PLoS One
·
2016
·Vol. 11
·期 7
·e0157759
·
IF 3.057
Shanshan Wang,Ting Lei,Man Zhang
Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM)-resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK-8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) , immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF STORED PRODUCTS RESEARCH
·
2026
·
IF 2.8
Chunxue You,Yao Yao,Kaidi Dai,Jinming Chen,Yanming Wu,Wenjuan Zhang,Xiaoxue Yu,Chao Jiang,Xiumei Gao
Tribolium castaneum (Herbst) is a major stored-product pest, necessitating safer alternatives targeting its destructive larval stage. This study investigated the synergistic insecticidal effects of 2-undecanone and decanal, two active constituents from Houttuynia cordata essential oil, against T. castaneum larvae and elucidated the underlying mechanisms via quantitative real-time PCR (qRT-PCR), RNA interference (RNAi), histopathology, molecular docking, ELISA, and enzyme activity assays. Contact toxicity assays identified the 5:5 mixture as optimally effective, exhibiting significant synergy (R ≥ 1.5) and the lowest LD 50 (14.8 μg/larva). Whereas 2-undecanone alone upregulated farnesol dehydrogenase ( FDa ), glutathione S-transferase ( GST ), and cytochrome P450 ( CYP6BQ7 ), the 5:5 mixture significantly suppressed the expression of FDa and GST (>60 %), accompanied by decreased GST enzyme activity and lower juvenile hormone (JH) III levels. RNAi silencing of FDa and GST confirmed their important roles in larval susceptibility. Molecular docking predicted interactions of both compounds with FDa and GST, implying potential cooperative inhibition. Histopathology revealed more severe midgut damage under the mixture than under either compound alone. In conclusion, the synergy arises from coordinated suppression of the GST-mediated detoxification and FDa-linked JH biosynthesis, offering a promising strategy for developing potent, eco-friendly botanical formulations for stored-product pest management.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Chao Hu,Ji-Yuan Liu,Wei Wang,David Mota-Sanchez,Shun He,Yu Shi,Xue-Qing Yang
Pest management is mostly accomplished by the use of insecticides. However, the overuse of insecticides has led to the development of resistance. Glutathione S-transferases (GSTs) are vital detoxification enzymes involved in insecticide resistance in insects. In this study, we report the involvement of GSTs in insecticide resistance to lambda-cyhalothrin in Cydia pomonella, a globally quarantined fruit pest. A total of 25 GST, including 22 cytosolic genes and 3 microsomal genes, are identified from the genome database of C. pomonella. These cytosolic genes are further classified into six classes, including four in delta, eight in epsilon, three in omega, three in sigma, one in theta, and one in zeta class, as well as two unclassified genes. The real-time quantitative polymerase chain reaction (RT-qPCR) shows that the majority of these genes are mainly expressed throughout the larval stage and in the midgut of the fourth-instar larvae. Exposure to an LD10 dose of lambda-cyhalothrin resulted in the upregulation of 17 GST genes. Moreover, mRNA levels of most GST genes, with the exception of CpGSTe6, CpGSTd2, CpGSTd4, and CpGSTz1, are considerably higher in a lambda-cyhalothrin-resistant population (ZW_R) than those of susceptible strains. Recombinant CpGSTd1, CpGSTd3, CpGSTe3, and CpGSTs2 can bind and metabolize lambda-cyhalothrin, with the highest metabolic rate observed for CpGSTd3 but no metabolite(s) was detected, supporting the role of GSTs in sequestration of lambda-cyhalothrin. Molecular dynamics simulation analysis indicates that key residues of hydrophobic pocket-derived lipophilic energy S(lipo) interactions with a hydrophobic pharmacophore of lambda-cyhalothrin are crucial for metabolism by CpGSTd3 and further lead to resistance. Our study is the first to experimentally confirm the involvement of GSTs in lambda-cyhalothrin resistance via sequestration and provides new insights into resistance management in C. pomonella.
研究领域:
昆虫学
·
分子生物学
·
害虫管理
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
ENZYME AND MICROBIAL TECHNOLOGY
·
2014
·
IF 2.966
Xue-Qing Yang,Ya-Lin Zhang
Glutathione S -transferases (GSTs) play a key role in detoxification of xenobiotics in organisms. However, their other functions, especially response to the natural toxin cantharidin produced by beetles in the Meloidae and Oedemeridae families, are less known. We obtained GST cDNAs from three sources: Cydia pomonella ( CpGSTd1 ), Sus scrofa ( SsGSTα1 ), and Triticum aestivum ( TaGSTf3 ). The predicted molecular mass is 24.19, 25.28 and 24.49 kDa, respectively. These proteins contain typical N-terminal and C-terminal domains. Recombinant GSTs were heterologously expressed in Escherichia coli as soluble fusion proteins. Their optimal activities are exhibited at pH 7.0–7.5 at 30 °C. Activity of CpGSTd1 is strongly inhibited by cantharidin and cantharidic acid, but is only slightly suppressed by the demethylated analog of cantharidin and cantharidic acid. Enzymatic assays revealed that cantharidin has no effect on SsGSTα1 activity, while it significantly stimulates TaGSTf3 activity, with an EC 50 value of 0.3852 mM. Activities of these proteins are potently inhibited by the known GST competitive inhibitor: S -hexylglutathione (GTX). Our results suggest that these GSTs from different sources share similar structural and biochemical characteristics. Our results also suggest that CpGSTd1 might act as a binding protein with cantharidin and its analogs.
研究领域:
生物化学
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Wangcang Su,Chen Zhang,Lanlan Sun,Hongle Xu,Guoyan Zhang,Fei Xue,Qiuli Leng,Yujia Niu,Renhai Wu
Mesosulfuron-methyl (MS), a sulfonylurea herbicide used in wheat, poses significant residual phytotoxicity risks to subsequent maize (Zea mays L.) crops. This study evaluated the protective role of the safener cyprosulfamide (CSA) through physiological, biochemical, and molecular analyses. MS treatment drastically reduced maize shoot length and fresh weight by 80.74% and 74.24%, respectively, while CSA pretreatment significantly relieved these inhibitory effects, with the mitigation rates of shoot length and fresh weight reaching 66.3% and 63.57%, respectively. Physiologically, CSA alleviated MS-induced chlorophyll and carotenoid losses and reduced oxidative stress by lowering malondialdehyde (MDA) levels (23.39% at 6 days after sowing) while enhancing superoxide dismutase (SOD) and glutathione S-transferase (GST) activity. Molecularly, CSA upregulated nine GST genes, competitively bound to ZmALS1/2, increasing acetolactate synthase (ALS) activity by 70–146%, and reduced MS residues in shoots (4.02%) and roots (33.78%). These findings demonstrate CSA’s multifunctional detoxification mechanism, combining gene activation, antioxidant regulation, and target-site competition, offering a viable strategy to mitigate herbicide carryover in crop rotations. CSA application could significantly reduce MS phytotoxicity, advancing sustainable herbicide management.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2026
·
IF 4.8
Xiaoyue Yu,Chenkang Xie,Qiqi Guo,Jinqiu Sun,Yongjie Yang,Wei Tang
Echinochloa crus-galli var. mitis (ECM) is one of the major Echinochloa species in the rice field, with increasing reports of herbicide resistance. This study identified an ECM population (ECM_2312) exhibiting cross-resistance to four acetyl-CoA carboxylase (ACCase)-inhibiting herbicides, including cyhalofop-butyl (8.7-fold), metamifop (15.8-fold), clodinafop-propargyl (16.1-fold) and fenoxaprop-P-ethyl (25.0-fold)，compared with the susceptible population ECM_2201. A Cys-2088-Arg mutation was detected in ACCase2C gene copy in ECM_2312, confirming the involvement of that target-site resistance. Liquid chromatography–tandem mass spectrometry (HPLC-MS) analysis revealed that the degradation of the herbicides active forms (cyhalofop-acid and metamifop) were faster in the resistant population than in the susceptible population. Pretreatment with the glutathione S-transferase (GST) inhibitor, 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) reduced the resistance level from 8.7-fold to 4.9 fold for cyhalofop-butyl and from 15.8-fold to 3.0-fold for metamifop. Moreover, GST activity was consistently higher in the resistant population than the susceptible population, both in the absence and presence of herbicide treatment. Furthermore, five GST genes exhibited sustained overexpression for 96 h in the resistant plants following exposure to either cyhalofop-butyl or metamifop. This study demonstrated an ECM population possesses both a target-site mutation (Cys-2088-Arg) and GST-mediated enhanced metabolic resistance to ACCase-inhibiting herbicides.
✓ 已验证
DOI
高影响因子
Frontiers in Aging Neuroscience
·
2024
·
IF 4.1
Yu Xingzhi,Tao Jie,Xiao Tian,Duan Xiaohua
Introduction: Gastrodia elata Blume is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing Gastrodia elata are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of Gastrodia elata, and, in recent years, this herb has also been used in the treatment of Alzheimer’s disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4′-methylenediphenol, a key active ingredient of Gastrodia elata, can mitigate amyloid-β (Aβ)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD.Methods: We investigated the effects of 4,4′-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4′-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action.Results: 4,4′-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4′-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aβ protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4′-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4′-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aβ toxicity; importantly, our results suggested that these effects of 4,4′-methylenediphenol were mediated, at least partly, via the activation of DAF-16.Conclusion: We have demonstrated that 4,4′-methylenediphenol can reduce Aβ-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of Gastrodia elata and its active ingredients.
研究领域:
神经科学
·
药理学
·
老年学
·
分子生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Jia Liu,Hui Du,Tao Liu,Cheng Chen,Ying Yan,Tianqiang Liu,Lei Liu,Erlong Wang
Hepatopancreas as the main organ detoxifying xenobiotics with higher detoxifying and antioxidant enzymes activities , could best reflected the status of antioxidant defence against virus infection in the organisms. Catalase ( CAT ) and glutathione S-transferase ( GST ) were two important enzymes associated with hepatopancreas antioxidation and detoxification. To obtain the accurate expression levels of CAT and GST gene which reflect the status of hepatopancreas antioxidation and detoxification, two or more reference genes expressed stably under different conditions should be selected for RT-qPCR analysis. In this study, eight candidate reference genes were investigated using RefFinder program to screen the most stable reference gene during virus (white spot syndrome virus, WSSV) infection and drug (matrine) treatments in Procambarus clarkii , the relative expression levels and the activities of CAT and GST in hepatopancreas were detected and compared to verify the validity of selected reference genes. The results showed that taken different tissues together, EIF and EF1 α were the most stable and unstable reference genes respectively in P. clarkii no matter under different WSSV infection periods (0, 24, 48, 72 h) or different matrine treatment methods according to RefFinder analysis. The optimal number of reference genes in hepatopancreas was two using geNorm analysis, i.e. EIF and TBP , which were top two most stable reference genes in hepatopancreas. Moreover, based on the comparison between the relative expression levels and the activities of CAT and GST, EIF and TBP as reference genes were proved to be necessary and practicable to evaluate hepatopancreas antioxidation during WSSV infection and matrine treatments. Besides, the optimal number of reference genes in other P. clarkii tissues was also two genes, i.e. EIF and TUB in intestine, EIF and EF1α in muscle, EIF and GAPDH in gills, EIF and TBP in brain , TBP and UB in gonads . Our study was helpful to acquire the accurate data of antioxidation and detoxification-related and immune-related gene expression during virus infection and drug treatments in crayfish, especially in hepatopancreas tissues
研究领域:
水产养殖
·
分子生物学
·
免疫学
·
兽医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Qiuxiang Li,Guowei Zhao,Fengling Wu,Xilan Tang,Zhenggen Liao,Xinli Liang,Wei Dong
Imperatorin (IMP) has demonstrated potential in reversing drug resistance in various tumor cells; however, its limited clinical application and development are attributed to its poor water solubility and low bioavailability. The current work is intended to enhance the oral bioavailability of IMP and its efficacy in overcoming tamoxifen (TAM) resistance in breast cancer cells. We employed mPEG–PLLA and Cremophor RH60 (RH60) to prepare imperatorin nanomicelles (IMP-RH60/mPEG–PLLA). The freeze-dried powder of IMP-RH60/mPEG–PLLA demonstrated a porous structure, and upon reconstitution, the resulting solution exhibited clarity and transparency. The particle size was measured to be 25.48 ± 0.92 nm, with a zeta potential of −5.50 ± 1.06 mV. The encapsulation efficiency was determined to be 85.78 ± 0.84%, while the drug loading was found to be 2.66 ± 0.03%. In comparison to the active pharmaceutical ingredients (APIs) of IMP, IMP-RH60/mPEG–PLLA exhibited a significant increase in in vitro release, improved bioavailability in rats, and enhanced uptake by MCF-7/TAM cells. The coadministration of IMP-RH60/mPEG–PLLA and TAM effectively inhibited the proliferation, colony formation, migration, and invasion of MCF-7/TAM cells. This outcome could potentially be attributed to the downregulation of GST-π and MDR1 drug resistance genes, consequently augmenting the susceptibility of MCF-7/TAM cells to TAM. An experimental model of BALB/c nude xenograft, consisting of human breast cancer cells resistant to tamoxifen (TAM), was established in order to assess the potential in vivo reversal of TAM resistance through the use of IMP-RH60/mPEG–PLLA. The growth of xenografts was inhibited by IMP-RH60/mPEG–PLLA, and it induced apoptosis in tumor tissues through the downregulation of Ki-67, GST-π, and MDR1 gene expression. The findings indicated that the utilization of IMP-RH60/mPEG–PLLA micelles resulted in an enhancement of IMP’s bioavailability and its efficacy in overcoming TAM resistance.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Wenmin Li,Yikun Zan,Tong Wu,Sa Yang,Linlin Liu,Shanshan Li,Pingli Dai,Jing Gao
Chlorantraniliprole (CAP), a diamide insecticide, is extensively applied to combat pests in various crops. However, the widespread use of insecticides has raised concerns about their potential impact on pollinators. In the present study, we explored the toxic effects of CAP in two important honey bee species, Apis mellifera and Apis cerana . The 48 h LC 50 values of CAP for A. mellifera and A. cerana was 256.052 mg/L and 109.709 mg/L, implying that A. cerana is more sensitive to CAP. Prolonged exposure to 40 mg/L CAP significantly impaired sucrose responsiveness and climbing activity in both bee species. Both species showed a decrease in GR activity and GSH content with increasing CAP concentration. By contrast, the activities of GST, CAT, P450 and NAD-MDH were increased in both A. mellifera and A. cerana , but the differences between the 10 mg/L and 40 mg/L treatments were less pronounced in A. mellifera . Moreover, the immune related genes exhibited differential responses to CAP when comparing the two species. Low CAP concentrations led to down-regulation in expression of toll but up-regulation in expression of apideacin and hymeopatecin in A. mellifera , whereas A. cerana exhibited minimal changes in these genes. Additionally, CAP significantly inhibited the expression of ER stress response genes gp - 93 and P58 in A. mellifera , while 10 mg/L of CAP promoted P58 expression in A. cerana . Our results highlight species-specific effects with the possible, distinct detoxification mechanisms and immune responses between A. mellifera and A. cerana . These findings serve as a foundation for further evaluating the safety of CAP for honey bee species and offer insights into the scientific use of pesticides.
研究领域:
昆虫学
·
毒理学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2021
·Vol. 29
·期 2
·1824-1835
·
IF 4.223
Chen Yuan,Chen Yuancai
At present, there are many studies on microbial reduction of Pd (II), although few of these studies assess the bacterial toxicity of Pd (II) before and after reduction by microorganisms. In this study, the toxicity of Pd (II) to Bacillus wiedmannii MSM ( B. wiedmannii MSM) was assessed before and after reduction by live B. wiedmannii MSM cells (referred to as “Pd (0)-loaded cells”) and after biosorption by dead B. wiedmannii MSM cells (referred to as “Pd (II)-loaded cells”). B. wiedmannii MSM is a widely occurring, nonpathogenic aerobic bacterium. Compared with Pd (II), the EC 20 , EC 50 , and EC 80 of Pd (0)-loaded cells increased by 77.73-, 112.75-, and 163.91-fold, respectively, while the EC 20 , EC 50 , and EC 80 of Pd (II)-loaded cells increased by only 11.55-, 9.77-, and 8.29-fold, respectively. The sterilization contribution rates of the mechanisms of action of Pd (0)-loaded cells were ranked in the order of: remaining Pd (II) > oxidative stress > physical puncture. Pd (II) was found to increase cell membrane permeability, glutathione S-transferase (GST) enzyme activity, and reactive oxygen species levels in cells and decrease the cell membrane potential. XPS results indicated that Pd (II) increased the content of polysaccharides and peptides and decreased the content of hydrocarbons in cells. These findings reveal the bactericidal mechanism of toxicity of Pd (II) and Pd (0)-loaded cells on Bacillus wiedmannii MSM and provide an environmentally friendly and inexpensive method for Pd (II) detoxification.
研究领域:
环境科学
·
微生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Agronomy-Basel
·
2022
·Vol. 12
·期 11
·2870
·
IF 3.949
Wei Tang,Jinqiu Sun,Xiaoyue Yu,Fengyan Zhou,Shengnan Liu,Mengjie Liu,Yongliang Lu,Yongjie Yang
Roegneria kamojiOhwi (Poaceae), a wild relative plant of wheat which is widely distributed across China, has become a dominant and problematic weed in wheat fields in some regions. We have previously confirmed thatR. kamojiis highly tolerant to foliar-applied acetyl-CoA carboxylase (ACCase) and acetolactate synthase (ALS) inhibitors in wheat (Triticum aestivumL.). The sensitivity ofR. kamojito pre-emergence (PRE) herbicides and the basis of fenclorim increase selectivity to butachlor between wheat andR. kamojiwere evaluated in this study. Screenhouse bioassay showed thatR. kamojiexhibited similar sensitivity to wheat to PRE herbicides at their recommended field doses (RFD); it also showed that buatchlor provides the highest relative control forR. kamoji(53.4% emergence and 81.5% fresh weight reduction, respectively), while it had no impact on seedling emergence of wheat among the six PRE herbicides. When butachlor was applied at four-fold RFD, noR. kamojiseedlings emerged; however, it significantly reduced the above-ground biomass of wheat compared with the non-treated control. Pre-treatment with herbicide safener fenclorim by seed soaking increased the ED10value of butachlor to wheat from 221.8 to 1600.1 g a.i. ha−1, thus increasing the selectivity index from 9.6 to 68.9 between wheat andR. kamoji. The activities of α-amylase activity and protein content during germination, and glutathione-S-transferase (GST) and β-ketoacyl-CoA synthase (KCS) in the seedlings, could be induced by butachlor in both wheat seeds with or without fenclorim pre-soaking. These results suggested that butachlor provides the highest control forR. kamojiand did not affect germination and emergence in wheat. The basis of fenclorim-increased selectivity to butachlor was associated with the induced GST and KCS-mediated enhanced herbicide metabolism in wheat.Keywords:Roegneria kamoji;wheat;herbicide safener;fenclorim;selectivity
研究领域:
农业科学
·
杂草科学
·
植物生理学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）