INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Qize Xuan,JinFeng Zhou,Feng Jiang,Wei Zhang,Anqi Wei,Wenxue Zhang,Qi Zhang,Hao Shen,Hui Li,Chao Chen,Ping Wang
The formidable virulence of methicillin-resistant staphylococcus aureus (MRSA) have thrown great challenges to biomedicine, which mainly derives from their autocrine phenol-soluble modulins (PSMs) toxins, especially the most toxic member termed phenol-soluble modulins α3 (PSMα3). PSMα3 cytotoxicity is attributed to its amyloidal fibrillation and subsequent formation of cross-α sheet fibrils. Inspired by the multiple biological activity of Sappanwood, herein, we adopted brazilin, a natural polyphenolic compound originated from Caesalpinia sappan , as a potential antidote of PSMα3 toxins, and attempted to prove that the regulation of PSMα3 fibrillation was an effective alexipharmic way for MRSA infections. In vitro results revealed that brazilin suppressed PSMα3 fibrillation and disassembled preformed amyloidal fibrils in a dose-dependent manner, in which molar ratio (brazilin: PSMα3) of efficient inhibition and disassembly were both 1:1. These desired regulations dominated by brazilin benefited from its bonding to core fibrils-forming residues of PSMα3 monomers urged by hydrogen bonding and pi-pi stacking, and such binding modes facilitated brazilin-mediated inhibition or disruption of interactions between neighboring PSMα3 monomers. In this context, these inhibited and disassembled PSMα3 assemblies could not easily insert into cell membrane and subsequent penetration, and thus alleviating the membrane disruption, cytoplasmic leakage, and reactive oxygen species (ROS) generation in normal cells. As such, brazilin dramatically decreased the cytotoxicity borne by toxic PSMα3 fibrils. In addition, in vivo experiments affirmed that brazilin relieved the toxicity of PSMα3 toxins and thus promoted the skin wound healing of mice. This study provides a new antidote of PSMα3 toxins, and also confirms the feasibility of the assembly-regulation strategy in development of antidotes against supramolecular fibrillation-dependent toxins.
研究领域:
药理学
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微生物学
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毒理学
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生物物理学
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DOI
PubMed
高影响因子
iScience
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2023
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IF 5.8
Yingjian Chen,Tianqi Cui,Shaorong Xiao,Tianyao Li,Yadi Zhong,Kaijia Tang,Jingyi Guo,Shangyi Huang,Jiabing Chen,Jiayu Li,Qi Wang,Jiawen Huang,Huafeng Pan,Yong Gao
Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
Theranostics
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2019
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IF 8.063
Shuai Wang,Yanke Lin,Ziyue Zhou,Lu Gao,Zemin Yang,Feng Li,Baojian Wu
Controlling bilirubin to a low level is necessary in physiology because of its severe neurotoxicity. Therefore, it is of great interest to understand the regulatory mechanisms for bilirubin homeostasis. In this study, we uncover a critical role for circadian clock in regulation of bilirubin detoxification and homeostasis. Methods : The mRNA and protein levels of Bmal1 (a core clock gene), metabolic enzymes and transporters were measured by qPCR and Western blotting, respectively. Luciferase reporter, mobility shift and chromatin immunoprecipitation were used to investigate transcriptional gene regulation. Experimental hyperbilirubinemia was induced by injection of bilirubin or phenylhydrazine. Unconjugated bilirubin (UCB) and conjugated bilirubin were assessed by ELISA. Results : We first demonstrated diurnal variations in plasma UCB levels and in main bilirubin-detoxifying genes Ugt1a1 and Mrp2 . Of note, the circadian UCB levels were antiphase to the circadian expressions of Ugt1a1 and Mrp2. Bmal1 ablation abrogated the circadian rhythms of UCB and bilirubin-induced hepatotoxicity in mice. Bmal1 ablation also decreased mRNA and protein expressions of both Ugt1a1 and Mrp2 in mouse livers, and blunted their circadian rhythms. A combination of luciferase reporter, mobility shift, and chromatin immunoprecipitation assays revealed that Bmal1 trans-activated Ugt1a1 and Mrp2 through specific binding to the E-boxes in the promoter region. Further, Bmal1 ablation caused a loss of circadian time-dependency in bilirubin clearance and sensitized mice to chemical induced-hyperbilirubinemia. Moreover, bilirubin stimulated Bmal1 expression through antagonism of Rev-erbα, constituting a feedback mechanism in bilirubin detoxification. Conclusion : These data supported a dual role for circadian clock in regulation of bilirubin detoxification, generating circadian variations in bilirubin level via direct transactivation of detoxifying genes Ugt1a1 and Mrp2, and defending the body against hyperbilirubinemia via Rev-erbα antagonism. Thereby, our study provided a potential mechanism for management of bilirubin related diseases.
研究领域:
分子生物学
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昼夜节律
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肝病学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2018
·Vol. 9
·期 1
·1-8
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IF 12.353
Wang Huidong,Shi Yu,Wang Lu,Liu Shuai,Wu Shuwen,Yang Yihua,Feyereisen René,Wu Yidong
The cotton bollworm Helicoverpa armigera , is one of the world’s major pest of agriculture, feeding on over 300 hosts in 68 plant families. Resistance cases to most insecticide classes have been reported for this insect. Management of this pest in agroecosystems relies on a better understanding of how it copes with phytochemical or synthetic toxins. We have used genome editing to knock out a cluster of nine P450 genes and show that this significantly reduces the survival rate of the insect when exposed to two classes of host plant chemicals and two classes of insecticides. Functional expression of all members of this gene cluster identified the P450 enzymes capable of metabolism of these xenobiotics. The CRISPR-Cas9-based reverse genetics approach in conjunction with in vitro metabolism can rapidly identify the contributions of insect P450s in xenobiotic detoxification and serve to identify candidate genes for insecticide resistance.
研究领域:
昆虫学
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遗传学
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分子生物学
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农业科学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2019
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IF 8.355
Hai-Bin Qiu,Yi Hu,Han-Juan Chong,Li Yuan,Guo-Ping Sheng
Ionic liquids (ILs) have been widely applied in chemical industry due to their unique properties. There is mounting evidence that they are toxic to various living organisms. Thus, it is crucial to develop methods to efficiently degrade and mineralize ILs to reduce their potential risks to the environment. In this work, the degradation of 1-butyl-3-methylimidazolium bromide ([C 4 MIM]Br), an imidazolium-based IL, was investigated in aqueous solution via 60 Co γ-ray irradiation. Results show that [C 4 MIM]Br could be effectively degraded by γ-ray irradiation. The irradiation-induced degradation of [C 4 MIM]Br fitted well to the pseudo-first-order kinetics model. The kinetic constant ( k ) increased linearly with the increase of irradiation dose rate (R 2 = 0.942) and solution pH value (R 2 = 0.974), and decreased with the increase of [C 4 MIM]Br concentration. Fourteen intermediates were detected using a liquid chromatography-mass spectrometry analysis. Based on these intermediate products, the degradation pathways and mechanisms of [C 4 MIM]Br were proposed. The free radicals (e.g., aqueous electron (e aq – ), hydroxyl radical ( OH), and hydrogen atom (H )) generated by γ-ray irradiation showed synergistic effects in the degradation and mineralization of [C 4 MIM]Br. Moreover, the toxicity assessment using C. elegans and Chlorella pyrenoidosa as model organisms demonstrates that sufficient γ-ray irradiation could effectively reduce the potential risks of [C 4 MIM]Br and its intermediates to the environment. These findings of this study may offer an efficient and environmentally friendly approach for effectively removing ILs and other persistent organic pollutants.
研究领域:
环境科学
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放射化学
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毒理学
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产品关联
DOI
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Shenglong Liu,Yu Zhou,Yan Feng,Qixia Peng,Yurong Li,Cheng He,Zemin Fang,Yazhong Xiao,Wei Fang
Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B 1 (AFB 1 ). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p -coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB 1 degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p- coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB 1 degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3–3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.
研究领域:
食品安全
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生物化学
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环境科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Wei Song,Yuxin Zhou,Zhuoyue Wang,Ji Li,Xiaolei Zhang,Caixia Fu,Xing Du,Zhihong Wang,Wenhui Qiu
Advanced oxidation process (AOPs) is one of the most effective technologies for organic pollutants removal. In this study, diverse reactive species generation and enhanced sulfamethoxazole (SMX) degradation were investigated based on persulfate (PDS) activated by Fe 2+ &dithionite (DTN). When involving Fe 2+ &dithionite in PDS, SMX degradation efficiency reached 84 % within 30 min following a pseudo-first-order kinetic, which was higher than those in Fe 2+ /PDS (50.4 %) and Fe 2+ /O 2 /DTN (41.3 %). SO 4 •− and • OH were identified as dominant reactive species with a crucial role of FeSO 3 + based on quenching experiment and electron spin resonance (ESR). The contributions of SO 4 ·− , · OH, and other species to SMX degradation were 60.1 %, 33.9 %, and 6 %, respectively. In Fe 2+ /DTN/PDS system, SMX was effectively degraded under nearly neutral pH (5.0–9.0), with activation energy of 96.04 kJ·mol −1 . The experiments and density functional theory (DFT) calculation demonstrated that three functional groups (benzenesulfonamido, benzene ring, and oxazole ring) were attacked for SMX degradation. Moreover, acute toxicity to Vibrio fischeri has enhanced in the earlier degradation process due to the intermediates and weaken with the continuous reaction. This work not only provides a high-activity SO 4 ·− -AOP for refractory pollutant treatment with possible dual radical generation resources, but elucidated diverse reactive species formation with Fe 2+ &dithionite.
研究领域:
环境科学
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化学工程
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
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IF 6.291
Jiashu Liu,Jianhui Chen,Kangjia Zuo,Huanan Li,Fang Peng,Qiuping Ran,Rui Wang,Zhengbing Jiang,Huiting Song
To alleviate the risk of textile effluent, the development of highly effective bioremediation strategies for synthetic dye removal is needed. Herein, we aimed to assess whether intensified bioactivity of Bacillus pumilus ZB1 by oxidative stress could improve the removal of textile dyes. Methyl methanesulfonate (MMS) induced oxidative stress significantly promoted laccase expression of B. pumilus ZB1. Both the level of hydrogen dioxide and superoxide anion showed a significant positive correlation with laccase activity (RSQ = 0.963 and 0.916, respectively) along with the change of MMS concentration. The regulation of laccase expression was closely related to oxidative stress. The overexpressed laccase in the supernatant improved the decolorization of synthetic dyes (16.43% for Congo Red, 54.05% for Crystal Violet, and 41.61% for Reactive Blue 4). Laccase was subsequently expressed in E. coli . Investigation of the potential of bacterial laccase in dye remediation using Congo Red showed that an effective degradation of azo dye could be achieved with laccase treatment. Laccase remediation alleviated the cytotoxicity of Congo Red to human hepatocytes. In silico study identified eight amino acid residues of laccase involved in binding with Congo Red. Overall, regulation of oxidative stress towards bacterium can be used as a promising approach for the improvement of bacterial bioactivity in synthetic dye remediation.
研究领域:
环境微生物学
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生物技术
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毒理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
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2023
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IF 8.3
Xiaoju Wang,Shanshan Hu,Haitao Mao,Xueyu Wei,Saraschandra Naraginti
In the recent past, the development of efficient materials for degradation and detoxification of antibiotics has gained more attention in wastewater treatment process . As a visible light active material AgVO 3 has attracted much concern in environmental remediation. To improve its efficiency and stability, a novel heterojunction was prepared by combining AgVO 3 with rGO and BiVO 4 through a hydrothermal method. The prepared AgVO 3 /rGO/BiVO 4 composite was further utilized for effective detoxification of Norfloxacin (NFC) antibiotic. The morphological analysis revealed the clear rod shaped AgVO 3 and leaf like BiVO 4 that are evenly distributed on reduced graphene oxide (rGO) layers. The visible light absorbance and the catalytic activity of AgVO 3 /rGO/BiVO 4 was dramatically improved compared to pure AgVO 3 and BiVO 4 . From the results it showed that the degradation efficiency of AgVO 3 /rGO/BiVO 4 (∼96.1%, k = 0.01782 min −1 ) was 2.5 times higher than pure AgVO 3 and 3.4 times higher than the pure BiVO 4 respectively towards NFC after 90 min. The higher efficiency could be attributed to the heterojunction formation and faster charge separation. The radical trapping experiments results indicated that the •OH, and O 2 •− are the main species responsible for degradation. The degradation products of NFC were analysed through ESI-LC/MS and pathway was proposed. Furthermore, the toxicity assessment of pure NFC and its degradation products was studied using E. coli as the model bacteria through colony forming unit assay and the results indicated the efficient detoxification was attained during the degradation process. Thus, our study provides new insight into detoxification of antibiotics using AgVO 3 based composites
研究领域:
环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2022
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IF 6.449
Guansong Shao,Jingsong Cao,Xiaodan Wu,Bingyang Qin,Zihan Wang,Ying Wang,Ying Zhang,Tao Wang,Yujie Fu
Ginkgo biloba extracts (GBE) is one of the most widely used natural drugs for the treatment of cardiovascular and cerebrovascular diseases, but how to remove ginkgolic acids (GAs) from extracts in a safe, efficient, and economical method is an urgent need. Combined with quantum chemistry theoretical calculations and surface molecular imprinting technology, an eco-friendly GAs molecularly imprinted polymer via dummy template molecules on silylated cellulose matrix (SCM-DMIP-GAs) has been developed to detoxify target GAs from GBE. The results of scanning electron microscope , Fourier transform infrared spectrum, X-ray diffraction, N 2 adsorption-desorption isotherm, thermogravimetry , and binding absorption experiments showed SCM-DMIP-GAs has homogeneous morphology, good selective adsorption performance, high absorption capacity and stable recyclability. Furthermore, as solid phase extraction adsorbent, SCM-DMIP-GAs displays an efficient detoxification effect (99.98 %) after once treatment. This study presents an economic, green, and efficient solution for pharmaceutical and medical fields in plant extracts detoxification.
研究领域:
药学
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材料科学
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分析化学
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环境科学
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产品关联
DOI
高影响因子
Journal of Cleaner Production
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2022
·
IF 11.072
Xu-Hui Huang,Rong Liu,Jia-Nan Chen,Xiu-Ping Dong,Bei-Wei Zhu,Lei Qin
Erythromycin has caused severe risk on the aquatic ecological environment and food chain propagation due to its extensive use, environmental persistence, and low efficiency of sewage removal. Our study monitored the erythromycin accumulation, self-detoxification behavior, and metabolic response of turbot in erythromycin-contaminated environments using a multi-omics method with the aim to improve the safety of turbot consumption and provide guidance for turbot culture. Erythromycin was found to rapidly accumulated and reached its peak in turbot in the first two days of exposure to erythromycin. Residual levels in the gill, liver, kidney, muscle, and blood were detected at 95.19, 72.80, 68.74, 51.3, and 12.33 ng/g, respectively. The risk of erythromycin residues in turbot can be effectively reduced by a withdrawal period longer than 12 d. Erythromycin-contaminated turbot muscles showed a significant decrease in flavor properties, particularly umami, sweet, and aroma precursors. A total of 232 lipids in four main categories, glycerides, phospholipids , fatty acyl, and sphingolipids, were found to show significant changes in the turbot muscles. The interacting metabolic network formed by taurine, glycerophospholipid, arginine, alanine , and glutamate metabolism, wherein turbot responded to erythromycin was verified through 14 significantly altered metabolites. A withdrawal period of at least half a month and the corresponding product labels for antibiotics should be formulated before the fish exposed to antibiotics during intensive culture are sold to protect the interests of consumers. This study could serve as a reference for the quality and safety risk assessment of turbot and other highly economical fishes affected by antibiotics exposure.
研究领域:
环境科学
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水产养殖学
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毒理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Yu-Xi Liu,Chao Hu,Yu-Ting Li,Ping Gao,Xue-Qing Yang
While previous studies have reported G protein-coupled receptor (GPCR)-mediated insecticide resistance in various arthropods, the understanding of GPCR-associated resistance mechanisms in Cydia pomonella remains limited. In this study, a total of 95 CpGPCR genes categorized into four families were identified in C. pomonella. Results revealed high expression levels of the majority of the CpGPCRs during the first larval stage and in the head of C. pomonella. Exposure to lambda-cyhalothrin significantly increased the expression of 15 CpGPCRs, including CpGPCR70, which is highly expressed in all larval stages and shows the highest expression in the midgut. RNA interference (RNAi) demonstrated that downregulation of CpGPCR70 leads to reduced expression of key resistance-related genes and a decreased tolerance of larvae to lambda-cyhalothrin. These findings indicate that CpGPCR70 plays a crucial role in regulating the expression of detoxifying genes involved in lambda-cyhalothrin resistance, offering valuable insights for the development of more effective pest control strategies.
研究领域:
昆虫学
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分子生物学
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害虫防治
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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）