FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Yajing Fang,Fuqiang Liang,Mengmeng Xia,Weiwei Cao,Siyi Pan,Ting Wu,Xiaoyun Xu
This study was aimed to investigate the inhibitory activity of flavonoids on P-glycoprotein (P-gp). Effects of 39 flavonoids on the cellular uptake (CU) of rhodamine123 (Rho) and daunomycin (DNR) were investigated in both parental KB and P-gp overexpressed KB/MDR cells. The inhibition mechanism of selected flavonoids was further investigated by measuring the ATPase activity and expression level of P-gp. Twelve flavonoids improved the uptake of Rho (↑Rho F ) and nineteen flavonoids increased the uptake of DNR (↑DNR F ) in KB/MDR cells with nine flavonoids overlapped. Structure-activity relationship (SAR) indicated that 8-OCH 3 , and 2′-OH have a negative effect on Rho and DNR transport. Whereas 5-OH, 5-OCH 3 , 6-OH, 7-OCH 3 , 3′-OH, and 4′-OH, are essential for inhibition of flavonoids on P-gp and reversing the resistance of Rho and DNR. Eleven selected flavonoids significantly induced the basal P-gp-ATPase activity but much lower than that induced by verapamil . Tangeretin , galangin , kaempferol , quercetin , and morin significantly reversed the ATPase activity stimulated by verapamil. Six of eleven flavonoids significantly decreased P-gp expression, whereas three flavonoids slightly increased P-gp expression. These results provide valuable information that flavonoids can effectively reverse multidrug resistance of P-gp-mediated transport of nutraceutical and drugs by co-administration.
研究领域:
药理学
·
肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Swati Mahato,Zhiwei Zhu,Da-Wen Sun
Biological interaction with extremely low-frequency electromagnetic fields (ELF-EMF) is complex and the 50 and 60 Hz frequencies are among a few ‘window’ frequency ranges reported with a stimulating effect. In the current study, ELF-EMF at frequencies from 40 to 70 Hz were examined for their possible significance in inducing biological effects during chilled storage of grass carp ( Ctenopharyngodon idellus ) at 4 °C for 4 and 6 h. The myofibrillar protein extracted from the grass carp was analyzed and the results indicate significant (p < 0.05) increases in Ca 2+ ATPase activity and pH, and a reduction in the total sulfhydryl content during the treatment of 50 and 60 Hz frequencies for both storage durations, in particular, the treatment of 50 Hz had pronounced effects with higher correlations. Therefore, the 50 Hz might be associated with the ‘window’ effect, enhancing myofibrillar protein quality during chilled storage.
研究领域:
食品科学
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生物化学
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电磁场生物学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Wenjing Li,Xinru Li,Yajie Gao,Yanxia Zhou,Shujin Ma,Yong Zhao,Jinwen Li,Yan Liu,Xinglin Wang,Dongdong Yin
The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic–lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.
研究领域:
药学
·
药理学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2018
·
IF 2.371
Guan Wang,Manman Liu,Liwei Cao,Jirawat Yongsawatdigul,Shanbai Xiong,Ru Liu
The effect of NaCl (0.1 − 3.0 M) on self-assembly of silver carp myosin at 4 °C was investigated in terms of microstructure, conformation, intermolecular interactions, and particle size distribution. During setting at 4 °C, the self-assembly of myosin showed an obvious concentration dependence. At low concentrations (<0.3 M), myosin assembled into filaments mainly through rod-rod ionic linkages, and showed significantly (P < 0.05) higher turbidity and lower solubility than at ≥0.3 M. The addition of NaCl (0.3 − 0.6 M) led to the extension and dissolution of myosin by interfering with electrostatic interactions. The myosin assemblies gradually became smaller and more uniform. The solubility and Ca 2+ -ATPase activity reached a maximum at 0.6 M NaCl. When the concentrations increased to >1.0 M, myosin further assembled into filaments dominated by hydrophobic interactions. Both rod-rod and head-head interactions contributed to the myosin filaments at high concentrations (1.0 − 3.0 M). The solubility and uniformity of the myosin assemblies decreased as the NaCl concentration increased from 1.0 to 3.0 M.
研究领域:
食品科学
·
蛋白质化学
·
生物物理学
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DOI
高影响因子
IMMUNITY
·
2024
·
IF 25.5
Jingjing Cong,Pianpian Liu,Zili Han,Wei Ying,Chaoliang Li,Yifei Yang,Shuling Wang,Jianbo Yang,Fei Cao,Juntao Shen,Yu Zeng,Yu Bai,Congzhao Zhou,Lilin Ye,Rongbin Zhou,Chunjun Guo,Chunlei Cang,Dennis L. Kasper,Xinyang Song,Lei Dai,Linfeng Sun,Wen Pan,Shu Zhu
Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8 + T cell effector function. Mechanistically, DCA suppressed CD8 + T cell responses by targeting plasma membrane Ca 2+ ATPase (PMCA) to inhibit Ca 2+ -nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8 + T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8 + T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8 + T cell response in CRC, suggesting potential directions for anti-tumor therapy.
研究领域:
肿瘤学
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免疫学
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微生物学
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产品关联
DOI
PubMed
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2024
·
IF 6.1
Chenghao Huang,Fei Huang,Xuke Wang,Dongru Wang,Jiawei Wang,Xinhua Zhan
Polycyclic aromatic hydrocarbons (PAHs) constitute a category of persistent organic contaminants that possess the potential to induce carcinogenic, teratogenic, and mutagenic consequences. Our previous findings have revealed that plant roots actively take up PAHs through co-transport with protons, and auxin can promote PAHs uptake by wheat roots. It remains unclear whether nitric oxide (NO), a signaling molecule involved in numerous physiological processes in plants and downstream of auxin, can affect PAHs uptake by plant roots. In our study, 50 μmol/L sodium nitroprusside (SNP) significantly enhanced phenanthrene uptake after 4 h of exposure. After the addition of SNP (50 μmol/L), the H + flux on root surface increased, and H + -ATPase activity was activated, indicating that exogenous NO promotes phenanthrene uptake by plant roots via activating H + -ATPase. By studying the effects of 50 μmol/L cyclic guanosine monophosphate (cGMP), 5 mmol/L Ca 2+ , and 50 μmol/L adenosine monophosphate (AMP) on phenanthrene uptake by ryegrass roots and measuring root calcium-dependent protein kinases (CDPK) activity, we demonstrated that exogenous NO promotes phenanthrene uptake through the signaling pathway of NO, cGMP, Ca 2+ , CDPK, 14-3-3 protein and H + -ATPase. The results contribute significant insights into elucidating the underlying mechanisms of NO modulating PAHs absorption by plant roots, thereby offering crucial strategies for advancing food safety measures and enhancing the phytoremediation potential of soils and waters contaminated with PAHs.
研究领域:
环境科学
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植物生理学
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植物修复
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土壤污染
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Xiaolong Yu,Xu Jin,Hang Liu,Yuanyuan Yu,Jin Tang,Rujin Zhou,Aiguo Yin,Jianteng Sun,Lizhong Zhu
Atrazine residue in the environment continues to threaten aquatic ecosystem and human health owing to its adverse effect. However, limited researches focused on degradation mechanism of atrazine by UV/bisulfite, especially risk of intermediates at cellular and molecular level has not been seriously elaborated. In current work, transformation patterns and residual toxicity of intermediates of atrazine by UV/bisulfite were systematically investigated. The atrazine degradation was described by a pseudo first-order kinetic model ( K obs = 0.1053 min −1 ). The presence of H 2 PO 4 − , HCO 3 − and HA had a powerful inhibition. Scavenging test of radicals illustrated that SO 4 •− , •OH and O 2 •− existed in UV/bisulfite system, SO 4 •− and •OH were mainly responsible for atrazine degradation. Eight degradation intermediates were identified, which were involved in dealkylation, alkyl oxidation, dechlorination-hydroxylation, and alkylic-hydroxylation. E. coli as a model microorganism was selected to assess the risk of degradation intermediates. The levels of reactive oxygen species , MDA and Na + /K + -ATPase were declined, suggesting that oxidative damage induced by these intermediates was weakened. According to differential metabolites expression analysis, several key metabolites including aspartate , L-tryptophan, L-asparagine, cytidine, cytosin, stearic acid , behenic acid, were up-regulated, and glutathione , cadaverin, L-2-hydroxyglutaric acid and phytosphingosine were downregulated, clarifying that effective detoxification of atrazine can be performed by UV/bisulfite.
研究领域:
环境科学
·
毒理学
·
化学工程
·
微生物学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
Toxics
·
2025
·Vol. 13
·期 9
·706
·
IF 4.1
Juntong Gao,Qimeng Yang,Xiarui Fan,Xinwei Zhou,Peng Ren
Toxicological effects of microplastics (MPs) have been confirmed in a variety of microorganisms in aquatic environments, and they are closely correlated with the physicochemical properties of the MPs. In a natural environment, different aging treatments always induce different alterations in the physicochemical properties of MPs, thus influencing their environmental behaviors and biotoxicity. In this work, physicochemical properties and toxicity towardsEscherichia coli(E. coli) were investigated in polystyrene (PS) MPs (3 and 10 μm) before and after aging by UV irradiation and biofilm formation, respectively. The results show that UV irradiation and biofilm formation led to different alterations in the surface morphologies and functional groups of PS. The UV-aged 3 μm PS had the strongest inhibitory effect onE. coligrowth, and the bio-aged 10 μm PS had the strongest beneficial effect onE. coligrowth. Also, the ATPase activity, production of intercellular ROS, and MDA content of theE. coliwere affected differently. UV aging enhanced the toxicity of PS towardsE. coli, while bio-aging had an opposite weakening effect. Overall, our research verified the remarkable differences in the physicochemical properties and biotoxicity of PS induced by UV aging and bio-aging.
研究领域:
环境毒理学
·
微生物学
·
生态毒理学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Ruizeng Luo,Yijie Fan,Yilin Qi,Yuan Bai,Meng Xiao,Yujia Lv,Jinrui Liang,Mingcheng Tang,Jiaping Zhang,Zhou Li,Dan Luo
Endogenous electric field (EF) originating from differences in ionic gradients plays a decisive role in the wound healing process. Based on this understanding, a self-manipulating sodium ion gradient-based endogenic electrical stimulation dressing (smig-EESD) is developed to achieve passive, non-invasive, endogenic electrical stimulation of wounds, which avoids the side effects of electrode occupancy, electrochemical reactions, and thermal effects present in traditional exogenous electrical stimulation. smig-EESD reduced the potential at the center of the wound by specifically absorbing Na+ in the exudate, ultimately strengthening the wound endogenous EF. Importantly, smig-EESD converted the active transport dependent on Na + /K + -ATPase into passive diffusion by adsorbing extracellular matrix Na+, and the saved ATP consumption promoted tissue repair process. smig-EESD regulated innate and adaptive immune responses by upregulating the secretion of multiple cytokines, thereby suppressing injury-associated inflammatory responses and reducing scar formation. smig-EESD reveals an endogenic electrical stimulation strategy that is independent of electrodes and circuits, and provides new insights into the future development of electronic medicine.
研究领域:
生物医学工程
·
伤口愈合
·
组织工程
·
电疗法
·
免疫学
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产品关联
DOI
PubMed
高影响因子
Journal of Environmental Sciences
·
2022
·
IF 6.796
Ruohua Qu,Mi Chen,Jingfu Liu,Qiting Xie,Na Liu,Fei Ge
Adenosine triphosphate (ATP) generation of aquatic organisms is often subject to nanoparticles (NPs) stress, involving extensive reprogramming of gene expression and changes in enzyme activity accompanied by metabolic disturbances. However, little is known about the mechanism of energy supply by ATP to regulate the metabolism of aquatic organisms under NPs stress. Here, we selected extensively existing silver nanoparticles (AgNPs) to investigate their implications on ATP generation and relevant metabolic pathways in alga ( Chlorella vulgaris ). Results showed that ATP content significantly decreased by 94.2% of the control (without AgNPs) in the algal cells at 0.20 mg/L AgNPs, which was mainly attributed to the reduction of chloroplast ATPase activity (81.4%) and the downregulation of ATPase-coding genes atp B and atp H (74.5%-82.8%) in chloroplast. Molecular dynamics simulations demonstrated that AgNPs competed with the binding sites of substrates adenosine diphosphate and inorganic phosphate by forming a stable complex with ATPase subunit beta, potentially resulting in the reduced binding efficiency of substrates. Furthermore, metabolomics analysis proved that the ATP content positively correlated with the content of most differential metabolites such as D-talose, myo-inositol, and L-allothreonine. AgNPs remarkably inhibited ATP-involving metabolic pathways, including inositol phosphate metabolism, phosphatidylinositol signaling system, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and glutathione metabolism. These results could provide a deep understanding of energy supply in regulating metabolic disturbances under NPs stress.
研究领域:
环境科学
·
分子生物学
·
生物化学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
Food Biophysics
·
2015
·Vol. 10
·期 4
·447-455
·
IF 1.63
Cao Liwei,Su Sisi,Regenstein Joe M.,Xiong Shanbai,Liu Ru
The role of Ca 2+ in gelation of myosin extracted from silver carp ( Hypophthalmichthys molitrix ) was investigated. Compared with the control, myosin with CaCl 2 showed higher turbidity and larger particle size, indicating that CaCl 2 contributed to myosin aggregation. Addition of CaCl 2 decreased the myosin thermostability and promoted the unfolding of myosin α-helical structure during heating. Moreover, CaCl 2 could increase surface hydrophobicity at low temperatures (20–40 °C) and promoted hydrophobic interactions. Meanwhile, it decreased the temperature of disulfide bond formation by about 10 °C. Addition of 10–40 mM CaCl 2 favored activation of the Ca 2+ -ATPase activity at 20 to 30 °C, but not obvious with elevated temperatures. Ca 2+ -ATPase activity of myosin was undetectable when heated above 60 °C because of severe structural damage of myosin heads. G’ at both the first and second peaks increased with increasing CaCl 2 concentration. Therefore, CaCl 2 was beneficial for gelation of myosin by inducing the unfolding of myosin and enhancing disulfide bonds along with hydrophobic interactions between neighboring myosin molecules.
研究领域:
食品科学
·
生物化学
·
蛋白质化学
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DOI
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2018
·Vol. 124
·期 5
·1060-1070
·
IF 2.16
Lin W.,Yi J.,Zhang Y.,Deng Z.,Chen Q.,Niu B.
AimsThe effects of a new glutaraldehyde–didecyldimethylammonium bromide combination disinfectant (GD) on the cell surface of Staphylococcus aureus, a representative Gram‐positive bacterium, were investigated in this study.Methods and ResultsResults of bacterial surface structural analysis showed that GD significantly changed the bacterial morphology. The membrane fluidity decreased and outer membrane permeabilization increased after contact with GD. Furthermore, the integrity of the cytoplasmic membrane was destroyed by over 99% after exposure to GD for a short time. Bacterial ATPase activity correlated negatively with the treatment of GD over time, and proteins were degraded. Assays of intracellular component leakage indicated that GD caused the rapid leakage of K+, Mg2+, ATP molecules, and proteins into the extracellular environment.ConclusionsThe effects of GD against S. aureus are probably attributable to the removal of the permeability barrier, changes in the S. aureus morphology, changes in the structures and functions of the cell membrane, leakage of intracellular substances and disturbance of the intracellular homeostasis. As a result, this irreversible damage accelerated the death of S. aureus.Significance and Impact of the StudyIn an earlier study, the bactericidal mechanism of GD against Escherichia coli was investigated. Hence, this study focused on the action of mechanism of GD against S. aureus. It is important to clarify the disinfectant bactericidal mechanisms of GD against bacterium, in general, and this study provides theoretical support to the prevention of bacterial resistance.
研究领域:
微生物学
·
药理学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）