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Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Protein & Cell 2020年第1期11卷 1-22页

作者： Si Wang Zheying Min Qianzhao Ji Lingling Geng Yao Su Zunpeng Liu Huifang Hu Lixia Wang Weiqi Zhang Keiichiro Suzuiki Yu Huang Puyao Zhang Tie-Shan Tang Jing Qu Yang Yu Guang-Hui Liu Jie Qiao Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China national laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China State key laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Beijing institute for Brain Disorders Beijing 100069China institute for Advanced Co-Creation Studies Osaka UniversityOsaka 560-8531Japan Graduate School of Engineering Science Osaka UniversityOsaka 560-8531Japan Department of Medical Genetics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China State key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China

Cockayne syndrome(CS)is a rare autosomal recessive inherited disorder characterized by a variety of clinical features,including increased sensitivity to sunlight,progressive neurological abnormalities,and the appearance of premature ***,the pathogenesis of CS remains unclear due to the limitations of current disease ***,we generate integration-free induced pluripotent stem cells(iPSCs)from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs(GC-iPSCs)using the CRISPR/Cas9 ***-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells(MSCs)and neural stem cells(NSCs),both of which display increased susceptibility to DNA damage *** aging defects in CS-MSCs are rescued by the targeted correction of mutant *** next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives(MSCs and NSCs)in the absence or presence of ultraviolet(UV)and replicative stresses,revealing that defects in DNA repair account for CS ***,we generate autologous GC-MSCs free of pathogenic mutation under a cGMP(Current Good Manufacturing Practice)-compliant condition,which hold potential for use as improved biomaterials for future stem cell replacement therapy for ***,our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.

关键词： Cockayne syndrome CRISPR/Cas9 gene correction disease modelling mesenchymal stem cell neural stem cell

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Improving the surveillance and response system to achieve and maintain malaria elimination:a retrospective analysis in Jiangsu Province,China

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Infectious Diseases of Poverty 2022年第1期11卷 56-67页

作者： Yuanyuan Cao Guangyu Lu Chris Cotter Weiming Wang Mengmeng Yang Yaobao Liu Cheng Liang Huayun Zhou Yan Lu Jun Yan Guoding Zhu Jun Cao key laboratory of national health.commission(NHC)On Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory On Parasite and Vector Control TechnologyJiangsu Institute of Parasitic DiseasesWuxi214064JiangsuChina institute of Public health Medical College of Yangzhou UniversityJiangsu ProvinceYangzhou city225000China Malaria Elimination Initiative Institute for Global Health SciencesUniversity of California San FranciscoSan FranciscoCAUSA Department of Women’s and children’s health International Maternal and Child HealthUppsala UniversityUppsalaSweden Center for Global health School of Public HealthNanjing Medical UniversityNanjing211166China health.and Quarantine Department Nanjing CustomsNanjing210001China Chinese Center for Disease Control and Prevention Beijing102206China

Background:Following initiation of China’s national Malaria Elimination Action Plan(NMEAP)in 2010,the'1-3-7’approach was developed and rolled out in China to facilitate the malaria elimination programme and accelerate malaria *** study aims to summarize and condense these experiences through a retrospective analysis in Jiangsu Province,which could be adapted and applied in other malaria elimination settings ***:A retrospective analysis of imported malaria cases into China identified through an improved surveillance and response system in Jiangsu Province was carried out for the period of *** improve the malaria surveillance and response system,Centers for Diseases Control and Prevention from the prefectures and counties in Jiangsu province conducted population-level health.education to improve health.are seeking behavior,strengthened capacity of health.facilities to improve performance of malaria diagnosis and treatment,and raised the capacity of public health.providers to improve implementation of the'1-3-7’*** variables were carried out by Chi square tests with Fisher’s exact ***:From 2001 to 2020,a total of 9,879 malaria cases were reported in Jiangsu *** 2012,no indigenous malaria cases have been reported in Jiangsu ***,in recent years,there has been a substantial increase of imported falciparum malaria *** 2012 and 2020,an estimated 61.57 million individuals have benefited from population-level health.education in Jiangsu *** health.are-seeking services among the 2,423 imported malaria cases,687(28.4%)and 1,104(45.6%)cases visited hospitals on the first day and the second day from symptom onset,respectively.A total of 1,502(61.9%)cases were diagnosed on the first day at medical *** Province achieved 100%,99.4%and 98.3%completion rate in terms of case detection and notification(within one day),case investigation(within three days)and foci

关键词： China 1-3-7 approach Surveillance and response Malaria Elimination Imported case Jiangsu Retrospective study

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Chemical screen identifies a geroprotective role of quercetin in premature aging

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Protein & Cell 2019年第6期10卷 417-435页

作者： Lingling Geng Zunpeng Liu Weiqi Zhang Wei Li Zeming Wu Wei Wang Ruotong Ren Yao Su Peichang Wang Liang Sun Zhenyu Ju Piu Chan Moshi Song Jing Qu Guang-Hui Liu Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital of Capital Medical University Beijing 100053 China national laboratory of Biomacromolecules CAS Center for Excellenee in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China State key laboratory of Stem Cell and reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China State key laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China institute of Stem cell and Regeneration Chinese Academy of Sciences Beijing 100101 China key laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Jinan University Guangzhou 510632 China The MOH key laboratory of Geriatrics Beijing Hospital National Center of Gerontology Beijing 100730 China

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

关键词： Quercetin Stem cell Aging Werner syndrome Hutchinson-Gilford progeria syndrome

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The integrative roles of chemokines at the maternal-feta interface in early pregnancy

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Cellular & Molecular Immunology 2014年第5期11卷 438-448页

作者： Mei-Rong Du Song-Cun Wang Da-Jin Li M-RD and S-CW contributed equally to this work. laboratory for reproductive Immunology Hospital and Institute of Obstetrics and Gynecology Fudan University Shanghai Medical College Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai China

Embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

关键词： chemokine decidua pregnancy pregnant complications trophoblast

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Gonadal mosaicism mediated female-biased gender control in mice

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Protein & Cell 2022年第11期13卷 863-868页

作者： Meizhu Bai Dan Liang Yan Cheng Guolong Liu Qiudao Wang Jinsong Li Yuxuan Wu State key laboratory of Cell Biology Shanghai Key Laboratory of Molecular AndrologyCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China NHC key laboratory of Study on Abnormal Gametes and reproductive Tract(Anhui Medical University) Hefei 230032China key laboratory of Population health.Across Life Cycle(Anhui Medical University) Ministry of Education of the People’s Republic of ChinaHefei 230032China

Dear Editor, In nature or during artificial breeding,evolutionary interven-tion or desirable trait selection could be achieved by means of gender control in an *** reported approaches including sex-sorted semen and genetic manipulation of a certain gene(Holden and Butler,2018;Yosef et al.,2019).In mice,a recent study demonstrated a genetic system for biasing sex ratio through crossing two genetically engineered mouse lines(Yosef et al.,2019).The maternal line encodes functional Cas9 protein on an auto-somal chromosome,whereas the paternal encodes guide RNAs on Y chromosome targeting vital *** fertil-ization,males carrying both Cas9 and guide RNAs were self-destructed,resulting in a female biased sex ***,the litter size is proximate half of normal size since half of the progeny are ***,a reproductive reservoir of males and females must be maintained for ***,we established a mouse line carrying Hspa2 promoted Cas9 and constitutively expressed sgRNA targeting repetitive sequences on Y *** those mice,spermatogenic cells carrying Y chromosome were eliminated during sper-matogenesis,resulting in female biased sex ratio in proge-nies whereas the total number was unaffected.

关键词： female eliminated reservoir

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World Journal of Clinical Cases 2021年第22期9卷 6329-6342页

作者： Ya-Jing Sun Ling-Zi Xu Zeng-Hui Ma Yu-Lu Yang Ting-Ni Yin Xiao-Yun Gong Zi-Lin Gao Yan-Ling Liu Jing Liu Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Beijing 100191China Quanzhou children’s and Women’s Hospital Quanzhou 362000Fujian ProvinceChina Department of Mathematics Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina

BACKGROUND health.related risky behaviors generally refer to behaviors that have a negative impact on health.and quality of ***-related risky behaviors in adolescents with high-functioning autism(HFA)have not been well understood so *** with HFA may have more health.related risky behaviors than neurotypical *** To investigate health.related risky behaviors and their risk factors with *** This is an observational *** study enrolled 110 adolescents aged 12-19-years-old meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for *** were recruited from Peking University Sixth *** were also 110 age,sex and nationality matched controls enrolled who came from a public school in Beijing,*** groups completed the Adolescents health.related Risky Behavior *** tests were carried out for comparison of the Adolescents health.related Risky Behavior Inventory scores between the two *** recognition,the Inventory of Subjective Life Quality for child and Adolescent,Chinese Wechsler Intelligence Scale for children,Wechsler Intelligence Scale for Adult-Chinese Revised,Theory of Mind test and Autism Spectrum Screening Questionnaire were assessed in the autism group to explore factors associated with health.related risky *** regression analysis was conducted to explore the risk factors of health.related risky behaviors in the HFA *** The results showed that the total score of the Adolescents health.related Risky Behavior Inventory and scores of“aggression and violence,”“suicide and selfinjury,”“health.compromising behavior”and“unprotected sex”subscales in the HFA group were significantly higher than those in the control group(Z range-4.197 to-2.213,P<0.05).Among the associated factors,poor emotional experience(B=-0.268,P<0.001),depression(B=-0.321,P<0.001),low score of intelligence(B=-0.032,P=0.042),low score of Theory of Mind test

关键词： High-functioning autism Adolescents health.related risky behaviors Associated factors Risk factors Cross-sectional study

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Biallelic mutations in UGDH cause congenital microcephaly

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Genes & Diseases 2023年第5期10卷 1816-1819页

作者： Li Shu Guangyao Xie Daoqi Mei Rui Xu Shixian Liu Bo Xiao Xing Li Yuanyuan Xie Xiao Mao Hua Wang national health.commission key laboratory for Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangshaHunan 410005China Departments of Biochemistry Molecular Biology and Medical GeneticsCumming School of MedicineUniversity of CalgaryCalgary T2N 4N1Canada Alberta children's Hospital Research institute University of CalgaryCalgary T2N 4N1Canada Department of Neurology Children's Hospital Affiliated to Zhengzhou UniversityZhengzhouHenan 450018China Department of Cell Biology and Genetics School of Basic Medical ScienceXinjiang Medical UniversityUrumqiXinjiang 830054China Department of Pediatric Neurological and Rehabilitation Ganzhou Women and Children's Health Care HospitalGanzhouJiangxi 341000China Department of Neurology Xiangya HospitalChangshaHunan 410005China Department of Pediatrics The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Department of Medical Genetics Hunan Provincial Maternal and Child Health Care HospitalChangshaHunan 410005China Clinical Research Center for Placental Medicine in Hunan Province Hunan Provincial Maternal and Child Health Care HospitalChangshaHunan 410005China Department of Medical Genetics Hunan Children's HospitalChangshaHunan 410007China

Hengel et al recently reported that bi-allelic loss-of-function mutations in UDP-Glucose 6-Dehydrogenase(UGDH)caused a severe epileptic encephalopathy syndrome-Jamuar syndrome(OMIM#618792).1 The functional studies partially recapitulated the clinical phenotypes in the patient-derived cerebral organoid.A reduced number of proliferating neuronal progenitors in cerebral organoids was shown,which is a critical mechanism in congenital microcephaly(CM)whose patients were born with an occipitofrontal circumference(OCF)more than 2 standard deviations below average for age and ***,none of the reported patients in the article presented the phenotype as CM.

关键词： congenital cerebral patients

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Roles of protein tyrosine phosphatases in reproduction and related diseases

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reproductive and Developmental Medicine 2023年第4期7卷 252-256页

作者： Ruo-Heng Du Huai-Yan Chen Lu Gao Department of Physiology Naval Medical UniversityShanghai 200433China Shanghai key laboratory for Assisted Reproduction and reproductive Genetics Shanghai 200433China Shanghai key laboratory of Embryo Original Diseases Shanghai 200433China.

Protein tyrosine phosphatases(PTPs)remove phosphate groups from protein tyrosine residues to regulate various cell signaling processes,subsequently affecting the growth,metabolism,differentiation,immune response,and other cellular *** studies have investigated the functions of PTPs in tumor and organism ***,only a few studies have focused on their roles in reproductive ***,in this review,we summarize the roles and underlying molecular mechanisms of PTPs in infertility,spontaneous abortion,pregnancy-induced hypertension,gestational diabetes mellitus,early embryonic developmental abnormalities,and preterm *** review can contribute to future research on PTPs and their potential applications as targets in the treatment of reproductive diseases.

关键词： Protein tyrosine phosphatase Embryo implantation Spontaneous abortion Pregnancy-induced hypertension Gestational diabetes mellitus Early embryonic developmental abnormalities Preterm birth

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Vitamin C alleviates aging defects in a stem cell model for Werner syndrome

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Protein & Cell 2016年第7期7卷 478-488页

作者： Ying Li Weizhou Zhang Liang Chang Yan Han Liang Sun Xiaojun Gong Hong Tang Zunpeng Liu Huichao Deng Yanxia Ye Yu Wang Jian Li Jie Qiao Jing Qu Weiqi Zhang Guang-Hui Liu national laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China State key laboratory of Stem Cell and reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Department of Pathology Carver College Of Medicine University of lowa lowa City IA 52242 USA The key laboratory of Geriatrics Beijing Hospital & Beijing Institute of Geriatrics Ministry of Health Beijing 100730 China FSU-CAS Innovation institute Foshan University Foshan 528000 China Beijing institute for Brain Disorders Beijing 100069 China Department of Pediatrics Beijing Shijitan Hospital Capital Medical University Peking University Ninth School of Clinical Medicine Beijing 100038 China

Werner syndrome （WS） is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells （MSCs）. This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, teiomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN- deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.

关键词： Vitamin C stem cell aging Wernersyndrome

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A heterozygous N-terminal truncation mutation of NFKBIA results in an impaired NF-κB dependent inflammatory response

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Genes & Diseases 2022年第1期9卷 176-186页

作者： Wen Wen Li Wang Mengyue Deng Yue Li Xuemei Tang Huawei Mao Xiaodong Zhao Chongqing key laboratory of child Infection and Immunity Children's Hospital of Chongqing Medical UniversityChongqing 400014PR China Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical UniversityChongqing400014 PR China Pediatric Research institute Chongqing400014 PR China Ministry of Education key laboratory of child Development and Disorders Chongqing 400014PR China national Clinical Research Center for child health.and Disorders Chongqing400014 PR China China International Science and Technology Cooperation Base of child Development and Critical Disorders Chongqing 400014PR China children's Hospital of Chongqing Medical University Chongqing 400014PR China

Germline heterozygous gain-of-function (GOF) mutation of NFKBIA, encoding IκBα, would affect the activation of NF-κB pathway and cause an autosomal dominant (AD) form of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Here we reported a Chinese patient with a heterozygous N-terminal truncation mutation of NFKBIA/IκBα. She presented recurrent fever, infectious pneumonia and chronic diarrhea with EDA-ID. Impaired NF-κB translocation and IL1R and TLR4 pathway activation were revealed in this patient. The findings suggested that the truncation mutation of IκBα caused medium impaired of activation of NF-κB but the early death. Furthermore, we reviewed all the reported patients with NFKBIA mutation to learn more about this disease.

关键词： AD-EDA-ID HSCT kBa NF-kB activation NFKBIA

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