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Senp2.regulates adipose lipid storage by de-SUMOylation of Setdbl

Journal of Molecular Cell Biology 2018年第3期10卷 258-266页

作者： Quan Zheng Ying Cao Yalan chen Jiqiu Wang Qiuju Fan xian Huang Yiping Wang Tianshi Wang Xiuzhi Wang Jiao Ma Jinke cheng Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai liao Tong University School of Medicine Shanghai 200025 China Department of Endocrinology and Metabolism Ruijin Hospital Shanghai liao Tong University School of Medicine Shanghai 200025 China Cancer Metabolism Laboratory Institutes of Biomedical Science Shanghai Medical College Fudan University Shanghai 200032 China

One major function of adipocytes is to store excess energy in the form of triglycerides. Insufficient adipose lipid storage is asso- ciated with many pathological conditions including hyperlipidemia, insulin resistance, and type 2.diabetes. In this study, we observed the overexpression of SUMO-specific protease 2.（Senp2. in adipose tissues during obesity. Adipocyte 5enp2.deficiency resulted in less adipose lipid storage accompanied by an ectopic fat accumulation and insulin resistance under high-fat diet feeding. We further found that SET domain bifurcated 1 （Setdbl） was a SUMOylated protein and that SUMOylation promoted Setdbl occupancy on the promoter locus of Pparg and Cebpa genes to suppress their expressions by H3Kgme3. Senp2.could suppress Setdbl function by de-SUMOylation. In adipocyte 5enp2.deficiency mice, accumulation of the SUMOylated Setdbl suppressed the expression of Pparg and Cebpo genes as welt as lipid metabolism-related target genes, which would decrease the ability of lipid storage in adipocytes. These results revealed the crucial role of Senp2.Setdbl axis in controlling adipose lipid storage.

关键词： lipid storage Senp2 Setdbl H3Kgme3 Pparg and Cebpa

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IRF8新发移码突变的基因功能分析

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复旦学报（医学版） 2024年第3期51卷 359-367页

作者：李乐盈陈尧周维涛何晨张端午钱莉玲国家儿童医学中心/复旦大学附属儿科医院呼吸科上海201102 国家儿童医学中心/复旦大学附属儿科医院儿科研究所上海201102 复旦大学生物医学研究院上海200032

目的对反复肺炎患儿队列病因筛查中发现的干扰素调节因子8基因(interferon regulator factor 8,IRF8)新发突变(c.12.6dupA)进行分子细胞水平的功能研究与验证。方法针对IRF8突变序列构建野生与突变蛋白过表达载体,通过质粒转染或构建慢... 详细信息

目的对反复肺炎患儿队列病因筛查中发现的干扰素调节因子8基因(interferon regulator factor 8,IRF8)新发突变(c.12.6dupA)进行分子细胞水平的功能研究与验证。方法针对IRF8突变序列构建野生与突变蛋白过表达载体,通过质粒转染或构建慢病毒感染不同工具细胞,通过qPCR、Western blot、免疫荧光等实验手段检测其表达差异及对下游炎症相关基因表达调控的改变。结果IRF8野生及突变过表达载体构建成功,且转染效率可观,包装成的慢病毒感染效率亦较高。突变基因IRF8(c.12.6dupA)相较于野生型IRF8转录水平降低,表达蛋白的相对分子质量略增大,表达量降低,突变蛋白IRF8mut相对野生型IRF8蛋白核质比增加,IRF8(c.12.6dupA)对下游ISRE元件的抑制功能增强。结论IRF8新发移码突变属于功能获得型(gain of function,GOF)突变。

关键词：干扰素调节因子8(IRF8) 移码突变反复感染转录调控

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从快照到电影:捕捉单核苷酸分辨率的真核生物转录起始过程

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Science Bulletin 2024年第7期69卷 853-855页

作者：尚雪莹徐从玲陈飞 fudan university Shanghai Cancer Center Institutes of Biomedical SciencesShanghai Key Laboratory of Radiation OncologyShanghai Key Laboratory of Medical EpigeneticsShanghai Medical College of Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative MedicineTranslational Research Institute of Brain and Brain-Like IntelligenceShanghai Fourth People’s HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

The process of transcription is generally delineated into three sequential phases:initiation,elongation,and *** transition between these phases,particularly from initiation to elongation,requires substantial conformational and compositional reconfigurations within the transcription machinery to enable functional *** initiation is characterized by the assembly of a preinitiation complex(PIC).

关键词： figuration enable termination

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Clinical features of acute hepatitis E super-infections on chronic hepatitis B

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World Journal of Gastroenterology 2016年第47期22卷 10388-10397页

作者： Chong chen Shu-Ye Zhang Dan-Dan Zhang Xin-Yan Li Yu-Ling Zhang Wei-Xia Li Jing-Jing Yan Min Wang Jing-Na Xun Chuan Lu Yun Ling Yu-xian Huang Liang chen Wenzhou Medical university Wenzhou 325000 Zhejiang Province China Shanghai Public Health Clinical Center Fudan University Shanghai 201508 China institutes of biomedical {2. Fudan UniversityShanghai 200433 China School of Life sciences Hebei Normal University Shijiazhuang 050000 Hebei Province China

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 2.8 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, china. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse *** The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 2..4%, P 2..3% vs 7.5%, P = 0.002.. Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012., alcohol consumption(OR: 6.4, P = 0.02.), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 2..7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in sup

关键词： Cirrhosis Co-infections Liver failure Liver decompensation Stages of hepatitis B virus infection

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Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong Hu Quentin Liu Yi-Zhou Jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu fudan university Shanghai Cancer Center & {2. of biomedical sciences State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent Pathology Institute and Department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen university Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Department of Breast Surgery Xiangya HospitalChangsha 410008China Department of Breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant ***,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in ***,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant ***,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and *** studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 ***1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase ***1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

关键词： NOD1 breast chemotherapy

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The roles of cysteines in the heme domain of human soluble guanylate cyclase

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Chinese Chemical Letters 2012年第8期23卷 973-976页

作者： Fang Fang Zhong Xiao Xiao Liu Jie Pan Zhong xian Huang xiang Shi Tan Department of Chemistry Fudan UniversityShanghai 200433China institutes of biomedical {2. Fudan UniversityShanghai 200433China

Soluble guanylate cyclase（sGC） is a critical heme-containing enzyme involved in NO *** dimerization of sGC subunits is necessary for its bioactivity and its mechanism is a striking and an indistinct *** roles of heme domain cysteines of the sGC on the dimerization and heme binding were investigated *** site-directed mutations of three conserved cysteines（C78A,C12.A and C174S） were studied systematically and the three mutants were characterized by gel filtration analysis,UV-vis spectroscopy and heme transfer ***78 was involved in heme binding but not referred to the dimerization,while Cys174 was demonstrated to be involved in the *** results provide new insights into the cysteine-related dimerization regulation of sGC.

关键词： Human soluble guanylate cyclase sGC Heine domain Cysteine Dimerization

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Metal organic frameworks as advanced extraction adsorbents for separation and analysis in proteomics and environmental research

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Science china Chemistry 2022年第4期65卷 650-677页

作者： Yonglei Wu Haolin chen Yijie chen Nianrong Sun Chunhui Deng Department of Gastroenterology and Hepatology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Chemistry Institutes of Biomedical SciencesFudan UniversityShanghai 200433China

Human health is always under global spotlight, but now it suffers from severe environmental issue and various *** highly selective and effective extraction technique for environmental pollutant removal and target protein/peptide molecules conduces to the solution of environmental contamination and early disease detection, which will promise human health to a great degree. Metal-organic frameworks(MOFs) are typical porous nanomaterials featuring rigid structure, large specific surface area, thermal and chemical stability, numerous active sites and easy functionalization. Moreover, multitudinous combination of metal centers and organic ligands often endows MOFs with structure and function diversity. Owing to such splendid merits, MOFs are able to act as advanced adsorbents for sample-pretreatment in proteomics and environmental field,which indicates great efficiency, reproducibility, convenience and cost-effectiveness. In this review, the novel design of MOFs and their applications in proteomics and environmental research are roughly summarized. We first introduce the representative researches of functional MOFs in protein post-translational modifications including glycosylation and phosphorylation, mainly focusing on hydrophilic interaction liquid chromatography(HILIC) or metal-oxide affinity chromatography(MOAC). The important role of MOFs in enzyme immobilization is also covered. Then MOF-based adsorptive removal of diverse environmental contaminants embracing plasticizers, pesticides and varied water pollutants(pharmaceutical and personal care products,organic dyes and heavy metals), in which multiple chemical and non-chemical interactions play a vital role, is emphatically discussed. Finally, we analyze the existing problems and challenges in the way of wider practical applications and put forward prospective anticipation.

关键词： metal-organic frameworks adsorbent sample pre-treatment proteomics research environmental research

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Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system

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Genes & Diseases 2015年第1期2卷 96-105页

作者： xiang chen Jing Cui Zhengjian Yan Hongmei Zhang xian chen Ning Wang Palak Shah Fang Deng chen Zhao Nisha Geng Melissa Li Sahitya K.Denduluri Rex C.Haydon Hue H.Luu Russell R.Reid Tong-Chuan He Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoILUSA Department of Pediatric Oncology Baylor College of MedicineHoustonTXUSA Ministry of Education Key Laboratory of Diagnostic Medicine and The Affiliated Hospitals of Chongqing Medical UniversityChongqingChina Department of Laboratory Medicine The Affiliated Hospitals of Qingdao UniversityQingdaoChina Departments of Oncology Cell Biology and Laboratory MedicineThird Military Medical UniversityChongqingChina Section of Plastic&Reconstructive Surgery Department of SurgeryThe University of Chicago Medical CenterChicagoILUSA

Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene ***,stable transgene expression has been accomplished by using retroviral or lentiviral ***,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling *** piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian *** its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation ***,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac *** engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase *** further determine the drug selection timeline to achieve optimal stable transgene ***,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral *** the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high ***,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression.

关键词： Mesenchymal stem cells piggyBac transposon piggyBac transposase Retroviral vectors Stable transgene expression Transposition

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biomedical polymers: synthesis, properties, and applications

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Science china Chemistry 2022年第6期65卷 1010-1075页

作者： Wei-Hai chen Qi-Wen chen Qian chen Chunyan Cui Shun Duan Yongyuan Kang Yang Liu Yun Liu Wali Muhammad Shiqun Shao chengqiang Tang Jinqiang Wang Lei Wang Meng-Hua Xiong Lichen Yin Kuo Zhang Zhanzhan Zhang Xu Zhen Jun Feng Changyou Gao Zhen Gu Chaoliang He Jian Ji Xiqun Jiang Wenguang Liu Zhuang Liu Huisheng Peng Youqing Shen Linqi Shi Xuemei Sun Hao Wang Jun Wang Haihua Xiao Fu-Jian Xu Zhiyuan Zhong xian-Zheng Zhang Xuesi chen Key Laboratory of biomedical Polymers of Ministry of Education&Department of Chemistry Wuhan UniversityWuhan430072China Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou215123China School of Materials Science and Engineering Tianjin Key Laboratory of Composite and Functional MaterialsTianjin UniversityTianjin300350China Key Laboratory of biomedical Materials of Natural Macromolecules(Beijing university of Chemical Technology) Ministry of EducationBeijing Laboratory of Biomedical MaterialsCollege of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing100029China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Functional Polymer Materials of Ministry of EducationCollege of ChemistryNankai UniversityTianjin300071China Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Jinhua Institute of Zhejiang university Jinhua321299China Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou310027China ZJU-Hangzhou Global Scientific and Technological Innovation Center Hangzhou311215China State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular Science and Laboratory of Advanced MaterialsFudan UniversityShanghai200438China CAS Key Laboratory for biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nano-scienceNational Center for Nanoscience and Technology(NCNST)Beijing100190China School of biomedical sciences and Engineering Guangzhou International CampusSouth China University of TechnologyGuangzhou510006China Institute of Functional Nano and So

biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

关键词： biomedical polymer nanomedicine cancer therapy drug delivery bioimaging and biosensing tissue engineering regenerative medicine cytotoxicity biocompatibility

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New prognostic parameters for very-low-risk gastrointestinal stromal tumors

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Chinese Medical Journal 2011年第13期124卷 1964-1969页

作者： WU xian-hua HOU Ying-yong XU chen LIU Ya-lan SHI Yuan TAN Yun-shan ZHU Xiong-zeng Department of Thoracic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China Department of Pathology Zhongshan Hospital Fudan University Shanghai 200032 China Department of Pathology Cancer Hospital Fudan UniversityShanghai 200032 China

Background According to the National institutes of Health consensus criteria, gastrointestinal stromal tumors （GISTs） smaller than 2.cm in diameter with less than 5 mitotic figures per 50 high-power fields are considered very-low-risk GISTs but these two indices alone cannot reliably predict a benign outcome during long-term follow-ups. Therefore, identification of additional parameters for predicting the clinical behavior of GISTs is necessary. Methods Eighty-eight patients with tumors that meet the very-low-risk GIST criteria were retrospectively investigated and morphological parameters of tumors associated with the biological behavior of very-low-risk GISTs were evaluated in the present study. The Kaplan-Meier method was used to calculate disease-free survival rates. Results Eighty-one patients were followed up for one to 16.3 years. Five cases of relapses were identified in the patients. Distinctive infiltrative growth patterns such as muscularis propria, muscularis mucosa, or nerve infiltration were identified by microscopy in 4 patients with the relapse, including three patients who experienced multiple recurrences. The infiltrative growth features became more obvious in multiple recurrent tumors compared to the single recurrent tumor, while only one developed relapse in 76 patients without infiltration （P 〈0.0001）. Conclusion Microscopic infiltrative growth patterns of the tumor may have clinical significance in predicting the prognosis of very-low-risk GISTs.

关键词： gastrointestinal stromal tumors risk morphology

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