropriate guidelines. More data is required to guide the selection between PPI and H2RA, specifically the more cost-effective use of H2RA in patients with lower gastrointestinal risk or in whom PPI has no clear advantage. PMID:26445624

Dose-dependent competitive block by topical acetylsalicylic and salicylic acid of low pH-induced cutaneous pain.

PubMed

Steen, K H; Reeh, P W; Kreysel, H W

1996-01-01

In a human acid pain model, which uses continuous intradermal pressure infusion of a phosphate-buffered solution (pH 5.2) to induce localized non-adapting pain, the flow was adjusted to result in constant pain ratings of about 20% or 50% on a visual analog scale (VAS). Six volunteers in each group participated in 4 different placebo-controlled double-blind cross-over studies to measure rapidly evolving cutaneous analgesia from topically applied new ointment formulations of acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial ibuprofen and benzocain creams. Similar, log-linear dose-response curves were found for both ASA and SA, significant in effect at 3 g/kg and higher drug contents and reaching saturation level at 15 or 30 g/kg, respectively, which, 20 min after application, caused a mean pain suppression of 95% using ASA and 80% using SA. Half-maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The SA action was also clearly slower to develop. With an increased flow of the acidic buffer, producing lower effective tissue pH and more intense pain, the effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA, pain reduction could be reversed by increasing the buffer flow by a factor of 1.75, on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg) were comparably as effective as ASA and SA, but the local anesthetic caused a loss of all cutaneous sensations while the touch threshold (von Frey) under the specific analgesics was the same as under the placebo ointment. Thus, topical applications of non-steroidal anti-inflammatory drugs (NSAIDS) dissolved in different ointment formulations have proven dose-dependently effective and specific in suppressing experimental acidotic pain by a local and competitive mechanism.

Measuring ability to enhance and suppress emotional expression: The Flexible Regulation of Emotional Expression (FREE) Scale.

PubMed

Burton, Charles L; Bonanno, George A

2016-08-01

Flexibility in self-regulatory behaviors has proved to be an important quality for adjusting to stressful life events and requires individuals to have a diverse repertoire of emotion regulation abilities. However, the most commonly used emotion regulation questionnaires assess frequency of behavior rather than ability, with little evidence linking these measures to observable capacity to enact a behavior. The aim of the current investigation was to develop and validate a Flexible Regulation of Emotional Expression (FREE) Scale that measures a person's ability to enhance and suppress displayed emotion across an array of hypothetical contexts. In Studies 1 and 2, a series of confirmatory factor analyses revealed that the FREE Scale consists of 4 first-order factors divided by regulation and emotional valence type that can contribute to 2 higher order factors: expressive enhancement ability and suppression ability. In Study 1, we also compared the FREE Scale to other commonly used emotion regulation measures, which revealed that suppression ability is conceptually distinct from suppression frequency. In Study 3, we compared the FREE Scale with a composite of traditional frequency-based indices of expressive regulation to predict performance in a previously validated emotional modulation paradigm. Participants' enhancement and suppression ability scores on the FREE Scale predicted their corresponding performance on the laboratory task, even when controlling for baseline expressiveness. These studies suggest that the FREE Scale is a valid and flexible measure of expressive regulation ability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Evaporation suppression from reservoirs using floating covers: Lab scale wind-tunnel observations and mechanistic model predictions

NASA Astrophysics Data System (ADS)

Or, Dani; Lehmann, Peter; Aminzadeh, Milad; Sommer, Martina; Wey, Hannah; Krentscher, Christiane; Wunderli, Hans; Breitenstein, Daniel

2017-04-01

The competition over dwindling fresh water resources is expected to intensify with projected increase in human population in arid regions, expansion of irrigated land and changes in climate and drought patterns. The volume of water stored in reservoirs would also increase to mitigate seasonal shortages due to rainfall variability and to meet irrigation water needs. By some estimates up to half of the stored water is lost to evaporation, thereby exacerbating the water scarcity problem. Recently, there is an upsurge in the use of self-assembling floating covers to suppress evaporation, yet the design and implementation remain largely empirical. We report a systematic experimental evaluation of different cover types and external drivers (radiation, wind, wind plus radiation) on evaporation suppression and energy balance of a 1.4 m2 basin placed in a wind-tunnel. Surprisingly, evaporation suppression by black and white floating covers (balls and plates) were similar despite significantly different energy balance regimes over the cover surfaces. Moreover, the evaporation suppression efficiency was a simple function of the uncovered area (square root of the uncovered fraction) with linear relations with the covered area in some cases. The thermally decoupled floating covers offer an efficient solution to the evaporation suppression with limited influence of the surface energy balance (water temperature for black and white covers was similar and remained nearly constant). The results will be linked with a predictive evaporation-energy balance model and issues of spatial scales and long exposure times will be studied.

Comparative Genomic Analysis of Lactobacillus plantarum GB-LP1 Isolated from Traditional Korean Fermented Food.

PubMed

Yu, Jihyun; Ahn, Sojin; Kim, Kwondo; Caetano-Anolles, Kelsey; Lee, Chanho; Kang, Jungsun; Cho, Kyungjin; Yoon, Sook Hee; Kang, Dae-Kyung; Kim, Heebal

2017-08-28

As probiotics play an important role in maintaining a healthy gut flora environment through antitoxin activity and inhibition of pathogen colonization, they have been of interest to the medical research community for quite some time now. Probiotic bacteria such as Lactobacillus plantarum , which can be found in fermented food, are of particular interest given their easy accessibility. We performed whole-genome sequencing and genomic analysis on a GB-LP1 strain of L. plantarum isolated from Korean traditional fermented food; this strain is well known for its functions in immune response, suppression of pathogen growth, and antitoxin effects. The complete genome sequence of GB-LP1 is a single chromosome of 3,040,388 bp with 2,899 predicted open reading frames. Genomic analysis of GB-LP1 revealed two CRISPR regions and genes showing accelerated evolution, which may have antibiotic and antitoxin functions. The aim of the present study was to predict strain specific-genomic characteristics and assess the potential of this new strain as lactic acid bacteria at the genomic level using in silico analysis. These results provide insight into the L. plantarum species as well as confirm the possibility of its utility as a candidate probiotic.

Inducing amnesia through systemic suppression

PubMed Central

Hulbert, Justin C.; Henson, Richard N.; Anderson, Michael C.

2016-01-01

Hippocampal damage profoundly disrupts the ability to store new memories of life events. Amnesic windows might also occur in healthy people due to disturbed hippocampal function arising during mental processes that systemically reduce hippocampal activity. Intentionally suppressing memory retrieval (retrieval stopping) reduces hippocampal activity via control mechanisms mediated by the lateral prefrontal cortex. Here we show that when people suppress retrieval given a reminder of an unwanted memory, they are considerably more likely to forget unrelated experiences from periods surrounding suppression. This amnesic shadow follows a dose-response function, becomes more pronounced after practice suppressing retrieval, exhibits characteristics indicating disturbed hippocampal function, and is predicted by reduced hippocampal activity. These findings indicate that stopping retrieval engages a suppression mechanism that broadly compromises hippocampal processes and that hippocampal stabilization processes can be interrupted strategically. Cognitively triggered amnesia constitutes an unrecognized forgetting process that may account for otherwise unexplained memory lapses following trauma. PMID:26977589

When suppressing one stereotype leads to rebound of another: on the procedural nature of stereotype rebound.

PubMed

Geeraert, Nicolas

2013-09-01

A known consequence of stereotype suppression is post-suppressional rebound (PSR), an ironic activation of the suppressed stereotype. This is typically explained as an unintended by-product from a dual-process model of mental control. Relying on this model, stereotype rebound is believed to be conceptual. Alternative accounts predict PSR to be featural or procedural. According to the latter account, stereotype rebound would not be limited to the suppressed social category, but could occur for a target from any social category. The occurrence of procedural stereotype rebound was examined across five experiments. Suppression of one particular stereotype consistently led to rebound for social targets belonging to the same or a different stereotype in an essay-writing task (Experiments 1-3) and led to facilitation in recognition of stereotype-consistent words (Experiment 4). Finally, stereotype suppression was shown to impact on assessments of stereotype use but not on heuristic thinking (Experiment 5).

Below-baseline suppression of competitors during interference resolution by younger but not older adults.

PubMed

Healey, M Karl; Ngo, K W Joan; Hasher, Lynn

2014-01-01

Resolving interference from competing memories is a critical factor in efficient memory retrieval, and several accounts of cognitive aging suggest that difficulty resolving interference may underlie memory deficits such as those seen in the elderly. Although many researchers have suggested that the ability to suppress competitors is a key factor in resolving interference, the evidence supporting this claim has been the subject of debate. Here, we present a new paradigm and results demonstrating that for younger adults, a single retrieval attempt is sufficient to suppress competitors to below-baseline levels of accessibility even though the competitors are never explicitly presented. The extent to which individual younger adults suppressed competitors predicted their performance on a memory span task. In a second experiment, older adults showed no evidence of suppression, which supports the theory that older adults' memory deficits are related to impaired suppression.

Measurement of pattern roughness and local size variation using CD-SEM: current status

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Kawasaki, Takahiro; Kawada, Hiroki; Sakai, Kei; Kato, Takashi; Yamaguchi, Satoru; Ikota, Masami; Momonoi, Yoshinori

2018-03-01

Measurement of line edge roughness (LER) is discussed from four aspects: edge detection, PSD prediction, sampling strategy, and noise mitigation, and general guidelines and practical solutions for LER measurement today are introduced. Advanced edge detection algorithms such as wave-matching method are shown effective for robustly detecting edges from low SNR images, while conventional algorithm with weak filtering is still effective in suppressing SEM noise and aliasing. Advanced PSD prediction method such as multi-taper method is effective in suppressing sampling noise within a line edge to analyze, while number of lines is still required for suppressing line to line variation. Two types of SEM noise mitigation methods, "apparent noise floor" subtraction method and LER-noise decomposition using regression analysis are verified to successfully mitigate SEM noise from PSD curves. These results are extended to LCDU measurement to clarify the impact of SEM noise and sampling noise on LCDU.

Emotion regulation and risk taking: predicting risky choice in deliberative decision making.

PubMed

Panno, Angelo; Lauriola, Marco; Figner, Bernd

2013-01-01

Only very recently has research demonstrated that experimentally induced emotion regulation strategies (cognitive reappraisal and expressive suppression) affect risky choice (e.g., Heilman et al., 2010). However, it is unknown whether this effect also operates via habitual use of emotion regulation strategies in risky choice involving deliberative decision making. We investigated the role of habitual use of emotion regulation strategies in risky choice using the "cold" deliberative version of the Columbia Card Task (CCT; Figner et al., 2009). Fifty-three participants completed the Emotion Regulation Questionnaire (ERQ; Gross & John, 2003) and--one month later--the CCT and the PANAS. Greater habitual cognitive reappraisal use was related to increased risk taking, accompanied by decreased sensitivity to changes in probability and loss amount. Greater habitual expressive suppression use was related to decreased risk taking. The results show that habitual use of reappraisal and suppression strategies predict risk taking when decisions involve predominantly cognitive-deliberative processes.

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.

Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity

NASA Astrophysics Data System (ADS)

Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo

2016-10-01

The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

Physics of thermal transport and increased electron temperature turbulence in the edge pedestal of ELM-free, H-mode regimes on DIII-D

NASA Astrophysics Data System (ADS)

Sung, Choongki

2017-10-01

It has been observed, for the first time, that suppression of Edge Localized Modes (ELMs) in tokamak plasmas is accompanied by an increase in electron temperature turbulence. A correlation electron cyclotron emission technique has been utilized to quantify the observed increase: 40% increase in Quiescent H-mode (QH-mode) and 70% increase in 3D field ELM suppressed H-mode. Since reliable ELM-free H-mode operation is essential for future burning plasma experiments, it is crucial to develop a validated predictive capability for these plasmas. Linear stability analysis using TGLF has provided an explanation for the observations and has indicated that the underlying physical mechanisms are different in the two regimes. In QH-mode, profile gradients and the associated linear growth rate are decreased compared to ELMing H-mode. However, the ExB shearing rate is reduced by an even greater factor such that turbulent transport is no longer suppressed by flow shear. In contrast, during 3D field ELM suppressed H-mode, gradients are increased and TGLF predicts that a large increase in linear growth rate is primarily responsible for the increased turbulence. Power balance analysis using ONETWO is also consistent with the changes in electron thermal transport being due to the increased turbulence. These new findings are significant since they i) provide a physics explanation of these changes via TGLF analysis and enable validation of the model in the key pedestal region, and ii) support the hypothesis that turbulent transport partially replaces ELM-dominated transport during ELM-free operation. These results form a basis to develop a predictive understanding of pedestal regulation in ELM suppressed regimes. Supported by the US DOE under DE-FG02-08ER54984, DE-FC02-04ER54698.

Assessing predictive services' 7-day fire potential outlook

Treesearch

Karin Riley; Crystal Stonesifer; Dave Calkin; Haiganoush Preisler

2015-01-01

The Predictive Services program was created under the National Wildfire Coordinating Group in 2001 to address the need for long- and short-term decision support information for fire managers and operations personnel. The primary mission of Predictive Services is to integrate fire weather, fire danger, and resource availability to enable strategic fire suppression...

Pine beauty moth (Panolis flammea Schiff.) outbreak management: suppression versus natural enemies

Treesearch

Paulius Zolubas

2003-01-01

Pine beauty moth (Panolis flammea Schiff.) is one of the most serious defoliators that periodically threatens Scotch pine forests on poor sandy soils in Lithuania. Population increase of this pest began in 1999. Because a maximum of only 15% defoliation was predicted in particular areas, no additional funding was required for suppressing the...

Diameter and height growth of suppressed grand fir saplings after overstory removal.

Treesearch

K.W. Seidel

1980-01-01

The 2- and 5-year diameter and height growth of suppressed grand fir (Abies grandis (Dougl. ex D. Don) Lindl.) advance reproduction was measured in central Oregon after the overstory was removed. Multiple regression analyses were used to predict growth response as a function of individual tree variables. The resulting equations, although highly...

Nonrandom Acts of Kindness: Parasympathetic and Subjective Empathic Responses to Sadness Predict Children’s Prosociality

PubMed Central

Miller, Jonas G.; Nuselovici, Jacob N.; Hastings, Paul D.

2016-01-01

How does empathic physiology unfold as a dynamic process, and which aspect of empathy predicts children’s kindness? In response to empathy induction videos, 4–6 year-old children (N = 180) showed an average pattern of dynamic respiratory sinus arrhythmia (RSA) change characterized by early RSA suppression followed by RSA recovery, and modest subsequent suppression during positive resolution of the empathic event. Children’s capacity for this pattern of flexible RSA change was associated with their subjective empathic feelings, which were concurrently associated with more sympathetic and prosocial responses to others. Conversely, only children’s dynamic RSA change longitudinally predicted prosocial behavior two years later. These findings have implications for understanding the dynamic and multifaceted nature of empathy, and its relation with prosocial development. PMID:28262932

The botanical molecule p-hydroxycinnamic acid as a new osteogenic agent: insight into the treatment of cancer bone metastases.

PubMed

Yamaguchi, Masayoshi

2016-10-01

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder.

Cinnamic acid 4-hydroxylase of sorghum [Sorghum biocolor (L.) Moench] gene SbC4H1 restricts lignin synthesis in Arabidopsis

USDA-ARS?s Scientific Manuscript database

Cinnamic acid 4-hydroxylase (C4H) is the first hydroxylase enzyme of the phenylpropanoid pathway, and its content and activity affects the lignin synthesis. In this study, we isolated a C4H gene SbC4H1 from the suppression subtractive hybridization library of brown midrib (bmr) mutants of Sorghum b...

Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives.

PubMed

Cipollina, Chiara; Salvatore, Sonia R; Muldoon, Matthew F; Freeman, Bruce A; Schopfer, Francisco J

2014-01-01

Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the precept that the benefit of ω-3 PUFA-rich diets can be attributed to the generation of electrophilic oxygenated metabolites that transduce anti-inflammatory actions rather than the suppression of pro-inflammatory AA metabolites. ClinicalTrials.gov NCT00663871.

Evaporation suppression from water reservoirs using floating covers: Lab scale observations and model predictions

NASA Astrophysics Data System (ADS)

Or, D.; Lehmann, P.; Aminzadeh, M.; Sommer, M.; Wey, H.; Wunderli, H.; Breitenstein, D.

2016-12-01

The competition over dwindling fresh water resources is expected to intensify with projected increase in human population in arid regions, expansion of irrigated land and changes in climate and drought patterns. The volume of water stored in reservoirs would also increase to mitigate seasonal shortages due to rainfall variability and to meet irrigation water needs. By some estimates up to half of the stored water is lost to evaporation thereby exacerbating the water scarcity problem. Recently, there is an upsurge in the use of self-assembling floating covers to suppress evaporation, yet the design, and implementation remain largely empirical. Studies have shown that evaporation suppression is highly nonlinear, as also known from a century of research on gas exchange from plant leaves (that often evaporate as free water surfaces through stomata that are only 1% of leaf area). We report a systematic evaluation of different cover types and external drivers (radiation, wind, wind+radiation) on evaporation suppression and energy balance of a 1.4 m2 basin placed in a wind-tunnel. Surprisingly, evaporation suppression by black and white floating covers (balls and plates) were similar despite significantly different energy balance regimes over the cover surfaces. Moreover, the evaporation suppression efficiency was a simple function of the uncovered area (square root of the uncovered fraction) with linear relations with the covered area in some cases. The thermally decoupled floating covers offer an efficient solution to the evaporation suppression with limited influence of the surface energy balance (water temperature for black and white covers was similar and remained nearly constant). The results will be linked with a predictive evaporation-energy balance model and issues of spatial scales and long exposure times will be studied.

Heterogeneous binary interactions of taste primaries: perceptual outcomes, physiology, and future directions.

PubMed

Wilkie, Lynn M; Capaldi Phillips, Elizabeth D

2014-11-01

Complex taste experiences arise from the combinations of five taste primaries. Here we review the literature on binary interactions of heterogeneous taste primaries, focusing on perceptual results of administering mixtures of aqueous solutions to human participants. Some interactions proved relatively consistent across tastants and experimental methods: sour acids enhanced saltiness, salts and sweeteners suppressed bitterness, sweeteners suppressed sourness, and sour acids enhanced bitterness. However, for the majority of interactions there were differential effects based on the tastants and their concentrations. Drawing conclusions about interactions with umami is currently not possible due to the low number of primary source studies investigating it and the confounding sodium ions in monosodium glutamate (MSG). Speculative physiological explanations are provided that fit the current data and suggestions for future research studies are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated glucose transport in skeletal muscle cells in a BCAT2-dependent manner

PubMed Central

Moghei, Mahshid; Tavajohi-Fini, Pegah; Beatty, Brendan

2016-01-01

Although leucine has many positive effects on metabolism in multiple tissues, elevated levels of this amino acid and the other branched-chain amino acids (BCAAs) and their metabolites are implicated in obesity and insulin resistance. While some controversies exist about the direct effect of leucine on insulin action in skeletal muscle, little is known about the direct effect of BCAA metabolites. Here, we first showed that the inhibitory effect of leucine on insulin-stimulated glucose transport in L6 myotubes was dampened when other amino acids were present, due in part to a 140% stimulation of basal glucose transport (P < 0.05). Importantly, we also showed that α-ketoisocaproic acid (KIC), an obligatory metabolite of leucine, stimulated mTORC1 signaling but suppressed insulin-stimulated glucose transport (−34%, P < 0.05) in an mTORC1-dependent manner. The effect of KIC on insulin-stimulated glucose transport was abrogated in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that catalyzes the reversible transamination of KIC to leucine. We conclude that although KIC can modulate muscle glucose metabolism, this effect is likely a result of its transamination back to leucine. Therefore, limiting the availability of leucine, rather than those of its metabolites, to skeletal muscle may be more critical in the management of insulin resistance and its sequelae. PMID:27488662

The antagonistic regulation of abscisic acid-inhibited root growth by brassinosteroids is partially mediated via direct suppression of ABSCISIC ACID INSENSITIVE 5 expression by BRASSINAZOLE RESISTANT 1.

PubMed

Yang, Xiaorui; Bai, Yang; Shang, Jianxiu; Xin, Ruijiao; Tang, Wenqiang

2016-09-01

Brassinosteroids (BRs) and abscisic acid (ABA) are plant hormones that antagonistically regulate many aspects of plant growth and development; however, the mechanisms that regulate the crosstalk of these two hormones are still not well understood. BRs regulate plant growth and development by activating BRASSINAZOLE RESISTANT 1 (BZR1) family transcription factors. Here we show that the crosstalk between BRs and ABA signalling is partially mediated by BZR1 regulated gene expression. bzr1-1D is a dominant mutant with enhanced BR signalling; our results showed that bzr1-1D mutant is less sensitive to ABA-inhibited primary root growth. By RNA sequencing, a subset of BZR1 regulated ABA-responsive root genes were identified. Of these genes, the expression of a major ABA signalling component ABA INSENSITIVE 5 (ABI5) was found to be suppressed by BR and by BZR1. Additional evidences showed that BZR1 could bind strongly with several G-box cis-elements in the promoter of ABI5, suppress the expression of ABI5 and make plants less sensitive to ABA. Our study demonstrated that ABI5 is a direct target gene of BZR1, and modulating the expression of ABI5 by BZR1 plays important roles in regulating the crosstalk between the BR and ABA signalling pathways. © 2016 John Wiley & Sons Ltd.

DAX1 suppresses FXR transactivity as a novel co-repressor

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

Li, Jin; Lu, Yan; Liu, Ruya

2011-09-09

Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor familymore » due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.« less

Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.

PubMed

Lim, Kyung-Min; Bae, SeungJin; Koo, Jung Eun; Kim, Eun-Sun; Bae, Ok-Nam; Lee, Joo Young

2015-04-01

Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.

Biological Potential of Bioorganic Fertilizer Fortified with Bacterial Antagonist for the Control of Tomato Bacterial Wilt and the Promotion of Crop Yields.

PubMed

Wu, Kai; Fang, Zhiying; Wang, Lili; Yuan, Saifei; Guo, Rong; Shen, Biao; Shen, Qirong

2016-10-28

The application of Bacillus sp. in the biological control of plant soilborne diseases has been shown to be an environmentally friendly alternative to the use of chemical fungicides. In this study, the effects of bioorganic fertilizer (BOF) fortified with Bacillus amyloliquefaciens SQY 162 on the suppression of tomato bacterial wilt were investigated in pot experiments. The disease incidence of tomato wilt after the application of BOF was 65.18% and 41.62% lower at 10 and 20 days after transplantation, respectively, than in the control condition. BOF also promoted the plant growth. The SQY 162 populations efficiently colonized the tomato rhizosphere, which directly suppressed the number of Ralstonia solanacearum in the tomato rhizosphere soil. In the presence of BOF, the activities of defense-related enzymes in tomato were lower than in the presence of the control treatment, but the expression levels of the defense-related genes of the plants in the salicylic acid and jasmonic acid pathways were enhanced. It was also found that strain SQY 162 could secrete antibiotic surfactin, but not volatile organic compounds, to suppress Ralstonia . The strain could also produce plant growth promotion compounds such as siderophores and indole-3-acetic acid. Thus, owing to its innate multiple-functional traits and its broad biocontrol activities, we found that this antagonistic strain isolated from the tobacco rhizosphere could establish itself successfully in the tomato rhizosphere to control soilborne diseases.

Effect of essential amino acids on enteroids: Methionine deprivation suppresses proliferation and affects differentiation in enteroid stem cells

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

Saito, Yuki; Iwatsuki, Ken; Hanyu, Hikaru

We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation. In addition, mRNA levels of the stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) decreased in enteroids grown in Met deprivationmore » conditions. Consistent with this observation, Met deprivation also attenuated Lgr5-EGFP fluorescence intensity in enteroids. In contrast, Met deprivation enhanced mRNA levels of the enteroendocrine cell marker chromogranin A (ChgA) and markers of K cells, enterochromaffin cells, goblet cells, and Paneth cells. Immunofluorescence experiments demonstrated that Met deprivation led to an increase in the number of ChgA-positive cells. These results suggest that Met deprivation suppresses stem cell proliferation, thereby promoting differentiation. In conclusion, Met is an important nutrient in the maintenance of intestinal stem cells and Met deprivation potentially affects cell differentiation. - Highlights: • Met influences the proliferation of enteroids. • Met plays a crucial role in the maintenance of stem cells. • Met deprivation potentially promotes differentiation into secretory cells.« less

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.

Suppression of allene oxide synthase 3 in potato increases degree of arbuscular mycorrhizal fungal colonization.

PubMed

Morcillo, Rafael Jorge León; Navarrete, María Isabel Tamayo; Bote, Juan Antonio Ocampo; Monguio, Salomé Prat; García-Garrido, José Manuel

2016-01-15

Arbuscular mycorrhizal (AM) is a mutually beneficial interaction among higher plants and soil fungi of the phylum Glomeromycota. Numerous studies have pointed that jasmonic acid plays an important role in the development of the intraradical fungus. This compound belongs to a group of biologically active compounds known as oxylipins which are derived from the oxidative metabolism of polyunsaturated fatty acids. Studies of the regulatory role played by oxylipins in AM colonization have generally focused on jasmonates, while few studies exist on the 9-LOX pathway of oxylipins during AM formation. Here, the cDNA of Allene oxide synthase 3 (AOS3), a key enzyme in the 9-LOX pathway, was used in the RNA interference (RNAi) system to transform potato plants in order to suppress its expression. Results show increases in AOS3 gene expression and 9-LOX products in roots of wild type potato mycorrhizal plants. The suppression of AOS3 gene expression increases the percentage of root with mycorrhizal colonization at early stages of AM formation. AOS3 RNA interference lead to an induction of LOXA and 13-LOX genes, a reduction in AOS3 derived 9-LOX oxylipin compounds and an increase in jasmonic acid content, suggesting compensation between 9 and 13-LOX pathways. The results in a whole support the hypothesis of a regulatory role for the 9-LOX oxylipin pathway during mycorrhization. Copyright © 2015 Elsevier GmbH. All rights reserved.

Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice.

PubMed

Bruner-Tran, Kaylon L; Eisenberg, Esther; Yeaman, Grant R; Anderson, Ted A; McBean, Judith; Osteen, Kevin G

2002-10-01

The cyclic expression of matrix metalloproteinases (MMPs) by human endometrium has been suggested to play a role in the invasive process necessary to establish endometriosis. The ability of progesterone exposure to inhibit endometrial MMP-3 and MMP-7 expression requires the local action of TGF beta and may also be linked to the local production of retinoic acid by stromal cells. A continuous expression of several MMPs in endometriotic lesions has been reported, indicating a failure of progesterone or locally produced factors to suppress these enzymes. To address cell-specific MMP regulation associated with endometriosis, we examined expression of MMP-3 and MMP-7 mRNA in eutopic endometrium and endometriotic lesions acquired during the secretory phase of the menstrual cycle. We examined the in vitro regulation of MMP-3 and MMP-7 protein in similar tissues. We also examined the in vitro regulation of MMP secretion by progesterone, retinoic acid, and TGF beta in endometriosis tissues relative to the establishment of experimental disease. Our studies indicate that either eutopic or ectopic tissue from women with endometriosis exhibit patterns of altered MMP regulation in vivo. A lack of responsiveness to progesterone was demonstrated in vitro, associated with a failure to suppress MMP expression and an enhanced ability of the tissue to establish experimental endometriosis. However, in vitro treatments with retinoic acid and TGF beta restored the ability of progesterone to suppress MMPs in vitro and prevented the establishment of experimental disease.

Path of carbon flow during NO/sub 3//sup -/-induced photosynthetic suppression in N-limited Selenastrum minutum

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

Elrifi, I.R.; Turpin, D.H.

Nitrate addition to nitrate-limited cultures of Selenastrum minutum Naeg. Collins (Chlorophyta) resulted in a 70% suppression of photosynthetic carbon fixation. In /sup 14/CO/sub 2/ pulse/chase experiments nitrate resupply increased radiolabel incorporation into amino and organic acids and decreased radiolabel incorporation into insoluble material. Nitrate resupply increased the concentration of phosphoenolpyruvate and increased the radiolabeling of phosphoenolpyruvate, pyruvate and tricarboxylic acid cycle intermediates, notably citrate, fumarate, and malate. Furthermore, nitrate also increased the pool sizes and radiolabeling of most amino acids, with alanine, aspartate, glutamate, and glutamine showing the largest changes. Nitrate resupply increased the proportion of radiolabel in the C-4more » position of malate and increased the ratios of radiolabel in aspartate to phosphoenolpyruvate and in pyruvate to phosphoenolpyruvate, indicative of increased phosphoenolpyruvate carboxylase and pyruvate kinase activities. Analysis of these data showed that the rate of carbon flow through glutamate (10.6 ..mu..moles glutamate per milligram chlorophyll per hour) and the rate of net glutamate production (7.9 ..mu..moles glutamate per milligram chlorophyll per hour) were both greater than the maximum rate of carbon export from the Calvin cycle which could be maintained during steady state photosynthesis. These results are consistent with the hypothesis that nitrogen resupply to nitrogen-limited microalgae results in a transient suppression of photosynthetic carbon fixation due, in part, to the severity of competition for carbon skeletons between the Calvin cycle and nitrogen assimilation.« less

The Path of Carbon Flow during NO3−-Induced Photosynthetic Suppression in N-Limited Selenastrum minutum1

PubMed Central

Elrifi, Ivor R.; Turpin, David H.

1987-01-01

Nitrate addition to nitrate-limited cultures of Selenastrum minutum Naeg. Collins (Chlorophyta) resulted in a 70% suppression of photosynthetic carbon fixation. In 14CO2 pulse/chase experiments nitrate resupply increased radiolabel incorporation into amino and organic acids and decreased radiolabel incorporation into insoluble material. Nitrate resupply increased the concentration of phosphoenolpyruvate and increased the radiolabeling of phosphoenolpyruvate, pyruvate and tricarboxylic acid cycle intermediates, notably citrate, fumarate, and malate. Furthermore, nitrate also increased the pool sizes and radiolabeling of most amino acids, with alanine, aspartate, glutamate, and glutamine showing the largest changes. Nitrate resupply increased the proportion of radiolabel in the C-4 position of malate and increased the ratios of radiolabel in aspartate to phosphoenolpyruvate and in pyruvate to phosphoenolpyruvate, indicative of increased phosphoenolpyruvate carboxylase and pyruvate kinase activities. Analysis of these data showed that the rate of carbon flow through glutamate (10.6 μmoles glutamate per milligram chlorophyll per hour) and the rate of net glutamate production (7.9 μmoles glutamate per milligram chlorophyll per hour) were both greater than the maximum rate of carbon export from the Calvin cycle which could be maintained during steady state photosynthesis. These results are consistent with the hypothesis that nitrogen resupply to nitrogen-limited microalgae results in a transient suppression of photosynthetic carbon fixation due, in part, to the severity of competition for carbon skeletons between the Calvin cycle and nitrogen assimilation (IR Elrifi, DH Turpin 1986 Plant Physiol 81: 273-279). PMID:16665223

The Path of Carbon Flow during NO(3)-Induced Photosynthetic Suppression in N-Limited Selenastrum minutum.

PubMed

Elrifi, I R; Turpin, D H

1987-01-01

Nitrate addition to nitrate-limited cultures of Selenastrum minutum Naeg. Collins (Chlorophyta) resulted in a 70% suppression of photosynthetic carbon fixation. In (14)CO(2) pulse/chase experiments nitrate resupply increased radiolabel incorporation into amino and organic acids and decreased radiolabel incorporation into insoluble material. Nitrate resupply increased the concentration of phosphoenolpyruvate and increased the radiolabeling of phosphoenolpyruvate, pyruvate and tricarboxylic acid cycle intermediates, notably citrate, fumarate, and malate. Furthermore, nitrate also increased the pool sizes and radiolabeling of most amino acids, with alanine, aspartate, glutamate, and glutamine showing the largest changes. Nitrate resupply increased the proportion of radiolabel in the C-4 position of malate and increased the ratios of radiolabel in aspartate to phosphoenolpyruvate and in pyruvate to phosphoenolpyruvate, indicative of increased phosphoenolpyruvate carboxylase and pyruvate kinase activities. Analysis of these data showed that the rate of carbon flow through glutamate (10.6 mumoles glutamate per milligram chlorophyll per hour) and the rate of net glutamate production (7.9 mumoles glutamate per milligram chlorophyll per hour) were both greater than the maximum rate of carbon export from the Calvin cycle which could be maintained during steady state photosynthesis. These results are consistent with the hypothesis that nitrogen resupply to nitrogen-limited microalgae results in a transient suppression of photosynthetic carbon fixation due, in part, to the severity of competition for carbon skeletons between the Calvin cycle and nitrogen assimilation (IR Elrifi, DH Turpin 1986 Plant Physiol 81: 273-279).

Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

PubMed

Navarro-Meléndez, Ariana L; Heil, Martin

2014-07-01

Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

Glycyrrhizic acid attenuates stem cell-like phenotypes of human dermal papilla cells.

PubMed

Kiratipaiboon, Chayanin; Tengamnuay, Parkpoom; Chanvorachote, Pithi

2015-12-15

Although the growth of unwanted hair or hirsutism is a harmless condition, many people find it bothersome and embarrassing. Maintaining stem cell features of dermal papilla cells is a critical biological process that keeps the high rate of hair growth. Glycyrrhizic acid has been reported to impair hair growth in some studies; however, its underlying mechanism has not yet been investigated. This study aimed to explore the effect and underlying mechanism of glycyrrhizic acid on stemness of human dermal papilla cells. The stem cell molecular markers, epithelial to mesenchymal markers and Wnt/β-catenin-associated proteins of human dermal papilla cell line and primary human dermal papilla cells were analysed by western blot analysis and immunocytochemistry. The present study demonstrated that glycyrrhizic acid significantly depressed the stemness of dermal papilla cells in dose- and time-dependent manners. Clonogenicity and stem cell markers in the glycyrrhizic acid-treated cells were found to gradually decrease in the culture in a time-dependent manner. Our results demonstrated that glycyrrhizic acid exerted the stem cell suppressing effects through the interruption of ATP-dependent tyrosine kinase/glycogen synthase kinase3β-dependent mechanism which in turn down-regulated the β-catenin signalling pathway, coupled with decreased its down-stream epithelial-mesenchymal transition and self-renewal transcription factors, namely, Oct-4, Nanog, Sox2, ZEB1 and Snail. The effect of glycyrrhizic acid on the reduction of stem cell features was also observed in the primary dermal papilla cells directly obtained from human hair follicles. These results revealed a novel molecular mechanism of glycyrrhizic acid in regulation of dermal papilla cells and provided the evidence supporting the use of this compound in suppressing the growth of unwanted hair. Copyright © 2015 Elsevier GmbH. All rights reserved.

Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor.

PubMed

Willart, M A M; van Nimwegen, M; Grefhorst, A; Hammad, H; Moons, L; Hoogsteden, H C; Lambrecht, B N; Kleinjan, A

2012-12-01

Ursodeoxycholic acid (UDCA) is the only known beneficial bile acid with immunomodulatory properties. Ursodeoxycholic acid prevents eosinophilic degranulation and reduces eosinophil counts in primary biliary cirrhosis. It is unknown whether UDCA would also modulate eosinophilic inflammation outside the gastrointestinal (GI) tract, such as eosinophilic airway inflammation seen in asthma. The working mechanism for its immunomodulatory effect is unknown. The immunosuppressive features of UDCA were studied in vivo, in mice, in an ovalbumin (OVA)-driven eosinophilic airway inflammation model. To study the mechanism of action of UDCA, we analyzed the effect of UDCA on eosinophils, T cells, and dendritic cell (DCs). DC function was studied in greater detail, focussing on migration and T-cell stimulatory strength in vivo and interaction with T cells in vitro as measured by time-lapse image analysis. Finally, we studied the capacity of UDCA to influence DC/T cell interaction. Ursodeoxycholic acid treatment of OVA-sensitized mice prior to OVA aerosol challenge significantly reduced eosinophilic airway inflammation compared with control animals. DCs expressed the farnesoid X receptor for UDCA. Ursodeoxycholic acid strongly promoted interleukin (IL)-12 production and enhanced the migration in DCs. The time of interaction between DCs and T cells was sharply reduced in vitro by UDCA treatment of the DCs resulting in a remarkable T-cell cytokine production. Ursodeoxycholic acid-treated DCs have less capacity than saline-treated DCs to induce eosinophilic inflammation in vivo in Balb/c mice. Ursodeoxycholic acid has the potency to suppress eosinophilic inflammation outside the GI tract. This potential comprises to alter critical function of DCs, in essence, the effect of UDCA on DCs through the modulation of the DC/T cell interaction. © 2012 John Wiley & Sons A/S.

Toxins, Butyric Acid, and Other Short-Chain Fatty Acids Are Coordinately Expressed and Down-Regulated by Cysteine in Clostridium difficile

PubMed Central

Karlsson, Sture; Lindberg, Anette; Norin, Elisabeth; Burman, Lars G.; Åkerlund, Thomas

2000-01-01

It was recently found that a mixture of nine amino acids down-regulate Clostridium difficile toxin production when added to peptone yeast extract (PY) cultures of strain VPI 10463 (S. Karlsson, L. G. Burman, and T. Åkerlund, Microbiology 145:1683–1693, 1999). In the present study, seven of these amino acids were found to exhibit a moderate suppression of toxin production, whereas proline and particularly cysteine had the greatest impact, on both reference strains (n = 6) and clinical isolates (n = 28) of C. difficile (>99% suppression by cysteine in the highest toxin-producing strain). Also, cysteine derivatives such as acetylcysteine, glutathione, and cystine effectively down-regulated toxin expression. An impact of both cysteine and cystine but not of thioglycolate on toxin yield indicated that toxin expression was not regulated by the oxidation-reduction potential. Several metabolic pathways, including butyric acid and butanol production, were coinduced with the toxins in PY and down-regulated by cysteine. The enzyme 3-hydroxybutyryl coenzyme A dehydrogenase, a key enzyme in solventogenesis in Clostridium acetobutylicum, was among the most up-regulated proteins during high toxin production. The addition of butyric acid to various growth media induced toxin production, whereas the addition of butanol had the opposite effect. The results indicate a coupling between specific metabolic processes and toxin expression in C. difficile and that certain amino acids can alter these pathways coordinately. We speculate that down-regulation of toxin production by the administration of such amino acids to the colon may become a novel approach to prophylaxis and therapy for C. difficile-associated diarrhea. PMID:10992498