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Genes & Diseases 2024年第4期11卷 39-41页

作者： Tong Qiao Beining Yin Jun Liang Li Wei Department of Thoracic Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China reproductive Medicine center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Breast Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China

Due to the profound heterogeneity exhibited amongst patients with lung adenocarcinoma(LUAD),considerable variances in clinical efficacy emerge.1 For the aims of precision medicine,a clinical instrument to delineate distinct disease phenotypes and anticipate susceptibility to intervention is *** cytotoxicity mediated through T lymphocytes constitutes a pivotal mechanism of anti-tumoral immunity and the foundation for cancer immunotherapy.?Numerous genes regulating the sensitivity of tumor cells to killing mediated by T lymphocytes(GSTKKs)are conducive to satisfying the aforesaid medical necessity.

关键词： clinical mediated adenocarcinoma

Probiotic microorganisms affect the reproductive and nervous systems of male rats treated with acrylamide

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Asian pacific Journal of Reproduction 2024年第4期13卷 178-186页

作者： Seyedhossein Hekmatimoghaddam Maryam Yadegari Fateme Zare Fatemeh Zakizadeh Seyed Mohammad Seifati Hematology and Oncology Research center Shahid Sadoughi University of Medical SciencesYazdIran Department of Laboratory Sciences School of ParamedicineShahid Sadoughi University of Medical SciencesYazdIran Neuroendocrine Research center Shahid Sadoughi University of Medical SciencesYazdIran Department of Anatomy and Cell Biology Faculty of MedicineShahid Sadoughi University of Medical SciencesYazdIran reproductive Immunology Research center Shahid Sadoughi University of Medical SciencesYazdIran

Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with ***:Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage(control),acrylamide 20 mg/kg body weight,acrylamide plus probiotic microorganisms(Lactobacillus acidophilus,Lactobacillus casei,Lactobacillus bulgaricus,Lactobacillus rhamnosus,Bifidobacterium breve,Bifidobacterium infantis,Streptococcus thermophilus and fructooligosaccharides,all mixed in sachets)20 or 200 mg/kg body weight,*** 30 days,the testis,prostate,seminal vesicle and cerebellum were removed,fixed and stained with hematoxylin-eosin(H&E).The Johnsen score was used to classify ***'s principle method was used to evaluate the total volume(in mm3)of the *** number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting *** analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell ***:The testis weight decreased significantly in the acrylamide-treated group compared to the other groups(P<0.001).The number of spermatogonia,spermatocytes,spermatids and Leydig cells in the acrylamide-treated group were significantly less compared to the control group(P<0.05),while they were increased significantly in the acrylamide+200 mg/kg probiotic group(P<0.05;P<0.01).The mean Johnsen score in the acrylamide-treated group was lower than in the control group(P<0.001).Acrylamide-induced changes including congestion,vacuolization in the secretory epithelial cells,and epithelial rupture were observed in the prostate and seminal *** volumes of cerebellar layers were decreased in the acrylamide group compared to the control group while recovered in both probiotic treated ***:Probiotic microorganisms alleviate acryl

关键词： Acrylamide Cerebellum Microorganisms Probiotics Prostate Rats Testis

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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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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ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate:immune mechanisms of recurrent early pregnancy loss

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National Science Review 2024年第06期 129-145页

作者： Wentong Jia Liyang Ma Xin Yu Feiyang Wang Qian Yang Xiaoye Wang Mengjie Fan Yan Gu Ran Meng Jian Wang Yuxia Li Rong Li Xuan Shao Yan-Ling Wang State Key Laboratory of Stem cell and reproductive Biology Key Laboratory of Organ Regeneration and ReconstructionInstitute of ZoologyChinese Academy of Sciences Beijing Institute for Stem Cell and Regenerative Medicine University of the Chinese Academy of Sciences NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drug and Devices Shanghai Institute for Biomedical and Pharmaceutical Technologies National Clinical center for Obstetrics and Gynecology Peking University Third Hospital Department of Family Planning The Second Hospital of Tianjin Medical University Department of Prenatal Screening Haidian Maternal and Child Health Hospital

Decidual natural killer（dNK） cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss（RPL） at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG（NOD/Shi-scid/IL-2Rγnull） mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients（dNK-RPL）remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+dNK *** studies revealed that CD56+CD39+dNK subset facilitates early differentiation of mouse trophoblast stem cells（m TSCs） towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor（M-CSF）. Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

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Current therapies for osteoarthritis and prospects of CRISPR-based genome,epigenome,and RNA editing in osteoarthritis treatment

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Journal of Genetics and Genomics 2024年第2期51卷 159-183页

作者： Yuxi Chen Xiao Luo Rui Kang Kaixin Cui Jianping Ou Xiya Zhang Puping Liang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China center for reproductive Medicine The Third Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhouGuangdong 510630China

Osteoarthritis(OA)is one of the most common degenerative joint diseases worldwide,causing pain,disability,and decreased quality of *** balance between regeneration and inflammation-induced degradation results in multiple etiologies and complex pathogenesis of ***,there is a lack of effective therapeutic strategies for OA *** the development of CRISPR-based genome,epigenome,and RNA editing tools,OA treatment has been improved by targeting genetic risk factors,activating chondrogenic elements,and modulating inflammatory *** by cell therapy and in vivo delivery vectors,genome,epigenome,and RNA editing tools may provide a promising approach for personalized OA *** review summarizes CRISPR-based genome,epigenome,and RNA editing tools that can be applied to the treatment of OA and provides insights into the development of CRISPR-based therapeutics for OA ***,in-depth evaluations of the efficacy and safety of these tools in human OA treatment are needed.

关键词： Osteoarthritis Genome editing Epigenone editing RNA editing

Regulable toehold lock for the effective control of strand displacement reaction sequence and circuit leakage

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Chinese Chemical Letters 2024年第7期35卷 372-376页

作者： Kuangdi Luo Yang Qin Xuehao Zhang Hanxu Ji Heao Zhang Jiangtian Li Xianjin Xiao Xinyu Wang Department of Breast Surgery Second Hospital of Jilin UniversityChangchun 130041China Institute of reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pancreatic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Life Science and Technology Wuhan Polytechnic UniversityWuhan 430023China

Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and *** has the characteristics of high efficiency,universality and ***,the existing regulation tools cannot enable effective control of the reaction sequence,which undoubtedly limits the construction of complex nucleic acid ***,we developed a regulation tool,toehold lock,and achieved strict control of reaction sequence without loss of the main reaction signal ***,we applied the tool to scenarios such as seesaw circuits,AND/OR logic gates,and entropy-driven circuits,and respectively demonstrated its significant superiority compared to the original *** believe that the proposed toehold lock has greatly optimized the efficiency of DNA strand displacement-based networks,and we anticipate that the tool will be widely used in multiple fields.

关键词： DNA circuit Toehold lock DNA strand displacement Reaction sequence Seesaw circuit

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DNA methylation clocks for estimating biological age in Chinese cohorts

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Protein & Cell 2024年第8期15卷 575-593页

作者： Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China Division of Orthopaedics Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China The Joint Innovation center for Engineering in Medicine Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Biomarker Consortium Beijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China nstitute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China State Key Laboratory of Stem Cell and reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National Genomics Data center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG ***,a systematic comparison between DNA methylation data and other omics datasets has not yet been ***,available DNAm age predictors are based on datasets with limited ethnic *** address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm ***,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological *** clocks were further employed to predict factors influencing aging *** DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age *** findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关键词： DNA methylation aging clock aging age prediction

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2123-2140页

作者： Hong-Xia Bai Xue-Mei Qiu Chun-Hong Xu Jian-Qiang Guo Department of Gastroenterology The Second Hospital of Shandong UniversityJinan 250000Shandong ProvinceChina Department of Gastroenterology Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of reproductive center Zaozhuang Maternal and Child Health Care HospitalZaozhuang 277000Shandong ProvinceChina

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer ***,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of *** Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and *** ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,*** proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow *** of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western *** of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter *** family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical *** correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot *** association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and *** mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude *** GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this *** of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 ***-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 *** mouse tumorigenesis experiments confirmed that miR-145-5p target

关键词： Gastric cancer MicroRNA-145-5p Serpin family E member 1 Epithelial-mesenchymal transition Proliferation Extracellular signal-regulated kinase-1/2