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Association of interleukin-6 promoter polymorphism with knee osteoarthritis： a meta-analysis

Chinese Medical Journal 2014年第13期127卷 2492-2496页

作者： Ai Zhipeng Ning Xianming Shou Tao Tang Wenru Luo Ying Zhang Jihong laboratory of molecular genetics of aging & tumor MedicalFaculty Kunming University of Science & Technology KunmingYunnan 650500 China Orthopedics Department the First People's Hospital of YunnanProvince Kunming Ytmnan 650034 China

Background Osteoarthritis （OA） is the most common form of human polyarthritis.Many genetic factors have been implicated in OA.It was reported that a polymorphism in the gene of interleukin-6 （IL-6） was associated with OA of knee.The aim of this study was to determine whether functional IL-6 promoter-174G/C （rs1800795） polymorphisms confer susceptibility to knee OA.Methods A meta-analysis was conducted on the association between the IL-6 polymorphism and knee OA.Electronic search at PubMed,EMBASE,Weipu database,and Wanfang database was conducted to select studies.Case-control studies containing available genotype frequencies of IL-6-174G/C were chosen,and odds ratio （OR） with 95％ confidence interval （C/） was used to assess the strength of this association.Results A total of seven studies involving 6 464 subjects （knee OA 3 331 and controls 3 133） were considered in this study.The results suggested that the variant genotypes were not associated with knee OA risk in all genetic models （additive model：OR=1.144,95％ CI 0.934-1.402,P=0.194; recessive model：OR=1.113,95％ CI 0.799-1.550,P=0.526;dominant model：OR=1.186,95％ CI 0.918-1.531,P=0.191）.A symmetric funnel plot,the Begg＇s test （P ＞0.05）,suggested that the data lacked publication bias.Conclusions This meta-analysis does not support the idea that rs1800795 genotype is associated with increased risk of knee OA.However,to draw comprehensive and more reliable conclusions,further prospective studies with larger numbers of participants worldwide are needed to examine the association between rs1800795 polymorphism and knee OA.

关键词： interleukin-6 polymorphisms knee osteoarthritis meta-analysis

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Characterization of tree shrew telomeres and telomerase

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Journal of genetics and Genomics 2021年第7期48卷 631-639页

作者： Jian Sun Wenjing Liu Yongbo Guo Hailin Zhang Dewei Jiang Ying Luo Rong Liu Ceshi Chen Key laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province National Resource Center for Non-Human PrimatesKunming Primate Research CenterNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyKunmingYunnan 650201China Kunming College of Life Sciences University of Chinese Academy SciencesKunmingYunnan 650204China State Key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Laboratory of Molecular Genetics of Aging&Tumor Medical FacultyKunming University of Science and TechnologyKunmingYunnan 650500China

The use of tree shrews as experimental animals for biomedical research is a new practice.Several recent studies suggest that tree shrews are suitable for studying cancers,including breast cancer,glioblastoma,lung cancer,and hepatocellular carcinoma.However,the telomeres and the telomerase of tree shrews have not been studied to date.Here,we characterize telomeres and telomerase in tree shrews.The telomere length of tree shrews is approximately 23 kb,which is longer than that of primates and shorter than that of mice,and it is extended in breast tumor tissues according to Southern blot and flow-fluorescence in situ hybridization(FISH)analyses.Tree shrew spleen,bone marrow,testis,ovary,and uterus show high telomerase activities,which are increased in breast tumor tissues by telomeric repeat amplification protocol assays.The telomere length becomes shorter,and telomerase activity decreases with age.The tree shrew TERT and TERC are more highly similar to primates than to rodents.These findings lay a solid foundation for using tree shrews to study aging and cancers.

关键词： Tree shrews Telomere TERT TERC Breast cancer

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T8590C polymorphism of CYP4A11 is a risk factor for hypertension： a meta-analysis

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Chinese Medical Journal 2014年第12期127卷 2382-2385页

作者： Jiang Yuan Hou Jing Zhang Qiang Tang Wenru Luo Ying Lab of molecular genetics of aging and tumor Faculty of Life Science and Technology Kunming University of Science and TechnologyKunmingYunnan 650500China Lab of molecular genetics of aging and tumor Medical Faculty Kunming University of Science and TechnologyKunmingYunnan 650500China

Background T8590C polymorphism of CYP4A11 has been associated with hypertension,though with conflicting results.The aim of this study was to quantitatively summarize the evidence for CYP4A 11 T8590C polymorphism and hypertension risk.Methods Electronic search of PubMed and the Chinese Biomedicine database was conducted to select studies.Casecontrol studies containing available genotype frequencies of T8590C were chosen,and odds ratio （OR） with 95％ confidence interval （CI） was used to assess the strength of this association.Results Seven case-control studies,including 3 295 cases and 3 192 controls,were identified.The meta-analysis,stratified by ethnicity,showed that individuals with the C allele carriers （CC＋CT） had increased risk of hypertension in over all （OR=1.184,95％ CI：1.063-1.319,P=0.002） and in others （OR=1.217,95％ CI：1.045-1.419,P=0.012）.The results among Asians did not suggest an association （OR=1.152,95％ CI：0.990-1.342,P=0.068）.A symmetric funnel plot,the Egger＇s test （P=0.863）,and the Begg test （P=0.393） were all suggestive of the lack of publication bias.Conclusions This meta-analysis suggests the CYP4A11 T8590C polymorphism may be a risk factor for hypertension.Future well-designed large studies might be necessary to validate this association in different populations incorporated with environmental factors in the susceptibility of hypertension.

关键词： CYP 4A11 meta-analysis hypertension

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Association Between rs1344706 of ZNF804A and Schizophrenia: A Meta-analysis

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Genomics, Proteomics & Bioinformatics 2014年第6期12卷 292-296页

作者： Meiyan Zhu Tongyang Liu Jihong Zhang Shuting Jia Wenru Tang Ying Luo Lab of molecular genetics of aging & tumor Medical Faculty Kunming University of Science and Technology

Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of Pub Med database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis,involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio（OR） with 95% confidence interval（CI） was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations（P = 0.028, OR = 1.138, 95% CI：1.014–1.278; P = 0.004 for heterogeneity） and Asian populations（P = 0.008, OR = 1.092, 95%CI： 1.023–1.165; P = 0.001 for heterogeneity）, but not in other populations（P = 0.286,OR = 1.209, 95% CI： 0.853–1.714, P = 0.120 for heterogeneity）. Egger’s test（P 〉 0.05） and Begg’s test（P 〉 0.05） are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.

关键词： Meta-analysis ZNF804A Schizophrenia Association Caucasians Asians

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p53 mutation regulates PKD genes and results in co-occurrence of PKD and tumorigenesis

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Cancer Biology & Medicine 2019年第1期16卷 79-88页

作者： Haili Li Yongjin Zhang Juhua Dan Ruoyu Zhou Cui Li Rong Li Xiaoming Wu Sanjay Kumar Singh Jeffrey T.Chang Julun Yang Ying Luo Faculty of Environmental Science and Engineering Kunming University of Science and Technology laboratory of molecular genetics of aging &tumor Kunming University of Science and Technology Division of Nephrology The First People's Hospital of Yunnan Province Department of Cancer Systems Imaging The University of Texas MD Anderson Cancer Center Department of Integrative Biology and Pharmacology University of Texas Health Science Center at Houston Department of Pathology Kunming General Hospital

Objective: Polycystic kidney disease(PKD) is the major cause of kidney failure and mortality in humans. It has always been suspected that the development of cystic kidney disease shares features with tumorigenesis, although the evidence is unclear.Methods: We crossed p53 mutant mice(p53N236S, p53S) with Werner syndrome mice and analyzed the pathological phenotypes.The RNA-seq, ss GSEA analysis, and real-time PCR were performed to dissect the gene signatures involved in the development of disease phenotypes.Results: We found enlarged kidneys with fluid-filled cysts in offspring mice with a genotype of G3mTerc^(-/-)WRN^(-/-)p53^(S/S)(G3TM).Pathology analysis confirmed the occurrence of PKD, and it was highly correlated with the incidence of tumorigenesis. RNA-seq data revealed the gene signatures involved in PKD development, and demonstrated that PKD and tumorigenesis shared common pathways, including complement pathways, lipid metabolism, mitochondria energy homeostasis and others. Interestingly, this G3TM PKD and the classical PKD1/2 deficient PKD shared common pathways, possibly because the mutant p53S could regulate the expression levels of PKD1/2, Pkhd1, and Hnf1b.Conclusions: We established a dual mouse model for PKD and tumorigenesis derived from abnormal cellular proliferation and telomere dysfunction. The innovative point of our study is to report PKD occurring in conjunction with tumorigenesis. The gene signatures revealed might shed new light on the pathogenesis of PKD, and provide new molecular biomarkers for clinical diagnosis and prognosis.

关键词： p53 mutation telomere dysfunction polycystic kidney disease tumorigenesis

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FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis

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Science China(Life Sciences) 2021年第11期64卷 1884-1894页

作者： Cui-Fang Zhang Han-Ming Wang Andong Wu Yang Li Xiao-Li Tian Department of Human Population genetics Institute of Molecular MedicinePeking UniversityBeijing 100871China aging and Vascular Diseases Human Aging Research Institute and School of Life ScienceNanchang Universityand Jiangxi Key Laboratory of Human AgingNanchang 330031China

Angiogenic factor with G-patch and FHA domains 1(AGGF1) exhibits a dynamic distribution from the nucleus to the cytoplasm in endothelial cells during angiogenesis, but the biological significance and underlying mechanism of this nucleocytoplasmic transport remains unknown. Here, we demonstrate that the dynamic distribution is essential for AGGF1 to execute its angiogenic function. To search the structural bases for this nucleocytoplasmic transport, we characterized three potential nuclear localization regions, one potential nuclear export region, forkhead-associated(FHA), and G-patch domains to determine their effects on nucleocytoplasmic transport and angiogenesis, and we show that AGGF1 remains intact during the dynamic subcellular distribution and the region from 260 to 288 amino acids acts as a signal for its nuclear localization. The distribution of AGGF1 in cytoplasm needs both FHA domain and 14-3-3α/β. Binding of AGGF1 via FHA domain to 14-3-3α/β is required to complete the transport. Thus, we for the first time established structural bases for the nucleocytoplasmic transport of AGGF1 and revealed that the FHA domain of AGGF1 is essential for its nucleocytoplasmic transport and angiogenesis.

关键词： AGGF1 nucleocytoplasmic transport angiogenesis FHA domain 14-3-3α/β

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Single-cell RNA sequencing reveals Nestin+active neural stem cells outside the central canal after spinal cord injury

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Science China(Life Sciences) 2022年第2期65卷 295-308页

作者： Muya Shu Xiaoyu Xue Hu Nie Xianming Wu Minghan Sun Lianyong Qiao Xing Li Bai Xu Zhifeng Xiao Yannan Zhao Yongheng Fan Bing Chen Jixiang Zhang Ya Shi Yaming Yang Falong Lu Jianwu Dai State Key laboratory of molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100080China University of the Chinese Academy of Sciences Beijing 100101China Key laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangsha 410008China

Neural stem cells(NSCs)in the spinal cord hold great potential for repair after spinal cord injury(SCI).The ependyma in the central canal(CC)region has been considered as the NSCs source in the spinal cord.However,the ependyma function as NSCs after SCI is still under debate.We used Nestin as a marker to isolate potential NSCs and their immediate progeny,and characterized the cells before and after SCI by single-cell RNA-sequencing(scRNA-seq).We identified two subgroups of NSCs:the subgroup located within the CC cannot prime to active NSCs after SCI,while the subgroup located outside the CC were activated and exhibited the active NSCs properties after SCI.We demonstrated the comprehensive dynamic transcriptome of NSCs from quiescent to active NSCs after SCI.This study reveals that Nestin+cells outside CC were NSCs that activated upon SCI and may thus serve as endogenous NSCs for regenerative treatment of SCI in the future.

关键词： neural stem cell Nestin scRNA-seq Smart-seq2 ependymal cell

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Hypermethylation in H3K9me3 regions characterizes the centenarian methylomes in healthy aging

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National Science Review 2023年第6期10卷 60-63页

作者： Fu-Hui Xiao Hao-Tian Wang Xiao-Qiong Chen Ming-Xia Ge Dongjing Yan Xing-Li Yang Li-Qin Yang Rong Lin Rong-Hui Guo Wen Zhang Nelson Leung-Sang Tang Yonghan He Jumin Zhou Wang-Wei Cai Qing-Peng Kong State Key laboratory of Genetic Resources and Evolution Key Laboratory of Healthy Aging Research of Yunnan Province Kunming Key Laboratory of Healthy Aging Study Kunming Institute of ZoologyChinese Academy of Sciences KIZ/CUHK Joint laboratory of Bioresources and molecular Research in Common Diseases Kunming College of Life Science University of Chinese Academy of Sciences Department of Biochemistry and molecular Biology Hainan Medical College Department of Biology Hainan Medical College Department of Chemical Pathology and laboratory for genetics of Disease Susceptibility Li Ka Shing Institute of Health Sciences and School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences Key Laboratory of Healthy Aging Research of Yunnan Province Kunming Institute of Zoology CAS Center for Excellence in Animal Evolution and genetics Chinese Academy of Sciences

Centenarians,as excellent examples of extreme yet successful aging,not only display a much longer lifespan but can also delay or even escape major agerelated diseases,such as cardiovascular disorders,neurodegenerative diseases,and cancer [1].Studies have suggested that genetic factors account for 20%-30%of human longevity [2];however,only a handful of longevity-associated genes/mutations have been observed in long-lived individuals,even with the use of genome-wide scanning/sequencing assays [3,4].In contrast,evidence has shown the crucial roles of epigenetic alternations in aging and age-related diseases [5],suggesting that epigenetic modifications play central roles in human healthy aging.Thus,a comprehensive analysis of the epigenomic landscape of centenarians is urgently needed.

关键词： LONGEVITY DNA

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Potential clinical treatment for Ebola pandemic

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Science China(Life Sciences) 2014年第10期57卷 982-984页

作者： ZHONG Ying XU Jun LI TaiSheng YU XueZhong SHENG MiaoMiao State Key laboratory of Medical molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Department of Biochemistry and molecular Biology Peking Union Medical College Tsinghua University Department of Emergency Medicine Peking Union Medical Collage Hospital Peking Union Medical College Chinese Academy of Medical Sciences Department of Infectious Diseases Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences laboratory of molecular genetics of aging & tumor Medical Faculty Kunming University of Science and Technology Chenggong Campus

West African countries are currently suffering the most severe pandemic of Ebola virus disease ever recorded,with4269 human cases and 2288 deaths(through 6 September2014),and the number of cases in the current outbreak exceeds the number from all previous outbreaks combined.Ebola virus disease was first described in 1976 originating from the Ebola River in the Democratic Republic of the Congo.Five Ebola viruses have been reported to

关键词：埃博拉病毒临床治疗刚果民主共和国扎伊尔死亡人数感染病例象牙海岸传染病

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Actin polymerization induces mitochondrial distribution during collective cell migration

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Journal of genetics and Genomics 2023年第1期50卷 46-49页

作者： Chen Qu Yating Kan Hui Zuo Mengqi Wu Zhixiang Dong Xinyi Wang Qing Zhang Heng Wang Dou Wang Jiong Chen MOE Key laboratory of Model Animals for Disease Study Model Animal Research CenterJiangsu Key Laboratory of Molecular MedicineMedical School of Nanjing UniversityNanjingJiangsu 210008China State Key laboratory of molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Collective cell migration plays critical roles in various developmental,physiological,and pathological processes such as morphogenesis,wound healing,and tumor metastasis(Friedl and Gilmour,2009).During collective migration,each coherent group of associated cells needs to interpret external directional signal and convert it into a front-back asymmetry across a collective group(Rorth,2011).But the underlying mechanism for the establishment and maintenance of front-back asymmetry during collective migration is still not well understood.

关键词： healing collective wound

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