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The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1071-1092页

作者： Minxuan Xu Jun Tan Liancai Zhu Chenxu Ge Wei Dong Xianling Dai Qin Kuang Shaoyu Zhong Lili Lai Chao Yi Qiang Li deshuai lou Linfeng Hu Xi Liu Gang Kuang Jing Luo Jing Feng Bochu Wang Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region School of Biological and Chemical EngineeringChongqing University of EducationChongqing 400067China College of Modern Health Industry Chongqing University of EducationChongqing 400067China Key Laboratory of Biorheological Science and Technology(Chongqing University) Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400030China Shandong Cancer Hospital and Institute Shandong First Medical University&Shandong Academy of Medical SciencesJinan 250117China

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis(NASH)have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are *** rhomboid protein 2(IRHOM2),a promising target for treatment of inflammation-related diseases,contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis(NASH)***,the molecular mechanism underlying Irhom2 regulation is still not completely *** this work,we identify the ubiquitin-specific protease 13(USP13)as a critical and novel endogenous blocker of IRHOM2,and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in ***-specific loss of the Usp13 disrupts liver metabolic homeostasis,followed by glycometabolic disorder,lipid deposition,increased inflammation,and markedly promotes NASH ***,transgenic mice with Usp13 overexpression,lentivirus(LV)-or adeno-associated virus(AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of ***,in response to metabolic stresses,USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N(UBC13),a ubiquitin E2 conjugating enzyme,and thus prevents its activation of downstream cascade ***13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

关键词： Usp13 Irhom2 NASH Hepatosteatosis Ubc13 NAFLD Ubiquitination Liver inflammation

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Multicombination Nanoparticle Suppresses Listeria monocytogenes-Induced Septicemia-Associated Acute Hepatic Failure

Multicombination Nanoparticle Suppresses Listeria monocytoge...

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2018年第十二届中国药物制剂大会

作者： XU Minxuan GE Chenxu lou deshuai 谭君 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region Chongqing University of Education 三峡库区药用资源重庆市重点实验室重庆第二师范学院

＜正＞Septicemia is a severe bacterial infection–induced inflammatory *** has been confirmed that immune suppression and uncontrolled inflammatory responses are one of the major pathophysiological mechanisms of *** studies indicate that septicemia is a common and major cause of the observed high mortality and morbidity rates in *** due to septicemia in China increases

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