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Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural Regeneration Research 2025年第6期20卷 1709-1710页

作者： Martin-Paul Agbaga Mohiuddin Ahmad Department of cell Biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-center for Neuroscience and cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu Stem cell Clinical Research center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of Stem cell and Precision Medicine DalianLiaoning ProvinceChina Institute(College)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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

CCL5 as a potential immunotherapeutic target in triple-negative breast cancer

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cellular & Molecular immunology 2013年第4期10卷 303-310页

作者： Dandan Lv Yan Zhang Ha-Jeong Kim Lixing Zhang Xiaojing Ma Sheng Yushou center of cell Biology and immunology School of Life Science and Biotechnology Shanghai Jiaotong University Shanghai China Department of Microbiology and immunology Weill Cornell Medical College New York NY USA

Breast cancer （BC） is a leading cause of mortality among women in the world. To date, a number of molecules have been established as disease status indicators and therapeutic targets. The best known among them are estrogen receptor-α （ER-α）, progesterone receptor （PR） and H ER-2/neu. About 15%-20% BC patients do not respond effectively to thera pies targeting these classes of tumor-promoting factors. Thus, additional targets are strongly and urgently sought after in therapy for human BCs negative for ER, PR and HER-2, the so-called triple-negative BC （TNBC）. Recent clinical work has revealed that CC chemokine ligand 5 （CCL5） is strongly associated with the progression of BC, particularly TNBC. How CCL5 contributes to the development of TN BC is not well understood. Experimental animal studies have begun to address the mechanistic issue. In this article, we will review the clinical and laboratory work in this area that has led to our own hypothesis that targeting CCL5 in TNBCs will have favorable therapeutic outcomes with minimal adverse impact on the general physiology.

关键词： triple negative breast cancer CCL5 myeloid derived suppressor cell immunotherapy

Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic 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 Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine 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 Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Pediatric Allergy-immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye center for Stem cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of Child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye center for Regenerative Medicine and Stem cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye center for Stem cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation Stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation