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Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2024年第4期13卷 2289-2309页

作者： Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu kamil kuca Tushuai Li Wenda Wu School of Biology and Food Engineering Changshu Institute of TechnologySuzhou 215500China Center for Clinical Mass Spectrometry School of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic College of Life Science Yangtze UniversityJingzhou 434025China Wuxi Medical College Jiangnan UniversityWuxi 214122China Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch Wuxi 214013China

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关键词： Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation

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MicroRNA regulates the toxicological mechanism of four mycotoxins in vivo and in vitro

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Journal of Animal Science and Biotechnology 2022年第4期13卷 923-934页

作者： Jia Chen Shuhua Yang Peng Li Aibo Wu Eugenie Nepovimova Miao Long Wenda Wu kamil kuca College of Animal Science&Veterinary Medicine Shenyang Agricultural UniversityShenyang 110866China SIBS-UGENT-SJTU Joint Laboratory of Mycotoxin Research CAS Key Laboratory of NutritionMetabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Biomedical Research Center University Hospital Hradec KraloveHradec Kralove 50003Czech Republic.

Mycotoxins can cause body poisoning and induce carcinogenesis,often with a high mortality rate.Therefore,it is of great significance to seek new targets that indicate mycotoxin activity and to diagnose and intervene in mycotoxin-induced diseases in their early stages.MicroRNAs(miRNAs)are physiological regulators whose dysregulation is closely related to the development of diseases.They are thus important markers for the occurrence and development of diseases.In this review,consideration is given to the toxicological mechanisms associated with four major mycotoxins(ochratoxin A,aflatoxin B1,deoxynivalenol,and zearalenone).The roles that miRNAs play in these mechanisms and the interactions between them and their target genes are explained,and summarize the important role of histone modifications in their toxicity.As a result,the ways that miRNAs are regulated in the pathogenicity signaling pathways are revealed which highlights the roles played by miRNAs in preventing and controlling the harmful effects of the mycotoxins.It is hoped that this review will provide a theoretical basis for the prevention and control of the damage caused by these mycotoxins.

关键词： Histone Methylation MicroRNA Mycotoxin

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Toxic Potential of Palytoxin

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第5期35卷 773-780页

作者： Ji?í PATOCKA Ramesh C.GUPTA 吴庆华 kamil kuca University of South Bohemia Ceske Budejovice Faculty of Health and Social StudiesDepartment of Radiology and Toxicology Biomedical Research Center University Hospital Toxicology Department Murray State University College of Life Science Yangtze University Faculty of Informatics and Management University of Hradec Kralove

This review briefly describes the origin,chemistry,molecular mechanism of action,pharmacology,toxicology,and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids（i.e. Palythoa）,and Cyanobacteria（Trichodesmium）. Palytoxin is a very large,non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na＋/K＋-ATPase with a Kd of 20 p M and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 p S. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous,intraperitoneal,intramuscular,subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal,yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation,cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals,and currently this toxin is of great concern worldwide.

关键词： dermal extremely subcutaneous analogues noted intravenous intramuscular potent intake hydrophilic

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Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA， downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2023年

作者： Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu kamil kuca Tushuai Li Wenda Wu Wuxi Medical College Jiangnan University MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University Department of Chemistry Faculty of Science University of Hradec Kralove Center for Clinical Mass Spectrometry School of Pharmaceutical Sciences Soochow University College of Life Science Yangtze University School of Biology and Food Engineering Changshu Institute of Technology Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch School of Food and Biological Engineering Hefei University of Technology

Aflatoxin B1 (AFB1) is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin， particularly causing damages to kidney. Glomerular podocytes are terminally differentiated epithelial cells. AFB1 induces podocyte inflammation， proteinuria and renal dysfunction. Studying the mechanism of AFB1-induced podocyte inflammation and murine kidney dysfunction， we detected that AFB1 increased ubiquitin-dependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7 (TRIM7) in mouse podocyte clone-5 (MPC-5) and mouse glomeruli. Reduction of RelA resulted in decreasing microRNA-9 (miR-9) and activating the chemokine receptor 4 (CXCR4)， thioredoxin interacting protein (TXNIP)， and NOD-like receptor pyrin domain-containing 3 (NLRP3) signaling axis (CXCR4/TXNIP/NLRP3 pathway)， leading to podocyte inflammation. We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation. Overexpression of miR-9 or deletion of CXCR4 suppressed AFB1-induced CXCR4/TXNIP/NLRP3 pathway， resulting in alleviating podocyte inflammation and kidney dysfunction. Our findings indicated that ubiquitin-dependent proteolysis of RelA， downregulation of miR-9， and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB1-induced glomerular podocyte inflammation. Our study revealed a novel mechanism， via RelA， for the control of AFB1’s nephrotoxicity， leading to an effective protection of food safety and public health.

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实验室用数字图像处理进行三维表面轮廓诊断

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Journal of Central South University 2020年第3期27卷 811-823页

作者： Robert FRISCHER Ondrej KREJCAR Ali SELAMAT kamil kuca Center for Basic and Applied Research Faculty of Informatics and ManagementUniversity of Hradec KraloveRokitanskeho 62Hradec Kralove 50003Czech Republic Malaysia Japan International Institute of Technology(MJIIT) Universiti Teknologi Malaysia Kuala LumpurJalan Sultan Yahya PetraKuala Lumpur 54100Malaysia Media and Games Center of Excellence(MagicX) Universiti Teknologi MalaysiaSkudai 81310Malaysia School of Computing Faculty of EngineeringUniversiti Teknologi Malaysia(UTM)Skudai 81310Malaysia

表面质量和轮廓精度的测量难是许多工业行业中存在的主要问题,半成品的表面质量直接影响到后续的生产步骤。虽然有许多方法可以获得所需的数据,但根据问题的复杂性所需要的测量硬件,比如二维或三维扫描仪,都比较昂贵。因此,本文提出一... 详细信息

表面质量和轮廓精度的测量难是许多工业行业中存在的主要问题,半成品的表面质量直接影响到后续的生产步骤。虽然有许多方法可以获得所需的数据,但根据问题的复杂性所需要的测量硬件,比如二维或三维扫描仪,都比较昂贵。因此,本文提出一种新颖的算法,并在简单的三维扫描仪模型上,以0.1 mm的分辨率的图像处理进行了验证。扫描表面轮廓的方法有很多,但图像处理是目前工业自动化中最热门的课题。最重要的是,为了获得表面图像,使用标准的高分辨率反射相机,以MatLab为软件环境实现后处理。因此,这种解决方案可以替代昂贵的扫描仪,利用单一用途设备的额外功能扩展来实现。

关键词：剖面诊断图像处理三维曲面 MatLab 测量

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