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Genes & Diseases 2024年第5期11卷 105-108页

作者： Liang Zhou Youyou Li Jiaren Li Hanyu Yao Jin Huang Cheng Li Long Wang Department of Urology The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China

In aging males,benign prostatic hyperplasia(BPH)is a chronic pathological process that primarily causes lower urinary tract *** to histopathology,BPH is caused by an imbalance between cell death and proliferation.1 However,the exact pathophysiology remains *** is a newly discovered form of programmed cell *** cell morphology is characterized primarily by the reduction or disappearance of mitochondrial cristae and mitochondrial shrinkage.2,3 Competing endogenous RNAs(ceRNAs)are important regulators of many biological processes and have been involved in various diseases.

关键词： prostatic endogenous BPH

Repurposing disulfiram with CuET nanocrystals:Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2698-2715页

作者： Xueming Xu Yuanfeng Han Jiali Deng Shengfeng Wang Shijie Zhuo Kai Zhao Wenhu Zhou Hematology and Department of Critical Care Medicine The Third Xiangya HospitalCentral South UniversityChangsha 410013China xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Hunan Chidren's hospital Changsha 410007China Department of Pharmacy The Third Xiangya HospitalCentral South UniversityChangsha 410013China Key Laboratory of Biological Nanotechnology of National Health Commission Changsha 410008China

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing ***,disulfiram(DSF),a drug primarily used for alcohol addiction treatment,has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis,a form of programmed cell *** therapeutic activity of DSF can be further enhanced by the presence of Cu^(2+),although the underlying mechanism of this enhancement remains *** this study,we investigated the mechanistic basis of Cu^(2+)-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate(CuET)*** exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of ***,despite its potent activity,CuET suffered from poor solubility and limited permeability,as revealed by our druggability *** overcome these intrinsic limitations,we developed a scalable method to prepare CuET nanocrystals(CuET NCs)using a metal coordination-driven self-assembly *** studies demonstrated that CuET NCs exhibited a 6-fold improvement in ***,CuET NCs exhibited high biodistribution in the intestine,suggesting their potential application for the treatment of inflammatory bowel diseases(IBDs).To evaluate their therapeutic efficacy in vivo,we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis *** findings highlight the discovery of CuET as a potent anti-pyroptotic agent,and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

关键词： Drug repurposing Pyroptosis Nanoparticles Bioavailability Disulfiram DSS-induced colitis NLRP3 inflammasome CuET

Early senescence of pancreatic β cells induced by unfolded protein response deficiency prevents type 1 diabetes

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第9期25卷 796-799页

作者： Haipeng CHENG Zhenwang ZHAO Dan LIU Yufei WANG Min ZHANG Department of Pathology the Second Xiangya HospitalCentral South UniversityChangsha410011China Institute of Cardiovascular Disease Key Laboratory for Arteriosclerology of Hunan ProvinceHunan International Scientific and Technological Cooperation Base of Arteriosclerotic DiseaseDepartment of Bioinformatics and Medical Big DataHengyang Medical SchoolUniversity of South ChinaHengyang421001China School of Basic Medicine Health Science CenterHubei University of Arts and ScienceXiangyang441053China Guangxi Key Laboratory of Diabetic Systems Medicine Guilin Medical UniversityGuilin541199China Medical Education Department Guangdong Provincial People’s HospitalZhuhai Hospital(Jinwan Central Hospital of Zhuhai)Zhuhai519041China

Type 1 diabetes(T1D)is a T lymphocyte-mediated autoimmune disease caused by pancreaticβ-cell destruction,which eventually leads to reduced insulin level and increased blood glucose level(Syed,2022).As a multifactorial disease,T1D is characterized by a genetic predisposition associated with various environmental and cellular elements(Syed,2022).Pancreaticβcells have long been considered the"innocent victims"in T1D pathogenesis since the pancreas is attacked by the immune cells,resulting in a process known as insulitis,in which the immune cells infiltrate pancreatic islets and secrete pro-inflammatory ***,growing evidence suggests that variousβ-cell stresses,dysfunction,and death contribute to T1D pathogenesis,as it has been observed thatβ-cell dysfunction in autoantibody-positive(Aabt)individuals exists long before T1D diagnosis(Evans-Molina et al.,2018).

关键词： diagnosis diabetes pathogenesis

树突状细胞亚群介导系统性红斑狼疮和狼疮肾炎的程序性细胞死亡模式失衡

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中南大学学报（医学版） 2024年第3期49卷 331-348页

作者：许若瑶张颖曹清泰廖晟唐又周庄权中南大学湘雅三医院器官移植中心长沙410013 中南大学湘雅三医院肾病风湿病科长沙410013 国家卫生健康委员会移植医学工程技术研究中心长沙410013

目的:免疫细胞的异常程序性死亡与自身免疫性疾病相关,但系统性红斑狼疮(systemic lupus erythematosus,SLE),尤其是狼疮肾炎(lupus nephritis,LN)的程序性死亡模式尚不清楚。本研究旨在探究SLE和LN与免疫细胞死亡模式的关联。方法:在... 详细信息

目的:免疫细胞的异常程序性死亡与自身免疫性疾病相关,但系统性红斑狼疮(systemic lupus erythematosus,SLE),尤其是狼疮肾炎(lupus nephritis,LN)的程序性死亡模式尚不清楚。本研究旨在探究SLE和LN与免疫细胞死亡模式的关联。方法:在高通量基因表达(Gene Expression Omnibus,GEO)数据库中下载批量RNA测序(bulk RNA sequencing,bulk RNA-seq)和单细胞RNA测序(single-cell RNA sequencing,scRNA-seq)数据,通过生物信息学分析探究SLE患者外周血单个核细胞中3种细胞死亡模式相关基因的表达水平;通过scRNA-seq确定参与细胞死亡模式失衡的关键细胞亚群;采用免疫荧光法检测树突状细胞(dendritic cell,DC)中受体相互作用丝氨酸/苏氨酸激酶3(receptor interacting serine/threonine kinase 3,RIPK3)、混合谱系激酶结构域样蛋白(mixed-lineage kinase domainlike protein、MLKL)、磷酸化MLKL(phosphorylated MLKL,pMLKL)、含半胱氨酸的天冬氨酸蛋白水解酶1(caspase1、CASP1)、CD1c分子(CD1cmolecule、CD1C)、含C型凝集素结构域9A(C-typelectindomaincontaining9A、CLEC9A)和X-C基序趋化因子受体1(X-C motif chemokine receptor 1,XCR1)的表达水平;对中南大学湘雅三医院收集的LN患者和健康对照者(healthy control,HC)的肾组织进行scRNA-seq,并通过生物信息学分析参与细胞死亡模式失衡的关键细胞亚群;采用拟时序分析和配受体分析探究不同DC亚群的分化方向和细胞通信。采用瞬时转染技术分别在RAW264.7细胞中转染空质粒、空质粒+dsDNA(HSV-DNA)、空质粒+200μmol/L叔丁基过氧化氢(tert-butylhydroperoxide,TBHP)、STING shRNA质粒、STING shRNA质粒+dsDNA(HSV-DNA)、STING shRNA质粒+200μmol/L TBHP;采用Annexin V-mCherry和SYTOX Green染色检测各组细胞死亡情况;蛋白质印迹法检测各组CASP1、消皮素D(gasdermin D,GSDMD)、RIPK3和MLKL的活化情况。结果:生物信息学分析显示SLE和LN患者存在3种细胞死亡模式的失衡:促炎型细胞焦亡和坏死性凋亡被激活,抗炎型细胞凋亡被抑制。其中的关键细胞亚群为DC亚群,并聚焦于CLEC9A+cDC1。免疫荧光法结果显示在外周血中SLE组DC中RIPK3、MLKL和CASP1表达水平较HC组DC升高;通过CLEC9A和XCR1标记肾组织中的c DC1,结果显示LN组cDC1的pMLKL和CASP1表达水平高于HC组。拟时序分析和配受体分析提示LN肾组织中CLEC9A+cDC1亚群存在外周循环起源。Annexin V-mCherry和SYTOX Green染色结果显示,在RAW264.7细胞中,与转染空质粒组相比,转染STING shRNA质粒组的死亡细胞数目减少;蛋白质印迹法结果显示与转染空质粒组相比,转染STING shRNA质粒组CASP1、GSDMD、RIPK3和MLKL的活化减少。结论:本研究为CLEC9A+cDC1在SLE和LN的细胞死亡模式失衡中的作用提供了新的思路。

关键词：细胞死亡失衡树突状细胞系统性红斑狼疮狼疮肾炎单细胞RNA测序

Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair

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Chinese Medical Journal 2024年第15期137卷 1857-1869页

作者： Chengming Fan Kele Qin Chukwuemeka Daniel Iroegbu Kun Xiang Yibo Gong Qing Guan Wenxiang Wang Jun Peng Jianjun Guo Xun Wu Jinfu Yang Department of Cardiovascular Surgery The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Department of Pharmacology Xiangya School of Pharmaceutical SciencesCentral South UniversityChangshaHunan 410078China Hunan Fangsheng Pharmaceutical Co. Ltd.ChangshaHunan 410000China Department of Thoracic Surgery The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaHunan 41000China

Background:We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse ***,we sought to identify the effect of magnesium lithospermate B(MLB)on hiPSC-CMs during myocardial repair using a myocardial infarction(MI)mouse ***:In C57BL/6 mice,MI was surgically induced by ligating the left anterior descending coronary *** mice were randomly divided into five groups(n=10 per group);a MI group(treated with phosphate-buffered saline only),a hiPSC-CMs group,a MLB group,a hiPSC-CMs+MLB group,and a Sham operation *** function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after *** identify the associated mechanism,nuclear factor(NF)-κB p65 and intercellular cell adhesion molecule-1(ICAM1)signals,cell adhesion ability,generation of reactive oxygen species,and rates of apoptosis were detected in human umbilical vein endothelial cells(HUVECs)and ***:After 4 weeks of transplantation,the number of cells that engrafted in the hiPSC-CMs+MLB group was about five times higher than those in the hiPSC-CMs ***,MLB treatment significantly reduced tohoku hospital pediatrics-1(THP-1)cell adhesion,ICAM1 expression,NF-κB nuclear translocation,reactive oxygen species production,NF-κB p65 phosphorylation,and cell apoptosis in HUVECs cultured under ***,treatment with MLB significantly inhibited the apoptosis of hiPSC-CMs via enhancing signal transducer and activator of transcription 3(STAT3)phosphorylation and B-cell lymphoma-2(BCL2)expression,promoting STAT3 nuclear translocation,and downregulating BCL2-Associated X,dual specificity phosphatase 2(DUSP2),and cleaved-caspase-3 expression under ***,MLB significantly suppressed the production of malondialdehyde and lactat

关键词： Myocardial infarction Cell therapy Induced pluripotent stem cells Magnesium lithospermate B Cardiomyocyte Disease modeling hiPSC-CMs

Extracellular vesicles from human urine-derived stem cells delay aging through the transfer of PLAU and TIMP1

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1166-1186页

作者： Shanshan Rao Zehui He Zun Wang Hao Yin Xiongke Hu Yijuan Tan Tengfei Wan Hao Zhu Yi Luo Xin Wang Hongming Li Zhenxing Wang Xinyue Hu Chungu Hong Yiyi Wang Mingjie Luo Wei Du Yuxuan Qian Siyuan Tang Hui Xie Chunyuan Chen Department of Orthopedics Movement System Injury and Repair Research CenterXiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Angmedicine Changsha 410008China xiangya School of Nursing Central South UniversityChangsha 410013China Department of Pediatric Orthopedics Hunan Children’s HospitalUniversity of South ChinaChangsha 410007China Department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangsha 410008China School of Nursing Xinjiang Medical UniversityUrumqiXinjiang 830000China Department of Rehabilitation Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China

Aging increases the risks of various diseases and the vulnerability to *** senescence is a hallmark of aging that contributes greatly to aging and aging-related *** study demonstrates that extracellular vesicles from human urine-derived stem cells(USC-EVs)efficiently inhibit cellular senescence in vitro and in *** intravenous injection of USC-EVs improves cognitive function,increases physical fitness and bone quality,and alleviates aging-related structural changes in different organs of senescence-accelerated mice and natural aging *** anti-aging effects of USC-EVs are not obviously affected by the USC donors’ages,genders,or health *** analysis reveals that USC-EVs are enriched with plasminogen activator urokinase(PLAU)and tissue inhibitor of metalloproteinases 1(TIMP1).These two proteins contribute importantly to the anti-senescent effects of USC-EVs associated with the inhibition of matrix metalloproteinases,cyclin-dependent kinase inhibitor 2A(P16INK4a),and cyclin-dependent kinase inhibitor 1A(P21cip1).These findings suggest a great potential of autologous USC-EVs as a promising anti-aging agent by transferring PLAU and TIMP1 proteins.

关键词： Extracellular vesicles Urine-derived stem cells Cellular senescence Anti-aging PLAU TIMP1 Senescence-accelerated mice Natural aging mice

Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第1期18卷 68-80页

作者： Yanling Liu Xi He Yanchun Yuan Bin Li Zhen Liu Wanzhen Li Kaixuan Li Shuo Tan Quan Zhu Zhengyan Tang Feng Han Ziqiang Wu Lu Shen Hong Jiang Beisha Tang Jian Qiu Zhengmao Hu Junling Wang Department of Neurology Xiangya HospitalCentral South UniversityJiangxiNational Regional Center for Neurological DiseasesNanchang330038China Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease Department of UrologyXiangya HospitalCentral South UniversityChangsha410078China Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhou310002China Department of Neurology Xiangya HospitalCentral South UniversityChangsha410078China National Clinical Research Center for Geriatric Diseases Xiangya HospitalCentral South UniversityChangsha410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha410008China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha410078China Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha410078China Hunan Key Laboratory of Molecular Precision Medicine Xiangya HospitalCentral South UniversityChangsha410078China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons,and it demonstrates high clinical heterogeneity and complex genetic architecture.A variation within TRMT2B(c.1356G>T;p.K452N)was identified to be associated with ALS in a family comprising two patients with juvenile ALS(JALS).Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS,and three more variants were identified in a public ALS database including 3317 patients with ALS.A decreased number of mitochondria,swollen mitochondria,lower expression of ND1,decreased mitochondrial complex I activities,lower mitochondrial aerobic respiration,and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 ***,TRMT2B variations overexpression cells also displayed decreased *** conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.

关键词： TRMT2B amyotrophic lateral sclerosis mitochondrial complex I tRNA methylation reactive oxygen species

Extent, reasons and consequences of off-labeled and unlicensed drug prescription in hospitalized children: a narrative review

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World Journal of Pediatrics 2021年第4期17卷 341-354页

作者： Wasim Shuib Xin-Yin Wu Fang Xiao xiangya School of Public Health Central South UniversityChangsha410078China

Background Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric *** aimed to summarize the up-to-date evidence on the extent,reasons,and consequences of off-label and unlicensed drugs in hospitalized pediatric *** We systematically searched PubMed,EMBASE,SCOPUS,Web of Science and Google Scholar between 1990 and 2020 in which the last search was conducted on 12 February *** included studies with the following inclusion criteria:(1)observational studies in design;(2)target population was hospitalized pediatric patients whether admitted in the intensive care unit or in the general ward;(3)study reporting the prevalence of off-label,unlicensed prescriptions or both;and(4)published in *** A total of 47 studies were eligible for *** proportion of off-label and unlicensed prescriptions ranged from 7.4%to 99.5%and 0.1%to 74.4%,*** most frequent category of off-label prescriptions was prescription outside the age range,with the most commonly reported reason for off-label prescriptions being the lack of information specifically for pediatrics on the drug information *** consequences of off-label and unlicensed prescriptions ranged from minor and bearable skin reactions to debilitating renal failure,risking *** Off-label and unlicensed prescriptions are extensive and require progressively meditative ***,the pediatric population is currently a“therapeutic orphan”.Unless adequate pediatric clinical trials and licensed drugs become available,off-label and unlicensed drug prescription should not entirely be banned but rather promoted in an organized manner.

关键词： Licensed medicines Off-label prescribing Pediatrics Unlicensed prescribing

Sacral chondroblastoma — a rare location, a rare pathology: A case report and review of literature

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World Journal of Clinical Cases 2021年第20期9卷 5709-5716页

作者： Bo-Wen Zheng Hua-Qing Niu Xiao-Bin Wang Jing Li Department of Spine Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011Hunan ProvinceChina Department of Orthopedics Surgery General Hospital of the Central Theater CommandWuhan 430061Hubei ProvinceChina

BACKGROUND Chondroblastoma(CB)is an intermediate tumor of cartilage *** involving the sacrum is a very rare *** SUMMARY A 17-year-old male with sacral CB was diagnosed as CB during the first surgery,and 18 mo later,the tumor recurred and a second surgery was performed with the same pathology result of *** We recommend complete removal of the tumor in a timely manner,provided that surgical conditions are *** the same time,other diseases should be carefully differentiated in terms of imaging or pathological features so as to avoid erroneous diagnostic conclusions.

关键词： Sacrum Chondroblastoma Spine Pathology Immunohistochemistry Case report

Donor-derived infections among Chinese donation after cardiac death liver recipients

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World Journal of Gastroenterology 2017年第31期23卷 5809-5816页

作者： Qi-Fa Ye Wei Zhou Qi-Quan Wan Department of Transplant Surgery the Third Xiangya Hospital of Central South University Department of Transplant Surgery Zhongnan Hospital of Wuhan University

AIM To investigate blood cultures of deceased donors and report the confirmed transmission of bacterial infection from donors to liver *** We retrospectively studied the results of blood cultures among our donation after cardiac death(DCD) donors and calculated the donor-derived bacterial infection rates among liver recipients. Study participants underwent liver transplantation between January 1, 2010 and February 1, 2017. The study involved a total of 67 recipients of liver grafts from 67 DCD donors. We extracted the data of donors' and patients' characteristics, culture results and clinical outcomes, especially the post-transplant complications in liver recipients, from electronic medical records. We analyzed the characteristics of the donors and the corresponding liver recipients with emphasis put on donor-derived *** Head trauma was the most common origin of death among our 67 DCD donors(46.3%). Blood taken prior to the procurement operation was cultured for 53 of the donors, with 17 episodes of bloodstream infections developing from 13 donors. The predominant organism isolated from the blood of donors was Gram-positive bacteria(70.6%). Only three(4.5%) of 67 liver recipients developed confirmed donor-derived bacterial infections,with two isolates of multidrug-resistant Klebsiella pneumoniae and one isolate of multidrug-resistant Enterobacter aerogenes. The liver recipients with donorderived infections showed relation to higher crude mortality and graft loss rates(33.3% each) within 3 mo post transplantation, as compared to those without donor-derived infections(9.4% and 4.7%, respectively). All three liver recipients received appropriate antimicrobial *** Liver recipients have high occurrence of donor-derived infections. The liver recipients with donor-derived multidrug-resistant Enterobacteriaceae infections can have good outcome if appropriate antimicrobial therapy is given.

关键词： Liver transplant Donation after cardiac death donor Infection Multidrug resistant Bacteria Transmission