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Targeting CXCR4 and EDN1 for the treatment of recurrent miscarriage using stearic acid from traditional Chinese medicine

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Traditional Medicine Research 2024年第11期9卷 65-75页

作者： Fang Liu Dong-Mei Shi Wen-Ye Ma Da-Wei Tang Gang Bai Xin-You Yu Reproductive center of Yinchuan Maternal and Child Health Hospital Yinchuan 750001China prenatal diagnosis center of Ningxia Medical University General Hospital Yinchuan 750004China

Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught *** study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM ***,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic ***:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched ***-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target *** employed molecular docking strategies to assess the affinity of TCM components for key ***:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited *** set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling *** human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell ***-cell RNA analysis revealed distinct cellular populations between normal and RM *** pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these ***:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic *** acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.

关键词： RM gene expression single-cell RNA analysis CXCR4 EDN1 stearic acid

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Clinical manifestations and the prenatal diagnosis of trisomy 7 mosaicism:Two case reports

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World Journal of Clinical Cases 2024年第8期12卷 1544-1548页

作者： Fei Hou Yan Li Hua Jin Department of prenatal diagnosis Jinan Maternal and Child Health HospitalJinan 250001Shandong ProvinceChina

BACKGROUND The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific,so prenatal diagnosis is very *** SUMMARY Two pregnant women with abnormal prenatal screening results were *** was a 22-year-old woman(G1P0).At 31st week of gestation,ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 *** other pregnant woman was 33 years old(G2P1L1A0),and her fetus was found to have a cardiac malformation at the 24th week of *** number variation sequencing,whole-exome sequencing and karyotype analysis were carried out after amniocentesis,and both fetuses were diagnosed with trisomy 7 *** parental counseling,one woman continued the pregnancy,and the other woman terminated the *** In trisomy 7 mosaicism,the low proportion of trisomy does not lead to abortion,but can result in abnormal fetal development,which can be detected via ***,clinicians need to pay more attention to various aspects of fetal growth and development,combining with imaging,cellular,molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.

关键词： Trisomy 7 mosaicism Copy number variation sequencing Whole-exome sequencing Karyotype analysis prenatal diagnosis Case report

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Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway

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Science China(Life Sciences) 2024年第9期67卷 1915-1927页

作者： Ling Li Lei Lu Ziqi Xiao Jingyi Lv Hefeng Huang Bo Wu Tongjin Zhao Chengtao Li Weimin Wang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Reproduction and Developmentand Children’s HospitalFudan UniversityShanghai 200090China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China prenatal diagnosis center of Shenzhen Maternity&Child Healthcare Hospital Shenzhen 518028China Shanghai Medical College Fudan UniversityShanghai 200032China Department of Pharmacy College of Life SciencesChina Jiliang UniversityHangzhou 310018China

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue ***6 encodes a negative regulator of BMP,and rare variants of SMAD6 are recurrently found in individuals with birth ***,we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling *** sought to determine whether these SMAD6 variants have common pathogenic ***,we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in ***,increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes,both of which lead to BMP signaling pathway ***,two residues,N262 and N404,in SMAD6 were identified as the crucial sites of deamidation,which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2(GFPT2).Additionally,treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling ***,when wild-type SMAD6 was manually simulated to mimic the deamidated state,the reversed function of activating BMP signaling was *** together,these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity,which can be induced by a subset of various SMAD6 *** study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation,which might prevent the off-target effects of gene editing.

关键词： SMAD6 deamidation BMP signaling pathway GFPT2

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genetic testing and prenatal diagnosis of 64 pedigrees with autosomal dominant polycystic kidney disease

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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 53-54页

作者：王莉 genetic&prenatal Diag center 1st Affil HospZhengzhou UnivZhengzhou 450052

Objective To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD),and explore the detection efficiency of multiple gene analysis techniques and variation *** The clinical data of 64 pedigrees with ADPKD from Nephrology Department or genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed.

关键词： diagnosis kidney clinical

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Effect of male HBV infection on the outcomes of IVF/ICSI cycles:a retrospective cohort study based on propensity score matching

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Asian Journal of Andrology 2024年第4期26卷 415-420页

作者： Su-Qin Zhu Xiu-Hua Liao Wen-Wen Jiang Yan Sun Hui-Ling Xu Xiao-Jing Chen Bei-Hong Zheng Fujian Provincial Reproductive Medicine center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics and Gynecology and PediatricsFujian Medical UniversityFuzhou 350001China Fujian Key Laboratory of prenatal diagnosis and Birth Defect Fuzhou 350001China Fujian Maternal-Fetal Clinical Medicine Research center Fuzhou 350001China.

This study aimed to investigate the effects of male hepatitis B virus(HBV)infection on male fertility,embryonic development,and in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)*** performed a retrospective cohort study that included 3965 infertile couples who received fresh embryo transfer cycles for the first time at the Fujian Maternity and Child Health Hospital(Fuzhou,China)from January 2018 to January *** couples were categorized based on their HBV infection status into the HBV group(HBV-positive men and HBV-negative women)and the control group(HBV-negative couples).A 1:1 propensity score matching was performed with relatively balanced *** characteristics,semen parameters,laboratory outcomes,clinical outcomes,and obstetric and neonatal outcomes were compared between *** propensity score matching,821 couples were included in each *** groups had similar semen parameters and obstetric and neonatal *** HBV group showed a significantly lower live birth rate than the control group(P<0.05).The HBV group had a significantly higher abortion rate than the control group(P<0.05).The rates of high-quality embryos and blastocyst formation were significantly lower in the HBV group than those in the control group(both P<0.05).In conclusion,in couples who undergo IVF/ICSI,male HBV infection reduces the live birth rate and increases the risk of ***,the incidence of low birth weight in women with IVF/ICSI does not increase with male HBV infection.

关键词： hepatitis B virus in vitro fertilization intracytoplasmic sperm injection live birth rate propensity score matching

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Gene expression profiles contribute to robustly predicting prognosis in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 593-596页

作者： Long Liu Yuhui Wang Yuyuan Zhang Siyuan Weng Hui Xu Zaoqu Liu Xinwei Han Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China prenatal diagnosis center The Third Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Interventional Institute of Zhengzhou University ZhengzhouHenan 450052China Interventional Treatment and Clinical Research center of Henan Province ZhengzhouHenan 450052China

Hepatocellular carcinoma(HCC)is characterized by both inter-and intra-tumor heterogeneity and has distinct clinical outcomes.1 A promising clinical tool to perform patient stratification,prognosis evaluation,and treatment recommendations is ***,we enrolled a total of 1595 tumor patients from 13 independent cohorts,including seven cohorts with survival data,four cohorts with immunotherapy information,and two cohorts with transcatheter arterial chemoembolization(TACE)and Sorafenib information,respectively(Table S1).Using 96 algorithms combinations derived from 10 popular machinelearning approaches,a novel framework was constructed and described in Figure ***,a total of 26 stable consensus prognostic genes were screened in seven cohorts harboring complete survival information via univariate Cox regression analysis(Fig.S2A).

关键词： prognosis clinical arterial

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PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han Zhang Kai Gao Shuang Wang Yue-Hua Zhang Zhi-Xian Yang Ye Wu Yu-Wu Jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular diagnosis and Study on Pediatric genetic Diseases BeijingChina Children Epilepsy center Peking University First HospitalBeijingChina Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular *** phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial *** We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation *** information obtained from these patients was analyzed along with that obtained from previously reported *** With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related *** patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental *** most common pathogenic missense variants were PACSI ***203Trp and PACS2 *** addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset *** The clinical phenotypes of the different PACS heterozygous missense variants were *** pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be *** findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

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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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To open early or late:Decoding the mystery of diurnal floret opening time in rice

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Plant Communications 2024年第5期5卷 91-93页

作者： Jian Che Xu Li Yidan Ouyang National Key Laboratory of Crop genetic Improvement and National center of Plant Gene Research(Wuhan) Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

DIFFERENTIATED DIURNAL FLORET OPENING TIME PROMOTES PREZYGOTIC REPRODUCTIVE BARRIERS IN PLANTS As one of the most diverse groups within the plant kingdom,flowering plants have achieved tremendous success on earth and have evolved diversified flowering habits as a result of longterm adaptation to changing *** diurnal floret opening time(DFOT),which represents the time at which a flower opens each day,is a key flowering habit characterized by an internal rhythm and regular environmental cycles.

关键词： diurnal flowering earth

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The key mediator of diabetic kidney disease:Potassium channel dysfunction

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Genes & Diseases 2024年第4期11卷 188-200页

作者： Jia Guo Chaojie Zhang Hui Zhao Yufan Yan Zhangsuo Liu Nephrology Research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Key Laboratory of Precision diagnosis and Treatment for Chronic Kidney Disease in Henan Province ZhengzhouHenan 450052China Research center for Kidney Disease ZhengzhouHenan 450052China

Diabetic kidney disease is a leading cause of end-stage renal disease,making it a global public health *** molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex ***,exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney *** channels are important proteins that maintain the physiological functions of cells and *** ion channels,potassium channels stand out,because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell *** potassium channel abnormalities have been found to be closely related to diabetic kid-ney disease progression and genetic susceptibility,such as K_(ATP),K_(ca),K_(ir),and K_(v).In this review,we summarized the roles of different types of potassium channels in the occurrence and devel-opment of diabetic kidney disease to discuss whether the development of DKD is due to potas-sium channel dysfunction and present new ideas for the treatment of DKD.

关键词： Channel dysfunction Diabetic kidney disease End-stage renal disease lon channel Potassium

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