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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key laboratory of New Drug Development and clinical Trial of Stem cell therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Continuous R-DA-EDOCH alternated with high-dose Ara-C induces deep remission and overcomes high-risk factors in young patients with newly diagnosed mantle cell lymphoma

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Cancer Biology & Medicine 2025年第02期22卷 177-189页

作者： Yi Wang Yuting Yan Dandan Shan Jiawen Chen Wei Liu Tingyu Wang Gang An Weiwei Sui Wenyang Huang Wenjie Xiong Huimin Liu Qi Sun Huijun Wang Zhijian Xiao Jianxiang Wang Lugui Qiu Dehui Zou Shuhua Yi 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 Tianjin Institutes of Health Science

Objective: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma(MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate(CRR) at the end of induction(EOI).Methods: A total of 55 patients were enrolled. The CRR at the EOI was 89.1% [95% confidence interval(CI) 78%±96%], and the overall response rate was 98.1%(95% CI 90%±100%). Most patients with bone marrow involvement quickly attained minimal residual disease(MRD) negative status, with a 95.7% rate at the ***: The 3-year progression-free survival(PFS) and overall survival rates were 66.3% and 83.2%, respectively. No patients discontinued treatment because of adverse events. Univariate analysis identified pathologic morphology and TP53 mutations as risk factors for PFS. However, high tumor proliferative activity and certain cytogenetic abnormalities showed no significant adverse prognostic ***: Intensive therapy based on a high cytarabine dose and continuously administered EDOCH achieved a high MRDnegative rate and provides an optional induction choice for young patients with MCL with high-risk factors.

关键词： Mantle cell lymphoma adverse events high-risk factors immunochemotherapy minimal residual disease

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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)

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Efficient generation of all ESC-derived mice carrying a homozygous lethal mutation through eight-cell embryo injection

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Science China Life Sciences 2025年

作者： Xidi Yin Meng Yan Yanbo Cheng Zhoujie Li Chong Cui Yingyi Wang Nan Liu Yilai Shu Jinsong Li Qing Li Key laboratory of Multi-cell Systems Shanghai Key Laboratory of Molecular Andrology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences School of Life Science and Technology ShanghaiTech University Animal Core Facility Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University Key laboratory of Systems and Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences

Dear Editor,Large-scale phenotyping efforts have shown that placental defects correlate strongly with embryonic lethal mouse mutants(Perez-Garcia et al., 2018). To rescue normal development of these mutant embryos, tetraploid complementation can be a reliable strategy, in which,tetraploid cells form extraembryonic lineages thus providing the embryo with a wild-type placenta(Nagy et al., 1990).

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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)Wuhu 241000China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration(Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200082China Frontier Science Center for Stem cells School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Translational Medical Center for Stem cell therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200082China Research Institute of Intelligent Computing Zhejiang LabHangzhou 311121China Shanghai Research Institute for Intelligent Autonomous Systems Shanghai 201210China Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of MedicineShanghai 200025China National Key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Zhejiang Key laboratory of Precision Diagnosis and therapy for Major Gynecological Diseases Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Key laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal U

cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular *** 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 *** the inception of the first single-cell RNA technology,technologies related to single-cell sequencing have experienced rapid advancements in recent *** 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 scRNA-seq and CRISPR ***-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases,including ***,we comprehensively summarize recent advances in single-cell omics technologies,with a specific focus on the methodology *** 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

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FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年第03期 722-733页

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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The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia

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Journal of Animal Science and Biotechnology 2025年第1期16卷 121-135页

作者： Hao Wu Yingxue Han Jikang Liu Rong Zhao Shizhen Dai Yajun Guo Nan Li Feng Yang Shenming Zeng National Engineering laboratory for Animal Breeding Key Laboratory of Animal Genetics and Breeding of the Ministry of AgricultureCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Department of clinical Sciences College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China College of Animal Science and Technology Henan Agricultural UniversityZhengzhou 450046China

Background Follicular atresia significantly impairs female fertility and hastens reproductive *** of granulosa cells is the primary cause of follicular *** and necroptosis,as additional forms of pro-grammed cell death,have been reported in mammalian ***,the understanding of pyroptosis and necrop-tosis pathways in granulosa cells during follicular atresia remains *** study explored the effects of pro-grammed cell death in granulosa cells on follicular atresia and the underlying *** The results revealed that granulosa cells undergo programmed cell death including apoptosis,pyroptosis,and necroptosis during follicular *** the first time,we identified the formation of a PANoptosome com-plex in porcine granulosa *** complex was initially identified as being composed of ZBP1,RIPK3,and RIPK1,and is recruited through the RHIM ***,we demonstrated that caspase-6 is activated and cleaved,interacting with RIPK3 as a component of the *** stress may exacerbate the activation of the PANop-tosome,leading to programmed cell death in granulosa *** Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular *** findings provide new insights into the molecular mechanisms underlying follicular atresia.

关键词： Follicular atresia Granulosa cells PANoptosome Programmed cell death

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Plasma circulating cell–free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy:a cross-sectional study

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Neural Regeneration Research 2025年第12期20卷 3553-3563页

作者： Chao Ying Chao Han Yuan Li Mingkai Zhang Shuying Xiao Lifang Zhao Hui Zhang Qian Yu Jing An Wei Mao Yanning Cai Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Municipal Geriatric Medical Research Center BeijingChina Key laboratory for Neurodegenerative Diseases of the Ministry of Education Beijing Key Laboratory of Parkinson’s DiseaseParkinson’s Disease Center for Beijing Institute on Brain DisordersClinical and Research Center for Parkinson’s DiseaseCapital Medical UniversityBeijingChina National clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of clinical Biobank and Central laboratory Xuanwu HospitalCapital Medical UniversityBeijingChina School of Health Professions Stony Brook UniversityStony BrookNYUSA

In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing *** Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative *** addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific *** premise formed the basis for investigating cell–free DNA as a potential *** DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully *** study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system *** our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early *** diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education *** results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(Pcell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operatin

关键词： biomarkers cell-free DNA diagnosis multiple system atrophy neurodegenerative diseases Parkinson’s disease risk factors

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Fibrotic liver extracellular matrix induces cancerous phenotype in biomimetic micro-tissues of hepatocellular carcinoma model

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Hepatobiliary & Pancreatic Diseases International 2025年第1期24卷 92-103页

作者： Kosar Nouri Abbas Piryaei Homeyra Seydi Ibrahim Zarkesh Ibrahim Ghoytasi Bahare Shokouhian Mustapha Najimi Massoud Vosough Department of Developmental Biology University of Science and CultureACECR 14155-4364 TehranIran Department of Regenerative Medicine Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Stem cells and Developmental Biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Biology and Anatomical Sciences School of MedicineShahid Beheshti University of Medical SciencesTehranIran Department of Tissue Engineering and Applied cell Sciences School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran Department of cell Engineering Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR 14155-4364 TehranIran Department of Medical Biotechnology School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran laboratory of Pediatric Hepatology and cell therapy Institute of Experimental and Clinical Research(IREC)UCLouvainBrusselsBelgium Experimental Cancer Medicine Institution for Laboratory MedicineKarolinska InstituteStockholmSweden

Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a

关键词： Liver fibrosis Decellularized extracellular matrix Spheroid Epithelial-to-mesenchymal transition cell differentiation Hepatocellular carcinoma

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