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MACS-annexin V cell sorting of semen samples with high TUNEL values decreases the concentration of cells with abnormal chromosomal content:a pilot study

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Asian Journal of Andrology 2022年第5期24卷 445-450页

作者： Sahar El Fekih Nadia Gueganic Corinne Tous Habib Ben Ali Mounir Ajina Nathalie Douet-Guilbert Hortense Drapier Damien Beauvillard Frédéric Morel Aurore Perrin University of Brest InsermUMR U1078Faculty of Medicine and Health SciencesBrest 29238France Laboratory of human Cytogenetics Molecular Genetics and Reproductive BiologyFarhat Hached University HospitalSousse 4031Tunisia Departement of Medical Genetics and reproductive Biology Brest University Regional HospitalBrest 29609France Department of reproductive Medicine Farhat Hached Teaching HospitalSousse 4031Tunisia

We question whether,in men with an abnormal rate of sperm DNA fragmentation,the magnetic-activated cell sorting(MACS)could select spermatozoa with lower rates of DNA fragmentation as well as spermatozoa with unbalanced chromosome *** spermatozoa from six males were separated into nonapoptotic and apoptotic *** determined the percentages of spermatozoa with(i)externalization of phosphatidylserine(EPS)by annexin V-Fluorescein isothiocyanate(FITC)labeling,(ii)DNA fragmentation by TdT-mediated-dUTP nick-end labeling(TUNEL),and(iii)numerical abnormalities for chromosomes X,Y,13,18,and 21 by fluorescence in situ hybridization(FISH),on the whole ejaculate and selected spermatozoa in the same *** to the nonapoptotic fraction,the apoptotic fraction statistically showed a higher number of spermatozoa with EPS,with DNA fragmentation,and with numerical chromosomal *** to the whole ejaculate,we found a significant decrease in the percentage of spermatozoa with EPS and decrease tendencies of the DNA fragmentation rate and the sum of disomy levels in the nonapoptotic ***,we observed statistically significant higher rates of these three parameters in the apoptotic *** may help to select spermatozoa with lower rates of DNA fragmentation and unbalanced chromosome content in men with abnormal rates of sperm DNA fragmentation.

关键词： chromosomal abnormalities DNA fragmentation externalization of phosphatidylserine magnetic-activated cell separation spermatozoa

Emerging molecular classifications and therapeutic implications for gastric cancer

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Chinese Journal of Cancer 2016年第8期35卷 393-402页

作者： Tao Chen Xiao-Yue Xu Ping-Hong Zhou endoscopy Center Zhongshan Hospital of Fudan University endoscopy Research Institute Fudan University

Gastric cancer(GC) is a highly aggressive and life-threatening *** with radical surgical removal and front-line chemotherapy,more than half of GCs locally relapse and metastasize at a distant *** dismal outcomes reflect the ineffectiveness of a one-size fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular *** recent comprehensive genomic and molecular profiling has led to our deepened understanding of *** emerging molecular classification schemes based on the genetic,epigenetic,and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise *** this end,the Cancer Genome Atlas(TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes:Epstein-Barr virus-associated tumors,microsatellite unstable tumors,genomically stable tumors,and tumors with chromosomal *** review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy *** believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs.

关键词： Gastric cancer Molecular classification Personalized therapy The Cancer Genome Atlas research network

reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment

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Science China(Life Sciences) 2015年第9期58卷 829-838页

作者： XIONG WenPing WANG DaYong GAO Yuan GAO Ya WANG HongYang GUAN Jing LAN Lan YAN JunHao ZONG Liang YUAN Yuan DONG Wei HUANG SeXin WU KeLiang WANG YaoShen WANG ZhiLi PENG HongMei LU YanPing XIE LinYi ZHAO Cui WANG Li ZHANG QiuJing GAO Yun LI Na YANG Ju YIN ZiFang HAN Bing WANG Wei CHEN Zi-Jiang WANG QiuJu Department of Otolaryngology-Head and Neck surgery Chinese PLA Institute of Otolaryngology Chinese PLA General Hospital Center for reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong University National Research Center for Assisted reproductive Technology and reproductive Genetics BGI-Shenzhen Department of Ultrasonography Chinese PLA General Hospital Department of Obstetrics and Gynecology Chinese PLA General Hospital The Key laboratory for reproductive Endocrinology of Ministry of Education

A couple with a proband child of GJB2 （encoding the gap junction protein connexin 26）-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a cus- tomized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagno- sis （PGD）, noninvasive prenatal testing （NIPT）, and noninvasive prenatal diagnosis （N1PD） into the strategy. Auditory and ge- netic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a sin- gleton pregnancy. At the 13th week of gestation, genomic DNA （gDNA） from the trio family and cell-free DNA （cfDNA） from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by inva- sire procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing im- pairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

关键词： preimplantation genetic diagnosis(PGD) noninvasive prenatal testing(NIPT) noninvasive prenatal diagnosis(NIPD) GJB2(encoding the

Male fertility following childhood cancer: current conceptsand future therapies

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Asian Journal of Andrology 2003年第4期5卷 325-337页

作者： Mark F. H. Brougham Christopher J. H.Kelnar Richard M.Sharpe W.Hamish B.Wallace Royal hospital for Sick Children Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United KingdomMRC Human Reproductive Sciences Unit Centre for Reproductive Biology University of Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United Kingdom

Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeu tic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for Hodgkin's disease, are particularly associated with subsequent infertility. Radiotherapy may also cause gonadal damage, most notably following direct testicular irradiation or total body irradiation. Because of the varied nature of the cytotoxic insult, it can be difficult to predict the likelihood of infertility in later life. Currently it is not possible to detect gonadal damage early due to the lack of a sensitive marker of gonadal function in the prepubertal age *** cryopreservation is currently the only method of preserving fertility in patients receiving gonadotoxic therapy. This is only applicable to postpubertal patients and can be problematic in the adolescent age group. At present there is no provision for the prepubertal boy, although there are a number of experimental methods currently being investigated. By harvesting testicular tissue prior to gonadotoxic therapy, restoration of fertility could be achieved following treatment, either by germ cell transplantation or by in vitro maturation of the germ cells harvested. Alternatively, rendering the testes quiescent during cytotoxic treatment may protect the germ cells from subsequent damage. In addition to the many scientific and technical issues to be overcome prior to clinical application of these techniques, a number of ethical and legal issues must also be addressed to ensure a safe and realistic prospect for future fertility in these patients.

关键词： infertility childhood cancer semen cryopreservation germ cell transplantation In vitro germ cell maturation assisted reproductive techniques

Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers

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Signal Transduction and Targeted Therapy 2019年第1期4卷 116-126页

作者： Wanxue Xu Mengyao Xu Longlong Wang Wei Zhou Rong Xiang Yi Shi Yunshan Zhang Yongjun Piao School of Medicine Nankai UniversityTianjinChina Tianjin Key Laboratory of human Development and reproductive Regulation Nankai University Affiliated Hospital of Obstetrics and GynecologyTianjinChina reproductive Medical Center Nankai University Affiliated Hospital of Obstetrics and GynecologyTianjinChina

Cervical cancer is the leading cause of death among women with cancer ***,we performed an integrative analysis of Illumina humanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation *** first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene *** DNA methylation profiles of 12 types of cancers,including cervical cancer,were used to generate a candidate set,and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate ***,we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal *** methylation was negatively correlated with the local regulation of gene *** the distant regulation of gene expression,the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression,while the methylation of hypomethylated genes was more likely to be positively correlated with gene ***,we identified four cervical cancer-specific methylation markers,cg07211381(RAB3C),cg12205729(GABRA2),cg20708961(ZNF257),and cg26490054(SLC5A8),with 96.2%sensitivity and 95.2%specificity by using the tenfold cross-validation of TCGA *** four markers could distinguish tumors from normal tissues with a 94.2,100,100,and 100%AUC in four independent validation sets from the GEO ***,our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.

关键词： cervical diagnosis specificity

Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

Pediatric gastrointestinal bleeding: Perspectives from the Italian Society of Pediatric Gastroenterology

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World Journal of Gastroenterology 2017年第8期23卷 1328-1337页

作者： Claudio Romano Salvatore Oliva Stefano Martellossi Erasmo Miele Serena Arrigo Maria Giovanna Graziani Sabrina Cardile Federica Gaiani Gian Luigi de'Angelis Filippo Torroni Unit of Pediatrics Department of Human Pathology in Adulthood and Childhood“G.Barresi”University of Messina Department of Pediatrics and Infantile Neuropsychiatry Pediatric Gastroenterology and Liver UnitSapienza University of Rome Institute for Maternal and Child Health IRCCS‘Burlo Garofalo’ Department of Translational Medical Science Section of PediatricsUniversity of Naples“Federico II” Gastroenterology and endoscopy Unit G.Gaslini Children’s Hospital-IRCCS Gastroenterology and endoscopy Unit “San Giovanni Addolorata”Hospital Hepatology Gastroenterology and Nutrition UnitBambino GesùChildren’s Hospital Gastroenterology and endoscopy Unit University of Parma Department of surgery and Transplantation Digestive Surgery and Endoscopy UnitBambino GesùChildren’s Hospital

There are many causes of gastrointestinal bleeding(GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality. To assist medical care providers in the evaluation and management of children with GIB, the "Gastro-Ped Bleed Team" of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition(SIGENP) carried out a systematic search on MEDLINE via Pub Med(http://***/pubmed/) to identify all articles published in English from January 1990 to 2016; the following key words were used to conduct the electronic search: "upper GIB" and "pediatric" [all fields]; "lower GIB" and "pediatric" [all fields]; "obscure GIB" and "pediatric" [all fields]; "GIB" and "endoscopy" [all fields]; "GIB" and "therapy" [all fields]. The identified publications included articles describing randomized controlled trials, reviews, case reports, cohort studies, casecontrol studies and observational studies. References from the pertinent articles were also reviewed. This paper expresses a position statement of SIGENP that can have an immediate impact on clinical practice and for which sufficient evidence is not available in literature. The experts participating in this effort were selected according to their expertise and professional qualifications.

关键词： Gastrointestinal bleeding endoscopy Lower gastrointestinal bleeding Upper gastrointestinal bleeding Pediatric

Novel PLCZ1 mutation caused polyspermy during in vitro fertilization

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Asian Journal of Andrology 2024年第4期26卷 389-395页

作者： Ke-Ya Tong Wei-Wei Liu Li-Wei Sun Dong-Yun Liu Ye-Zhou Xiang Chong Li Lu-Wei Chai Ke Chen Guo-Ning Huang Jing-Yu Li Chongqing Key Laboratory of human Embryo Engineering Center for Reproductive MedicineWomen and Children’s Hospital of Chongqing Medical UniversityChongqing 400012China Chongqing Clinical Research Center for reproductive Medicine Center for Reproductive MedicineChongqing Health Center for Women and ChildrenChongqing 400012China.

Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental *** studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains ***-exome sequencing(WES)was performed to identify candidate mutations in couples with primary *** sequencing was used to validate the *** PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was *** oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte *** identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,*** formation failure was observed during the ICSI ***,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN *** after ICSI enabled normal fertilization,and all patients achieved successful *** findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking ***,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

关键词： AOA PLCZ1 polyspermy pronuclear formation

Protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium on ovarian damage

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Journal of Molecular Cell Biology 2020年第5期12卷 372-385页

作者： Liming Hong Long Yan Zhimin Xin Jie Hao Wenjing Liu Shuyu Wang Shujie Liao Hongmei Wang Xiaokui Yang Department of human reproductive Medicine Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijing 100026China State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Department of Gynaecology and Obstetrics Reproductive Medical CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Chemotherapeutic agents are extensively used to treat ***,chemotherapy-induced ovarian damage and reduced fertility are severe side ***,stem cell transplantation has been reported to be an effective strategy for premature ovarian insufficiency(POI)treatment,but safety can still be an issue in stem cell-based ***,we show the protective effects of human umbilical cord mesenchymal stem cell-derived conditioned medium(hUCMSC-CM)on a cisplatin(Cs)-induced ovarian injury ***-CM can relieve Cs-induced depletion of follicles and preserve *** addition,hUCMSC-CM can decrease apoptosis of oocytes and granulosa cells induced by *** sequencing analysis reveals the differentially expressed genes of ovaries after Cs and hUCMSC-CM treatments,including genes involved in cell ***,we show that the granulocyte colony-stimulating factor(G-CSF)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway plays an important role in protecting granulosa cells from Cs-induced ***,we confirm the protective effects of hUCMSC-CM on ovarian reserve and fertility in mice treated with Cs,highlighting the remarkable therapeutic effects of hUCMSC-CM.

关键词： stem cell ovarian damage RNA sequencing