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Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

World Journal of Stem Cells 2024年第4期16卷 410-433页

作者： Shafiqa Naeem Rajput Bushra Kiran Naeem Anwar Ali Asmat Salim Irfan Khan Dr.Panjwani Center for Molecular medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Surgical Unit 4 Dr.Ruth KM Pfau Civil HospitalKarachi 74400Pakistan Department of physiology University of KarachiKarachi 75270Pakistan Center for Regenerative medicine and Stem Cells Research and Department of Ophthalmology and Visual SciencesThe Aga Khan UniversityKarachi 74800SindhPakistan

BACKGROUND Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple *** humans,their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or *** suggested that mesenchymal stem cells(MSCs),necessary for repair and regeneration via transplantation,require doses ranging from 10 to 400 million ***,the limited expansion of MSCs restricts their therapeutic *** To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy *** Human umbilical cord(hUC)tissue derived MSCs were obtained and *** cultured cells were subjected to the following evaluation pro-cedures:Immunophenotyping,immunocytochemical staining,trilineage differentiation,population doubling time and number,gene expression markers for proliferation,cell cycle progression,senescence-associatedβ-galactosidase assay,human telomerase reverse transcriptase(hTERT)expression,mycoplasma,cytomegalovirus and endotoxin *** Analysis of pluripotent gene markers Oct4,Sox2,and Nanog in recultured hUC-MSC revealed no significant *** immunophenotypic markers CD90,CD73,CD105,CD44,vimentin,CD29,Stro-1,and Lin28 were positively expressed by these recultured expanded MSCs,and were found negative for CD34,CD11b,CD19,CD45,and *** recultured hUC-MSC population continued to expand through passage *** gene expression of Pax6,BMP2,and TGFb1 showed no significant variation between recultured hUC-MSC ***,a significant increase(P<0.001)in the mitotic phase of the cell cycle was observed in recultured *** senescence markers(hTERT expression andβ-galactosidase activity)did not show any negative effect on recultured hUC-

关键词： Human umbilical cord Mesenchymal stem cells Expansion Cell proliferation In vitro expansion Senescence

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State Key Laboratory of Traditional Chinese medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina Department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of Chinese medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina Department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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Respiratory Flow Rates of Metal Welders Compared to a Population Not Exposed to Metal Welding Dust

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Open Journal of Respiratory Diseases 2024年第2期14卷 51-59页

作者： Robert Faomowe Foko Abdou Khadir Sow Awa Ba Mor Diaw Fatoumata Bah Mame Saloum Coly Absa Lam Cheikh Diop Aminata Toure Abdoulaye Ba Abdoulaye Samb Arame Mbengue Mathilde Cabral Mamadou Fall Laboratory of Toxicology and Hydrology Faculty of Medicine Pharmacy and Odontostomatology Cheikh Anta Diop University of Dakar Dakar-Fann Senegal Laboratory of physiology and Functional Exploration Faculty of Medicine Pharmacy and Odontostomatology Cheikh Anta Diop University of Dakar Dakar-Fann Senegal Laboratory of physiology and Functional Exploration Alioune DIOP University of Bambey Bambey Senegal Laboratory of physiology UFR of Health Sciences Functional Exploration Department Thies Regional Hospital Center Thies Senegal

Background: The welding trade includes many industrial activities in both the formal and informal sectors. Workers in this professional environment do not have access to individual and collective means of protection adapted to the activity, which exposes them to the dust emitted during their activity and therefore contributes to increasing the risk of developing respiratory disorders in this population. Objective: Our study aimed to evaluate the ventilatory function of metal welders in the city of Dakar. Method: This was a comparative study based on the analysis of the spirometric parameters of metal welders working in the city of Dakar (Senegal) with those of a control group of the same kind, selected from the general population. Measurements of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and maximum mid expiratory flow (MMEF) were measured. Results: A total of 75 men between the ages of 19 and 61 were recruited and divided into two groups (43 controls and 32 welders). The welding population had more frequent distal and central obstructions and pulmonary restriction compared to the control group. The metals most commonly used by welders were aluminum for welders who had an obstruction, while for those who had a restriction, iron was the most used metal. Signs of metal fever were frequently found in welders, especially those with ventilatory disorders. Conclusion: The prevalence of respiratory disorders observed is close to that observed in industrial environments, where exposure levels are the highest. The lack of personal protective equipment could also be a significant risk factor in the development of these disorders.

关键词： Welder Occupational Exposure Spirometric Disorder Metal Fever Dakar

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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)

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Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

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Engineering 2024年第7期38卷 77-99页

作者： Jingyan Han Quan Li Kai Sun Chunshui Pan Jian Liu Ping Huang Juan Feng Yanchen Liu Gerald A.Meininger Department of Integration of Chinese and Western medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China Tasly Microcirculation Research Center Peking University Health Science CenterBeijing 100191China Key Laboratory of Stasis and Phlegm State Administration of Traditional Chinese Medicine of the People’s Republic of ChinaBeijing 100191China Beijing Laboratory of Integrative Microangiopathy Peking University Health Science CenterBeijing 100191China Dalton Cardiovascular Research Center and Department of Medical Pharmacology and physiology University of MissouriColumbiaMO 65211USA

Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and *** disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and *** clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory *** products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory *** recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international *** 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,*** review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue *** on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.

关键词： Ischemia/reperfusion Lipopolysaccharide Natural products Leukocyte activation Hyperpermeability

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Developmental Patterns and Gender Differences of Vocal Production in Marmoset Monkeys

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Neuroscience Bulletin 2024年第1期40卷 133-138页

作者： Ruixin An Chaocheng Lu Chen Wang Liangtang Chang Junfeng Huang Fan Jiang Tian-Le Xu Neng Gong Center for Brain Science Shanghai Children's Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Anatomy and physiology Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Critical Care medicine Huashan HospitalFudan University12 Middle Wulumuqi RoadShanghai 200040China Institute of Neuroscience Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Lingang Laboratory Shanghai 200031China Shanghai Center for Brain Science and Brain-Inspired Technology Shanghai 201210China

Dear Editor,The common marmoset(Callithrix jacchus),a small New World monkey species,is considered an ideal non-human primate model for studying the evolution and neural mechanism of vocal behavior due to their rich call repertoire and vocal communication[1-3].Especially,the early vocal development of marmoset monkeys has attracted much attention,because newborn marmosets have been shown to exhibit a vocal development *** two months after birth,marmosets'vocalizations undergo dramatic changes from cries to adult-like mature calls,a process that is influenced not only by inner physical maturation but also by parental care and feedback[4].

关键词： parental birth Pattern

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Pathological and Physiological High-frequency Oscillations on Electroencephalography in Patients with Epilepsy

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Neuroscience Bulletin 2024年第5期40卷 609-620页

作者： Hongyi Ye Cong Chen Shennan A.Weiss Shuang Wang Department of Neurology Epilepsy CenterSecond Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009China Department of Neurology State University of New York DownstateBrooklynNY11203USA Department of physiology and Pharmacology State University of New York DownstateBrooklynNY11203USA Department of Neurology New York City Health+Hospitals/Kings CountyBrooklynNY11203USA

High-frequency oscillations(HFOs)encompass ripples(80 Hz–200 Hz)and fast ripples(200 Hz–600 Hz),serving as a promising biomarker for localizing the epileptogenic zone in *** fast ripples are always pathological,while ripples may be physiological or *** physiological from pathological ripples is important not only for designating epileptogenic brain regions,but also for investigations that study ripples in the context of memory encoding,consolidation,and recall in patients with *** studies have sought to identify distinguishing features between pathological and physiological ripples over the past two *** and pathological ripples differ with respect to their spatial location,cellular mechanisms,morphology,and coupling with background electroencephalographic *** studies have demonstrated that differentiating between pathological and physiological ripples can improve surgical outcome *** this review,we summarize the characteristics,differences,and applications of pathological and physiological HFOs and discuss strategies for their clinical translation.

关键词： Ripples Epilepsy Memory Sleep Surgical outcome

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Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

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Animal Models and Experimental medicine 2024年第1期7卷 24-35页

作者： Xiaojun Deng Xiaoyi Hu Shang Wang Hui Zhao Yaqin Wei Jiaqi Fu Wenhui Wu Jinming Liu Caicai Zhang Lili Wang Ping Yuan Department of Critical Care medicine Shanghai Sixth People's HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of physiology Hainan Medical University HaikouHainanChina Department of Clinical Medical Laboratory Center Hangzhou Red Cross HospitalZhejiangChina

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 ***,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain ***,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 ***:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on ***:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic *** overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic ***,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell ***1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell *** structures were observed in the regions of the hippocampus and cortex in hypoxia-induced ***,EXO treatment improved cerebrovascular ***:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic ***,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

关键词： brain microvascular endothelial cells exosomes Hes1 miR-9 neural stem cells

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative Center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Department of physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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Autophagy in neural stem cells and glia for brain health and diseases

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Neural Regeneration Research 2024年第4期19卷 729-736页

作者： Aarti Nagayach Chenran Wang Department of Cancer Biology University of Cincinnati College of Medicine

Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and *** facilities the utilization of energy and the microenvironment for developing neural stem *** arbitrates structural and functional remodeling during the cell differentiation *** also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of *** recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the *** cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured ***,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative *** review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

关键词： astrocyte autophagy glia microglia neural stem cells neurodegenerative diseases neurodevelopmental disorders oligodendrocyte

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