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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing Chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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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

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The priming induction regimen of HAG as a low dose chemotherapy strategy in AML clonal evolution

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Science China(Life Sciences) 2015年第12期58卷 1302-1305页

作者： CHEN AiLi YANG JingYi HU ShaoYan WANG Qian-Fei Key laboratory of genomic and Precision medicine Beijing Institute of Genomics Chinese Academy of Sciences The Children's Hospital of Soochow University

Chemotherapy employs chemical substances to interfere with the growth of cancer cells,and is a major treatment strategy in human cancer including acute myeloid leukemia（AML）.Although they often effectively kill fast... 详细信息

关键词： regimen chemotherapy clonal interfere myeloid dividing subgroup induction clone relapse

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Non-coding RNA: a new frontier in regulatory biology

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National Science Review 2014年第2期1卷 190-204页

作者： Xiang-Dong Fu Department of Cellular and Molecular medicine Institute of Genomic Medicine University of California

A striking inding in the past decade is the production of numerous non-coding RNAs(nc RNAs) from mammalian genomes. While it is entirely possible that many of those nc RNAs are transcription noises or by-products of RNA processing, increasing evidence suggests that a large fraction of them are functional and provide various regulatory activities in the cell. hus, functional genomics and proteomics are incomplete without understanding functional ribonomics. As has been long suggested by the ‘RNA world’hypothesis, many nc RNAs have the capacity to act like proteins in diverse biochemical processes. he enormous amount of information residing in the primary sequences and secondary structures of nc RNAs makes them particularly suited to function as scafolds for molecular interactions. In addition, their functions appear to be stringently controlled by default via abundant nucleases when not engaged in speciic interactions. his review focuses on the functional properties of regulatory nc RNAs in comparison with proteins and emphasizes both the opportunities and challenges in future nc RNA research.

关键词： the RNA world non-coding RNA biological functions regulatory mechanisms experimental approaches functional genomics

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Computational Methods for Single-cell DNA Methylome Analysis

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genomics, Proteomics & Bioinformatics 2023年第1期21卷 48-66页

作者： Waleed Iqbal Wanding Zhou Center for Computational and genomic medicine Children’s Hospital of PhiladelphiaPhiladelphiaPA 19104USA Department of Pathology and laboratory medicine University of PennsylvaniaPhiladelphiaPA 19104USA

Dissecting intercellular epigenetic differences is key to understanding tissue *** advances in single-cell DNA methylome profiling have presented opportunities to resolve this heterogeneity at the maximum *** these advances enable us to explore frontiers of chromatin biology and better understand cell lineage relationships,they pose new challenges in data processing and *** review surveys the current state of computational tools developed for single-cell DNA methylome data *** discuss critical components of single-cell DNA methylome data analysis,including data preprocessing,quality control,imputation,dimensionality reduction,cell clustering,supervised cell annotation,cell lineage reconstruction,gene activity scoring,and integration with transcriptome *** also highlight unique aspects of single-cell DNA methylome data analysis and discuss how techniques common to other single-cell omics data analyses can be adapted to analyze DNA ***,we discuss existing challenges and opportunities for future development.

关键词： Single-cell genomics Bioinformatics DNA methylation Computational tool Epigenetics

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Establishment and application of minigene models for studying pre-mRNA alternative splicing

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Science China(Life Sciences) 2004年第3期47卷 211-218页

作者： LI Jing CHEN Xianhua LIN Wanmin LI Lishu HAN Yu XU Ping laboratory of genomic Physiology School of Life Sciences Fudan University Shanghai 200433 China

The objective of the present study is to establish a minigene model for studying pre-mRNA alternative splicing. To prepare the minigene DNA constructs, with human or mouse genomic DNA as templates, GluR-B , FGF-2R and Zis 搈inigene?fragments were amplified us-ing PCR and cloned to the eukaryotic expression vectors. The three constructed minigenes and the expression vectors of Tra2b1 and Zis2 were co-transfected in Hela cells. RT-PCR analysis was performed to semi-quantitatively determine the spliced products from the minigenes. The results demonstrated that the constructed minigenes are useful in studying the pre-mRNA al-ternative splicing in cultured cells. With the established Zis minigene, we for the first time found that Zis2 isoform regulates the alternative splicing of Zis minigene.

关键词： minigene GluR-B FGF-2R Zis Tra2β pre-mRNA splicing.

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteraction<0.001).Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs（P=0.040） and sqNSCLCs（P=0.014）,*** the POPLAR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Single-cell transcriptomics reveals cell type diversity of human prostate

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Journal of Genetics and genomics 2022年第11期49卷 1002-1015页

作者： Yang Chen Peng Zhang Jinling Liao Jiwen Cheng Qin Zhang Tianyu Li Haiying Zhang Yonghua Jiang Fangxing Zhang Yanyu Zeng Linjian Mo Haibiao Yan Deyun Liu Qinyun Zhang Chunlin Zou Gong-Hong Wei Zengnan Mo Center for genomic and Personalized medicine Guangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Key laboratory of Metabolism and Molecular medicine of the Ministry of Education&Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan University Shanghai Cancer CenterFudan UniversityShanghai 201114China Biocenter Oulu Faculty of Biochemistry and Molecular MedicineUniversity of OuluOuluFinland Key laboratory of Longevity and Ageing-Related Disease of Chinese Ministry of Education Center for Translational Medicine and School of Preclinical MedicineGuangxi Medical UniversityNanningGuangxi 530021China

Extensive studies have been performed to describe the phenotypic changes occurring during malignant transformation of the ***,the cell types and associated changes that contribute to the development of prostate diseases and cancer remain elusive,largely due to the heterogeneous composition of prostatic ***,we conduct a comprehensive evaluation of four human prostate tissues by singlecell RNA sequencing(sc RNA-seq)to analyze their cellular *** identify 18 clusters of cell types,each with distinct gene expression profiles and unique features;of these,one cluster of epithelial cells(Ep)is found to be associated with immune *** addition,we characterize a special cluster of fibroblasts and aberrant signaling changes associated with prostate cancer(PCa).Moreover,we provide insights into the epithelial changes that occur during the cellular senescence and *** results expand our understanding of the unique functional associations between the diverse prostatic cell types and the contributions of specific cell clusters to the malignant transformation of prostate tissues and PCa development.

关键词： scRNA-seq Human prostate Cell type diversity Immunity Cellular senescence Prostate cancer

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Report-21st century medical genetic and genomic medicine in China

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2005年第12期6卷 1223-1226页

作者： HUANG Taosheng QI Ming Department of Pediatrics/Genetics ＆ Metabolism Developmental ＆ Cell Biology University of California Irvine USA Center for Genetic and genomic medicine Zhejiang University Hangzhou 310003 China Department of Pathology ＆ laboratory medicine University of Rochester NY USA

The First Hangzhou International Symposium on the Medical and laboratory Applications of Medical Genetics and genomics was held in Hangzhou from October 6-8, 2005. The symposium was organized and sponsored by the First Affiliated Hospital, School of medicine, Zhejiang University and co-sponsored by the Zhejiang Medical Association; School of medicine of Zhejiang University; the James Watson Institute of genomics Sciences and Beijing genomics Institute/Huada genomics Center of the Chinese Academy of Science. Many internationally prominent geneticists were invited to the meeting, including Arno Motulsky, Peter Byers, Douglas Wallace, Judith Hall, and David Weatherall. The invited speakers presented discussions of recent advances in human and medical genetics, genomics, and in cutting-edge research.

关键词：中国医学遗传药物遗传学学术交流

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An Old Story Retold: Loss of G1 Control Defines A Distinct genomic Subtype of Esophageal Squamous Cell Carcinoma

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genomics, Proteomics & Bioinformatics 2015年第4期13卷 258-270页

作者： Qiyan Wang Jian Bai Amir Abliz Ying Liu Kenan Gong Jingjing Li Wenjie Shi Yaqi Pan Fangfang Liu Shujuan Lai Haijun Yang Changdong Lu Lixin Zhang Wei Chen Ruiping Xu Hong Cai Yang Ke Changqing Zeng MOE Key laboratory of Carcinogenesis and Translational Research Laboratory of Genetics Peking UniversityCancer Hospital & Institute Beijing University of Chinese medicine CAS Key laboratory of genomic and Precision medicine Beijing Institute of Genomics Chinese Academy of Sciences University of Chinese Academy of Sciences Anyang Cancer Hospital

Esophageal squamous cell carcinoma （ESCC） has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional sam- ples using Sanger sequencing. Whole-genomc SNP arrays were employed to detect copy number alteration （CNA） and loss of heterozygosity （LOH） in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations （NSSMs） in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology （GO） analysis. Tumor genomes with TP53 mutations were signifi- cantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B （30.9%）, amplification of 1 1q13.3 covering CCND1 （30.9%）, and TP53 point mutation （50.9%） occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p 11.2, and 3p 12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.

关键词： Esophageal squamous cell carcinoma genomic subtype somatic mutation Copy number alteration Cell cycle deregulation

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