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Elimination of GGTA1,CMAH,β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions

Animal Models and Experimental Medicine 2024年第4期7卷 584-590页

作者： Jing Xu Jilong Ren Kai Xu Minghui Fang Meina Ka Fei Xu Xin Wang Jing Wang Zhiqiang Han Guihai Feng Ying Zhang Tang Hai Wei Li Zheng Hu State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Key Laboratory of Organ Regeneration and Reconstruction Chinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education The First HospitalJilin UniversityChangchunChina Beijing Farm Animal research center Institute of ZoologyChinese Academy of SciencesBeijingChina

Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to im-prove the immune compatibility between humans and *** knockout strat-egies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHC II molecule plays critical ***:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions ***:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue ***,the safety of our animals after gene editing was verified by using whole-genome sequencing and *** have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional ***:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHC I and II deletion.

关键词： CD4 T cell genetically edited pig immune rejection major histocompatibility complex II xenotransplantation

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Active Molecular Network Discovery Links Lifestyle Variables to Breast Cancer in the Long Island Breast Cancer Study Project

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Environment & health 2024年第6期2卷 401-410页

作者： Miao Yu Qian Li Georgia Dolios Peijun Tu Susan Teitelbaum Jia Chen Lauren Petrick Department of Environmental Medicine and Public health Icahn School of Medicine at Mount SinaiNew YorkNew York 10029United States The Jackson Laboratory FarmingtonConnecticut 06032United States The Institute for Exposomics research Icahn School of Medicine at Mount SinaiNew YorkNew York 10029United States The Bert Strassburger Metabolic center Sheba Medical CenterTel-Hashomer 5266202Israel

A healthy lifestyle has been associated with decreased risk of developing breast *** untargeted metabolomics profiling,which provides unbiased information regarding lifestyle choices such as diet and exercise,we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis.A total of 100 postmenopausal women,50 with breast cancer and 50 cancer-free controls,were selected from the Long Island Breast Cancer Study Project(LIBCSP).We measured untargeted plasma metabolomics using liquid chromatography-high-resolution mass spectrometry(LCHRMS).Using the“enet”package,we retained highly correlated metabolites representing active molecular network(AMN)clusters for *** was used to examine associations between cancer status and AMN metabolites and covariates such as BMI,age,and reproductive *** was then repeated to examine associations between AMN metabolites and 10 lifestyle-related variables including smoking,physical activity,alcohol consumption,meat consumption,fruit and vegetable consumption,and supplemental vitamin *** were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer *** filtering,851“active”metabolites out of 1797 metabolomics were retained in 197 correlation AMN *** LASSO,breast cancer status was associated with 71“active”*** of these metabolites were associated with lifestyle variables including meat consumption,alcohol consumption,and supplementalβ-carotene,B12,and folate *** metabolites could potentially serve as molecular-level biological intermediaries connecting healthy lifestyle factors to breast cancer,even though direct associations between breast cancer and the investigated lifestyles at the phenotype level are not *** particular,DiHODE,a metabolite linked with inflammation,was associated with breast cancer status and connected toβ-carotene supplement usage through an *** foun

关键词： Metabolomics exposome machine learning network analysis public health

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MiR-450b-5p enhances the radiosensitivity of HR^(+) and HER2^(−) breast cancer by targeting CDK6

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Oncology and Translational Medicine 2024年第4期10卷 198-203页

作者： Ruxing Wu Hanwang Zhang Xiaoyuan Huang Liang Zhuang reproductive Medicine center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Biology research Centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative *** studies have reported that microRNAs(miRNAs)are involved in the radiosensitivity of human breast cancer *** miRNA microarray study showed that miR-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor–positive(ER^(+))and human epidermal growth factor receptor 2–negative(HER2−)breast cancer and no local relapse compared with local relapse ***,its underlying mechanism of action remains ***:The predicted target mRNAs of miR-450b-5p were screened using the TargetScan,miRDB,and miRWalk *** blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent kinase 6(CDK6)and *** cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 *** formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 ***:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demonstrated that CDK6 was the target gene of ***,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cell cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tumors after irradiation by regulating ***:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor–positive(HR^(+))and HER2−breast cancer cells and elucidates its ***-450b-5p may be considered a therapeutic target in HR^(+)and HER2−breast cancer treated with radiotherapy.

关键词： Breast cancer Cyclin-dependent kinase 6 miR-450b-5p Radiosensitivity

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Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

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Oncology and Translational Medicine 2024年第2期10卷 73-78页

作者： Ru-Xing Wu Dan Hu Han-Wang Zhang Xiao-Yuan Huang Liang Zhuang reproductive Medicine center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer Biology research Centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Cancer center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain *** study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with ***:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate ***,we validated the protein levels of these candidates using ***,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression ***:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight *** expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,*** 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

关键词： Breast cancer Obesity PER2 Prognosis

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Maternal Preconception Serum Alanine Aminotransferase Levels and Risk of Preterm Birth among reproductive-Aged Women—China,2013-2017

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China CDC weekly 2024年第10期6卷 181-188,I0001页

作者： Chuanyu Zhao Jiajing Jia Hanbin Wu Qin Xu Xinyi Lyu Meiya Liu Xuan Hu Jueming Lei Yuzhi Deng Yuan He Yuanyuan Wang Zuoqi Peng Ya Zhang Hongguang Zhang Qiaomei Wang Haiping Shen Yiping Zhang Donghai Yan Ying Yang Xu Ma National research Institute for Family Planning BeijingChina National Human Genetic Resources center BeijingChina Graduate School of Peking Union Medical College BeijingChina Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Summary What is already known about this topic?The significance of maternal liver health concerning preterm birth(PTB)is well recognized;however,there is a gap in understanding the precise influence of preconception s... 详细信息

关键词： Serum precise concerning

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Prevalence of retinopathy of prematurity in Iran： asystematic review and Meta-analysis

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International Journal of Ophthalmology(English edition) 2017年第8期10卷 1273-1279页

作者： Saman Maroufizadeh Amir A lmasi-Hashiani Reza Omani Samani Mahdi Sepidarkish Department of Epidemiology and reproductive health Reproductive Epidemiology Research Center Royan Institute for Reproductive Biomedicine ACECR Tehran 16635-148Iran

AIM： To estimate overall prevalence of retinopathy of prematurity （ROP） in Iran using a systematic review and Meta-analysis. METHODS： A systematic review and Meta-analysis was performed of all published studies pertaining to prevalence of ROP using international and national electronic databases （ISI Web of Sciences, PubMed, Scopus, Google Scholar, SlD, Maglran, and IranMedex） from their inception until May 2016 with standard keywords. Begg and Egger tests were used to examine the publication bias and Cochran test and f statistics were used to evaluate the statistical heterogeneity. Pooled estimate of the prevalence of ROP were calculated using random effects Meta- analysis. RESULTS： The publication bias assumption was rejected by Egger tests with P-value equal to 0.024. The results of Cochran test and 12 statistics revealed substantial heterogeneity （Q=1099.02, df=25, f=97.7%, P=-0.001）. The overall prevalence of ROP using the random effect model in Iran was 26.1% （95% Ch 20.3%-31.8%）. CONCLUSION： The prevalence of ROP is relatively high in Iran. Low birth weight and gestational age are significant risk factors for the disease. Improved care, including oxygen delivery and monitoring, for preterm babies in all facility settings would reduce the number of babies affected with ROP.

关键词： retinopathy of prematurity preterm birth infant Meta-analysis systematic review Iran

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Integrative analysis of tumor stemness and immune microenvironment deciphers novel molecular subtypes in hepatocellular carcinoma

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Genes & Diseases 2024年第5期11卷 81-84页

作者： Zhiyi Wang Shuang Chen Dongxiao Li Hui Xu Siyuan Weng Yuyuan Zhang Yuqing Ren Chunguang Guo Xiuling Li Zaoqu Liu Xinwei Han Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Gastroenterology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhouHenan 450004China center of reproductive Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100730China

Hepatocellular carcinoma(HCC)is a highly heterogeneous tumor,with dynamic equilibrium and complex interplay between its intricate tumor nature and ambient tumor immune microenvironment(TIME).1 Elegant research has indicated that cancer stem cells,a small subset of neoplastic cells confined within dedicated niches,display stem cell-like properties and interact with cells in TIME,thereby imparting an indelible impact on stemness regulation,tumor heterogeneity,and cancer cell plasticity.2 Previous taxonomies solely from the perspective of stemness or TIME may introduce some degree of bias in the comprehension of HCC carcinogenesis,3,4 and thus it is of paramount importance to systematically consider tumor stemness and TIME as a whole to truly portray the biological landscape of HCC.

关键词： thereby landscape stem

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Impact of Periconceptional Multi-micronutrient Supplementation on Gestation:A Population-based Study

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Biomedical and Environmental Sciences 2013年第1期26卷 23-31页

作者： WANG Ya Fei PEI Li Jun SONG Xin Ming CHEN Gong ZHENG Xiao Ying Institute of Population research/WHO Collaborating center on reproductive health and Population Science Peking University

Objective To examine the effect of periconceptional multi‐micronutrient supplementation on gestation and birth *** A population‐based community intervention program was conducted in 18 counties in *** were divided into an intervention group,who received multi‐micronutrient supplementation from at least 3 months before pregnancy throughout the first trimester,and a control *** women were followed up to record information about birth *** socio‐economic characteristics and main birth outcomes were *** age was further analyzed using survival analysis,to determine the time distribution of *** Periconceptional multi‐micronutrient supplementation was associated with higher birth weight,birth length and occipitofrontal head circumference,and with lower incidence rates for stillbirth,low birth weight,and preterm ***,periconceptional multi‐micronutrient supplementation changed the time distribution of delivery,making the deliveries more clustered in the period between day 275 and day 295 of *** Our study shows that periconceptional multi‐micronutrient supplementation is beneficial for fetal development and optimizes all measured aspects of health in neonates in socioeconomically disadvantaged areas in *** change in time distribution of deliveries caused by multi‐micronutrient supplementation needs further clarification.

关键词： Multi‐micronutrient Supplementation Gestation Birth weight Gestational age

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Transcriptome profiling and RXR gene family identification reveals the molecular mechanism of rapid aging after spawning of cuttlefish Sepiella japonica

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Journal of Oceanology and Limnology 2024年第3期42卷 865-880页

作者： Zhenyu DONG Jiemei ZHAO Feng GUO Shuangrui LIN Huai YANG Yingying YE Changfei CHI Hongfei LI Baoying GUO College of Marine Science and Technology Zhejiang Ocean UniversityZhoushan 316022China National Engineering research center for Marine Aquaculture Zhejiang Ocean UniversityZhoushan 316022China Donghai Laboratory Zhoushan 316021China

Sepiella japonica is a worldwide marine cuttlefish species of high economic *** routinely modifying behaviors in reproductive life,such as rapid aging until death after spawning,has been recognized in artificial ***,reproductive behavior at the level of genes is rarely reported,thus,the research on the genetic basis of behavior,reproduction,and artificial breeding was *** applied RNA-seq in different stages of reproduction to investigate the reason of rapid aging after spawning,pre-maturity,pre-spawning after maturity,and *** retinoid X receptor(RXR)gene family in *** was identified,and 1343–1452 differentially expressed genes(DEGs)in all 3 stages of reproductive life were identified from pairwise m RNA ***,through the GO term and KEGG analysis,*** could handle neuronal development and network formation before maturity and have a functional degradation of neural communication,signal transduction,vision,and gene expression after *** Sj RXRαs have been identified and they played different roles in growth development or ***,the regulation of several channels and receptors is the intrinsic molecular mechanism of rapid aging after spawning in *** study revealed the survival strategy and provided fundamental data on the level of genes for understanding the reproductive behavior and the reproduction of ***.

关键词： Sepiella japonica RAN-seq retinoid X receptor(RXR)gene family rapid aging intrinsic molecular mechanism

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Cadherin-18 loss in prospermatogonia and spermatogonial stem cells enhances cell adhesion through a compensatory mechanism

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Zoological research 2024年第5期45卷 1048-1060页

作者： Xiao-Xiao Li Dan-Chen Zhang Yan Wang Jian Wen Xing-Ju Wang Yu-Lu Cao Ru Jiang Jia-Rui Li Yi-Nuo Li He-He Liu Wen-Hai Xie Zheng-Feng Xu Ping Hu Kang Zou Germline Stem Cells and Microenvironment Lab College of Animal Science and TechnologyNanjing Agricultural UniversityNanjingJiangsu 210095China Stem Cell research and Translation center Nanjing Agricultural UniversityNanjingJiangsu 210095China School of Life Sciences and Medicine Shandong University of TechnologyZiboShandong 255000China Department of Prenatal Diagnosis Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu 210004China

Extracellular membrane proteins are crucial for mediating cell attachment,recognition,and signal transduction in the testicular microenvironment,particularly germline stem *** 18(CDH18),a type Ⅱ classical cadherin,is primarily expressed in the nervous and reproductive ***,we investigated the expression of CDH18in neonatal porcine prospermatogonia(ProSGs)and murine spermatogonial stem cells(SSCs).Disruption of CDH18 expression did not adversely affect cell morphology,proliferation,self-renewal,or differentiation in cultured porcine ProSGs,but enhanced cell adhesion and prolonged cell *** analysis indicated that the down-regulation of CDH18 in ProSGs significantly up-regulated genes and signaling pathways associated with cell *** further elucidate the function of CDH18 in germ cells,Cdh18 knockout mice were generated,which exhibited normal testicular morphology,histology,*** analysis showed increased expression of genes associated with adhesion,consistent with the observations in porcine *** interaction of CDH18withβ-catenin and JAK2 in both porcine ProSGs and murine SSCs suggested an inhibitory effect on the canonical Wnt and JAK-STAT signaling pathways during CDH18 ***,these findings highlight the crucial role of CDH18 in regulating cell adhesion in porcine ProSGs and mouse *** this regulatory mechanism provides significant insights into the testicular niche.

关键词： Extracellular signal Fertility Quiescency Wnt signaling pathway

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