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Unraveling brain aging through the lens of oral microbiota

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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Single-cell technologies: current and near future

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Science China Life Sciences 2025年第01期 1-4页

作者： Chenfei Wang Qi Liu Xiaohui Fan Tieliu Shi key laboratory of Spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationOrthopedics DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem cells School of Life Sciences and TechnologyTongji University Translational medical center for Stem cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University research Institute of Intelligent Computing Zhejiang Lab Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University National key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for Bioinformatics and Computational biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University key laboratory of Advanced Theory and Application in Statistics and Data Science (MOE) School of StatisticsEast China Normal University

Single-cell technologies enable the indepth exploration of multiple biological hierarchies at the scale of individual cells,which have deepened our knowledge of cellular diversity, tissue organization, and overall organism function(Sun et al.,2024). In 2009, single-cell RNA sequencing(sc RNA-seq) was first developed as a powerful tool to dissect gene expression and uncover transcriptional *** the rapid advancement of technology, single-cell approaches have expanded to encompass other omics, such as genomics, epigenomics, proteomics,and metabolomics.

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Expression of survivin mRNA in peritoneal lavage fluid from patients with gastric carcinoma

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Chinese medical Journal 2004年第8期117卷 1210-1216页

作者：王振宁徐惠绵姜莉周欣鲁翀张学 Department of SurgicalOncology No.1 Hospital of China medical University Shenyang110001ChinaResearch Center for Medical Genomics and MOH Key Laboratory of Cell BiologyChina Medical UniversityShenyang110001China Department of SurgicalOncology No.1 Hospital of China medical University Shenyang110001China research center for medical genomics and moh key laboratory of cell biology China medical University Shenyang110001China research center for medical genomics and moh key laboratory of cell biology China medical University Shenyang110001ChinaDepartment of Medical Genetics and National Key Laboratory of Medical Molecular BiologyChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijing100005China

Background Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma with serosal invasion In the present study, we reported the clinical relevance of a new diagnostic method involving RT-PCR, using survivin as the target gene, for the detection of free cancer cells in peritoneal washes Methods Intraoperative peritoneal washes were obtained from 48 patients who underwent surgery for gastric cancer RT-PCR analysis with primers specific for survivin and conventional cytological examinations were both performed Results Survivin mRNA was not detected in any peritoneal wash samples from patients with benign disease, but was detected in 28 of 48 samples taken from patients with gastric cancer and in all metastastic nodules Survivin expression in the peritoneal cavity significantly correlated with depth of cancer invasion, lymph node metastasis, and TNM stage There were 92% of clinically evident peritoneal metastasis cases showed detectable survivin expression The combination of survivin RT-PCR and cytological examination yielded positive results in 66 7% (32/48) of patients with gastric cancer, much higher than the results produced by cytological method alone KH*2/5DConclusions Survivin mRNA detected in peritoneal lavage fluid might indicate the presence of free cancer cells in the peritoneal cavity The high sensitivity of the RT-PCR-based survivin assay suggests that survivin serves as a molecular marker for detecting peritoneal micrometastasis Its ubiquitous expression in peritoneal cancer cells and metastatic nodules also suggests a promising future therapeutic strategy based on survivin inhibition for cases of gastric cancer involving peritoneal metastasis.

关键词： gastric carcinoma survivin peritoneal metastasis cytology

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A single-cell transcriptomic atlas of primate pancreatic islet aging

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National Science Review 2021年第2期8卷 17-31页

作者： Jingyi Li Yuxuan Zheng Pengze Yan Moshi Song Si Wang Liang Sun Zunpeng Liu Shuai Ma Juan Carlos Izpisua Belmonte Piu Chan Qi Zhou Weiqi Zhang Guang-Hui Liu Fuchou Tang Jing Qu State key laboratory of Membrane biology Institute of ZoologyChinese Academy of Sciences National laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of Sciences Beijing Institute for Brain Disorders Advanced Innovation Center for Human Brain ProtectionNational Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical University University of Chinese Academy of Sciences Beijing Advanced Innovation center for genomics Biomedical Pioneering Innovation CenterCollege of Life SciencesPeking University Ministry of Education key laboratory of cell Proliferation and Differentiation Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking University Institute for Stem cell and Regeneration Chinese Academy of Sciences The moh key laboratory of Geriatrics Beijing HospitalNational Center of Gerontology State key laboratory of Stem cell and Reproductive biology Institute of ZoologyChinese Academy of Sciences Gene Expression laboratory Salk Institute for Biological Studies CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences China National center for Bioinformation

Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and *** cells age heterogeneously, complicating the efforts to unravel the molecular drivers underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased transcriptional variations, aged β-cells showed increased unfolded protein response(UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling pathways, comprising adaptive UPR during pancreatic aging. Notably, we found aging-related β-cell-specific upregulation of HSP90 B1, an endoplasmic reticulum-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis,suggesting an avenue to delaying β-cell aging and preventing aging-related diabetes.

关键词： islet β-cell aging single-cell RNA sequencing primate

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Follicular hyperandrogenism and insulin resistance in polycystic ovary syndrome patients with normal circulating testosterone levels

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The Journal of Biomedical research 2018年第3期32卷 208-214页

作者： Andi Li Lu Zhang Jiajia Jiang Nan Yang Ying Liu Lingbo Cai Yugui Cui Feiyang Diao Xiao Han Jiayin Liu Yujie Sun key laboratory of Human Functional genomics of Jiangsu Province Nanjing Medical University State key laboratory of Reproductive Medicine Clinical Center of Reproductive Medicine the First Affiliated Hospital of Nanjing Medical University Department of cell biology Nanjing Medical University

Polycystic ovary syndrome（PCOS） is a common reproductive disease with high heterogeneity. The role of excess androgen in PCOS etiology remains disputed, since around 20%-50% of PCOS women do not display hyperandrogenemia. The microenvironment of the ovary critically influences follicular development. In the present study, we assessed the role of androgen in PCOS by investigating whether excessive follicular fluid androgen was present in PCOS patients with normal serum androgen levels and influenced by follicular fluid insulin resistance（IR）.Follicular fluid samples of 105 women with PCOS and 105 controls were collected. Levels of steroid hormones,glucose and insulin in the follicular fluid were examined and compared with data from serum biochemistry tests. We found that 64.9%（63/97） of PCOS patients with normal serum androgen levels displayed abnormally high follicular fluid androgen level. The follicular fluid androgen level was positively correlated with follicular fluid IR within a certain range and follicular fluid estrogen-to-testosterone（E2/T） ratio was significantly reduced in these *** results indicated that there existed a subgroup of PCOS patients who displayed excessive follicular fluid androgen and IR despite their normal circulating testosterone（T） levels. Our study highlights the importance of ovary hyperandrogenism and IR in the etiology of PCOS.

关键词： polycystic ovary syndrome hyperandrogenism insulin resistance follicular fluid

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Expression of pituitary homeobox 1 gene in human gastric carcinogenesis and its clinicopathological significance

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World Journal of Gastroenterology 2008年第2期14卷 292-297页

作者： Ya-Nan Chen Hong Chen Yan Xu Xue Zhang Yang Luo research center for medical genomics and moh key laboratory of cell biology China Medical University Shenyang 110001Liaoning Province China Department of Surgical Oncology the First Hospital of China Medical University Shenyang 110001 Liaoning ProvinceChina

AIM： To investigate the effect of pituitary homeobox 1 （PITX1） expression in cases of human gastric cancer on cancer differentiation and progression, and carcinogenesis. METHODS： Using polyclonal PITX1 antibodies, we studied the expression of PITX1 in normal gastric mucosa, atypical hyperplasia, intestinal metaplasia, and cancer tissue samples from 83 gastric cancer patients by immunohistochemistry. Moreover, semi-reverse transcription polymerase chain reaction （semi-RT-PCR） was performed to detect the mRNA level of PITX1 in three gastric cancer cell lines and a normal gastric epithelial cell line. Subsequently, somatic mutations of the PITX1 gene in 71 gastric cancer patients were analyzed by a combination of denaturing high performance liquid chromatography （DHPLC） and DNA sequencing. RESULTS： Immunohistochemistry showed that PITXl was strongly or moderately expressed in the parietal cells of normal gastric mucosa （100%）, while 55 （66.3%） out of 83 samples of gastric cancers showed decreased PITXl expression. Moreover, PITXl expression was reduced in 20 out of 28 cases （71.5%） of intestinal metaplasia, but in only 1 out of 9 cases （11%） of atypical hyperplasia. More importantly, PITXl expression was significantly associated with the differentiation, position and invasion depth of gastric cancers （r = -0.316, P 〈 0.01; r = 0.213, P 〈 0.05; r = -0.259, P 〈 0.05, respectively）. Similarly, levels of PITXl mRNA were significantly decreased in 2 gastric cancer cell lines, BGC-823 and SGC-7901, compared with the normal gastric epithelial cell line GES-1 （0.306 ± 0.060 vs 0.722 ± 0.102, P 〈 0.05; 0.356 ± 0.081 vs 0.722 ± 0.102, P 〈 0.05, respectively）. Nevertheless, no somatic mutation of PITX1 gene was found in 71 samples of gastric cancer by DHPLC analysis followed by sequencing. CONCLUSION： Down-regulation of PITX1 may be a frequent molecular event in gastric carcinogenesis. Aberrant levels of PITXl expression may be closely correlated with the progression and diff

关键词： Pituitary homeobox 1 Gastric cancer Immunohistochemistry Reverse transcription polymerase chain reaction Denaturing high performance liquid chromatography

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Cold-chain food contamination as the possible origin of COVID-19 resurgence in Beijing

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National Science Review 2020年第12期7卷 1861-1864页

作者： Xinghuo Pang Lili Ren Shuangsheng Wu Wentai Ma Jian Yang Lin Di Jie Li Yan Xiao Lu Kang Shichang Du Jing Du Jing Wang Gang Li Shuguang Zhai Lijuan Chen Wenxiong Zhou Shengjie Lai Lei Gao Yang Pan Quanyi Wang Mingkun Li Jianbin Wang Yanyi Huang Jianwei Wang COVID-19 Field Response Group COVID-19 laboratory Testing Group Beijing center for Disease Prevention and Control(CDC) research Centre for Preventive Medicine of Beijing NHC key laboratory of Systems biology of Pathogens and Christophe Mérieux laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences and Peking Union Medical College Beijing Institute of genomics Chinese Academy of Sciencesand China National Center for Bioinformation University of Chinese Academy of Sciences NHC key laboratory of Systems biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Beijing Advanced Innovation center for genomics (ICG) Biomedical Pioneering Innovation Center (BIOPIC)College of Chemistryand Peking-Tsinghua Center for Life SciencesPeking University School of Life Sciences Tsinghua-Peking Center for Life SciencesTsinghua University World Pop School of Geography and Environmental ScienceUniversity of Southampton center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Beijing Advanced Innovation center for Structural biology(ICSB) Tsinghua University Chinese Institute for Brain research(CIBR) Institute for cell Analysis Shenzhen Bay Laboratory

COVID-19,caused by SARS-CoV-2[1,2],has been contained in China through stringent non-pharmaceutical *** control and quarantine have effectively prevented the virus from being spread by infected travellers,but the risk...

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Chemical reprogramming:the CiPSCs and the CiNs

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National Science Review 2017年第1期4卷 7-10页

作者： Xiang Li Yang Yang Zhen Yang Hongkui Deng The MOE key laboratory of cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking University Department of cell biology School of Basic Medical SciencesPeking University Stem Cell Research CenterCenter for Molecular and Translational MedicineState Key Laboratory of Natural and Biomimetic DrugsPeking University Health Science Center Shenzhen Stem cell Engineering laboratory Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate School laboratory of Chemical genomics School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate School key laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education and Beijing National Laboratory for Molecular Science(BNLMS)Peking-Tsinghua Center for Life SciencesPeking University key laboratory of Marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of China

TRANSGENIC APPROACH TO INDUCE cell FATE REPROGRAMMING To generate desirable cells and to restore biological function,manipulating somatic cell fates is one of fundamental scientiic goals in regenerative *** study of Myod-converted myoblasts in 1987 demonstrated the concept to convert cell fates by introducing a single transcription factor[1].he development of induced pluripotent stem cells(i PSCs)demonstrated the feasibility of using a combination of

关键词： PSCs Chemical reprogramming:the CiPSCs and the CiNs cell

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Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation

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Protein & cell 2019年第1期10卷 20-30页

作者： Haibo Li Chaoran Zhao Jun Xu Yaxing Xu Chunmei Cheng Yinan Liu Ting Wang Yaqin Du Liangfu Xie Jingru Zhao Yanchuang Han Xiaobao Wang Yun Bai Hongkui Deng Department of cell biology School of Basic Medical SciencesPeking University Stem Cell Research CenterState Key Laboratory of Natural and Biomimetic DrugsPeking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and DifferentiationCollege of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100191China Shenzhen Stem cell Engineering laboratory Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhen 518055China Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program College of Life SciencesPeking UniversityBeijing 100871China BeiHao Stem cell and Regenerative Medicine Translational research Institute BeijingChina

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem(ES)cells,which is used to produce gene-targeted mice for wide applications in ***,a major bottleneck in this approach is that the robustness of germiine transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing,which impairs the efficiency and robustness of mouse model ***,we have established a new type of pluripotent cells termed extended pluripotent stem(EPS)cells,which have superior developmental potency and robust germline competence compared to conventional mouse ES *** this study,we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term *** on gene targeting in mouse EPS cells,we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation,Haibo Li and Chaoran Zhao contributed equally to this *** supplementary material The online version of this article(https://***/10.1007/s13238-018-0556-1)contains supplementary material,which is available to authorized *** could be accomplished in approximately 2 ***,using this approach,we successfully constructed mouse models in which the human interleukin 3(IL3)or interleukin 6(IL6)gene was knocked into its corresponding locus in the mouse *** study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting,which have great application potential in biomedical research.

关键词： tetraploid complementation EPS mouse model CRISPR/Cas9

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Innate immunity in tuberculosis: host defense vs pathogen evasion

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cellular & Molecular Immunology 2017年第12期14卷 963-975页

作者： Cui Hua Liu Haiying Liu Baoxue Ge CAS key laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid medical School University of Chinese Academy of SciencesBeijing 101408China moh key laboratory of Systems biology of Pathogens Institute of Pathogen Biologyand Center for Tuberculosis ResearchChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100176China Shanghai key Lab of Tuberculosis Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China

The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)*** immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis(Mtb)through various pattern recognition receptors(PRRs),including but not limited to Toll-like receptors(TLRs),Nod-like receptors(NLRs)and C-type lectin receptors(CLRs).Upon infection by Mtb,the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis,autophagy,apoptosis and inflammasome *** contrast,Mtb utilizes numerous exquisite strategies to evade or circumvent host innate *** we discuss recent research on major host innate immune cells,PRR signaling,and the cellular functions involved in Mtb infection,with a specific focus on the host’s innate immune defense and Mtb immune evasion.A better understanding of the molecular mechanisms underlying host–pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.

关键词： host–pathogen interactions immune evasion innate immune defense Mycobacterium tuberculosis tuberculosis

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