Synergistic effects in threshold models on networks.

PubMed

Juul, Jonas S; Porter, Mason A

2018-01-01

Network structure can have a significant impact on the propagation of diseases, memes, and information on social networks. Different types of spreading processes (and other dynamical processes) are affected by network architecture in different ways, and it is important to develop tractable models of spreading processes on networks to explore such issues. In this paper, we incorporate the idea of synergy into a two-state ("active" or "passive") threshold model of social influence on networks. Our model's update rule is deterministic, and the influence of each meme-carrying (i.e., active) neighbor can-depending on a parameter-either be enhanced or inhibited by an amount that depends on the number of active neighbors of a node. Such a synergistic system models social behavior in which the willingness to adopt either accelerates or saturates in a way that depends on the number of neighbors who have adopted that behavior. We illustrate that our model's synergy parameter has a crucial effect on system dynamics, as it determines whether degree-k nodes are possible or impossible to activate. We simulate synergistic meme spreading on both random-graph models and networks constructed from empirical data. Using a heterogeneous mean-field approximation, which we derive under the assumption that a network is locally tree-like, we are able to determine which synergy-parameter values allow degree-k nodes to be activated for many networks and for a broad family of synergistic models.

Synergistic effects in threshold models on networks

NASA Astrophysics Data System (ADS)

Juul, Jonas S.; Porter, Mason A.

2018-01-01

Network structure can have a significant impact on the propagation of diseases, memes, and information on social networks. Different types of spreading processes (and other dynamical processes) are affected by network architecture in different ways, and it is important to develop tractable models of spreading processes on networks to explore such issues. In this paper, we incorporate the idea of synergy into a two-state ("active" or "passive") threshold model of social influence on networks. Our model's update rule is deterministic, and the influence of each meme-carrying (i.e., active) neighbor can—depending on a parameter—either be enhanced or inhibited by an amount that depends on the number of active neighbors of a node. Such a synergistic system models social behavior in which the willingness to adopt either accelerates or saturates in a way that depends on the number of neighbors who have adopted that behavior. We illustrate that our model's synergy parameter has a crucial effect on system dynamics, as it determines whether degree-k nodes are possible or impossible to activate. We simulate synergistic meme spreading on both random-graph models and networks constructed from empirical data. Using a heterogeneous mean-field approximation, which we derive under the assumption that a network is locally tree-like, we are able to determine which synergy-parameter values allow degree-k nodes to be activated for many networks and for a broad family of synergistic models.

Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research

PubMed Central

Zhou, Xian; Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Razmovski-Naumovski, Valentina; Chan, Kelvin; Bensoussan, Alan

2016-01-01

Traditional Chinese medicine (TCM) is an important part of primary health care in Asian countries that has utilized complex herbal formulations (consisting 2 or more medicinal herbs) for treating diseases over thousands of years. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine (CHM) derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of CHM, misconceptions about synergy and methodological challenges to study design. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. We discuss the strengths and weaknesses of these models in the context of CHM and summarize the current status of synergy research in CHM. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low, and the clinical relevancy of most of these findings is undetermined. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations. PMID:27462269

Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells.

PubMed

van Haaften, Caroline; Boot, Arnoud; Corver, Willem E; van Eendenburg, Jaap D H; Trimbos, Baptist J M Z; van Wezel, Tom

2015-04-25

Ovarian cancer remains still the leading cause of death of gynecological malignancy, in spite of first-line chemotherapy with cisplatin and paclitaxel. Although initial response is favorably, relapses are common and prognosis for women with advanced disease stays poor. Therefore efficacious approaches are needed. Previously, an anti-cancer agent, EPD exhibited potent cytotoxic effects towards ovarian cancer and not towards normal cells. Cell viability and cell cycle analysis studies were performed with EPD, in combination with cisplatin and/or paclitaxel, using the ovarian carcinoma cell lines: SK-OV-3, OVCAR-3, JC, JC-pl and normal fibroblasts. Cell viability was measured using Presto Blue and cell cycle analysis using a flow cytometer. Apoptosis was measured in JC and JC-pl , using the caspase 3 assay kit. In JC-pl, SK-OV-3 and JC, synergistic interactions between either EPD and cisplatin or EPD and paclitaxel were observed. For the first time the effects of EPD on the cell cycle of ovarian cancer cells and normal cells was studied. EPD and combinations of EPD with cisplatin and/ or paclitaxel showed cell cycle arrest in the G2/M phase. The combination of EPD and cisplatin showed a significant synergistic effect in cell line JC-pl, while EPD with paclitaxel showed synergistic interaction in JC. Additionally, synergistic drug combinations showed increased apoptosis. Our results showed a synergistic effect of EPD and cisplatin in an ovarian drug resistant cell line as well as a synergistic effect of EPD and paclitaxel in two other ovarian cell lines. These results might enhance clinical efficacy, compared to the existing regimen of paclitaxel and cisplatin.

Synergistic anti-inflammatory effects of Nobiletin and Sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells

PubMed Central

Guo, Shanshan; Qiu, Peiju; Xu, Guang; Wu, Xian; Dong, Ping; Yang, Guanpin; Zheng, Jinkai; McClements, David Julian; Xiao, Hang

2012-01-01

Inflammation plays important roles in initiation and progress of many diseases including cancers in multiple organ sites. Herein, we investigated the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN) in combination. Non-cytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that combined NBN and SFN treatments produced much stronger inhibitory effects on the production of nitric oxide (NO) than NBN or SFN alone at higher concentrations. These enhanced inhibitory effects were synergistic based on the isobologram analysis. Western blot analysis showed that combined NBN and SFN treatments synergistically decreased iNOS and COX-2 protein expression levels and induced heme oxygenase-1 (HO-1) protein expression. Real-time PCR analysis indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels, and synergistically increased HO-1 mRNA levels. Overall our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells. PMID:22335189

The synergistic effect of treatment with triptolide and MK-801 in the rat neuropathic pain model

PubMed Central

Wang, Jian; Qiao, Yu; Yang, Ri-Sheng; Zhang, Chun-Kui; Wu, Huang-Hui; Lin, Jia-Ji; Zhang, Ting

2017-01-01

Triptolide (T10), an active component of Tripterygium wilfordii Hook F, is reported to have potent anti-inflammatory and analgesic effects. Additionally, MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, can reduce glutamate toxicity and has a significant analgesic effect on chronic pain. In this study, we tested the possible synergistic analgesic ability by intrathecal administration of T10 and MK-801 for the treatment of neuropathic pain. Single T10 (3, 10, or 30 µg/kg), MK-801 (10, 30, or 90 µg/kg), or a combination of them were intrathecally administrated in rats with spinal nerve ligation. We found that single administration of T10 caused a slow-acting but long-term analgesic effect, while single administration of MK-801 caused a fast-acting but short-term effect. Administration of their combination showed obviously synergic analgesia and the 1:3 ratio of T10 to MK-801 reached the peak effect. Furthermore, application of T10 and/or MK-801 significantly inhibited the activation of microglia and astrocyte and phosphorylation of STAT3 and NR2B in the spinal dorsal horn induced by chronic neuropathic pain. Our data suggest that the combination of T10 and MK-801 may be a potentially novel strategy for treatment of neuropathic pain. PMID:29166839

Achieving large linear elasticity and high strength in bulk nanocompsite via synergistic effect

DOE PAGES

Hao, Shijie; Cui, Lishan; Guo, Fangmin; ...

2015-03-09

Elastic strain in bulk metallic materials is usually limited to only a fraction of 1%. Developing bulk metallic materials showing large linear elasticity and high strength has proven to be difficult. Here, based on the synergistic effect between nanowires and orientated martensite NiTi shape memory alloy, we developed an in-situ Nb nanowires-orientated martensitic NiTi matrix composite showing an ultra-large linear elastic strain of 4% and an ultrahigh yield strength of 1.8 GPa. This material also has a high mechanical energy storage efficiency of 96% and a high energy storage density of 36 J/cm 3 that is almost one order ofmore » larger than that of spring steel. It is demonstrated that the synergistic effect allows the exceptional mechanical properties of nanowires to be harvested at macro scale and the mechanical properties of matrix to be greatly improved, resulting in these superior properties. This research provides new avenues for developing advanced composites with superior properties by using effective synergistic effect between components.« less

Calculation and characteristic analysis on synergistic effect of CF3I gas mixtures

NASA Astrophysics Data System (ADS)

Su, ZHAO; Yunkun, DENG; Yuhao, GAO; Dengming, XIAO

2018-06-01

CF3I is a potential SF6 alternative gas. In order to study the insulation properties and synergistic effects of CF3I/N2 and CF3I/CO2 gas mixtures, two-term approximate Boltzmann equations were used to obtain the ionization coefficient α, attachment coefficient η and the critical equivalent electrical field strength (E/N)cr. The results show that the (E/N)cr of CF3I gas at 300 K is 1.2 times that of SF6 gas, and CF3I/N2 and CF3I/CO2 gas mixtures both have synergistic effect occurred. The synergistic effect coefficient of CF3I/CO2 gas mixture was higher than that of CF3I/N2 gas mixture. But the (E/N)cr of CF3I/N2 is higher than that of CF3I/CO2 under the same conditions. When the content of CF3I exceeds 20%, the (E/N)cr of CF3I/N2 and CF3I/CO2 gas mixture increase linearly with the increasing of CF3I gas content. The breakdown voltage of CF3I/N2 gas mixture is also higher than that of CF3I/CO2 gas mixture in slightly non-uniform electrical field under power frequency voltage, but the synergistic effect coefficients of the two gas mixtures are basically the same.

Synergistic effect of casein glycomacropeptide on sodium caseinate foaming properties.

PubMed

Morales, R; Martinez, M J; Pilosof, A M R

2017-11-01

Several strategies to improve the interfacial properties and foaming properties of proteins may be developed; among them, the use of mixtures of biopolymers that exhibit synergistic interactions. The aim of the present work was to evaluate the effect of casein glycomacropeptide (CMP) on foaming and surface properties of sodium caseinate (NaCas) and to establish the role of protein interactions in the aqueous phase. To this end particles size, interfacial and foaming properties of CMP, NaCas and NaCas-CMP mixtures at pH 5.5 and 7 were determined. At both pH, the interaction between CMP and NaCas induced a decrease in the aggregation state of NaCas. Single CMP foams showed the highest and NaCas the lowest foam overrun (FO) and the mixture exhibited intermediate values. CMP foam quickly drained. The drainage profile of mixed foams was closer to NaCas foams; at pH 5.5, mixed foams drained even slower than NaCas foam, exhibiting a synergistic performance. Additionally, a strong synergism was observed on the collapse of mixed foams at pH 5.5. Finally, a model to explain the synergistic effect observed on foaming properties in CMP-NaCas mixtures has been proposed; the reduced aggregation state of NaCas in the presence of CMP, made it more efficient for foam stabilization. Copyright © 2017 Elsevier B.V. All rights reserved.

[Synergistic effects of lysozyme with EDTA-2Na on antibacterial activity].

PubMed

Li, Xiao-man; Wang, Xiao-yan; Gao, Xue-jun

2015-02-18

To evaluate the synergistic antibacterial effects of lysozyme with ethylenediaminetetraacetic acid disodium salt (EDTA-2Na) on Enterococcus faecalis (E. faecalis) and Porphyromonas endodontalis (P. endodontalis). E. faecalis and P. endodontalis were cultured and adjusted to 10(8) CFU/mL. Then 0.3, 0.5, 1, 2, 5, 10, 50, 100, 150 and 300 g/L of lysozyme were prepared with deionized water; and the lysozyme solutions were mixed with 0.5, 1.0, 2.0 g/L of EDTA-2Na, respectively. The bacteria and lysosome with/without EDTA-2Na interacted for 15 min, then water-soluble tetrazolium (WST) working solution was added and the activity of the bacteria was calculated by measuring optical densities at 450 nm and 630 nm with microplate spectrophotometer. Regarding the pure lysozyme from 0.5 g/L to 150 g/L, more E. faecalis and P. endodontalis were inhibited when the concentration of lysozyme was higher, especially for E. faecalis. There was synergistic effect of lysozyme with EDTA-2Na on antibacterial activity, which was related to the concentration of lysozyme. On E. faecalis, the antibacterial activity of lysozyme with EDTA-2Na was 1.2-3.7 folds than the pure lysozyme when the concentration of lysozyme was 0.5-50 g/L (P<0.05), and on P. endodontalis, the antibacterial activity of lysozyme with EDTA-2Na was 1.3-3.5 folds than the pure lysozyme when the concentration of lysozyme was 0.5-10 g/L (P<0.05). When the concentration of lysozyme was higher than 100 g/L, EDTA-2Na did not show synergistic effect on the antibacterial activity (P>0.05). For E. faecalis and P. endodontalis, a low concentration of lysozyme with EDTA-2Na showed significant synergistic antibacterial activity, while a high concentration of lysozyme with EDTA-2Na did not.

Effect of defect state on photon synergistic process in KLu2F7:Yb3+, Er3+ nanoparticles

NASA Astrophysics Data System (ADS)

Bian, Wenjuan; Lu, Wei; Qi, Yushuang; Yu, Xue; Zhou, Dacheng; Yang, Yong; Qiu, Jianbei; Xu, Xuhui

2016-10-01

The synergistic effect appeared due to the cooperative dual-wavelength excitation by near-infrared (NIR) and ultraviolet (UV) light in rare-earth doped nano-particles (NPs) is very important to improve solar cell efficiency. Herein, we studied the synergistic effect combined with the energy levels of Er3+ ions and the defect states in KLu2F7 NPs. The introduction of Ce3+ ions in KLu2F7:16%Yb3+, 2%Er3+ NPs results in significant improvement of synergistic effect by producing more vacancy defects (VK‧) which serves as shallow traps. We verify unambiguously that the control of the defects distribution exerts a facile approach to promote the synergistic effect with the assistance of Ce3+ ions doping.

Determining lower threshold concentrations for synergistic effects.

PubMed

Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas; Nørgaard, Katrine Banke; Mayer, Philipp; Cedergreen, Nina

2017-01-01

Though only occurring rarely, synergistic interactions between chemicals in mixtures have long been a point of focus. Most studies analyzing synergistic interactions used unrealistically high chemical concentrations. The aim of the present study is to determine the threshold concentration below which proven synergists cease to act as synergists towards the aquatic crustacean Daphnia magna. To do this, we compared several approaches and test-setups to evaluate which approach gives the most conservative estimate for the lower threshold for synergy for three known azole synergists. We focus on synergistic interactions between the pyrethroid insecticide, alpha-cypermethrin, and one of the three azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia magna immobilization. Three different experimental setups were applied: A standard 48h acute toxicity test, an adapted 48h test using passive dosing for constant chemical exposure concentrations, and a 14-day test. Synergy was defined as occuring in mixtures where either EC 50 values decreased more than two-fold below what was predicted by concentration addition (horizontal assessment) or as mixtures where the fraction of immobile organisms increased more than two-fold above what was predicted by independent action (vertical assessment). All three tests confirmed the hypothesis of the existence of a lower azole threshold concentration below which no synergistic interaction was observed. The lower threshold concentration, however, decreased with increasing test duration from 0.026±0.013μM (9.794±4.897μgL -1 ), 0.425±0.089μM (145.435±30.46μgL -1 ) and 0.757±0.253μM (249.659±83.44μgL -1 ) for prochloraz, propiconazole and epoxiconazole in standard 48h toxicity tests to 0.015±0.004μM (5.651±1.507μgL -1 ), 0.145±0.025μM (49.619±8.555μgL -1 ) and 0.122±0.0417μM (40.236±13.75μgL -1 ), respectively, in the 14-days tests. Testing synergy in relation to concentration addition provided

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

PubMed Central

Saha, Subbroto Kumar; Yin, Yingfu; Kim, Kyeongseok; Yang, Gwang-Mo; Abdal Dayem, Ahmed; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC. PMID:28498322

As(V) and Sb(V) co-adsorption onto ferrihydrite: synergistic effect of Sb(V) on As(V) under competitive conditions.

PubMed

Wu, Debo; Sun, Sheng-Peng; He, Minghe; Wu, Zhangxiong; Xiao, Jie; Chen, Xiao Dong; Wu, Winston Duo

2018-05-01

Competitive adsorption of As(V) and Sb(V) at environmentally relevant concentrations onto ferrihydrite was investigated. Batch experiments and XPS analyses confirmed that in a binary system, the presence of Sb(V) exhibited a slight synergistic effect on As(V) adsorption. XPS analyses showed that As(V) and Sb(V) adsorption led to obvious diminishment of Fe-O-Fe and Fe-O-H bonds respectively. At pH of 9, a more significant decrease of Fe-O-Fe was observed in the binary system than that in a single system, indicating that As(V) displayed an even stronger interaction with lattice oxygen atoms under competitive conditions. Basically, ionic strength demonstrated a negligible or positive influence on As(V) and Sb(V) adsorption in binary system. Study of adsorption sequence also indicated that the presence of Sb(V) showed a promotion effect on As(V) adsorption at neutral pHs. Considering that co-contamination of As and Sb in waters has been of great concern throughout the world, our findings contributed to a better understanding of their distribution, mobility, and fate in environment.

Synergistic effect of ultrasound and PEI on DNA transfection in vitro

PubMed Central

Deshpande, Mangesh C.; Prausnitz, Mark R.

2007-01-01

Ultrasound and poly(ethylenimine) (PEI) have each separately been shown to increase DNA transfection efficiency. This study tested the hypothesis that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. This in vitro study assessed transfection efficiency of two different DNA plasmids encoding green fluorescent protein and firefly luciferase in two different cells types, a primary culture of human aortic smooth muscle cells and an immortal line of human prostrate cancer cells. We found that ultrasound sonication increased transfection up to 18-fold, DNA complexation with PEI increased transfection up to 90-fold, and the combination of ultrasound and PEI synergistically increased transfection up to 200-fold, which resulted in reporter gene expression by 34% of cells. Kinetic measurements found that the effects of ultrasound alone acted quickly, whereas increased transfection by PEI either alone or in combination with ultrasound strongly benefited from a 4-h incubation with the DNA plasmid after sonication. Although serum reduced absolute expression levels, it did not affect the relative increase in transfection when ultrasound was added to PEI enhancement. Flow cytometry measurements showed that sonication increased intracellular uptake of labelled DNA complexed to PEI by 55% relative to PEI complexation alone. Electrophoresis assay showed no damage to DNA or PEI-DNA complexes after sonication. Overall, these results suggest that the combination of ultrasound and PEI can have a synergistic effect to increase DNA transfection. PMID:17258835

Combined Treatment of Xenon and Hypothermia in Newborn Rats - Additive or Synergistic Effect?

PubMed Central

Sabir, Hemmen; Walløe, Lars; Dingley, John; Smit, Elisa; Liu, Xun; Thoresen, Marianne

2014-01-01

Background Breathing the inert gas Xenon (Xe) enhances hypothermic (HT) neuroprotection after hypoxia-ischemia (HI) in small and large newborn animal models. The underlying mechanism of the enhancement is not yet fully understood, but the combined effect of Xe and HT could either be synergistic (larger than the two effects added) or simply additive. A previously published study, using unilateral carotid ligation followed by hypoxia in seven day old (P7) rats, showed that the combination of mild HT (35°C) and low Xe concentration (20%), both not being neuroprotective alone, had a synergistic effect and was neuroprotective when both were started with a 4 h delay after a moderate HI insult. To examine whether another laboratory could confirm this finding, we repeated key aspects of the study. Design/Methods After the HI-insult 120 pups were exposed to different post-insult treatments: three temperatures (normothermia (NT) NT37°C, HT35°C, HT32°C) or Xe concentrations (0%, 20% or 50%) starting either immediately or with a 4 h delay. To assess the synergistic potency of Xe-HT, a second set (n = 101) of P7 pups were exposed to either HT35°C+Xe0%, NT+Xe20% or a combination of HT35°C+Xe20% starting with a 4 h delay after the insult. Brain damage was analyzed using relative hemispheric (ligated side/unligated side) brain tissue area loss after seven day survival. Results Immediate HT32°C (p = 0.042), but not HT35°C significantly reduced brain injury compared to NT37°C. As previously shown, adding immediate Xe50% to HT32°C increased protection. Neither 4 h-delayed Xe20%, nor Xe50% at 37°C significantly reduced brain injury (p>0.050). In addition, neither 4 h-delayed HT35°C alone, nor HT35°C+Xe20% reduced brain injury. We found no synergistic effect of the combined treatments in this experimental model. Conclusions Combining two treatments that individually were ineffective (delayed HT35°C and delayed Xe20%) did not exert neuroprotection when combined

Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium.

PubMed

Liu, Li; Li, Wei; Wei, Ke; Cao, Jun; Luo, Jie; Wang, Bin; Min, Su

2013-06-01

Inhaled anesthetics increase the incidence of postoperative residual neuromuscular blockade, and the mechanism is still unclear. We have investigated the synergistic effect of low-concentration inhaled anesthetics and rocuronium on inhibition of the inward current of the adult-type muscle nicotinic acetylcholine receptor (ε-nAChR). Adult-type mouse muscle ε-nAChR was expressed in HEK293 cells by liposome transfection. The inward current of the ε-nAChR was activated by use of 10 μmol/L acetylcholine alone or in combination with different concentrations of sevoflurane, isoflurane, or rocuronium. The concentration-response curves of five cells were constructed, and the data yielded the 5, 25, and 50 % inhibitory concentrations (IC5, IC25, and IC50, respectively) for single-drug application. Subsequently, the functional channels were perfused by adding 0.5 IC5 of either sevoflurane or isoflurane (aqueous concentrations 140 and 100 μmol/L, respectively) to the solution, followed by addition of IC5, IC25, or IC50 rocuronium. The amount of inhibition was calculated to quantify their synergistic effect. The inhibitory effect of rocuronium was enhanced by sevoflurane or isoflurane in a concentration-dependent manner. Sevoflurane or isoflurane (0.5 IC5) with rocuronium at IC5, IC25, and IC50 synergistically inhibited the current amplitude of adult-type muscle ε-nAChR. When the IC5 of rocuronium was used, isoflurane had a stronger synergistic effect than sevoflurane (p < 0.05). When rocuronium was applied at higher concentrations (IC25 and IC50), sevoflurane had an effect similar to that of isoflurane. For both inhaled anesthetics, the synergistic effect was more intense for rocuronium at IC5 than for rocuronium at IC25 or IC50. Residual-concentration sevoflurane or isoflurane has a strong synergistic effect with rocuronium at clinically relevant residual concentrations. A lower rocuronium concentration resulted in a stronger synergistic effect.

Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.

PubMed

Pofali, P A; Singh, B; Dandekar, P; Jain, R D; Maharjan, S; Choi, Y J; Arote, R B; Cho, C S

2016-05-01

The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders. © 2015 Wiley Periodicals, Inc.

Synergistic effects of fire and elephants on arboreal animals in an African savanna.

PubMed

Pringle, Robert M; Kimuyu, Duncan M; Sensenig, Ryan L; Palmer, Todd M; Riginos, Corinna; Veblen, Kari E; Young, Truman P

2015-11-01

Disturbance is a crucial determinant of animal abundance, distribution and community structure in many ecosystems, but the ways in which multiple disturbance types interact remain poorly understood. The effects of multiple-disturbance interactions can be additive, subadditive or super-additive (synergistic). Synergistic effects in particular can accelerate ecological change; thus, characterizing such synergies, the conditions under which they arise, and how long they persist has been identified as a major goal of ecology. We factorially manipulated two principal sources of disturbance in African savannas, fire and elephants, and measured their independent and interactive effects on the numerically dominant vertebrate (the arboreal gekkonid lizard Lygodactylus keniensis) and invertebrate (a guild of symbiotic Acacia ants) animal species in a semi-arid Kenyan savanna. Elephant exclusion alone (minus fire) had negligible effects on gecko density. Fire alone (minus elephants) had negligible effects on gecko density after 4 months, but increased gecko density twofold after 16 months, likely because the decay of fire-damaged woody biomass created refuges and nest sites for geckos. In the presence of elephants, fire increased gecko density nearly threefold within 4 months of the experimental burn; this occurred because fire increased the incidence of elephant damage to trees, which in turn improved microhabitat quality for geckos. However, this synergistic positive effect of fire and elephants attenuated over the ensuing year, such that only the main effect of fire was evident after 16 months. Fire also altered the structure of symbiotic plant-ant assemblages occupying the dominant tree species (Acacia drepanolobium); this influenced gecko habitat selection but did not explain the synergistic effect of fire and elephants. However, fire-driven shifts in plant-ant occupancy may have indirectly mediated this effect by increasing trees' susceptibility to elephant damage. Our

NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning

PubMed Central

Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

2016-01-01

Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

Making Pedagogical Adaptability Less Obvious

ERIC Educational Resources Information Center

Vagle, Mark D.

2016-01-01

In this article, I try to make pedagogical adaptability a bit less obvious. In particular, I use some post-structural philosophical ideas and some concepts at the intersections of social class and race to re-interpret Dylan Wiliam's conception of formative assessment. I suggest that this interpretation can provide opportunities to resist the urge…

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.

PubMed

Cazzola, Mario; Calzetta, Luigino; Ora, Josuel; Puxeddu, Ermanno; Rogliani, Paola; Matera, Maria Gabriella

2015-10-01

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synergistic effect of cellulase and xylanase during hydrolysis of natural lignocellulosic substrates.

PubMed

Song, Hui-Ting; Gao, Yuan; Yang, Yi-Min; Xiao, Wen-Jing; Liu, Shi-Hui; Xia, Wu-Cheng; Liu, Zi-Lu; Yi, Li; Jiang, Zheng-Bing

2016-11-01

Synergistic combination of cellulase and xylanase has been performed on pre-treated substrates in many previous studies, while few on natural substrates. In this study, three unpretreated lignocellulosic substrates were studied, including corncob, corn stover, and rice straw. The results indicated that when the mixed cellulase and xylanase were applied, reducing sugar concentrations were calculated as 19.53, 15.56, and 17.35mg/ml, respectively, based on the 3,5 dinitrosalicylic acid (DNS) method. Compared to the treatment with only cellulose, the hydrolysis yields caused by mixed cellulase and xylanase were improved by 133%, 164%, and 545%, respectively. In addition, the conversion yield of corncob, corn stover, and rice straw by cellulase-xylanase co-treatment reached 43.9%, 48.5%, and 40.2%, respectively, based on HPLC analysis, which confirmed the synergistic effect of cellulase-xylanase that was much higher than either of the single enzyme treatment. The substrate morphology was also evaluated to explore the synergistic mechanism of cellulase-xylanase. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic Effect of Light and Fusicoccin on Stomatal Opening 1

PubMed Central

Assmann, Sarah M.; Schwartz, Amnon

1992-01-01

Upon incubation of epidermal peels of Commelina communis in 1 millimolar KCl, a synergistic effect of light and low fusicoccin (FC) concentrations on stomatal opening is observed. In 1 millimolar KCl, stomata remain closed even in the light. However, addition of 0.1 micromolar FC results in opening up to 12 micrometers. The same FC concentration stimulates less than 5 micrometers of opening in darkness. The synergistic effect (a) decreases with increasing FC or KCl concentrations; (b) is dark-reversible; (c) like stomatal opening in high KCl concentrations (120 millimolar) is partially inhibited by the K+ channel blocker, tetraethyl-ammonium+ (20 millimolar). In whole-cell patch-clamp experiments with guard cell protoplasts of Vicia faba, FC (1 or 10 micromolar) stimulates an increase in outward current that is essentially voltage independent between - 100 and +60 millivolts, and occurs even when the membrane potential is held at a voltage (−60 millivolts) at which K+ channels are inactivated. These results are indicative of FC activation of a H+ pump. FC effects on the magnitude of inward and outward K+ currents are not observed. Epidermal peel and patch clamp data are both consistent with the hypothesis that the plasma membrane H+ ATPase of guard cells is a primary locus for the FC effect on stomatal apertures. PMID:16668799

Synergistic effects between intrathecal clonidine and neostigmine in the formalin test.

PubMed

Yoon, M H; Yoo, K Y; Jeong, C Y

2001-08-01

Spinal alpha-2 adrenoceptors and cholinergic receptors are involved in the regulation of acute nociception and the facilitated processing. The aim of this study was to examine the pharmacological effect of an intrathecal alpha-2 agonist and a cholinesterase inhibitor on the facilitated pain model induced by formalin injection and to determine the nature of drug interaction using an isobolographic analysis. Both intrathecal clonidine and neostigmine dose-dependently suppressed the flinching during phase 1 and phase 2. Intrathecal pretreatment with atropine reversed the antinociceptive effects of clonidine and neostigmine in both phases. Pretreatment with intrathecal yohimbine attenuated the effect of clonidine. The antinociception of clonidine and neostigmine was not reversed by mecamylamine. Isobolographic analysis showed that intrathecal clonidine and neostigmine acted synergistically in both phase 1 and 2. Intrathecal pretreatment with atropine and yohimbine antagonized the effect of the mixture of clonidine and neostigmine in both phases, but no antagonism was observed with mecamylamine pretreatment. These data indicate that spinal clonidine and neostigmine are effective to counteract the facilitated state evoked formalin stimulus, and these two drugs interact in a synergistic fashion. In addition, the analgesic action of intrathecal clonidine is mediated by spinal muscarinic receptors as well as alpha-2 adrenoceptors.

In vitro synergistic effects of fisetin and norfloxacin against aquatic isolates of Serratia marcescens.

PubMed

Dong, Jing; Ruan, Jing; Xu, Ning; Yang, Yibin; Ai, Xiaohui

2016-01-01

Serratia marcescens is a common pathogenic bacterium that can cause infections in both humans and animals. It can cause a range of diseases, from slight wound infections to life-threatening bacteraemia and pneumonia. The emergence of antimicrobial resistance has limited the treatment of the diseases caused by the bacterium to a great extent. Consequently, there is an urgent need to develop novel antimicrobial strategies against this pathogen. Synergistic strategy is a new approach to treat the infections caused by drug-resistant bacteria. In this paper, we isolated and identified the first multi-resistant pathogenic Serratia marcescens strain from diseased soft-shelled turtles (Pelodiscus sinensis) in China. We then performed a checkerboard assay; the results showed that out of 10 tested natural products fisetin had synergistic effects against S. marcescens when combined with norfloxacin. The time-kill curve assay further confirmed the results of the checkerboard assay. We found that this novel synergistic effect could significantly reduce the dosage of norfloxacin against S. marcescens. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Synergistic effect of ozonation and ionizing radiation for PVA decomposition.

PubMed

Sun, Weihua; Chen, Lujun; Zhang, Yongming; Wang, Jianlong

2015-08-01

Ozonation and ionizing radiation are both advanced oxidation processes (AOPs) without chemical addition and secondary pollution. Also, the two processes' efficiency is determined by different pH conditions, which creates more possibilities for their combination. Importantly, the combined process of ozonation and ionizing radiation could be suitable for treating wastewaters with extreme pH values, i.e., textile wastewater. To find synergistic effects, the combined process of ozonation and ionizing radiation mineralization was investigated for degradation of polyvinyl alcohol (PVA) at different pH levels. A synergistic effect was found at initial pH in the range 3.0-9.4. When the initial pH was 3.0, the combined process of ozonation and ionizing radiation gave a PVA mineralization degree of 17%. This was 2.7 times the sum achieved by the two individual processes, and factors of 2.1 and 1.7 were achieved at initial pH of 7.0 and 9.4, respectively. The combined process of ozonation and ionizing radiation was demonstrated to be a feasible strategy for treatment of PVA-containing wastewater. Copyright © 2015. Published by Elsevier B.V.

Synergistic effect on co-gasification reactivity of biomass-petroleum coke blended char.

PubMed

Wei, Juntao; Guo, Qinghua; Gong, Yan; Ding, Lu; Yu, Guangsuo

2017-06-01

In this work, effects of gasification temperature (900°C-1100°C) and blended ratio (3:1, 1:1, 1:3) on reactivity of petroleum coke and biomass co-gasification were studied in TGA. Quantification analysis of active AAEM transformation and in situ investigation of morphological structure variations in gasification were conducted respectively using inductively coupled plasma optical emission spectrometer and heating stage microscope to explore synergistic effect on co-gasification reactivity. The results indicated that char gasification reactivity was enhanced with increasing biomass proportion and gasification temperature. Synergistic effect on co-gasification reactivity was presented after complete generation of biomass ash, and gradually weakened with increasing temperature from 1000°C to 1100°C after reaching the most significant value at 1000°C. This phenomenon was well related with the appearance of molten biomass ash rich in glassy state potassium and the weakest inhibition effect on active potassium transformation during co-gasification at the temperature higher than 1000°C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

PubMed

Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

2016-11-16

The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

Synergistic effect of business reputation in the result of application of innovations on the enterprises of the transport industry

NASA Astrophysics Data System (ADS)

Doroshin, Ivan; Diakonova, Sophia; Sharapova, Elena

2017-10-01

In the conditions of dynamic innovative development of the enterprises of transport branch along with maintaining economic instability it has become necessary to consider not only traditional factors at assessment of efficiency of activity and cost of business, but also consider business reputation factor, which depends on the level of innovative development of the enterprise and generates effect of synergy. Paper considers the concept of synergistic effect. Classification of types of synergistic effects is cited. Estimation procedure for influence of the technical level and innovative development of transport enterprises on the value of business reputation is considered. Functional dependence of the cost of business reputation on the innovative development and synergistic effect is defined.

Discovering Synergistic Drug Combination from a Computational Perspective.

PubMed

Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen; Li, Guanghui

2018-03-30

Synergistic drug combinations play an important role in the treatment of complex diseases. The identification of effective drug combination is vital to further reduce the side effects and improve therapeutic efficiency. In previous years, in vitro method has been the main route to discover synergistic drug combinations. However, many limitations of time and resource consumption lie within the in vitro method. Therefore, with the rapid development of computational models and the explosive growth of large and phenotypic data, computational methods for discovering synergistic drug combinations are an efficient and promising tool and contribute to precision medicine. It is the key of computational methods how to construct the computational model. Different computational strategies generate different performance. In this review, the recent advancements in computational methods for predicting effective drug combination are concluded from multiple aspects. First, various datasets utilized to discover synergistic drug combinations are summarized. Second, we discussed feature-based approaches and partitioned these methods into two classes including feature-based methods in terms of similarity measure, and feature-based methods in terms of machine learning. Third, we discussed network-based approaches for uncovering synergistic drug combinations. Finally, we analyzed and prospected computational methods for predicting effective drug combinations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

An enhanced Petri-net model to predict synergistic effects of pairwise drug combinations from gene microarray data.

PubMed

Jin, Guangxu; Zhao, Hong; Zhou, Xiaobo; Wong, Stephen T C

2011-07-01

Prediction of synergistic effects of drug combinations has traditionally been relied on phenotypic response data. However, such methods cannot be used to identify molecular signaling mechanisms of synergistic drug combinations. In this article, we propose an enhanced Petri-Net (EPN) model to recognize the synergistic effects of drug combinations from the molecular response profiles, i.e. drug-treated microarray data. We addressed the downstream signaling network of the targets for the two individual drugs used in the pairwise combinations and applied EPN to the identified targeted signaling network. In EPN, drugs and signaling molecules are assigned to different types of places, while drug doses and molecular expressions are denoted by color tokens. The changes of molecular expressions caused by treatments of drugs are simulated by two actions of EPN: firing and blasting. Firing is to transit the drug and molecule tokens from one node or place to another, and blasting is to reduce the number of molecule tokens by drug tokens in a molecule node. The goal of EPN is to mediate the state characterized by control condition without any treatment to that of treatment and to depict the drug effects on molecules by the drug tokens. We applied EPN to our generated pairwise drug combination microarray data. The synergistic predictions using EPN are consistent with those predicted using phenotypic response data. The molecules responsible for the synergistic effects with their associated feedback loops display the mechanisms of synergism. The software implemented in Python 2.7 programming language is available from request. stwong@tmhs.org.

Synergistic anticonvulsant effects of pregabalin and amlodipine on acute seizure model of epilepsy in mice.

PubMed

Qureshi, Itefaq Hussain; Riaz, Azra; Khan, Rafeeq Alam; Siddiqui, Afaq Ahmed

2017-08-01

Status epilepticus is a life threatening neurological medical emergency. It may cause serious damage to the brain and even death in many cases if not treated properly. There is limited choice of drugs for the short term and long term management of status epilepticus and the dugs recommended for status epilepticus possess various side effects. The present study was designed to investigate synergistic anticonvulsant effects of pregabalin with amlodipine on acute seizure model of epilepsy in mice. Pentylenetetrazole was used to induce acute seizures which mimic status epilepticus. Pregabalin and amlodipine were used in combination to evaluate synergistic anti-seizure effects on acute seizure model of epilepsy in mice. Diazepam and valproate were used as reference dugs. The acute anti-convulsive activity of pregabalin with amlodipine was evaluated in vivo by the chemical induced seizures and their anti-seizure effects were compared with pentylenetetrazole, reference drugs and to their individual effects. The anti-seizure effects of tested drugs were recorded in seconds on seizure characteristics such as latency of onset of threshold seizures, rearing and fallings and Hind limbs tonic extensions. The seizure protection and mortality to the animals exhibited by the drugs were recorded in percentage. Combination regimen of pregabalin with amlodipine exhibited dose dependent significant synergistic anticonvulsant effects on acute seizures which were superior to their individual effects and equivalent to reference drugs.

Synergistic Effect of Co-utilization of Coal and Biomass Char: An Overview

NASA Astrophysics Data System (ADS)

Paiman, M. E. S.; Hamzah, N. S.; Idris, S. S.; Rahman, N. A.; Ismail, K.

2018-05-01

Global concerns on impact of greenhouse gases emission, mostly released from coal-fired power plant, and the depletion of fossil fuel particularly coal, has led the production of electricity from alternatives resources such as co-utilization technologies. Previous studies proved that the co-utilization of coal and biomass/biomass chars has significantly reduced the emission of greenhouse gases either during the pyrolysis, combustion or gasification process in laboratories, pilots as well as in the industrial scales. Interestingly, most of the studies reported the presence of synergistic effect during the co-utilization processes particularly between coal and biomass char while some are not. Biomass chars were found to have porous and highly disorder carbon structure and belong to the class of most reactive carbon material, resulting to be more reactive than those hard coal and lignite. Up to date, microwave assisted pyrolysis is one of the best and latest techniques employed to produce better quality of biomass chars and it is also reduce the processing cost. Lot of works has been done regarding on the existence of synergistic effects during its co-utilization. However, the knowledge is limited to thermal and product characteristics so far. Even so, the specific reasons behind its existence are yet to understand well. Therefore, in this paper, the emphasis will be given on the synergistic effects on emission characteristics of co-utilization of coal and biomass chars so that it can be apply in energy-based industries to help in reduction of the greenhouse gases emission.

Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus

PubMed Central

Morán-Santibañez, Karla; Cruz-Suárez, Lucia Elizabeth; Ricque-Marie, Denis; Robledo, Daniel; Freile-Pelegrín, Yolanda; Peña-Hernández, Mario A.; Rodríguez-Padilla, Cristina

2016-01-01

Sulfated polysaccharides (SPs) extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera, Eisenia arborea, Pelvetia compressa, Ulva intestinalis, and Solieria filiformis) were tested in this study in order to evaluate their effect on measles virus in vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation) and low cytotoxicity (MTT assay) at inhibitory concentrations. SPs from Eisenia arborea and Solieria filiformis showed the highest antiviral activities (confirmed by qPCR) and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL of E. arborea and S. filiformis SPs, resp.), which exhibited by far a higher inhibitory effect (96% syncytia reduction) in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL of E. arborea and S. filiformis, resp.). Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents. PMID:27419139

Kinetic model of water disinfection using peracetic acid including synergistic effects.

PubMed

Flores, Marina J; Brandi, Rodolfo J; Cassano, Alberto E; Labas, Marisol D

2016-01-01

The disinfection efficiencies of a commercial mixture of peracetic acid against Escherichia coli were studied in laboratory scale experiments. The joint and separate action of two disinfectant agents, hydrogen peroxide and peracetic acid, were evaluated in order to observe synergistic effects. A kinetic model for each component of the mixture and for the commercial mixture was proposed. Through simple mathematical equations, the model describes different stages of attack by disinfectants during the inactivation process. Based on the experiments and the kinetic parameters obtained, it could be established that the efficiency of hydrogen peroxide was much lower than that of peracetic acid alone. However, the contribution of hydrogen peroxide was very important in the commercial mixture. It should be noted that this improvement occurred only after peracetic acid had initiated the attack on the cell. This synergistic effect was successfully explained by the proposed scheme and was verified by experimental results. Besides providing a clearer mechanistic understanding of water disinfection, such models may improve our ability to design reactors.

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells.

PubMed

Labsch, Sabrina; Liu, Li; Bauer, Nathalie; Zhang, Yiyao; Aleksandrowicz, Ewa; Gladkich, Jury; Schönsiegel, Frank; Herr, Ingrid

2014-05-01

Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs.

Non-equilibrium synergistic effects in atmospheric pressure plasmas.

PubMed

Guo, Heng; Zhang, Xiao-Ning; Chen, Jian; Li, He-Ping; Ostrikov, Kostya Ken

2018-03-19

Non-equilibrium is one of the important features of an atmospheric gas discharge plasma. It involves complicated physical-chemical processes and plays a key role in various actual plasma processing. In this report, a novel complete non-equilibrium model is developed to reveal the non-equilibrium synergistic effects for the atmospheric-pressure low-temperature plasmas (AP-LTPs). It combines a thermal-chemical non-equilibrium fluid model for the quasi-neutral plasma region and a simplified sheath model for the electrode sheath region. The free-burning argon arc is selected as a model system because both the electrical-thermal-chemical equilibrium and non-equilibrium regions are involved simultaneously in this arc plasma system. The modeling results indicate for the first time that it is the strong and synergistic interactions among the mass, momentum and energy transfer processes that determine the self-consistent non-equilibrium characteristics of the AP-LTPs. An energy transfer process related to the non-uniform spatial distributions of the electron-to-heavy-particle temperature ratio has also been discovered for the first time. It has a significant influence for self-consistently predicting the transition region between the "hot" and "cold" equilibrium regions of an AP-LTP system. The modeling results would provide an instructive guidance for predicting and possibly controlling the non-equilibrium particle-energy transportation process in various AP-LTPs in future.

Fast dissolving drug-drug eutectics with improved compressibility and synergistic effects.

PubMed

Thipparaboina, Rajesh; Thumuri, Dinesh; Chavan, Rahul; Naidu, V G M; Shastri, Nalini R

2017-06-15

Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties. A 6 to 9 fold enhancement in % dissolution efficiency was found at 1min suggesting the fast dissolving capabilities of the eutectic mixtures when compared to plain drug. In addition, eutectic mixtures have shown improved hardness compared to plain drugs. EP and EPHC have shown around 5 fold and 3 fold improvements in hardness respectively at 10MPa when compared to plain etodolac. Cell culture studies have shown improved effects of EP. Western blotting analysis revealed that the said combination successfully reduced various inflammatory mediators like TNF-α, COX-2 and IL-6. Whereas, the eutectic combination EPHC has shown enhanced cytotoxic effects with synergistic combination index and favorable dose reduction index. The generated multi-component systems EP and EPHC with fast dissolving capabilities, improved hardness at lower pressures and synergistic effects represent prospective combinations for effective treatment of osteoarthritis and cancer chemotherapy respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates.

PubMed

Denardi, Laura Bedin; Mario, Débora Alves Nunes; Loreto, Érico Silva; Santurio, Janio Morais; Alves, Sydney Hartz

2015-03-01

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata , a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro , notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

Synergistic effect of baicalein, wogonin and oroxylin A mixture: multistep inhibition of the NF-κB signalling pathway contributes to an anti-inflammatory effect of Scutellaria root flavonoids.

PubMed

Shimizu, Tomofumi; Shibuya, Nobuhiko; Narukawa, Yuji; Oshima, Naohiro; Hada, Noriyasu; Kiuchi, Fumiyuki

2018-01-01

Scutellaria root, the root of Scutellaria baicalensis Georgi, is a crude drug used for inflammatory diseases. In our previous report, the combination of flavonoids contained in Scutellaria root have been found to inhibit PGE 2 production more strongly than individual flavonoids. Here, to investigate the mechanism of the synergistic effect, we examined the effects of an equimolar mixture (F-mix) of baicalein (1), wogonin (2) and oroxylin A (3) on the production of PGE 2 in LPS-treated J774.1 cells. Although 1 and 3 inhibited COX-2 activity, the F-mix showed no synergistic effect on COX-2 inhibition. Therefore, we investigated the steps leading to the activation of COX-2 protein. Compounds 1-3 and F-mix inhibited the expression of COX-2 protein. However, only 2 inhibited the expression of COX-2 mRNA among the flavonoids, and the F-mix showed no synergistic effect. Only 1 inhibited NF-κB translocation into the nucleus, and the F-mix showed no synergistic effect. Although 2 did not affect NF-κB translocation, it strongly inhibited NF-κB-dependent transcriptional activity, and the F-mix inhibited the activity slightly more than 2. Compounds 1-3 also inhibited NO production, and the F-mix showed a synergistic effect. However, the effects of each flavonoid on the expression of iNOS mRNA were not consistent with those on COX-2 mRNA. Because the flavonoids inhibit different steps in the production of PGE 2 and NO, and their mixture did not show apparent synergistic effects in each step, we conclude that the synergistic effect of the flavonoid mixture reflects the total effect of the flavonoids inhibiting different steps in the NF-κB signalling pathway.

Seasonal variation of Brazilian red propolis: Antibacterial activity, synergistic effect and phytochemical screening.

PubMed

Regueira, M S; Tintino, Saulo Relison; da Silva, Ana Raquel Pereira; Costa, Maria do Socorro; Boligon, Aline Augusti; Matias, Edinardo F F; de Queiroz Balbino, Valdir; Menezes, Irwin R A; Melo Coutinho, Henrique Douglas

2017-09-01

The aim of this study was to investigate the effect of the dry and rainy season on the antibacterial activity and chemical composition of the Brazilian red propolis. The samples were collected in rainy (RP-PER) and dry (RP-PED) seasons and analyzed by HPLC-DAD. The extracts were tested alone and in association with antibiotics against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The HPLC analysis identified luteolin and quercetin as the main compounds. Seasonal variation was observed according to concentrations of the compounds. The MIC values against E. coli ranged from 128 μg/mL to 512 μg/mL (EC 06 and EC ATCC). The red propolis showed MIC values of 512 μg/mL against both strains of P. aeruginosa used in our study (PA03 and PA24) and against strains of Gram-positive bacteria S. aureus the MICs ranged from 64 μg/mL to ≥1024 μg/mL (SA10). A synergistic effect was observed when we combined the RP-PED with gentamicin against all the strains tested. When we combined the RP-PED with Imipenem, we only observed synergistic effect against P. aeruginosa. According to our synergistic activity results, the utilization of red propolis collected in the drier periods can be used as an adjuvant against multiresistant bacterial infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections.

PubMed

Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen

2016-09-01

Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dihydroartemisinin and Curcumin Synergistically Induce Apoptosis in SKOV3 Cells Via Upregulation of MiR-124 Targeting Midkine.

PubMed

Zhao, Jiaojiao; Pan, Yuchen; Li, Xiujun; Zhang, Xuefang; Xue, Yaxian; Wang, Tingting; Zhao, Shuli; Hou, Yayi

2017-01-01

Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay. The cell cycle and apoptosis of SKOV3 cells were monitored by flow cytometry. The mRNA and protein expression levels of target genes were respectively examined by qRT-PCR and western blot. The biological effects of miR-124 on midkine (MK) were verified by a luciferase activity analysis. Combined treatment of DHA and Cur synergistically decreased cell viability, arrested cell cycle, and promoted apoptosis in SKOV3 cells. Moreover, it significantly attenuated the expression of oncogene MK and synergistically upregulated the expression of miR-124. Furthermore, miR-124 was verified to bind directly to the 3'-untranslated region of MK mRNA, resulting in mRNA degradation and reduced MK protein levels. The combination of DHA with Cur significantly inhibited tumor growth in xenograft nude mice without obvious toxicity. Co-treatment with DHA and Cur exhibited a synergistic anti-tumor effect on SKOV3 cells both in vitro and in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.

Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment.

PubMed

Wang, Jia; Xia, Shi'an; Zhu, Zhizhen

2015-03-01

Biguanides, used for anti-diabetic drugs, bring more attention in cancer research for their beneficial effects. Phenformin is more potent than metformin. However its potential application as a anti-cancer regent is far behind metformin. In order to investigate any beneficial effect of combination of Phenformin and radiotherapy, non-small cell lung cancer cell lines A549 and H1299 were exposure under different dose of ionizing radiation with or without Phenformin. Results indicated Phenformin showed synergistic effect and could induce more cancer cell apoptosis and inhibition of tumor growth compared with ionizing radiation alone. Furthermore, this synergistic effect may be through different pathway according to cancer cell genotype background. Our results showed Phenformin induced AMPK activation in A549 but not H1299. However, Phenformin activated eIF2α in both cell lines. Our findings implicated Phenformin may be used as radiosensitizer for non-small cell lung cancer therapy.

Evaluation of synergistic anticandidal and apoptotic effects of ferulic acid and caspofungin against Candida albicans.

PubMed

Canturk, Zerrin

2018-01-01

This study aimed to investigate the synergy between anticandidal and apoptotic effects of ferulic acid and caspofungin against Candida albicans and Candida glabrata, with the help of a quantitative checkerboard microdilution assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) as a viability dye. Apoptotic effects of caspofungin and ferulic acid concentrations (alone and combined) were analyzed for C. albicans and C. glabrata based on annexin V-propidium iodide binding capacities using flow cytometric analysis. C. albicans showed a synergistic effect, represented by a fractional inhibitory concentration index of < 0.5, but C. glabrata showed no synergistic effect (fractional inhibitory concentration index > 0.5). Early and late apoptotic effects of caspofungin and ferulic acid concentrations (1 μg/mL and 1000 μg/mL) were calculated as 55.7% and 18.3%, respectively, while their necrotic effects were determined as 5.8% and 51.6%, respectively, using flow cytometric analyses. The apoptotic effects of the combination of caspofungin and ferulic acid at concentrations of 1 μg/mL and 1000 μg/mL on C. albicans and C. glabrata were 73.0% and 48.7%, respectively. Ferulic acid also demonstrated a synergistic effect in combination with caspofungin against C. albicans. Another possibility is to combine the existing anticandidal drug with phytochemicals to enhance the efficacy of anticandidal drug. Copyright © 2017. Published by Elsevier B.V.

Synergistic effect of ultrasonic pre-treatment combined with UV irradiation for secondary effluent disinfection.

PubMed

Jin, Xin; Li, Zifu; Xie, Lanlan; Zhao, Yuan; Wang, Tingting

2013-11-01

The ultraviolet (UV) disinfection efficiency is often affected by suspended solids (SS). Given their high concentration or large particle size, SS can scatter UV light and provide shielding for bacteria. Thus, ultrasound is often employed as a pre-treatment process to improve UV disinfection. This work investigated the synergistic effect of ultrasound combined with UV for secondary effluent disinfection. Bench-scale experiments were conducted in using samples obtained from secondary sedimentation tanks. These tanks belonged to three wastewater treatment plants in Beijing that use different kinds of biological treatment methods. Several parameters may contribute to the changes in the efficiency of ultrasound and UV disinfection. Thus, the frequency and energy density of ultrasound, as well as the SS, were investigated. Results demonstrated that samples which have relatively higher SS concentrations or higher percentages of larger particles have less disinfection efficiency using UV disinfection alone. However, the presence of ultrasound could improve the disinfection efficiency because it has synergistic effect. Changes in the particle size distribution and SS concentration notably affected the efficiency of UV disinfection. The efficiency of Escherichia coli elimination can be decreased by 1.2 log units as the SS concentration increases from 16.9 mg/l to 25.4 mg/l at a UV energy density of 40 mJ/cm(2). UV disinfection alone reduced the E. coli population by 3.4 log units. However, the synergistic disinfection of ultrasound and UV could reach 5.4 log units during the reduction of E. coli at a 40 kHz frequency and an energy density of 2.64 kJ/l. The additional synergistic effect is 1.1 log units. Copyright © 2013 Elsevier B.V. All rights reserved.

St8sia2 deficiency plus juvenile cannabis exposure in mice synergistically affect higher cognition in adulthood.

PubMed

Tantra, Martesa; Kröcher, Tim; Papiol, Sergi; Winkler, Daniela; Röckle, Iris; Jatho, Jasmin; Burkhardt, Hannelore; Ronnenberg, Anja; Gerardy-Schahn, Rita; Ehrenreich, Hannelore; Hildebrandt, Herbert

2014-12-15

The neural cell adhesion molecule (NCAM) and its functionally linked polysialyltransferases, ST8SIA2 and ST8SIA4, are crucial for synaptic plasticity. Variations in encoding genes have been associated with mental illness. Since cannabinoids can alter NCAM polysialylation, we hypothesized that delta-9-tetrahydrocannabinol (Δ9-THC) might act as environmental 'second hit' regarding cognition of St8sia2(-/-) mice. These mice show per se minor behavioral abnormalities, consisting of reduced anxiety and mild cognitive deficits. Chronic Δ9-THC treatment of juvenile male wildtype mice (St8sia2(+/+)) (7mg/kg every other day over 3 weeks) did not appreciably affect cognition. St8sia2(-/-) mice, however, displayed a synergistic negative consequence of Δ9-THC on learning/memory, accompanied by polysialic acid-free NCAM-180 reduction in hippocampus and polysialic acid increase in dentate outer molecular layer. These synergistic effects became obvious only months after the last Δ9-THC. We conclude that juvenile cannabis exposure may cause delayed but lasting damage on cognition in subjects genetically predisposed to altered NCAM polysialylation. Copyright © 2014 Elsevier B.V. All rights reserved.

Synergistic effect on thermal behavior during co-pyrolysis of lignocellulosic biomass model components blend with bituminous coal.

PubMed

Wu, Zhiqiang; Wang, Shuzhong; Zhao, Jun; Chen, Lin; Meng, Haiyu

2014-10-01

Co-thermochemical conversion of lignocellulosic biomass and coal has been investigated as an effective way to reduce the carbon footprint. Successful evaluating on thermal behavior of the co-pyrolysis is prerequisite for predicting performance and optimizing efficiency of this process. In this paper, pyrolysis and kinetics characteristics of three kinds of lignocellulosic biomass model components (cellulose, hemicellulose, and lignin) blended with a kind of Chinese bituminous coal were explored by thermogravimetric analyzer and Kissinger-Akahira-Sunose method. The results indicated that the addition of model compounds had different synergistic effects on thermal behavior of the bituminous coal. The cellulose showed positive synergistic effects on the thermal decomposition of the coal bituminous coal with lower char yield than calculated value. For hemicellulose and lignin, whether positive or negative synergistic was related to the mixed ratio and temperature range. The distribution of the average activation energy values for the mixtures showed nonadditivity performance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Can obviously intoxicated patrons still easily buy alcohol at on-premise establishments?

PubMed Central

Toomey, Traci L.; Lenk, Kathleen M.; Nederhoff, Dawn M.; Nelson, Toben F.; Ecklund, Alexandra M.; Horvath, Keith J.; Erickson, Darin J.

2015-01-01

Background Excessive alcohol consumption at licensed alcohol establishments (i.e., bars and restaurants) has been directly linked to alcohol-related problems such as traffic crashes and violence. Historically, alcohol establishments have had a high likelihood of selling alcohol to obviously intoxicated patrons (also referred to as “overservice”) despite laws prohibiting these sales. Given the risks associated with overservice and the need for up-to-date data, it is critical that we monitor the likelihood of sales to obviously intoxicated patrons. Methods To assess the current likelihood of a licensed alcohol establishment selling alcohol to an obviously intoxicated patron, we conducted pseudo-intoxicated purchase attempts (i.e., actors attempt to purchase alcohol while acting out obvious signs of intoxication) at 340 establishments in one Midwestern metropolitan area. We also measured characteristics of the establishments, the pseudo-intoxicated patrons, the servers, the managers, and the neighborhoods to assess whether these characteristics were associated with likelihood of sales of obviously intoxicated patrons. We assessed these associations with bivariate and multivariate regression models. Results Pseudo-intoxicated buyers were able to purchase alcohol at 82% of the establishments. In the fully adjusted multivariate regression model, only one of the characteristics we assessed was significantly associated with likelihood of selling to intoxicated patrons–establishments owned by a corporate entity had 3.6 greater odds of selling alcohol to a pseudo-intoxicated buyer compared to independently-owned establishments. Discussion Given the risks associated with overservice of alcohol, more resources should be devoted first to identify effective interventions for decreasing overservice of alcohol and then to educate practitioners who are working in their communities to address this public health problem. PMID:26891204

Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system

PubMed Central

Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

2016-01-01

The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects. PMID:26220010

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

PubMed Central

LABSCH, SABRINA; LIU, LI; BAUER, NATHALIE; ZHANG, YIYAO; ALEKSANDROWICZ, EWA; GLADKICH, JURY; SCHÖNSIEGEL, FRANK; HERR, INGRID

2014-01-01

Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs. PMID:24626333

Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.

PubMed

Priengprom, Thongkoon; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Suebsasana, Supawadee; Aromdee, Chantana; Pientong, Chamsai

2015-03-11

An andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). In this study, we examined the anti-viral activity of IPAD on HSV wild types (HSV-1 strain KOS and HSV-2 clinical isolate) and HSV-1 drug-resistant strains (DRs). Synergistic effects of IPAD with acyclovir (ACV) were also evaluated. MTT and cytopathic effect (CPE) reduction assays were performed to determine cytotoxicity and anti-viral activities, respectively. A combination assay was used to determine synergistic effects of IPAD and ACV. Presence of viral DNA and protein in experimental cells was investigated using the polymerase chain reaction and western blotting, respectively. A non-cytotoxic concentration of IPAD (20.50 μM) completely inhibited CPE formation induced by HSV wild types and HSV-1 DRs after viral entry into the cells. The anti-HSV activities included inhibition of viral DNA and protein synthesis. The minimum inhibitory concentrations of ACV for HSV wild types and HSV-1 DRs were 20.20 and 2,220.00 μM, respectively. Combination of ACV with IPAD showed synergistic effects in inhibition of CPE formation, viral DNA and protein synthesis by HSV wild types as well as HSV-1 DRs. For the synergistic effects on HSV wild types and HSV-1 DRs, the effective concentrations of ACV were reduced. These results showed the inhibitory potential of IPAD on HSV wild types and HSV-1 DRs and suggested that IPAD could be used in combination with ACV for treatment of HSV-1 DRs infections.

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

NASA Astrophysics Data System (ADS)

Wang, Jie; Li, Yanli; Dong, Xia; Wang, Ying; Chong, Xiaodan; Yu, Tai; Zhang, Fulei; Chen, Di; Zhang, Li; Gao, Jie; Yang, Cheng; Han, Jun; Li, Wei

2017-01-01

Nanomedicine offers new hope to overcome the low solubility and high side toxicity to normal tissue appeared in traditional chemotherapy. The biocompatibility and intracellular drug accumulation is still a big challenge for the nano-based formulations. Herein, a medical-used biocompatible arabinoxylan (AX) is used to develop to delivery chemodrug doxorubicin (DOX). The solubility of DOX is obviously enhanced via the hydrogen bond formed with AX which results in an amphiphilic AX-DOX. A micelle with pH-cleavable bond is thus self-assembled from such AX-DOX with DOX core and AX shell. The inner DOX can be easily released out at low intracellular pH, which obviously enhanced its in vitro cytotoxicity against breast cancer cells (MCF-7). Interestingly, an unexpected apoptosis is evoked except for the proliferation inhibition. Moreover, the therapeutic effects are further synergistically promoted by the enhanced permeability and retention (EPR) and intracellular pH-triggered drug release. Consequently, the in vivo intratumor accumulation of DOX, the tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing MCF-7 tumors. These in vitro/vivo results indicated that the AX-DOX micellular formulation holds high potential in cancer therapy.

Change of Cu+ species and synergistic effect of copper and cerium during reduction-oxidation treatment for preferential CO oxidation

NASA Astrophysics Data System (ADS)

Zhang, Hao; Zhao, Xiaozhou; Wang, Shuang; Zeng, Shanghong; Su, Haiquan

2018-05-01

The CuO-CeO2@SiO2 catalyst with flower-sphere morphology was prepared by the impregnation method and then experienced the reduction-oxidation treatment at different temperatures. The multi-technique characterization shows that the reduction-oxidation treatment can remodel CuO, improve textural and surface properties and change Cu+ content and synergistic effect of copper and cerium. The importance of this work lies in the fact that the decrease of Cu+ content and synergistic effect of copper and cerium that occurs in the reduction-oxidation process results in the decrease of catalytic activity over the CuO-CeO2@SiO2 catalyst for preferential CO oxidation. The process of reaction in rich-hydrogen streams is equivalent to a reduction procedure which decreases Cu+ content and synergistic effect of copper and cerium.

Co-pyrolysis behavior of microalgae biomass and low-quality coal: Products distributions, char-surface morphology, and synergistic effects.

PubMed

Wu, Zhiqiang; Yang, Wangcai; Li, Yaowu; Yang, Bolun

2018-05-01

In this work, the distributions and releasing properties of the primary volatile products during co-pyrolysis of low-rank coal and green algae (GA) has been studied using fixed-bed reactor with online mass spectrometry. Surface morphology of the char was described quantitatively by SEM combined with fractal theory. Different forms of synergistic effects existed from both the yields of products and composition of the main gaseous products. Positive synergistic effects from tar yield were observed under 25% of GA from 600 to 850 °C, indicating GA promoted the formation of tar. Opposite synergistic effects on the content of H 2 and CO were gained when the mass ratio of GA was 50%. The fractal dimensions of co-pyrolysis char were less than the calculated values except under 650 °C, which meant the GA promoted the homogeneity of char surface. This work could provide essential data for proper operation parameters selecting for co-pyrolysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells.

PubMed

Alizadeh Zarei, M; Takhshid, M A; Behzad Behbahani, A; Hosseini, S Y; Okhovat, M A; Rafiee Dehbidi, Gh R; Mosleh Shirazi, M A

2017-09-01

Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to explore the potential synergistic effects of N-Myc Downstream-Regulated Gene 2 (NDRG2) overexpression, a newly identified candidate tumor suppressor gene, with radiotherapy against proliferation of prostate LNCaP cell line. In this study, LNCaP cells were exposed to X-ray radiation in the presence or absence of NDRG2 overexpression using plasmid PSES- pAdenoVator-PSA-NDRG2-IRES-GFP. The effects of NDRG2 overexpression, X-ray radiation or combination of both on the cell proliferation and apoptosis of LNCaP cells were then analyzed using MTT assay and flow cytometery, respectively. Results of MTT assay showed that NDRG2 overexpression and X-ray radiation had a synergistic effect against proliferation of LNCaP cells. Moreover, NDRG2 overexpression increased apoptotic effect of X-ray radiation in LNCaP cells synergistically. Our findings suggested that NDRG2 overexpression in combination with radiotherapy may be an effective therapeutic option against prostate cancer.

Antioxidant synergistic effects of Osmanthus fragrans flowers with green tea and their major contributed antioxidant compounds.

PubMed

Mao, Shuqin; Wang, Kaidi; Lei, Yukun; Yao, Shuting; Lu, Baiyi; Huang, Weisu

2017-04-19

The antioxidant synergistic effects of Osmanthus fragrans flowers with green tea were evaluated, and their major antioxidant compounds contributed to the total amount of synergy were determined. The antioxidant compounds in O. fragrans flowers with green tea were identified by LC-MS and quantified by UPLC-PDA. The synergistic antioxidant interactions between O. fragrans flowers with green tea and their antioxidant compounds were tested using the Prieto's model after the simulated digestion. The main antioxidant compounds in O. fragrans flowers were acteoside and salideroside, whereas the main antioxidant compounds in green tea were caffeine, gallic acid, and L-epicatechin. The significant synergistic effect between O. fragrans flowers and green tea was observed and among nearly all of the combinations of their antioxidant compounds. Among the combinations, acteoside and gallic acid contributed most to the antioxidant synergy between O. fragrans flowers and green tea. However, the simulated digestion decreased this antioxidant synergy because it reduced the contents and the antioxidant capacities of their compounds, as well as the antioxidant synergy among the compounds.

Synergistic effect of tartaric acid with 2,6-diaminopyridine on the corrosion inhibition of mild steel in 0.5 M HCl

PubMed Central

Qiang, Yujie; Guo, Lei; Zhang, Shengtao; Li, Wenpo; Yu, Shanshan; Tan, Jianhong

2016-01-01

The inhibitive ability of 2,6-diaminopyridine, tartaric acid and their synergistic effect towards mild steel corrosion in 0.5 M HCl solution was evaluated at various concentrations using potentiodynamic polarization measurements, electrochemical impedance spectroscopy (EIS), and weight loss experiments. Corresponding surfaces of mild steel were examined by atomic force microscope (AFM), field emission scanning electron microscope (FE-SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) analysis. The experimental results are in good agreement and reveal a favorable synergistic effect of 2,6-diaminopyridine with tartaric acid, which could protect mild steel from corrosion effectively. Besides, quantum chemical calculations and Monte Carlo simulation were used to clarify the inhibition mechanism of the synergistic effect. PMID:27628901

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer

PubMed Central

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents – liposomal apigenin and tyroservatide – was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer. PMID:28761344

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer.

PubMed

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents - liposomal apigenin and tyroservatide - was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer.

Achievement of High-Response Organic Field-Effect Transistor NO₂ Sensor by Using the Synergistic Effect of ZnO/PMMA Hybrid Dielectric and CuPc/Pentacene Heterojunction.

PubMed

Han, Shijiao; Cheng, Jiang; Fan, Huidong; Yu, Junsheng; Li, Lu

2016-10-21

High-response organic field-effect transistor (OFET)-based NO₂ sensors were fabricated using the synergistic effect the synergistic effect of zinc oxide/poly(methyl methacrylate) (ZnO/PMMA) hybrid dielectric and CuPc/Pentacene heterojunction. Compared with the OFET sensors without synergistic effect, the fabricated OFET sensors showed a remarkable shift of saturation current, field-effect mobility and threshold voltage when exposed to various concentrations of NO₂ analyte. Moreover, after being stored in atmosphere for 30 days, the variation of saturation current increased more than 10 folds at 0.5 ppm NO₂. By analyzing the electrical characteristics, and the morphologies of organic semiconductor films of the OFET-based sensors, the performance enhancement was ascribed to the synergistic effect of the dielectric and organic semiconductor. The ZnO nanoparticles on PMMA dielectric surface decreased the grain size of pentacene formed on hybrid dielectric, facilitating the diffusion of CuPc molecules into the grain boundary of pentacene and the approach towards the conducting channel of OFET. Hence, NO₂ molecules could interact with CuPc and ZnO nanoparticles at the interface of dielectric and organic semiconductor. Our results provided a promising strategy for the design of high performance OFET-based NO₂ sensors in future electronic nose and environment monitoring.

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

PubMed Central

Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

Higher Performance of DSSC with Dyes from Cladophora sp. as Mixed Cosensitizer through Synergistic Effect

PubMed Central

Haji Manaf, Noramaliyana; Tennakoon, Kushan; Chandrakanthi, R. L. N.; Lim, Linda Biaw Leng; Bandara, J. M. R. Sarath; Ekanayake, Piyasiri

2015-01-01

Chlorophyll and xanthophyll dyes extracted from a single source of filamentous freshwater green algae (Cladophora sp.) were used to sensitize dye sensitized solar cells and their performances were investigated. A more positive interaction is expected as the derived dyes come from a single natural source because they work mutually in nature. Cell sensitized with mixed chlorophyll and xanthophyll showed synergistic activity with improved cell performance of 1.5- to 2-fold higher than that sensitized with any individual dye. The effect of temperature and the stability of these dyes were also investigated. Xanthophyll dye was found to be more stable compared to chlorophyll that is attributed in the ability of xanthophyll to dissipate extra energy via reversible structural changes. Mixing the dyes resulted to an increase in effective electron life time and reduced the process of electron recombination during solar cell operation, hence exhibiting a synergistic effect. PMID:25688266

Higher Performance of DSSC with Dyes from Cladophora sp. as Mixed Cosensitizer through Synergistic Effect.

PubMed

Lim, Andery; Haji Manaf, Noramaliyana; Tennakoon, Kushan; Chandrakanthi, R L N; Lim, Linda Biaw Leng; Bandara, J M R Sarath; Ekanayake, Piyasiri

2015-01-01

Chlorophyll and xanthophyll dyes extracted from a single source of filamentous freshwater green algae (Cladophora sp.) were used to sensitize dye sensitized solar cells and their performances were investigated. A more positive interaction is expected as the derived dyes come from a single natural source because they work mutually in nature. Cell sensitized with mixed chlorophyll and xanthophyll showed synergistic activity with improved cell performance of 1.5- to 2-fold higher than that sensitized with any individual dye. The effect of temperature and the stability of these dyes were also investigated. Xanthophyll dye was found to be more stable compared to chlorophyll that is attributed in the ability of xanthophyll to dissipate extra energy via reversible structural changes. Mixing the dyes resulted to an increase in effective electron life time and reduced the process of electron recombination during solar cell operation, hence exhibiting a synergistic effect.

Strong and Nonspecific Synergistic Antibacterial Efficiency of Antibiotics Combined with Silver Nanoparticles at Very Low Concentrations Showing No Cytotoxic Effect.

PubMed

Panáček, Aleš; Smékalová, Monika; Kilianová, Martina; Prucek, Robert; Bogdanová, Kateřina; Večeřová, Renata; Kolář, Milan; Havrdová, Markéta; Płaza, Grażyna Anna; Chojniak, Joanna; Zbořil, Radek; Kvítek, Libor

2015-12-28

The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.

Synergistic Anti-Cancer Effect of Phenformin and Oxamate

PubMed Central

Miskimins, W. Keith; Ahn, Hyun Joo; Kim, Ji Yeon; Ryu, Sun; Jung, Yuh-Seog; Choi, Joon Young

2014-01-01

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively. PMID:24465604

Synergistic anti-cancer effect of phenformin and oxamate.

PubMed

Miskimins, W Keith; Ahn, Hyun Joo; Kim, Ji Yeon; Ryu, Sun; Jung, Yuh-Seog; Choi, Joon Young

2014-01-01

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

PubMed

Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

2016-05-31

Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT. Micro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups. We report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

Synergistic effect of Ebselen and gamma radiation on breast cancer cells.

PubMed

Thabet, Noura M; Moustafa, Enas M

2017-08-01

To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or γ-radiation to exert antitumor effects on human breast cancer (MCF-7) cell line in vitro. Ebs cytotoxicity at various concentrations (10, 25, 50 and 75 μg), cell proliferation and clonogenic assay of Ebs and/or γ-radiation (at 1, 3 and 6 Gy), expression of p-IκBα and NF-κB, inflammatory cytokines levels (TNF-α, IL-2, INF-γ, IL-10 and TGF-β), apoptotic factors (Caspase-3, Granzyme-B and TRAIL) and angiogenic factor (VEGF) were investigated. The results showed that the effective dosage of this combination was observed at 25 μg/ml of Ebs with γ-radiation at 6 Gy. Data displayed a significant reduction in NF-κB mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-IκBα and p-NF-κB(p65) protein expression was reduced significantly. Also, a significant decline in TNF-α, IL-2, INF-γ, TGF-β with a significant increase in IL-10 levels were revealed. Meanwhile, a significant decrease in VEGF level and proliferation capacity were observed. We conclude that a combination of Ebs with radiotherapy has a major antitumor efficiency in inducing apoptosis and inhibiting cancer cell progression, due to the synergistic effect in regulating gene and protein expression, and in a modulating response of pro-and anti-inflammatory cytokines.

Synergistic effects of food and predators on annual reproductive success in song sparrows.

PubMed

Zanette, Liana; Smith, James N M; van Oort, Harry; Clinchy, Michael

2003-04-22

The behaviour literature is full of studies showing that animals in every taxon balance the probability of acquiring food with the risk of being preyed upon. While interactions between food and predators clearly operate at an individual scale, population-scale studies have tended to focus on only one factor at a time. Consequently, interactive (or 'synergistic') effects of food and predators on whole populations have only twice before been experimentally demonstrated in mammals. We conducted a 2 x 2 experiment to examine the joint effects of food supply and predator pressure on the annual reproductive success of song sparrows (Melospiza melodia). Our results show that these two factors do not operate in an additive way, but instead have a synergistic effect on reproduction. Relative to controls, sparrows reared 1.1 more young when food was added and 1.3 more when predator pressure was low. When these treatments were combined 4.0 extra young were produced, almost twice as many as expected from an additive model. These results are a cause for optimism for avian conservation because they demonstrate that remedial actions, aimed at simultaneously augmenting food and reducing predators, can produce dramatic increases in reproductive success.

Synergistic inhibitory effect of berberine and d-limonene on human gastric carcinoma cell line MGC803.

PubMed

Zhang, Xiu-Zhen; Wang, Ling; Liu, Dong-Wu; Tang, Guang-Yan; Zhang, Hong-Yu

2014-09-01

This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24-48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou-Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway.

Synergistic Inhibitory Effect of Berberine and d-Limonene on Human Gastric Carcinoma Cell Line MGC803

PubMed Central

Wang, Ling; Liu, Dong-Wu; Tang, Guang-Yan; Zhang, Hong-Yu

2014-01-01

Abstract This study aims at evaluating the anticancer effects of berberine hydrochloride (berberine) and d-limonene, alone and in combination, on human gastric carcinoma cell line MGC803 to determine whether berberine and d-limonene work synergistically and elucidate their mechanisms. MGC803 cells were treated with berberine and d-limonene, alone and in combination, for 24–48 h. The inhibitory effects of these drugs on growth were determined by MTT assay. The combination index and drug reduction index were calculated with the Chou–Talalay method based on the median-effect principle. Flow cytometry and laser scanning confocal microscopy were employed to evaluate the effects of both drugs on cell-cycle perturbation and apoptosis, generation of reactive oxygen species (ROS), mitochondrial membrane potential, and expression of Bcl-2 and caspase-3 in MGC803 cells. Berberine or d-limonene alone can inhibit the growth of MGC803 cells in a dose- and time-dependent manner. Berberine and d-limonene at a combination ratio of 1:4 exhibited a synergistic effect on anti-MGC803 cells. The two drugs distinctly induced intracellular ROS generation, reduced the mitochondrial transmembrane potential (ΔΨm), enhanced the expression of caspase-3, and decreased the expression of Bcl-2. The combination of berberine and d-limonene showed more remarkable effects compared with drugs used singly in MGC803 cells. The combination of berberine and d-limonene exerted synergistic anticancer effects on MGC803 cells by cell-cycle arrest, ROS production, and apoptosis induction through the mitochondria-mediated intrinsic pathway. PMID:25045784

Synergistic effects of loxoprofen and glycine on the micturition reflex in conscious rats.

PubMed

Fukiya, Yumiko; Yoshizumi, Masaru; Saito, Mikako; Matsumoto-Miyai, Kazumasa; Nimura, Toshie; Kawatani, Masahito

2014-01-01

We examined the inhibitory effects of loxoprofen, a cyclooxygenase inhibitor, and glycine, a major inhibitory neurotransmitter, on the micturition reflex in conscious rats and hypothesized that these drugs would interact synergistically to inhibit micturition. Voiding behaviors were assessed using a metabolic cage. Oral loxoprofen decreased the urinary frequency, and only a high dose(10 mg/kg) significantly reduced the voided volume. With cystometry, intravenous loxoprofen(0.1-3 mg/kg) and glycine (30 and 100 mg/kg) prolonged the intercontraction intervals (ICI) in adose-dependent manner, but did not change the maximum voiding pressure (MVP) in conscious rats. The combination of loxoprofen (3 mg/kg) and glycine (100 mg/kg) strongly prolonged the ICI more than with either drug alone. The lowest dose of loxoprofen (0.1 mg/kg) and glycine(30 mg/kg) did not affect either the ICI or the MVP, but their combination resulted in a significant increase in the ICI. These results suggest that the combined administration of loxoprofen and glycine produced a synergistic inhibitory effect on the micturition reflex.

Achievement of High-Response Organic Field-Effect Transistor NO2 Sensor by Using the Synergistic Effect of ZnO/PMMA Hybrid Dielectric and CuPc/Pentacene Heterojunction

PubMed Central

Han, Shijiao; Cheng, Jiang; Fan, Huidong; Yu, Junsheng; Li, Lu

2016-01-01

High-response organic field-effect transistor (OFET)-based NO2 sensors were fabricated using the synergistic effect the synergistic effect of zinc oxide/poly(methyl methacrylate) (ZnO/PMMA) hybrid dielectric and CuPc/Pentacene heterojunction. Compared with the OFET sensors without synergistic effect, the fabricated OFET sensors showed a remarkable shift of saturation current, field-effect mobility and threshold voltage when exposed to various concentrations of NO2 analyte. Moreover, after being stored in atmosphere for 30 days, the variation of saturation current increased more than 10 folds at 0.5 ppm NO2. By analyzing the electrical characteristics, and the morphologies of organic semiconductor films of the OFET-based sensors, the performance enhancement was ascribed to the synergistic effect of the dielectric and organic semiconductor. The ZnO nanoparticles on PMMA dielectric surface decreased the grain size of pentacene formed on hybrid dielectric, facilitating the diffusion of CuPc molecules into the grain boundary of pentacene and the approach towards the conducting channel of OFET. Hence, NO2 molecules could interact with CuPc and ZnO nanoparticles at the interface of dielectric and organic semiconductor. Our results provided a promising strategy for the design of high performance OFET-based NO2 sensors in future electronic nose and environment monitoring. PMID:27775653

Synergistic effect of EDTA and boric acid on corneal penetration of CS-088.

PubMed

Kikuchi, Takayuki; Suzuki, Masahiko; Kusai, Akira; Iseki, Ken; Sasaki, Hitoshi

2005-02-16

In order to investigate the effects of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088, an ophthalmic agent, the apparent permeability coefficient of CS-088 in the presence of EDTA/boric acid across the isolated corneal membranes of rabbits was measured using an in vitro penetration chamber system. FITC-dextran (M.W. 4400) and an electrical method based on membrane resistance were used to provide a quantitative assessment of the enhancing effect of EDTA/boric acid. The corneal penetration of CS-088 was significantly enhanced in the presence of EDTA/boric acid by approximately 1.6-fold. The permeability-enhancing effect of EDTA/boric acid was apparently synergistic and concentration-dependent on both EDTA and boric acid. The penetration of FITC-dextran, a paracellular marker, and electrical resistance of corneal membranes were not affected in the presence of EDTA/boric acid. Furthermore, no enhancing effect of EDTA/boric acid was observed in de-epithelialized corneas, although de-epithelialized corneas exhibited a markedly higher permeability of CS-088 that was 24-fold greater than that for intact corneas. In conclusion, EDTA/boric acid synergistically enhances the transcellular permeability of CS-088 in the outer layer but not in the inner layers of the corneal membrane.

In vitro synergistic effect of farnesol and human gingival cells against Candida albicans.

PubMed

Saidi, Said; Luitaud, Cyril; Rouabhia, Mahmoud

2006-07-15

Farnesol prevents the germination of yeast cells into mycelia, a fact that may be useful in eliminating C. albicans pathogenicity. Given the clinical potential of farnesol, its impact on C. albicans and host cells merited further investigation. We thus studied the effect of farnesol on C. albicans growth and filamentation and on gingival epithelial cells and fibroblasts and the synergistic effect of both gingival cells and farnesol on C. albicans filamentation. Repeated additions of farnesol reduced the growth of C. albicans. Farnesol was also effective at reducing C. albicans germ tube formation. While farnesol inhibited germ tube formation under the conditions tested, it was most effective at inhibiting C. albicans filamentation when added to the culture medium at the same time as the serum. Farnesol also had an effect on gingival cells. In a serum-free medium, farnesol reduced fibroblast adhesion and proliferation, promoted epithelial cell differentiation and reduced proliferation up to 48 h post-treatment. These effects were not seen in the presence of serum. When C. albicans, farnesol and gingival cells were present in the same culture, significantly greater inhibition of the yeast-to-hyphal transition was observed than germ tube inhibition in cultures containing only C. albicans and farnesol, suggesting a synergistic effect between the gingival cells and farnesol in inhibiting the transition. Overall, the data suggest that farnesol is effective against C. albicans and may have an effect on host cells at certain concentrations.

Synergistic Effects among the Structure, Martensite Transformation and Shear Band in a Shape Memory Alloy-Metallic Glass Composite

NASA Astrophysics Data System (ADS)

Zhang, Xudong; Ren, Junqiang; Ding, Xiangdong

2018-05-01

In this work, we use the finite element method to investigate the free volume evolution, as well as the martensite transformation effect and its connection with the pretreatment strain, in a shape memory alloy-metallic glass composite. Our simulation results show that the martensite phase transformation can enhance the blocking effect while relieving the free volume localization. The synergistic effect among the martensite transformation effect, blocking effect, and shear band interaction in the composite is responsible for the tensile plasticity and work-hardening capability. In addition, we design a Sierpinski carpet-like fractal microstructure so that the composite exhibits improved tensile performance as a result of the enhanced synergistic effect. However, the tensile performance of the composite deteriorates with increasing pretreatment strain since the martensite transformation effect is weakened.

Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy.

PubMed

Lin, Gan; Zhang, Yang; Zhu, Congqing; Chu, Chengchao; Shi, Yesi; Pang, Xin; Ren, En; Wu, Yayun; Mi, Peng; Xia, Haiping; Chen, Xiaoyuan; Liu, Gang

2018-05-22

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synergistic effect of heat and solar UV on DNA damage and water disinfection of E. coli and bacteriophage MS2.

PubMed

Theitler, Dana Jennifer; Nasser, Abid; Gerchman, Yoram; Kribus, Abraham; Mamane, Hadas

2012-12-01

The response of a representative virus and indicator bacteria to heating, solar irradiation, or their combination, was investigated in a controlled solar simulator and under real sun conditions. Heating showed higher inactivation of Escherichia coli compared to the bacteriophage MS2. Heating combined with natural or simulated solar irradiation demonstrated a synergistic effect on the inactivation of E. coli, with up to 3-log difference for 50 °C and natural sun insolation of 2,000 kJ m(-2) (compared to the sum of the separate treatments). Similar synergistic effect was also evident when solar-UV induced DNA damage to E. coli was assessed using the endonuclease sensitive site assay (ESS). MS2 was found to be highly resistant to irradiation and heat, with a slightly synergistic effect observed only at 59 °C and natural sun insolation of 5,580 kJ m(-2). Heat treatment also hindered light-dependent recovery of E. coli making the treatment much more effective.

Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

PubMed

Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

Tramadol and Propentofylline Coadministration Exerted Synergistic Effects on Rat Spinal Nerve Ligation-Induced Neuropathic Pain

PubMed Central

Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system. PMID:24009718

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

PubMed

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

A review of helium-hydrogen synergistic effects in radiation damage observed in fusion energy steels and an interaction model to guide future understanding

NASA Astrophysics Data System (ADS)

Marian, Jaime; Hoang, Tuan; Fluss, Michael; Hsiung, Luke L.

2015-07-01

Under fusion reactor conditions, large quantities of irradiation defects and transmutation gases are produced per unit time by neutrons, resulting in accelerated degradation of structural candidate ferritic (F) and ferritic/martensitic (F/M) steels. Due to the lack of a suitable fusion neutron testing facility, we must rely on high-dose-rate ion-beam experiments and present-day crude modeling estimates. Of particular interest is the possibility of synergistic (positive feedback) effects on materials properties due to the simultaneous action of He, H, and displacement damage (dpa) during operation. In this paper we discuss the state-of-the-art in terms of the experimental understanding of synergistic effects and carry out simulations of triple-species irradiation under ion-beam conditions using first-of-its-kind modeling techniques. Although, state-of-the-art modeling and simulation is not sufficiently well developed to shed light on the experimental uncertainties, we are able to conclude that it is not clear whether synergistic effects, the evidence of which is still not conclusive, will ultimately play a critical role in material performance under fusion energy conditions. We review here some of the evidence for the synergistic effects of hydrogen in the presence of helium and displacement damage, and also include some recent data from our research. While the experimental results to date suggest possible mechanisms for the observed synergistic effects, it is only with more advanced modeling that we can hope to understand the details underlying the experimental observations. By employing modeling and simulation we propose an interaction model that is qualitatively consistent with experimental observations of dpa/He/H irradiation behavior. Our modeling, the results of which should be helpful to researchers going forward, points to gaps and voids in the current understanding of triple ion-beam irradiation effects (displacement damage produced simultaneously with

Synergistic retention strategy of RGD active targeting and radiofrequency-enhanced permeability for intensified RF & chemotherapy synergistic tumor treatment.

PubMed

Zhang, Kun; Li, Pei; He, Yaping; Bo, Xiaowan; Li, Xiaolong; Li, Dandan; Chen, Hangrong; Xu, Huixiong

2016-08-01

Despite gaining increasing attention, chelation of multiple active targeting ligands greatly increase the formation probability of protein corona, disabling active targeting. To overcome it, a synergistic retention strategy of RGD-mediated active targeting and radiofrequency (RF) electromagnetic field-enhanced permeability has been proposed here. It is validated that such a special synergistic retention strategy can promote more poly lactic-co-glycolic acid (PLGA)-based capsules encapsulating camptothecin (CPT) and solid DL-menthol (DLM) to enter and retain in tumor in vitro and in vivo upon exposure to RF irradiation, receiving an above 8 fold enhancement in HeLa retention. Moreover, the PLGA-based capsules can respond RF field to trigger the entrapped DLM to generate solid-liquid-gas (SLG) tri-phase transformation for enhancing RF ablation and CPT release. Therefore, depending on the enhanced RF ablation and released CPT and the validated synergistic retention effect, the inhibitory outcome for tumor growth has gained an over 10-fold improvement, realizing RF ablation & chemotherapy synergistic treatment against HeLa solid tumor, which indicates a significant promise in clinical RF ablation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of the effects of simulated synergistic LEO environment on solar panels

NASA Astrophysics Data System (ADS)

Allegri, G.; Corradi, S.; Marchetti, M.; Scaglione, S.

2007-02-01

The effects due to the LEO environment exposure of a solar array primary structure are here presented and discussed in detail. The synergistic damaging components featuring LEO environment are high vacuum, thermal cycling, neutral gas, ultraviolet (UV) radiation and cold plasma. The synergistic effects due to these environmental elements are simulated by "on ground" tests, performed in the Space Environment Simulator (SAS) at the University of Rome "La Sapienza"; numerical simulations are performed by the Space Environment Information System (SPENVIS), developed by the European Space Agency (ESA). A "safe life" design for a solar array primary structure is developed, taking into consideration the combined damaging action of the LEO environment components; therefore results from both numerical and experimental simulations are coupled within the framework of a standard finite element method (FEM) based design. The expected durability of the solar array primary structure, made of laminated sandwich composite, is evaluated assuming that the loads exerted on the structure itself are essentially dependent on thermo-elastic stresses. The optical degradation of surface materials and the stiffness and strength degradation of structural elements are taken into account to assess the global structural durability of the solar array under characteristic operative conditions in LEO environment.

Synergistic interactions between edge and area effects in a heavily fragmented landscape.

PubMed

Ewers, Robert M; Thorpe, Stephen; Didham, Raphael K

2007-01-01

Both area and edge effects have a strong influence on ecological processes in fragmented landscapes, but there is little understanding of how these two factors might interact to exacerbate local species declines. To test for synergistic interactions between area and edge effects, we sampled a diverse beetle community in a heavily fragmented landscape in New Zealand. More than 35,000 beetles of approximately 900 species were sampled over large gradients in habitat area (10(-2) 10(6) ha) and distance from patch edge (2(0)-2(10) m from the forest edge into both the forest and adjacent matrix). Using a new approach to partition variance following an ordination analysis, we found that a synergistic interaction between habitat area and distance to edge was a more important determinant of patterns in beetle community composition than direct edge or area effects alone. The strength of edge effects in beetle-species composition increased nonlinearly with increasing fragment area. One important consequence of the synergy is that the slopes of species area (SA) curves constructed from habitat islands depend sensitively on the distance from edge at which sampling is conducted. Surprisingly, we found negative SA curves for communities sampled at intermediate distances from habitat edges, caused by differential edge responses of matrix- vs. forest-specialist species in fragments of increasing area. Our data indicate that distance to habitat edge has a consistently greater impact on beetle community composition than habitat area and that variation in the strength of edge effects may underlie many patterns that are superficially related to habitat area.

Synergistic effect of tungsten carbide and palladium on graphene for promoted ethanol electrooxidation.

PubMed

Yang, Jun; Xie, Ying; Wang, Ruihong; Jiang, Baojiang; Tian, Chungui; Mu, Guang; Yin, Jie; Wang, Bo; Fu, Honggang

2013-07-24

The synergistic effect of WC and Pd has large benefit for ethanol electrooxidation. The small-sized Pd nanoparticles (NPs) decorated tungsten carbide on graphene (Pd-WC/GN) will be a promising anode catalyst for the direct ethanol fuel cells. The density functional theory (DFT) calculations reveal that the strong interaction exists at the interface between Pd and WC, which induces the electron transfer from WC to Pd. Fortunately, the nanoscale architecture of Pd-WC/GN has been successfully fabricated in our experiments. X-ray photoelectron spectrum further confirms the existence of electron transfer from WC to Pd in a Pd-WC/GN nanohybrid. Notably, electrochemical tests show that the Pd-WC/GN catalyst exhibits low onset potential, a large electrochemical surface area, high activity, and stability for ethanol electrooxidation in alkaline solution compared with Pd/graphene and Pd/commercial Vulcan 72R carbon catalysts. The enhancement can be attributed to the synergistic effect of Pd and WC on graphene. At the interface between Pd and WC, the electron transfer from WC to Pd leads to the increased electron densities of surface Pd, which is available for weakening adsorption of intermediate oxygen-containing species such as CO and activating catalyst. Meanwhile, the increased tungsten oxide induced by electron transfer can facilitate the effective removal of intermediate species adsorbed on the Pd surface through a bifunctional mechanism or hydrogen spillover effect.

Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

PubMed Central

Li, Bo; Wang, Hai; Qiu, Guixing; Su, Xinlin

2016-01-01

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs), as key mediators in angiogenesis and osteogenesis, are used in a combined delivery manner as a novel strategy in bone tissue engineering. VEGF has the potential to enhance BMPs induced bone formation. Both gene delivery and material-based delivery systems were incorporated in previous studies to investigate the synergistic effects of VEGF and BMPs. However, their results were controversial due to variation of methods incorporated in different studies. Factors influencing the synergistic effects of VEGF on BMPs induced bone formation were identified and analyzed in this review to reduce confusion on this issue. The potential mechanisms and directions of future studies were also proposed here. Further investigating mechanisms of the synergistic effects and optimizing these influencing factors will help to generate more effective bone regeneration. PMID:28070506

Antagonistic and synergistic interactions among predators.

PubMed

Huxel, Gary R

2007-08-01

The structure and dynamics of food webs are largely dependent upon interactions among consumers and their resources. However, interspecific interactions such as intraguild predation and interference competition can also play a significant role in the stability of communities. The role of antagonistic/synergistic interactions among predators has been largely ignored in food web theory. These mechanisms influence predation rates, which is one of the key factors regulating food web structure and dynamics, thus ignoring them can potentially limit understanding of food webs. Using nonlinear models, it is shown that critical aspects of multiple predator food web dynamics are antagonistic/synergistic interactions among predators. The influence of antagonistic/synergistic interactions on coexistence of predators depended largely upon the parameter set used and the degree of feeding niche differentiation. In all cases when there was no effect of antagonism or synergism (a ( ij )=1.00), the predators coexisted. Using the stable parameter set, coexistence occurred across the range of antagonism/synergism used. However, using the chaotic parameter strong antagonism resulted in the extinction of one or both species, while strong synergism tended to coexistence. Whereas using the limit cycle parameter set, coexistence was strongly dependent on the degree of feeding niche overlap. Additionally increasing the degree of feeding specialization of the predators on the two prey species increased the amount of parameter space in which coexistence of the two predators occurred. Bifurcation analyses supported the general pattern of increased stability when the predator interaction was synergistic and decreased stability when it was antagonistic. Thus, synergistic interactions should be more common than antagonistic interactions in ecological systems.

Synthesis of graphene oxide-quaternary ammonium nanocomposite with synergistic antibacterial activity to promote infected wound healing.

PubMed

Liu, Tengfei; Liu, Yuqing; Liu, Menglong; Wang, Ying; He, Weifeng; Shi, Gaoqiang; Hu, Xiaohong; Zhan, Rixing; Luo, Gaoxing; Xing, Malcolm; Wu, Jun

2018-01-01

Bacterial infection is one of the most common complications in burn, trauma, and chronic refractory wounds and is an impediment to healing. The frequent occurrence of antimicrobial-resistant bacteria due to irrational application of antibiotics increases treatment cost and mortality. Graphene oxide (GO) has been generally reported to possess high antimicrobial activity against a wide range of bacteria in vitro . In this study, a graphene oxide-quaternary ammonium salt (GO-QAS) nanocomposite was synthesized and thoroughly investigated for synergistic antibacterial activity, underlying antibacterial mechanisms and biocompatibility in vitro and in vivo . The GO-QAS nanocomposite was synthesized through amidation reactions of carboxylic group end-capped QAS polymers with primary amine-decorated GO to achieve high QAS loading ratios on nanosheets. Next, we investigated the antibacterial activity and biocompatibility of GO-QAS in vitro and in vivo . GO-QAS exhibited synergistic antibacterial activity against bacteria through not only mechanical membrane perturbation, including wrapping, bacterial membrane insertion, and bacterial membrane perforation, but also oxidative stress induction. In addition, it was found that GO-QAS could eradicate multidrug-resistant bacteria more effectively than conventional antibiotics. The in vitro and in vivo toxicity tests indicated that GO-QAS did not exhibit obvious toxicity towards mammalian cells or organs at low concentrations. Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and promoted infected wound healing in vivo . The GO-QAS nanocomposite exhibits excellent synergistic antibacterial activity and good biocompatibility both in vitro and in vivo . The antibacterial mechanisms involve both mechanical membrane perturbation and oxidative stress induction. In addition, GO-QAS accelerated the healing process of infected wounds by promoting re-epithelialization and granulation

The in vitro synergistic inhibitory effect of human amniotic fluid and gentamicin on growth of Escherichia coli.

PubMed

Miglioli, P A; Schoffel, U; Gianfranceschi, L

1996-01-01

The activity of serum and its synergistic effect with many antibiotics against bacteria are well known. Few reports are available on similar phenomena produced by human amniotic fluid (HAF). Thus we investigated the antibacterial activity of HAF and the presence of a synergistic effect with gentamicin (GM) against Escherichia coli strains. Antimicrobial activity was evaluated as a delay of the growth curve, using a turbidimetric method. E. coli ATCC 10798 and E. coli SC 12155 were employed as test micro-organisms in nutrient broth, and GM was used at a subinhibitory concentration. HAF exerted antibacterial activity and, cooperating with GM at subinhibitory concentration, enhanced its antibiotic activity against E. coli. The presence of Schlievert's glycoprotein in HAF could explain these results.

The synergistic antimicrobial effects of novel bombinin and bombinin H peptides from the skin secretion of Bombina orientalis.

PubMed

Xiang, Jie; Zhou, Mei; Wu, Yuxin; Chen, Tianbao; Shaw, Chris; Wang, Lei

2017-10-31

Bombinin and bombinin H are two antimicrobial peptide (AMP) families initially discovered from the skin secretion of Bombina that share the same biosynthetic precursor-encoding cDNAs, but have different structures and physicochemical properties. Insight into their possible existing relationship lead us to perform the combination investigations into their anti-infectious activities. In this work, we report the molecular cloning and functional characterization of two novel AMPs belonging to bombinin and bombinin H families from secretions of Bombina orientalis Their mature peptides (BHL-bombinin and bombinin HL), coded by single ORF, were chemically synthesized along with an analogue peptide that replaced L-leucine with D-leucine from the second position of the N-terminus (bombinin HD). CD analysis revealed that all of them displayed well-defined α-helical structures in membrane mimicking environments. Furthermore, BHL-bombinin displayed broad-spectrum bactericidal activities on a wide range of microorganisms, while bombinin H only exhibited a mildly bacteriostatic effect on the Gram-positive bacteria Staphylococcus aureus The combination potency of BHL-bombinin with either bombinin HL or bombinin HD showed the synergistic inhibition activities against S. aureus (fractional inhibitory concentration index (FICI): 0.375). A synergistic effect has also been observed between bombinin H and ampicillin, which was further systematically evaluated and confirmed by in vitro time-killing investigations. Haemolytic and cytotoxic examinations exhibited a highly synergistic selectivity and low cytotoxicity on mammalian cells of these three peptides. Taken together, the discovery of the potent synergistic effect of AMPs in a single biosynthetic precursor with superior functional selectivity provides a promising strategy to combat multidrug-resistant pathogens in clinical therapy. © 2017 The Author(s).

Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure.

PubMed

Bao, Haibo; Shao, Xusheng; Zhang, Yixi; Deng, Yayun; Xu, Xiaoyong; Liu, Zewen; Li, Zhong

2016-06-29

Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid-specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products.

Interaction and its induced inhibiting or synergistic effects during co-gasification of coal char and biomass char.

PubMed

Ding, Liang; Zhang, Yongqi; Wang, Zhiqing; Huang, Jiejie; Fang, Yitian

2014-12-01

Co-gasification of coal char and biomass char was conducted to investigate the interactions between them. And random pore model (RPM) and modified random pore model (MRPM) were applied to describe the gasification behaviors of the samples. The results show that inhibiting effect was observed during co-gasification of corn stalk char with Hulunbeier lignite coal char, while synergistic effects were observed during co-gasification of corn stalk char with Shenmu bituminous coal char and Jincheng anthracite coal char. The inhibiting effect was attributed to the intimate contact and comparable gasification rate between biomass char and coal char, and the loss of the active form of potassium caused by the formation of KAlSiO4, which was proved to be inactive during gasification. While the synergistic effect was caused by the high potassium content of biomass char and the significant difference of reaction rate between coal char and biomass char during gasification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synergistic antifungal effect of lactoferrin with azole antifungals against Candida albicans and a proposal for a new treatment method for invasive candidiasis.

PubMed

Kobayashi, Tsutomu; Kakeya, Hiroshi; Miyazaki, Taiga; Izumikawa, Koichi; Yanagihara, Katsunori; Ohno, Hideaki; Yamamoto, Yoshihiro; Tashiro, Takayoshi; Kohno, Shigeru

2011-01-01

The combination of lactoferrin with fluconazole has been reported to synergistically enhance the antifungal activity of fluconazole against Candida spp. and inhibit the hyphal formation in fluconazole-resistant strains of Candida albicans. In this study, we investigated the association between the therapeutic effects of this combination and the pharmacological characteristics of fluconazole and itraconazole and the variation in these effects with differences among the strains in terms of the susceptibility and resistance mechanisms. Lactoferrin enhanced the growth-inhibitory activity of fluconazole against two different ergosterol mutants but not againt pump mutants or an azole-susceptible strain; but increased the activity of itraconazole against all the strains tested in this study. Exogenous iron cancelled the synergistic effect, which suggests that the iron-chelating function of lactoferrin may contribute to the synergism. Besides, radiolabeled fluconazole assays revealed that lactoferrin did not affect the intracellular concentrations of fluconazole, thereby indicating that these synergistic effects were not due to the alteration of the intracellular uptake of the drug. The development of new clinical treatments and therapeutic method against resistant Candida will depend on our understanding of the resistance mechanisms and methods to overcome them by the application of suitable drug combinations with synergistic effects. The results of this study might contribute to the improvement of our understand of the mechanisms underlying the resistance of Candida strains.

Synergistic antibacterial effects of β-lactam antibiotic combined with silver nanoparticles

NASA Astrophysics Data System (ADS)

Li, Ping; Li, Juan; Wu, Changzhu; Wu, Qingsheng; Li, Jian

2005-09-01

The bactericidal action of silver (0) nanoparticles and amoxicillin on Escherichia coli is studied, respectively. Increasing concentration of both amoxicillin (0-0.525 mg ml-1) and silver nanoparticles (0-40 µg ml-1) showed a higher antibacterial effect in Luria-Bertani (LB) medium. Escherichia coli cells have different bactericidal sensitivity to them. When amoxicillin and silver nanoparticles are combined, it results in greater bactericidal efficiency on Escherichia coli cells than when they were applied separately. Dynamic tests on bacterial growth indicated that exponential and stationary phases are greatly decreased and delayed in the synergistic effect of amoxicillin and silver nanoparticles. In addition, the effect induced by a preincubation with silver nanoparticles is examined. The results show that solutions with more silver nanoparticles have better antimicrobial effects. One hypothesized mechanism is proposed to explain this phenomenon.

A review of helium–hydrogen synergistic effects in radiation damage observed in fusion energy steels and an interaction model to guide future understanding

DOE PAGES

Marian, Jaime; Hoang, Tuan; Fluss, Michael; ...

2014-12-29

Here, under fusion reactor conditions, large quantities of irradiation defects and transmutation gases are produced per unit time by neutrons, resulting in accelerated degradation of structural candidate ferritic (F) and ferritic/martensitic (F/M) steels. Due to the lack of a suitable fusion neutron testing facility, we must rely on high-dose-rate ion-beam experiments and present-day crude modeling estimates. Of particular interest is the possibility of synergistic (positive feedback) effects on materials properties due to the simultaneous action of He, H, and displacement damage (dpa) during operation. In this paper we discuss the state-of-the-art in terms of the experimental understanding of synergistic effectsmore » and carry out simulations of triple-species irradiation under ion-beam conditions using first-of-its-kind modeling techniques. Although, state-of-the-art modeling and simulation is not sufficiently well developed to shed light on the experimental uncertainties, we are able to conclude that it is not clear whether synergistic effects, the evidence of which is still not conclusive, will ultimately play a critical role in material performance under fusion energy conditions. We review here some of the evidence for the synergistic effects of hydrogen in the presence of helium and displacement damage, and also include some recent data from our research. While the experimental results to date suggest possible mechanisms for the observed synergistic effects, it is only with more advanced modeling that we can hope to understand the details underlying the experimental observations. By employing modeling and simulation we propose an interaction model that is qualitatively consistent with experimental observations of dpa/He/H irradiation behavior. Our modeling, the results of which should be helpful to researchers going forward, points to gaps and voids in the current understanding of triple ion-beam irradiation effects (displacement damage produced

Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles.

PubMed

Lu, Meng-Meng; Wang, Qiu-Jing; Chang, Zhi-Min; Wang, Zheng; Zheng, Xiao; Shao, Dan; Dong, Wen-Fei; Zhou, Yan-Min

2017-01-01

Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli . Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.

Synergistic effect of artocarpin on antibacterial activity of some antibiotics against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

PubMed

Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

2016-01-01

Antibacterial resistance has dramatically increased and resulted in serious health problems worldwide. One appealing strategy to overcome this resistance problem is the use of combinations of antibacterial compounds to increase their potency. The objective of this study is to determine the synergistic effects of artocarpin for ampicillin, norfloxacin, and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA) as well as the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli. A broth microdilution method (1.95-250 µg/mL) was used to determine the minimum inhibitory concentration (MIC) of artocarpin and the antibiotics. Any synergistic effects were evaluated at their own MIC using the checkerboard method and a time-kill assay at 37 °C for 24 h. Artocarpin showed antibacterial activity against MRSA and E. coli with an MIC value of 62.5 µg/mL, and against P. aeruginosa with an MIC value of 250 µg/mL. The interaction of artocarpin with all tested antibiotics produced synergistic effects against MRSA with a fractional inhibitory concentration index (FICI) of 0.15-0.37. In addition, a combination of artocarpin and norfloxacin showed a synergistic effect against E. coli with an FICI value of 0.37, while the combinations of artocarpin and tetracycline as well as artocarpin and norfloxacin exhibited synergy interactions against P. aeruginosa with FICI values of 0.24 and 0.37, respectively. Time-kill assays indicated that artocarpin enhanced the antimicrobial activities of tetracycline, ampicillin, and norfloxacin against MRSA as well as Gram-negative bacteria.

Synergistic effects of acyclic retinoid and OSI-461 on growth inhibition and gene expression in human hepatoma cells.

PubMed

Shimizu, Masahito; Suzui, Masumi; Deguchi, Atsuko; Lim, Jin T E; Xiao, Danhua; Hayes, Julia H; Papadopoulos, Kyriakos P; Weinstein, I Bernard

2004-10-01

Hepatoma is one of the most frequently occurring cancers worldwide. However, effective chemotherapeutic agents for this disease have not been developed. Acyclic retinoid, a novel synthetic retinoid, can reduce the incidence of postsurgical recurrence of hepatoma and improve the survival rate. OSI-461, a potent derivative of exisulind, can increase intracellular levels of cyclic GMP, which leads to activation of protein kinase G and induction of apoptosis in cancer cells. In the present study, we examined the combined effects of acyclic retinoid plus OSI-461 in the HepG2 human hepatoma cell line. We found that the combination of as little as 1.0 micromol/L acyclic retinoid and 0.01 micromol/L OSI-461 exerted synergistic inhibition of the growth of HepG2 cells. Combined treatment with low concentrations of these two agents also acted synergistically to induce apoptosis in HepG2 cells through induction of Bax and Apaf-1, reduction of Bcl-2 and Bcl-xL, and activation of caspase-3, -8, and -9. OSI-461 enhanced the G0-G1 arrest caused by acyclic retinoid, and the combination of these agents caused a synergistic decrease in the levels of expression of cyclin D1 protein and mRNA, inhibited cyclin D1 promoter activity, decreased the level of hyperphosphorylated forms of the Rb protein, induced increased cellular levels of the p21(CIP1) protein and mRNA, and stimulated p21(CIP1) promoter activity. Moreover, OSI-461 enhanced the ability of acyclic retinoid to induce increased cellular levels of retinoic acid receptor beta and to stimulate retinoic acid response element-chloramphenicol acetyltransferase activity. A hypothetical model involving concerted effects on p21(CIP1) and retinoic acid receptor beta expression is proposed to explain these synergistic effects. Our results suggest that the combination of acyclic retinoid plus OSI-461 might be an effective regimen for the chemoprevention and chemotherapy of human hepatoma and possibly other malignancies.

The Synergistic Effects of MoS2 and Liquid Lubrication

NASA Astrophysics Data System (ADS)

Buttery, M.; Roberts, E.; Stanley, S.; Murer, J.

2015-09-01

We present an overview of a three-stage program on the potential for hybrid lubrication of MoS2 and PFPE fluids (Fomblin Z25 & Braycote 601EF) performed at the European Space Tribology Laboratory (ESTL).Tests were performed using a spiral orbit tribometer (SOT) and a pin-on-disc tribometer (POD), demonstrating encouraging results. Hybrid lubrication allows for extended periods of in-air running of MoS2 with no detrimental effect to the subsequent in-vacuum lifetime. In addition, hybrid lubrication was shown to be synergistic, with the lifetime of the hybrid fluid/MoS2 lubrication extended in comparison to the individual constituents, with no detriment to the friction.

Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation.

PubMed

Liu, Guizhi; Xue, Xiaolin; Gao, Chuanyu; Huang, Jiaqi; Qi, Datun; Zhang, Yanzhou; Dong, Jian-Zeng; Ma, Chang-Sheng; Yan, Gan-Xin

2017-05-18

Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations. Dofetilide or mexiletine alone mildly to moderately prolonged atrial ERP, but their combined use produced a markedly rate-dependent increase in atrial ERP. Dofetilide (3 nmol/L) plus mexiletine (10 μmol/L) increased the ERP by 28.2% from 72.2±5.7 to 92.8±5.9 ms (n=9, P <0.01) at a pacing rate of 0.5 Hz and by 94.5% from 91.7±5.2 to 178.3±12.0 ms (n=9, P <0.01) at 3.3 Hz. Dofetilide plus mexiletine strongly suppressed AF inducibility. On the other hand, dofetilide at 10 nmol/L produced marked QT and T p-e prolongation, steeper QT-BCL and T p-e -BCL slopes, and induced early afterdepolarizations and torsade de pointes in the ventricular wedges. Mexiletine at 10 μmol/L reduced dofetilide-induced QT and T p-e prolongation, QT-BCL and T p-e -BCL slopes, and abolished early afterdepolarizations and torsade de pointes. In rabbits, combined use of dofetilide and mexiletine not only synergistically increases atrial ERP and effectively suppresses AF inducibility, but also markedly reduces QT liability and torsade de pointes risk posed by dofetilide alone. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung cancers.

PubMed

Kim, Bomi; Seo, Bohyung; Park, Sanghyun; Lee, Changkyu; Kim, Jong Oh; Oh, Kyung Taek; Lee, Eun Seong; Choi, Han-Gon; Youn, Yu Seok

2017-10-01

Albumin nanoparticles are well-known as effective drug carriers used to deliver hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin and doxorubicin were fabricated using slightly modified nanoparticle albumin-bound (nab™) technology, and the synergistic effects of these two drugs were examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both curcumin and doxorubicin were prepared using a high pressure homogenizer. The sizes of albumin nanoparticles were ∼130nm, which was considered to be suitable for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles gradually released drugs over a period of 24h without burst effect. To confirm the synergistic effect of two drugs, in vitro cytotoxicity assay was performed using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was highest when co-treated with both curcumin and doxorubicin compared to single treatment of either curcumin and doxorubicin. The combined index calculated by medium-effect equation was 0.6069, indicating a synergistic effect. Results of confocal laser scanning microscopy and fluorescence-activated cell sorting corresponded to results from an in vitro cytotoxicity assay, indicating synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by B16F10 lung metastasis was used to study in vivo therapeutic effects. When curcumin and doxorubicin were simultaneously treated, the metastatic melanoma mass in the lungs macroscopically decreased compared to curcumin or doxorubicin alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to have an effective therapeutic result and would be an excellent way to treat resistant lung cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability.

PubMed

Septama, Abdi Wira; Xiao, Jianbo; Panichayupakaranant, Pharkphoom

2017-01-01

Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Escherichia coli . A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis. Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA.

Synergistes Group Organisms of Human Origin

PubMed Central

Horz, Hans-Peter; Citron, Diane M.; Warren, Yumi A.; Goldstein, Ellie J. C.; Conrads, Georg

2006-01-01

The bacterial division Synergistes represents a poorly characterized phylotype of which only a few isolates have been cultured, primarily from natural environments. Recent detection of Synergistes-like sequence types in periodontal pockets and caries lesions of humans prompted us to search the R. M. Alden culture collection (Santa Monica, Calif.) for biochemically unidentifiable, slow-growing, obligately anaerobic gram-negative bacilli. Here we report on five clinical isolates cultured from peritoneal fluid and two isolates from soft-tissue infections that together constitute three separate evolutionary lineages within the phylogenetic radiation of the division Synergistes. One of these clusters was formed by the peritoneal isolates and had an 85% similarity to Synergistes jonesii, the first described Synergistes species, which was isolated from the rumen of a goat. The isolates from soft-tissue infections, on the other hand, formed two distinct lineages moderately related to each other with a similarity of approximately 78%. In addition, by using a newly designed 16S rRNA gene-based PCR assay with intended target specificity for Synergistes, we found that the dominant phylotype from a fecal sample was nearly identical to that of the strains obtained from peritonitis. Conversely, sequence types detected in periodontal pockets formed a separate cluster that shared a similarity of only 80% with the soft-tissue isolates. These findings suggest a high diversity of medically important Synergistes clades that apparently are unique to individual ecological niches in the human body. In conclusion, we now have available the first characterized human isolates of the division Synergistes which are colonizing, and probably infecting, several sites in the human body. PMID:16891512

Isolated and synergistic effects of PM10 and average temperature on cardiovascular and respiratory mortality.

PubMed

Pinheiro, Samya de Lara Lins de Araujo; Saldiva, Paulo Hilário Nascimento; Schwartz, Joel; Zanobetti, Antonella

2014-12-01

OBJECTIVE To analyze the effect of air pollution and temperature on mortality due to cardiovascular and respiratory diseases. METHODS We evaluated the isolated and synergistic effects of temperature and particulate matter with aerodynamic diameter < 10 µm (PM10) on the mortality of individuals > 40 years old due to cardiovascular disease and that of individuals > 60 years old due to respiratory diseases in Sao Paulo, SP, Southeastern Brazil, between 1998 and 2008. Three methodologies were used to evaluate the isolated association: time-series analysis using Poisson regression model, bidirectional case-crossover analysis matched by period, and case-crossover analysis matched by the confounding factor, i.e., average temperature or pollutant concentration. The graphical representation of the response surface, generated by the interaction term between these factors added to the Poisson regression model, was interpreted to evaluate the synergistic effect of the risk factors. RESULTS No differences were observed between the results of the case-crossover and time-series analyses. The percentage change in the relative risk of cardiovascular and respiratory mortality was 0.85% (0.45;1.25) and 1.60% (0.74;2.46), respectively, due to an increase of 10 μg/m3 in the PM10 concentration. The pattern of correlation of the temperature with cardiovascular mortality was U-shaped and that with respiratory mortality was J-shaped, indicating an increased relative risk at high temperatures. The values for the interaction term indicated a higher relative risk for cardiovascular and respiratory mortalities at low temperatures and high temperatures, respectively, when the pollution levels reached approximately 60 μg/m3. CONCLUSIONS The positive association standardized in the Poisson regression model for pollutant concentration is not confounded by temperature, and the effect of temperature is not confounded by the pollutant levels in the time-series analysis. The simultaneous exposure

The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury.

PubMed

Liu, Ying; Yang, HongNa; Jia, GuoYong; Li, Lan; Chen, Hui; Bi, JianZhong; Wang, CuiLan

2018-06-01

It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury. Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset. We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1β (IL-1β) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1β, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group. Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis

PubMed Central

Ohyama, Kana; Nogusa, Yoshihito; Shinoda, Kosaku; Suzuki, Katsuya

2016-01-01

Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues. PMID:26936964

Synergistic Antibacterial Effect of the Combination of ε-Polylysine and Nisin against Enterococcus faecalis.

PubMed

Liu, Fang; Liu, Mei; Du, Lihui; Wang, Daoying; Geng, Zhiming; Zhang, Muhan; Sun, Chong; Xu, Xiaoxi; Zhu, Yongzhi; Xu, Weimin

2015-12-01

This study evaluated the antibacterial effect of the combination of ε-polylysine (ε-PL) and nisin against Enterococcus faecalis strains. The combination of ε-PL and nisin showed synergistic antibacterial activity against three Enterococcus strains. Scanning electron microscopy and a membrane permeability assay revealed that the combined treatment with ε-PL and nisin synergistically damaged the cell morphology of E. faecalis strain R612Z1 cells. Both ε-PL and nisin can dissipate the transmembrane electric potential of E. faecalis R612Z1 cells, but these peptides did not affect the transmembrane pH gradient. The combination of ε-PL and nisin can produce a high reactive oxygen species level in E. faecalis R612Z1 cells. The results indicated that the uptake of ε-PL into cells was promoted through nisin and that the combination of ε-PL and nisin could produce a high reactive oxygen species level in E. faecalis R612Z1 cells, leading to cell growth inhibition.

Synergistic effect between ammonium polyphosphate and expandable graphite on flame-retarded poly(butylene terephthalate)

NASA Astrophysics Data System (ADS)

Zhang, Weizhou; Ren, Jiawei; Wei, Ting; Guo, Weihong

2018-02-01

In this paper, the synergistic effect of ammonium polyphosphate (APP) and expandable graphite (EG) on flame-retarded poly(butylene terephthalate) (PBT) was systermically investigated using limiting oxygen index (LOI), UL-94 testing, microscale combustion calorimetry (MCC), thermal-gravimetric analysis (TGA) and scanning electronic microscopy (SEM). PBT composites containing 20 wt% of APP: EG (1:3) combinations exhibits a high LOI value of 29.8 and reaches V-0 rating in UL-94 testing, indicating that the flame retardant property is greatly enhanced compared to the composites solely with APP or EG. SEM images show that the combination of APP and EG could promote the formation of a compact char layer. The compact char layer protects the PBT resin efficiently by preventing penetration of heat flux inside the matrix and retards the decomposition of PBT, consequently improves the thermal stability of PBT materials as revealed by TGA. All of the results demonstrate that APP and EG are high efficiency synergists for improving the flame retardation of PBT materials.

Iodine-131-labeled, transferrin-capped polypyrrole nanoparticles for tumor-targeted synergistic photothermal-radioisotope therapy.

PubMed

Song, Xuejiao; Liang, Chao; Feng, Liangzhu; Yang, Kai; Liu, Zhuang

2017-08-22

Combining different therapeutic functions within single tumor-targeted nanoscale delivery systems is promising to overcome the limitations of conventional cancer therapies. Herein, transferrin that recognizes transferrin receptors up-regulated on tumor cells is pre-labeled with iodine-131 ( 131 I) and then utilized as the stabilizer in the fabrication of polypyrrole (PPy) nanoparticles. The obtained transferrin-capped PPy@Tf- 131 I nanoparticles could be used for tumor-targeted radioisotope therapy (RIT) and photothermal therapy (PTT), by employing beta-emission from 131 I and the intrinsic high near-infrared (NIR) absorbance of PPy, respectively. Owing to the transferrin-mediated tumor targeting, PPy@Tf- 131 I nanoparticles exhibit obviously enhanced in vitro cancer cell binding and in vivo tumor uptake compared to its non-targeting counterpart. The combined RIT and PTT based on PPy@Tf- 131 I nanoparticles is then conducted, achieving a remarkable synergistic therapeutic effect. This work thus demonstrates a rather simple one-step approach to fabricate tumor-targeting nanoparticles based on protein-capped conjugated polymers, promising for combination cancer therapy with great efficacy and high safety.

Synergistic effects of nucleating agents and plasticizers on the crystallization behavior of poly(lactic acid).

PubMed

Shi, Xuetao; Zhang, Guangcheng; Phuong, Thanh Vu; Lazzeri, Andrea

2015-01-19

The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK (sulfates) were compared with each other as heterogeneous nucleating agents. Both the DSC isothermal and non-isothermal studies indicated that talc and LAK were the more effective nucleating agents among the selected fillers. Poly(D-lactic acid) (PDLA) acted also as a nucleating agent due to the formation of the PLA stereocomplex. The half crystallization time was reduced by the addition of talc to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study. The dynamic mechanical thermal study (DMTA) indicated that nanofillers acted as both reinforcement fillers and nucleating agents in relation to the higher storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass transition temperature with the increasing of the PEG content. The addition of nanofiller increased the Young's modulus. PEG had the plasticization effect of increasing the break deformation, while sharply decreasing the stiffness and strength of PLA. The synergistic effect of nanofillers and plasticizer achieved the balance between stiffness and toughness with well-controlled crystallization.

Synergistic Effects Between Phosphonium-Alkylphosphate Ionic Liquids and Zinc Dialkyldithiophosphate (ZDDP) as Lubricant Additives

DOE PAGES

Qu, Jun; Barnhill, William C.; Luo, Huimin; ...

2015-07-14

Unique synergistic effects between phosphonium-alkylphosphate ionic liquids and zinc dialkyldithiophosphate (ZDDP) are discovered when used together as lubricant additives, resulting in significant friction and wear reduction along with distinct tribofilm composition and mechanical properties. The synergism is attributed to the 30-70× higher-than-nominal concentrations of hypothetical new compounds (via anion exchange between IL and ZDDP) on the fluid surface/interface.

Synergistic combination dry powders for inhaled antimicrobial therapy

NASA Astrophysics Data System (ADS)

Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

2013-06-01

Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

An Effective Solution to Discover Synergistic Drugs for Anti-Cerebral Ischemia from Traditional Chinese Medicinal Formulae

PubMed Central

Lu, Peng; Chen, Chang; Fu, Meihong; Fang, Jing; Gao, Jian; Zhu, Li; Liang, Rixin; Shen, Xin; Yang, Hongjun

2013-01-01

Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM). Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ), which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G), berberine (B) and jasminoidin (J) was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G): 2(B): 0.5(J), and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could greatly

Synergistic effect of fragrant herbs in Japanese scent sachets.

PubMed

Fujiwara, Yumi; Ito, Michiho

2015-02-01

The sedative activity of eight aromatic natural medicines that are traditionally used in Japanese scent sachets was examined using an open field test with mice. Galangal (Kaempferia galanga), patchouli (Pogostemon cablin), sandalwood (Santalum album), spikenard (Nardostachys chinensis), cinnamon (Cinnamomum cassia), clove (Syzygium aromaticum), star anise (Illicium verum), and borneol (Dryobalanops aromatica) distilled oils were used. These natural medicines have various pharmacological effects. For example, galangal has insecticidal activity and clove extracts possess strong total antioxidant activity. Aromatherapy, a well-known complementary medicine system that uses inhalation, has recently attracted much attention. The sedative activity of inhaled aromatic compounds or essential oils has been examined by measuring the spontaneous motor activity of mice in an open field test. The galangal, patchouli, sandalwood, spikenard, and borneol oils showed significant sedative effects. The effect was stronger for a mixture of the five oils than for any of the single oils. This suggests that the oil mixture may have synergistic activity. Sedative activity was not observed when inactive oils (cinnamon, clove, and star anise) were added to the mixture of the five active oils. Georg Thieme Verlag KG Stuttgart · New York.

Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model.

PubMed

Zhao, Lei; Gong, Neng; Liu, Meng; Pan, Xiaoli; Sang, Shaoming; Sun, Xiaojing; Yu, Zhe; Fang, Qi; Zhao, Na; Fei, Guoqiang; Jin, Lirong; Zhong, Chunjiu; Xu, Tianle

2014-12-01

Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone. Copyright © 2014 Elsevier Inc. All rights reserved.

HIV infection across aging: Synergistic effects on intrinsic functional connectivity of the brain.

PubMed

Egbert, Anna R; Biswal, Bharat; Karunakaran, Keerthana; Pluta, Agnieszka; Wolak, Tomasz; Rao, Stephen; Bornstein, Robert; Szymańska, Bogna; Horban, Andrzej; Firląg-Burkacka, Ewa; Sobańska, Marta; Gawron, Natalia; Bieńkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Ścińska-Bieńkowska, Anna; Łojek, Emilia

2018-06-12

The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV-) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20-55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not

A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability

PubMed Central

Septama, Abdi Wira; Xiao, Jianbo; Panichayupakaranant, Pharkphoom

2017-01-01

Aim/Backgrounds: Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Escherichia coli. Materials and Methods: A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis. Results and Discussion: Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. Conclusion: These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA. PMID:28512600

Effects of a Hybrid Online and In-Person Training Program Designed to Reduce Alcohol Sales to Obviously Intoxicated Patrons.

PubMed

Toomey, Traci L; Lenk, Kathleen M; Erickson, Darin J; Horvath, Keith J; Ecklund, Alexandra M; Nederhoff, Dawn M; Hunt, Shanda L; Nelson, Toben F

2017-03-01

Overservice of alcohol (i.e., selling alcohol to intoxicated patrons) continues to be a problem at bars and restaurants, contributing to serious consequences such as traffic crashes and violence. We developed a training program for managers of bars and restaurants, eARM™, focusing on preventing overservice of alcohol. The program included online and face-to-face components to help create and implement establishment-specific policies. We conducted a large, randomized controlled trial in bars and restaurants in one metropolitan area in the midwestern United States to evaluate effects of the eARM program on the likelihood of selling alcohol to obviously intoxicated patrons. Our outcome measure was pseudo-intoxicated purchase attempts-buyers acted out signs of intoxication while attempting to purchase alcohol-conducted at baseline and then at 1 month, 3 months, and 6 months after training. We conducted intention-to-treat analyses on changes in purchase attempts in intervention (n = 171) versus control (n = 163) bars/restaurants using a Time × Condition interaction, as well as planned contrasts between baseline and follow-up purchase attempts. The overall Time × Condition interaction was not statistically significant. At 1 month after training, we observed a 6% relative reduction in likelihood of selling to obviously intoxicated patrons in intervention versus control bars/restaurants. At 3 months after training, this difference widened to a 12% relative reduction; however, at 6 months this difference dissipated. None of these specific contrasts were statistically significant (p = .05). The observed effects of this enhanced training program are consistent with prior research showing modest initial effects followed by a decay within 6 months of the core training. Unless better training methods are identified, training programs are inadequate as the sole approach to reduce overservice of alcohol.

Effects of a Hybrid Online and In-Person Training Program Designed to Reduce Alcohol Sales to Obviously Intoxicated Patrons

PubMed Central

Toomey, Traci L.; Lenk, Kathleen M.; Erickson, Darin J.; Horvath, Keith J.; Ecklund, Alexandra M.; Nederhoff, Dawn M.; Hunt, Shanda L.; Nelson, Toben F.

2017-01-01

Objective: Overservice of alcohol (i.e., selling alcohol to intoxicated patrons) continues to be a problem at bars and restaurants, contributing to serious consequences such as traffic crashes and violence. We developed a training program for managers of bars and restaurants, eARMTM, focusing on preventing overservice of alcohol. The program included online and face-to-face components to help create and implement establishment-specific policies. Method: We conducted a large, randomized controlled trial in bars and restaurants in one metropolitan area in the midwestern United States to evaluate effects of the eARM program on the likelihood of selling alcohol to obviously intoxicated patrons. Our outcome measure was pseudo-intoxicated purchase attempts—buyers acted out signs of intoxication while attempting to purchase alcohol—conducted at baseline and then at 1 month, 3 months, and 6 months after training. We conducted intention-to-treat analyses on changes in purchase attempts in intervention (n = 171) versus control (n = 163) bars/restaurants using a Time × Condition interaction, as well as planned contrasts between baseline and follow-up purchase attempts. Results: The overall Time × Condition interaction was not statistically significant. At 1 month after training, we observed a 6% relative reduction in likelihood of selling to obviously intoxicated patrons in intervention versus control bars/restaurants. At 3 months after training, this difference widened to a 12% relative reduction; however, at 6 months this difference dissipated. None of these specific contrasts were statistically significant (p = .05). Conclusions: The observed effects of this enhanced training program are consistent with prior research showing modest initial effects followed by a decay within 6 months of the core training. Unless better training methods are identified, training programs are inadequate as the sole approach to reduce overservice of alcohol. PMID:28317507

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study

PubMed Central

Kuok, Chiu-Fai; Hoi, Sai-On; Hoi, Chi-Fai; Chan, Chi-Hong; Fong, Io-Hong; Ngok, Cheong-Kei; Fong, Pedro

2017-01-01

Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA. Impact statement Antibiotic resistant is a well-known threat to global health and

Synergistic antibacterial effects of herbal extracts and antibiotics on methicillin-resistant Staphylococcus aureus: A computational and experimental study.

PubMed

Kuok, Chiu-Fai; Hoi, Sai-On; Hoi, Chi-Fai; Chan, Chi-Hong; Fong, Io-Hong; Ngok, Cheong-Kei; Meng, Li-Rong; Fong, Pedro

2017-04-01

Antibiotic resistance has become a serious global concern, and the discovery of antimicrobial herbal constituents may provide valuable solutions to overcome the problem. In this study, the effects of therapies combining antibiotics and four medicinal herbs on methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Specifically, the synergistic effects of Magnolia officinalis, Verbena officinalis, Momordica charantia, and Daphne genkwa in combination with oxacillin or gentamicin against methicillin-resistant (ATCC43300) and methicillin-susceptible (ATCC25923) S. aureus were examined. In vitro susceptibility and synergistic testing were performed to measure the minimum inhibitory concentration and fractional inhibitory concentration (FIC) index of the antibiotics and medicinal herbs against MRSA and methicillin-susceptible S. aureus. To identify the active constituents in producing these synergistic effects, in silico molecular docking was used to investigate the binding affinities of 139 constituents of the four herbs to the two common MRSA inhibitory targets, penicillin binding proteins 2a (PBP2a) and 4 (PBP4). The physicochemical and absorption, distribution, metabolism, and excretion properties and drug safety profiles of these compounds were also analyzed. D. genkwa extract potentiated the antibacterial effects of oxacillin against MRSA, as indicated by an FIC index value of 0.375. M. officinalis and V. officinalis produced partial synergistic effects when combined with oxacillin, whereas M. charantia was found to have no beneficial effects in inhibiting MRSA. Overall, tiliroside, pinoresinol, magnatriol B, and momorcharaside B were predicted to be PBP2a or PBP4 inhibitors with good drug-like properties. This study identifies compounds that deserve further investigation with the aim of developing therapeutic agents to modulate the effect of antibiotics on MRSA. Impact statement Antibiotic resistant is a well-known threat to global health and

Antifungal activity of secondary plant metabolites from potatoes (Solanum tuberosum L.): Glycoalkaloids and phenolic acids show synergistic effects.

PubMed

Sánchez-Maldonado, A F; Schieber, A; Gänzle, M G

2016-04-01

To study the antifungal effects of the potato secondary metabolites α-solanine, α-chaconine, solanidine and caffeic acid, alone or combined. Resistance to glycoalkaloids varied among the fungal species tested, as derived from minimum inhibitory concentrations assays. Synergistic antifungal activity between glycoalkaloids and phenolic compounds was found. Changes in the fluidity of fungal membranes caused by potato secondary plant metabolites were determined by calculation of the generalized polarization values. The results partially explained the synergistic effect between caffeic acid and α-chaconine and supported findings on membrane disruption mechanisms from previous studies on artificial membranes. LC/MS analysis was used to determine variability and relative amounts of sterols in the different fungal species. Results suggested that the sterol pattern of fungi is related to their resistance to potato glycoalkaloids and to their taxonomy. Fungal resistance to α-chaconine and possibly other glycoalkaloids is species dependent. α-Chaconine and caffeic acid show synergistic antifungal activity. The taxonomic classification and the sterol pattern play a role in fungal resistance to glycoalkaloids. Results improve the understanding of the antifungal mode of action of potato secondary metabolites, which is essential for their potential utilization as antifungal agents in nonfood systems. © 2016 The Society for Applied Microbiology.

The obviously ill patient in need of treatment: a fourth standard for civil commitment.

PubMed

Treffert, D A

1985-03-01

The three relatively standard criteria currently contained in most state civil commitment laws (danger to self, danger to others, and gravely disabled) have forced many obviously ill patients to deteriorate to the point of dangerousness before receiving treatment, to become criminalized, or to wander the streets untreated. After discussing the origins of present civil commitment laws and the plight of obviously ill patients, the author details the cooperative effort of several groups in Wisconsin to codify a fourth standard for civil commitment that would ensure that obviously ill patients receive treatment with proper procedural and due process safeguards. Other statutory alternatives to remedy the plight of obviously ill patients are also discussed.

Fatigue Resistant Bioinspired Composite from Synergistic Two-Dimensional Nanocomponents.

PubMed

Wan, Sijie; Zhang, Qi; Zhou, Xiaohang; Li, Dechang; Ji, Baohua; Jiang, Lei; Cheng, Qunfeng

2017-07-25

Portable and wearable electronics require much more flexible graphene-based electrode with high fatigue life, which could repeatedly bend, fold, or stretch without sacrificing its mechanical properties and electrical conductivity. Herein, a kind of ultrahigh fatigue resistant graphene-based nanocomposite via tungsten disulfide (WS 2 ) nanosheets is synthesized by introducing a synergistic effect with covalently cross-linking inspired by the orderly layered structure and abundant interfacial interactions of nacre. The fatigue life of resultant graphene-based nanocomposites is more than one million times at the stress level of 270 MPa, and the electrical conductivity can be kept as high as 197.1 S/cm after 1.0 × 10 5 tensile testing cycles. These outstanding properties are attributed to the synergistic effect from lubrication of WS 2 nanosheets for deflecting crack propagation, and covalent bonding between adjacent GO nanosheets for bridging crack, which is verified by the molecular dynamics (MD) simulations. The WS 2 induced synergistic effect with covalent bonding offers a guidance for constructing graphene-based nanocomposites with high fatigue life, which have great potential for applications in flexible and wearable electronic devices, etc.

Is the European Patent Office's approach to assessing obviousness of antibody inventions consistent?

PubMed

Rigby, Barbara

2014-12-01

Antibodies can be highly effective in the diagnosis and/or treatment of a wide range of diseases, including certain cancers, viral infections and inflammatory diseases. The development of any new therapeutic antibody is very time consuming, requires significant resources and only a small percentage of initial candidates ever make it onto the market. Patent protection therefore plays a key role in allowing companies to obtain a good return on this investment. However, in Europe, the bar for assessing the inventiveness (obviousness) of antibodies is currently set particularly high, so there is a significant risk that new antibodies may be denied patent protection despite having beneficial properties. This article looks at the rationale behind the European Patent Office's (EPO) current approach to assessing the patentability of antibodies, contrasting it with US practice as well as the EPO's assessment of obviousness in the chemical field. It also explores whether a recent decision by an EPO Appeal Board may help to bring about a change in this practice.

Esterase inhibition by synergists in the western flower thrips Frankliniella occidentalis.

PubMed

López-Soler, Neus; Cervera, Amelia; Quinto, Vicente; Abellán, Jaime; Bielza, Pablo; Martínez-Pardo, Rafael; Garcerá, Maria Dolores

2011-12-01

Western flower thrips (WFT), Frankliniella occidentalis (Pergande), is among the most important crop pests in the south-eastern region of Spain. Its increasing resistance to insecticides constitutes a serious problem, and understanding the mechanisms involved is therefore of great interest. Use of synergists to inhibit the enzymes involved in insecticide detoxification is widely used to determine their responsibility for insecticide resistance. However, they do not always act as intended or expected, and caution must be exercised when interpreting synergist results. Laboratory-selected strains of WFT were used to analyse the effects of the synergists piperonyl butoxide (PBO), S,S,S-tributyl phosphorotrithioate (DEF) and methiocarb on total esterase activity. Significant differences were found, indicating esterase activity inhibition by DEF, a lower effect for methiocarb and a small inhibition of the activity by PBO. Esterase isoenzyme inhibition by these compounds showed a similar result; this assay revealed an extreme sensitivity of Triplet A (resistance-associated esterases) to DEF. In an in vivo assay carried out with these compounds at different incubation times, only DEF caused posterior in vitro esterase activity inhibition, with a maximum effect 1 h after treatment. In this work, only DEF shows true synergistic inhibition of WFT esterases. Copyright © 2011 Society of Chemical Industry.

Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

PubMed

Du, Qin; Hu, Bing; An, Hong-Mei; Shen, Ke-Ping; Xu, Ling; Deng, Shan; Wei, Meng-Meng

2013-05-01

Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine.

Synergistic Effects of Toxic Elements on Heat Shock Proteins

PubMed Central

Mahmood, Khalid; Mahmood, Qaisar; Irshad, Muhammad; Hussain, Jamshaid

2014-01-01

Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as “suit of biomarkers in a set of organisms” requires further investigation. PMID:25136596

Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice.

PubMed

Medhat, Amina M; Azab, Khaled Sh; Said, Mahmoud M; El Fatih, Neama M; El Bakary, Nermeen M

2017-10-01

Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.

Synergistic anticancer effect of the extracts from Polyalthia evecta caused apoptosis in human hepatoma (HepG2) cells

PubMed Central

Machana, Sasipawan; Weerapreeyakul, Natthida; Barusrux, Sahapat; Thumanu, Kanjana; Tanthanuch, Waraporn

2012-01-01

Objective To evaluate the anticancer activity of the extract fraction of Polyalthia evecta (P. evecta) (Pierre) Finet & Gagnep and the synergistic anticancer effect of the extracts from P. evecta by using the ATR/FT-IR spectroscopy. Methods The 50% ethanol-water crude leaf extract of P. evecta (EW-L) was prepared and was further fractionated to isolate various fractions. The anticancer activity was investigated from cytotoxicity against HepG2 using a neutral red assay and apoptosis induction by evaluation of nuclei morphological changes after DAPI staining. Synergistic anticancer effects of the extracts from P. evecta were performed using the ATR/FT-IR spectroscopy. Results The result showed that the EW-L showed higher cytotoxicity and apoptosis induction in HepG2 cells than its fractionated extracts. The hexane extract exhibited higher cytotoxicity and apoptosis induction than the water extracts, but less than the EW-L. The combined water and hexane extracts apparently increased cytotoxicity and apoptosis induction. The %apoptotic cells induced by the extract mixture were increased about 2-fold compared to the single hexane extract. Conclusions The polar extract fraction is necessary for the anticancer activity of the non-polar extract fraction. The ATR/FT-IR spectra illustrates the physical interaction among the constituents in the extract mixture and reveals the presence of polyphenolic constituents in the EW-L, which might play a role for the synergistic anticancer effect. PMID:23569977

Antibiotic and synergistic effect of Leu-Lys rich peptide against antibiotic resistant microorganisms isolated from patients with cholelithiasis.

PubMed

Jeong, Nari; Kim, Jin-Young; Park, Seong-Cheol; Lee, Jong-Kook; Gopal, Ramamourthy; Yoo, Suyeon; Son, Byoung Kwan; Hahm, Joon Soo; Park, Yoonkyung; Hahm, Kyung-Soo

2010-09-03

Pseudomonas aeruginosa has eventually developed resistance against flomoxef sodium, isepamicin and cefpiramide. Therefore, in this study, the antibacterial activity and synergistic effects of the amphipathic-derived P5-18mer antimicrobial peptide were tested against pathogens associated with cholelithiasis that have developed resistance against commonly used antibiotics. The results were then compared with the activities of the amphipathic-derived peptide, P5-18mer, melittin and common antibiotics. Growth inhibition of planktonic bacteria was tested using the National Committee for Clinical Laboratory Standards (NCCLS). The bactericidal activity of the antimicrobial peptides was measured using time-kill curves. Synergistic effects were evaluated by testing the effects of P5-18mer alone and in combination with flomoxef sodium, isepamicin or cefpiramide at 0.5xMIC. P5-18mer peptide displayed strong activity against pathogens and flomoxef sodium, isepamicin and cefpiramide-resistant bacteria cell lines obtained from a patient with gallstones; however, it did not exert cytotoxicity against the human keratinocyte HaCat cell line. In addition, the results of time-kill curves indicated that P5-18mer peptide exerted bactericidal activity against four strains of P. aeruginosa. Finally, the use of P5-18mer and antibiotics exerted synergistic effects against cell lines that were resistant to commonly used antibiotics. These results indicate that this class of peptides has a rapid microbicidal effect on flomoxef sodium, isepamicin and cefpiramide-resistant strains of P. aeruginosa. Therefore, these peptides may be used as a lead drug for the treatment of acquired pathogens from patients with cholelithiasis who are affected with antibiotic-resistant bacteria. Copyright 2010 Elsevier Inc. All rights reserved.

Synergistic effects of some essential oils against fungal spoilage on pear fruit.

PubMed

Nikkhah, Mehdi; Hashemi, Maryam; Habibi Najafi, Mohammad B; Farhoosh, Reza

2017-09-18

The development of natural protective agents as alternatives to chemical fungicides is currently in the spotlight. In the present investigation, chemical composition and antifungal activities of thyme, cinnamon, rosemary and marjoram essential oils (EO), as well as synergism of their possible double and triple combinations were investigated. The compositions of the oils were determined by GC/MS. For determination of antifungal activity against Penicillium expansum and Botrytis cinerea, a broth microdilution method was used. The possible interactions of some essential oil combinations were performed by the two and three-dimensional checkerboard assay and isobologram construction. An in vivo antifungal assay was performed by artificial wounding of pear fruits. The maximum antifungal activity was demonstrated by thyme and cinnamon oils which displayed lower MIC values whereas rosemary and marjoram oils with MIC range between 2500 and 10,000μg/mL exhibited weak antifungal activities against tested fungi. In synergy testing, some double combinations (thyme/cinnamon, thyme/rosemary, cinnamon/rosemary) were found to be synergistic (FICi≤0.5). The triple combination of thyme, cinnamon and rosemary was synergistic for B. cinerea and P. expansum (FICi values of 0.5 and 0.375, respectively); while combination of cinnamon, marjoram and thyme exhibited additive and synergistic effect against P. expansum (FIC=0.625) and B. cinerea (FIC=0.375) respectively. The usage of a mathematical Gompertz model in relation to fungal kinetics, showed that the model could be used to predict growth curves (R 2 =0.993±0.05). For B. cinerea, Gompertz parameters for double and triple combination treatments showed significant increase in lag phase (1.92 and 2.92days, respectively) compared to single treatments. Increase lag time up to 2.82days (P<0.05) also observed in P. expansum treated by triple combination of EOs. Base on the results, the lowest maximum growth rate (0.37mm/day) was observed

Beneficial synergistic effect on bio-oil production from co-liquefaction of sewage sludge and lignocellulosic biomass.

PubMed

Leng, Lijian; Li, Jun; Yuan, Xingzhong; Li, Jingjing; Han, Pei; Hong, Yuchun; Wei, Feng; Zhou, Wenguang

2018-03-01

Co-liquefaction of municipal sewage sludge (MSS) and lignocellulosic biomass such as rice straw or wood sawdust at different mixing ratios and the characterization of the obtained bio-oil and bio-char were investigated. Synergistic effects were found during co-processing of MSS with biomass for production of bio-oil with higher yield and better fuel properties than those from individual feedstock. The co-liquefaction of MSS/rice straw (4/4, wt) increased the bio-oil yield from 22.74% (bio-oil yield from liquefaction of MSS individually) or 23.67% (rice straw) to 32.45%. Comparable increase on bio-oil yield was also observed for MSS/wood sawdust mixtures (2/6, wt). The bio-oils produced from MSS/biomass mixtures were mainly composed of esters and phenols with lower boiling points (degradation temperatures) than those from individual feedstock (identified with higher heavy bio-oil fractions). These synergistic effects were probably resulted from the interactions between the intermittent products of MSS and those of biomass during processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synergistic Effects of Expectancy and Value on Homework Engagement: The Case for a Within-Person Perspective.

PubMed

Nagengast, Benjamin; Trautwein, Ulrich; Kelava, Augustin; Lüdtke, Oliver

2013-05-01

Historically, expectancy-value models of motivation assumed a synergistic relation between expectancy and value: motivation is high only when both expectancy and value are high. Motivational processes were studied from a within-person perspective, with expectancies and values being assessed or experimentally manipulated across multiple domains and the focus being placed on intraindividual differences. In contrast, contemporary expectancy-value models in educational psychology concentrate almost exclusively on linear effects of expectancy and value on motivational outcomes, with a focus on between-person differences. Recent advances in latent variable methodology allow both issues to be addressed in observational studies. Using the expectancy-value model of homework motivation as a theoretical framework, this study estimated multilevel structural equation models with latent interactions in a sample of 511 secondary school students and found synergistic effects between domain-specific homework expectancy and homework value in predicting homework engagement in 6 subjects. This approach not only brings the "×" back into expectancy-value theory but also reestablishes the within-person perspective as the appropriate level of analysis for latent expectancy-value models.

Effect of synergist piperonyl butoxide (PBO) on the toxicity of some essential oils against mosquito larvae.

PubMed

Yadav, S; Mittal, P K; Saxena, P N; Singh, R K

2008-12-01

Effect of a known synergist piperonyl butoxide on the toxicity of steam distillate essential oils of Jamarosa (Cymbopogan nardus), Pacholli (Pogostemon pacholli), Basil (Ocimum basilicum), and Peppermint (Mentha pipreta) plant species against Anopheles stephensi larvae were evaluated. The purpose of the present study was to identify the insecticidal potential of these oils against mosquito larvae. The Piperonyl Butoxide (PBO) was used to enhance the activity of these oils with the aim of developing essential oil based formulations. The bioassays of these oils with and without PBO were performed against late 3rd instar larvae of An. stephensi. The LC50 values against An. stephensi were 44.19 ppm for Ocimum basilicum oil, followed by, Mentha pipreta, Cymbopogan nardus, and Pogostemon pacholli oil which gave LC50 values above 250 ppm. Thus in the present study the Ocimum basilicum oil was found to be most effective, whereas Pogostemon pacholli oil was found to least effective against mosquitoes for larvicidal action. The effect of synergist PBO led to the enhancement of toxicity of oils, the LC50 value for Ocimum basilicum were reduced from 44.19 ppm to 23.87 ppm. Similarly the oil of Pogostemon pacholli showed most significant results where the LC50 value was >250 ppm it was reduced to 50 ppm with PBO.

Effect of synergist piperonyl butoxide (PBO) on the toxicity of some essential oils against mosquito larvae.

PubMed

Yadav, S; Mittal, P K; Saxena, P N; Singh, R K

2009-03-01

Effect of a known synergist piperonyl butoxide on the toxicity of steam distillate essential oils of Jamarosa (Cymbopogan nardus), Pacholli (Pogostemon pacholli), Basil (Ocimum basilicum), and Peppermint (Mentha pipreta) plant species against Anopheles stephensi larvae were evaluated. The purpose of the present study was to identify the insecticidal potential of these oils against mosquito larvae. The Piperonyl Butoxide (PBO) was used to enhance the activity of these oils with the aim of developing essential oil based formulations. The bioassays of these oils with and without PBO were performed against late 3rd instar larvae of An. stephensi. The LC50 values against An. stephensi were 44.19 ppm for Ocimum basilicum oil, followed by, Mentha pipreta, Cymbopogan nardus, and Pogostemon pacholli oil which gave LC50 values above 250 ppm. Thus in the present study the Ocimum basilicum oil was found to be most effective, whereas Pogostemon pacholli oil was found to least effective against mosquitoes for larvicidal action. The effect of synergist PBO led to the enhancement of toxicity of oils, the LC50 value for Ocimum basilicum were reduced from 44.19 ppm to 23.87 ppm. Similarly the oil of Pogostemon pacholli showed most significant results where the LC50 value was > 250 ppm it was reduced to 50 ppm with PBO.

Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562.

PubMed

Li, Nianyi; Chen, Qinfen; Gu, Jingwen; Li, Shuang; Zhao, Guangjie; Wang, Wei; Wang, Zhicheng; Wang, Xiaoqin

2017-05-30

A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines. The combination of DFX and DAC was much greater than the effect of using either drug alone. DFX showed a synergistic effect with DAC on cell apoptosis in all three cell lines and on cell cycle arrest at the G0/G1 phase in K-562 cells. DFX decreased the ROS levels to varying degrees. In contrast, DAC increased ROS levels and an increase in ROS was also noted when the two drugs were used in combination. Treatment of cells with DAC induced re-expression of ABAT, APAF-1, FADD, HJV, and SMPD3, presumably through demethylation. However the combination of DAC and DFX just had strong synergistic effect on the re-expression of HJV.

Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562

PubMed Central

Li, Nianyi; Chen, Qinfen; Gu, Jingwen; Li, Shuang; Zhao, Guangjie; Wang, Wei; Wang, Zhicheng; Wang, Xiaoqin

2017-01-01

A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines. The combination of DFX and DAC was much greater than the effect of using either drug alone. DFX showed a synergistic effect with DAC on cell apoptosis in all three cell lines and on cell cycle arrest at the G0/G1 phase in K-562 cells. DFX decreased the ROS levels to varying degrees. In contrast, DAC increased ROS levels and an increase in ROS was also noted when the two drugs were used in combination. Treatment of cells with DAC induced re-expression of ABAT, APAF-1, FADD, HJV, and SMPD3, presumably through demethylation. However the combination of DAC and DFX just had strong synergistic effect on the re-expression of HJV. PMID:28388554

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

PubMed Central

Hsieh, Chih-Hsiung; Lu, Chueh-Hsuan; Chen, Wei-Ting; Ma, Bo-Lun

2017-01-01

Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy. PMID:29186186

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells.

PubMed

Hsieh, Chih-Hsiung; Lu, Chueh-Hsuan; Chen, Wei-Ting; Ma, Bo-Lun; Chao, Chih-Yu

2017-01-01

Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy.

Stability of strong species interactions resist the synergistic effects of local and global pollution in kelp forests.

PubMed

Falkenberg, Laura J; Russell, Bayden D; Connell, Sean D

2012-01-01

Foundation species, such as kelp, exert disproportionately strong community effects and persist, in part, by dominating taxa that inhibit their regeneration. Human activities which benefit their competitors, however, may reduce stability of communities, increasing the probability of phase-shifts. We tested whether a foundation species (kelp) would continue to inhibit a key competitor (turf-forming algae) under moderately increased local (nutrient) and near-future forecasted global pollution (CO(2)). Our results reveal that in the absence of kelp, local and global pollutants combined to cause the greatest cover and mass of turfs, a synergistic response whereby turfs increased more than would be predicted by adding the independent effects of treatments (kelp absence, elevated nutrients, forecasted CO(2)). The positive effects of nutrient and CO(2) enrichment on turfs were, however, inhibited by the presence of kelp, indicating the competitive effect of kelp was stronger than synergistic effects of moderate enrichment of local and global pollutants. Quantification of physicochemical parameters within experimental mesocosms suggests turf inhibition was likely due to an effect of kelp on physical (i.e. shading) rather than chemical conditions. Such results indicate that while forecasted climates may increase the probability of phase-shifts, maintenance of intact populations of foundation species could enable the continued strength of interactions and persistence of communities.

Induction of Early Autophagic Process on Leishmania amazonensis by Synergistic Effect of Miltefosine and Innovative Semi-synthetic Thiosemicarbazone

PubMed Central

Scariot, Débora B.; Britta, Elizandra A.; Moreira, Amanda L.; Falzirolli, Hugo; Silva, Cleuza C.; Ueda-Nakamura, Tânia; Dias-Filho, Benedito P.; Nakamura, Celso V.

2017-01-01

Drug combination therapy is a current trend to treat complex diseases. Many benefits are expected from this strategy, such as cytotoxicity decrease, retardation of resistant strains development, and activity increment. This study evaluated in vitro combination between an innovative thiosemicarbazone molecule – BZTS with miltefosine, a drug already consolidated in the leishmaniasis treatment, against Leishmania amazonensis. Cytotoxicity effects were also evaluated on macrophages and erythrocytes. Synergistic antileishmania effect and antagonist cytotoxicity were revealed from this combination therapy. Mechanisms of action assays were performed in order to investigate the main cell pathways induced by this treatment. Mitochondrial dysfunction generated a significant increase of reactive oxygen and nitrogen species production, causing severe cell injuries and promoting intense autophagy process and consequent apoptosis cell death. However, this phenomenon was not strong enough to promote dead in mammalian cell, providing the potential selective effect of the tested combination for the protozoa. Thus, the results confirmed that drugs involved in distinct metabolic routes are promising agents for drug combination therapy, promoting a synergistic effect. PMID:28270805

The Synergistic Effect of Teaching a Combined Explicit Movement and Phonological Awareness Program to Preschool Aged Students

ERIC Educational Resources Information Center

Callcott, Deborah; Hammond, Lorraine; Hill, Susan

2015-01-01

While movement is critical to young children's development, there is an ongoing debate about the time devoted to teaching movement in early childhood classrooms. Nevertheless, research has established a link between specific precursor motor skills and early literacy development. This study investigated the synergistic effect of practising specific…

75 FR 53643 - Examination Guidelines Update: Developments in the Obviousness Inquiry After KSR v.Teleflex

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

...The United States Patent and Trademark Office (USPTO or Office) is issuing an update (2010 KSR Guidelines Update) to its obviousness guidelines for its personnel to be used when applying the law of obviousness under 35 U.S.C. 103. This 2010 KSR Guidelines Update highlights case law developments on obviousness under 35 U.S.C. 103 since the 2007 decision by the United States Supreme Court (Supreme Court) in KSR Int'l Co. v. Teleflex Inc. These guidelines are intended to be used by Office personnel in conjunction with the guidance in the Manual of Patent Examining Procedure when applying the law of obviousness under 35 U.S.C. 103. Members of the public are invited to provide comments on the 2010 KSR Guidelines Update. The Office is especially interested in receiving suggestions of recent decisional law in the field of obviousness that would have particular value as teaching tools.

Role of nutraceutical SIRT1 modulators in AMPK and mTOR pathway: Evidence of a synergistic effect.

PubMed

Giovannini, Luca; Bianchi, Sara

2017-02-01

The aim of this study was to evaluate the effect of different natural substances on SIRT1 expression and on AMPK and mTOR phosphorylation. Moreover, we investigated the presence of a synergistic effect between the substances. Human cervical carcinoma cells were seeded in 12-well plates, then incubated with the nine tested substances (resveratrol, quercetin, berberine, catechin, tyrosol, ferulic acid, niclosamide, curcumin, and malvidin) at different concentrations and left in incubation for 3, 6, and 24 h. The targeting proteins' expression and phosphorylation were evaluated by immunoblotting, and cytotoxicity tests were performed by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (P > 0.05) in the number of viable cells was found. The expression of SIRT1 was significantly increased in all experimental groups compared with the control group (P < 0.001). Instead, the simultaneous administration involved a significant and synergistic increase in the expression of SIRT1 for some but not all of the tested compounds. Finally, the individual administration of berberine, quercetin, ferulic acid, and tyrosol resulted in a statistically significant increase in AMPK activation and mTOR inhibition, whereas their associated administration did not reveal a synergistic effect. Our results provide evidence that all compounds have the potential to stimulate SIRT1 and sustain the stimulating action of resveratrol on SIRT1, already widely reported in the literature. In this regard, we confirm the interaction of these substances also with the pathway of AMPK and mTOR, in support of the studies that highlight the importance of SIRT1/AMPK and mTOR pathway in many diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Overserving and Allowed Entry of Obviously Alcohol-Intoxicated Spectators at Sporting Events.

PubMed

Elgán, Tobias H; Durbeej, Natalie; Holder, Harold D; Gripenberg, Johanna

2018-02-01

Alcohol intoxication among spectators at sporting events and related problems, such as violence, are of great concern in many countries around the world. However, knowledge is scarce about whether or not alcohol is served to obviously intoxicated spectators at licensed premises inside and outside the sporting arenas, and if obviously intoxicated spectators are allowed entrance to these events. The objective of this study was therefore to examine the occurrences of overserving at licensed premises inside and outside arenas, and of allowed entry of obviously intoxicated spectators into arenas. An observational study assessing the rate of denied alcohol service and denied entry to arenas of trained professional actors portraying a standardized scene of obvious alcohol intoxication (i.e., pseudo-patrons) was conducted. The scene was developed by an expert panel, and each attempt was monitored by an observer. The settings were 2 arenas hosting matches in the Swedish Premier Football League in the largest city in Sweden and 1 arena in the second largest city, including entrances and licensed premises inside and outside the arenas. The rates of denied alcohol service were 66.9% at licensed premises outside the arenas (n = 151) and 24.9% at premises inside the arenas (n = 237). The rate of denied entry to the arenas (n = 102) was 10.8%. Overserving and allowed entry of obviously alcohol-intoxicated spectators are problematic at sporting events in Sweden and may contribute to high overall intoxication levels among spectators. The differences in server intervention rates indicate that serving staff at licensed premises inside the arenas and entrance staff are not likely to have been trained in responsible beverage service. This result underscores the need for server training among staff at the arenas. Copyright © 2017 by the Research Society on Alcoholism.

Abnormal synergistic effects between Lewis acid-base interaction and halogen bond in F3B···NCX···NCM

NASA Astrophysics Data System (ADS)

Tang, Qingjie; Li, Qingzhong

2015-12-01

An abnormal synergistic effect was found between the Lewis acid-base interaction and halogen bond in triads F3B···NCX···NCM (X and M are halogen atoms), where the strong Lewis acid-base interaction between F3B and NCX has a larger enhancement than the weak halogen bond between NCX and NCM. This is in contrast with the traditional cooperative effect. It is interesting that the alkali-metal substituent as well as the heavier halogen atom play a more remarkable role in the enhancement of the interaction F3B···NCX than that of NCX···NCM, particularly, the alkali-metal substituent makes the abnormal synergistic effect be the traditional cooperative one.

Synergistic effect of fluorination on molecular energy level modulation in highly efficient photovoltaic polymers.

PubMed

Zhang, Maojie; Guo, Xia; Zhang, Shaoqing; Hou, Jianhui

2014-02-01

The synergistic effect of fluorination on molecular energy level modulation is realized by introducing fluorine atoms onto both the donor and the acceptor moieties in a D-A polymer, and as a result, the polymer solar cell device based on the trifluorinated polymer, PBT-3F, shows a high efficiency of 8.6%, under illumination of AM 1.5G, 100 mW cm(-) (2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"Synergistic selection": a Darwinian frame for the evolution of complexity.

PubMed

Corning, Peter A; Szathmáry, Eörs

2015-04-21

Non-Darwinian theories about the emergence and evolution of complexity date back at least to Lamarck, and include those of Herbert Spencer and the "emergent evolution" theorists of the later nineteenth and early twentieth centuries. In recent decades, this approach has mostly been espoused by various practitioners in biophysics and complexity theory. However, there is a Darwinian alternative - in essence, an economic theory of complexity - proposing that synergistic effects of various kinds have played an important causal role in the evolution of complexity, especially in the "major transitions". This theory is called the "synergism hypothesis". We posit that otherwise unattainable functional advantages arising from various cooperative phenomena have been favored over time in a dynamic that the late John Maynard Smith characterized and modeled as "synergistic selection". The term highlights the fact that synergistic "wholes" may become interdependent "units" of selection. We provide some historical perspective on this issue, as well as a brief explication of the underlying theory and the concept of synergistic selection, and we describe two relevant models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lapatinib in combination with paclitaxel plays synergistic antitumor effects on esophageal squamous cancer.

PubMed

Guo, Xiao-Fang; Li, Sai-Sai; Zhu, Xiao-Fei; Dou, Qiao-Hua; Liu, Duan

2018-06-16

Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), combined with paclitaxel on the esophageal squamous cancer. MTT assays were used to evaluate the effects of the combination of lapatinib and paclitaxel on the growth of esophageal squamous cancer cell lines (KYSE150, KYSE450, KYSE510 and TE-7). The activity of the combination of two agents on cell invasion, migration and apoptosis was measured by wound healing assay, transwell assay and Annexin V-FITC/PI stain assay. Western blot assay was used to analyze the effects of the two agents on the EGFR/HER2 signaling. The in vivo efficacy was evaluated in KYSE450 xenograft nude mouse model. The combination of lapatinib and paclitaxel was highly synergistic in inhibiting cell growth with a combination index of < 1, and suppressed significantly the invasion and migration capability of esophageal squamous cancer cells. Esophageal squamous cancer cells displayed increased rates of apoptosis after treatment with lapatinib plus paclitaxel. The phosphorylated EGFR and HER2 as well as the activation of downstream molecules MAPKs and AKT significantly decreased when exposed to lapatinib and paclitaxel. In vivo studies showed that the combination of two agents had greater antitumor efficacy than either agent alone. The combination of lapatinib with paclitaxel showed synergistic antitumor activity, suggesting their potential in treating patients with esophageal squamous cancer.

Synergistic electron transfer effect-based signal amplification strategy for the ultrasensitive detection of dopamine.

PubMed

Lu, Qiujun; Chen, Xiaogen; Liu, Dan; Wu, Cuiyan; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

2018-05-15

The selective and sensitive detection of dopamine (DA) is of great significance for the identification of schizophrenia, Huntington's disease, and Parkinson's disease from the perspective of molecular diagnostics. So far, most of DA fluorescence sensors are based on the electron transfer from the fluorescence nanomaterials to DA-quinone. However, the limited electron transfer ability of the DA-quinone affects the level of detection sensitivity of these sensors. In this work, based on the DA can reduce Ag + into AgNPs followed by oxidized to DA-quinone, we developed a novel silicon nanoparticles-based electron transfer fluorescent sensor for the detection of DA. As electron transfer acceptor, the AgNPs and DA-quinone can quench the fluorescence of silicon nanoparticles effectively through the synergistic electron transfer effect. Compared with traditional fluorescence DA sensors, the proposed synergistic electron transfer-based sensor improves the detection sensitivity to a great extent (at least 10-fold improvement). The proposed sensor shows a low detection limit of DA, which is as low as 0.1 nM under the optimal conditions. This sensor has potential applicability for the detection of DA in practical sample. This work has been demonstrated to contribute to a substantial improvement in the sensitivity of the sensors. It also gives new insight into design electron transfer-based sensors. Copyright © 2018. Published by Elsevier B.V.

Synergistic Effect of Curcumin in Combination with Anticancer Agents in Human Retinoblastoma Cancer Cell Lines.

PubMed

Sreenivasan, Seethalakshmi; Krishnakumar, Subramanian

2015-01-01

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of the herb Curcuma longa, is known to have anti-proliferative and anti-tumor properties. In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line. A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive. We also performed the apoptosis and cell-cycle kinetics study with single drugs in combination with curcumin in a human RB cell lines (Y79 and Weri-Rb1). Curcumin caused concentration-dependent decrease in cell proliferation, cell kinetics, and also induced apoptosis in both the RB cell lines. When combination of curcumin with individual drugs like carboplatin or etoposide or vincristine was treated on to RB cells, both cell viability and cell cycling were reduced and increased apoptosis was noted, in comparison with single drug treatment. These effects were significant in both the cell lines, indicating the ability of curcumin to increase the sensitivity of RB cells to chemotherapy drugs. Our in vitro findings showed that the combination of curcumin with single drug treatment showed marked synergistic inhibitory effect against RB cell lines. These results suggest that curcumin can be used as a modulator which may have a potential therapeutic value for the treatment of RB cancer patients.

Craniometaphyseal dysplasia with obvious biochemical abnormality and rickets-like features.

PubMed

Wu, Bo; Jiang, Yan; Wang, Ou; Li, Mei; Xing, Xiao-Ping; Xia, Wei-Bo

2016-05-01

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones, and biochemical indexes were mostly normal. To further the understanding of the disease from a biochemical perspective, we reported a CMD case with obviously abnormal biochemical indexes. A 1-year-old boy was referred to our clinic. Biochemical test showed obviously increased alkaline phosphatase (ALP) and parathyroid hormone (PTH), mild hypocalcemia and hypophosphatemia. Moreover, significant elevated receptor activator of nuclear factor kappa-B ligand (RANKL) level, but normal β-C-terminal telopeptide of type I collagen (β-CTX) concentration were revealed. He was initially suspected of rickets, because the radiological examination also showed broadened epiphysis in his long bones. Supplementation with calcium and calcitriol alleviated biochemical abnormality. However, the patient gradually developed osteosclerosis which was inconformity with rickets. Considering that he was also presented with facial paralysis and nasal obstruction symptom, the diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. Our study revealed that obvious biochemical abnormality and rickets-like features might present as uncommon characteristics in CMD patients, and the calcium and calcitriol supplementation could alleviate biochemical abnormalities. Furthermore, although early osteoclast differentiation factor was excited in CMD patient, activity of osteoclast was still inert. Copyright © 2016. Published by Elsevier B.V.

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

PubMed

Kolberg, Marit; Paur, Ingvild; Balstad, Trude R; Pedersen, Sigrid; Jacobs, David R; Blomhoff, Rune

2013-10-01

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P < .001), and for thyme and oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P < .001). Dose dependent synergistic and antagonistic effects were observed for all combinations tested. In conclusion, this work presents a methodological tool to define synergy in experimental studies. Our results support the hypothesis that phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases. © 2013 Elsevier Inc. All rights reserved.

Synergistic effect of rice husk addition on hydrothermal treatment of sewage sludge: fate and environmental risk of heavy metals.

PubMed

Shi, Wansheng; Liu, Chunguang; Shu, Youju; Feng, Chuanping; Lei, Zhongfang; Zhang, Zhenya

2013-12-01

Hydrothermal treatment (HTT) at 200°C was applied to immobilize heavy metals (HMs) and the effect of rice husk (RH) addition was investigated based on total HMs concentration, fractionation and leaching tests. The results indicated that a synergistic effect of RH addition and HTT could be achieved on reducing the risk of HMs from medium and low risk to no risk. Metals were redistributed and transformed from weakly bounded state to stable state during the HTT process under RH addition. Notably at a RH/sludge ratio of 1/1.75 (d.w.), all the HMs showed no eco-toxicity and no leaching toxicity, with the concentrations of leachable Cr, Ni, Cu and Cd decreased by 17%, 89%, 95% and 93%, respectively. This synergistic effect of RH addition and HTT on the risk reduction of HMs implies that HTT process with RH addition could be a promising and safe disposal technology for sewage sludge treatment in practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systematic chemical analysis approach reveals superior antioxidant capacity via the synergistic effect of flavonoid compounds in red vegetative tissues

NASA Astrophysics Data System (ADS)

Qin, Xiaoxiao; Lu, Yanfen; Peng, Zhen; Fan, Shuangxi; Yao, Yuncong

2018-02-01

The flavonoid system comprises an abundance of compounds with multiple functions; however, their potential synergism in antioxidant function remains unclear. We established an approach using ever-red (RL) and ever-green leaves (GL) of crabapple cultivars during their development to determine interrelationships among flavonoid compounds. RL scored significantly better than GL in terms of the type, composition, and diversity of flavonoids than GL. Principal component analysis predicted flavonoids in RL to have positive interaction effects, and the total antioxidant capacity was significantly higher than the sum of antioxidant capacities of the individual compounds. This synergy was verified by the high antioxidant capacity in rat serum after feeding on red leaves. Our findings suggest that the synergistic effect is a result of the high transcription levels regulated by McMYBs in RL. In summary, individual flavonoids cooperate in a flavonoid system, thus producing a synergistic antioxidant effect, and the approach used herein can provide insights into the roles of flavonoids and other compounds in future studies.

Systematic Chemical Analysis Approach Reveals Superior Antioxidant Capacity via the Synergistic Effect of Flavonoid Compounds in Red Vegetative Tissues

PubMed Central

Qin, Xiaoxiao; Lu, Yanfen; Peng, Zhen; Fan, Shuangxi; Yao, Yuncong

2018-01-01

The flavonoid system comprises an abundance of compounds with multiple functions; however, their potential synergism in antioxidant function remains unclear. We established an approach using ever-red (RL) and ever-green leaves (GL) of crabapple cultivars during their development to determine interrelationships among flavonoid compounds. RL scored significantly better than GL in terms of the type, composition, and diversity of flavonoids than GL. Principal component analysis predicted flavonoids in RL to have positive interaction effects, and the total antioxidant capacity was significantly higher than the sum of antioxidant capacities of the individual compounds. This synergy was verified by the high antioxidant capacity in rat serum after feeding on red leaves. Our findings suggest that the synergistic effect is a result of the high transcription levels regulated by McMYBs in RL. In summary, individual flavonoids cooperate in a flavonoid system, thus producing a synergistic antioxidant effect, and the approach used herein can provide insights into the roles of flavonoids and other compounds in future studies. PMID:29468147

Synergistic effect in an Au-Ag alloy nanocatalyst: CO oxidation.

PubMed

Liu, Jun-Hong; Wang, Ai-Qin; Chi, Yu-Shan; Lin, Hong-Ping; Mou, Chung-Yuan

2005-01-13

Au-Ag alloy nanoparticles supported on mesoporous aluminosilicate have been prepared by one-pot synthesis using hexadecyltrimethylammonium bromide (CTAB) both as a stabilizing agent for nanoparticles and as a template for the formation of mesoporous structure. The formation of Au-Ag alloy nanoparticles was confirmed by X-ray diffraction (XRD), ultraviolet-visible (UV-vis) spectroscopy, and transmission electron microscopy (TEM). Although the Au-Ag alloy nanoparticles have a larger particle size than the monometallic gold particles, they exhibited exceptionally high activity in catalysis for low-temperature CO oxidation. Even at a low temperature of 250 K, the reaction rate can reach 8.7 x 10(-6) mol.g(cat.)(-1).s(-1) at an Au/Ag molar ratio of 3/1. While neither monometallic Au@MCM-41 nor Ag@MCM-41 shows activity at this temperature, the Au-Ag alloy system shows a strongly synergistic effect in high catalytic activity. In this alloy system, the size effect is no longer a critical factor, whereas Ag is believed to play a key role in the activation of oxygen.

ZD6474, a new treatment strategy for human osteosarcoma, and its potential synergistic effect with celecoxib

PubMed Central

Pan, Changchuan; Zhou, Yi; Du, Wuying; Chen, Jie-min; Zhu, Xiaofeng; Shen, Jingnan; Chen, Shuai; Liu, Ran-yi; Huang, Wenlin

2015-01-01

ZD6474, a small molecule VEGFR and EGFR tyrosine kinase inhibitor, has been considered as a promising tumor-targeted drug in various malignancies. EGFR and cyclooxygenase-2 (COX-2) were found overexpressed in osteosarcoma in previous reports, so here we tried to explore the anti-osteosarcoma effect of ZD6474 alone or combination with celecoxib, a COX-2 inhibitor. The data demonstrated that ZD6474 inhibited the growth of osteosarcoma cells, and promoted G1-phase cell cycle arrest and apoptosis by inhibiting the activity of EGFR tyrosine kinase, and consequently suppressing its downstream PI3k/Akt and MAPK/ERK pathway. Additionally, daily administration of ZD6474 produced a dose-dependent inhibition of tumor growth in nude mice. Celecoxib also significantly inhibited the growth of osteosarcoma cells in dose-dependent manner, while combination of ZD6474 and celecoxib displayed a synergistic or additive antitumor effect on osteosarcoma in vitro and in vivo. The possible molecular mechanisms to address the synergism are likely that ZD6474 induces the down-regulation of COX-2 expression through inhibiting ERK phosphorylation, while celecoxib promotes ZD6474-directed inhibition of ERK phosphorylation. In conclusion, ZD6474 exerts direct anti-proliferative effects on osteosarcoma cells, and the synergistic antitumor effect of the combination of ZD6474 with celecoxib may indicate a new strategy of the combinative treatment of human osteosarcoma. PMID:26050198

Synergistic Effect of Sarocladium sp. and Cryptococcus sp. Co-Culture on Crude Oil Biodegradation and Biosurfactant Production.

PubMed

Kamyabi, Aliyeh; Nouri, Hoda; Moghimi, Hamid

2017-05-01

This study was conducted to evaluate the co-culture ability of two yeast (Sarocladium sp. and Cryptococcus sp.) isolates as compared to their individual cultures in surfactant production and oil degradation. The results showed that individual culture of each strain was capable of producing surfactant, degrading oil, and pyrene; also, a synergistic effect was observed when a co-culture was applied. Oil removal and biomass production were 28 and 35% higher in the co-culture than in individual cultures, respectively. To investigate the synergistic effects of mix culture on oil degradation, the surface tension, emulsification activity (EA), and cell surface hydrophobicity of individual and co-culture were studied. A comparison between the produced biosurfactant and chemical surfactants showed that individual culture of each yeast strain could reduce the surface tension like SDS and about 10% better than Tween 80. The results showed that the microbial consortium could reduce the surface tension more, by 10 and 20%, than SDS and Tween 80, respectively. Both individual cultures of Sarocladium sp. and Cryptococcus sp. showed good emulsification activity (0.329 and 0.412, respectively) when compared with a non-inoculated medium. Emulsification activity measurement for the two yeast mix cultures showed an excellent 33 and 67% increase as compared to the individual culture of Sarocladium sp. and Cryptococcus sp., respectively. The cell surface hydrophobicity of Sarocladium sp. and Cryptococcus sp. increased (38 and 85%) when the cells were treated with pyrene as a hydrophobic substrate for four generations. Finally, a 40% increase for pyrene degradation was measured in a co-culture of the two yeast mix culture. According to the results of the present study, the co-culture system exhibited better performance and this study will enhance the understanding of the synergistic effects of yeast co-culture on oil degradation.

Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy

NASA Astrophysics Data System (ADS)

Qin, Chenchen; Fei, Jinbo; Wang, Anhe; Yang, Yang; Li, Junbai

2015-11-01

To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular

Synergistic and Antagonistic Effects of Piperonyl Butoxide in Fipronil-Susceptible and Resistant Rice Stem Borrers, Chilo suppressalis

PubMed Central

Huang, Qingchun; Deng, Yunfei; Zhan, Taisong; He, Yuan

2010-01-01

Using the phenylpyrazole insecticide, fipronil for selection in the laboratory, a resistant Wenzhou strain of the rice stem borer, Chilo suppressalis (Walker) (Lepidoptera: Crambidae) had an LD50 at least 45.3 times greater than the susceptible Anhui strain. The realized resistant heritability (h2) of 0.213 showed that the tolerant phenotype was moderately heritable and had potential to develop higher tolerance to fipronil. Piperonyl butoxide decreased the effects of fipronil on the mortality of the susceptible larvae with 0.27–0.44 times synergistic rates, but increased the toxicity of fipronil on the resistant larvae with 1.85–2.53 times synergistic rates as compared to that of fipronil alone. The inhibitory effect of piperonyl butoxide on the activity of microsomal O-demethylase was greater in susceptible larvae than in the resistant larvae. The differential synergism of fipronil by piperonyl butoxide in the susceptible and resistant C. suppressalis may be caused by the reduced penetration of fipronil in the lab-selected Wenzhou strain. PMID:21062143

A Synergistic Approach to Faculty Mentoring

ERIC Educational Resources Information Center

Goodwin, Laura D.

2004-01-01

Following a comparison of two approaches to mentoring--the traditional model and a relatively new "synergistic" or co-mentoring model--a new formal mentoring program for faculty in the School of Education at the University of Colorado at Denver, based on the synergistic approach, is described. First-year program evaluation data revealed…

Synergistic cytogenetic and antineoplastic effects by the combined action of esteric steroidal derivatives of nitrogen mustards.

PubMed

Mourelatos, Constantinos; Nikolaropoulos, Sotiris; Fousteris, Manolis; Pairas, Georgios; Argyraki, Maria; Kareli, Dimitra; Dafa, Evaggelia; Mourelatos, Dionisios; Lialiaris, Theodore

2012-06-01

We studied the effect of five newly synthesized steroidal derivatives of nitrogen mustards. These derivatives have as alkylators either P-N, N-bis(2-chloroethyl)aminophenyl-butyrate (CHL) or P-N, N-bis(2-chloroethyl)aminophenyl-acetate (PHE) groups esterified with different modified steroidal nuclei. We examined them alone or in combination, on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds, alone or in combination, was also tested on Leukemia P388-bearing mice. A pronounced cytogenetic and antineoplastic action was demonstrated by the compounds that contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17 position of the D-ring. The exocyclical insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) yielded a compound demonstrating a distinct cytogenetic and antineoplastic effect. In contrast, the ketone group in the D-ring being inserted endocyclically in the steroidal nucleus (androstene) esterified with either CHL or with PHE gave negative cytogenetic and antineoplastic effects. However, the combined action of cholestene esterified with either CHL or with PHE in combination with either the androstene ester of PHE or with the androstene ester of CHL, respectively, gave synergistic cytogenetic and antineoplastic effects. Also the amide ester of PHE in combination with the androstene ester of CHL gave distinct cytogenetic and antineoplastic effects in a synergistic manner.

Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats.

PubMed

Chang, Qing; Liu, Zhe; Ma, Wen-Zhi; Hei, Chang-Chun; Shen, Xin-Sheng; Qian, Xiao-Jing; Xu, Zeng-Lu

2011-06-01

Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen. Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods. Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group. The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal

Synergistic and Non-synergistic Associations for Cigarette Smoking and Non-tobacco Risk Factors for Cardiovascular Disease Incidence in the Atherosclerosis Risk In Communities (ARIC) Study.

PubMed

Lubin, Jay H; Couper, David; Lutsey, Pamela L; Yatsuya, Hiroshi

2017-07-01

Cigarette smoking, various metabolic and lipid-related factors and hypertension are well-recognized cardiovascular disease (CVD) risk factors. Since smoking affects many of these factors, use of a single imprecise smoking metric, for example, ever or never smoked, may allow residual confounding and explain inconsistencies in current assessments of interactions. Using a comprehensive model in pack-years and cigarettes/day for the complex smoking-related relative risk (RR) of CVD to reduce residual confounding, we evaluated interactions with non-tobacco risk factors, including additive (non-synergistic) and multiplicative (synergistic) forms. Data were from the prospective Atherosclerosis Risk in Communities (ARIC) Study from four areas of the United States recruited in 1987-1989 with follow-up through 2008. Analyses included 14 127 participants, 207 693 person-years and 2857 CVD events. Analyses revealed distinct interactions with smoking: including statistical consistency with additive (body mass index [BMI], waist to hip ratio [WHR], diabetes mellitus [DM], glucose, insulin, high density lipoproteins [HDL] and HDL(2)); and multiplicative (hypertension, total cholesterol [TC], low density lipoproteins [LDLs], apolipoprotein B [apoB], TC to HDL ratio and HDL(3)) associations, as well as indeterminate (apolipoprotein A-I [apoA-I] and triglycerides) associations. The forms of the interactions were revealing but require confirmation. Improved understanding of joint associations may help clarify the public health burden of smoking for CVD, links between etiologic factors and biological mechanisms, and the consequences of joint exposures, whereby synergistic associations highlight joint effects and non-synergistic associations suggest distinct contributions. Joint associations for cigarette smoking and non-tobacco risk factors were distinct, revealing synergistic/multiplicative (hypertension, TC, LDL, apoB, TC/HDL, HDL(3)), non-synergistic/additive (BMI, WHR, DM, glucose

Synergistic Effect of Combined Hollow Viscus Injuries on Intra-Abdominal Abscess Formation.

PubMed

Paulus, Elena M; Croce, Martin A; Shahan, Charles P; Zarzaur, Ben L; Sharpe, John P; Dileepan, Amirtha; Boyd, Brandon S; Fabian, Timothy C

2015-07-01

The strong association between penetrating colon injuries and intra-abdominal abscess (IAA) formation is well established and attributed to high colon bacterial counts. Since trauma patients are rarely fasting at injury, stomach and small bowel colony counts are also elevated. We hypothesized that there is a synergistic effect of increased IAA formation with concomitant stomach and/or colon injuries when compared to small bowel injuries alone. Consecutive patients at a level one trauma center with penetrating small bowel (SB), stomach (S), and/or colon (C) injuries from 1996 to 2012 were reviewed. Logistic regression determined associations with IAA, adjusting for age, gender, Injury Severity Score (ISS), admission Glasgow Coma Score, transfusions, and concurrent pancreas or liver injury. A total of 1518 patients (91% male, ISS = 15.9 ± 8.4) were identified: 496 (33%) SB, 231 (15%) S, 288 (19%) C, 40 (3%) S + SB, 69 (5%) S + C, 338 (22%) C + SB, and 56 (4%) S + C + SB. 148 (10%) patients developed IAA: 4 per cent SB, 9 per cent S, 10 per cent C, 5 per cent S + SB, 22 per cent S + C, 13 per cent C + SB, and 25 per cent S + C + SB. Multiple logistic regression demonstrated that ISS, 24 hour blood transfusions, and concomitant pancreatic or liver injuries were associated with IAA. Compared with reference SB, S or S + SB injuries were no more likely to develop IAA. However, S + C, SB + C, and S + C + SB injuries were significantly more likely to have IAA. In conclusion, combined stomach + colon, small bowel + colon, and stomach, colon, + small bowel injuries have a synergistic effect leading to increased IAA formation after penetrating injuries. Heightened clinical suspicion for IAA formation is necessary in these combined hollow viscus injury patients.

Synergistic Effect of Honey and Propolis on Cutaneous Wound Healing in Rats.

PubMed

Takzaree, Nasrin; Hadjiakhondi, Abbas; Hassanzadeh, Gholamreza; Rouini, Mohammad Reza; Manayi, Azadeh

2016-04-01

Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day's rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P<0.05). The macroscopic and microscopic evaluation showed that the percentage of wound healing on different days in combined propolis and honey experimental group was significantly different from the control group (Multivariate ANOVA test) (P<0.05). Combined application of propolis and honey on the open wound healing in rats has a synergistic effect.

HIFU and Chemotherapy Synergistic Inhibitory Effect on Dunning AT2 Tumour-Bearing Rats

NASA Astrophysics Data System (ADS)

Curiel, Laura; Paparel, Philipe; Chesnais, Sabrina; Gelet, Albert; Chapelon, Jean-Yves

2005-03-01

Since there is no 100% satisfactory treatment for localized prostate cancer in patients presenting symptoms representing a poor prognosis (stage T3, high Gleason score, PSA level greater than 15 ng/ml, etc.), this study aimed to evaluate the therapeutic and synergistic inhibition effects of using High Intensity Focused Ultrasound (HIFU) in combination with chemotherapy (Taxane + Estramustine). Forty-one Dunning AT2 tumour-bearing Copenhagen rats receiving HIFU and/or chemotherapy were divided into four groups: control group; chemotherapy group; HIFU group; and HIFU-chemotherapy combined group. Increase in the tumour volume was observed over 3 weeks and the tumour volume doubling time was evaluated. Growth curves for each group were then plotted and statistically evaluated. HIFU treatment combined with Taxane + Estramusine was found to have a significant synergistic effect; on day 30, the distribution of tumour volume relative to the treatment group was significantly different (p = 0.0007). The control group volumes were significantly greater than those of the chemotherapy-only (p = 0.006) or HIFU-only group (p = 0.006). The greatest difference was observed between the chemotherapy plus HIFU combined group and the control group. Additionally, tumour-doubling times were 7.7 days for the control group, 13.2 days for the HIFU-only group, and 31.2 days for the chemotherapy plus HIFU group. The differences in tumour growth rates between the chemotherapy plus HIFU combined group and a chemotherapy-only + HIFU-only grouping was 3.8% (p = 0.0020). Thus, the combined chemotherapy plus HIFU treatment was clearly more effective in reducing the tumour size than HIFU only or chemotherapy only, which indicates a synergy between the two types of treatment. Our results suggest that this combined therapy could be useful for the treatment of high-risk prostate cancer.

Synergistic Tumor-Killing Effect of Radiation and Berberine Combined Treatment in Lung Cancer: The Contribution of Autophagic Cell Death

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

Peng Peiling; Division of Gastroenterology, Armed Forces Taichung Hospital, Taichung, Taiwan; Kuo, W.-H.

2008-02-01

Purpose: Radiotherapy is the most efficacious strategies for lung cancer. The radiation-enhancing effects and the underlying mechanisms of berberine were investigated both in vitro and in vivo. Methods and Materials: Clonogenic survival assays were used to evaluate the radio-sensitivity of berberine on non-small-cell lung cancer. Electron microscopic observation of the features of cell death, flow cytometry of acidic vascular organelles formation, mitochondria membrane potential and cell-cycle progression, and Western blotting of caspase 3, PARP, and LC3 were performed to identify the mechanisms underlying the enhancing effects. Lewis lung carcinoma model in mice was conducted to evaluate the possible application ofmore » berberine in synergistic treatment with irradiation. Results: Compared with radiation alone (SF2 = 0.423; D{sub 0} = 5.29 Gy), berberine at 5 and 10 {mu}M concentrations in combination with radiation showed significant enhancement on radiation-induced clonogenic inhibition (SF2 = 0.215: D{sub 0} = 2.70 Gy and SF2 = 0.099: D{sub 0} = 1.24 Gy) on A549 cells. The cellular ultrastructure showed the presence of autophagosome and an increased proportion of acridine orange stain-positive cells, demonstrating that berberine enhanced radiosensitivity via autophagy. The process involved LC3 modification and mitochondrial disruption. The animal model verified the synergistic cytotoxic effect of berberine and irradiation resulting in a substantial shrinkage of tumor volume. Conclusion: Supplement of berberine enhanced the cytotoxicity of radiation in both in vivo and in vitro models of lung cancer. The mechanisms underlying this synergistic effect involved the induction of autophagy. It suggests that berberine could be used as adjuvant therapy to treat lung cancer.« less

Effects of antagonistic and synergistic muscles' co-activation on mechanics of activated spastic semitendinosus in children with cerebral palsy.

PubMed

Ateş, Filiz; Temelli, Yener; Yucesoy, Can A

2018-02-01

Most activities involve co-activation of several muscles and epimuscular myofascial force transmission (EMFT) can affect their mechanics. This can be relevant for spastic muscles of cerebral palsy (CP) patients. Isometric spastic semitendinosus (ST) forces vs. knee angle (KA-F ST ) data were collected intra-operatively to test the following hypotheses: (i) Inter-antagonistic EMFT elevates F ST , (ii) changes the shape of KA-F ST characteristics, (iii) reduces the muscle's joint range of force exertion (Range-F ST ) and (iv) combined inter-antagonistic and synergistic EMFT further changes those effects. 11 limbs of 6 patients with CP (mean (SD) = 7.7 (4.7) years; GMFCS levels = II-IV) were tested in 3 conditions from 120° to full extension: ST activated (I) exclusively, (II) simultaneously with an antagonist, and (III) with added activation of synergists. Condition II increased F ST (e.g., peak force = 87.6 N (30.5 N)) significantly (by 33.6%), but condition III caused no further change. No condition changed the muscle's wide Range-F ST (100.7° (15.9°)) significantly. Therefore, only the first hypothesis was confirmed. Co-activating its antagonist elevates forces of activated spastic ST substantially, but does not change its joint range of force exertion. Added activation of its synergists causes no further effects. Therefore, EMFT effects in CP can be relevant and need to be tested in other knee flexors. Copyright © 2017 Elsevier B.V. All rights reserved.

A pharmacoproteomic study confirms the synergistic effect of chondroitin sulfate and glucosamine

PubMed Central

Calamia, Valentina; Mateos, Jesús; Fernández-Puente, Patricia; Lourido, Lucía; Rocha, Beatriz; Fernández-Costa, Carolina; Montell, Eulalia; Vergés, Josep; Ruiz-Romero, Cristina; Blanco, Francisco J.

2014-01-01

Osteoarthritis (OA) is the most common age-related rheumatic disease. Chondrocytes play a primary role in mediating cartilage destruction and extracellular matrix (ECM) breakdown, which are main features of the OA joint. Quantitative proteomics technologies are demonstrating a very interesting power for studying the molecular effects of some drugs currently used to treat OA patients, such as chondroitin sulfate (CS) and glucosamine (GlcN). In this work, we employed the iTRAQ (isobaric tags for relative and absolute quantitation) technique to assess the effect of CS and GlcN, both alone and in combination, in modifying cartilage ECM metabolism by the analysis of OA chondrocytes secretome. 186 different proteins secreted by the treated OA chondrocytes were identified. 36 of them presented statistically significant differences (p ≤ 0.05) between untreated and treated samples: 32 were increased and 4 decreased. The synergistic chondroprotective effect of CS and GlcN, firstly reported by our group at the intracellular level, is now demonstrated also at the extracellular level. PMID:24912619

In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model.

PubMed

Agarwal, Drishti; Sharma, Manish; Dixit, Sandeep K; Dutta, Roshan K; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

2015-02-05

Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their anti-malarial interaction in combination with artemisinin in vitro, against Plasmodium falciparum 3D7 strain, employing fixed-ratio combination isobologram method. In addition, the efficacy of these compounds was evaluated intraperitoneally in BALB/c mice infected with chloroquine-resistant Plasmodium berghei ANKA strain in the Peters' four-day suppressive test. Promising results were obtained in the form of synergistic or additive interactions. Compounds 10 and 12 were found to have highly synergistic interactions with artemisinin. Antiplasmodial effect was further verified by the convincing ED50 values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW). In vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.

Oxidation and biodegradation of polyethylene films containing pro-oxidantadditives: Synergistic effects of sunlight exposure, thermal aging and fungal biodegradation

USDA-ARS?s Scientific Manuscript database

Synergistic effects of sunlight exposure, thermal aging and fungal biodegradation on the oxidation and biodegradation of linear low density poly (ethylene) PE-LLD films containing pro-oxidant were examined. To achieve oxidation and degradation, films were first exposed to the sunlight for 93 days du...

Gold nanoparticles and electroporation impose both separate and synergistic radiosensitizing effects in HT-29 tumor cells: an in vitro study.

PubMed

Rezaee, Zohre; Yadollahpour, Ali; Bayati, Vahid; Negad Dehbashi, Fereshteh

2017-01-01

Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of radiosensitizers to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy. Radiosensitizing effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR. Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, 2.61, and 2.89, indicating synergistic radiosensitizing effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines. Combined GNPs-EP protocols induced synergistic radiosensitizing effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less radiosensitive tumors.

Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling

PubMed Central

Shirode, Amit B.; Sylvester, Paul W.

2009-01-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, γ-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of γ-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and γ-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFκB and prostaglandin E2 (PGE2) synthesis was assessed following a 3- or 4-day culture period. Treatment with 3–4 μM γ-tocotrienol or 7.5–10 μM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of γ-tocotrienol (0.25 μM) and celecoxib (2.5 μM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitor effect was associated with a reduction in PGE2 synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFκB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and γ-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. PMID:19954924

A selective decoy-doxorubicin complex for targeted co-delivery, STAT3 probing and synergistic anti-cancer effect.

PubMed

Wang, Shao-Jen; Hou, Yung-Te; Chen, Lin-Chi

2015-09-04

A novel selective decoy oligodeoxynucleotide (dODN)-doxorubicin (DOX) complex is reported for cancer theranostics. It eliminates the use of a ligand or carrier for targeted delivery and disassembles into therapeutic dODN and DOX upon encountering over-activated STAT3 in cancer cells. Hence, in situ STAT3 probing and synergistic anti-cancer effect are attained at the same time.

Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions

NASA Astrophysics Data System (ADS)

Biswas, Rajib; Bagchi, Biman

2018-01-01

In nature, water is often found in contact with surfaces that are extended on the scale of molecule size but small on a macroscopic scale. Examples include lipid bilayers and reverse micelles as well as biomolecules like proteins, DNA and zeolites, to name a few. While the presence of surfaces and interfaces interrupts the continuous hydrogen bond network of liquid water, confinement on a mesoscopic scale introduces new features. Even when extended on a molecular scale, natural and biological surfaces often have features (like charge, hydrophobicity) that vary on the scale of the molecular diameter of water. As a result, many new and exotic features, which are not seen in the bulk, appear in the dynamics of water close to the surface. These different behaviors bear the signature of both water-surface interactions and of confinement. In other words, the altered properties are the result of the synergistic effects of surface-water interactions and confinement. Ultrafast spectroscopy, theoretical modeling and computer simulations together form powerful synergistic approaches towards an understanding of the properties of confined water in such systems as nanocavities, reverse micelles (RMs), water inside and outside biomolecules like proteins and DNA, and also between two hydrophobic walls. We shall review the experimental results and place them in the context of theory and simulations. For water confined within RMs, we discuss the possible interference effects propagating from opposite surfaces. Similar interference is found to give rise to an effective attractive force between two hydrophobic surfaces immersed and kept fixed at a separation of d, with the force showing an exponential dependence on this distance. For protein and DNA hydration, we shall examine a multitude of timescales that arise from frustration effects due to the inherent heterogeneity of these surfaces. We pay particular attention to the role of orientational correlations and modification of the

Synergistic effect of gamma (γ)-irradiation and microencapsulated antimicrobials against Listeria monocytogenes on ready-to-eat (RTE) meat.

PubMed

Huq, Tanzina; Vu, Khanh Dang; Riedl, Bernard; Bouchard, Jean; Lacroix, Monique

2015-04-01

Oregano essential oil (Origanum compactum; 250 μg/ml), cinnamon essential oil (Cinnamomum cassia; 250 μg/ml) and nisin (16 μg/ml) were used alone or in combination to evaluate their efficiency to inhibit the growth of Listeria monocytogenes on RTE ham. Microencapsulation of the antimicrobial formulations was done to verify the potential effect of the polymer to protect the antimicrobial efficiency during storage. Combined treatments of antimicrobial formulation with γ-irradiation were done to verify the synergistic effect against L. monocytogenes. Microencapsulation of essential oils-nisin and γ-irradiation treatment in combination showed synergistic antimicrobial effect during storage on RTE meat products. Microencapsulated cinnamon and nisin in combination with γ-irradiation (at 1.5 kGy) showed 0.03 ln CFU/g/day growth rate of L. monocytogenes whereas the growth rate of non-microencapsulated cinnamon and nisin in combination with γ-irradiation was 0.17 ln CFU/g/day. Microencapsulation significantly (P ≤ 0.05) improved the radiosensitivity of L. monocytogenes. Microencapsulated oregano and cinnamon essential oil in combination with nisin showed the highest bacterial radiosensitization 2.89 and 5, respectively, compared to the control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synergistic Anti-arrhythmic Effects in Human Atria with Combined Use of Sodium Blockers and Acacetin

PubMed Central

Ni, Haibo; Whittaker, Dominic G.; Wang, Wei; Giles, Wayne R.; Narayan, Sanjiv M.; Zhang, Henggui

2017-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Developing effective and safe anti-AF drugs remains an unmet challenge. Simultaneous block of both atrial-specific ultra-rapid delayed rectifier potassium (K+) current (IKur) and the Na+ current (INa) has been hypothesized to be anti-AF, without inducing significant QT prolongation and ventricular side effects. However, the antiarrhythmic advantage of simultaneously blocking these two channels vs. individual block in the setting of AF-induced electrical remodeling remains to be documented. Furthermore, many IKur blockers such as acacetin and AVE0118, partially inhibit other K+ currents in the atria. Whether this multi-K+-block produces greater anti-AF effects compared with selective IKur-block has not been fully understood. The aim of this study was to use computer models to (i) assess the impact of multi-K+-block as exhibited by many IKur blokers, and (ii) evaluate the antiarrhythmic effect of blocking IKur and INa, either alone or in combination, on atrial and ventricular electrical excitation and recovery in the setting of AF-induced electrical-remodeling. Contemporary mathematical models of human atrial and ventricular cells were modified to incorporate dose-dependent actions of acacetin (a multichannel blocker primarily inhibiting IKur while less potently blocking Ito, IKr, and IKs). Rate- and atrial-selective inhibition of INa was also incorporated into the models. These single myocyte models were then incorporated into multicellular two-dimensional (2D) and three-dimensional (3D) anatomical models of the human atria. As expected, application of IKur blocker produced pronounced action potential duration (APD) prolongation in atrial myocytes. Furthermore, combined multiple K+-channel block that mimicked the effects of acacetin exhibited synergistic APD prolongations. Synergistically anti-AF effects following inhibition of INa and combined IKur/K+-channels were also observed. The attainable maximal

Synergistic cytotoxic effects of ions released by zinc-aluminum bronze and the metallic salts on osteoblastic cells.

PubMed

Grillo, Claudia A; Morales, María L; Mirífico, María V; Fernández Lorenzo de Mele, Mónica A

2013-07-01

The use of copper-based alloys for fixed dental crowns and bridges is increasingly widespread in several countries. The aim of this work is to study the dissolution of a zinc-aluminum-bronze and the cytotoxic effects of the ions released on UMR-106 osteoblastic cell line. Two sources of ions were used: (1) ions released by the metal alloy immersed in the cell culture and (2) salts of the metal ions. Conventional electrochemical techniques, atomic absorption spectroscopy [to obtain the average concentration of ions (AC) in solution], and energy dispersive X-ray (EDX) spectroscopy analysis were used to study the corrosion process. Corrosion tests revealed a strong influence of the composition of the electrolyte medium and the immersion time on the electrochemical response. The cytotoxicity was evaluated with (a) individual ions, (b) combinations of two ions, and (c) the mixture of all the ions released by a metal disc of the alloy. Importantly, synergistic cytotoxic effects were found when Al-Zn ion combinations were used at concentration levels lower than the cytotoxic threshold values of the individual ions. Cytotoxic effects in cells in the vicinity of the metal disc were also found. These results were interpreted considering synergistic effects and a diffusion controlled mechanism that yields to concentration levels, in the metal surroundings, several times higher than the measured AC value. Copyright © 2013 Wiley Periodicals, Inc.

Synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria

PubMed Central

Talei, Gholam-Reza; Mohammadi, Mohsen; Bahmani, Mahmoud; Kopaei, Mahmoud Rafieian

2017-01-01

Background: Infectious diseases have always been an important health issue in human communities. In the recent years, much research has been conducted on antimicrobial effects of nature-based compounds because of increased prevalence of antibiotic resistance. The present study was conducted to investigate synergistic effect of Carum copticum and Mentha piperita essential oils with ciprofloxacin, vancomycin, and gentamicin on Gram-negative and Gram-positive bacteria. Materials and Methods: In this experimental study, the synergistic effects of C. copticum and M. piperita essential oils with antibiotics on Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus epidermidis (ATCC 14990), and Listeria monocytogenes (ATCC 7644) were studied according to broth microdilution and the MIC and fractional inhibitory concentration (FIC) of these two essential oils determined. Results: C. copticum essential oil at 30 μg/ml could inhibit S. aureus, and in combination with vancomycin, decreased MIC from 0.5 to 0.12 μg/ml. Moreover, the FIC was derived 0.24 μg/ml which represents a potent synergistic effect with vancomycin against S. aureus growth. C. copticum essential oil alone or combined with other antibiotics is effective in treating bacterial infections. Conclusions: In addition, C. copticum essential oil can strengthen the activities of certain antibiotics, which makes it possible to use this essential oil, especially in drug resistance or to lower dosage or toxicity of the drugs. PMID:28929050

Towards an understanding of adult judgments of synergistic health benefits.

PubMed

Dawson, Ian G J; Dohle, Simone

2016-02-01

Numerous scientific studies show that certain combinations of dietary and/or lifestyle factors produce health benefits which are greater than the sum of the benefits associated with each factor alone. To address an existing knowledge gap, we assessed the extent to which individuals understand that certain combinations present these 'synergistic health benefits'. Health benefit judgments were obtained from lay adults for a range of dietary and/or lifestyle combinations that have been found to present synergistic benefits. Association between these judgments and socio-cognitive characteristics such as numeracy, education, and health interest (HI) were examined. Three hundred and fifty-two Swiss adults were presented with a description of one of eight synergistically beneficial combinations. Each participant provided a categorical benefit judgment (i.e., subadditive, additive, or synergistic) for the combination and explained the cognitive reasoning underlying their judgment. Participants completed measures of numeracy and HI. The proportion of combinations judged to present a synergistic benefit was modest for 'macro-level' combinations (e.g., diet and exercise), but low for 'micro-level' combinations (e.g., two phytochemicals). Cognitive reasoning data showed that a higher proportion of judgments for micro-level (cf. macro-level) combinations were based on greater subjective epistemic uncertainty. Higher interest in health was associated with a better understanding of synergistic benefits, but numeracy and education level were not. There is considerable scope to improve the extent to which lay adults understand that specific combination of diet and lifestyle behaviours can synergistically benefit their health. Our results enable us to make informed recommendations for public health interventions. What is already known on this subject? Combining certain dietary and/or lifestyle factors can result in synergistic health benefits. People could maintain/enhance their

State and local law enforcement agency efforts to prevent sales to obviously intoxicated patrons

PubMed Central

Lenk, Kathleen M.; Toomey, Traci L.; Nelson, Toben F.; Jones-Webb, Rhonda; Erickson, Darin J.

2013-01-01

Alcohol sales to intoxicated patrons are illegal and may lead to public health issues such as traffic crashes and violence. Over the past several decades, considerable effort has been made to reduce alcohol sales to underage persons but less attention has been given to the issue of sales to obviously intoxicated patrons. Studies have found a high likelihood of sales to obviously intoxicated patrons (i.e., overservice), but little is known about efforts by enforcement agencies to reduce these sales. We conducted a survey of statewide alcohol enforcement agencies and local law enforcement agencies across the U.S. to assess their strategies for enforcing laws prohibiting alcohol sales to intoxicated patrons at licensed alcohol establishments. We randomly sampled 1,631 local agencies (1082 participated), and surveyed all 49 statewide agencies that conduct alcohol enforcement. Sales to obviously intoxicated patrons were reported to be somewhat or very common in their jurisdiction by 55% of local agencies and 90% of state agencies. Twenty percent of local and 60% of state agencies reported conducting enforcement efforts to reduce sales to obviously intoxicated patrons in the past year. Among these agencies, fewer than half used specific enforcement strategies on at least a monthly basis to prevent overservice of alcohol. Among local agencies, enforcement efforts were more common among agencies that had a full-time officer specifically assigned to carry out alcohol enforcement efforts. Enforcement of laws prohibiting alcohol sales to obviously intoxicated patrons is an underutilized strategy to reduce alcohol-related problems, especially among local law enforcement agencies. PMID:24068596

State and local law enforcement agency efforts to prevent sales to obviously intoxicated patrons.

PubMed

Lenk, Kathleen M; Toomey, Traci L; Nelson, Toben F; Jones-Webb, Rhonda; Erickson, Darin J

2014-04-01

Alcohol sales to intoxicated patrons are illegal and may lead to public health issues such as traffic crashes and violence. Over the past several decades, considerable effort has been made to reduce alcohol sales to underage persons but less attention has been given to the issue of sales to obviously intoxicated patrons. Studies have found a high likelihood of sales to obviously intoxicated patrons (i.e., overservice), but little is known about efforts by enforcement agencies to reduce these sales. We conducted a survey of statewide alcohol enforcement agencies and local law enforcement agencies across the US to assess their strategies for enforcing laws prohibiting alcohol sales to intoxicated patrons at licensed alcohol establishments. We randomly sampled 1,631 local agencies (1,082 participated), and surveyed all 49 statewide agencies that conduct alcohol enforcement. Sales to obviously intoxicated patrons were reported to be somewhat or very common in their jurisdiction by 55 % of local agencies and 90 % of state agencies. Twenty percent of local and 60 % of state agencies reported conducting enforcement efforts to reduce sales to obviously intoxicated patrons in the past year. Among these agencies, fewer than half used specific enforcement strategies on at least a monthly basis to prevent overservice of alcohol. Among local agencies, enforcement efforts were more common among agencies that had a full-time officer specifically assigned to carry out alcohol enforcement efforts. Enforcement of laws prohibiting alcohol sales to obviously intoxicated patrons is an underutilized strategy to reduce alcohol-related problems, especially among local law enforcement agencies.

The non-obvious basis of ownership: Preschool children trace the history and value of owned objects

PubMed Central

Gelman, Susan A.; Manczak, Erika M.; Noles, Nicholaus S.

2012-01-01

For adults, ownership is non-obvious: (a) determining ownership depends more on an object’s history than on perceptual cues, and (b) ownership confers special value on an object (“endowment effect”). This study examined these concepts in preschoolers (2.0–4.4) and adults (N=112). Participants saw toy-sets in which one toy was designated as the participant’s, and one as the researcher’s. Toys were then scrambled and participants were asked to identify their toy and the researcher’s toy. By three years of age, participants used object history to determine ownership, and identified even undesirable toys as their own. Furthermore, participants at all ages showed an endowment effect (greater liking of items designated as their own). Thus, even 2-year-olds appreciate the non-obvious basis of ownership. PMID:22716967

Copyrolysis of Biomass and Coal: A Review of Effects of Copyrolysis Parameters, Product Properties, and Synergistic Mechanisms

PubMed Central

2016-01-01

Concerns in the last few decades regarding the environmental and socioeconomic impacts of the dependence on fossil fuels have resulted in calls for more renewable and alternative energy sources. This has led to recent interest in copyrolysis of biomass and coal. Numerous reviews have been found related to individual pyrolysis of coal and biomass. This review deals mainly with the copyrolysis of coal and biomass and then compares their results with those obtained using coal and biomass pyrolysis in detail. It is controversial whether there are synergistic or additive behaviours when coal and biomass are blended during copyrolysis. In this review, the effects of reaction parameters such as feedstock types, blending ratio, heating rate, temperature, and reactor types on the occurrence of synergy are discussed. Also, the main properties of the copyrolytic products are pointed out. Some possible synergistic mechanisms are also suggested. Additionally, several outlooks based on studies in the literature are also presented in this paper. PMID:27722171

Synergistic Synthetic Biology: Units in Concert

PubMed Central

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert.

PubMed

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Synergistic effect of atorvastatin and cyanidin-3-glucoside against angiotensin II-mediated vascular smooth muscle cell proliferation and migration through MAPK and PI3K/Akt pathways.

PubMed

Pantan, Rungusa; Tocharus, Jiraporn; Phatsara, Manussabhorn; Suksamrarn, Apichart; Tocharus, Chainarong

2016-09-13

This study aimed to investigate the mechanism of cyanidin-3-glucoside (C3G) in synergy with atorvastatin, even when it is used in low concentrations. Human aortic smooth muscle cells (HASMCs) were used to verify the synergistic mechanism of atorvastatin and C3G against angiotensin II-induced proliferation and migration. BrdU incorporation assay was used to evaluate cell proliferation. Wound healing and Boyden chamber assays were used to investigate cell migration. The cell cycle was examined using flow cytometry. The results revealed that atorvastatin and C3G exhibit a synergistic effect in ameliorating HASMC proliferation and migration by enhancing cell cycle arrest. In addition, these effects also decreased mitogen-activated protein kinase (MAPK) activity by attenuating the expression of phospho-p38, phospho-extracellular signaling-regulated kinase 1/2, and phospho-c-Jun N-terminal kinase. Furthermore, the combination of atorvastatin and C3G modulated the PI3K/Akt pathway and upregulated p21 Cip1 , which was associated with decreases in cyclin D 1 and phospho-retinoblastoma expressions. The synergistic effect of atorvastatin and C3G induced anti-proliferation and anti-migration through MAPK and PI3K/Akt pathways mediated by AT 1 R. These results suggest that the synergistic effect of atorvastatin and C3G may be an alternative therapy for atherosclerosis patients.

Synergistic effects of fibronectin and bone morphogenetic protein on the bioactivity of titanium metal.

PubMed

Biao, M N; Chen, Y M; Xiong, S B; Wu, B Y; Yang, B C

2017-09-01

To improve the biological properties of bioactive titanium metal, recombinant human bone morphogenetic protein 2(rhBMP-2) and fibronectin (Fn) were adsorbed on its surface solely or contiguously to modify the anodic oxidized titanium (AO-Ti), acid-alkali-treated titanium (AA-Ti), and polished titanium (P-Ti). It is found that the different bioactive titanium surface structures had great influence on protein adsorption. The adsorption amounts of BMP adsorbed solely and Fn/BMP adsorbed contiguously were AA-Ti > P-Ti > AO-Ti, and that for Fn adsorbed solely was AA-Ti ≈ P-Ti > AO-Ti. The conformation of proteins was changed remarkably after the adsorption. For BMP, the α-helix decreased on AA-Ti and stabilized on P-Ti and AO-Ti. For Fn, the β-sheet on PT-Ti and AA-Ti increased significantly. For Fn/BMP, the percentage of β-sheet on AA-Ti increased, and that of α-helix on all samples was stable. MSCs showed greater adhesion and spreading on Fn/BMP groups. MTT and Elisa tests showed that the synergistic effects of proteins made the cells proliferate and differentiate faster. It indicated both the surface structure and the synergistic effects of proteins could influence the biological properties of titanium metals. It provides research foundation for improving the biological properties of bioactive titanium metals by simultaneous application of several proteins. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2485-2498, 2017. © 2017 Wiley Periodicals, Inc.

Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling.

PubMed

Shirode, Amit B; Sylvester, Paul W

2010-05-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, gamma-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of gamma-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and gamma-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFkappaB and prostaglandin E(2) (PGE(2)) synthesis were assessed following a 3- or 4-day culture period. Treatment with 3-4 microM gamma-tocotrienol or 7.5-10 microM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of gamma-tocotrienol (0.25 microM) and celecoxib (2.5 microM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitory effect was associated with a reduction in PGE(2) synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFkappaB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and gamma-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. 2009 Elsevier Masson SAS. All rights reserved.

Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing.

PubMed

Ding, Jie; Kwan, Peter; Ma, Zengshuan; Iwashina, Takashi; Wang, Jianfei; Shankowsky, Heather A; Tredget, Edward E

2016-09-01

Dermal wound healing, in which transforming growth factor beta 1 (TGFβ1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFβ1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFβ1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFβ1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFβ1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFβ1 increased gene expression of TGFβ1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFβ1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFβ1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

White piedra: further evidence of a synergistic infection.

PubMed

Youker, Summer R; Andreozzi, Robert J; Appelbaum, Peter C; Credito, Kim; Miller, Jeffrey J

2003-10-01

White piedra is a fungal infection of the hair shaft caused by Trichosporon beigelii. A synergistic coryneform bacterial infection is often present with T beigelii. White piedra, although not commonly reported to infect scalp hair in North America, is an important consideration in the differential diagnosis of scalp hair concretions. We report a case of white piedra of scalp hair with synergistic coryneform bacterial infection in two sisters, both US natives. Culture and light and electronmicroscopic evidence of the synergistic infection are presented.

Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system on essential hypertension in Kazakhs in Xinjiang.

PubMed

Niu, Shudong; Zhang, Bin; Zhang, Keyong; Zhu, Pengcheng; Li, Jingping; Sun, Yujing; He, Ning; Zhang, Mingtao; Gao, Zhiying; Li, Xueyan; Simayi, Amuti; Ge, Jie; Cong, Mingyu; Zhou, Wenna; Qiu, Changchun

2016-01-01

To assess the synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on essential hypertension (EH) in Kazakhs in Xinjiang. A cross-sectional case-control association study was conducted in 52 1 hypertensive and 623 normotensive subjects of Kazakh ethnicity on eight common single nucleotide polymorphisms (SNPs) interspersed over five genes of the RAAS. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Interactions among the SNPs were analyzed by the multifactor dimensionality reduction method (MDR). In single-locus analysis, subjects with AGT -6G, ACE D, and CYP11B2 -344C had increased susceptibility to EH (OR: 1.249; 1.425; 1.201). When subgrouped by sex, males with the t allele of REN Taq I had decreased risk for EH (OR: 0.529), and those with AGT -6G and CYP11B2 -344 C had increased risk for EH (OR: 1.498; 1.449). In females, carrying ACE D increased the risk for EH. (OR: 1.327). In six AGT haplotypes, H1 was protective, while H3 increased susceptibility to EH (OR: 0.683; 2.025). Interaction analysis by MDR showed that there was a strong synergistic effect between ACE I/D and CY11B2 (T-344C) and a moderate interaction between both ACE I/D and CY11B2 T-344C and AGT A-6G. There was a strong synergistic effect between ACE I/D and CY11B2 T-344C and a moderate effect between both ACE I/D and CY11B2 T-344C and AGT A-6G. AGT -6G, ACE D, and CY11B2 -344C increased susceptibility to EH. REN Taq I, AGT -6G, CY11B2 -344 C and ACE D were associated with male and female EH, respectively. H1 and H3 of AGT were protective and risk haplotypes, respectively.

Synergistic effect of interaction between perceived health and social activity on depressive symptoms in the middle-aged and elderly: a population-based longitudinal study.

PubMed

Chun, Sung-Youn; Han, Kyu-Tae; Lee, Seo Yoon; Kim, Chan Ok; Park, Eun-Cheol

2015-03-13

To examine the synergistic effect of interaction between perceived health and social activity on depressive symptoms. We investigated whether the interaction between perceived health and social activity has a synergistic effect on depressive symptoms in the middle-aged and elderly using data from 6590 respondents aged 45 and older in the Korean Longitudinal Study on Aging (KLoSA), 2006-2012. A generalised linear mixed-effects model was used to investigate the association in a longitudinal data form. Depressive symptoms were measured using the Center for Epidemiological Studies Depression 10 Scale (CES-D10). Perceived health and level of social activity were categorical variables with three values. Participation in six social activities was assessed. Interactions between perceived health status and social activity were statistically significant for almost all social activity/perceived health combinations. Addition of the interaction term significantly decreased CES-D10 scores, confirming the synergistic effect of the interaction between perceived health status and social activity ('normal×moderate', β=-0.1826; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In addition, we performed stratified analyses by region: urban or rural. In urban respondents, the additional effect of the interaction term decreased CES-D10 scores and all social activity/perceived health combinations were statistically significant ('normal×moderate', β=-0.2578; 'normal×active', β=-0.3945; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In rural respondents, only one social activity/perceived health combination was statistically significant, and the additional effect of the interaction term showed no consistent trend on CES-D10 scores. The interaction between perceived health and social activity has a synergistic effect on depressive symptoms; the additional effect of the interaction term significantly decreased CES-D10 scores in our models. Published by the BMJ

Synergistic effects of acarbose and an Oroxylum indicum seed extract in streptozotocin and high-fat-diet induced prediabetic mice.

PubMed

Sun, Wenlong; Sang, Yuanbin; Zhang, Bowei; Yu, Xiaoxia; Xu, Qinmin; Xiu, Zhilong; Dong, Yuesheng

2017-03-01

Prediabetes is defined as blood glucose levels above normal but below diabetes thresholds, and up to 70% of individuals with prediabetes will eventually develop diabetes if left untreated. Acarbose, the first FDA approved anti-prediabetes agent, has some disadvantages, such as reducing the risk of diabetes by only 36%, side effects and limited effects on complications. The aim of this study is to develop a new agent to treat prediabetes and to investigate the anti-prediabetes effects and mechanisms of acarbose and an Oroxylum indicum seed extract (OISE) in prediabetic mice. The combined drugs can reduce the dose of acarbose by 80% and reduce the risk of diabetes by 75%, which is one fold higher than acarbose monotherapy. The combined drugs showed synergistic anti-prediabetes effects and could be effective in preventing the complications of prediabetes. The combined drugs could improve glucose tolerance, improve lipid metabolism and reduce oxidative stress and tissue damage. For the mechanisms, the combined drugs can reduce synergistically postprandial hyperglycaemia by inhibiting α-glucosidase. Furthermore, baicalein in OISE was demonstrated to be a major component in reducing oxidative stress and chrysin was the primary compound that activated PPARγ. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Synergistic Effects between Doped Nitrogen and Phosphorus in Metal-Free Cathode for Zinc-Air Battery from Covalent Organic Frameworks Coated CNT.

PubMed

Li, Zhongtao; Zhao, Weinan; Yin, Changzhi; Wei, Liangqin; Wu, Wenting; Hu, Zhenpeng; Wu, Mingbo

2017-12-27

A covalent organic framework that is composed of hexachlorocyclotriphosphazene and dicyanamide has been coated on CNT to prepare metal-free oxygen reduction reaction catalyst through thermal polymerization of the Zn-air battery cathode. The N,P-codoped nanohybrids have highly porous structure and active synergistic effect between graphitic-N and -P, which promoted the electrocatalytic performance. The electrocatalysts exhibits remarkable half-wave potential (-0.162 V), high current density (6.1 mA/cm -2 ), good stability (83%), and excellent methanol tolerance for ORR in alkaline solution. Furthermore, the N,P-codoped nanohybrids were used as an air electrode for fabrication of a high performance Zn-air battery. The battery achieves a high open-circuit potential (1.53 V) and peak power density (0.255 W cm -2 ). Moreover, the effect of N,P codoping on the conjugate carbon system and the synergistic effect between graphitic-N and P have been calculated through density functional theory calculations, which are essentially in agreement with experimental data.

The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment

PubMed Central

JIA, LILI; MA, SHUMEI; HOU, XUE; WANG, XIN; QASED, ABU BAKER LAYTH; SUN, XUEFEI; LIANG, NAN; LI, HUICHENG; YI, HEQING; KONG, DEJUAN; LIU, XIAODONG; FAN, FEIYUE

2013-01-01

Traditional Chinese medicine (TCM) has been demonstrated to have potent cytotoxic activity against certain malignant tumors. Ionizing radiation (IR) is one of the most effective methods used in the clinical treatment of cancer. The drawback of a single formula is that it limits the treatment efficacy for cancer, while comprehensive strategies require additional theoretical support. However, a combination of different antitumor treatment modalities is advantageous in restricting the non-specific toxicity often observed with an extremely high dose of a single regimen. The induction of apoptotic cell death is a significant process in tumor cells following radiotherapy or chemotherapy, and resistance to these treatments has been linked to a low propensity for apoptosis. Autophagy is a response of cancer cells to IR or chemotherapy, and involves the prominent formation of autophagic vacuoles in the cytoplasm. In this review, the synergistic effects of TCM and radiotherapy are summarized and the underlying mechanisms are illustrated, providing new therapeutic strategies for cancer. PMID:23760551

Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects.

PubMed

Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L

2014-01-01

There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors.

Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects

PubMed Central

Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L.

2014-01-01

Background There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. Aims To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Method Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. Results There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Conclusions Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors. PMID:24627297

Silver-loaded nanotubular structures enhanced bactericidal efficiency of antibiotics with synergistic effect in vitro and in vivo.

PubMed

Xu, Na; Cheng, Hao; Xu, Jiangwen; Li, Feng; Gao, Biao; Li, Zi; Gao, Chenghao; Huo, Kaifu; Fu, Jijiang; Xiong, Wei

2017-01-01

Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag) nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat. Ag nanoparticle-loaded TiO 2 nanotube (NT) arrays (Ag-NTs) were fabricated on titanium implants for a customized release of Ag ion. The antibacterial properties of silver combined with antibiotics vancomycin, rifampin, gentamicin, and levofloxacin, respectively, were tested in vitro by minimum inhibitory concentration (MIC) assay, disk diffusion assay, and antibiofilm formation test. Enhanced antibacterial activity of combination therapy was observed for all the chosen bacterial strains, including gram-negative Escherichia coli (ATCC 25922), gram-positive Staphylococcus aureus (ATCC 25923), and methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591 and ATCC 43300). Moreover, after a relative short (3 weeks) combinational treatment, animal experiments in vivo further proved the synergistic antibacterial effect by X-ray and histological and immunohistochemical analyses. These results demonstrated that the combination of Ag nanoparticles and antibiotics significantly enhanced the antibacterial effect both in vitro and in vivo through the synergistic effect. The strategy is promising for clinical application to reduce the usage of antibiotics and shorten the administration time of implant-associated infection.

Improving computer-aided detection assistance in breast cancer screening by removal of obviously false-positive findings.

PubMed

Mordang, Jan-Jurre; Gubern-Mérida, Albert; Bria, Alessandro; Tortorella, Francesco; den Heeten, Gerard; Karssemeijer, Nico

2017-04-01

Computer-aided detection (CADe) systems for mammography screening still mark many false positives. This can cause radiologists to lose confidence in CADe, especially when many false positives are obviously not suspicious to them. In this study, we focus on obvious false positives generated by microcalcification detection algorithms. We aim at reducing the number of obvious false-positive findings by adding an additional step in the detection method. In this step, a multiclass machine learning method is implemented in which dedicated classifiers learn to recognize the patterns of obvious false-positive subtypes that occur most frequently. The method is compared to a conventional two-class approach, where all false-positive subtypes are grouped together in one class, and to the baseline CADe system without the new false-positive removal step. The methods are evaluated on an independent dataset containing 1,542 screening examinations of which 80 examinations contain malignant microcalcifications. Analysis showed that the multiclass approach yielded a significantly higher sensitivity compared to the other two methods (P < 0.0002). At one obvious false positive per 100 images, the baseline CADe system detected 61% of the malignant examinations, while the systems with the two-class and multiclass false-positive reduction step detected 73% and 83%, respectively. Our study showed that by adding the proposed method to a CADe system, the number of obvious false positives can decrease significantly (P < 0.0002). © 2017 American Association of Physicists in Medicine.

Dacarbazine and the Agonistic TRAIL Receptor-2 Antibody Lexatumumab Induce Synergistic Anticancer Effects in Melanoma

PubMed Central

Engesæter, Birgit; Engebraaten, Olav; Flørenes, Vivi Ann; Mælandsmo, Gunhild Mari

2012-01-01

Mapatumumab and lexatumumab (targeting death receptor 4 (DR4) and 5 (DR5), respectively) are agonistic TRAIL receptor antibodies that induce apoptosis in a wide range of cancer cells. The potency of mapatumumab and lexatumumab was assessed in mono therapy protocols, and the ability to sensitize for dacarbazine (DTIC) treatment was explored in ten different melanoma cell lines. Our data indicated that melanoma cell lines tend to be resistant to mapatumumab, most likely due to low expression of DR4, while a dose dependent response to lexatumumab was observed. Combining DTIC and lexatumumab induced an additive or synergistic effect on cell death in the various melanoma cell lines. The synergistic effect observed in the FEMX-1 cell line was related to enhanced cleavage of Bid in parallel with elevated expression of the pro-apoptotic proteins Bim, Bax and Bak. Furthermore, the anti-apoptotic proteins Bcl-XL, cIAP-1, XIAP and livin were down regulated. Cleavage of Bid and down regulation of cIAP-2 and livin were observed in vivo. Altogether, these data suggest a change in the balance between pro- and anti-apoptotic proteins favoring induction of apoptosis. In the more therapy resistant cell line, HHMS, no changes in the pro- and anti-apoptotic proteins were observed. FEMX-1 xenografts treated with DTIC and lexatumumab showed reduced growth and increased level of apoptosis compared to the control groups, providing arguments for further evaluation of this combination in melanoma patients. PMID:23029050

Dacarbazine and the agonistic TRAIL receptor-2 antibody lexatumumab induce synergistic anticancer effects in melanoma.

PubMed

Engesæter, Birgit; Engebraaten, Olav; Flørenes, Vivi Ann; Mælandsmo, Gunhild Mari

2012-01-01

Mapatumumab and lexatumumab (targeting death receptor 4 (DR4) and 5 (DR5), respectively) are agonistic TRAIL receptor antibodies that induce apoptosis in a wide range of cancer cells. The potency of mapatumumab and lexatumumab was assessed in mono therapy protocols, and the ability to sensitize for dacarbazine (DTIC) treatment was explored in ten different melanoma cell lines. Our data indicated that melanoma cell lines tend to be resistant to mapatumumab, most likely due to low expression of DR4, while a dose dependent response to lexatumumab was observed. Combining DTIC and lexatumumab induced an additive or synergistic effect on cell death in the various melanoma cell lines. The synergistic effect observed in the FEMX-1 cell line was related to enhanced cleavage of Bid in parallel with elevated expression of the pro-apoptotic proteins Bim, Bax and Bak. Furthermore, the anti-apoptotic proteins Bcl-XL, cIAP-1, XIAP and livin were down regulated. Cleavage of Bid and down regulation of cIAP-2 and livin were observed in vivo. Altogether, these data suggest a change in the balance between pro- and anti-apoptotic proteins favoring induction of apoptosis. In the more therapy resistant cell line, HHMS, no changes in the pro- and anti-apoptotic proteins were observed. FEMX-1 xenografts treated with DTIC and lexatumumab showed reduced growth and increased level of apoptosis compared to the control groups, providing arguments for further evaluation of this combination in melanoma patients.

Candida albicans and Escherichia coli are synergistic pathogens during experimental microbial peritonitis.

PubMed

Klaerner, H G; Uknis, M E; Acton, R D; Dahlberg, P S; Carlone-Jambor, C; Dunn, D L

1997-07-01

Candida albicans has been isolated with increasing frequency during intraabdominal infection; yet its role as a pathogen or copathogen remains controversial. A recent experimental study of its effect during polymicrobial peritonitis indicated that it did not enhance mortality when added to an Escherichia coli challenge, but that study used fecal or mucin-based adjuvants which are known to markedly potentiate the lethality of intraperitoneal bacteria. Therefore, we sought to examine the hypothesis that C. albicans and E. coli are synergistic copathogens that act in concert to increase mortality rates in experimental models of polymicrobial peritonitis, irrespective of the presence of growth adjuvant. To test this hypothesis, we assessed the mortality rates of previously healthy Swiss-Webster mice (20 g) that were challenged intraperitoneally (i.p.) with E. coli, C. albicans, or both, in either the presence or the absence of hemoglobin-mucin. In the absence of hemoglobin-mucin, E. coli plus C. albicans resulted in 83.3% mortality (P < 0.02) compared to either E. coli (0%) or C. albicans (0%) alone. In the presence of hemoglobin-mucin, the synergistic effect was not observed, lower numbers of E. coli alone (62.5%), C. albicans alone (75%), or both organisms together (100%, P > 0.05) provoked high lethality. These data demonstrate that in the absence of adjuvant, E. coli plus C. albicans provoked synergistic lethality. However, in the presence of hemoglobin-mucin the synergistic effect was no longer observed. Therefore, this study provides support for the contention that C. albicans is capable of acting as a copathogen during experimental peritonitis, but that this effect may be obscured by the presence of an adjuvant substance that itself markedly potentiates microbial growth.

Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation.

PubMed

Cheung, Ka Lung; Khor, Tin Oo; Kong, Ah-Ng

2009-01-01

Accumulating evidence from epidemiologic and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. Curcumin (CUR) has been strongly linked to the anti-inflammatory effect. On the other hand, isothiocyanates such as sulforaphane (SFN) and phenethyl isothiocyanate (PEITC) are strong phase-II detoxifying/antioxidant enzymes inducer. Therefore it is interesting to see if combination of these drugs can inhibit inflammation with higher combined efficacies. We used nitric oxide (NO) assay to assess the synergism of the different combinations of CUR, SFN and PEITC. The inflammatory markers, e.g. iNOS, COX-2, prostaglandin E2 (PGE2), tumor necrosis factor (TNF) and interleukin-1 (IL-1) levels were determined using RT-PCR, Western blot and ELISA assays. We report that combination of PEITC + SFN or CUR + SFN has a synergistic effect in down-regulating inflammation markers like TNF, IL-1, NO, PGE2. The synergism is probably due to the synergistic induction of phase II/antioxidant enzymes including heme-oxygenase1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1). Our data suggest that CUR + SFN and PEITC + SFN combinations could be more effective than used alone in preventing inflammation and possibly its associated diseases including cancer.

A synergistic effect of albumin and H₂O₂ accelerates corrosion of Ti6Al4V.

PubMed

Yu, Fei; Addison, Owen; Davenport, Alison J

2015-10-01

The synergistic effect of albumin and H2O2 on corrosion of titanium alloy Ti6Al4V in physiological saline was investigated with long-term immersion tests and electrochemical methods. It was found that in the presence of both albumin and H2O2, the rate of metal release in immersion tests was far higher than in the presence of either species alone. Electrochemical polarisation curves and potentiostatic tests showed that H2O2 increased both the rates of the anodic and cathodic reactions, whilst albumin significantly decreased the rate of the cathodic reaction and slightly decreased the rate of the anodic reaction. The synergistic effect of albumin and H2O2 during immersion tests was attributed to the effect of adsorption of albumin in lowering the rate of the cathodic reaction and thus lowering the open circuit potential into the active region of titanium where complexation by H2O2 increased the corrosion rate. The corrosion attack was found to be greater in the β-phase of the alloy. The findings suggest that current standard tests in physiological or phosphate-buffered saline may underestimate the rate of corrosion in the peri-implant environment, in which albumin is the predominant protein, and reactive oxygen species such as H2O2 can occur as a result of inflammatory reactions in response to surgery, infection, or implant corrosion products. Corrosion of many biomedical implant materials occurs in the body leading to adverse biological responses. Several components of the environment into which a metal implant is placed including proteins and products of cellular physiology, been shown to modify corrosion resistance. Previously all studies on such components including the common protein albumin and the inflammatory product H2O2 have considered the effects of these species in isolation. For the first time we report a synergistic interaction between albumin and H2O2 significantly accelerating corrosion of Ti6Al4V at physiological pH and temperature. This is

Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas

PubMed Central

Cheng, Yu-Chen; Hueng, Dueng-Yuan; Huang, Hua-Yin; Chen, Jang-Yi; Chen, Ying

2016-01-01

Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular and animal models. In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. In addition, phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, and Ki67 were decreased after Hono-Mag treatment, showing proliferation inhibition. Hono-Mag treatment also reduced p-p38 and p-JNK but elevated p-ERK expression. Besides, Hono-Mag treatment induced autophagy and intrinsic and extrinsic apoptosis. Both ERK and autophagy inhibitors enhanced Hono-Mag-induced apoptosis in LN229 cells, indicating a rescuer role of ERK. In human GBM orthotopic xenograft model, the Hono-Mag treatment inhibited the tumor progression and induced apoptosis more efficiently than Temozolomide, Hono, or Mag group. In conclusion, the Hono-Mag exerts a synergistic anti-tumor effect by inhibiting cell proliferation and inducing autophagy and apoptosis in human GBM cells. The Hono-Mag may be applied as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment. PMID:27074557

Synergistic interactions of ecosystem services: florivorous pest control boosts crop yield increase through insect pollination

PubMed Central

Albrecht, Matthias

2016-01-01

Insect pollination and pest control are pivotal functions sustaining global food production. However, they have mostly been studied in isolation and how they interactively shape crop yield remains largely unexplored. Using controlled field experiments, we found strong synergistic effects of insect pollination and simulated pest control on yield quantity and quality. Their joint effect increased yield by 23%, with synergistic effects contributing 10%, while their single contributions were 7% and 6%, respectively. The potential economic benefit for a farmer from the synergistic effects (12%) was 1.8 times greater than their individual contributions (7% each). We show that the principal underlying mechanism was a pronounced pest-induced reduction in flower lifetime, resulting in a strong reduction in the number of pollinator visits a flower receives during its lifetime. Our findings highlight the importance of non-additive interactions among ecosystem services (ES) when valuating, mapping or predicting them and reveal fundamental implications for ecosystem management and policy aimed at maximizing ES for sustainable agriculture. PMID:26865304

Phytic Acid and Sodium Chloride Show Marked Synergistic Bactericidal Effects against Nonadapted and Acid-Adapted Escherichia coli O157:H7 Strains

PubMed Central

Kim, Nam Hee

2015-01-01

The synergistic antimicrobial effects of phytic acid (PA), a natural extract from rice bran, plus sodium chloride against Escherichia coli O157:H7 were examined. Exposure to NaCl alone at concentrations up to 36% (wt/wt) for 5 min did not reduce bacterial populations. The bactericidal effects of PA alone were much greater than those of other organic acids (acetic, citric, lactic, and malic acids) under the same experimental conditions (P < 0.05). Combining PA and NaCl under conditions that yielded negligible effects when each was used alone led to marked synergistic effects. For example, whereas 0.4% PA or 3 or 4% NaCl alone had little or no effect on cell viability, combining the two completely inactivated both nonadapted and acid-adapted cells, reducing their numbers to unrecoverable levels (>7-log CFU/ml reduction). Flow cytometry confirmed that PA disrupted the cell membrane to a greater extent than did other organic acids, although the cells remained viable. The combination of PA and NaCl induced complete disintegration of the cell membrane. By comparison, none of the other organic acids acted synergistically with NaCl, and neither did NaCl-HCl solutions at the same pH values as the test solutions of PA plus NaCl. These results suggest that PA has great potential as an effective bacterial membrane-permeabilizing agent, and we show that the combination is a promising alternative to conventional chemical disinfectants. These findings provide new insight into the utility of natural compounds as novel antimicrobial agents and increase our understanding of the mechanisms underlying the antibacterial activity of PA. PMID:26637600

Phytic Acid and Sodium Chloride Show Marked Synergistic Bactericidal Effects against Nonadapted and Acid-Adapted Escherichia coli O157:H7 Strains.

PubMed

Kim, Nam Hee; Rhee, Min Suk

2016-02-15

The synergistic antimicrobial effects of phytic acid (PA), a natural extract from rice bran, plus sodium chloride against Escherichia coli O157:H7 were examined. Exposure to NaCl alone at concentrations up to 36% (wt/wt) for 5 min did not reduce bacterial populations. The bactericidal effects of PA alone were much greater than those of other organic acids (acetic, citric, lactic, and malic acids) under the same experimental conditions (P < 0.05). Combining PA and NaCl under conditions that yielded negligible effects when each was used alone led to marked synergistic effects. For example, whereas 0.4% PA or 3 or 4% NaCl alone had little or no effect on cell viability, combining the two completely inactivated both nonadapted and acid-adapted cells, reducing their numbers to unrecoverable levels (>7-log CFU/ml reduction). Flow cytometry confirmed that PA disrupted the cell membrane to a greater extent than did other organic acids, although the cells remained viable. The combination of PA and NaCl induced complete disintegration of the cell membrane. By comparison, none of the other organic acids acted synergistically with NaCl, and neither did NaCl-HCl solutions at the same pH values as the test solutions of PA plus NaCl. These results suggest that PA has great potential as an effective bacterial membrane-permeabilizing agent, and we show that the combination is a promising alternative to conventional chemical disinfectants. These findings provide new insight into the utility of natural compounds as novel antimicrobial agents and increase our understanding of the mechanisms underlying the antibacterial activity of PA. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Synergistic effects of sodium hypochlorite and ultraviolet radiation in reducing the levels of selected foodborne pathogenic bacteria.

PubMed

Ha, Ji-Hyoung; Ha, Sang-Do

2011-05-01

The purpose of this study was to determine whether combined treatment would produce synergistic effects to facilitate the sterilization of food products during production relative to single treatment. To assess this hypothesis, we investigated the bactericidal effects of ultraviolet (UV) irradiation and a commercial chemical disinfectant, sodium hypochlorite (NaClO), on Bacillus cereus F4810/72, Cronobacter sakazakii KCTC 2949, Staphylococcus aureus ATCC 35556, Escherichia coli ATCC 10536, and Salmonella Typhimurium novobiocin/nalidixic acid in vitro. Various concentrations of NaClO (20, 60, 100, and 200 ppm NaClO) were tested along with exposure to UV radiation at various doses (6, 96, 216, 360, and 504 mW s/cm(2)). The combined NaClO/UV treatments resulted in greater reductions in bacterial counts than either treatment alone. The synergy values against B. cereus, C. sakazakii, S. aureus, Salmonella Typhimurium, and E. coli were 0.25-1.17, 0.33-1.97, 0.42-1.72, 0.02-1.44, and 0.01-0.85 log(10) CFU/mL, respectively. The results of this study suggest that a significant synergistic benefit results from combined NaClO/UV processing against food-borne pathogenic bacteria in vitro.

A Titanium Oxo Cluster Model Study of Synergistic Effect of Co-coordinated Dye Ligands on Photocurrent Responses.

PubMed

Hou, Jin-Le; Huo, Peng; Tang, Zheng-Zhen; Cui, Li-Na; Zhu, Qin-Yu; Dai, Jie

2018-05-24

The use of multiple sensitizers in dye sensitized solar cells has been attractive as a promising way to achieve highly efficient photovoltaic performance. However, except for the complementary absorption, synergistic effects among the dye components have not been well understood. Herein, using ferrocene-1-carboxylate (FcCO 2 ) and catechol (Cat) as dye ligands, two titanium oxo clusters (TOCs), [Ti 3 O(O i Pr) 6 (Cat)(FcCO 2 ) 2 ] (1) and [Ti 7 O 4 (O i Pr) 8 (Cat) 5 (FcCO 2 ) 2 ] (2), were synthesized and structurally characterized. Another TOC, [Ti 7 O 3 (O i Pr) 12 (Cat) 4 ( o-BDC)] (3) ( o-BDC = o-benzene dicarboxylate), was also prepared as a contrast. Electronic spectra and theoretical calculations showed that charge transfer occurs from ligands FcCO 2 and Cat to the TiO cluster core and the contribution of redox active FcCO 2 is greater than that of Cat. Using the clusters as TiO-dye pre-anchored precursors, multi-dye sensitized TiO 2 electrodes were prepared. Although the two dyes FcCO 2 and Cat do not complement each other in spectra, a synergistic effect on the enhancement of photocurrent responses was found and discussed in view of the inter-dyes electron communication.

The Next Decade in Higher Education: Obvious Problems and Possible Solutions.

ERIC Educational Resources Information Center

Cheit, Earl F.

Problems confronting higher education are considered from the perspective of state coordinating agencies. Ten obvious problems are as follows: adjusting to new enrollment patterns; attempting to close the cost-income gap; expenditures increasing more rapidly than income; supporting the capacity for research and advanced study; meeting new…

Synergistically combined gene delivery for enhanced VEGF secretion and anti-apoptosis

PubMed Central

Won, Young-Wook; Lee, Minhyung; Kim, Hyun Ah; Nam, Kihoon; Bull, David A.; Kim, Sung Wan

2013-01-01

With current pharmacological treatments, preventing the remodeling of the left ventricle and the progression to heart failure is a difficult task. Gene therapy is considered to provide a direct treatment to the long-term complications of ischemic heart diseases. Although current gene therapies that use single molecular targets seem potentially possible, they have not achieved a success in the treatment of ischemic diseases. With an efficient polymeric gene carrier, PAM-ABP, we designed a synergistically combined gene delivery strategy to enhance vascular endothelial growth factor (VEGF) secretion and prolong anti-apoptotic effects. A hypoxia-inducible plasmid expressing both hypoxia-inducible heme oxygenase-1 (HO-1) and the Src homology domain-2 containing tyrosine phosphatase-1 microRNA (miSHP 1) and a hypoxia-responsive VEGF plasmid were combined in this study. The positive feedback circuit between HO-1 and VEGF, and the negative regulatory role of SHP-1 in angiogenesis enhance VEGF secretion synergistically. The synergy in VEGF secretion as a consequence of the gene combination and the prolonged HO-1 activity was confirmed in hypoxic cardiomyocytes and cardiomyocyte apoptosis under hypoxia, and was decreased synergistically. These results suggest that the synergistic combination of VEGF, HO-1, and miSHP-1 may be promising for the clinical treatment of ischemic diseases. PMID:24007285

Critical Synergistic Concentration of Lecithin Phospholipids Improves the Antimicrobial Activity of Eugenol against Escherichia coli.

PubMed

Zhang, Haoshu; Dudley, Edward G; Harte, Federico

2017-11-01

In this study, the effect of individual lecithin phospholipids on the antimicrobial properties of eugenol against Escherichia coli C600 was investigated. We tested five major phospholipids common in soy or egg lecithin (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine [DPPC], 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine [DSPC], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine [DPPE], 1,2-dihexadecanoyl-sn-glycero-3-phosphate [sodium salt] [DPPA], and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine [DPPS]) and one synthetic cationic phospholipid (1,2-dioctadecanoyl-sn-glycero-3-ethylphosphocholine [18:0 EPC]). Among the six phospholipids, DPPC, DSPC, DPPE, DPPA, and the cationic 18:0 EPC showed critical synergistic concentrations that significantly improved the inactivation effect of eugenol against E. coli after 30 min of exposure. At the critical synergistic concentration, an additional ca. 0.4 to 1.9 log reduction (ca. 0.66 to 2.17 log CFU/ml reduction) in the microbial population was observed compared to eugenol-only (control) treatments (ca. 0.25 log reduction). In all cases, increasing the phospholipid amount above the critical synergistic concentration (which was different for each phospholipid) resulted in antimicrobial properties similar to those seen with the eugenol-only (control) treatments. DPPS did not affect the antimicrobial properties of eugenol at the tested concentrations. The critical synergistic concentration of phospholipids was correlated with their critical micelle concentrations (CMC). IMPORTANCE Essential oils (EOs) are naturally occurring antimicrobials, with limited use in food due to their hydrophobicity and strong aroma. Lecithin is used as a natural emulsifier to stabilize EOs in aqueous systems. We previously demonstrated that, within a narrow critical-concentration window, lecithin can synergistically enhance the antimicrobial properties of eugenol. Since lecithin is a mixture of different phospholipids, we aimed to identify

Critical Synergistic Concentration of Lecithin Phospholipids Improves the Antimicrobial Activity of Eugenol against Escherichia coli

PubMed Central

Zhang, Haoshu; Dudley, Edward G.

2017-01-01

ABSTRACT In this study, the effect of individual lecithin phospholipids on the antimicrobial properties of eugenol against Escherichia coli C600 was investigated. We tested five major phospholipids common in soy or egg lecithin (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine [DPPC], 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine [DSPC], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine [DPPE], 1,2-dihexadecanoyl-sn-glycero-3-phosphate [sodium salt] [DPPA], and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine [DPPS]) and one synthetic cationic phospholipid (1,2-dioctadecanoyl-sn-glycero-3-ethylphosphocholine [18:0 EPC]). Among the six phospholipids, DPPC, DSPC, DPPE, DPPA, and the cationic 18:0 EPC showed critical synergistic concentrations that significantly improved the inactivation effect of eugenol against E. coli after 30 min of exposure. At the critical synergistic concentration, an additional ca. 0.4 to 1.9 log reduction (ca. 0.66 to 2.17 log CFU/ml reduction) in the microbial population was observed compared to eugenol-only (control) treatments (ca. 0.25 log reduction). In all cases, increasing the phospholipid amount above the critical synergistic concentration (which was different for each phospholipid) resulted in antimicrobial properties similar to those seen with the eugenol-only (control) treatments. DPPS did not affect the antimicrobial properties of eugenol at the tested concentrations. The critical synergistic concentration of phospholipids was correlated with their critical micelle concentrations (CMC). IMPORTANCE Essential oils (EOs) are naturally occurring antimicrobials, with limited use in food due to their hydrophobicity and strong aroma. Lecithin is used as a natural emulsifier to stabilize EOs in aqueous systems. We previously demonstrated that, within a narrow critical-concentration window, lecithin can synergistically enhance the antimicrobial properties of eugenol. Since lecithin is a mixture of different phospholipids, we aimed to

Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous oxide emissions from vegetable field in south China.

PubMed

Yi, Qiong; Tang, Shuanghu; Fan, Xiaolin; Zhang, Mu; Pang, Yuwan; Huang, Xu; Huang, Qiaoyi

2017-01-01

Globally, vegetable fields are the primary source of greenhouse gas emissions. A closed-chamber method together with gas chromatography was used to measure the fluxes of nitrous oxide (N2O) emissions in typical vegetable fields planted with four vegetables sequentially over time in the same field: endive, lettuce, cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with the N2O emission peak varying greatly among the crops. In addition, N2O emissions were linearly associated with the nitrogen (N) application rate (r = 0.8878, n = 16). Excessive fertilizer N application resulted in N loss through nitrous oxide gas emitted from the vegetable fields. Compared with a conventional fertilization (N2) treatment, the cumulative N2O emissions decreased significantly in the growing seasons of four plant species from an nitrogen synergist (a nitrification inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively. However, the effects of biochar on reducing N2O emissions became more obvious than that of dicyandiamide over time. The yield-scaled N2O emissions in consecutive growing seasons for four species increased with an increase in the N fertilizer application rate, and with continuous application of N fertilizer. This was especially true for the high N fertilizer treatment that resulted in a risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and biochar significantly decreased yield-scaled N2O-N emissions by an average of 45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive four vegetable seasons. The results demonstrated that the addition of dicyandiamide or biochar in combination with application of a rational amount of N could provide the best strategy for the reduction of greenhouse gas emissions in vegetable field in south China.

Effects of nitrogen application rate, nitrogen synergist and biochar on nitrous oxide emissions from vegetable field in south China

PubMed Central

Zhang, Mu; Pang, Yuwan; Huang, Xu; Huang, Qiaoyi

2017-01-01

Globally, vegetable fields are the primary source of greenhouse gas emissions. A closed-chamber method together with gas chromatography was used to measure the fluxes of nitrous oxide (N2O) emissions in typical vegetable fields planted with four vegetables sequentially over time in the same field: endive, lettuce, cabbage and sweet corn. Results showed that N2O fluxes occurred in pulses with the N2O emission peak varying greatly among the crops. In addition, N2O emissions were linearly associated with the nitrogen (N) application rate (r = 0.8878, n = 16). Excessive fertilizer N application resulted in N loss through nitrous oxide gas emitted from the vegetable fields. Compared with a conventional fertilization (N2) treatment, the cumulative N2O emissions decreased significantly in the growing seasons of four plant species from an nitrogen synergist (a nitrification inhibitor, dicyandiamide and biochar treatments by 34.6% and 40.8%, respectively. However, the effects of biochar on reducing N2O emissions became more obvious than that of dicyandiamide over time. The yield-scaled N2O emissions in consecutive growing seasons for four species increased with an increase in the N fertilizer application rate, and with continuous application of N fertilizer. This was especially true for the high N fertilizer treatment that resulted in a risk of yield-scaled N2O emissions. Generally, the additions of dicyandiamide and biochar significantly decreased yield-scaled N2O-N emissions by an average of 45.9% and 45.7%, respectively, compared with N2 treatment from the consecutive four vegetable seasons. The results demonstrated that the addition of dicyandiamide or biochar in combination with application of a rational amount of N could provide the best strategy for the reduction of greenhouse gas emissions in vegetable field in south China. PMID:28419127

Hepatocellular carcinoma repression by TNFα‐mediated synergistic lethal effect of mitosis defect‐induced senescence and cell death sensitization

PubMed Central

Li, Dan; Fu, Jing; Du, Min; Zhang, Haibin; Li, Lu; Cen, Jin; Li, Weiyun; Chen, Xiaotao; Lin, Yunfei; Conway, Edward M.; Pikarsky, Eli; Wang, Hongyan; Pan, Guoyu

2016-01-01

Hepatocellular carcinoma (HCC) is a cancer lacking effective therapies. Several measures have been proposed to treat HCCs, such as senescence induction, mitotic inhibition, and cell death promotion. However, data from other cancers suggest that single use of these approaches may not be effective. Here, by genetic targeting of Survivin, an inhibitor of apoptosis protein (IAP) that plays dual roles in mitosis and cell survival, we identified a tumor necrosis factor alpha (TNFα)‐mediated synergistic lethal effect between senescence and apoptosis sensitization in malignant HCCs. Survivin deficiency results in mitosis defect‐associated senescence in HCC cells, which triggers local inflammation and increased TNFα. Survivin inactivation also sensitizes HCC cells to TNFα‐triggered cell death, which leads to marked HCC regression. Based on these findings, we designed a combination treatment using mitosis inhibitor and proapoptosis compounds. This treatment recapitulates the therapeutic effect of Survivin deletion and effectively eliminates HCCs, thus representing a potential strategy for HCC therapy. Conclusion: Survivin ablation dramatically suppresses human and mouse HCCs by triggering senescence‐associated TNFα and sensitizing HCC cells to TNFα‐induced cell death. Combined use of mitotic inhibitor and second mitochondrial‐derived activator of caspases mimetic can induce senescence‐associated TNFα and enhance TNFα‐induced cell death and synergistically eliminate HCC. (Hepatology 2016;64:1105‐1120) PMID:27177758

Anethole, a potential antimicrobial synergist, converts a fungistatic dodecanol to a fungicidal agent.

PubMed

Fujita, Ken-Ichi; Fujita, Tomoko; Kubo, Isao

2007-01-01

Anethole shows synergistic effects on the antifungal activities of phytochemicals including polygodial and (2E)-undecenal against Saccharomyces cerevisiae and Candida albicans. It was found that a fungistatic dodecanol combined with a sublethal amount of anethole showed a fungicidal activity against S. cerevisiae. The MIC of dodecanol quickly reduced cell viability, but the cell viability recovered shortly after and then finally became no longer different from the control, indicating that the effect of dodecanol on this yeast was classified as sublethal damage. On the other hand, anethole completely restricted the recovery of cell viability. Therefore the expression of the synergistic effect was probably due to a blockade of the recovery process from dodecanol-induced stress.

Synergistic effect of co-exposure to cadmium (II) and 4-n-nonylphenol on growth inhibition and oxidative stress of Chlorella sorokiniana.

PubMed

Wang, Lu; Kang, Yuan; Liang, Siyun; Chen, Danying; Zhang, Qiuyun; Zeng, Lixuan; Luo, Jiwen; Jiang, Feng

2018-06-15

Toxicological effect of freshwater algae co-exposure to Cd and 4-n-nonylphenol (4-n-NP) was seldom reported. In the present study, Chlorella sorokiniana was selected for testing the single and combined effect of Cd and 4-n-NP by detecting the growth inhibition and oxidative stress after exposure for 48 h, 72 h, and 96 h. The combined effects were evaluated by using toxic units (TU) method and concentration addition（CA）model. The synergistic effect of mixture on algal growth inhibition was both observed at 48 h and 72 h, and the additive effect was observed at 96 h. In addition, the significant alterations of superoxide, thiobarbituric acid reactive substances and antioxidant defenses (superoxide dismutase, catalase, glutathione) have been detected. It could be observed that the mixture predominantly lead to synergistic effects in superoxide induction, and the antagonistic effects in the GSH induction. A similar trend between the superoxide induction and growth inhibition were observed, which may indicate that the oxidative effects of Chlorella sorokiniana contributed to the growth inhibition after exposure to Cd and 4-n-NP. These findings may have important implications in the risk assessments of heavy metals and endocrine disruptors in the aquatic environment. Copyright © 2018 Elsevier Inc. All rights reserved.

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration.

PubMed

Heinemann, Scott D; Posimo, Jessica M; Mason, Daniel M; Hutchison, Daniel F; Leak, Rehana K

2016-08-01

The dual-hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, a relatively high-throughput dual-hit model of stress synergy was developed in primary hippocampal neurons. In order to increase the rigor of the study and strengthen the interpretations, three independent, unbiased viability assays were employed at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48 h. MG132 and paraquat only elicited additive effects 24 h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48 h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. These findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, a new model of hippocampal vulnerability was developed for the testing of therapies

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual hit hypothesis of neurodegeneration

PubMed Central

Heinemann, Scott D.; Posimo, Jessica M.; Mason, Daniel M.; Hutchison, Daniel F.; Leak, Rehana K.

2016-01-01

The dual hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, we developed a relatively high-throughput dual hit model of stress synergy in primary hippocampal neurons. In order to increase the rigor of our study and strengthen our interpretations, we employed three independent, unbiased viability assays at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48h. MG132 and paraquat only elicited additive effects 24h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. Our findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, we present a new model of hippocampal vulnerability in which to test therapies, because

Non-obvious influences on perception-action abilities.

PubMed

Turvey, Michael T; Sheya, Adam

2017-10-01

The sciences of development and learning have been slow to acknowledge that absence of an identifiable experience that relates straightforwardly to a given perception-action ability need not mean that experience per se is irrelevant to the emergence of that ability. A recent study reveals that a difference in diet (plain vs. energy rich) leads to a difference in how rats navigate (use of geometry vs. use of features, respectively). It is a good example of how a seemingly unrelated experience (e.g., what the rats eat) can be a non-obvious yet crucial determiner of perception-action modes. We situate this finding in the broader context of the related conceptions of Schneirla's and Lehrman's Developmental Systems Theory, Gottlieb's Probabilistic Epigenesis, and Bolles's Structure of Learning (see article for references). In doing so we highlight that such phenomena may be the norm, both in development and learning, rather than the exception.

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

PubMed

Tang, Hailin; Guo, Yuan; Peng, Li; Fang, Hui; Wang, Zhigang; Zheng, Yuanyi; Ran, Haitao; Chen, Yu

2018-05-09

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe 3 O 4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T 2 -weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.

Overview of Corrosion, Erosion, and Synergistic Effects of Erosion and Corrosion in the WTP Pre-treatment Facility

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

Imrich, K. J.

2015-03-27

Corrosion is an extremely complex process that is affected by numerous factors. Addition of a flowing multi-phase solution further complicates the analysis. The synergistic effects of the multiple corrosive species as well as the flow-induced synergistic effects from erosion and corrosion must be thoroughly evaluated in order to predict material degradation responses. Public domain data can help guide the analysis, but cannot reliably provide the design basis especially when the process is one-of-a-kind, designed for 40 plus years of service, and has no viable means for repair or replacement. Testing in representative simulants and environmental conditions with prototypic components willmore » provide a stronger technical basis for design. This philosophy was exemplified by the Defense Waste Processing Facility (DWPF) at the Savannah River Site and only after 15 plus years of successful operation has it been validated. There have been “hiccups”, some identified during the cold commissioning phase and some during radioactive operations, but they were minor and overcome. In addition, the system is robust enough to tolerate most flowsheet changes and the DWPF design allows minor modifications and replacements – approaches not available with the Hanford Waste Treatment Plant (WTP) “Black Cell” design methodology. Based on the available data, the synergistic effect between erosion and corrosion is a credible – virtually certain – degradation mechanism and must be considered for the design of the WTP process systems. Testing is recommended due to the number of variables (e.g., material properties, process parameters, and component design) that can affect synergy between erosion and corrosion and because the available literature is of limited applicability for the complex process chemistries anticipated in the WTP. Applicable testing will provide a reasonable and defensible path forward for design of the WTP Black Cell and Hard-to-Reach process equipment

Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

PubMed

Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

2018-02-02

Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.

PubMed

Eriksson, Andreas C; Whiss, Per A; Nilsson, Ulrika K

2006-07-01

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.

Synergistic protective effect of picrorhiza with honey in acetaminophen induced hepatic injury.

PubMed

Gupta, Prashant; Tripathi, Alok; Agrawal, Tripti; Narayan, Chandradeo; Singh, B M; Kumar, Mohan; Kumar, Arvind

2016-08-01

Rhizome of picrorhiza along with honey prevents hepatic damage and cure the acetaminophen (paracetamol) induced hepatotoxicity by modulating the activity of hepatic enzymes. Here, we studied the in vivo effects of Picrorhiza kurroa and honey on acetaminophen induced hepatotoxicity Balb/c mice model. Hepatic histopathological observations of acetaminophen fed (day-6) group showed more congestion, hemorrhage, necrosis, distorted hepatic architecture and nuclear inclusion. Such damages were recompensed to normal by picrorhiza or honey alone or both in combinations. We observed increased activity of SGPT and SGOT in injured liver tissues, and that too was compensated to normal with picrorhiza or honey alone or both in combinations. We observed 1.27 and 1.23-fold enhanced activity of SGPT in serum and liver lysate, respectively while SGOT showed 1.66 and 1.11 fold enhanced activity. These two enzymes are signature enzymes of liver damage. Thus, our results support that honey may be used with drug picrorhiza due to its synergistic role to enhance hepatoprotective and hepatoregenerative ability along with allopathic drugs to mitigate the hepatotoxic effects.

Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells.

PubMed

Li, Xu; Zhu, Feng; Jiang, Jianxin; Sun, Chengyi; Wang, Xin; Shen, Ming; Tian, Rui; Shi, Chengjian; Xu, Meng; Peng, Feng; Guo, Xingjun; Wang, Min; Qin, Renyi

2015-02-01

Application of oxaliplatin for the treatment of pancreatic cancer (PC) is restricted owing to its toxic side effects and drug resistance. We investigated how withaferin A (WA), a bioactive component isolated from the medicinal plant Withania somnifera, acts synergistically with oxaliplatin on human PC in vitro and in vivo. We found that WA enhanced oxaliplatin-induced growth suppression and apoptosis in PC cells dramatically through a mechanism involving mitochondrial dysfunction and inactivation of the PI3K/AKT pathway. Combination treatment resulted in significant accumulation of intracellular reactive oxygen species (ROS). Pretreatment of cells with the ROS scavenger N-acetylcysteine completely blocked the apoptosis induced by combination treatment, and recovered expression of AKT inactivation, which revealed the important role of ROS in apoptosis and AKT regulation. In vivo, combination therapy showed the strongest anti-tumor effects compared with single agents, without obvious additional toxicity. These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth

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

Chen, You-Shuang; Peng, Yin-Bo; Yao, Min

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model.more » We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm{sup 2}) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.« less

Synergistic interactions of ecosystem services: florivorous pest control boosts crop yield increase through insect pollination.

PubMed

Sutter, Louis; Albrecht, Matthias

2016-02-10

Insect pollination and pest control are pivotal functions sustaining global food production. However, they have mostly been studied in isolation and how they interactively shape crop yield remains largely unexplored. Using controlled field experiments, we found strong synergistic effects of insect pollination and simulated pest control on yield quantity and quality. Their joint effect increased yield by 23%, with synergistic effects contributing 10%, while their single contributions were 7% and 6%, respectively. The potential economic benefit for a farmer from the synergistic effects (12%) was 1.8 times greater than their individual contributions (7% each). We show that the principal underlying mechanism was a pronounced pest-induced reduction in flower lifetime, resulting in a strong reduction in the number of pollinator visits a flower receives during its lifetime. Our findings highlight the importance of non-additive interactions among ecosystem services (ES) when valuating, mapping or predicting them and reveal fundamental implications for ecosystem management and policy aimed at maximizing ES for sustainable agriculture. © 2016 The Author(s).

Synergistic effects of non-Apis bees and honey bees for pollination services

PubMed Central

Brittain, Claire; Williams, Neal; Kremen, Claire; Klein, Alexandra-Maria

2013-01-01

In diverse pollinator communities, interspecific interactions may modify the behaviour and increase the pollination effectiveness of individual species. Because agricultural production reliant on pollination is growing, improving pollination effectiveness could increase crop yield without any increase in agricultural intensity or area. In California almond, a crop highly dependent on honey bee pollination, we explored the foraging behaviour and pollination effectiveness of honey bees in orchards with simple (honey bee only) and diverse (non-Apis bees present) bee communities. In orchards with non-Apis bees, the foraging behaviour of honey bees changed and the pollination effectiveness of a single honey bee visit was greater than in orchards where non-Apis bees were absent. This change translated to a greater proportion of fruit set in these orchards. Our field experiments show that increased pollinator diversity can synergistically increase pollination service, through species interactions that alter the behaviour and resulting functional quality of a dominant pollinator species. These results of functional synergy between species were supported by an additional controlled cage experiment with Osmia lignaria and Apis mellifera. Our findings highlight a largely unexplored facilitative component of the benefit of biodiversity to ecosystem services, and represent a way to improve pollinator-dependent crop yields in a sustainable manner. PMID:23303545

Anti-inflammatory and antimicrobial effects of garlic and synergistic effect between garlic and ciprofloxacin in a chronic bacterial prostatitis rat model.

PubMed

Sohn, Dong Wan; Han, Chang Hee; Jung, Yun Seok; Kim, Sung In; Kim, Sae Woong; Cho, Yong-Hyun

2009-09-01

Chronic bacterial prostatitis (CBP), which is characterised by recurrent urinary tract infection (UTI) and persistence of pathogenic bacteria and evidence of inflammation in the prostatic secretions, is one of the most common causes of relapsing UTI in men. In this study, we evaluated the antimicrobial and anti-inflammatory effects of garlic as well as the synergistic effect of garlic with ciprofloxacin on the treatment of CBP in an animal model. An experimental CBP model was induced in 60 adult male Sprague-Dawley rats by instillation of 0.2 mL of bacterial suspension (Escherichia coli Z17, O2:K1:H-) containing 1 x 10(8) colony-forming units/mL into the prostatic urethra. Microbiologically and histologically proven CBP was demonstrated in 68.3% (41/60) of the rats after 4 weeks of bacterial instillation. The 41 rats demonstrating CBP were randomly divided into four treatment groups: control; garlic; ciprofloxacin; and garlic plus ciprofloxacin. After 3 weeks of treatment, microbiological cultures of the urine and prostate samples as well as histological findings of the prostate were analysed. Microbiological cultures and histological findings of the prostate samples demonstrated reduced bacterial growth and improved inflammatory responses in all three experimental groups compared with the control group. The garlic group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the control group. The garlic plus ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group. These results suggest that garlic may have anti-inflammatory and antimicrobial effects as well as a synergistic effect with ciprofloxacin. We therefore suggest that the combination of garlic and ciprofloxacin may be effective in treating CBP with a higher success rate.

Polycatechol nanosheet: a superior nanocarrier for highly effective chemo-photothermal synergistic therapy in vivo

NASA Astrophysics Data System (ADS)

Bai, J.; Jia, X. D.; Ma, Z. F.; Jiang, X. E.; Sun, X. P.

2016-02-01

The integration of phototherapy and chemotherapy in a single system holds great promise to improve the therapeutic efficacy of tumor treatment, but it remains a key challenge. In this study, we describe our recent finding that polycatechol nanosheet (PCCNS) can be facilely prepared on a large scale via chemical polymerization at 4 °C, as an effective nanocarrier for loading high-density CuS nanocrystals as a photothermal agent. The resulting CuS/PCCNS nanocomposites exhibit good biocompatibility, strong stability, and a high photothermal conversion efficiency of ~45.7%. The subsequent loading of anticancer drug doxorubicin (Dox) creates a superior theranostic agent with pH- and heat-responsive drug release, leading to almost complete destruction of mouse cervical tumor under NIR laser irradiation. This development offers an attractive theranostic agent for in vivo chemo-photothermal synergistic therapy toward biomedical applications.The integration of phototherapy and chemotherapy in a single system holds great promise to improve the therapeutic efficacy of tumor treatment, but it remains a key challenge. In this study, we describe our recent finding that polycatechol nanosheet (PCCNS) can be facilely prepared on a large scale via chemical polymerization at 4 °C, as an effective nanocarrier for loading high-density CuS nanocrystals as a photothermal agent. The resulting CuS/PCCNS nanocomposites exhibit good biocompatibility, strong stability, and a high photothermal conversion efficiency of ~45.7%. The subsequent loading of anticancer drug doxorubicin (Dox) creates a superior theranostic agent with pH- and heat-responsive drug release, leading to almost complete destruction of mouse cervical tumor under NIR laser irradiation. This development offers an attractive theranostic agent for in vivo chemo-photothermal synergistic therapy toward biomedical applications. Electronic supplementary information (ESI) available: The calculation of the photothermal conversion

Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs.

PubMed

Hess, Ricarda; Jaeschke, Anna; Neubert, Holger; Hintze, Vera; Moeller, Stephanie; Schnabelrauch, Matthias; Wiesmann, Hans-Peter; Hart, David A; Scharnweber, Dieter

2012-12-01

In vivo, bone formation is a complex, tightly regulated process, influenced by multiple biochemical and physical factors. To develop a vital bone tissue engineering construct, all of these individual components have to be considered and integrated to gain an in vivo-like stimulation of target cells. The purpose of the present studies was to investigate the synergistic role of defined biochemical and physical microenvironments with respect to osteogenic differentiation of human mesenchymal stem cells (MSCs). Biochemical microenvironments have been designed using artificial extracellular matrices (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya), formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL) scaffolds. As part of the physical microenvironment, cells were exposed to pulsed electric fields via transformer-like coupling (TC). Results showed that aECM containing sHya enhanced osteogenic differentiation represented by increases in ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX-2, ALP, OPN). Electric field stimulation alone did not influence cell proliferation, but osteogenic differentiation was enhanced if osteogenic supplements were provided, showing synergistic effects by the combination of sHya and electric fields. These results will improve the understanding of bone regeneration processes and support the development of effective tissue engineered bone constructs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

PubMed

Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

2010-12-15

The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

Synergistic effect of tincture of Crataegus and Mangifera indica L. extract on hyperlipidemic and antioxidant status in atherogenic rats.

PubMed

Akila, Manickam; Devaraj, Halagowder

2008-01-01

This study was designed to address the synergistic effect of tincture of Crataegus (TCR) and Mangifera indica L. (MNG) extracts on the lipid and antioxidant parameters in the development of aortic lesions in diet-induced atherosclerosis in rats. TCR, is an alcoholic extract made from the berries of Hawthorn, Crataegus oxyacantha with flavanoids as the main constituent. MNG, is an alcoholic extract made from the stem bark of Mangifera indica L. with polyphenols as the main constituent. Simultaneous oral administration of these two extracts (0.5 ml/100 g body weight) to rats fed with an atherogenic (4% cholesterol, 1% cholic acid, 0.5% thiouracil) diet prevented the elevation of lipids in the serum and heart and also caused a significant decrease in lipid accumulation in the liver and aorta reverting the hyperlipidaemic condition of these rats. These extracts significantly restored the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione, thereby restoring the antioxidant status of the organism to almost normal levels. This effect could be attributed to the synergistic activity of flavonoids in TCR and polyphenols of MNG.

The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model.

PubMed

Feng, Jiuhuan; Qin, Shukui

2018-01-01

Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib mono-therapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib. We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased. The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time. The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment.

Synergistic effect of dicarbollide anions in liquid-liquid extraction: a molecular dynamics study at the octanol-water interface.

PubMed

Chevrot, G; Schurhammer, R; Wipff, G

2007-04-28

We report a molecular dynamics study of chlorinated cobalt bis(dicarbollide) anions [(B(9)C(2)H(8)Cl(3))(2)Co](-)"CCD(-)" in octanol and at the octanol-water interface, with the main aim to understand why these hydrophobic species act as strong synergists in assisted liquid-liquid cation extraction. Neat octanol is quite heterogeneous and is found to display dual solvation properties, allowing to well solubilize CCD(-), Cs(+) salts in the form of diluted pairs or oligomers, without displaying aggregation. At the aqueous interface, octanol behaves as an amphiphile, forming either monolayers or bilayers, depending on the initial state and confinement conditions. In biphasic octanol-water systems, CCD(-) anions are found to mainly partition to the organic phase, thus attracting Cs(+) or even more hydrophilic counterions like Eu(3+) into that phase. The remaining CCD(-) anions adsorb at the interface, but are less surface active than at the chloroform interface. Finally, we compare the interfacial behavior of the Eu(BTP)(3)(3+) complex in the absence and in the presence of CCD(-) anions and extractant molecules. It is found that when the CCD(-)'s are concentrated enough, the complex is extracted to the octanol phase. Otherwise, it is trapped at the interface, attracted by water. These results are compared to those obtained with chloroform as organic phase and discussed in the context of synergistic effect of CCD(-) in liquid-liquid extraction, pointing to the importance of dual solvation properties of octanol and of the hydrophobic character of CCD(-) for synergistic extraction of cations.

Synergistic Antitumor Effect of Oligogalacturonides and Cisplatin on Human Lung Cancer A549 Cells.

PubMed

Huang, Cian-Song; Huang, Ai-Chun; Huang, Ping-Hsiu; Lo, Diana; Wang, Yuh-Tai; Wu, Ming-Chang

2018-06-14

Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.

Synergistic effects of androgen and estrogen on the mouse uterus and mammary gland.

PubMed

Zhang, Jian; Sun, Yibin; Liu, Yunhai; Sun, Yi; Liao, Dezhong Joshua

2004-10-01

Many studies have suggested that elevated estrogens and androgens may be etiologically related to the development of breast cancer, endometrial cancer and uterine leiomyomas. We and other investigators have previously shown that estrogen and androgen are synergistic in the induction of mammary carcinogenesis in the Noble rat. However, the mechanisms behind the synergy is unknown, and it is unclear whether such synergy is unique for the Noble rat and for the mammary gland. In this study we treated female FVB mice with 17beta-estradiol (E2) and 5alpha-dihydrotestosterone-bezonate (DHT-B), alone and in combination, using silastic tubing for 2-7 months. The results showed that DHT-B alone induced proliferation of uterine endometrial epithelium and myometrial smooth muscle cells, whereas E2 alone induced much more pronounced growth of endometrial epithelium without affecting smooth muscle cells. Combined treatment with E2+DHT-B caused an even more severe hyperplasia of endometrial epithelium and myometrial muscle cells, compared with the treatment with each hormone alone. Uterine leiomyomas were observed in 2 of 6 mice at 7 months of combined treatment but not in any of 6 or 7 mice receiving each single hormone. DHT-B alone induced growth and secretion of mammary ductal cells, as well as growth of mammary stroma. E2 alone stimulated much more pronounced growth of both ductal cells and alveolar cells and secretion of alveolar cells, but had no effect on mammary stroma. Treatment with both E2 and DHT-B caused more severe hyperplasia of mammary ducts and alveoli, compared to the treatment with each hormone alone. Intraductal hyperplasia occurred early and frequently in the E2+DHT-B- treated mice, but no mammary tumors were observed. These results suggest that E2 and DHT-B have synergistic effects on the growth of uterine endometrial epithelium and myometrial muscle cells, as well as mammary epithelial ducts and alveoli.

Synergistic effect of solar radiation and solar heating to disinfect drinking water sources.

PubMed

Rijal, G K; Fujioka, R S

2001-01-01

Waterborne diseases are still common in developing countries as drinking water sources are contaminated and feasible means to reliably treat and disinfect these waters are not available. Many of these developing countries are in the tropical regions of the world where sunlight is plentiful. The objective of this study was to evaluate the effectiveness of combining solar radiation and solar heating to disinfect contaminated water using a modified Family Sol*Saver System (FSP). The non-UV transmittable cover sheet of the former FSP system was replaced with an UV transmittable plastic cover sheet to enable more wavelengths of sunlight to treat the water. Disinfection efficiency of both systems was evaluated based on reduction of the natural populations of faecal coliform, E. coli, enterococci, C. perfringens, total heterotrophic bacteria, hydrogen sulphide producing bacteria and FRNA virus. The results showed that under sunny and partly sunny conditions, water was heated to critical temperature (60 degrees C) in both the FSP systems inactivating more than 3 log (99.9%) of the concentrations of faecal coliform and E. coli to undetectable levels of < 1 CFU/100 mL within 2-5 h exposure to sunlight. However, under cloudy conditions, the two FSP systems did not reduce the concentrations of faecal indicator bacteria to levels of < 1 CFU/100 mL. Nonetheless, sufficient evidence was obtained to show that UV radiation of sunlight plus heat worked synergistically to enhance the inactivation of faecal indicator bacteria. The relative log removal of indicator microorganism in the FSP treated water was total heterotrophic bacteria < C. perfringens < F RNA virus < enterococci < E. coli < faecal coliform. In summary, time of exposure to heat and radiation effects of sunlight were important in disinfecting water by solar units. The data indicated that direct radiation of sunlight worked synergistically with solar heating of the water to disinfect the water. Thus, effective

Synergistic antibacterial effect of apigenin with β-lactam antibiotics and modulation of bacterial resistance by a possible membrane effect against methicillin resistant Staphylococcus aureus.

PubMed

Akilandeswari, K; Ruckmani, K

2016-12-30

Methicillin-resistant Staphylococcus aureus (MRSA) infections are easily spread among infected patients, where resistance has dramatically increased resulted in serious health issues. Therefore, there is a need to develop alternative natural or combination drug therapies. Apigenin (AP) is a natural poly phenolic flavonoid has been found to possess many beneficial biological actions. The aim of this study was to investigate the anti-MRSA efficacy and synergistic effect of apigenin (AP) and in combination with ampicillin (AM) and ceftriaxone (CEF). The antibacterial activity of apigenin was assessed by the broth macro dilution, checkerboard micro dilution method and time-kill assay.  The mode of action was studied by outer and inner membrane permeabilisation assays, scanning electron microscopy and transmission electron microscopy. The minimum inhibitory concentration (MIC) of apigenin against gram positive and gram negative strain ranged from 32.5 to 62.5µg/ml. In checkerboard method apigenin markedly reduced the MIC of the antibiotics ampicillin 800 µg/ml shifted to 107 µg/ml (AM+AP) and ceftriaxone 58 µg/ml shifted to 2.6 µg/ml (CEF+AP) against MRSA. The synergistic activity of ampicillin and ceftriaxone plus apigenin combinations with FIC indices (CI) between 0.18-0.47. The modulation of methicillin-resistance by apigenin significantly enhanced the activities of ampicillin and ceftriaxone. The result of time-kill assays of the two drug combinations AM +AP and CEF+AP against MRSA showed significant inhibitory effect and reduced the colony count by approximately 99% after 8 h The results for outer membrane (OM) and inner membrane (IM) permeabilization showed that ampicillin and ceftriaxone in combination with apigenin damaged MRSA cytoplasmic membrane and caused subsequent leakage of intracellular constituents. Electron microscopy clearly showed that the above said combination also caused marked morphological damage of cell wall, cell shape and plasma

Evaluation of synergistic antioxidant potential of complex mixtures using oxygen radical absorbance capacity (ORAC) and electron paramagnetic resonance (EPR).

PubMed

Parker, Tory L; Miller, Samantha A; Myers, Lauren E; Miguez, Fernando E; Engeseth, Nicki J

2010-01-13

Previous research has demonstrated that certain combinations of compounds result in a decrease in toxic or pro-oxidative effects, previously noted when compounds were administered singly. Thus, there is a need to study many complex interactions further. Two in vitro techniques [electron paramagnetic resonance (EPR) and oxygen radical absorbance capacity (ORAC) assays] were used in this study to assess pro- and antioxidant capacity and synergistic potential of various compounds. Rutin, p-coumaric acid, abscisic acid, ascorbic acid, and a sugar solution were evaluated individually at various concentrations and in all 26 possible combinations at concentrations found in certain foods (honey or papaya), both before and after simulated digestion. EPR results indicated sugar-containing combinations provided significantly higher antioxidant capacity; those combinations containing sugars and ascorbic acid demonstrated synergistic potential. The ORAC assay suggested additive effects, with some combinations having synergistic potential, although fewer combinations were significantly synergistic after digestion. Finally, ascorbic acid, caffeic acid, quercetin, and urate were evaluated at serum-achievable levels. EPR analysis did not demonstrate additive or synergistic potential, although ORAC analysis did, principally in combinations containing ascorbic acid.

[Synergistic lethal effect of combined treatment of arsenic trioxide and aclacinomycin on human acute myeloid leukemia cell line KG-1a].

PubMed

Ye, Y B; Xu, X J; Chen, Y H; Zhang, M W; Qiu, D F; Guo, Z W; He, H Q

2017-04-23

Objective: To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a. Methods: Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis. Results: The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 μmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 μmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone ( P <0.05). The apoptotic rate of KG-1a cells treated with both 1.5 μmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 μmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone ( P <0.05). The apoptotic rate of KG-1a cells treated with both 3.0 μmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 μmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone ( P <0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents. Conclusions: Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell

Synergistic Effects of Frequency and Temperature on Damage Evolution and Life Prediction of Cross-Ply Ceramic Matrix Composites under Tension-Tension Fatigue Loading

NASA Astrophysics Data System (ADS)

Longbiao, Li

2017-10-01

In this paper, the synergistic effects of loading frequency and testing temperature on the fatigue damage evolution and life prediction of cross-ply SiC/MAS ceramic-matrix composite have been investigated. The damage parameters of the fatigue hysteresis modulus, fatigue hysteresis dissipated energy and the interface shear stress were used to monitor the damage evolution inside of SiC/MAS composite. The evolution of fatigue hysteresis dissipated energy, the interface shear stress and broken fibers fraction versus cycle number, and the fatigue life S-N curves of SiC/MAS composite under the loading frequency of 1 and 10 Hz at 566 °C and 1093 °C in air condition have been predicted. The synergistic effects of the loading frequency and testing temperature on the degradation rate of fatigue hysteresis dissipated energy and the interface shear stress have been analyzed.

[Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

PubMed

Ueki, H

1987-11-01

We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

Synergistic antibacterial activity of Salvia officinalis and Cichorium intybus extracts and antibiotics.

PubMed

Stefanović, Olgica D; Stanojević, Dragana D; Comić, Ljiljana R

2012-01-01

Synergistic activity of Salvia officinalis and Cichorium intybus extracts and commonly used antibiotics, amoxicillin and chloramphenicol, were evaluated. Interactions between plant extracts and antibiotics were tested by checkerboard method and interpreted as FIC index. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and clinical isolates Staphylococcus aureus, Bacillus subtilis, Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were used. Salvia officinalis showed better synergistic capacity than Cichorium intybus. Synergistic interactions were observed between amoxicillin and acetone or ethyl acetate extract of Salvia officinalis and between chloramphenicol and ethyl acetate extract of Salvia officinalis. In the presence of sub-inhibitory concentration (1/4 MIC to 1/32 MIC) of sage extracts, the MIC values of antibiotics were decreased by 2- to 10-fold. Synergism was observed against all test bacteria, except Escherichia coli. The combinations of acetone and ethyl acetate extract from Cichorium intybus and antibiotics resulted in additive and indifferent effects against tested bacteria.

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine.

PubMed

Moore, R A; Derry, C J; Derry, S; Straube, S; McQuay, H J

2012-04-01

Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. We tested measured effects of combination analgesics against the sum of the absolute benefits in acute pain and migraine using meta-analysis where individual components and combinations were tested against placebo in the same trials, and verified the result with meta-analyses where individual components and combinations were tested against placebo in different trials. Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects. © 2011 European Federation of International Association for the Study of Pain Chapters.

Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

PubMed Central

Oz, Helieh S.

2014-01-01

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy.

PubMed

Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

2012-12-01

The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. The in vitro addition of AM significantly increased SCEs only in SCLC patients (p<0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p<0.001, NSCLC: p=0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p<0.001, NSCLC: p=0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p>0.05). These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer. Copyright © 2012 Elsevier B.V. All rights reserved.

Inoculum and zeolite synergistic effect on anaerobic digestion of poultry manure.

PubMed

Fotidis, Ioannis A; Kougias, Panagiotis G; Zaganas, Ioannis D; Kotsopoulos, Thomas A; Martzopoulos, Gerasimos G

2014-01-01

Poultry manure is an ammonia-rich substrate due to its high content of proteins and amino acids. Ammonia is the major inhibitor of anaerobic digestion (AD) process, affecting biogas production and causing great economic losses to the biogas plants. In this study, the effect of different natural zeolite dosages on the mesophilic AD of poultry manure inoculated with a non-acclimatized to ammonia inoculum (dairy manure) was investigated. Additionally, a comparative analysis was performed between the data extracted from this study and the results of a previous study, which has been conducted under the same experimental conditions but with the use of ammonia acclimatized inoculum (swine manure). At 5 and 10 g zeolite L(-1), the methane yield of poultry manure was 43.4% and 80.3% higher compared with the experimental set without zeolite addition. However, the ammonia non-acclimatized inoculum was not efficient in digesting poultry manure even in the presence of 10 g zeolite L(-1), due to low methane production (only 39%) compared with the maximum theoretical yield. Finally, ammonia acclimatized inoculum and zeolite have demonstrated a possible 'synergistic effect', which led to a more efficient AD of poultry manure. The results of this study could potentially been used by the biogas plant operators to efficiently digest poultry manure.

Multisource Synergistic Electrocatalytic Oxidation Effect of Strongly Coupled PdM (M = Sn, Pb)/N-doped Graphene Nanocomposite on Small Organic Molecules

PubMed Central

Wu, Peng; Huang, Yiyin; Kang, Longtian; Wu, Maoxiang; Wang, Yaobing

2015-01-01

A series of palladium-based catalysts of metal alloying (Sn, Pb) and/or (N-doped) graphene support with regular enhanced electrocatalytic activity were investigated. The peak current density (118.05 mA cm−2) of PdSn/NG is higher than the sum current density (45.63 + 47.59 mA cm−2) of Pd/NG and PdSn/G. It reveals a synergistic electrocatalytic oxidation effect in PdSn/N-doped graphene Nanocomposite. Extend experiments show this multisource synergetic catalytic effect of metal alloying and N-doped graphene support in one catalyst on small organic molecule (methanol, ethanol and Ethylene glycol) oxidation is universal in PdM(M = Sn, Pb)/NG catalysts. Further, The high dispersion of small nanoparticles, the altered electron structure and Pd(0)/Pd(II) ratio of Pd in catalysts induced by strong coupled the metal alloying and N-doped graphene are responsible for the multisource synergistic catalytic effect in PdM(M = Sn, Pb) /NG catalysts. Finally, the catalytic durability and stability are also greatly improved. PMID:26434949

Synergistic action between sisomicin and mezlocillin against gram-negative bacteria and Staphylococcus aureus.

PubMed

Soares, L A; Trabulsi, L R

1979-01-01

The combined effect of sisomicin and 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido-a1-penicillanic acid sodium salt (mezlocillin, Baypen) was studied against 50 bacterial strains, including Pseudomonas aeruginosa, Proteus spp. Klebsiella-Enterobacter, E. coli and Staphylococcus aureus. No antagonism or indifference was detected with the strains studied. Both antibiotics were synergistic against 62% of the strains, and partially synergistic against 38%. Out of the bacteria studied, Staphylococcus aureus was the most susceptible to the combined action of sisomicin and mezlocillin.

Identification of Cardiometabolic Vulnerabilities Caused by Effects of Synergistic Stressors that are Commonly Encountered During Space Missions

NASA Technical Reports Server (NTRS)

Ruger, M.; Scheer, F. A. J.; Barger, L. K.; Lockley, S. W.; Wang, W.; Johnston, S. L. III; Crucian, B.; Shea, A. S.

2011-01-01

Microgravity is a physiologically challenging state even when at rest. Astronauts experience additional physical and mental stresses, such as prolonged exertion, sleep loss and circadian misalignment, that could impact cardiovascular function. The main goals of this four year NASA project are to characterize the independent and synergistic effects on cardiovascular and immune function of: (1) circadian misalignment; (2) sleep loss; and (3) varied physical and mental stressors, mimicking some of the synergistic stressors experienced by astronauts. Sixteen healthy volunteers, aged 35-55 years, will be studied with standardized behavioral stressors occurring across all circadian phases, both with and without accruing sleep loss, achieved via two 11-day "forced desynchrony" protocols performed in each subject (randomized, within-subject design), where wake periods are advanced 4-h each "day" (i.e. recurring 20-h "days"). One protocol permits 8.33 h sleep opportunity per 20-h "day" (=10 h sleep per 24-h), and the other permits 5 h sleep per 20-h "day" (=6 h sleep per 24-h; matching the reported sleep duration of astronauts). In both protocols, subjects will perform a standardized stress battery including a cognitively challenging task; bicycle exercise, and passive 60deg head up tilt. Outcome variables include blood pressure, heart rate, arrhythmia frequency, cardiac vagal tone (from heart rate variability), sympathetic activity (catecholamines), and endothelial function. Additional measures of cardiac function (echocardiography), responses to a passive 80deg head up tilt, maximal oxygen uptake, and immune function will be assessed at the beginning and at the end of each protocol (i.e., without and with sleep loss, and before and after circadian misalignment). We hope to identify the relative impact on cardiovascular risk markers of varied behavioural stressors while subjects experience circadian misalignment and sleep loss, mimicking some of the synergistic stressors

C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics.

PubMed

Navrátilová, Alice; Nešuta, Ondřej; Vančatová, Irena; Čížek, Alois; Varela-M, Ruben E; López-Abán, Julio; Villa-Pulgarin, Janny A; Mollinedo, Faustino; Muro, Antonio; Žemličková, Helena; Kadlecová, Daniela; Šmejkal, Karel

2016-08-01

Context C-6-Geranylated flavonoids possess promising biological activities. These substances could be a source of lead compounds for the development of therapeutics. Objective The study was designed to evaluate their antibacterial and antileishmanial activity. Materials and methods C-6-Geranylated flavanones were tested in micromolar concentrations against promastigote forms of Leishmania brazilensis, L. donovani, L. infantum, and L. panamensis against methicillin-resistant Staphylococcus aureus (MRSA); and synergistic potential with antibiotics was analyzed. IC50 values (after 72 h) were calculated and compared with that of miltefosine. Flow cytometry and DNA fragmentation analysis were used the mechanism of the effect. Geranylated flavanones or epigallocatechin gallate were combined with oxacillin, tetracycline, and ciprofloxacin, and the effects of these two-component combinations were evaluated. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were established (after 24 h), the synergy was measured by the checkerboard titration technique, and the sums of the fractional inhibitory concentrations (∑FICs) were computed. Results 3'-O-Methyl-5'-O-methyldiplacone and 3'-O-methyldiplacone showed good antileishmanial activities (IC50 8-42 μM). 3'-O-Methyl-5'-hydroxydiplacone activates the apoptotic death at leishmanias, the effect of 3'-O-methyl-5'-O-methyldiplacone has another mechanism. The test of the antibacterial activity showed good effects of 3'-O-methyldiplacol and mimulone against MRSA (MIC 2-16 μg/mL), and in six cases, the results showed synergistic effects when combined with oxacillin. Synergistic effects were also found for the combination of epigallocatechin gallate with tetracycline or oxacillin. Conclusion This work demonstrates anti-MRSA and antileishmanial potential of geranylated flavanones and uncovers their promising synergistic activities with antibiotics. In addition, the mechanism of

c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.

PubMed

Zhao, Xiaofei; Kong, Feng; Wang, Lei; Zhang, Han

2017-01-01

Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synergistic effect of interleukin-17 and tumour necrosis factor-α on inflammatory response in hepatocytes through interleukin-6-dependent and independent pathways.

PubMed

Beringer, A; Thiam, N; Molle, J; Bartosch, B; Miossec, P

2018-04-20

The proinflammatory cytokines interleukin (IL)-17 and tumour necrosis factor (TNF)-α are targets for treatment in many chronic inflammatory diseases. Here, we examined their role in liver inflammatory response compared to that of IL-6. Human hepatoma cells (HepaRG, Huh7.5 and HepG2 cells) and primary human hepatocytes (PHH) were cultured with IL-6, IL-17 and/or TNF-α. To determine the contribution of the IL-6 pathway in the IL-17/TNF-α-mediated effect, an anti-IL-6 receptor antibody was used. IL-17 and TNF-α increased in synergy IL-6 secretion by HepaRG cells and PHH but not by Huh7.5 and HepG2 cells. This IL-17/TNF-α synergistic cooperation enhanced the levels of C-reactive protein (CRP) and aspartate aminotransferase (ASAT) in HepaRG cell and PHH cultures through the induction of IL-6. IL-17/TNF-α also up-regulated IL-8, monocyte chemoattractant protein (MCP)-1 and chemokine (C-C motif) ligand 20 (CCL20) chemokines in synergy through an IL-6-independent pathway. Interestingly, first exposure to IL-17, but not to TNF-α, was crucial for the initiation of the IL-17/TNF-α synergistic effect on IL-6 and IL-8 production. In HepaRG cells, IL-17 enhanced IL-6 mRNA stability resulting in increased IL-6 protein levels. The IL-17A/TNF-α synergistic effect on IL-6 and IL-8 induction was mediated through the activation of extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase, nuclear factor-κB and/or protein kinase B (Akt)-phosphatidylinositol 3-kinase signalling pathways. Therefore, the IL-17/TNF-α synergistic interaction mediates systemic inflammation and cell damage in hepatocytes mainly through IL-6 for CRP and ASAT induction. Independently of IL-6, the IL-17A/TNF-α combination may also induce immune cell recruitment by chemokine up-regulation. IL-17 and/or TNF-α neutralization can be a promising therapeutic strategy to control both systemic inflammation and liver cell attraction. © 2018 British Society for Immunology.

Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.

PubMed

Gadjeva, V; Koldamova, R

2001-01-01

A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

NASA Astrophysics Data System (ADS)

Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

2018-04-01

Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model

PubMed Central

Feng, Jiuhuan; Qin, Shukui

2018-01-01

Introduction Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib mono-therapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib. Materials and methods We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased. Results The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time. Conclusion The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment. PMID:29872316

Chlorine inactivation of Tubifex tubifex in drinking water and the synergistic effect of sequential inactivation with UV irradiation and chlorine.

PubMed

Nie, Xiao-Bao; Li, Zhi-Hong; Long, Yuan-Nan; He, Pan-Pan; Xu, Chao

2017-06-01

The inactivation of Tubifex tubifex is important to prevent contamination of drinking water. Chlorine is a widely-used disinfectant and the key factor in the inactivation of T. tubifex. This study investigated the inactivation kinetics of chlorine on T. tubifex and the synergistic effect of the sequential use of chlorine and UV irradiation. The experimental results indicated that the Ct (concentration × time reaction ) concept could be used to evaluate the inactivation kinetics of T. tubifex with chlorine, thus allowing for the use of a simpler Ct approach for the assessment of T. tubifex chlorine inactivation requirements. The inactivation kinetics of T. tubifex by chlorine was found to be well-fitted to a delayed pseudo first-order Chick-Watson expression. Sequential experiments revealed that UV irradiation and chlorine worked synergistically to effectively inactivate T. tubifex as a result of the decreased activation energy, E a , induced by primary UV irradiation. Furthermore, the inactivation effectiveness of T. tubifex by chlorine was found to be affected by several drinking water quality parameters including pH, turbidity, and chemical oxygen demand with potassium permanganate (COD Mn ) concentration. High pH exhibited pronounced inactivation effectiveness and the decrease in turbidity and COD Mn concentrations contributed to the inactivation of T. tubifex. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toluidine Blue with a Synergistic Effect in Morphological Assessment of Oral Cytosmears.

PubMed

Ratna Kumari, T V N; Ahmed Mujib, B R

2018-01-01

One percent toluidine blue being the most effective adjunct is often used to detect dysplasia. Not much attention has been given to the effect of toluidine blue in enhancement of cytological smears. The present study assessed the smears before and after application of toluidine blue in smokers against non-smokers using three different stains [Papanicolaou (PAP), Hematoxylin and Eosin (H and E), and Giemsa]. Twenty-five individuals from each group participated in the study. The oral cytosmears were obtained before and after application of toluidine blue and assessed for clumping of squamous cells, cellular and nuclear pleomorphism, micronuclei, binucleation, bacterial colony units, and keratin flakes. In smokers, the maximum enhancement in cytological smears post-toluidine blue application was shown by Giemsa stain than PAP and H and E stains. Among the individual parameters, nuclear pleomorphism exhibited greatest significant difference between smokers and non-smokers. Toluidine blue enhanced the staining characteristics both in terms of sensitivity and specificity and thereby was found to be synergistic in assessment of cytosmears. The cellular alterations noticed in the smears of smokers with clinically normal buccal mucosa can be used as a means of education tool in counselling for smoking cessation.

Synergistic Effect of Auto-Activation and Small RNA Regulation on Gene Expression

NASA Astrophysics Data System (ADS)

Xiong, Li-Ping; Ma, Yu-Qiang; Tang, Lei-Han

2010-09-01

Auto-activation and small ribonucleic acid (RNA)-mediated regulation are two important mechanisms in controlling gene expression. We study the synergistic effect of these two regulations on gene expression. It is found that under this combinatorial regulation, gene expression exhibits bistable behaviors at the transition regime, while each of these two regulations, if working solely, only leads to monostability. Within the stochastic framework, the base pairing strength between sRNA and mRNA plays an important role in controlling the transition time between on and off states. The noise strength of protein number in the off state approaches 1 and is smaller than that in the on state. The noise strength also depends on which parameters, the feedback strength or the synthesis rate of small RNA, are tuned in switching the gene expression on and off. Our findings may provide a new insight into gene-regulation mechanism and can be applied in synthetic biology.

Potent Synergistic Effect of Doxycycline with Fluconazole against Candida albicans Is Mediated by Interference with Iron Homeostasis

PubMed Central

2012-01-01

Doxycycline was found to act synergistically with the antifungal fluconazole against Candida albicans. Combination with doxycycline converts fluconazole from fungistatic to fungicidal, prevents the onset of drug resistance, and is also effective against a clinical isolate characterized by elevated resistance to fluconazole. Investigation of the interactions between the two drugs by way of checkerboard assays indicated that doxycycline had an influence on the MIC for fluconazole, as defined by CLSI standards, only at high concentrations (200 μg/ml). However, lower concentrations were effective at eliminating residual cell growth at supra-MICs of fluconazole. Using MIC-0, defined as a drug combination resulting in optically clear wells, as an endpoint, doxycycline was found to be synergistic with fluconazole at a concentration as low as 25 μg/ml, with a fractional inhibitory concentration index of <0.5. Doxycycline-mediated growth inhibition can be reversed by externally added iron, indicating that iron depletion may account for the synergism. Consistently, we confirmed old literature data about iron-chelating activity of doxycycline. Synergism of fluconazole with doxycycline does not appear to be mediated by calcineurin, since doxycycline further aggravates the susceptibility to fluconazole of mutants lacking the catalytic or the regulatory subunits of calcineurin. Growth in the presence of fluconazole and doxycycline is restored by an elevated dosage of ERG11 in Saccharomyces cerevisiae but not in C. albicans, despite the full competence of the pathogen's protein to act as a suppressor in baker's yeast. PMID:22564841

Motivating learning, performance, and persistence: the synergistic effects of intrinsic goal contents and autonomy-supportive contexts.

PubMed

Vansteenkiste, Maarten; Simons, Joke; Lens, Willy; Sheldon, Kennon M; Deci, Edward L

2004-08-01

Three field experiments with high school and college students tested the self-determination theory hypotheses that intrinsic (vs. extrinsic) goals and autonomy-supportive (vs. controlling) learning climates would improve students' learning, performance, and persistence. The learning of text material or physical exercises was framed in terms of intrinsic (community, personal growth, health) versus extrinsic (money, image) goals, which were presented in an autonomy-supportive versus controlling manner. Analyses of variance confirmed that both experimentally manipulated variables yielded main effects on depth of processing, test performance, and persistence (all ps <.001), and an interaction resulted in synergistically high deep processing and test performance (but not persistence) when both intrinsic goals and autonomy support were present. Effects were significantly mediated by autonomous motivation.

Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo-Chemotherapy.

PubMed

Deng, Yibin; Huang, Li; Yang, Hong; Ke, Hengte; He, Hui; Guo, Zhengqing; Yang, Tao; Zhu, Aijun; Wu, Hong; Chen, Huabing

2017-02-01

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light-responsive nanoparticles that can maximize the potency of synergistic thermo-chemotherapy under light irradiation. Here, spatially confined cyanine-anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J-type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π-π interaction with cyanine dye. Under near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J-type Cypate aggregates, trigger the light-driven drug release through the destabilization of temperature-sensitive π-π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light-driven nanoparticles for synergistic cancer therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synergistic Effects of Nonthermal Plasma and Disinfecting Agents against Dental Biofilms In Vitro

PubMed Central

Koban, Ina; Geisel, Marie Henrike; Holtfreter, Birte; Jablonowski, Lukasz; Hübner, Nils-Olaf; Matthes, Rutger; Masur, Kai; Weltmann, Klaus-Dieter; Kramer, Axel; Kocher, Thomas

2013-01-01

Aim. Dental biofilms play a major role in the pathogenesis of many dental diseases. In this study, we evaluated the synergistic effect of atmospheric pressure plasma and different agents in dentistry on the reduction of biofilms. Methods and Results. We used monospecies (S. mutans) and multispecies dental biofilm models grown on titanium discs in vitro. After treatment with one of the agents, the biofilms were treated with plasma. Efficacy of treatment was determined by the number of colony forming units (CFU) and by live-dead staining. For S. mutans biofilms no colonies could be detected after treatment with NaOCl or H2O2. For multispecies biofilms the combination with plasma achieved a higher CFU reduction than each agent alone. We found an additive antimicrobial effect between argon plasma and agents irrespective of the treatment order with cultivation technique. For EDTA and octenidine, antimicrobial efficacy assessed by live-dead staining differed significantly between the two treatment orders (P < 0.05). Conclusions. The effective treatment of dental biofilms on titanium discs with atmospheric pressure plasma could be increased by adding agents in vitro. PMID:24159388

Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line.

PubMed

Polo, M P; Crespo, R; de Bravo, M G

2011-08-01

Simvastatin is a competitive inhibitor of 3-hydroxymethylglutaryl coenzyme A reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. Both of them inhibit growth and proliferation of many cell lines. The present study was designed to determine the action of geraniol, in combination with simvastatin, by assessing their effects in vitro on human hepatocarcinoma cell line (Hep G2). The treatment of Hep G2 cells with concentrations of simvastatin or geraniol that did not inhibit cell proliferation (5 µmol·l⁻¹ of simvastatin and 50 µmol·l⁻¹ of geraniol) resulted in a significant inhibition of cell proliferation. We also examined the effect of simvastatin, geraniol and the combination of both on the biosynthesis of lipids from [¹⁴C]-acetate. Our results demonstrate that the combination of simvastatin and geraniol synergistically inhibited cholesterol biosynthesis and proliferation of Hep G2 cell line, contributing to a better understanding of the action of a component of essential oils targeting a complex metabolic pathway, which would improve the use of drugs or their combination in the fight against cancer and/or cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

Turmeric powder and its derivatives from Curcuma longa rhizomes: Insecticidal effects on cabbage looper and the role of synergists.

PubMed

de Souza Tavares, Wagner; Akhtar, Yasmin; Gonçalves, Gabriel Luiz Padoan; Zanuncio, José Cola; Isman, Murray B

2016-11-02

Curcuma longa has well-known insecticidal and repellent effects on insect pests, but its impact on Trichoplusia ni is unknown. In this study, the compound ar-turmerone, extracted and purified from C. longa rhizomes, was identified, and its insecticidal effects, along with turmeric powder, curcuminoid pigments and crude essential oil were evaluated against this important agricultural pest. The role of natural (sesamol and piperonal) and synthetic [piperonyl butoxide (PBO)] synergists under laboratory and greenhouse conditions were also evaluated. The concentration of ar-turmerone in C. longa rhizomes harvested was 0.32% (dwt). Turmeric powder and its derivatives caused 10-20% mortality in third instar T. ni at a very low dose (10 μg/larva). Addition of PBO increased toxicity of turmeric powder and its derivatives (90-97% mortality) in most binary combinations (5 μg of turmeric powder or its derivatives +5 μg of PBO), but neither piperonal nor sesamol were active as synergists. The compound ar-turmerone alone and the combination with PBO reduced larval weight on treated Brassica oleracea in the laboratory and in greenhouse experiments, compared with the negative control. The compound ar-turmerone could be used as a low cost botanical insecticide for integrated management of cabbage looper in vegetable production.

Turmeric powder and its derivatives from Curcuma longa rhizomes: Insecticidal effects on cabbage looper and the role of synergists

PubMed Central

de Souza Tavares, Wagner; Akhtar, Yasmin; Gonçalves, Gabriel Luiz Padoan; Zanuncio, José Cola; Isman, Murray B.

2016-01-01

Curcuma longa has well-known insecticidal and repellent effects on insect pests, but its impact on Trichoplusia ni is unknown. In this study, the compound ar-turmerone, extracted and purified from C. longa rhizomes, was identified, and its insecticidal effects, along with turmeric powder, curcuminoid pigments and crude essential oil were evaluated against this important agricultural pest. The role of natural (sesamol and piperonal) and synthetic [piperonyl butoxide (PBO)] synergists under laboratory and greenhouse conditions were also evaluated. The concentration of ar-turmerone in C. longa rhizomes harvested was 0.32% (dwt). Turmeric powder and its derivatives caused 10–20% mortality in third instar T. ni at a very low dose (10 μg/larva). Addition of PBO increased toxicity of turmeric powder and its derivatives (90–97% mortality) in most binary combinations (5 μg of turmeric powder or its derivatives +5 μg of PBO), but neither piperonal nor sesamol were active as synergists. The compound ar-turmerone alone and the combination with PBO reduced larval weight on treated Brassica oleracea in the laboratory and in greenhouse experiments, compared with the negative control. The compound ar-turmerone could be used as a low cost botanical insecticide for integrated management of cabbage looper in vegetable production. PMID:27804972

Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction.

PubMed

Kong, Xiang; Ma, Ming-Zhe; Qin, Li; Zhang, Yan; Li, Xiao-Yong; Wang, Guo-Dong; Su, Qing; Zhang, Dao-You

2014-09-01

This study was designed to investigate the underlying mechanisms of synergistic antihypertensive effect produced by combination therapy of losartan and pioglitazone in metabolic syndrome (MS) rats. An MS model was induced by feeding rats a high-fat, high-sodium diet and 20% sucrose solution. Losartan (20 mg/kg/day), pioglitazone (10 mg/kg/day), and their combination were orally administered for eight consecutive weeks. Systolic blood pressure (SBP) and mean arterial pressure (MAP) were measured using the tail-cuff method and carotid arterial catheterization, respectively. The aortas were isolated and in vitro vascular reactivity studies were performed. The protein expression of angiotensin type 1 receptor (AT1), endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox), level of nitrotyrosine as well as activity of eNOS and NADPH oxidase in aortas of MS rats were detected. After eight weeks of treatment, the SBP and MAP in the losartan (115 ± 5 and 106 ± 6 mmHg), pioglitazone (130 ± 6 and 118 ± 6 mmHg), and combination therapy (105 ± 6 and 98 ± 5 mmHg) groups were lower than those in the model group (150 ± 8 and 136 ± 9 mmHg). Combination therapy of losartan and pioglitazone reduced BP more than either monotherapy, and showed additive effects on improving endothelial dysfunction and abolishing the increased vascular responsiveness to angiotensin II. These synergistic effects were associated with further reductions in protein expression of p47(phox) and AT1, NADPH oxidase activity, and nitrotyrosine level. Our data indicate that combined treatment exerts more beneficial effects on lowering BP and improving vascular lesions. © The Author(s) 2013.

Synergistic Effects of Temperature and Oxidation on Matrix Cracking in Fiber-Reinforced Ceramic-Matrix Composites

NASA Astrophysics Data System (ADS)

Longbiao, Li

2017-06-01

In this paper, the synergistic effects of temperatrue and oxidation on matrix cracking in fiber-reinforced ceramic-matrix composites (CMCs) has been investigated using energy balance approach. The shear-lag model cooperated with damage models, i.e., the interface oxidation model, interface debonding model, fiber strength degradation model and fiber failure model, has been adopted to analyze microstress field in the composite. The relationships between matrix cracking stress, interface debonding and slipping, fiber fracture, oxidation temperatures and time have been established. The effects of fiber volume fraction, interface properties, fiber strength and oxidation temperatures on the evolution of matrix cracking stress versus oxidation time have been analyzed. The matrix cracking stresses of C/SiC composite with strong and weak interface bonding after unstressed oxidation at an elevated temperature of 700 °C in air condition have been predicted for different oxidation time.

Synergistic Mechanisms Between Traumatic Brain Injury and Migraine

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-15-1-0209 TITLE: Synergistic Mechanisms Between Traumatic Brain Injury and Migraine PRINCIPAL INVESTIGATOR: Amynah Pradhan...SUBTITLE Synergistic Mechanisms Between Traumatic Brain Injury and Migraine 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0209 5c. PROGRAM ELEMENT...and can persist for months after the initial trauma. The most severe and long lasting posttraumatic headaches are usually classified as migraine ; and

Synergistic effect of PEGylated resveratrol on delivery of anticancer drugs.

PubMed

Wang, Wenlong; Zhang, Liang; Le, Yuan; Chen, Jian-Feng; Wang, Jiexin; Yun, Jimmy

2016-02-10

Resveratrol (RES) is a natural polyphenol which can be considered as a nutraceutical because of its benefits such as anticancer and antioxidant activity. In this paper, we designed polymer-RES conjugates as anticancer drug carrier for synergistic therapeutic effect in cancer treatment. Bicalutamide (BIC) was used as a model drug to investigate the drug release behaviors and in vitro anticancer performance. PEG-RES and PEG-Glycine-RES nanoparticles were prepared and characterized. The size of the prepared particles was around 50 nm with RES content of 17.2 and 16.3 wt% for PEG-RES and PEG-Glycine-RES, respectively, and BIC loading efficiency were of 81.6% and 84.5%, separately. Release rate of RES from conjugates depended on the stability of ester group against hydrolysis. BIC release was much faster than RES release. The anticancer activity of BIC loaded PEGylated RES nanoparticles was much better than that of free BIC, indicating the conjugates provided a synergetic cytotoxicity to cancer cells. Confocal laser scanning microscopy observation and flow cytometry analyses indicated that PEGylated RES conjugates were more efficiently internalized into cells, released drug into cytoplasm. These results suggest that PEGylated RES conjugates show great potential for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Synergistic Effect of Mixed Oxide on the Adsorption of Ammonia with Metal–Organic Frameworks

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

Mounfield, III, William P.; Taborga Claure, Micaela; Agrawal, Pradeep K.

A hydrotalcite-derived MgAl oxide (MMO) was evaluated in combination with the metal–organic frameworks (MOFs) UiO-66 and UiO-66-NH 2 for the adsorption of ammonia. Analysis of the materials’ textural properties after ammonia breakthrough adsorption revealed no change in the PXRD patterns or FTIR spectra; however, a slight decrease in surface area was observed, consistent with the hypothesized presence of strongly adsorbed species after adsorption. UiO-66:MMO and UiO-66-NH 2:MMO composites maintained ammonia adsorption capacity under dry conditions. An almost 2-fold increase in humid ammonia capacity was observed for the UiO-66:MMO composite, far beyond that expected through a linear combination of the twomore » materials’ capacities. As a result, the synergistic effect observed in humid conditions was further investigated with water adsorption experiments, which suggested the effect is the result of the high water affinity of MMO.« less

Synergistic Effect of Mixed Oxide on the Adsorption of Ammonia with Metal–Organic Frameworks

DOE PAGES

Mounfield, III, William P.; Taborga Claure, Micaela; Agrawal, Pradeep K.; ...

2016-06-08

A hydrotalcite-derived MgAl oxide (MMO) was evaluated in combination with the metal–organic frameworks (MOFs) UiO-66 and UiO-66-NH 2 for the adsorption of ammonia. Analysis of the materials’ textural properties after ammonia breakthrough adsorption revealed no change in the PXRD patterns or FTIR spectra; however, a slight decrease in surface area was observed, consistent with the hypothesized presence of strongly adsorbed species after adsorption. UiO-66:MMO and UiO-66-NH 2:MMO composites maintained ammonia adsorption capacity under dry conditions. An almost 2-fold increase in humid ammonia capacity was observed for the UiO-66:MMO composite, far beyond that expected through a linear combination of the twomore » materials’ capacities. As a result, the synergistic effect observed in humid conditions was further investigated with water adsorption experiments, which suggested the effect is the result of the high water affinity of MMO.« less

Enhanced synergistic anti-Lewis lung carcinoma effect of a DNA vaccine harboring a MUC1-VEGFR2 fusion gene used with GM-CSF as an adjuvant.

PubMed

Ruan, Junzhong; Duan, Yong; Li, Fugen; Wang, Zitong

2017-01-01

In order to achieve a synergistic effect on anti-tumour and anti-angiogenesis activity, we designed and constructed a DNA vaccine that expresses MUC1and VEGFR2 in the same reading frame. The aim of this study was to investigate the anti-tumour activity of this DNA vaccine. Furthermore, we also investigated the enhanced synergistic anti-Lewis lung carcinoma effect of this DNA vaccine by using GM-CSF as an adjuvant. A series of DNA plasmids encoding MUC1, VEGFR2, GM-CSF, and their conjugates were constructed and injected into mice intramuscularly (i.m.) followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT), respectively. To evaluate the anti-tumour efficacy of these plasmids, murine models with MUC1-expressing tumours were generated. After injection into the tumour-bearing mouse model, the plasmid carrying the fusion gene of MUC1 and VEGFR2 showed stronger inhibition of tumour growth than the plasmid expressing MUC1 or VEGFR2 alone, which indicated that MUC1 and VEGFR2 could exert a synergistic anti-tumour effect. Furthermore, mice vaccinated with the combination of the GM-CSF expressing plasmid and the plasmid carrying the fusion gene of MUC1 and VEGFR2 showed an increased inhibition in the growth of MUC1-expressing tumours and prolonged mouse survival. These observations emphasize the potential of the synergistic anti-tumour and anti-angiogenesis strategy used in DNA vaccines, and the potential of the GM-CSF gene as an adjuvant for DNA vaccines, which could represent a promising approach for tumour immunotherapy. © 2016 John Wiley & Sons Australia, Ltd.

Synergistic Moel of Organizational Structure.

ERIC Educational Resources Information Center

Wolfe, Richard O.

1985-01-01

Defines the concept of the synergistic model of organizational structure. The primary components of the model are cooperative action and job integration, which have as a direct result the increased energy in staff members using the model. (MD)

Synergistic bioleaching of chalcopyrite and bornite in the presence of Acidithiobacillus ferrooxidans.

PubMed

Zhao, Hongbo; Wang, Jun; Hu, Minghao; Qin, Wenqing; Zhang, Yansheng; Qiu, Guanzhou

2013-12-01

Bioleaching of chalcopyrite and bornite in the presence of Acidithiobacillus ferrooxidans was carried out to investigate the influences between each other during bioleaching. Bioleaching results indicated that bornite accelerated the dissolution of chalcopyrite, and chalcopyrite also accelerated the dissolution of bornite, it could be described as a synergistic effect during bioleaching, this synergistic effect might be attributed to the galvanic effect between chalcopyrite and bornite, and to the relatively low solution potential as the addition of bornite. Significantly amount of elemental sulfur and jarosite formed on the minerals surface might be the main passivation film inhibiting the further dissolution, and the amount of elemental sulfur significantly increased with the addition of bornite. Results of electrochemical measurements indicated that the oxidation and reduction mechanisms of chalcopyrite and bornite were similar, the addition of bornite or chalcopyrite did not change the oxidative and reductive mechanisms, but increased the oxidation rate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Functionalized cell nucleus-penetrating peptide combined with doxorubicin for synergistic treatment of glioma.

PubMed

Zhang, Li; Zhang, Yanyu; Tai, Lingyu; Jiang, Kuan; Xie, Cao; Li, Zhuoquan; Lin, Yao-Zhong; Wei, Gang; Lu, Weiyue; Pan, Weisan

2016-09-15

Clinical application of cell-penetrating peptides (CPPs) in cancer therapy is greatly restricted due to lack of tissue selectivity and tumor-targeting ability. CB5005, a rationally designed CPP that targets and inhibits intracellular NF-κB activation, is constituted by a unique membrane-permeable sequence (CB5005M) cascading to a NF-κB nuclear localization sequence (CB5005N). In vitro cellular evaluation confirmed that CB5005 was effectively taken up by brain capillary endothelial cell bEnd.3 and glioma cells U87. The intracellular localization analysis further demonstrated that CB5005 could not only penetrate into the cells but also enter into their nuclei. More interestingly, CB5005 permeated deeply into the tumor spheroids of U87 cell. In vivo imaging illustrated that the fluorescence-labeled CB5005 distributed itself into the brain and accumulated at the tumor site after intravenous injection. Given the important role of over expressed NF-κB in tumor growth and development, we further investigated CB5005 for its potential in treatment of glioma. When combined administration in vitro with doxorubicin (DOX), CB5005 exhibited a synergistic effect in killing U87 cells. In a nude mice xenograft model, CB5005 inhibited the growth of tumor when applied alone, and displayed a synergistic anti-tumor effect with DOX. In conclusion, CB5005 functioned simultaneously as a cell penetrating peptide and a tumor growth inhibitor, therefore can work as a potential synergist for chemotherapy of human tumor. Clinical application of cell-penetrating peptides in cancer therapy is restricted due to lack of tissue selectivity and tumor-targeting ability. In this manuscript, we reported a rationally designed peptide, named CB5005, which had an attractive capability of translocation into the cell nucleus and blocking nuclear translocation of endogenous NF-κB protein. CB5005 had unique affinity with brain and glioma, and could rapidly accumulate in these tissues after intravenous

Synergistic Catalysis: A Powerful Synthetic Strategy for New Reaction Development

PubMed Central

Allen, Anna E.; MacMillan, David W. C.

2012-01-01

Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature. PMID:22518271

Antivirulent Properties of Underexplored Cinnamomum tamala Essential Oil and Its Synergistic Effects with DNase against Pseudomonas aeruginosa Biofilms – An In Vitro Study

PubMed Central

Farisa Banu, Sanaulla; Rubini, Durairajan; Rakshitaa, Sairam; Chandrasekar, Kamaraj; Murugan, Ramar; Wilson, Aruni; Gowrishankar, Shanmugaraj; Pandian, Shunmugiah Karutha; Nithyanand, Paramasivam

2017-01-01

Pseudomonas aeruginosa is a nosocomial pathogen colonizing patients with chronic infectious diseases and has gained resistance to all the known broad spectrum antibiotics available today. The present study showcases the antibiofilm potential of an essential oil (EO) from an underexplored Cinnamomum species namely, C. tamala, against P. aeruginosa biofilms. Furthermore, the synergistic effects of the EO along with a commercially available DNase (DNaseI) and a DNase (MBD) isolated from a marine bacterium were explored for its antibiofilm activity. The results showed that the synergized action has maximum efficacy in inhibiting young and preformed biofilms. The synergized effect of EO and DNaseI showed 70% inhibition against matured biofilms of P. aeruginosa. The EO from C. tamala also showed quorum sensing inhibitory potential as it could inhibit the swarming motility behavior of P. aeruginosa. The synergistic action of EO and DNases offers a novel alternate therapeutic strategy for combating P. aeruginosa biofilm associated infections. PMID:28694794

The synergistic effects for the co-cultivation of oleaginous yeast-Rhodotorula glutinis and microalgae-Scenedesmus obliquus on the biomass and total lipids accumulation.

PubMed

Yen, Hong-Wei; Chen, Pin-Wen; Chen, Li-Juan

2015-05-01

In this co-culture of oleaginous yeast-Rhodotorula glutinis and microalgae-Scenedesmus obliquus, microalgae potentially acts as an oxygen generator for the growth of aerobic yeast while the yeast mutually provides CO2 to the microalgae as both carry out the production of lipids. To explore the synergistic effects of co-cultivation on the cells growth and total lipids accumulation, several co-culture process parameters including the carbon source concentration, temperature and dissolved oxygen level would be firstly investigated in the flask trials. The results of co-culture in a 5L photobioreactor revealed that about 40-50% of biomass increased and 60-70% of total lipid increased was observed as compared to the single culture batches. Besides the synergistic effects of gas utilization, the providing of trace elements to each other after the natural cells lysis was believed to be another benefit to the growth of the overall co-culture system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synergistic Anticancer Action of Lysosomal Membrane Permeabilization and Glycolysis Inhibition.

PubMed

Kosic, Milica; Arsikin-Csordas, Katarina; Paunovic, Verica; Firestone, Raymond A; Ristic, Biljana; Mircic, Aleksandar; Petricevic, Sasa; Bosnjak, Mihajlo; Zogovic, Nevena; Mandic, Milos; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

2016-10-28

We investigated the in vitro and in vivo anticancer effect of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-d-glucose (2DG). NDI-triggered LMP and 2DG-mediated glycolysis block synergized in inducing rapid ATP depletion, mitochondrial damage, and reactive oxygen species production, eventually leading to necrotic death of U251 glioma cells but not primary astrocytes. NDI/2DG-induced death of glioma cells was partly prevented by lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol, suggesting the involvement of LMP and oxidative stress in the observed cytotoxicity. LMP-inducing agent chloroquine also displayed a synergistic anticancer effect with 2DG, whereas glucose deprivation or glycolytic inhibitors iodoacetate and sodium fluoride synergistically cooperated with NDI, thus further indicating that the anticancer effect of NDI/2DG combination was indeed due to LMP and glycolysis block. The two agents synergistically induced ATP depletion, mitochondrial depolarization, oxidative stress, and necrotic death also in B16 mouse melanoma cells. Moreover, the combined oral administration of NDI and 2DG reduced in vivo melanoma growth in C57BL/6 mice by inducing necrotic death of tumor cells, without causing liver, spleen, or kidney toxicity. Based on these results, we propose that NDI-triggered LMP causes initial mitochondrial damage that is further increased by 2DG due to the lack of glycolytic ATP required to maintain mitochondrial health. This leads to a positive feedback cycle of mitochondrial dysfunction, ATP loss, and reactive oxygen species production, culminating in necrotic cell death. Therefore, the combination of LMP-inducing agents and glycolysis inhibitors seems worthy of further exploration as an anticancer strategy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Synergistic antioxidant activity of milk sphingomyeline and its sphingoid base with α-tocopherol on fish oil triacylglycerol.

PubMed

Shimajiri, Junki; Shiota, Makoto; Hosokawa, Masashi; Miyashita, Kazuo

2013-08-21

The effects of milk phospholipids (PLs), sphingolipids (SLs), and their sphingoid backbone on the oxidation of fish oil triacylglycerol (TAG) were examined with or without α-tocopherol. All compounds had little effect on the TAG oxidation in the absence of α-tocopherol. On the other hand, they could act synergistically with α-tocopherol. The highest synergistic activity was shown by sphingoid bases, followed by sphingomyelin (SPM) and other amine-containing PLs and SLs. This result showed that the synergistic activity increased with an increasing concentration of amine group of PLs, SLs, or sphingoid bases in the reaction mixture. The comparison of changes in α-tocopherol content in fish oil TAG and tricaprylin suggested that antioxidant compounds would be formed from the amine group and the lipid oxidation products in a mild oxidation condition controlled by α-tocopherol.

Synergistic cytotoxic action of vitamin C and vitamin K3.

PubMed

Zhang, W; Negoro, T; Satoh, K; Jiang, Y; Hashimoto, K; Kikuchi, H; Nishikawa, H; Miyata, T; Yamamoto, Y; Nakano, K; Yasumoto, E; Nakayachi, T; Mineno, K; Satoh, T; Sakagami, H

2001-01-01

We investigated the combination effect of sodium ascorbate (vitamin C) and menadione (vitamin K3) on the viability of various cultured cells. Human oral squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60) cells were more sensitive to these vitamins as compared to normal cells (human gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp cell HPC). The combination of vitamin C and vitamin K3 produced synergistic cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin K3, or their combination, induced internucleosomal DNA fragmentation only in HL-60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR spectroscopy showed that vitamins C and K3 produce radicals under alkaline conditions and that the combination of these two vitamins synergistically enhanced their respective radical intensities.

SU-F-T-677: Synergistic Effect(s) of Clotrimazole On Radiation Cell Survival of A549 Lung Cancer Cells in Glucose Vs. Galactose Media

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

Boss, G; Tambasco, M; Garakani, M

Purpose: In order to determine the synergistic effect of clotrimazole on radiosensitivity of A549 lung cancer cells, and the effect of oxidative pathways on modulating radiosensitivity, we studied how these cells survived under varying amounts of radiation and clotrimazole as well ass when glucose was switched for galactose media. Methods: The glucose media was used to determine the presence of any synergistic effect of clotrimazole on radiation using values of radiation and clotrimazole concentrations, varying from 0 – 8 Gy and 0 – 20 µM, respectively. As a galactose diet is known to activate oxidative pathways, which do not relymore » on hexokinase II (HK2), all trials were repeated using galactose media to determine the extent that HK2 unbinding from the mitochondrial membrane plays a role in modulating the observed radiosensitivity. An apoptosis vs. necrosis assay was implemented to find out the modality by which cell death occurred. An intracellular lactate assay was performed to exhibit the extent of anaerobic glycolysis. Results: After running the primary experiments, it was found that in glucose media, the cancer cells showed higher cell kill when clotrimazole was added to the media, followed by the cells being irradiated. Conclusion: Given the preliminary results it is validated that under higher concentrations of clotrimazole, in glucose media, A549 lung cancer cells exhibit a lower amount of survival. While all results have not yet been gathered. We anticipate that in galactose media the A549 cells will exhibit this effect to a much smaller degree, if at all.« less

Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations

PubMed Central

Choudhary, Sinjan; Save, Shreyada N.; Kishore, Nand; Hosur, Ramakrishna V.

2016-01-01

We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular. PMID:27870861

Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

PubMed

Choudhary, Sinjan; Save, Shreyada N; Kishore, Nand; Hosur, Ramakrishna V

2016-01-01

We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

Synergistic Activation of Latent HIV-1 Expression by Novel Histone Deacetylase Inhibitors and Bryostatin-1.

PubMed

Martínez-Bonet, Marta; Clemente, Maria Isabel; Serramía, Maria Jesús; Muñoz, Eduardo; Moreno, Santiago; Muñoz-Fernández, Maria Ángeles

2015-11-13

Viral reactivation from latently infected cells has become a promising therapeutic approach to eradicate HIV. Due to the complexity of the viral latency, combinations of efficient and available drugs targeting different pathways of latency are needed. In this work, we evaluated the effect of various combinations of bryostatin-1 (BRY) and novel histone deacetylase inhibitors (HDACIs) on HIV-reactivation and on cellular phenotype. The lymphocyte (J89GFP) or monocyte/macrophage (THP89GFP) latently infected cell lines were treated with BRY, panobinostat (PNB) and romidepsin (RMD) either alone or in combination. Thus, the effect on the viral reactivation was evaluated. We calculated the combination index for each drug combination; the BRY/HDACIs showed a synergistic HIV-reactivation profile in the majority of the combinations tested, whereas non-synergistic effects were observed when PNB was mixed with RMD. Indeed, the 75% effective concentrations of BRY, PNB and RMD were reduced in these combinations. Moreover, primary CD4 T cells treated with such drug combinations presented similar activation and proliferation profiles in comparison with single drug treated cells. Summing up, combinations between BRY, PNB and/or RMD presented a synergistic profile by inducing virus expression in HIV-latently infected cells, rendering these combinations an attractive novel and safe option for future clinical trials.

Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture.

PubMed

Yang, S; Tamai, R; Akashi, S; Takeuchi, O; Akira, S; Sugawara, S; Takada, H

2001-04-01

An analog of 1alpha,25-dihydroxyvitamin D3, 22-oxyacalcitriol (OCT), differentiated human monocytic THP-1 and U937 cells to express membrane CD14 and rendered the cells responsive to bacterial cell surface components. Both THP-1 and U937 cells expressed Toll-like receptor 4 (TLR4) on the cell surface and TLR4 mRNA in the cells, irrespective of OCT treatment. In contrast, OCT-treated U937 cells scarcely expressed TLR2 mRNA, while OCT-treated THP-1 cells expressed this transcript. Muramyldipeptide (MDP) by itself exhibited only a weak ability to induce secretion of inflammatory cytokines such as interleukin-8 (IL-8) in the OCT-differentiated THP-1 cells but showed marked synergistic effects with Salmonella lipopolysaccharide (LPS) or lipoteichoic acid (LTA) from Staphylococcus aureus, both of which exhibited strong activities. Combinatory stimulation with LPS plus LTA did not show a synergistic effect on OCT-differentiated THP-1 cells. Similar results were observed in OCT-differentiated U937 cells, although combination experiments were carried out only with MDP plus LPS. Anti-CD14 monoclonal antibody (MAb) MY4, anti-TLR4 MAb HTA125, and the synthetic lipid A precursor LA-14-PP almost completely inhibited the IL-8-inducing activities of LTA as well as LPS on OCT-treated THP-1 cells, but these treatments increased MDP activity. OCT-treated THP-1 cells primed with MDP exhibited enhanced production of IL-8 upon stimulation with LPS, while the cells primed with LPS showed no change in production upon stimulation with MDP. MDP up-regulated mRNA expression of an adapter molecule to TLRs, MyD88, to an extent similar to that for LPS in OCT-treated THP-1 cells. These findings suggested that LTA as well as LPS activated human monocytic cells in a CD14- and TLR4-dependent manner, whereas MDP exhibited activity in a CD14-, TLR4-, and probably TLR2-independent manner and exhibited synergistic and priming effects on the cells for cytokine production in response to various bacterial

Synergistic Effects of High Hydrostatic Pressure, Mild Heating, and Amino Acids on Germination and Inactivation of Clostridium sporogenes Spores

PubMed Central

Ishimori, Takateru; Takahashi, Katsutoshi; Goto, Masato; Nakagawa, Suguru; Kasai, Yoshiaki; Konagaya, Yukifumi; Batori, Hiroshi; Kobayashi, Atsushi

2012-01-01

The synergistic effects of high hydrostatic pressure (HHP), mild heating, and amino acids on the germination of Clostridium sporogenes spores were examined by determining the number of surviving spores that returned to vegetative growth after pasteurization following these treatments. Pressurization at 200 MPa at a temperature higher than 40°C and treatment with some of the 19 l-amino acids at 10 mM or higher synergistically facilitated germination. When one of these factors was omitted, the level of germination was insignificant. Pressures of 100 and 400 MPa were less effective than 200 MPa. The spores were effectively inactivated by between 1.8 and 4.8 logs by pasteurization at 80°C after pressurization at 200 MPa at 45°C for 120 min with one of the amino acids with moderate hydrophobicity, such as Leu, Phe, Cys Met, Ala, Gly, or Ser. However, other amino acids showed poor inactivation effects of less than 0.9 logs. Spores in solutions containing 80 mM of either Leu, Phe, Cys, Met, Ala, Gly, or Ser were successfully inactivated by pasteurization by more than 5.4 logs after pressurization at 200 MPa at 70°C for 15 to 120 min. Ala and Met reduced the spore viability by 2.8 and 1.8 logs, respectively, by pasteurization at a concentration of 1 mM under 200 MPa at 70°C. These results indicate that germination of the spores is facilitated by a combination of high hydrostatic pressure, mild heating, and amino acids. PMID:22983975

Synergistic effect of DDT and its metabolites in lipopolysaccharide-mediated TNF-α production is inhibited by progesterone in peripheral blood mononuclear cells.

PubMed

Dominguez-Lopez, Pablo; Diaz-Cueto, Laura; Aguilar-Rojas, Arturo; Arechavaleta-Velasco, Fabian

2017-07-01

Increased TNF-α levels have been associated with adverse pregnancy outcomes. Lipopolysaccharide (LPS), 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) induce TNF-α release in peripheral blood mononuclear cells (PBMC). Conversely, progesterone (P4) inhibits TNF-α secretion. Pregnant women in malaria endemic areas may be co-exposure to these compounds. Thus, this study was to investigate the synergistic effect of LPS and these pesticides in PBMC and to assess P4 influence on this synergy. Cultured PBMC were exposed to each pesticide in the presence of LPS, P4, or their combination. TNF-α was measured by ELISA. All pesticides enhanced TNF-α synthesis in PBMC. Co-exposure with LPS synergizes TNF-α production, which is blocked by progesterone. These results indicate that these organochlorines act synergistically with LPS to induce TNF-α secretion in PBMC. This effect is blocked by P4. © 2017 Wiley Periodicals, Inc.

Synergistic dynamics of nitrogen and phosphorous influences lipid productivity in Chlorella minutissima for biodiesel production.

PubMed

Arora, Neha; Patel, Alok; Pruthi, Parul A; Pruthi, Vikas

2016-08-01

The study synergistically optimized nitrogen and phosphorous concentrations for attainment of maximum lipid productivity in Chlorella minutissima. Nitrogen and phosphorous limited cells (N(L)P(L)) showed maximum lipid productivity (49.1±0.41mg/L/d), 1.47 folds higher than control. Nitrogen depletion resulted in reduced cell size with large sized lipid droplets encompassing most of the intracellular space while discrete lipid bodies were observed under nitrogen sufficiency. Synergistic N/P starvations showed more prominent effect on photosynthetic pigments as to individual deprivations. Phosphorous deficiency along with N starvation exhibited 17.12% decline in carbohydrate while no change in nitrogen sufficient cells were recorded. The optimum N(L)P(L) concentration showed balance between biomass and lipid by maintaining intermediate cell size, pigments, carbohydrate and proteins. FAME profile showed C14-C18 carbon chains in N(L)P(L) cells with biodiesel properties comparable to plant oil methyl esters. Hence, synergistic N/P limitation was effective for enhancing lipid productivity with reduced consumption of nutrients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity.

PubMed

Tristão, Vivian Regina; Pessoa, Edson A; Nakamichi, Renata; Reis, Luciana A; Batista, Marcelo Costa; Durão Junior, Marcelino de Souza; Monte, Júlio Cesar Martins

2016-01-01

Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.

Expression profiling of Bombyx mori gloverin2 gene and its synergistic antifungal effect with cecropin A against Beauveria bassiana.

PubMed

Lü, Dingding; Geng, Tao; Hou, Chengxiang; Qin, Guangxing; Gao, Kun; Guo, Xijie

2017-02-05

Gloverin2 is a cationic and glycine-rich antimicrobial peptide whose expression can be induced in fat body of silkworm (Bombyx mori) larvae exposed to bacteria. The purpose of this study is to identify the roles of Bombyx mori gloverin2 (Bmgloverin2) during entomopathogenic fungus Beauveria bassiana infection. Fluorescent quantitative real-time PCR analysis indicated that the relative expression level of Bmgloverin2 gene was up-regulated in the silkworm larvae infected by B. bassiana. The cDNA of Bmgloverin2 was cloned from the silkworm by RT-PCR and the DNA segment of the Bmgloverin2 peptide (without signal peptide sequence) was inserted into pCzn1 expression plasmid and expressed in E. coli ArcticExpress (DE3). SDS-PAGE results revealed that soluble recombinant Bmgloverin2 was successfully expressed and purified. Polyclonal antibody against the Bmgloverin2 was successfully produced with the expressed recombinant protein. Western blot analysis indicated that Bmgloverin2 could be detected in the fat body of silkworm larvae infected with B. bassiana, suggesting that the expression of Bmgloverin2 could be induced by B. bassiana infection in silkworm. Antifungal assays indicated that the Bmgloverin2 had a synergistic antifungal activity with B. mori cecropin A (BmCecA) to entomopathogenic fungus B. bassiana both in vitro and in vivo in the silkworm larvae. This is the first report that Bmgloverin2 exhibits synergistic effect with BmCecA in antifungal activity against B. bassiana. The study demonstrates that Bmgloverin2 is an antifungal protein which plays an important role in synergistic antifungal activity with other antimicrobial peptide in silkworm. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

NASA Astrophysics Data System (ADS)

Camacho, Kathryn Militar

Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly

Oxygen vacancy induces self-doping effect and metalloid LSPR in non-stoichiometric tungsten suboxide synergistically contributing to the enhanced photoelectrocatalytic performance of WO3-x/TiO2-x heterojunction.

PubMed

Huang, Weicheng; Wang, Jinxin; Bian, Lang; Zhao, Chaoyue; Liu, Danqing; Guo, Chongshen; Yang, Bin; Cao, Wenwu

2018-06-27

A WO3-x/TiO2-x nanotube array (NTA) heterojunction photoanode was strategically designed to improve photoelectrocatalytic (PEC) performance by establishing a synergistic vacancy-induced self-doping effect and localized surface plasmon resonance (LSPR) effect of metalloid non-stoichiometric tungsten suboxide. The WO3-x/TiO2-x NTA heterojunction photoanode was synthesized through a successive process of anodic oxidation to form TiO2 nanotube arrays, magnetron sputtering to deposit metalloid WO3-x, and post-hydrogen reduction to engender oxygen vacancy in TiO2-x as well as crystallization. On the merits of such a synergistic effect, WO3-x/TiO2-x shows higher light-harvesting ability, stronger photocurrent response, and resultant improved photoelectrocatalytic performance than the contrast of WO3-x/TiO2, WO3/TiO2 and TiO2, confirming the importance of oxygen vacancies in improving PEC performance. Theoretical calculation based on density functional theory was applied to investigate the electronic structural features of samples and reveal how the oxygen vacancy determines the optical property. The carrier density tuning mechanism and charge transfer model were considered to be associated with the synergistic effect of self-doping and metalloid LSPR effect in the WO3-x/TiO2-x NTA.

Toluidine Blue with a Synergistic Effect in Morphological Assessment of Oral Cytosmears

PubMed Central

Ratna Kumari, T V. N.; Ahmed Mujib, B. R.

2018-01-01

Objectives: One percent toluidine blue being the most effective adjunct is often used to detect dysplasia. Not much attention has been given to the effect of toluidine blue in enhancement of cytological smears. The present study assessed the smears before and after application of toluidine blue in smokers against non-smokers using three different stains [Papanicolaou (PAP), Hematoxylin and Eosin (H and E), and Giemsa]. Study Design: Twenty-five individuals from each group participated in the study. The oral cytosmears were obtained before and after application of toluidine blue and assessed for clumping of squamous cells, cellular and nuclear pleomorphism, micronuclei, binucleation, bacterial colony units, and keratin flakes. Results: In smokers, the maximum enhancement in cytological smears post-toluidine blue application was shown by Giemsa stain than PAP and H and E stains. Among the individual parameters, nuclear pleomorphism exhibited greatest significant difference between smokers and non-smokers. Conclusion: Toluidine blue enhanced the staining characteristics both in terms of sensitivity and specificity and thereby was found to be synergistic in assessment of cytosmears. The cellular alterations noticed in the smears of smokers with clinically normal buccal mucosa can be used as a means of education tool in counselling for smoking cessation. PMID:29403163

The synergistic effect in the Fe-Co bimetallic catalyst system for the growth of carbon nanotube forests

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

Hardeman, D.; Esconjauregui, S., E-mail: cse28@cam.ac.uk; Cartwright, R.

2015-01-28

We report the growth of multi-walled carbon nanotube forests employing an active-active bimetallic Fe-Co catalyst. Using this catalyst system, we observe a synergistic effect by which—in comparison to pure Fe or Co—the height of the forests increases significantly. The homogeneity in the as-grown nanotubes is also improved. By both energy dispersive spectroscopy and in-situ x-ray photoelectron spectroscopy, we show that the catalyst particles consist of Fe and Co, and this dramatically increases the growth rate of the tubes. Bimetallic catalysts are thus potentially useful for synthesising nanotube forests more efficiently.

Novel sequential process for enhanced dye synergistic degradation based on nano zero-valent iron and potassium permanganate.

PubMed

Wang, Xiangyu; Liu, Peng; Fu, Minglai; Ma, Jun; Ning, Ping

2016-07-01

A novel synergistic technology based on nano zero-valent iron (NZVI) and potassium permanganate (KMnO4) was developed for treatment of dye wastewater. The synergistic technology was significantly superior, where above 99% of methylene blue (MB) was removed, comparatively, removal efficiencies of MB with the sole technology of NZVI and KMnO4 at pH 6.39 being 52.9% and 63.1%, respectively. The advantages of this technology include (1) the in situ formed materials (manganese (hydr)oxides, iron hydroxides and MnFe oxide), resulting in the stable and high removal efficiency of MB and (2) high removal capacity in a wide range of pH value. Compared with simultaneous addition system of NZVI and KMnO4, MB removal was remarkably improved by sequential addition system, especially when KMnO4 addition time was optimized at 20 min. Analyses of crystal structure (XRD), morphological difference (FE-SEM), element valence and chemical groups (XPS) of NZVI before and after reaction had confirmed the formation of in situ materials, which obviously enhanced removal of MB by oxidation and adsorption. More importantly, the roles of in situ formed materials and degradation mechanism were innovatively investigated, and the results suggested that NCH3 bond of MB molecule was attacked by oxidants (KMnO4 and in situ manganese (hydr)oxides) at position C1 and C9, resulting in cleavage of chromophore. This study provides new insights about an applicable technology for treatment of dye wastewater. Copyright © 2016. Published by Elsevier Ltd.

Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice

PubMed Central

Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

2017-01-01

Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer. PMID:28252027

Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.

PubMed

Xia, Chenglai; Chen, Ruihong; Chen, Jinman; Qi, Qianqian; Pan, Yanbin; Du, Lanying; Xiao, Guohong; Jiang, Shibo

2017-03-02

Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer.

Lack of a synergistic effect of arginine-glutamic acid on the physical stability of spray-dried bovine serum albumin.

PubMed

Reslan, Mouhamad; Demir, Yusuf K; Trout, Bernhardt L; Chan, Hak-Kim; Kayser, Veysel

2017-09-01

Improving the physical stability of spray-dried proteins is essential for enabling pulmonary delivery of biotherapeutics as a noninvasive alternative to injections. Recently, a novel combination of two amino acids - l-arginine (l-Arg) and l-glutamic acid (l-Glu), has been reported to have synergistic protein-stabilizing effects on various protein solutions. Using spray-dried bovine serum albumin (BSA) reconstituted in solution as a model protein, we investigated the synergistic effect of these amino acids on the physical stability of proteins. Five BSA solutions were prepared: (1) BSA with no amino acids (control); (2) with 50 mM l-Arg; (3) with 200 mM l-Arg, (4) with 50 mM l-Glu and (5) with 25:25 mM of Arg:Glu. All solutions were spray-dried and accelerated studies at high temperatures were performed. Following accelerated studies, monomer BSA loss was measured using SE-HPLC. We found that l-Arg significantly improved the physical stability of spray-dried BSA even at low concentrations, however, when combined with l-Glu, was ineffective at reducing monomer BSA loss. Our findings demonstrate the limitations in using Arg-Glu for the stabilization of spray-dried BSA. Furthermore, we found that a low concentration of l-Glu enhanced monomer BSA loss. These findings may have significant implications on the design of future biotherapeutic formulations.

Integrated ternary artificial nacre via synergistic toughening of reduced graphene oxide/double-walled carbon nanotubes/poly(vinyl alcohol)

NASA Astrophysics Data System (ADS)

Gong, Shanshan; Wu, Mengxi; Jiang, Lei; Cheng, Qunfeng

2016-07-01

The synergistic toughening effect of building blocks and interface interaction exists in natural materials, such as nacre. Herein, inspired by one-dimensional (1D) nanofibrillar chitin and two-dimensional (2D) calcium carbonate platelets of natural nacre, we have fabricated integrated strong and tough ternary bio-inspired nanocomposites (artificial nacre) successfully via the synergistic effect of 2D reduced graphene oxide (rGO) nanosheets and 1D double-walled carbon nanotubes (DWNTs) and hydrogen bonding cross-linking with polyvinyl alcohol (PVA) matrix. Moreover, the crack mechanics model with crack deflection by 2D rGO nanosheets and crack bridging by 1D DWNTs and PVA chains induces resultant artificial nacre exhibiting excellent fatigue-resistance performance. These outstanding characteristics enable the ternary bioinspired nanocomposites have many promising potential applications, for instance, aerospace, flexible electronics devices and so forth. This synergistic toughening strategy also provides an effective way to assemble robust graphene-based nanocomposites.

Synergistic atmospheric retrievals: Using OMEGA and PFS to retrieve martian CO

NASA Astrophysics Data System (ADS)

Robert, S.; Aoki, S.; Piccialli, A.; Audouard, J.; Montmessin, F.; Ferron, S.; Altieri, F.; Bellucci, G.; Geminale, A.; Giuranna, M.; Sindoni, G.; Vandaele, A. C.

2017-09-01

Recently, a theoretical study was published showing how science return can benefit from synergistic retrievals [Robert et al., 2017]. The same approach is here applied to experimental data. OMEGA and PFS instruments, both on Mars Express spacecraft, have collected high-quality data enabling us to retrieve CO volume mixing ratio, among others. The synergy between OMEGA and PFS channels will be presented and the benefits of the synergy will be described by comparing synergistic spectral retrievals and non-synergistic ones.

Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway.

PubMed

Sun, Shuben; Gong, Fanger; Liu, Ping; Miao, Qilong

2018-04-17

The aim of present study was to examine whether metformin in association with quercetin has any synergistically anti-tumor effects on prostate cancer. Our findings showed that metformin in combination with quercetin synergistically inhibited the growth, migration and invasion of both PC-3 and LNCaP cells. Co-treatment of these two agents induced more apoptosis than single agent treatment. The co-treatment-induced apoptosis was caspase-dependent and accompanied by the down-regulation of Bcl-2 family members. Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway. Moreover, these two agents acted synergistically to repress the growth of human prostate cancer cell xenograft in vivo in nude mice. In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway. Thus, combination treatment of metformin and quercetin would be a promising therapeutic strategy for prostate cancer patients. Copyright © 2017. Published by Elsevier B.V.

Synergistic effect of amino acids modified on dendrimer surface in gene delivery.

PubMed

Wang, Fei; Wang, Yitong; Wang, Hui; Shao, Naimin; Chen, Yuanyuan; Cheng, Yiyun

2014-11-01

Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neonicotinoid pesticides and nutritional stress synergistically reduce survival in honey bees.

PubMed

Tosi, Simone; Nieh, James C; Sgolastra, Fabio; Cabbri, Riccardo; Medrzycki, Piotr

2017-12-20

The honey bee is a major pollinator whose health is of global concern. Declines in bee health are related to multiple factors, including resource quality and pesticide contamination. Intensive agricultural areas with crop monocultures potentially reduce the quality and quantity of available nutrients and expose bee foragers to pesticides. However, there is, to date, no evidence for synergistic effects between pesticides and nutritional stress in animals. The neonicotinoids clothianidin (CLO) and thiamethoxam (TMX) are common systemic pesticides that are used worldwide and found in nectar and pollen. We therefore tested if nutritional stress (limited access to nectar and access to nectar with low-sugar concentrations) and sublethal, field-realistic acute exposures to two neonicotinoids (CLO and TMX at 1/5 and 1/25 of LD 50 ) could alter bee survival, food consumption and haemolymph sugar levels. Bee survival was synergistically reduced by the combination of poor nutrition and pesticide exposure (-50%). Nutritional and pesticide stressors reduced also food consumption (-48%) and haemolymph levels of glucose (-60%) and trehalose (-27%). Our results provide the first demonstration that field-realistic nutritional stress and pesticide exposure can synergistically interact and cause significant harm to animal survival. These findings have implications for current pesticide risk assessment and pollinator protection. © 2017 The Author(s).

KML001 and doxercalciferol induce synergistic antileukemic effect in acute lymphoid leukemia cells.

PubMed

Liu, Yang; Shin, Dong-Yeop; Oh, Somi; Kim, Sujong; Koh, Youngil; Kim, Inho

2017-07-01

KML001 (NaAsO2, sodium metaarsenite, KOMINOX), a kind of arsenic compound, that has shown promising efficacy in non-Hodgkin's lymphoma (NHL) both in vitro and in vivo. In our study, the antileukemic effect of KML001 on acute lymphoid leukemia (ALL) and its mechanism of action were investigated. The results showed that KML001 inhibited cell proliferation in two types of ALL cell lines, CCRF-CEM and Molt-4. Exposure of ALL cells to KML001 induced apoptosis in a time-dependent manner. KML001 caused cell cycle arrest at G2/M phase instead of G0/G1 phase shown in other leukemia cells. In addition, we also tested the possibility of synergy of KML001 with doxercalciferol, a vitamin D2 derivative. Also, we found that a combination of KML001 with doxercalciferol showed a synergistic effect on ALL cell lines and this could be due to its different mechanism of action. Overall, our findings demonstrated KML001 could be a promising antileukemic agent especially when it is combined with doxercalciferol in ALL treatment.

Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

PubMed

Giddings, Jeffrey; Gagne, James; Sharp, Janice

2016-08-01

A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. © 2016 SETAC.

Why Do Lithium-Oxygen Batteries Fail: Parasitic Chemical Reactions and Their Synergistic Effect.

PubMed

Yao, Xiahui; Dong, Qi; Cheng, Qingmei; Wang, Dunwei

2016-09-12

As an electrochemical energy-storage technology with the highest theoretical capacity, lithium-oxygen batteries face critical challenges in terms of poor stabilities and low charge/discharge round-trip efficiencies. It is generally recognized that these issues are connected to the parasitic chemical reactions at the anode, electrolyte, and cathode. While the detailed mechanisms of these reactions have been studied separately, the possible synergistic effects between these reactions remain poorly understood. To fill in the knowledge gap, this Minireview examines literature reports on the parasitic chemical reactions and finds the reactive oxygen species a key chemical mediator that participates in or facilitates nearly all parasitic chemical reactions. Given the ubiquitous presence of oxygen in all test cells, this finding is important. It offers new insights into how to stabilize various components of lithium-oxygen batteries for high-performance operations and how to eventually materialize the full potentials of this promising technology. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Positive feedback loop and synergistic effects between hypoxia-inducible factor-2α and stearoyl-CoA desaturase-1 promote tumorigenesis in clear cell renal cell carcinoma.

PubMed

Zhang, Yujian; Wang, Hui; Zhang, Jin; Lv, Jianwei; Huang, Yiran

2013-04-01

Adapting to hypoxic stress is pivotal in tumor progression and determining tumor malignancy. The transcriptional factor hypoxia-inducible factor (HIF) is crucial in modulating tumorous hypoxic responses through altering cell energy metabolism, which includes the modification of glucose and lipid metabolism-associated gene expression. Stearoyl-CoA desaturase-1 (SCD1) is the main isoform of SCDs, the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, which is extensively activated in cancer progression. In this study, we found that SCD1 and HIF-2α were overexpressed in human clear cell renal cell carcinoma (ccRCC) tissues and ccRCC cell lines, and were upregulated in the 786-0 ccRCC cell line under hypoxia. Knockdown of SCD1 or HIF-2α impacted the other's expression. Enhancing SCD1 resulted in HIF-2α upregulation, which could be blocked by inhibiting the PI3K/Akt pathway. Deficiency of SCD1 or HIF-2α in 768-0 cells led to apoptosis, less colony formation ability, and decreased cell migration. More obvious effects were observed in 786-0 cells with double SCD1 and HIF-2α knockdown. These results indicate a PI3K/Akt-mediated loop between SCD1 and HIF-2α that mutually enhances their protein levels. Both SCD1 and HIF-2α are critical to promoting tumorigenesis by synergistically acting on maintaining cell survival, triggering cell migration, and enhancing the colony formation ability of cancer cells. © 2013 Japanese Cancer Association.

Anticandidal synergistic activity of green tea catechins, antimycotics and copper sulphate as a mean of combinational drug therapy against candidiasis.

PubMed

Anand, J; Rai, N

2017-03-01

The present investigation aims at evaluating synergistic herbal based composition of purified catechins with fluconazole, amphotericin B and copper sulphate against Candida albicans (MTCC 3017) and Candida glabrata (MTCC 3019). The catechins were isolated from green tea leaves of Assam, Himachal Pradesh and Uttarakhand regions of India. The synergistic activity of combinations against Candida species was assessed following microdilution checkerboard technique and time kill assay. The inhibitory action of most significant combination on treated Candida cells was assessed by scanning electron microscopy. Cytotoxicity of synergistic compositions was further analyzed by performing MTT assay on Vero cell lines. Purified catechins of Assam and Himachal Pradesh green tea showed synergistic activity with fluconazole and amphotericin B against Candida species. Time kill assay depicted synergistic activity at minimum inhibitory concentration and twice of minimum inhibitory concentration of purified catechins and antimycotics. Further, Copper sulphate increased anticandidal efficacy of synergistic combinations by 0.4% to 6.63%. SEM analysis revealed morphological distortions of treated Candida cells. Cytotoxicity analysis of synergistic composition depicted high percentage viability (≥91.4% to≥100%) of Vero cell line, which suggests non-cytotoxic activity of proposed composition on healthy cells. It can be inferred that present evaluated synergistic composition can confer promising anticandidal efficacy and requires further investigation of safety and translational guidelines for effective and safer green tea based potent therapeutic drug. Copyright © 2016. Published by Elsevier Masson SAS.

Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion.

PubMed

Khaldy, Hoda; Escames, Germaine; León, Josefa; Bikjdaouene, Leila; Acuña-Castroviejo, Darío

2003-01-01

Previous studies showed a synergistic effect of melatonin and deprenyl against dopamine (DA) autoxidation in vitro. Since oxidative stress is implicated in Parkinson's disease (PD), we explored the effects of melatonin plus deprenyl administration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in C57/Bl6 mice. Melatonin, but not deprenyl prevents the inhibition of mitochondrial complex I and the oxidative damage in nigrostriatal neurons induced by MPTP. With the dose used deprenyl recovers 50% DA levels and tyrosine hydroxylase activity depressed by the neurotoxin, normalizing locomotor activity of mice. Melatonin, which was unable to counteract MPTP-induced DA depletion and inhibition of tyrosine hydroxylase activity, potentiates the effect of deprenyl on catecholamine turnover and mice ambulatory activity. These results suggest a dissociation of complex I inhibition from DA depletion in this model of Parkinson's disease. The data also support that a combination of melatonin, which improves mitochondrial electron transport chain and reduces oxidative damage, and deprenyl, which promotes the specific function of the rescued neurons, i.e. DA turnover, may be a promising strategy for the treatment of PD.

Synergistic activity of biocides and antibiotics on resistant bacteria from organically produced foods.

PubMed

Fernández Fuentes, Miguel Angel; Abriouel, Hikmate; Gadea, Rebeca; Pérez Pulido, Rubén; Gálvez, Antonio; Ortega, Elena

2014-10-01

Synergism between biocides and antibiotics was investigated in 20 biocide and antibiotic-resistant bacterial strains that were previously isolated from organically produced foods, according to their antimicrobial resistance profiles. Most of the antibiotic/biocide combinations yielded synergistic interactions, reducing the inhibitory concentrations of biocides and antibiotics by 4- to 16-fold. Among enterococci, synergism with biocides was detected for amoxicillin (AM), cefuroxime (CX), erythromycin (EM), ciprofloxacin (CP), and trimethoprim/sulphametoxazol (T/S). Among staphylococci, interactions were synergistic (AM) and either synergistic or indifferent (CX and EM, depending on biocide). Among the three methicillin-resistant Staphylococcus aureus clinical strains included in the study, the combinations of methicillin and triclosan or hexachlorophene acted synergistically in all strains, but interactions were either synergistic or indifferent for the other biocides, depending on the strain. All combinations tested were synergistic for Lactobacillus (AM, CX, EM, and CP) and Micrococcus (AM, EM). In Salmonella, interactions were indifferent (AM, CX, EM, and CP) or synergistic (T/S). Synergism with biocides was also detected in Klebsiella isolates (AM, CX, and T/S), Enterobacter sp. (AM, CX, EM, and T/S), Pantoea (AM, CX, EM, CP, and T/S), and Chryseobacterium sp. (EM). These results suggest that combinations of biocides and antibiotics may open new possibilities to combat antimicrobial resistance.

Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis.

PubMed

Liu, Zhendong; Zhao, Yingxin; Wei, Fang; Ye, Lin; Lu, Fanghong; Zhang, Hua; Diao, Yutao; Song, Hongbin; Qi, Zaiwen

2014-03-01

To explore synergistic effect between angiotensin II receptor blockers (ARBs) and statins on Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. This study was a 2 × 2 factorial randomized, prospective, double-blind, placebo-controlled trial. One hundred and fifty nine hypertensive patients with carotid atherosclerosis were randomized to the administration of control group, telmisartan group, rosuvastatin group, and combination group (telmisartan plus rosuvastatin) base on hydrochlorothiazide treatment. Carotid ultrasonography, parameters of Th17/Treg functional axis, interleukin (IL)-1β, IL-2, interferon (IFN)-γ, hypersensitive C-reactive protein (hsCRP), monocyte chemotactic protein (MCP)-1 were evaluated. Blood pressure level markedly reduced in four groups. There was significantly synergistic effect of combination of telmisartan with rosuvastatin on reducing carotid imtima-media thickness (IMT), Th17 cells frequency, IL-17, IL-6, IL-23, tumor necrosis factor (TNF)-α, expression of retinoic acid receptor-related orphan receptor (ROR)γt mRNA, Th17/Treg ratio, IL-1β, IL-2, IFN-γ, hsCRP, and MCP-1, and increasing Treg cells frequency, IL-10, transforming growth factor(TGF)-β1, and expression of forkhead/winged helix transcription factor (Foxp3) mRNA (all P<0.05). Change rate of IMT statistical positively related to descent rates of Th17 cells frequency, IL-17, IL-6, IL-23, TNF-α, expression of RORγt mRNA, Th17/Treg ratio, IL-1β, IL-2, IFN-γ, hsCRP, and MCP-1, and negatively related to increased rates of Treg frequency, IL-10, TGF-β1, and expression of Foxp3 mRNA, respectively (all P<0.05). There is a synergistic effect of combination of telmisartan with rosuvastatin on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Study on Synergistic Mechanism of Inhibitor Mixture Based on Electron Transfer Behavior

PubMed Central

Han, Peng; He, Yang; Chen, Changfeng; Yu, Haobo; Liu, Feng; Yang, Hong; Ma, Yue; Zheng, Yanjun

2016-01-01

Mixing is an important method to improve the performance of surfactants due to their synergistic effect. The changes in bonding interaction and adsorption structure of IM and OP molecules before and after co-adsorbed on Fe(001) surface is calculated by DFTB+ method. It is found that mixture enable the inhibitor molecules with higher EHOMO donate more electrons while the inhibitor molecules with lower ELUMO accept more electrons, which strengthens the bonding interaction of both inhibitor agent and inhibitor additive with metal surface. Meanwhile, water molecules in the compact layer of double electric layer are repulsed and the charge transfer resistance during the corrosion process increases. Accordingly, the correlation between the frontier orbital (EHOMO and ELUMO of inhibitor molecules and the Fermi level of metal) and inhibition efficiency is determined. Finally, we propose a frontier orbital matching principle for the synergistic effect of inhibitors, which is verified by electrochemical experiments. This frontier orbital matching principle provides an effective quantum chemistry calculation method for the optimal selection of inhibitor mixture. PMID:27671332

Synergistic effect of Brønsted acid and platinum on purification of automobile exhaust gases

PubMed Central

Fu, Wei; Li, Xin-Hao; Bao, Hong-Liang; Wang, Kai-Xue; Wei, Xiao; Cai, Yi-Yu; Chen, Jie-Sheng

2013-01-01

The catalytic purification of automobile exhaust gases (CO, NOx and hydrocarbons) is one of the most practiced conversion processes used to lower the emissions and to reduce the air pollution. Nevertheless, the good performance of exhaust gas purification catalysts often requires the high consumption of noble metals such as platinum. Here we report that the Brønsted acid sites on the external surface of a microporous silicoaluminophosphate (SAPO) act as a promoter for exhaust gas purification, effectively cutting the loading amount of platinum in the catalyst without sacrifice of performance. It is revealed that in the Pt-loaded SAPO-CHA catalyst, there exists a remarkable synergistic effect between the Brønsted acid sites and the Pt nanoparticles, the former helping to adsorb and activate the hydrocarbon molecules for NO reduction during the catalytic process. The thermal stability of SAPO-CHA also makes the composite catalyst stable and reusable without activity decay. PMID:23907148

Synergistic effect of Brønsted acid and platinum on purification of automobile exhaust gases.

PubMed

Fu, Wei; Li, Xin-Hao; Bao, Hong-Liang; Wang, Kai-Xue; Wei, Xiao; Cai, Yi-Yu; Chen, Jie-Sheng

2013-01-01

The catalytic purification of automobile exhaust gases (CO, NOx and hydrocarbons) is one of the most practiced conversion processes used to lower the emissions and to reduce the air pollution. Nevertheless, the good performance of exhaust gas purification catalysts often requires the high consumption of noble metals such as platinum. Here we report that the Brønsted acid sites on the external surface of a microporous silicoaluminophosphate (SAPO) act as a promoter for exhaust gas purification, effectively cutting the loading amount of platinum in the catalyst without sacrifice of performance. It is revealed that in the Pt-loaded SAPO-CHA catalyst, there exists a remarkable synergistic effect between the Brønsted acid sites and the Pt nanoparticles, the former helping to adsorb and activate the hydrocarbon molecules for NO reduction during the catalytic process. The thermal stability of SAPO-CHA also makes the composite catalyst stable and reusable without activity decay.

Synergistic anti-tumor effect of glycosylphosphatidylinositol-anchored IL-2 and IL-12.

PubMed

Ji, Jianfei; Li, Jinhua; Holmes, Lillia M; Burgin, Kelly E; Yu, Xianzhong; Wagner, Thomas E; Wei, Yanzhang

2004-07-01

Preclinical and clinical studies have demonstrated that interleukin 2 (IL-2), interleukin 12 (IL-12), and some other cytokines, play important roles in activating host immune responses against tumor growth. However, severe side effects caused by systemic high-dose administration of these cytokines limit their clinical application. In our previous study, local high doses of IL-2 were achieved by a GPI-anchoring technology; therefore, it will be interesting to know if this technology works for other cytokines. A fusion gene containing murine IL-12 and the glycosylphosphatidylinositol (GPI) anchor signal sequence was generated and transfected into the murine melanoma tumor cell line B16F0 either alone or together with a vector encoding GPI-anchored IL-2. The GPI-anchored cytokine expression of the selected stable clones was assayed in vitro by ELISA and their anti-tumor effects were analyzed in vivo by tumor lymphocyte infiltration and tumor growth studies. GPI-anchored IL-12 was successfully expressed on the cell surface as indicated by FACS analysis and IL-12 ELISA assay. The GPI-anchored IL-12 enhanced lymphocyte infiltration and significantly inhibited tumor growth. More importantly, when GPI-anchored IL-12 and GPI-anchored IL-2 were co-delivered, a synergistic anti-tumor effect was observed in both subcutaneous and intravenous tumor models. GPI anchorage of cytokines represents a new approach to locally deliver high doses of cytokines without the severe adverse effects normally accompanied with systematic high-dose administration of these cytokines. Copyright 2004 John Wiley & Sons, Ltd.

Endosulfan and Cypermethrin Pesticide Mixture Induces Synergistic or Antagonistic Effects on Developmental Exposed Rats Depending on the Analyzed Behavioral or Neurochemical End Points.

PubMed

Gómez-Giménez, Belén; Llansola, Marta; Cabrera-Pastor, Andrea; Hernández-Rabaza, Vicente; Agustí, Ana; Felipo, Vicente

2018-02-21

Exposure to pesticides has been associated with neurodevelopmental toxicity. Usually people are exposed to mixtures of pesticides. However, most studies analyze the effects of individual pesticides. Developmental exposure to mixtures of pesticides may result in additive effects or in antagonistic or synergistic effects. The aim of this work was to compare the effects of developmental exposure of rats to cypermethrin or endosulfan with the effects of its mixture on cognitive and motor function and on some underlying mechanisms. Exposure to individual pesticides or the mixture was from gestational day 7 to postnatal day 21. We analyzed the effects, in males and females, on spatial learning and memory, associative learning, anxiety, motor coordination, and spontaneous motor activity. We also analyzed neuroinflammation and NMDA receptor subunits in hippocampus and extracellular GABA in cerebellum. Exposure to the mixture, but not to individual pesticides, impaired spatial memory in males, associative learning in females, and increased motor activity in males and females. This indicates a synergistic effect of cypermethrin and endolsufan exposure on these end points. In contrast, motor coordination was impaired by individual exposure to endosulfan or cypermethrin, associated with increased extracellular GABA in cerebellum, but these effects were prevented in rats exposed to the mixture, indicating an antagonistic effect of cypermethrin and endolsufan exposure on these end points. The results show different interaction modes (synergism or antagonism) of the pesticides, depending on the end point analyzed and the sex of the rats.

Apigenin shows synergistic anticancer activity with curcumin by binding at different sites of tubulin.

PubMed

Choudhury, Diptiman; Ganguli, Arnab; Dastidar, Debabrata Ghosh; Acharya, Bipul R; Das, Amlan; Chakrabarti, Gopal

2013-06-01

Apigenin, a natural flavone, present in many plants sources, induced apoptosis and cell death in lung epithelium cancer (A549) cells with an IC50 value of 93.7 ± 3.7 μM for 48 h treatment. Target identification investigations using A549 cells and also in cell-free system demonstrated that apigenin depolymerized microtubules and inhibited reassembly of cold depolymerized microtubules of A549 cells. Again apigenin inhibited polymerization of purified tubulin with an IC50 value of 79.8 ± 2.4 μM. It bounds to tubulin in cell-free system and quenched the intrinsic fluorescence of tubulin in a concentration- and time-dependent manner. The interaction was temperature-dependent and kinetics of binding was biphasic in nature with binding rate constants of 11.5 × 10(-7) M(-1) s(-1) and 4.0 × 10(-9) M(-1) s(-1) for fast and slow phases at 37 °C, respectively. The stoichiometry of tubulin-apigenin binding was 1:1 and binding the binding constant (Kd) was 6.08 ± 0.096 μM. Interestingly, apigenin showed synergistic anti-cancer effect with another natural anti-tubulin agent curcumin. Apigenin and curcumin synergistically induced cell death and apoptosis and also blocked cell cycle progression at G2/M phase of A549 cells. The synergistic activity of apigenin and curcumin was also apparent from their strong depolymerizing effects on interphase microtubules and inhibitory effect of reassembly of cold depolymerized microtubules when used in combinations, indicating that these ligands bind to tubulin at different sites. In silico modeling suggested apigenin bounds at the interphase of α-β-subunit of tubulin. The binding site is 19 Å in distance from the previously predicted curcumin binding site. Binding studies with purified protein also showed both apigenin and curcumin can simultaneously bind to purified tubulin. Understanding the mechanism of synergistic effect of apigenin and curcumin could be helped to develop anti-cancer combination drugs from cheap and readily

SYNERGISTIC EFFECT OF HALIDE IONS ON THE CORROSION INHIBITION OF MILD STEEL IN SULPHURIC ACID USING METHYL, N-METHYL ETHYL AND ETHYL SUBSTITUTED γ-2,c-6-DIPHENYL PIPERIDIN-4-ONE SEMICARBAZONES

NASA Astrophysics Data System (ADS)

Priya, V. Shanmuga; Rani, C. Uma; Velrani, S.

The synergistic effect of halide ions such as KCl, KBr and KI on the corrosion inhibition of mild steel in 1 N sulphuric acid by γ-2,c-6-diphenyl-t-3-methyl piperdin-4-ones with semicarbazone (01SC), γ-2,c-6-diphenyl-N-methyl-t-3-ethyl piperdin-4-ones with semicarbazone (02SC) and 2,6-diphenyl-t-3-ethyl piperdin-4-one with semicarbazone (03SC) has been examined by weight loss method, potentiodynamic polarization measurements and electrochemical AC impedance spectroscopy. Results show that substituted γ-2,c-6-diphenyl piperidin-4-ones with semicarbazone act as the perfect corrosion inhibitors and their inhibition efficiency increases with the addition of halide ions. The inhibitor (01SC) shows the inhibition efficiency of 78.28% (0.2mM) by using a weight loss method. The influence of I-, Br- and Cl- anions raises the inhibition efficiency of the substituted 2,6-diphenyl piperidin-4-ones with semicarbazone due to the synergistic effect. The synergistic effect of halide ions was formed in the following order: KI > KBr > KCl.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

PubMed

Kwon, T-R; Oh, C T; Park, H M; Han, H J; Ji, H J; Kim, B J

2015-08-01

Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans. © 2015 British Association of Dermatologists.

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

PubMed Central

Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

2015-01-01

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections. PMID:26048362

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans.

PubMed

Cui, Jinhui; Ren, Biao; Tong, Yaojun; Dai, Huanqin; Zhang, Lixin

2015-01-01

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections.

Predicting synergistic effects of resources and predators on foraging decisions by juvenile Steller sea lions.

PubMed

Frid, Alejandro; Burns, Jennifer; Baker, Gregory G; Thorne, Richard E

2009-01-01

Many theoretical and experimental studies suggest that synergistic interactions between resources and predators influence foraging decisions and their fitness consequences. This framework, however, has been ignored almost completely by hypotheses on causes of the population decline of Steller sea lions (SSLs) (Eumetopias jubatus) in western Alaska. By comparing predictions from a dynamic state variable model to empirical data on the behaviour of individuals instrumented with satellite-linked time-at-depth recorders, we develop and find preliminary support for the hypothesis that, during winter in Prince William Sound, juvenile SSLs (a) underutilise walleye pollock, a predictable resource in deep strata, due to predation risk from Pacific sleeper sharks, and (b) underutilise the potential energy bonanza of inshore aggregations of Pacific herring due to risk from either killer whales, larger conspecifics, or both. Further, under conditions of resource scarcity-induced by overfishing, long-term oceanographic cycles, or their combination-trade-offs between mortality risk and energy gain may influence demographic parameters. Accordingly, computer simulations illustrated the theoretical plausibility that a decline of Pacific herring in shallow strata would greatly increase the number of deep foraging dives, thereby increasing exposure to sleeper sharks and mortality rates. These results suggest that hypotheses on the decline of SSLs should consider synergistic effects of predators and resources on behaviour and mortality rates. Empirical support for our model, however, is limited and we outline tasks for empirical research that emerge from these limitations. More generally, in the context of today's conservation crises, our work illustrates that the greater the dearth of system-specific data, the greater the need to apply principles of behavioural ecology toward the understanding and management of large-scale marine systems.

Fibroblast growth factor 2 and cyclic AMP synergistically regulate bone sialoprotein gene expression.

PubMed

Shimizu, Emi; Nakayama, Youhei; Nakajima, Yu; Kato, Naoko; Takai, Hideki; Kim, Dong-Soon; Arai, Masato; Saito, Ryoichiro; Sodek, Jaro; Ogata, Yorimasa

2006-07-01

Bone sialoprotein (BSP) is a noncollagenous protein of the mineralized bone extracellular matrix. We here report that FGF2 and cAMP act synergistically to stimulate BSP gene expression. Treatment of ROS 17/2.8 cells with either 10 ng/ml FGF2 or 1 microM FSK for 6 h resulted in 5.4- and 8.2-fold increases, respectively, in the levels of BSP mRNA. However, in the presence of both FGF2 and forskolin (FGF/FSK), BSP mRNA levels were increased synergistically by 20.4-fold. Using a luciferase reporter construct, encompassing BSP promoter nucleotides -116 to +60, transcription was also increased synergistically by 15.0-fold with FGF/FSK, compared to stimulations of 2.6- and 5.3-fold, respectively, for FGF2 and FSK alone. Transcriptional stimulation by FGF/FSK abrogated in constructs included 2 bp mutations in the inverted CCAAT, CRE, FRE and Pit-1 elements. Whereas the FRE-protein complex was increased by FGF2 and FGF/FSK, the Pit-1-protein complex was decreased by FSK and FGF/FSK. Notably, transcriptional activity induced by FGF/FSK was blocked by protein kinase A, tyrosine kinase and MEK inhibitors. These studies indicate that the combinatorial effects of FGF and FSK act through PKA, tyrosine kinase and MAP-kinase-dependent pathways, which target the inverted CCAAT, CRE, FRE and Pit-1 elements in the BSP gene to synergistically increase BSP expression.

Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

PubMed Central

Oh, Euna; Jeon, Byeonghwa

2015-01-01

The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

Synergistic Man: Outcome Model for Counselors

ERIC Educational Resources Information Center

Rousseve, Ronald J.

1973-01-01

Drawing on the insights of Ruth Benedict and Abraham Maslow in their search for an ethical gauge by which to rate personal-social health, this article proposes synergistic man'' as the desired outcome model for counselors. (Author)

Synergistic effects of Candida and Escherichia coli on gut barrier function.

PubMed

Diebel, L N; Liberati, D M; Diglio, C A; Dulchavsky, S A; Brown, W J

1999-12-01

Disruption of the indigenous gut microflora with overgrowth of gram-negative bacteria and Candida species is common in the critically ill patient. These organisms readily translocate in vitro, which may cause septic complications and organ failure. A synergistic effect between Escherichia coli and C. albicans in polymicrobial infections has been demonstrated. An interaction between these organisms at the mucosal barrier is unknown. Ca(CO2) monolayers were grown to confluence in a two compartment culture system. E. coli and C. albicans or E. coli alone were added to the apical chambers. Secretory immunoglobulin A was added to half of the apical chambers as well. Cell cultures were incubated for a total of 240 minutes. Basal media were sampled at timed intervals for quantitative culture. Monolayer integrity was confirmed by serial measurement of transepithelial electrical resistance. Secretory immunoglobulin A decreased bacterial translocation across Ca(CO2) monolayers challenged with E. coli alone. Transepithelial passage of E. coli was significantly increased by coculture of bacteria with C. albicans. Augmentation of bacterial translocation by Candida occurred even in the presence of secretory immunoglobulin A. Candida colonization of the GI tract may impair mucosal barrier defense against gram-negative bacteria. The clinical role of gut antifungal prophylaxis in protecting against gut derived gram-negative sepsis is speculative.

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2.

PubMed

Ching, L Y; Yeung, Bonnie H Y; Wong, Chris K C

2012-06-01

Human stanniocalcin 1 (STC1) has recently been identified as a putative protein factor involved in cellular apoptosis. The use of histone deacetylase inhibitor (i.e. trichostatin A (TSA)) and doxorubicin (Dox) is one of the common treatment methods to induce apoptosis in human cancer cells. A study on TSA and Dox-mediated apoptosis may shed light on the regulation and function of STC1 in cancer treatment. In this study, TSA and Dox cotreatment in human nasopharyngeal carcinoma cells (CNE2) elicited synergistic effects on STC1 gene expression and cellular apoptosis. An activation of p53 (TP53) transcriptional activity in Dox- or Dox+TSA-treated cells was revealed by the increased expression levels of p53 mRNA/protein as well as p53-driven luciferase activities. To elucidate the possible involvement of p53 in STC1 gene transcription, a vector expressing wild-type or dominant negative (DN) p53 was transiently transfected into the cells. Both STC1 promoter luciferase constructs and chromatin immunoprecipitation assays did not support the direct role of p53 in STC1 gene transactivation. However, the synergistic effects of p53 on the induction of NF-κB phosphorylation and the recruitment of acetylated histone H3 in STC1 promoter were observed in TSA-cotreated cells. The overexpression of exogenous STC1 sensitized apoptosis in Dox-treated cells. Taken together, this study provides data to show the cross talk of NF-κB, p53, and histone protein in the regulation of STC1 expression and function.

Synergistic effect of pyrazoles derivatives and doxorubicin in claudin-low breast cancer subtype.

PubMed

Saueressig, Silvia; Tessmann, Josiane; Mastelari, Rosiane; da Silva, Liziane Pereira; Buss, Julieti; Segatto, Natalia Vieira; Begnini, Karine Rech; Pacheco, Bruna; de Pereira, Cláudio Martin Pereira; Collares, Tiago; Seixas, Fabiana Kömmling

2018-02-01

Breast cancer is a global public health problem. For some subtypes, such as Claudin-low, the prognosis is poorer and the treatment is still a challenge. Pyrazoles are an important class of heterocyclic compounds and are promising anticancer agents based on their chemical properties. The present study was aimed not only at testing pyrazoles previously prepared by our research group in two breast cancer cell lines characterized by intermediated response to conventional chemotherapy but also at analyzing the possible synergistic effect of these pyrazoles associated with doxorubicin. Four 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-1H pyrazoles were tested for the first time in MCF-7 and MDA-MB-231 culture cells. The pyrazoles with best results in cytotoxicity were used in combination with doxorubicin and compared with this drug alone as standard. The synergic effect was analyzed using Combination Index method. In addition, cell death and apoptosis assays were carried out. Two pyrazoles with cytotoxic effect in MCF-7 and especially in MDA-MB-231 were identified. This activity was markedly higher in pyrazoles containing bromine and chlorine substituents. The combination of these pyrazoles with doxorubicin had a significant synergic effect in both cells tested and mainly in MDA-MB-231. These data were confirmed with apoptosis and cell death analysis. The synergic effect observed with combination of these pyrazoles and doxorubicin deserves special attention in Claudin-low breast cancer subtype. This should be explored in order to improve treatment results and minimize side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Synergistic antitumor effect of 3-bromopyruvate and 5-fluorouracil against human colorectal cancer through cell cycle arrest and induction of apoptosis.

PubMed

Chong, Dianlong; Ma, Linyan; Liu, Fang; Zhang, Zhirui; Zhao, Surong; Huo, Qiang; Zhang, Pei; Zheng, Hailun; Liu, Hao

2017-09-01

3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest. Furthermore, there was an increase in reactive oxygen species levels and a decrease in adenosine triphosphate levels. It was also observed that Bax expression increased, whereas Bcl-2 expression reduced, which were indicative of mitochondria-dependent apoptosis. In addition, the combination of 3-BP and 5-FU significantly suppressed tumor growth in the BALB/c mice in vivo. Therefore, 3-BP inhibits tumor proliferation and induces S and G2/M phase arrest. It also exerts a synergistic antitumor effect with 5-FU on SW480 cells.

Synergistic Effects Induced by a Low Dose of Diesel Particulate Extract and Ultraviolet-A in Caenorhabditis elegans: DNA Damage-Triggered Germ Cell Apoptosis

PubMed Central

2015-01-01

Diesel exhaust has been classified as a potential carcinogen and is associated with various health effects. A previous study showed that the doses for manifesting the mutagenetic effects of diesel exhaust could be reduced when coexposed with ultraviolet-A (UVA) in a cellular system. However, the mechanisms underlying synergistic effects remain to be clarified, especially in an in vivo system. In the present study, using Caenorhabditis elegans (C. elegans) as an in vivo system we studied the synergistic effects of diesel particulate extract (DPE) plus UVA, and the underlying mechanisms were dissected genetically using related mutants. Our results demonstrated that though coexposure of wild type worms at young adult stage to low doses of DPE (20 μg/mL) plus UVA (0.2, 0.5, and 1.0 J/cm2) did not affect worm development (mitotic germ cells and brood size), it resulted in a significant induction of germ cell death. Using the strain of hus-1::gfp, distinct foci of HUS-1::GFP was observed in proliferating germ cells, indicating the DNA damage after worms were treated with DPE plus UVA. Moreover, the induction of germ cell death by DPE plus UVA was alleviated in single-gene loss-of-function mutations of core apoptotic, checkpoint HUS-1, CEP-1/p53, and MAPK dependent signaling pathways. Using a reactive oxygen species (ROS) probe, it was found that the production of ROS in worms coexposed to DPE plus UVA increased in a time-dependent manner. In addition, employing a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron spin resonance analysis, we demonstrated the increased 1O2 production in worms coexposed to DPE plus UVA. These results indicated that UVA could enhance the apoptotic induction of DPE at low doses through a DNA damage-triggered pathway and that the production of ROS, especially 1O2, played a pivotal role in initiating the synergistic process. PMID:24841043

Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

PubMed Central

García, Mónica Cristina; Ponce, Nicolás Eric; Sanmarco, Liliana Maria; Manzo, Rubén Hilario; Jimenez-Kairuz, Alvaro Federico

2016-01-01

Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-Trypanosoma cruzi effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ. In vitro studies, carried out using a checkerboard technique on trypomastigotes (T. cruzi strain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety. PMID:27067322

Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

PubMed Central

Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Konstantinos

2009-01-01

Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin-trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2•−) and hydroxyl (HO•) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis). Also, we observed synergistic effects in the generation of HO•, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM10, PM2.5 and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase. PMID:19440393

Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles.

PubMed

Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Konstantinos

2009-02-01

Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin-trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2 (*-)) and hydroxyl (HO(*)) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2'-deoxyguanosine (a biomarker for carcinogenesis). Also, we observed synergistic effects in the generation of HO(*), through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM(10), PM(2.5) and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM(2.5) and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and "bio-filters" with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase.

Saudi Arabias Implementation of Soft Power Policy to Confront Irans Obvious Threats

DTIC Science & Technology

2015-12-01

OBVIOUS THREATS Abdullah Khuliyf A. Alanazi Colonel, Saudi Arabia National Guard B.S., King Khalid Military College, 1993 Submitted in partial...inevitably growing power, particularly in the Persian Gulf, and throughout the Middle East. Such a situation advocates utilizing soft power as a new...www.educause.edu/ir/library/ pdf /ffpiu043. pdf , 34. 2 Giulio Gallarotti and Isam Yahia Al-Filali, “Saudi Arabia’s Soft Power.” International Studies 49

Synergistic antibacterial effect of silver and ebselen against multidrug-resistant Gram-negative bacterial infections.

PubMed

Zou, Lili; Lu, Jun; Wang, Jun; Ren, Xiaoyuan; Zhang, Lanlan; Gao, Yu; Rottenberg, Martin E; Holmgren, Arne

2017-08-01

Multidrug-resistant (MDR) Gram-negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult-to-treat MDR Gram-negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria. Silver ions were identified as strong inhibitors of Escherichia coli thioredoxin and thioredoxin reductase, which are required for ribonucleotide reductase and DNA synthesis and defense against oxidative stress. The bactericidal efficacy of silver and ebselen was further verified in the treatment of mild and acute MDR E. coli peritonitis in mice. These results demonstrate that thiol-dependent redox systems in bacteria can be targeted in the design of new antibacterial drugs. The silver and ebselen combination offers a proof of concept in targeting essential bacterial systems and might be developed for novel efficient treatments against MDR Gram-negative bacterial infections. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Synergistic interactions promote behavior spreading and alter phase transitions on multiplex networks

NASA Astrophysics Data System (ADS)

Liu, Quan-Hui; Wang, Wei; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng

2018-02-01

Synergistic interactions are ubiquitous in the real world. Recent studies have revealed that, for a single-layer network, synergy can enhance spreading and even induce an explosive contagion. There is at the present a growing interest in behavior spreading dynamics on multiplex networks. What is the role of synergistic interactions in behavior spreading in such networked systems? To address this question, we articulate a synergistic behavior spreading model on a double layer network, where the key manifestation of the synergistic interactions is that the adoption of one behavior by a node in one layer enhances its probability of adopting the behavior in the other layer. A general result is that synergistic interactions can greatly enhance the spreading of the behaviors in both layers. A remarkable phenomenon is that the interactions can alter the nature of the phase transition associated with behavior adoption or spreading dynamics. In particular, depending on the transmission rate of one behavior in a network layer, synergistic interactions can lead to a discontinuous (first-order) or a continuous (second-order) transition in the adoption scope of the other behavior with respect to its transmission rate. A surprising two-stage spreading process can arise: due to synergy, nodes having adopted one behavior in one layer adopt the other behavior in the other layer and then prompt the remaining nodes in this layer to quickly adopt the behavior. Analytically, we develop an edge-based compartmental theory and perform a bifurcation analysis to fully understand, in the weak synergistic interaction regime where the dynamical correlation between the network layers is negligible, the role of the interactions in promoting the social behavioral spreading dynamics in the whole system.

Synergistic cytotoxicity and mechanism of caffeine and lysozyme on hepatoma cell line HepG2

NASA Astrophysics Data System (ADS)

Yang, Hongchao; Li, Jingjuan; Cui, Lin; Ren, Yanqing; Niu, Liying; Wang, Xinguo; Huang, Yun; Cui, Lijian

2018-03-01

The influences of caffeine, lysozyme and the joint application of them on the hepatoma cell line HepG2 proliferation inhibition and cell apoptosis were observed by 3-(4, 5-dimethyl-2-thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide assay and Hoechst 33342, which showed the proliferation inhibition rate of the joint application on HepG2 cells was 47.21%, significantly higher than caffeine or lysozyme, and the joint application promoted the apoptosis of HepG2 cells obviously. Van't Hoff classical thermodynamics formula, the Föster theory of non-radiation energy transfer and fluorescence phase diagram were used to manifest that the process of lysozyme binding to caffeine followed a two-state model, which was spontaneous at low temperature driven by enthalpy change, and the predominant intermolecular force was hydrogen bonding or Van der Waals force to stabilize caffeine-lysozyme complex with the distance 5.86 nm. The attenuated total reflection-Fourier transform infrared spectra indicated that caffeine decreased the relative contents of α-helix and β-turn, which inferred the structure of lysozyme tended to be "loose". Synchronous fluorescence spectra and ultraviolet spectra supported the above conclusion. The amino acid residues in the cleft of lysozyme were exposed and electropositivity was increased attributing to the loose structure, which were conducive to increasing caffeine concentration on the HepG2 cell surface by electrostatic interaction to show synergistic effect. The great quantities of microvilli on the liver cancer cell membrane surface, is beneficial for the lysozyme-caffeine compound to aggregate on cell surface to increase the concentration of caffeine to play stronger physiological role by electrostatic effect.

Synergistic and Antagonistic Effects of Thermal Shock, Air Exposure, and Fishing Capture on the Physiological Stress of Squilla mantis (Stomatopoda)

PubMed Central

Raicevich, Saša; Minute, Fabrizio; Finoia, Maria Grazia; Caranfa, Francesca; Di Muro, Paolo; Scapolan, Lucia; Beltramini, Mariano

2014-01-01

This study is aimed at assessing the effects of multiple stressors (thermal shock, fishing capture, and exposure to air) on the benthic stomatopod Squilla mantis, a burrowing crustacean quite widespread in the Mediterranean Sea. Laboratory analyses were carried out to explore the physiological impairment onset over time, based on emersion and thermal shocks, on farmed individuals. Parallel field-based studies were carried out to also investigate the role of fishing (i.e., otter trawling) in inducing physiological imbalance in different seasonal conditions. The dynamics of physiological recovery from physiological disruption were also studied. Physiological stress was assessed by analysing hemolymph metabolites (L-Lactate, D-glucose, ammonia, and H+), as well as glycogen concentration in muscle tissues. The experiments were carried out according to a factorial scheme considering the three factors (thermal shock, fishing capture, and exposure to air) at two fixed levels in order to explore possible synergistic, additive, or antagonistic effects among factors. Additive effects on physiological parameters were mainly detected when the three factors interacted together while synergistic effects were found as effect of the combination of two factors. This finding highlights that the physiological adaptive and maladaptive processes induced by the stressors result in a dynamic response that may encounter physiological limits when high stress levels are sustained. Thus, a further increase in the physiological parameters due to synergies cannot be reached. Moreover, when critical limits are encountered, mortality occurs and physiological parameters reflect the response of the last survivors. In the light of our mortality studies, thermal shock and exposure to air have the main effect on the survival of S. mantis only on trawled individuals, while lab-farmed individuals did not show any mortality during exposure to air until after 2 hours. PMID:25133593

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner

PubMed Central

Dalecki, Alex G.; Haeili, Mehri; Shah, Santosh; Speer, Alexander; Niederweis, Michael; Kutsch, Olaf

2015-01-01

Tuberculosis is a severe disease affecting millions worldwide. Unfortunately, treatment strategies are hampered both by the prohibitively long treatment regimen and the rise of drug-resistant strains. Significant effort has been expended in the search for new treatments, but few options have successfully emerged, and new treatment modalities are desperately needed. Recently, there has been growing interest in the synergistic antibacterial effects of copper ions (CuII/I) in combination with certain small molecular compounds, and we have previously reported development of a drug screening strategy to harness the intrinsic bactericidal properties of CuII/I. Here, we describe the copper-dependent antimycobacterial properties of disulfiram, an FDA-approved and well-tolerated sobriety aid. Disulfiram was inhibitory to mycobacteria only in the presence of CuII/I and exerted its bactericidal activity well below the active concentration of CuII/I or disulfiram alone. No other physiologically relevant bivalent transition metals (e.g., FeII, NiII, MnII, and CoII) exhibited this effect. We demonstrate that the movement of the disulfiram-copper complex across the cell envelope is porin independent and can inhibit intracellular protein functions. Additionally, the complex is able to synergistically induce intracellular copper stress responses significantly more than CuII/I alone. Our data suggest that by complexing with disulfiram, CuII/I is likely allowed unfettered access to vulnerable intracellular components, bypassing the normally sufficient copper homeostatic machinery. Overall, the synergistic antibacterial activity of CuII/I and disulfiram reveals the susceptibility of the copper homeostasis system of Mycobacterium tuberculosis to chemical attacks and establishes compounds that act in concert with copper as a new class of bacterial inhibitors. PMID:26033731

Synergistic Response of Rifampicin with Hydroperoxides on Mycobacterium: A Mechanistic Study

PubMed Central

Patel, Yesha S.; Mehra, Sarika

2017-01-01

Prolonged chemotherapy as well as rapid development of antimicrobial resistance are two of the major concerns for treatment of mycobacterial infections. To enhance the effectiveness of current drug regimens, search for compounds having synergistic interaction with anti-mycobacterial drugs has become indispensable. Here, we have investigated the intervention by oxidative stress, a major factor in mycobacterial pathogenesis, in combination with rifampicin (RIF), a first-line drug used against Mycobacterium tuberculosis. We have observed that a sub-inhibitory concentration of cumene hydroperoxide (CHP), a hydrophobic oxidant, synergistically reduced the minimum inhibitory concentration of RIF by fourfold, with a Fractional Inhibitory Concentration Index (FICI) of 0.45. Also, this interaction was found to be robust and synergistic against different strains of M. smegmatis as well as on M. bovis BCG, with FICI ranging from 0.3 to 0.6. Various physiological, biochemical and molecular parameters were explored to understand the mechanism of synergy. It was observed that increased membrane permeability owing to the presence of the oxidant, led to higher uptake of the drug. Moreover, downregulation of the hydroperoxide reductases by RIF, a transcriptional inhibitor, prevented quenching of the reactive oxygen species produced in the presence of CHP. The lipid soluble reactive species triggered autocatalytic lipid peroxidation (LPO), observed here as extensive membrane damage eventually leading to growth inhibition. Furthermore, it was seen that in combination with hydrogen peroxide (H2O2), the effect was only additive, establishing LPO as a key aspect leading toward synergism. To conclude, this work suggests that targeting the bacterial membrane by a radical species can have a significant impact on the treatment of tuberculosis. PMID:29163385

In vitro anti-Acanthamoeba synergistic effect of chlorhexidine and cationic carbosilane dendrimers against both trophozoite and cyst forms.

PubMed

Heredero-Bermejo, I; Sánchez-Nieves, J; Soliveri, J; Gómez, R; de la Mata, F J; Copa-Patiño, J L; Pérez-Serrano, J

2016-07-25

Acanthamoeba sp. are the causative agents of severe illnesses in humans such as Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). Medical therapy is not yet well established. Treatments of AK last for several months and generate toxicity, resistances appear due to the cysts stage and recurrences can occur. In this study has been demonstrated that the combination of chlorhexidine digluconate (CLX) and carbosilane dendrimers containing ammonium or guanidine moieties has in vitro synergistic effect against Acanthamoeba polyphaga. This synergy provokes an important reduction in the minimal trophozoite amoebicidal concentration (MTAC) of CLX, which means a reduction of their toxic effects on human cells. Moreover, some CLX/dendrimer combinations show important activity against the cyst resistance stage. Copyright © 2016 Elsevier B.V. All rights reserved.

Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

DTIC Science & Technology

2012-10-01

W81XWH-10-2-0171 TITLE: Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Minocycline and N-acetylcysteine: a synergistic drug combination to treat traumatic brain injury 5a. CONTRACT NUMBER 5b...The grantee previously found screened that the combination of minocycline (MINO) and N-acetyl cysteine (NAC) synergistically improved brain function

The calcineruin inhibitor cyclosporine a synergistically enhances the susceptibility of Candida albicans biofilms to fluconazole by multiple mechanisms.

PubMed

Jia, Wei; Zhang, Haiyun; Li, Caiyun; Li, Gang; Liu, Xiaoming; Wei, Jun

2016-06-18

Biofilms produced by Candida albicans (C. albicans) are intrinsically resistant to fungicidal agents, which are a main cause of the pathogenesis of catheter infections. Several lines of evidence have demonstrated that calcineurin inhibitor FK506 or cyclosporine A (CsA) can remarkably enhance the antifungal activity of fluconazole (FLC) against biofilm-producing C. albicans strain infections. The aim of present study is thus to interrogate the mechanism underpinning the synergistic effect of FLC and calcineurin inhibitors. Twenty four clinical C. albicans strains isolated from bloodstream showed a distinct capacity of biofilm formation. A combination of calcineurin inhibitor CsA and FLC exhibited a dose-dependent synergistic antifungal effect on the growth and biofilm formation of C. albicans isolates as determined by a XTT assay and fluorescent microscopy assay. The synergistic effect was accompanied with a significantly down-regulated expression of adhesion-related genes ALS3, hypha-related genes HWP1, ABC transporter drug-resistant genes CDR1 and MDR1, and FLC targeting gene, encoding sterol 14alpha-demethylase (ERG11) in clinical C. albicans isolates. Furthermore, an addition of CsA significantly reduced the cellular surface hydrophobicity but increased intracellular calcium concentration as determined by a flow cytometry assay (p < 0.05). The results presented in this report demonstrated that the synergistic effect of CsA and FLC on inhibited C. albicans biofilm formation and enhanced susceptibility to FLC was in part through a mechanism involved in suppressing the expression of biofilm related and drug-resistant genes, and reducing cellular surface hydrophobicity, as well as evoking intracellular calcium concentration.

Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy

NASA Astrophysics Data System (ADS)

You, Yufeng; Wang, Zhigang; Ran, Haitao; Zheng, Yuanyi; Wang, Dong; Xu, Jinshun; Wang, Zhibiao; Chen, Yu; Li, Pan

2016-02-01

High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.

Design of Pd/PANI/Pd sandwich-structured nanotube array catalysts with special shape effects and synergistic effects for ethanol electrooxidation.

PubMed

Wang, An-Liang; Xu, Han; Feng, Jin-Xian; Ding, Liang-Xin; Tong, Ye-Xiang; Li, Gao-Ren

2013-07-24

Low cost, high activity, and long-term durability are the main requirements for commercializing fuel cell electrocatalysts. Despite tremendous efforts, developing non-Pt anode electrocatalysts with high activity and long-term durability at low cost remains a significant technical challenge. Here we report a new type of hybrid Pd/PANI/Pd sandwich-structured nanotube array (SNTA) to exploit shape effects and synergistic effects of Pd-PANI composites for the oxidation of small organic molecules for direct alcohol fuel cells. These synthesized Pd/PANI/Pd SNTAs exhibit significantly improved electrocatalytic activity and durability compared with Pd NTAs and commercial Pd/C catalysts. The unique SNTAs provide fast transport and short diffusion paths for electroactive species and high utilization rate of catalysts. Besides the merits of nanotube arrays, the improved electrocatalytic activity and durability are especially attributed to the special Pd/PANI/Pd sandwich-like nanostructures, which results in electron delocalization between Pd d orbitals and PANI π-conjugated ligands and in electron transfer from Pd to PANI.

Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia.

PubMed

Huang, Congwu; Cen, Chuan; Wang, ChengXu; Zhan, Haiyong; Ding, Xin

2014-04-17

Inflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown. Hyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed. Before the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin. Colchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Xue, Jingzhe; Luo, Zhihui; Li, Ping; Ding, Yaping; Cui, Yi; Wu, Qingsheng

2014-07-01

Here we reported a residue-free green nanotechnology which synergistically enhance the pesticides efficiency and successively eliminate its residue. We built up a composite antifungal system by a simple pre-treating and assembling procedure for investigating synergy. Investigations showed 0.25 g/L ZnO nanoparticles (NPs) with 0.01 g/L thiram could inhibit the fungal growth in a synergistic mode. More importantly, the 0.25 g/L ZnO NPs completely degraded 0.01 g/L thiram under simulated sunlight irradiation within 6 hours. It was demonstrated that the formation of ZnO-thiram antifungal system, electrostatic adsorption of ZnO NPs to fungi cells and the cellular internalization of ZnO-thiram composites played important roles in synergy. Oxidative stress test indicated ZnO-induced oxidative damage was enhanced by thiram that finally result in synergistic antifungal effect. By reducing the pesticides usage, this nanotechnology could control the plant disease economically, more significantly, the following photocatalytic degradation of pesticide greatly benefit the human social by avoiding negative influence of pesticide residue on public health and environment.

Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid

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

Eitsuka, Takahiro, E-mail: eitsuka@nupals.ac.jp; Tatewaki, Naoto; Nishida, Hiroshi

2014-10-24

Highlights: • δ-Tocotrienol (δ-T3) and ferulic acid (FA) synergistically inhibit cancer cell growth. • The combination of δ-T3 and FA induces G1 arrest by up-regulating p21. • The synergy is attributed to an increase in the cellular concentration of δ-T3 by FA. - Abstract: Rice bran consists of many functional compounds and thus much attention has been focused on the health benefits of its components. Here, we investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1more » (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. Our results suggest that the combination of δ-T3 and FA may present a new strategy for cancer prevention and therapy.« less

Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

PubMed Central

Huang, Suning; Rong, Minhua; Dang, Yiwu

2014-01-01

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC. PMID:24895573

Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.

PubMed

Huang, Suning; He, Rongquan; Rong, Minhua; Dang, Yiwu; Chen, Gang

2014-01-01

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

Effect of Eugenol against Streptococcus agalactiae and Synergistic Interaction with Biologically Produced Silver Nanoparticles

PubMed Central

Perugini Biasi-Garbin, Renata; Saori Otaguiri, Eliane; Fernandes da Silva, Mayara; Belotto Morguette, Ana Elisa; Armando Contreras Lancheros, César; Kian, Danielle; Perugini, Márcia Regina Eches; Durán, Nelson; Nakamura, Celso Vataru; Yamauchi, Lucy Megumi; Yamada-Ogatta, Sueli Fumie

2015-01-01

Streptococcus agalactiae (group B streptococci (GBS)) is an important infections agent in newborns associated with maternal vaginal colonization. Intrapartum antibiotic prophylaxis in GBS-colonized pregnant women has led to a significant reduction in the incidence of early neonatal infection in various geographic regions. However, this strategy may lead to resistance selecting among GBS, indicating the need for new alternatives to prevent bacterial transmission and even to treat GBS infections. This study reported for the first time the effect of eugenol on GBS isolated from colonized women, alone and in combination with silver nanoparticles produced by Fusarium oxysporum (AgNPbio). Eugenol showed a bactericidal effect against planktonic cells of all GBS strains, and this effect appeared to be time-dependent as judged by the time-kill curves and viability analysis. Combination of eugenol with AgNPbio resulted in a strong synergistic activity, significantly reducing the minimum inhibitory concentration values of both compounds. Scanning and transmission electron microscopy revealed fragmented cells and changes in bacterial morphology after incubation with eugenol. In addition, eugenol inhibited the viability of sessile cells during biofilm formation and in mature biofilms. These results indicate the potential of eugenol as an alternative for controlling GBS infections. PMID:25945115

Synergistic operation of photocatalytic degradation and Fenton process by magnetic Fe3O4 loaded TiO2

NASA Astrophysics Data System (ADS)

Sun, Qiong; Hong, Yong; Liu, Qiuhong; Dong, Lifeng

2018-02-01

The magnetic Fe3O4 loaded anatase TiO2 photocatalysts with different mass ratios were successfully synthesized by a one-step convenient calcining method. The morphology and structure analysis revealed that Fe3O4 was formed in TiO2 with very fine-grained particles. After a small amount of Fe3O4 loaded onto TiO2, the photocatalytic property enhanced obviously for the degradation of organic dye. Furthermore, the photo-Fenton-like catalysis of the iron-containing samples could also be induced after the addition of hydrogen peroxide. The apparent kinetic constant of the reaction that catalyzed by Fe-TiO2 was about 5.3 and 8.3 times of that catalyzed by TiO2 or Fe3O4 only, respectively, proving an effective synergistic contribution of the photocatalysis and Fenton reaction in the composite. Compared with Fe3O4 or free Fe3+ ions, only 13% of iron in TiO2 dissolved into acidic solution (25% for Fe3O4 and 100% for Fe3+) after the reaction, which confirmed the iron had been well immobilized onto TiO2. In addition, the extremely stable photocatalytic activity in cycling experiments proved the immobilized iron had been tightly attached onto TiO2, indicating the great potential of the catalyst for practical applications.

Synergistic Effects of Apigenin and Paclitaxel on Apoptosis of Cancer Cells

PubMed Central

Diao, Ying; Lu, Changyan; Fu, Jin; Luo, Lan; Yin, Zhimin

2011-01-01

Background It was well known that the clinical use of chemotherapeutic drugs is restricted by severe adverse reactions and drug resistances. Thus it is necessary to figure out a strategy to increase the specific anti-tumor efficiency of chemotherapeutic drugs. Apigenin, a kind of flavonoids, has been reported to possess anticancer activities with very low cytotoxicity to normal tissue. Methodology/Principal Findings Our results from cell viability assay, western-blots and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay demonstrated the synergistic pro-apoptotic effects of a low dose of apigenin and paclitaxel in human cancer cell lines. To analyze the underlying mechanism, we examined reactive oxygen species (ROS) staining after cells were treated with a combination of apigenin and paclitaxel, or each of them alone. Data from flow-cytometry showed that superoxides but not reduction of peroxides accumulated in HeLa cells treated with apigenin or a combination of apigenin and paclitaxel. Apigenin and paclitaxel-induced HeLa cell apoptosis was related to the level of ROS in cells. We further evaluated activity and protein level of superoxide dismutase (SOD). Apigenin significantly inhibited SOD activity but did not alter the SOD protein level suggesting that apigenin promoted ROS accumulation through suppressing enzyme activity of SOD. Addition of Zn2+, Cu2+ and Mn2+ to cell lysates inhibited apigenin's effects on SOD activity. At the same time, data from caspase-2 over-expression and knocked-down experiments demonstrated that caspase-2 participated in apigenin and paclitaxel-induced HeLa cell apoptosis. Conclusions/Significance Taken together, our study demonstrated that apigenin can sensitize cancer cells to paclitaxel induced apoptosis through suppressing SOD activity, which then led to accumulation of ROS and cleavage of caspase-2, suggesting that the combined use of apigenin and paclitaxel was an effective way to decrease the dose of paclitaxel taken

Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2.

PubMed

Kitagawa, Junichi; Hara, Takeshi; Tsurumi, Hisashi; Ninomiya, Soranobu; Ogawa, Kengo; Adachi, Seiji; Kanemura, Nobuhiro; Kasahara, Senji; Shimizu, Masahito; Moriwaki, Hisataka

2011-05-01

The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K(2) (VK(2)) in HL-60 cells. We used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V-binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies. ACR and VK(2) dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK(2) inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK(2) cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination. The synergistic effects of ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia.

Synergistic effect of graphene oxide on the methanol oxidation for fuel cell application

NASA Astrophysics Data System (ADS)

Siwal, Samarjeet; Ghosh, Sarit; Nandi, Debkumar; Devi, Nishu; Perla, Venkata K.; Barik, Rasmita; Mallick, Kaushik

2017-09-01

Aromatic polypyrene was synthesized by the oxidative polymerization of pyrene with potassium tetrachloropalladate (II), as oxidant. During the polymerization process the palladium salt was reduced to metallic palladium and forms the metal-polymer composite material. Polypyrene stabilized palladium nanoparticles showed electrocatalytic activity toward the oxidation of methanol. The performance of the electrocatalytic activity was substantially improved with the incorporation of graphene oxide to the palladium-polypyrene composite and the synergistic performance was attributed to the electronic and structural properties of the system.

Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor.

PubMed

Lim, Taekyu; Lee, Inkyoung; Kim, Jungmin; Kang, Won Ki

2015-10-01

We investigated the synergistic effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on the proliferation and survival of gastric cancer (GC) and colorectal cancer (CRC) cells. We also studied several genes involved in the simvastatin/radiation-induced effects. Gastric cancer (AGS, SNU601, MKN1, and MKN28) and CRC (CoLo320, SW48, HT29, and HCT8) cell lines were treated with 0.2 μM simvastatin alone, or in combination with 0 to 4 Gy of radiation, and subjected to clonogenic survival and proliferation assays in vitro. To assess the molecular mechanism of the combination treatment, we performed microarray analysis, immunoblot assays, small interfering RNA knockdown experiments, and plasmid rescue assays. The antitumoral effects of simvastatin and radiation were evaluated in vivo using xenograft models. The combination therapy of simvastatin plus radiation inhibited basal clonogenic survival and proliferation of GC and CRC cells in vitro. Simvastatin suppressed the expression of BIRC5 and CTGF genes in these cancer cells. In vivo, the combined treatment with simvastatin and radiation significantly reduced the growth of xenograft tumors compared with treatment with radiation alone. We suggest that simvastatin has a synergistic effect with radiation on GC and CRC through the induction of apoptosis, which may be mediated by a simultaneous inhibition of BIRC5 and CTGF expression. A clinical trial of simvastatin in combination with radiation in patients with GC or CRC is warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor

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

Lim, Taekyu; Lee, Inkyoung; Kim, Jungmin

Purpose: We investigated the synergistic effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on the proliferation and survival of gastric cancer (GC) and colorectal cancer (CRC) cells. We also studied several genes involved in the simvastatin/radiation-induced effects. Methods and Materials: Gastric cancer (AGS, SNU601, MKN1, and MKN28) and CRC (CoLo320, SW48, HT29, and HCT8) cell lines were treated with 0.2 μM simvastatin alone, or in combination with 0 to 4 Gy of radiation, and subjected to clonogenic survival and proliferation assays in vitro. To assess the molecular mechanism of the combination treatment, we performed microarray analysis, immunoblot assays, small interferingmore » RNA knockdown experiments, and plasmid rescue assays. The antitumoral effects of simvastatin and radiation were evaluated in vivo using xenograft models. Results: The combination therapy of simvastatin plus radiation inhibited basal clonogenic survival and proliferation of GC and CRC cells in vitro. Simvastatin suppressed the expression of BIRC5 and CTGF genes in these cancer cells. In vivo, the combined treatment with simvastatin and radiation significantly reduced the growth of xenograft tumors compared with treatment with radiation alone. Conclusion: We suggest that simvastatin has a synergistic effect with radiation on GC and CRC through the induction of apoptosis, which may be mediated by a simultaneous inhibition of BIRC5 and CTGF expression. A clinical trial of simvastatin in combination with radiation in patients with GC or CRC is warranted.« less

Synergistic protective effect of N-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats.

PubMed

Abdel-Wahab, Wessam M; Moussa, Farouzia I; Saad, Najwa A

2017-01-01

Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N -acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group. Cisplatin was administered as a single intraperitoneal injection at a concentration of 6 mg/kg. Three days after CDDP administration, NAC (50 mg/kg) and/or TAU (50 mg/kg) were administered three times weekly for four consecutive weeks. Kidney function markers in serum, urinary glucose and protein, as well as oxidant and antioxidant parameters in renal tissue were assessed. Administration of CDDP significantly elevated urinary glucose and protein, as well as serum creatinine, urea, and uric acid. Moreover, CDDP enhanced lipid peroxidation and suppressed the major enzymatic antioxidants in the kidney tissue. Treatment with NAC or TAU protected against the alterations in the serum, urine, and renal tissue when used individually along with CDDP. Furthermore, a combined therapy of both was more effective in ameliorating CDDP-induced nephrotoxicity, which points out to their synergistic effect.

Synergistic integration of sonochemical and electrochemical disinfection with DSA anodes.

PubMed

Cotillas, Salvador; Llanos, Javier; Castro-Ríos, Katherin; Taborda-Ocampo, Gonzalo; Rodrigo, Manuel A; Cañizares, Pablo

2016-11-01

This work focuses on the disinfection actual urban wastewater by the combination of ultrasound (US) irradiation and electrodisinfection with Dimensionally Stable Anodes (DSA). First, the inactivation of Escherichia coli (E. coli) during the sonochemical disinfection was studied at increasing ultrasound power. Results showed that it was not possible to achieve a complete disinfection, even at the highest US power (200 W) dosed by the experimental device used. Next, the electrodisinfection with DSA anodes at different current densities was studied, finding that it was necessary a minimum current density of 11.46 A m(-2) to reach the complete disinfection. Finally, an integrated sonoelectrodisinfection process was studied. Results showed a synergistic effect when coupling US irradiation with DSA electrodisinfection, with a synergy coefficient higher than 200% of the disinfection rate attained for the highest US power applied. In this process, hypochlorite and chloramines were identified as the main reagents for the disinfection process (neither chlorate nor perchlorate were detected), and the presence of trihalomethanes was far below acceptable values. Confirming this synergistic effect with DSA anodes opens the door to novel efficient disinfection processes, limiting the occurrence of hazardous disinfection by-products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergistic Enhancement of Microwave Absorption Using Hybridized Polyaniline@helical CNTs with Dual Chirality.

PubMed

Tian, Xin; Meng, Fanbin; Meng, Fanchen; Chen, Xiangnan; Guo, Yifan; Wang, Ying; Zhu, Wenjun; Zhou, Zuowan

2017-05-10

In this study, we designed a dual-chirality hierarchical structure to achieve a synergistically enhanced effect in microwave absorption via the hybridization of nanomaterials. Herein, polyaniline (PANi) nanorods with tunable chirality are grown on helical carbon nanotubes (HCNTs), a typical nanoscale chiral structure, through in situ polymerization. The experimental results show that the hierarchical hybrids (PANi@HCNTs) exhibit distinctly dual chirality and a significant enhancement in electromagnetic (EM) losses compared to those of either pure PANi or HCNTs. The maximum reflection loss of the as-prepared hybrids can reach -32.5 dB at 8.9 GHz. Further analysis demonstrates that combinations of chiral acid-doped PANi and coiled HCNTs with molecular and nanoscale chirality lead to synergistic effects resulting from the dual chirality. The so-called cross-polarization may result in additional interactions with induced EM waves in addition to multiscaled relaxations from functional groups and interfacial polarizations, which can benefit EM absorption.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

PubMed

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance

PubMed Central

Lewis, Adam J.; Mulvey, Matthew A.

2017-01-01

Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

Synergistic Effects on the Elderly People's Motor Control by Wearable Skin-Stretch Device Combined with Haptic Joystick

PubMed Central

Yoon, Han U.; Anil Kumar, Namita; Hur, Pilwon

2017-01-01

Cutaneous sensory feedback can be used to provide additional sensory cues to a person performing a motor task where vision is a dominant feedback signal. A haptic joystick has been widely used to guide a user by providing force feedback. However, the benefit of providing force feedback is still debatable due to performance dependency on factors such as the user's skill-level, task difficulty. Meanwhile, recent studies have shown the feasibility of improving a motor task performance by providing skin-stretch feedback. Therefore, a combination of two aforementioned feedback types is deemed to be promising to promote synergistic effects to consistently improve the person's motor performance. In this study, we aimed at identifying the effect of the combined haptic and skin-stretch feedbacks on the aged person's driving motor performance. For the experiment, 15 healthy elderly subjects (age 72.8 ± 6.6 years) were recruited and were instructed to drive a virtual power-wheelchair through four different courses with obstacles. Four augmented sensory feedback conditions were tested: no feedback, force feedback, skin-stretch feedback, and a combination of both force and skin-stretch feedbacks. While the haptic force was provided to the hand by the joystick, the skin-stretch was provided to the steering forearm by a custom-designed wearable skin-stretch device. We tested two hypotheses: (i) an elderly individual's motor control would benefit from receiving information about a desired trajectory from multiple sensory feedback sources, and (ii) the benefit does not depend on task difficulty. Various metrics related to skills and safety were used to evaluate the control performance. Repeated measure ANOVA was performed for those metrics with two factors: task scenario and the type of the augmented sensory feedback. The results revealed that elderly subjects' control performance significantly improved when the combined feedback of both haptic force and skin-stretch feedback was

Durability and synergistic effects of KI on the acid corrosion inhibition of mild steel by hydroxypropyl methylcellulose.

PubMed

Arukalam, I O

2014-11-04

The performance of hydroxypropyl methylcellulose (HPMC) as safe corrosion inhibitor for mild steel in aerated 0.5M H2SO4 solution was appraised by weight loss, impedance and polarization measurements. Results indicate that HPMC functions as a good inhibitor in the studied environment and inhibition efficiency increased with increasing concentration of inhibitor and temperature. Time-dependent effect of the inhibition efficiency reveals that inhibition efficiency increased with time up to the fourth day after which it waned, but improved on addition of KI. The synergism parameter evaluated confirmed the synergistic effect of KI and HPMC. Impedance results clearly show that HPMC inhibited the corrosion reaction via adsorption onto the metal/solution interface following Freundlich adsorption isotherm. Polarization results indicate that HPMC acts as a mixed-type inhibitor with predominant cathodic effect. Theoretical study using density functional theory was employed to establish the correlation between the structure (molecular and electronic) and the inhibition efficiency. Copyright © 2014. Published by Elsevier Ltd.

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

PubMed Central

Liu, Yan; Zhang, Pengcheng; Li, Feifei; Jin, Xiaodong; Li, Jin; Chen, Weiqiang; Li, Qiang

2018-01-01

Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed. PMID:29556359

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

PubMed

Nimrod, A

1977-09-01

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.

Synergistic activity of phenazines isolated from Pseudomonas aeruginosa in combination with azoles against Candida species.

PubMed

Nishanth Kumar, S; Nisha, G V; Sudaresan, A; Venugopal, V V; Sree Kumar, M M; Lankalapalli, Ravi S; Dileep Kumar, B S

2014-07-01

Candidiasis infections are caused by yeasts from the genus Candida. The types of infection range from superficial to systemic. Treatment often requires antifungals such as the azoles; however, increased use of these drugs has led to the generation of yeasts with increased resistance to these drugs. Here, we describe the synergistic anticandidal activity of three phenazines-phenazine-1-ol, phenazine-1-carboxylic acid, and phenazine-1-carboxamide. These phenazines were purified from Pseudomonas aeruginosa in combination with three clinically used azoles-fluconazole, itraconazole, and clotrimazole. The synergistic anticandidal activities of phenazines and azoles were assessed using the checkerboard microdilution and time-kill methods. Study results show that the combined effects of phenazines and azoles were predominantly synergistic activity (fractional inhibitory concentration index <0.5). The time-kill study, which included a combination of the minimum inhibitory concentration of phenazines and azoles, showed growth of Candida species that was completely attenuated after 0-6 h of treatment. These results, which suggest that the activity of phenazines and azoles may be beneficial, have potential implications in delaying the development of resistance, as the anticandidal effect is achieved with lower concentrations of both agents (phenazines and azoles). The cytotoxicity of phenazines was also tested against a normal human cell line (foreskin normal fibroblast). No cytotoxicity was recorded at concentrations up to 200 μg/ml. The in vitro synergistic activity of phenazines and azoles against Candida species is reported here for the first time. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

PubMed

Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2016-12-13

Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

Gallium and silicon synergistically promote osseointegration of dental implant in patients with osteoporosis.

PubMed

Liu, Jinsong; Wu, Zuosu; He, Hongli; Cai, Kaiyong; Zhang, Hualin; Xu, Lihua

2017-06-01

Over the last few decades, a wide variety of dental implants have been successfully placed in jaw bones to restore tooth function. But major challenges still remain in patients with osteoporosis involving compromised osseointegration, and the therapeutic methods is far from optimism. Gallium can directly inhibit bone osteolysis, prevent bone calcium release and augment bone mass, which makes Ga unique among the potential antiresorptive drugs. Silicon, as an indispensable modulator in bone formation, presents its bone anabolic effects, while reduces, at least doesn't increase, bone resorption. We hypothesize that the combination of bone anabolic effects of Si and antiresorptive effects of Ga will result in synergistic effects on the improvement of osteointegration under osteoporotic condition. In our strategy, in order to maximize the efficacy while minimize the side effects of ions, a novel titania mesoporous layer fabricated by electrochemical anodization on the surface of titanium implant will be employed as a promising local drug delivery system. The synergistic effects of Ga and Si on improving osseointegration will be verified by animal experiments, and be furthered by clinical trials. Our hypothesis could help to create an option to improve success rate of dental implants in osteoporotic patients. Copyright © 2017. Published by Elsevier Ltd.

Role of oxidants in DNA damage. Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke.

PubMed Central

Jackson, J H; Schraufstatter, I U; Hyslop, P A; Vosbeck, K; Sauerheber, R; Weitzman, S A; Cochrane, C G

1987-01-01

The mechanism by which cigarette smoking and asbestos exposure synergistically increase the incidence of lung cancer is unknown. We hypothesized that cigarette smoke and asbestos might synergistically increase DNA damage. To test this hypothesis we exposed isolated bacteriophage PM2 DNA to cigarette smoke and/or asbestos, and assessed DNA strand breaks as an index of DNA damage. Our results supported our hypothesis. 78 +/- 12% of the DNA exposed to both cigarette smoke and asbestos developed strand breaks, while only 9.8 +/- 7.0 or 4.3 +/- 3.3% of the DNA exposed to cigarette smoke or asbestos, respectively, developed strand breaks under the conditions of the experiment. Our experimental evidence suggested that cigarette smoke and asbestos synergistically increased DNA damage by stimulating .OH formation. First, significant amounts of .OH were detected by electron paramagnetic resonance (EPR) in DNA mixtures containing both cigarette smoke and asbestos, but no .OH was detected in mixtures containing cigarette smoke alone or asbestos alone. Second, the .OH scavengers, dimethylsulfoxide (DMSO), mannitol, or Na benzoate decreased both .OH detection by EPR and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. Third, the H2O2 scavenger, catalase, and the iron chelators, 1,10-phenanthroline and desferrithiocin, decreased both .OH detection and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos. These latter findings suggest that iron contained in asbestos may catalyze the formation of .OH from H2O2 generated by cigarette smoke. In summary, our study indicates that cigarette smoke and asbestos synergistically increase DNA damage and suggests that this synergism may involve .OH production. PMID:2821073

Co-gasification of bituminous coal and hydrochar derived from municipal solid waste: Reactivity and synergy.

PubMed

Wei, Juntao; Guo, Qinghua; He, Qing; Ding, Lu; Yoshikawa, Kunio; Yu, Guangsuo

2017-09-01

In this work, the influences of gasification temperature and blended ratio on co-gasification reactivity and synergy of Shenfu bituminous coal (SF) and municipal solid waste-derived hydrochar (HTC) were investigated using TGA. Additionally, active alkaline and alkaline earth metal (AAEM) transformation during co-gasification was quantitatively analyzed by inductively coupled plasma optical emission spectrometer for correlating synergy on co-gasification reactivity. The results showed that higher char gasification reactivity existed at higher HTC char proportion and gasification temperature, and the main synergy behaviour on co-gasification reactivity was performed as synergistic effect. Enhanced synergistic effect at lower temperature was mainly resulted from more obviously inhibiting the primary AAEM (i.e. active Ca) transformation, and weak synergistic effect still existed at higher temperature since more active K with prominent catalysis was retained. Furthermore, more active HTC-derived AAEM remaining in SF sample during co-gasification would lead to enhanced synergistic effect as HTC char proportion increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characteristics and synergistic effects of co-combustion of carbonaceous wastes with coal.

PubMed

Onenc, Sermin; Retschitzegger, Stefan; Evic, Nikola; Kienzl, Norbert; Yanik, Jale

2018-01-01

This study presents combustion behavior and emission results obtained for different fuels: poultry litter (PL) and its char (PLC), scrap tires (ST) and its char (STC) and blends of char/lignite (PLC/LIG and STC/LIG). The combustion parameters and emissions were investigated via a non-isothermal thermogravimetric method and experiments in a lab-scale reactor. Fuel indexes were used for the prediction of high temperature corrosion risks and slagging potentials of the fuels used. The addition of chars to lignite caused a lowering of the combustion reactivity (anti-synergistic effect). There was a linear correlation between the NO x emissions and the N content of the fuel. The form of S and the concentrations of alkali metals in the fuel had a strong effect on the extent of SO 2 emissions. The use of PL and PLC in blends reduced SO 2 emissions and sulphur compounds in the fly ash. The 2S/Cl ratio in the fuel showed that only PLC and STC/PLC would show a risk of corrosion during combustion. The ratio of basic to acidic oxides in fuel indicated that ST, STC and STC/LIG have low slagging potential. The molar (Si+P+K)/(Ca+Mg) ratio, which was used for PL, PLC and PLC containing blends, showed that the ash melting temperatures of these fuels would be higher than 1000 °C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Staurosporine synergistically potentiates the deoxycholate-mediated induction of COX-2 expression.

PubMed

Saeki, Tohru; Inui, Haruka; Fujioka, Saya; Fukuda, Suguru; Nomura, Ayumi; Nakamura, Yasushi; Park, Eun Young; Sato, Kenji; Kanamoto, Ryuhei

2014-08-01

Colorectal cancer is a major cause of cancer-related death in western countries, and thus there is an urgent need to elucidate the mechanism of colorectal tumorigenesis. A diet that is rich in fat increases the risk of colorectal tumorigenesis. Bile acids, which are secreted in response to the ingestion of fat, have been shown to increase the risk of colorectal tumors. The expression of cyclooxygenase (COX)-2, an inducible isozyme of cyclooxygenase, is induced by bile acids and correlates with the incidence and progression of cancers. In this study, we investigated the signal transduction pathways involved in the bile-acid-mediated induction of COX-2 expression. We found that staurosporine (sts), a potent protein kinase C (PKC) inhibitor, synergistically potentiated the deoxycholate-mediated induction of COX-2 expression. Sts did not increase the stabilization of COX-2 mRNA. The sts- and deoxycholate-mediated synergistic induction of COX-2 expression was suppressed by a membrane-permeable Ca(2+) chelator, a phosphoinositide 3-kinase inhibitor, a nuclear factor-κB pathway inhibitor, and inhibitors of canonical and stress-inducible mitogen-activated protein kinase pathways. Inhibition was also observed using PKC inhibitors, suggesting the involvement of certain PKC isozymes (η, θ, ι, ζ, or μ). Our results indicate that sts exerts its potentiating effects via the phosphorylation of p38. However, the effects of anisomycin did not mimic those of sts, indicating that although p38 activation is required, it does not enhance deoxycholate-induced COX-2 expression. We conclude that staurosporine synergistically enhances deoxycholate-induced COX-2 expression in RCM-1 colon cancer cells. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

PubMed Central

Qi, Xin; Liu, Yang; Ding, Zhen-yu; Cao, Jia-qing; Huang, Jing-huan; Zhang, Jie-yuan; Jia, Wei-tao; Wang, Jing; Liu, Chang-sheng; Li, Xiao-lin

2017-01-01

In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration. PMID:28230059

Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

NASA Astrophysics Data System (ADS)

Qi, Xin; Liu, Yang; Ding, Zhen-Yu; Cao, Jia-Qing; Huang, Jing-Huan; Zhang, Jie-Yuan; Jia, Wei-Tao; Wang, Jing; Liu, Chang-Sheng; Li, Xiao-Lin

2017-02-01

In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration.

Synergistic combination of fluoro chalcone and doxorubicin on HeLa cervical cancer cells by inducing apoptosis

NASA Astrophysics Data System (ADS)

Arianingrum, Retno; Arty, Indyah Sulistyo; Atun, Sri

2017-03-01

Doxorubicin (Dox), a primary chemotherapeutic agent used for cancer treatment is known to have various side effect included multidrug resistance (MDR) phenomenon. Combination chemotherapy is one of some approaches to reduce Dox side effect. Chalcones have been reported to reduce the proliferation of many cancer cells. The research were conducted to investigate the cytotoxic activity and apoptosis induction of a chalcone derivate which is containing fluoro substituent [1 - (4" - fluorophenyl) -3 - (4' - hydroxy - 3' - methoxyphenyl) - 2 - propene - 1 -on] (FHM) and its combination with Dox on HeLa cells line. The observation of the cytotoxic activity was conducted using MTT [3 - (4, 5 - dimethyl thiazol - 2 - y1) - 2.5 - diphenyltetrazolium bromide] assay. Apoptosis induction was determined by flow cytometric. The changes of cell morphology were observed using phase contrast microscopy. The combination index (CI) was used to determine the effect of the combination. The study showed that FHM inhibited the HeLa cell growth with IC50 of 34 μM, while the IC50 of Dox was 1 μM. The combination had a higher inhibitory effect on cell growth compare to the single treatment of FHM and Dox. All of the combination doses under IC50 of FHM and Dox gave synergistic (CI: - 0.7) up to strong synergistic effect (CI: 0.l - 0.3). The synergistic effects of the combination were due to their ability to induce apoptosis in the HeLa cells. According to the result, FHM was potential to be developed as a co-chemotherapeutic agent with Dox for cervical cancer.

Quercetin and pioglitazone synergistically reverse endothelial dysfunction in isolated aorta from fructose-streptozotocin (F-STZ)-induced diabetic rats.

PubMed

Kunasegaran, Thubasni; Mustafa, Mohd Rais; Achike, Francis I; Murugan, Dharmani Devi

2017-03-15

Pioglitazone is an anti-diabetic drug with potential to cause adverse effects following prolonged use. This study, therefore, investigated the effects of combination treatment of a subliminal concentration of pioglitazone and quercetin, a potent antioxidant, on vascular reactivity of aorta isolated from fructose-streptozotocin (F-STZ)-induced diabetic rats. Relaxation to acetylcholine and sodium nitroprusside, and contraction to phenylephrine were tested in organ bath chambers following pre-incubation with vehicle (DMSO; 0.05%), quercetin (10-7 M), pioglitazone (10-7 M), or their combination (P+Q; 10-7 M each drug). Subliminal concentration of quercetin or pioglitazone did not alter the acetylcholine- induced relaxation nor the phenylephrine-induced contraction in both normal rat and diabetic F-STZ induced tissues. However, P+Q combination synergistically improved the impaired acetylcholine-induced relaxation and decreased the elevated phenylephrine-induced contraction in aortic rings from diabetic, but not in the normal rats. Neither mono nor combination treatment altered sodium nitroprusside-induced relaxation. The combination also synergistically decreased superoxide anion and increased nitric oxide production compared to the individual treatments in aorta from diabetic rats. Overall, these data demonstrated a synergistic effect, in which, a combination (P+Q; 10-7 M each drug) caused a significantly greater effect than 10-6 M of either agent in improving endothelial function of isolated diabetic aorta. In conclusion, a combination of subliminal concentrations of pioglitazone and quercetin is able to decrease oxidative stress and provide synergistic vascular protection in type 2 diabetes mellitus and thus the possibility of using quercetin as a supplement to pioglitazone in the treatment of diabetes with the goal of reducing pioglitazone toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic disinfection and removal of biofilms by a sequential two-step treatment with ozone followed by hydrogen peroxide.

PubMed

Tachikawa, Mariko; Yamanaka, Kenzo

2014-11-01

Synergistic disinfection and removal of biofilms by ozone (O3) water in combination with hydrogen peroxide (H2O2) solution was studied by determining disinfection rates and observing changes of the biofilm structure in situ by confocal laser scanning microscopy (CLSM) using an established biofilm of Pseudomonas fluorescence. The sequential treatment with O3, 1.0-1.7 mg/L, followed by H2O2, 0.8-1.1%, showed synergistic disinfection effects, while the reversed treatment, first H2O2 followed by O3, showed only an additive effect. The decrease of synergistic disinfection effect by addition of methanol (CH3OH), a scavenger of hydroxyl radical (OH), into the H2O2 solution suggested generation of hydroxyl radicals on or in the biofilm by the sequential treatment with O3 followed by H2O2. The primary treatment with O3 increased disinfection rates of H2O2 in the secondary treatment, and the increase of O3 concentration enhanced the rates. The cold temperature of O3 water (14 °C and 8 °C) increased the synergistic effect, suggesting the increase of O3 adsorption and hydroxyl radical generation in the biofilm. CLSM observation showed that the sequential treatment, first with O3 followed by H2O2, loosened the cell connections and thinned the extracellular polysaccharides (EPS) in the biofilm. The hydroxyl radical generation in the biofilm may affect the EPS and biofilm structure and may induce effective disinfection with H2O2. This sequential treatment method may suggest a new practical procedure for disinfection and removal of biofilms by inorganic oxidants such as O3 and H2O2. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synergistic mixtures for control of slime-forming bacteria and other delete rious micro-organisms and processes using same

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

Tant, C.O.; Turner, N.E.; Bennett, E.O.

1969-09-30

Microbiocide compositions are described having a synergistic biocide effect on microorganisms, such as slime- forming bateria and other microorganisms considered to be deleterious or troublesome in water and especially in waterflooding operations, such as are used in the secondary recovery of petroleum oil in subterranean formations. The synergistic compositions consist of paired or multiple combinations of at least one of each of (1) compounds having furan, dihydrofuran or tetrahydrofuran nuclei, and (2) compounds having phenol nuclei or chloroanilines. (17 claims)

In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

PubMed Central

Rochon-Edouard, Stéphanie; Pestel-Caron, Martine; Lemeland, Jean-François; Caron, François

2000-01-01

Several studies have previously reported synergistic effects between vancomycin and a given β-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a β-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different β-lactam–vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the β-lactam–vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and

Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

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

Kaini, Ramesh R.; Hu, Chien-An A., E-mail: AHu@salud.unm.edu

2012-08-24

Highlights: Black-Right-Pointing-Pointer Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. Black-Right-Pointing-Pointer Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. Black-Right-Pointing-Pointer Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. Black-Right-Pointing-Pointer Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showedmore » that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.« less

Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

PubMed

Pan, Zhi-Yuan; Wang, Hai

2014-05-01

The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014

Synergistic inhibition of Haemonchus contortus exsheathment by flavonoid monomers and condensed tannins

PubMed Central

Klongsiriwet, Chaweewan; Quijada, Jessica; Williams, Andrew R.; Mueller-Harvey, Irene; Williamson, Elizabeth M.; Hoste, Hervé

2015-01-01

This study investigated the separate and combined anthelmintic (AH) effects of different phenolic compounds, including condensed tannins and flavonoids, all of which are known to occur in willow leaves, a potentially valuable dry season feed. A range of contrasting model tannins, which span the whole range of willow tannins, were isolated from tilia flowers, goat willow leaves, black currant leaves and red currant leaves. All together, the tested compounds represented the major tannin types (procyanidins and prodelphinidins) and flavonoid types (flavonols, flavones and flavanones). The larval exsheathment inhibition assay (LEIA) was used to assess their in vitro effects on Haemonchus contortus third stage larvae. Arbutin, vanillic acid, and taxifolin proved to be ineffective whereas naringenin, quercetin and luteolin were highly effective at 250 μM concentrations. Procyanidin (PC) tannins tended to be less active than prodelphinidin tannins (PD). Experiments with combinations of tannins and quercetin or luteolin revealed for the first time the existence of synergistic AH effects between tannins and flavonoid monomers. They also provided evidence that synergistic effects appear to occur at slightly lower concentrations of PC than PD. This suggests that the AH activity of condensed tannins can be significantly enhanced by the addition of quercetin or luteolin. This information may prove useful for plant breeding or selection and for designing optimal feed mixtures. PMID:26199861

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery.

PubMed

Merath, Katiuscha; Chen, Qinyu; Bagante, Fabio; Akgul, Ozgur; Idrees, Jay J; Dillhoff, Mary; Cloyd, Jordan M; Pawlik, Timothy M

2018-06-18

Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7). Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Synergistic enzymatic and microbial lignin conversion

DOE PAGES

Zhao, Cheng; Xie, Shangxian; Pu, Yunqiao; ...

2015-10-02

We represent the utilization of lignin for fungible fuels and chemicals and it's one of the most imminent challenges in modern biorefineries. However, bioconversion of lignin is highly challenging due to its recalcitrant nature as a phenolic heteropolymer. This study addressed the challenges by revealing the chemical and biological mechanisms for synergistic lignin degradation by a bacterial and enzymatic system, which significantly improved lignin consumption, cell growth and lipid yield. The Rhodococcus opacus cell growth increased exponentially in response to the level of laccase treatment, indicating the synergy between laccase and bacterial cells in lignin degradation. Other treatments like ironmore » and hydrogen peroxide showed limited impact on cell growth. Chemical analysis of lignin under various treatments further confirmed the synergy between laccase and cells at the chemical level. 31P nuclear magnetic resonance (NMR) suggested that laccase, R. opacus cell and Fenton reaction reagents promoted the degradation of different types of lignin functional groups, elucidating the chemical basis for the synergistic effects. 31P NMR further revealed that laccase treatment had the most significant impact for degrading the abundant chemical groups. The results were further confirmed by the molecular weight analysis and lignin quantification by the Prussian blue assay. The cell–laccase fermentation led to a 17-fold increase of lipid production. Overall, the study indicated that laccase and R. opacus can synergize to degrade lignin efficiently, likely through rapid utilization of monomers generated by laccase to promote the reaction toward depolymerization. The study provided a potential path for more efficient lignin conversion and development of consolidated lignin conversion.« less

Synergistic enzymatic and microbial lignin conversion

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

Zhao, Cheng; Xie, Shangxian; Pu, Yunqiao

We represent the utilization of lignin for fungible fuels and chemicals and it's one of the most imminent challenges in modern biorefineries. However, bioconversion of lignin is highly challenging due to its recalcitrant nature as a phenolic heteropolymer. This study addressed the challenges by revealing the chemical and biological mechanisms for synergistic lignin degradation by a bacterial and enzymatic system, which significantly improved lignin consumption, cell growth and lipid yield. The Rhodococcus opacus cell growth increased exponentially in response to the level of laccase treatment, indicating the synergy between laccase and bacterial cells in lignin degradation. Other treatments like ironmore » and hydrogen peroxide showed limited impact on cell growth. Chemical analysis of lignin under various treatments further confirmed the synergy between laccase and cells at the chemical level. 31P nuclear magnetic resonance (NMR) suggested that laccase, R. opacus cell and Fenton reaction reagents promoted the degradation of different types of lignin functional groups, elucidating the chemical basis for the synergistic effects. 31P NMR further revealed that laccase treatment had the most significant impact for degrading the abundant chemical groups. The results were further confirmed by the molecular weight analysis and lignin quantification by the Prussian blue assay. The cell–laccase fermentation led to a 17-fold increase of lipid production. Overall, the study indicated that laccase and R. opacus can synergize to degrade lignin efficiently, likely through rapid utilization of monomers generated by laccase to promote the reaction toward depolymerization. The study provided a potential path for more efficient lignin conversion and development of consolidated lignin conversion.« less

Protease inhibitors from several classes work synergistically against Callosobruchus maculatus.

PubMed

Amirhusin, Bahagiawati; Shade, Richard E; Koiwa, Hisashi; Hasegawa, Paul M; Bressan, Ray A; Murdock, Larry L; Zhu-Salzman, Keyan

2007-07-01

Targeting multiple digestive proteases may be more effective in insect pest control than inhibition of a single enzyme class. We therefore explored possible interactions of three antimetabolic protease inhibitors fed to cowpea bruchids in artificial diets, using a recombinant soybean cysteine protease inhibitor scN, an aspartic protease inhibitor pepstatin A, and soybean Kunitz trypsin inhibitor KI. scN and pepstatin, inhibiting major digestive cysteine and aspartic proteases, respectively, significantly prolonged the developmental time of cowpea bruchids individually. When combined, the anti-insect effect was synergistic, i.e., the toxicity of the mixture was markedly greater than that of scN or pepstatin alone. KI alone did not impact insect development even at relatively high concentrations, but its anti-insect properties became apparent when acting jointly with scN or scN plus pepstatin. Incubating KI with bruchid midgut extract showed that it was partially degraded. This instability may explain its lack of anti-insect activity. However, this proteolytic degradation was inhibited by scN and/or pepstatin. Protection of KI from proteolysis in the insect digestive tract thus could be the basis for the synergistic effect. These observations support the concept that cowpea bruchid gut proteases play a dual role; digesting protein for nutrient needs and protecting insects by inactivating dietary proteins that may otherwise be toxic. Our results also suggest that transgenic resistance strategies that involve multigene products are likely to have enhanced efficacy and durability.

Bamboo-like 3C-SiC nanowires with periodical fluctuating diameter: Homogeneous synthesis, synergistic growth mechanism, and their luminescence properties

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

Zhang, Meng; Zhao, Jian; Li, Zhenjiang, E-mail: zhenjiangli@qust.edu.cn

Herein, bamboo-like 3C-SiC nanowires have been successfully fabricated on homogeneous 6H-SiC substrate by a simple chemical vapor reaction (CVR) approach. The obtained 3C-SiC nanostructure with periodical fluctuating diameter, is composed of two alternating structure units, the typical normal-sized stem segment with perfect crystallinity and obvious projecting nodes segment having high-density stacking faults. The formation of the interesting morphology is significantly subjected to the peculiar growth condition provided by the homogeneous substrate as well as the varying growth elastic energy. Furthermore, the photoluminescence (PL) performance measured on the bamboo-like SiC nanowire shows an intensive emission peaks centered at 451 nm andmore » 467 nm, which has been expected to make a positive progress toward the optical application of the SiC-based one-dimensional (1D) nanostructures, such as light emission diode (LED). - Graphical abstract: Based on the synergistic growth mechanism from homogeneous substrate and elastic energy, bamboo-like 3C-SiC nanowires with periodically fluctuating diameter have been synthesized on 6H-SiC. The blue-violet light emission properties of the bamboo-like nanowires have also been investigated for exploring their peculiar optical application. - Highlights: • Bamboo-like 3C-SiC nanowires with periodically fluctuating diameter have been synthesized on 6H-SiC. • A synergistic growth mechanism from homogeneous substrate and elastic energy has been proposed firstly. • The blue-violet light emission properties of the products displayed peculiar optical application.« less

Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice.

PubMed

Feng, Yuxu; Zhou, Min; Zhang, Qunhu; Liu, Huan; Xu, Yong; Shu, Lei; Zhang, Jue; Miao, Dengshun; Ren, Yongxin

2015-03-28

In the present study, we investigated whether high dietary Ca and exogenous parathyroid hormone 1-34 fragments (PTH 1-34) have synergistic effects on bone formation in adult mice, and explored the related mechanisms. Adult male mice were fed a normal diet, a high-Ca diet, a PTH-treated diet, or a high-Ca diet combined with subcutaneously injected PTH 1-34 (80 μg/kg per d) for 4 weeks. Bone mineral density, trabecular bone volume, osteoblast number, alkaline phosphatase (ALP)- and type I collagen-positive areas, and the expression levels of osteoblastic bone formation-related genes and proteins were increased significantly in mice fed the high-Ca diet, the PTH-treated diet, and, even more dramatically, the high-Ca diet combined with PTH. Osteoclast number and surface and the ratio of receptor activator for nuclear factor-κB ligand (RANKL):osteoprotegerin (OPG) were decreased in the high-Ca diet treatment group, increased in the PTH treatment group, but not in the combined treatment group. Furthermore, third-passage osteoblasts were treated with high Ca (5 mM), PTH 1-34 (10⁻⁸ M) or high Ca combined with PTH 1-34. Osteoblast viability and ALP activity were increased in either the high Ca-treated or PTH-treated cultures and, even more dramatically, in the cultures treated with high Ca plus PTH, with consistent up-regulation of the expression levels of osteoblast proliferation and differentiation-related genes and proteins. These results indicate that dietary Ca and PTH play synergistic roles in promoting osteoblastic bone formation by stimulating osteoblast proliferation and differentiation.

A residue-free green synergistic antifungal nanotechnology for pesticide thiram by ZnO nanoparticles

PubMed Central

Xue, Jingzhe; Luo, Zhihui; Li, Ping; Ding, Yaping; Cui, Yi; Wu, Qingsheng

2014-01-01

Here we reported a residue-free green nanotechnology which synergistically enhance the pesticides efficiency and successively eliminate its residue. We built up a composite antifungal system by a simple pre-treating and assembling procedure for investigating synergy. Investigations showed 0.25 g/L ZnO nanoparticles (NPs) with 0.01 g/L thiram could inhibit the fungal growth in a synergistic mode. More importantly, the 0.25 g/L ZnO NPs completely degraded 0.01 g/L thiram under simulated sunlight irradiation within 6 hours. It was demonstrated that the formation of ZnO-thiram antifungal system, electrostatic adsorption of ZnO NPs to fungi cells and the cellular internalization of ZnO-thiram composites played important roles in synergy. Oxidative stress test indicated ZnO-induced oxidative damage was enhanced by thiram that finally result in synergistic antifungal effect. By reducing the pesticides usage, this nanotechnology could control the plant disease economically, more significantly, the following photocatalytic degradation of pesticide greatly benefit the human social by avoiding negative influence of pesticide residue on public health and environment. PMID:25023938

Functionalized Lipid-Polymer Hybrid Nanoparticles Mediated Codelivery of Methotrexate and Aceclofenac: A Synergistic Effect in Breast Cancer with Improved Pharmacokinetics Attributes.

PubMed

Garg, Neeraj K; Tyagi, Rajeev K; Sharma, Gajanand; Jain, Ashay; Singh, Bhupinder; Jain, Sanyog; Katare, O P

2017-06-05

The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231). We obtained LPHNPs in the nanosize range (<150 nm) with better particle size distribution (<0.3). The entrapment and loading efficiency of MTX and ACL was calculated as 85-90% and 10-12%, respectively. The coumarin-6 LPHNP formulations showed rapid internalization within 2 h incubation with MCF-7 and MDA-MB-231 cells. With 8-10 times, greater bioavailability of drug-loaded LPHNPs than free MTX and ACL was obtained. Also, antitumor efficacy of MTX- and ACL-loaded LPHNPs was determined on DMBA-induced experimental breast cancer mouse model. This model showed better control over tumor growth with MTX- and ACL-loaded LPHNPs than the combination of MTX and ACL or MTX alone. ACL-loaded LPHNPs showed prophylactic and anticancer activity in DMBA-induced mouse model at higher dose (10 mg/kg). ACL-LPHNPs confer synergistic anticancer effect when administered in combination with MTX. In conclusion, ACL enhances the therapeutic and anticancer efficacy of MTX, when coencapsulated into fucose-anchored LPHNPs, as confirmed by cell viability and serum angiogenesis (IL-6, TNF-α, IL-1β, COX2, and MMP1) at both transcript and proteome level.

Quantifying the synergistic effect of the precipitation and land use on sandy desertification at county level: a case study in Naiman Banner, Northern China.

PubMed

Xiaodong, Ge; Jinren, Ni; Zhenshan, Li; Ronggui, Hu; Xin, Ming; Qing, Ye

2013-07-15

Assessing the driving forces of sandy desertification is fundamental and important for its control. It has been widely accepted that both climatic conditions and land use have great impact on sandy desertification in northern China. However, the relative role and synergistic effect of each driving force of sandy desertification are still not clear. In this paper, an indicator named as SI was defined to represent the integrated probability of sandy desertification caused by land use. A quantitative method was developed for characterizing the relative roles of annual precipitation and land use to sandy desertification in both spatial and temporal dimensions at county level. Results showed that, at county level, land use was the main cause of sandy desertification for Naiman Banner since 1987-2009. In the case of spatial dimension, the different combination of land use types decided the distribution of sandy desertification probability and finally decided the spatial pattern of bared sand land. In the case of temporal dimension, the synergistic effect of land use and precipitation highly influenced the spatial distribution of sandy desertification. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria.

PubMed

Kim, Ji-Hoon; Yu, Daeung; Eom, Sung-Hwan; Kim, Song-Hee; Oh, Junghwan; Jung, Won-Kyo; Kim, Young-Mog

2017-06-08

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes , Staphylococcus epidermidis , Staphylococcus aureus , and Pseudomonas aeruginosa . Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL). Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC) indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC) values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris.

SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

EPA Science Inventory

The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.

Didecyldimethylammonium chloride [DDAC] was...

Synergistic effect of acupuncture and mirror therapy on post-stroke upper limb dysfunction: a study protocol for a randomized controlled trial.

PubMed

Xu, Ying; Lin, Shufang; Jiang, Cai; Ye, Xiaoqian; Tao, Jing; Wilfried, Schupp; Wong, Alex W K; Chen, Lidian; Yang, Shanli

2018-05-31

Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Chinese Clinical Trial Registry: ChiCTR-IOR-17011118 . Registered on April 11, 2017. Version number: 01.2016.09.1.

Sequential Exposure of Bortezomib and Vorinostat is Synergistic in Multiple Myeloma Cells

PubMed Central

Nanavati, Charvi; Mager, Donald E.

2018-01-01

Purpose To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. Methods U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures. p21 and cleaved PARP were measured using immunoblotting to assess critical biomarker dynamics. For xenografts, data were extracted from literature and modeled with a PK/PD model with an interaction parameter. Results Estimated model parameters for simultaneous in vitro and xenograft treatments suggested additive drug effects. The sequence of bortezomib preincubation for 24 hours, followed by vorinostat for 24 hours, resulted in an estimated interaction term significantly less than 1, suggesting synergistic effects. p21 and cleaved PARP were also up-regulated the most in this sequence. Conclusions Semi-mechanistic pharmacodynamic modeling suggests synergistic pharmacodynamic interactions for the sequential administration of bortezomib followed by vorinostat. Increased p21 and cleaved PARP expression can potentially explain mechanisms of their enhanced effects, which require further PK/PD systems analysis to suggest an optimal dosing regimen. PMID:28101809

Selenium and mercury have a synergistic negative effect on fish reproduction.

PubMed

Penglase, S; Hamre, K; Ellingsen, S

2014-04-01

Selenium (Se) can reduce the negative impacts of mercury (Hg) toxicity on growth and survival, but little is known about how these two elements interact in reproduction. In the following study we explored the effects of organic Hg and Se on the growth, survival and reproduction of female zebrafish (Danio rerio). Fish were fed one of four diets from 73 until 226 dpf in a 2 × 2 factorial design, using selenomethionine (SeMet) and methylmercury (MeHg) as the Se and Hg sources, respectively. Each diet contained Se at either requirement (0.7 mg Se/kg DM) or elevated levels (10 mg Se/kgDM), and Hg at either low (0.05 mg Hg/kg DM) or elevated (12 mg Hg/kg DM) levels. Between 151 and 206 dpf the female fish were pairwise crossed against untreated male fish and the mating success, fecundity, embryo survival, and subsequent overall reproductive success were measured. Elevated dietary Se reduced Hg levels in both the adult fish and their eggs. Elevated dietary Hg and Se increased egg Se levels to a greater extent than when dietary Se was elevated alone. At elevated maternal intake levels, egg concentrations of Se and Hg reflected the maternal dietary levels and not the body burdens of the adult fish. Elevated dietary Hg reduced the growth and survival of female fish, but these effects were largely prevented with elevated dietary Se. Elevated dietary Se alone did not affect fish growth or survival. Compared to other treatments, elevated dietary Hg alone increased both mating and overall reproductive success with <100 days of exposure, but decreased these parameters with >100 days exposure. Elevated dietary Se decreased fecundity, embryo survival, and overall reproductive success. The combination of elevated Se and Hg had a synergistic negative effect on all aspects of fish reproduction compared to those groups fed elevated levels of either Se or Hg. Overall the data demonstrate that while increased dietary Se may reduce adverse effects of Hg on the growth and survival in

Inhibition of ERK1/2 and activation of LXR synergistically reduce atherosclerotic lesions in ApoE-deficient mice.

PubMed

Chen, Yuanli; Duan, Yajun; Yang, Xiaoxiao; Sun, Lei; Liu, Mengyang; Wang, Qixue; Ma, Xingzhe; Zhang, Wenwen; Li, Xiaoju; Hu, Wenquan; Miao, Robert Q; Xiang, Rong; Hajjar, David P; Han, Jihong

2015-04-01

Activation of liver X receptor (LXR) inhibits atherosclerosis but induces hypertriglyceridemia. In vitro, it has been shown that mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor synergizes LXR ligand-induced macrophage ABCA1 expression and cholesterol efflux. In this study, we determined whether MEK1/2 (U0126) and LXR ligand (T0901317) can have a synergistic effect on the reduction of atherosclerosis while eliminating LXR ligand-induced fatty livers and hypertriglyceridemia. We also set out to identify the cellular mechanisms of the actions. Wild-type mice were used to determine the effect of U0126 on a high-fat diet or high-fat diet plus T0901317-induced transient dyslipidemia and liver injury. ApoE deficient (apoE(-/-)) mice or mice with advanced lesions were used to determine the effect of the combination of T0901317 and U0126 on atherosclerosis and hypertriglyceridemia. We found that U0126 protected animals against T0901317-induced transient or long-term hepatic lipid accumulation, liver injury, and hypertriglyceridemia. Meanwhile, the combination of T0901317 and U0126 inhibited the development of atherosclerosis in a synergistic manner and reduced advanced lesions. Mechanistically, in addition to synergistic induction of macrophage ABCA1 expression, the combination of U0126 and T0901317 maintained arterial wall integrity, inhibited macrophage accumulation in aortas and formation of macrophages/foam cells, and activated reverse cholesterol transport. The inhibition of T0901317-induced lipid accumulation by the combined U0126 might be attributed to inactivation of lipogenesis and activation of lipolysis/fatty acid oxidation pathways. Our study suggests that the combination of mitogen-activated protein kinase kinase 1/2 inhibitor and LXR ligand can function as a novel therapy to synergistically reduce atherosclerosis while eliminating LXR-induced deleterious effects. © 2015 American Heart Association, Inc.

Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts.

PubMed

Agah, Shima; Kim, Hyemee; Mertens-Talcott, Susanne U; Awika, Joseph M

2017-07-01

Cereals and legumes are traditionally consumed together in many cultures, and may provide complementary health benefits beyond what is known about improved indispensable amino acid intake. Here, we use an in vitro model of inflammatory pathways to investigate whether the different flavonoids in sorghum and cowpea could synergistically reduce inflammation. Interactive effect of combining apigenin and quercetin, as well as extracts (70% acetone, v/v) from a flavone-dominated white sorghum and flavonol-dominated white cowpea, against LPS-induced NF-κB and downstream cytokines (TNF-α, IL-6, IL-8) gene and protein expression was evaluated using the CCD18Co colon myofibroblasts. Combination of apigenin and quercetin, and sorghum and cowpea extracts synergistically downregulated LPS-induced NF-κB gene and protein expression in a dose-dependent manner, with additive effect producing IC 50 values that were 14.6 and 14.0 times, respectively, higher than 1:1 combined treatments. Similar strong synergistic interactions were observed for the downstream cytokines (IC 50 values for additive effect 8.3-21 times higher than combined treatments). Furthermore, the ratios of the different combined treatments significantly affected the magnitude of synergy. Combining the structurally related cereal flavones and legume flavonols elicit strong synergistic anti-inflammatory response in LPS-stimulated nonmalignant colonocytes, likely by targeting interdependent mechanisms. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ecological effects of scrubber water discharge on coastal plankton: Potential synergistic effects of contaminants reduce survival and feeding of the copepod Acartia tonsa.

PubMed

Koski, Marja; Stedmon, Colin; Trapp, Stefan

2017-08-01

To meet the oncoming requirements for lower sulphur emissions, shipping companies can install scrubbers where the exhaust is sprayed with seawater and subsequently discharged to the sea. The discharge water has a pH around 3 and contains elevated concentrations of vanadium, nickel, lead and hydrocarbons. We investigated 1) the threshold concentrations of scrubber discharge water for survival, feeding and reproduction of the copepod Acartia tonsa, 2) whether the effects depend on the exposure route and 3) whether exposure to discharge water can be detected in field-collected organisms. A direct exposure to discharge water increased adult copepod mortality and reduced feeding at metal concentrations which were orders of magnitude lower than the lethal concentrations in previous single-metal studies. In contrast, reproduction was not influenced by dietary uptake of contaminants. Scrubber water constituents could have synergistic effects on plankton productivity and bioaccumulation of metals, although the effects will depend on their dilution in the marine environment. Copyright © 2017 Elsevier Ltd. All rights reserved.