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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei haihe laboratory of cell ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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TNFSF15 facilitates the differentiation of CD11b^(+) myeloid cells into vascular pericytes in tumors

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Cancer Biology & Medicine 2023年第11期20卷 869-884页

作者： Xiangxiang Gu Yipan Zhu Cancan Zhao Yixin Cao Jingying Wang Qiangzhe Zhang Luyuan Li State Key laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai Universityand Haihe Laboratory of Cell EcosystemTianjin 300350China

Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell *** previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular *** main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into ***:A model of Lewis lung cancer was established in mice with red fluorescent bone *** TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were ***,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these ***:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial ***15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling ***:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.

关键词： TNFSF15 myeloid cell neovascularization CD11b^(+)cell pericyte

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Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

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Journal of Molecular cell Biology 2024年第1期16卷 15-28页

作者： Te Li Min Liu Fan Yu Song Yang Weiwen Bu Kai Liu Jia Yang Hua Ni Mulin Yang Hanxiao Yin Renjie Hong Dengwen Li Huĳie Zhao Jun Zhou haihe laboratory of cell ecosystem State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China laboratory of Tissue Homeostasis Haihe Laboratory of Cell EcosystemTianjin 300462China Center for cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongShandong Provincial Key Laboratory of Animal Resistance BiologyCollege of Life SciencesShandong Normal UniversityJinan 250014China

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan ***,the mechanistic link of cilia to CMD complications is still poorly ***,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar ***,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl *** studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium *** vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm *** findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

关键词： carbohydrate metabolism disorder aldose aldehyde cilium disassembly formyl group calcium influx HDAC6

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CCDC181 is required for proper spermiogenesis in mice

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Journal of Genetics and Genomics 2024年第11期51卷 1327-1330页

作者： Xirui Zi Qingchao Li Yue Lu Qian Lyu Heng Guo Xiaoqian Meng Jun Zhou Huijie Zhao Center for cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance BiologyCollaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinanShandong 250014China State Key laboratory of Medicinal Chemical Biology Haihe Laboratory of Cell EcosystemCollege of Life SciencesNankai UniversityTianjin 300071China

Cilia are hair-like cellular projections essential for development and homeostasis,which can be grouped into either immotile or motile cilia based on their *** vertebrates,motile cilia that line the brain ventricles,respiratory tracts,and reproductive tracts exist as multiple cilia and beat in a coordinated fashion to generate a directional fluid flow across the epithelial surfaces(Lyu et al.,2024).In contrast,sperm cells have a single flagellum that shares a similar axoneme arrangement but possesses unique accessory structures,including the mitochondrial sheath,the fibrous sheath,and the outer dense fibers(Linck et al.,2016).Some ciliary proteins display distinct cellular distributions in multiple motile cilia and sperm *** instance,outer dense fiber protein 2(ODF2)associates with basal bodies in tracheal motile cilia but is abundant in sperm flagella(Zhao et al.,2021;Zhu et al.,2022).These differences potentially grant sperm flagella distinctive properties.

关键词： outer arrangement fibers

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O-GlcNAcylation regulates phagocytosis by promoting Ezrin localization at the cell cortex

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Journal of Genetics and Genomics 2023年第7期50卷 486-496页

作者： Song Yang Hanyu Liu Hua Ni Lingyu Jiang Mulin Yang Quan Chen Jun Zhou Fan Yu State Key laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell ResponsesTianjin Key Laboratory of Protein ScienceHaihe Laboratory of Cell EcosystemCollege of Life SciencesNankai UniversityTianjin 300071China CNBG-Nankai Joint Research Center Nankai UniversityTianjin 300071China College of Life and Geographic Sciences Kashi UniversityXinjiang 844000China

O-GlcNAcylation is a post-translational modification that serves as a cellular nutrient sensor and participates in multiple physiological and pathological ***,it remains uncertain whether O-GlcNAcylation is involved in the regulation of ***,we demonstrate a rapid increase in protein OGlcNAcylation in response to phagocytotic *** of the O-GlcNAc transferase or pharmacological inhibition of O-GlcNAcylation dramatically blocks phagocytosis,resulting in the disruption of retinal structure and *** studies reveal that the O-GlcNAc transferase interacts with Ezrin,a membrane-cytoskeleton linker protein,to catalyze its *** data further show that Ezrin OGlcNAcylation promotes its localization to the cell cortex,thereby stimulating the membrane-cytoskeleton interaction needed for efficient *** findings identify a previously unrecognized role for protein O-GlcNAcylation in phagocytosis with important implications in both health and diseases.

关键词： O-GlcNAcylation Phagocytosis Retinal pigment epithelium Ezrin Cytoskeleton

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Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

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Neural Regeneration Research 2025年第10期20卷 2807-2822页

作者： Xizi Song Ruixin Li Xiaolei Chu Qi Li Ruihua Li Qingwen Li Kai-Yu Tong Xiaosong Gu Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina haihe laboratory of Brain-Machine Interface and Human-Machine Fusion TianjinChina Department of Rehabilitation Tianjin University Tianjin HospitalTianjinChina Department of Hand Microsurgery Tianjin University Tianjin HospitalTianjinChina School of Exercise and Health Tianjin University of SportTianjinChina Department of Biomedical Engineering the Chinese University of Hong KongHong Kong Special Administrative RegionChina

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and *** on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target *** has led to restrictions on current therapeutic *** this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target *** peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal *** nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury *** damage to target organs can occur,including skeletal muscle atrophy and sensory receptor *** then provide a brief review of the research advances in therapeutic approaches to peripheral nerve *** main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical ***,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ ***,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

关键词： central nervous system central peripheral target organ multilevel pathological analysis nerve regeneration peripheral nerve injury peripheral nervous system target organs therapeutic approach

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Peripheral and central control of obesity by primary cilia

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Journal of Genetics and Genomics 2023年第5期50卷 295-304页

作者： Yue Wu Jun Zhou Yunfan Yang Center for cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance BiologyCollaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinanShandong 250014China State Key laboratory of Medicinal Chemical Biology Haihe Laboratory of Cell EcosystemCollege of Life SciencesNankai UniversityTianjin 300071China Department of cell Biology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong 250012China

Primary cilia are hair-like structures that protrude from the cell *** are capable of sensing external cues and conveying a vast array of signals into cells to regulate a variety of physiological *** in cilium-associated genes are linked to a group of diseases with overlapping clinical manifestations,collectively known as ciliopathies.A significant proportion of human ciliopathy cases are accompanied by metabolic disorders such as obesity and type 2 ***,the mechanisms through which dysfunction of primary cilia contributes to obesity are *** this review,we present an overview of primary cilia and highlight obesity-related *** also discuss the potential role of primary cilia in peripheral organs,with a focus on adipose *** addition,we emphasize the significance of primary cilia in the central regulation of obesity,especially the involvement of ciliary signaling in the hypothalamic control of feeding *** review therefore proposes a framework of both peripheral and central regulation of obesity by primary cilia,which may benefit further exploration of the ciliary role in metabolic regulation.

关键词： Ciliopathy Metabolism Adipose tissue Adipogenesis Hypothalamus

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Skull and vertebral bone marrow in central nervous system inflammation

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Fundamental Research 2024年第2期4卷 246-250页

作者： Honglei Ren Qiang Liu Department of Neurology Tianjin Neurological InstituteTianjin Institute of ImmunologyState Key Laboratory of Experimental HematologyInternational Joint Laboratory of Ocular DiseasesMinistry of EducationHaihe Laboratory of Cell EcosystemTianjin Medical University General HospitalTianjin 300052China

Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system(CNS).CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory ***,we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS ***,we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.

关键词： Central nervous system Bone marrow Hematopoiesis Immune cells Neuroinflammation Stroke Multiple sclerosis

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Towards a blood ecosystem approach to dissect systemic diseases

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Science China(Life Sciences) 2024年第7期67卷 1528-1531页

作者： Hong Wang Tao Cheng State Key laboratory of Experimental Hematology Haihe Laboratory of Cell EcosystemNational Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China

Systemic diseases,in contrast to localized ailments,exert widespread effects and can impact the entire *** of systemic diseases encompass autoimmune disorders,infectious diseases,metabolic disorders,and chronic conditions like *** diseases often entail intricate interactions among diverse organs,tissues,and physiological systems,influenced by a myriad of factors.

关键词： diseases organs autoimmune

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Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing

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Genomics, Proteomics & Bioinformatics 2023年第6期21卷 1206-1220页

作者： Zhi-Xue Yang Ya-Wen Fu Juan-Juan Zhao Feng Zhang Si-Ang Li Mei Zhao Wei Wen Lei Zhang Tao Cheng Jian-Ping Zhang Xiao-Bing Zhang State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Center for Stem cell Medicine Chinese Academy of Medical SciencesTianjin 300020China Department of Stem cell&Regenerative Medicine Peking Union Medical CollegeTianjin 300020China

A series of clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPR associated protein 9(Cas9)systems have been engineered for genome *** most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus ***,a comparison of their detailed gene editing outcomes is still *** characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells(iPSCs)and K562 cells,we found that SaCas9 could edit the genome with greater efficiencies than *** also compared the effects of spacer lengths of single-guide RNAs(sgRNAs;18–21 nt for SpCas9 and 19–23 nt for SaCas9)and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9,***,the optimal spacer length for a particular sgRNA was 18–21 nt for SpCas9 and 21–22 nt for ***,SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end-joining(NHEJ)+1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif(PAM),indicating a characteristic of a staggered ***,editing with SaCas9 led to higher efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide(dsODN)insertion or homology-directed repair(HDR)-mediated adeno-associated virus serotype 6(AAV6)donor ***,GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with *** work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.

关键词： SpCas9 SaCas9 Spacer length Indel pattern Knock-in efficiency Off-target

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