FASEB JOURNAL
·
2022
·Vol. 36
·期 5
·e22266
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IF 5.834
Huiqing Hu,Ruxing Zhao,Qin He,Chen Cui,Jia Song,Xinghong Guo,Nan Zang,Mengmeng Yang,Ying Zou,Jingwen Yang,Jinquan Li,Liming Wang,Longqing Xia,Lingshu Wang,Falian He,Xinguo Hou,Fei Yan,Li Chen
Type 2 diabetes mellitus (T2DM) is an age-related disease characterized by impaired pancreatic β cell function and insulin resistance. Recent studies have shown that the accumulation of senescent β cells under metabolic stress conditions leads to the progression of T2DM, while senolysis can improve the prognosis. However, the specific mechanism of β cell senescence is still unclear. In this study, we found that the increased load of senescence pancreatic β cells in both older mice and obese mice induced by high-fat diet (HFD) (DIO mice) was accompanied by activation of the Cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway and using cGAS or STING small interfering RNA or STING inhibitor C176 to downregulate this pathway reduced the senescence-associated secretion profile (SASP) and senescence of Min6 cells treated with palmitic acid or hydrogen peroxide. C176 intervention in DIO mice also significantly reduced the inflammation and senescence of the islets, thereby protecting the function of pancreatic β cell and glucose metabolism. Our study further revealed that mitochondrial DNA (mtDNA) leakage under metabolic stress conditions was critical for the activation of the cGAS-STING pathway, which can be reversed by the mtDNA depleting agent ethidium bromide. Consistently, mtDNA leakage was more severe in older mice and was accelerated by a chronic HFD. In conclusion, we demonstrate that cytoplasmic mtDNA activates the cGAS-STING pathway to mediate SASP during the accelerated senescence of pancreatic β-cells induced by metabolic stress, and this process can be downregulated by the STING inhibitor C176.
研究领域:
内分泌学
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细胞生物学
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糖尿病研究
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分子生物学
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DOI
PubMed
高影响因子
Chemistry-An Asian Journal
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2019
·Vol. 15
·期 15
·2341-2345
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IF 3.698
Junjun Hou,Meihuizi Jiang,Xiao He,Pengchao Liu,Chang Long,Lian Yu,Zhiwei Huang,Jin Huang,Lianshan Li,Zhiyong Tang
Graphical A sub-10 nm polyamide nanofiltration membrane was synthesized through interfacial polymerization due to the extremely low solubility of the ethidium bromide monomer in organic phase, which strictly limits the polymerization process at the interface of the water and hexane. Thanks to the ultrathin thickness, these membranes show excellent water permeance and high dye rejection. To separate small molecules from the solvent with high permeability and selectivity, the membrane process is thought to be highly effective with much lower energy consumption when compared to the traditional thermal-based separation process. To achieve high solvent permeance, a sub-10 nm thick polyamide nanofiltration membrane was synthesized through interfacial polymerization of ethidium bromide (EtBr) and trimesoyl chloride (TMC). Thanks to the extremely low solubility of the EtBr monomer in the organic phase, the polymerization process was strictly limited at the interface of the water and hexane, leading to an ultrathin polyamide membrane with a thickness down to sub-10 nm. When used in nanofiltration, these ultrathin membranes display ultrafast water permeation of 40 liter per square meter per hour per bar (L m −2 h −1 bar −1 ), and a high Congo red rejection rate of 93 %. This work demonstrates a new route to synthesize ultrathin polyamide membranes by the traditional interfacial polymerization.
研究领域:
化学工程
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材料科学
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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 MEMBRANE SCIENCE
·
2023
·
IF 9.5
Zhixiao Liu,Zhiming Mi,Lingjun Meng,Yangyang Huang,Dexing Zhang,Junman Wang,Kaiyang Zhang,Jingling Xiao,Pingli Liu,Zhi Rao,Hongru He,Shuai Wang
Simultaneous separation of divalent co-ions and counter-ions from mixed ions water environment was urgently needed to improve separation efficiency and reduce energy consumption. The charged Janus nanofiltration membranes (NFMs) came into being based on the Donnan effect, however, its practical application was still limited by complex preparation, low permeability or poor ion selectivity. Here, with carboxylated polysulfone (PSF–COOH) ultrafiltration membrane as the support layer, a newly discovered quaternary ammonium salt containing diamine group (ethidium bromide, EB) was used to modify pristine polyamide nanofilm to prepare a novel charged Janus NFM. Structural characterization and molecular dynamics simulation indicated that the difference in electrostatic force of PSF-COOH with piperazine (PIP) and EB resulted in a difference of at least 20 times between their diffusion rates and hence achieved their regular distributions in the oil-water interface. As a result, EB modification induced the structure heterogeneity (charge and morphology) of the polyamide layer, which allowed the selectivity of both monovalent/divalent anions and cations to be higher than 45, while ensuring a permeability of up to 56.2 L/m 2 ⋅h. Moreover, other analogues of EB were applied and proved the generality of the mechanism for preparing charged Janus NFMs in this study, which represented a method for the scalable preparation of ultra-selective membranes with heterostructure for simultaneous separation of divalent co-ions and counter-ions.
研究领域:
材料科学
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化学工程
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膜技术
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环境科学
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产品关联
DOI
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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2019
·
IF 2.679
Xiao-Yu Zhu,Sheng-Ya Guo,Bo Xia,Chun-Qi Li,Lei Wang,Yong-Hui Wang
RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis . In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 μM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.
研究领域:
神经科学
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药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
eLife
·
2025
·
IF 0
Yajun Zhai,Peiyi Liu,Xueqin Hu,Changjian Fan,Xiaodie Cui,Qibiao He,Dandan He,Xiaoyuan Ma,Gongzheng Hu
Discovering new strategies to combat the multidrug-resistant bacteria constitutes a major medical challenge of our time. Previously, artesunate (AS) has been reported to exert antibacterial enhancement activity in combination with β-lactam antibiotics via inhibition of the efflux pump AcrB. However, combination of AS and colistin (COL) revealed a weak synergistic effect against a limited number of strains, and few studies have further explored its possible mechanism of synergistic action. In this article, we found that AS and EDTA could strikingly enhance the antibacterial effects of COL against mcr-1- and mcr-1+ Salmonella strains either in vitro or in vivo, when used in triple combination. The excellent bacteriostatic effect was primarily related to the increased cell membrane damage, accumulation of toxic compounds and inhibition of MCR-1. The potential binding sites of AS to MCR-1 (THR283, SER284, and TYR287) were critical for its inhibition of MCR-1 activity. Additionally, we also demonstrated that the CheA of chemosensory system and virulence-related protein SpvD were critical for the bacteriostatic synergistic effects of the triple combination. Selectively targeting CheA, SpvD, or MCR using the natural compound AS could be further investigated as an attractive strategy for the treatment of Salmonella infection. Collectively, our work opens new avenues toward the potentiation of COL and reveals an alternative drug combination strategy to overcome COL-resistant bacterial infections.
研究领域:
微生物学
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药理学
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传染病学
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耐药性
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产品关联
DOI
PubMed
JOURNAL OF FLUORESCENCE
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2025
·
IF 3.1
Zhang Hongmei,Yang Yunxia,Wang Yanqing
Sudan dyes are recognized as carcinogens, which are strictly determined whether there are them in food for food safety. Hence, in order to understand the mechanism at the molecular level, this work investigated the binding interactions of Sudan I-IV with calfthy mus DNA. The synchronous fluorescence and UV–vis spectral results suggested the complex formation between Sudan I-IV and ct-DNA. EB and Hoechst 33258 displacement experimental results confirmed the binding sites of Sudan I-IV in ct-DNA and the minor groove-binding mode of Sudan I-IV with ct-DNA. The molecular modeling computational method also proved binding mode, which is consistent with the spectral experiments. In addition, the aromatic rings of Sudan I-IV play important roles in binding with DNA. Compared to Sudan I and II, the increase of molecular conjugation system enhances the binding abilities of Sudan III and Sudan IV with DNA. Vdm + Hbond + desolv energies of them are the main contribution of their combined energies.
研究领域:
生物化学
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食品安全
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
·
IF 8.3
Qianwei Qu,Xingyu Huang,Zhenxin Zhu,Jun Wang,Mengmeng Zhao,Wenqiang Cui,Yadan Zheng,Yanyan Liu,Xueying Chen,Zhiyun Zhang,Na Dong,Chunliu Dong,Yanhua Li
Background Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti- S. aureus effect. Nevertheless, the specific mechanism of action of sanguinarine against S. aureus biofilms remains unexplored. Purpose The objective of this study was to elucidate the target site of sanguinarine in S. aureus , as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics. Methods Initially, we assessed the in vitro anti- S. aureus properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with S. aureus biofilm formation was preliminarily analyzed in vitro . Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated in vivo using mouse models of biofilm and bacteremia. Results Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering S. aureus biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the S. aureus load in mouse organs and the formation of biofilm on the surface of implants in vivo without any resistance. Conclusions In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of S. aureus and targeting IGPD. These findings suggest that sanguinarine holds potential for further development as a novel antibiotic to combat biofilm-associated infections.
研究领域:
微生物学
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药理学
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感染与免疫
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
·
IF 8
Mengyuan Chen,Chong Wang,Jing Tan,Jin Wang,Chen Wang
Nanofluidic membranes hold great prospects in sensitive and rapid detection of bioanalysts, while remaining lacking robust and general approaches for specificity. In this work, we introduce a cell membrane-inspired nanofluidic membrane with excellent ion current rectification properties as a simple and robust platform for label-free and ultrasensitive biosensing. The asymmetric nanofluidic membrane is prepared by coupling a two-dimensional covalent organic framework (COF) membrane to an anodic aluminum oxide (AAO) nanochannel via hydrogen bonding. The prepared COF/AAO membrane presents selective ion transport due to the asymmetric structure and anion selectivity of COF. With the large surface area and abundant functional modification sites of COF, further grafting of the recognition unit can be easily achieved to mimic the recognition process of receptors and ligands on cell membranes. As a proof of concept, the application in bacterial detection is demonstrated by covalently bonded Concanavalin A as recognition units. The highly amplified ionic current based on ion current rectification properties of the COF/AAO membrane allows sensitive and selective bioanalysis. Specifically, the proposed asymmetric nanofluidic membrane presents a linear detection range from 10 to 10 6 CFU/mL with an ultralow detection limit of 7 CFU/mL for E. coli . This work reveals the great potential of COF/AAO hybrid nanofluidic membrane as a sensor for rapid and precise bioanalysis.
研究领域:
生物传感器
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材料科学
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微生物学
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产品关联
DOI
高影响因子
RSC Advances
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2025
·Vol. 15
·期 7
·5413-5425
·
IF 4.6
Zhuo Li,Hui Li,Zhenrong Tang,Qingxia Tang,Chang Liao,Hua Tang,Dan Wang
Bacterial biofilms play a crucial role in the emergence of antibiotic resistance and the persistence of chronic infections. The challenge of effectively eradicating bacterial biofilms while ensuring minimal toxicity to normal cells persists. Carbon-based artificial nanoenzymes have attracted considerable attention as emerging nanotheranostic agents, owing to their biocompatibility, cost-effectiveness, and straightforward synthesis. In this study, we have developed a multifunctional carbon dots (CDs) system, specifically CDs functionalized with 1-(3-aminopropyl) imidazole (API), termed CDs-API. This system demonstrates acid-activated antibiofilm activity. The CDs-API were synthesized from chlorogenic acid (ChA), a bioactive compound naturally occurring in coffee, and subsequently functionalized with API to achieve charge-switchable properties under acidic conditions. This distinctive feature enables CDs-API to efficiently penetrate bacterial biofilms and selectively target the colonized bacteria. The enzyme-like activity of CDs-API effectively consumes high levels of glutathione (GSH) within the biofilm, leading to the accumulation of reactive oxygen species (ROS). Consequently, this process degrades the extracellular polymeric substance (EPS) matrix, damages bacterial DNA and protein structures, and disrupts the redox balance, ultimately leading to bacterial cell death. Experimental results demonstrated that CDs-API effectively inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAE) while promoting wound healing with minimal damage to healthy tissues. The acid-activated charge-switchable capability of CDs-API provides superior antibacterial efficacy compared to traditional antibiotics, rendering it a promising candidate for the treatment of bacterial biofilm infections.
研究领域:
纳米医学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Caiyuan Yu,Yuanwei Sun,Chunkai Yang,Yan Fang,Qi Meng,Yibin Qiu,Peng Lei,Hong Xu,Qi Zhang,Sha Li
Tremella fuciformis , one of the most approved mushrooms worldwide, possesses both edible and medicinal value. However, low transformation efficiency and high false positive rate, long verification period, and low expression of heterologous proteins hinder further genetic research. In this study, a polyethylene glycol-mediated genetic transformation system was established by using the homologous resistance marker carboxin in T. fuciformis . By optimizing the protoplast quality and transformation conditions, the transformation efficiency reached 8.23 CFU/μg, and the positive rate reached 64.95%. Moreover, Driselase-Heating-Freezing screening system was developed for rapid transformants verification, which took only 35–45 min and made the colony PCR 100% accurate. Considering the rationality of tRNA use frequency in heterologous genes, the coordinated relative synonymous codon usage (RSCU) strategy was adopted to recode the heterologous gene sequence, which ensured the protein expression level. This study comprehensively enhances molecular biology tools in T. fuciformis , and lays a foundation for further development.
研究领域:
分子生物学
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遗传学
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生物技术
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jiangli Song,Hanlian Chen,Rongkai Pan,Fangyu Jin,Jie Tang,Qianqian Huang,Guohua Zhou,Xiumei Song
Understanding the interactions between small molecules and calf thymus deoxyribonucleic acid (ctDNA) is critical for certain aspects of drug discovery. In this study, three 11 H -indeno[1,2-b]quinoxalin-11-one thiosemicarbazones were synthesized and their interaction with ctDNA was examined through various spectroscopic techniques, including ultraviolet (UV) spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectrum, and through physicochemical methods, including viscosity measurements. In addition, the effects of these thiosemicarbazone compounds 4a, 4b and 4c on several cancer cell lines were explored. The results of UV absorption, fluorescence quenching and CD experiments indicated that compounds 4a, 4b and 4c primarily bound to ctDNA by an intercalation. This mode of interaction was further corroborated by viscosity measurements. Docked poses of compound 4a revealed that it formed a crucial N position hydrogen bond with the DNA receptor. The chemical structure of compound 4a was further confirmed by X-ray crystallographic analysis. Through biological evaluation, it was found that the in vitro cytotoxicity of three compounds agreed with the order of their binding strength to ctDNA, indicating that the antitumor activity of these compounds correlated with their binding affinity to ctDNA.
研究领域:
生物化学
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药物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2024
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IF 2.7
Xiaodong Liu,Tianyi Jiang,Huiyun Jin,Chenxi Yan,Yuqi Tong,Jiaquan Ding,Yaqi Li,Lian Huang,Zhaohui Zhang
Beryllium sulfate (BeSO 4 ) can cause inflammation through the mechanism, which has not been elucidated. Mitochondrial DNA (mtDNA) is a key contributor of inflammation. With mitochondrial damage, released mtDNA can bind to specific receptors (e.g., cGAS) and then activate related pathway to promote inflammatory responses. To investigate the mechanism of mtDNA in BeSO 4 -induced inflammatory response in 16HBE cells, we established the BeSO 4 -induced 16HBE cell inflammation model and the ethidium bromide (EB)-induced ρ 0 16HBE cell model to detect the mtDNA content, oxidative stress-related markers, mitochondrial membrane potential, the expression of the cGAS-STING pathway, and inflammation-related factors. Our results showed that BeSO 4 caused oxidative stress, decline of mitochondrial membrane potential, and the release of mtDNA into the cytoplasm of 16HBE cells. In addition, BeSO 4 induced inflammation in 16HBE cells by activating the cGAS-STING pathway. Furthermore, mtDNA deletion inhibited the expression of cGAS-STING pathway, IL-10, TNF-α, and IFN-β. This study revealed a novel mechanism of BeSO 4 -induced inflammation in 16HBE cells, which contributes to the understanding of the molecular mechanism of beryllium and its compounds-induced toxicity.
研究领域:
毒理学
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细胞生物学
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免疫学
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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）