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FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年

作者： Rongmei Gao Kanchao Chen Yimin Wang Rongxia Guo Xiaoyu Zhang Peng Wu Weili Wang Qingxiang Huang Xuemei Xie Shangda Yang Yanling Lü Qian Ren Fei Liu Song Chen Fengxia Ma Tao Cheng Hui Cheng State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College CAMS Center for stem cell Medicine PUMC Department of Stem Cell and Regenerative Medicine

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C. albicans) infection model, we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates. Impaired myeloid hematopoiesis and immune cell production were evident, as proved by the decreased numbers of hematopoietic stem and progenitor cells (HSPCs) and granulocytes in the bone marrow of Fhl2-deficient mice. In conclusion, FHL2 regulated emergency myelopoiesis in response to C. albicans, affecting the host’s defense against pathogens.

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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)

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda Department of stem cell Biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and stem cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

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

Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells

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Science China Life Sciences 2025年

作者： Shi Chen Yuanyuan He Lejun Lv Bei Liu Cheng Li Hongkui Deng Jun Xu Department of cell Biology School of Basic Medical Sciences Peking University Stem Cell Research Center Peking University Health Science Center Peking University Academy of Advanced Interdisciplinary Studies Peking University Beicell Therapeutics School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University MOE Engineering research Center of Regenerative Medicine School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Human primed pluripotent stem cells are capable of generating all the embryonic ***,their extraembryonic trophectoderm potentials are *** remains unclear how to expand their developmental potential to trophectoderm *** we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic *** chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast *** and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent *** exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage *** findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering research Center of stem cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain research BeijingChina research unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)