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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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Metformin inhibits food intake and neuropeptide Y gene expression in the hypothalamus

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Neural Regeneration Research 2013年第25期8卷 2379-2388页

作者： Yale Duan Rui Zhang Min Zhang Lijuan Sun Suzhen Dong Gang Wang Jun Zhang Zheng Zhao Key laboratory of Brain Functional genomics Ministry of EducationShanghai Key Laboratory of Brain Functional GenomicsEast China Normal University Department of clinical laboratory Shanghai Public Health Clinical Center Affiliated to Fudan University

Metformin may reduce food intake and body weight, but the anorexigenic effects of metformin are still poorly understood. In this study, Sprague-Dawley rats were administered a single intracere- broventricular dose of metformin and compound C, in a broader attempt to investigate the regula- tory effects of metformin on food intake and to explore the possible mechanism. Results showed that central administration of metformin significantly reduced food intake and body weight gain, par- ticularly after 4 hours. A reduction of neuropeptide Y expression and induction of AMP-activated protein kinase phosphorylation in the hypothalamus were also observed 4 hours after metformin administration, which could be reversed by compound C, a commonly-used antagonist of AMP-activated protein kinase. Furthermore, metformin also improved lipid metabolism by reducing plasma low-density lipoprotein. Our findings suggest that under normal physiological conditions, central regulation of appetite by metformin is related to a decrease in neuropeptide Y gene expres- sion, and that the activation of AMP-activated protein kinase may simply be a response to the anorexigenic effect of metformin.

关键词： neural regeneration metformin food intake body weight gain hypothalamus AMP-activated pro-tein kinase neuropeptide Y grants-supported paper neuroregeneration

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Antiapoptotic activity of 30 kDa lipoproteins family from fat body tissue of silkworm, Bombyx moil

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Insect Science 2015年第5期22卷 629-638页

作者： Britto Cathrin Pakkianathan Nitin Kumar Singh Simone Konig Muthukalingan Krishnan Department of Environmental Biotechnology Bharathidasan University Tiruchirappalli India and Integrated Functional genomics Interdisciplinary Center for Clinical Research University of MEmster Germany

The family of 30kDa lipoproteins （LP1-5） is abundant in silkworm pupa fat body （FB） and hemolymph. One of its members, the 29 kDa protein decreased in concentration from peripheral （PP） FB tissue but was sustained in perivisceral （PV） FB tissue at the time of apoptosis. This study investigated the correlation of the 30kDa proteins with FB apoptosis. Two protein fractions were purified, a 29 and a 30/31 kDa protein fraction, and they were used to test for activity against actinomycin D-induced apoptosis in the FB tissues. Concentrations as little as 50/zg/mL of the 29 kDa protein fraction efficiently inhibited apoptosis. Less antiapoptotie activity was detected for the higher MW fraction; DNA fragmentation was observed in FB tissue treated with 50 #g/mL of the 30/31 kDa fraction. The viability of the cells in the 29 kDa protein-supplemented culture was 40% higher than in the 31 kDa protein-supplemented culture. However, the 30 kDa lipoproteins were not able to prevent scheduled FB degeneration during silkworm metamorphosis. Thus, it is hypothesized that the antiapoptotic 29 kDa protein needs to be proteolytically degraded by a regulatory mechanism to allow programmed cell death of FB tissue.

关键词： actinomycin D apoptosis Bombyx mori fat body tissue 30 kDa proteins

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Ratiometric fluorescence immunoassay of SARS-CoV-2 nucleocapsid protein via Si-FITC nanoprobe-based inner filter effect

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Nano Research 2023年第4期16卷 5383-5390页

作者： Guobin Mao Yang Yang Shijie Cao Silu Ye Yifang Li Wei Zhao Hongwei An Yingxia Liu Junbiao Dai Yingxin Ma CAS Key laboratory of Quantitative Engineering Biology Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic GenomicsShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangxi University of Chinese Medicine Nanning 530001China Shenzhen Key laboratory of Pathogen and Immunity National Clinical Research Center for infectious diseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China

The global pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus has necessitated rapid,easy-to-use,and accurate diagnostic methods to monitor the virus ***,a ratiometric fluorescence enzyme-linked immunosorbent assay(ELISA)was developed using Si-fluorescein isothiocyanate nanoparticles(FITC NPs)for detecting SARSCoV-2 nucleocapsid(N)***-FITC NPs were prepared by a one-pot hydrothermal method using 3-aminopropyl triethoxysilane(APTES)-FITC as the Si *** method did not need post-modification and avoided the reduction in quantum yield and *** p-nitrophenyl(pNP)produced by the alkaline phosphatase(ALP)-mediated hydrolysis of pnitrophenyl phosphate(pNPP)could quench Si fluorescence in Si-FITC NPs via the inner filter *** ELISA,an immunocomplex was formed by the recognition of capture antibody/N protein/reporter ***-linked secondary antibody bound to the reporter antibody and induced pNPP hydrolysis to specifically quench Si fluorescence in Si-FITC *** change in fluorescence intensity ratio could be used for detecting N protein,with a wide linearity range(0.01-10.0 and 50-300 ng/mL)and low detection limit(0.002 ng/mL).The concentration of spiked SARS-CoV-2 N protein could be determined accurately in human ***,this proposed method can accurately distinguish coronavirus disease 2019(COVID-19)and non-COVID-19 patient ***,this simple,sensitive,and accurate method can be applied for the early diagnosis of SARS-CoV-2 virus infection.

关键词： Si-fluorescein isothiocyanate(FITC)nanoparticles ratiometric fluorescent probe severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) inner filter effect enzyme-linked immunosorbent assay(ELISA)

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Maternally inherited H4K16 acetylation primes zygotic gene activation in Drosophila

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Science China(Life Sciences) 2020年第12期63卷 1950-1952页

作者： Lei Qiu Xueqin Liu Junhong Han Research laboratory of Tumor Epigenetics and genomics Department of General SurgeryFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer Centerand National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China Department of clinical Research Management West China HospitalSichuan UniversityChengdu 610041China

In a recent study published in Cell, Samata et al. demonstrated a novel mechanism that guided the genomic reprogramming. They showed that the acetylation of histone H4 at Lysine 16(H4K16ac) was intergenerationally maintained from the mother’s oocyte to the young embryo and primed zygotic gene activation in Drosophila(Samata et al., 2020).Embryonic development is initially directed by maternal gene products. Then gradually, developmental control is handed to the zygotic genome during the maternal-to-zygotic transition(MZT).

关键词： activation maintained initially

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Identification of genomic features associated with immunotherapy response in gastrointestinal cancers

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World Journal of Gastrointestinal Oncology 2019年第4期11卷 270-280页

作者： Yin He Zhi-Xian Liu Ze-Hang Jiang Xiao-Sheng Wang Biomedical Informatics Research Lab School of Basic Medicine and Clinical Pharmacy Cancer genomics Research Center School of Basic Medicine and Clinical Pharmacy Big Data Research Institute China Pharmaceutical University

Gastrointestinal(GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency(dMMR) or microsatellite instability(MSI). Thus,immunotherapy could be a promising treatment approach for GI ***, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden(TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.

关键词： Gastrointestinal cancer Tumor immunity Tumor immunotherapy DNA mismatch repair Tumor mutation burden Tumor aneuploidy

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Transcriptomics and proteomics in stem cell research

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Frontiers of Medicine 2014年第4期8卷 433-444页

作者： Hai Wang Qian Zhang Xiangdong Fang CAS Key laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences Beij'ing 100101China

Stem cells are capable of self-renewal and differentiation, and the processes regulating these events are among the most comprehensively investigated topics in life sciences. In particular, the molecular mechanisms of the self-renewal, proliferation, and differentiation of stem cells have been extensively examined. Multi-omics integrative analysis, such as transcriptomics combined with proteomics, is one of the most promising approaches to the systemic investigation of stem cell biology. We reviewed the available information on stem cells by examining published results using transcriptomic and proteomic characterization of the different stem cell processes. Comprehensive understanding of these important processes can only be achieved using a systemic methodology, and employing such method will strengthen the study on stem cell biology and promote the clinical applications of stem cells.

关键词： embryonic stem cells transcriptomics proteomics

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Interplay between diet and genetic susceptibility in obesity and related traits

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Frontiers of Medicine 2018年第6期12卷 601-607页

作者： Tiange Wang Min Xu Yufang Bi Guang Ning State Key laboratory of Medical genomics Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of HealthNational Clinical Research Center for Metabolic DiseasesShanghai Institute of Endocrine and Metabolic DiseasesDepartment of Endocrine and Metabolic DiseasesRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.

关键词： diet genetic susceptibility interaction obesity

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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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Mucosal-associated invariant T cells and oral microbiome in persistent apical periodontitis

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International Journal of Oral Science 2019年第2期11卷 131-142页

作者： Haleh Davanian Rogier Aaron Gaiser Mikael Silfverberg Luisa W. Hugerth Michal J. Sobkowiak Liyan Lu Katie Healy Johan K. Sandberg Peggy Nasman Jorgen Karlsson Leif Jansson Lars Engstrand Margaret Sallberg Chen Department of Dental Medicine Karolinska InstitutetHuddingeSweden Department of Microbiology Tumor and Cell Biology and Science for Life LaboratoryKarolinska InstitutetStockholmSweden clinical genomics Facility Science for Life LaboratorySolnaSweden Department of Medicine Karolinska InstitutetHuddingeSweden Clinic of Endodontics and Periodontology Eastman Institute StockholmStockholmSweden

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic ***-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal *** was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is ***,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell ***,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ *** gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial *** merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue *** conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take *** findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.

关键词： apical periodontitis(AP) Mucosal-associated invariant T(MAIT) AP

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