Laser-heated diamond-anvil cell (LHDAC) is emerging as the most suitable, economical and versatile tool for the measurement of a large spectrum of physical properties of materials under extreme pressure and temperatur...Laser-heated diamond-anvil cell (LHDAC) is emerging as the most suitable, economical and versatile tool for the measurement of a large spectrum of physical properties of materials under extreme pressure and temperature conditions. In this review, the recent developments in the instrumentation, pressure and temperature measurement techniques, results of experimental investigations from the literature were discussed. Also, the future scope of the technique in various avenues of science was explored.展开更多
Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic ...Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.展开更多
Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse ...Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.展开更多
Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not r...Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.展开更多
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t...Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.展开更多
Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerati...Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.展开更多
In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant inter...In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant interest for their potential to serve as natural scaffolds for cells.In this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J Stem Cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee joints.Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).Stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can generate.Collectively,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration.The interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.展开更多
BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown...BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.展开更多
Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and foun...Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.展开更多
This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular ...This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.展开更多
BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone an...BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.展开更多
Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alle...Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.展开更多
Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinat...Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of ...BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.展开更多
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
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 surv...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 survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy 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 diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial 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 tissues.Thus,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 diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.展开更多
文摘Laser-heated diamond-anvil cell (LHDAC) is emerging as the most suitable, economical and versatile tool for the measurement of a large spectrum of physical properties of materials under extreme pressure and temperature conditions. In this review, the recent developments in the instrumentation, pressure and temperature measurement techniques, results of experimental investigations from the literature were discussed. Also, the future scope of the technique in various avenues of science was explored.
基金supported by the National Natural Science Foundation of China,No.31960120Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(both to ZW).
文摘Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.
文摘Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.
基金supported by NIH Core Grants P30-EY008098the Eye and Ear Foundation of Pittsburghunrestricted grants from Research to Prevent Blindness,New York,NY,USA(to KCC)。
文摘Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.
基金supported by the National Natural Science Foundation of China,No.82171380(to CD)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program,No.202110304098Y(to DJ)。
文摘Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
基金supported by the National Natural Science Foundation of China,No.82171336(to XX)。
文摘Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.
文摘In recent years,there has been considerable exploration into methods aimed at enhancing the regenerative capacity of transplanted and/or tissue-resident cells.Biomaterials,in particular,have garnered significant interest for their potential to serve as natural scaffolds for cells.In this editorial,we provide commentary on the study by Wang et al,in a recently published issue of World J Stem Cells,which investigates the use of a decellularized xenogeneic extracellular matrix(ECM)derived from antler stem cells for repairing osteochondral defects in rat knee joints.Our focus lies specifically on the crucial role of biological scaffolds as a strategy for augmenting stem cell potential and regenerative capabilities,thanks to the establishment of a favorable microenvironment(niche).Stem cell differen-tiation heavily depends on exposure to intrinsic properties of the ECM,including its chemical and protein composition,as well as the mechanical forces it can generate.Collectively,these physicochemical cues contribute to a bio-instructive signaling environment that offers tissue-specific guidance for achieving effective repair and regeneration.The interest in mechanobiology,often conceptualized as a form of“structural memory”,is steadily gaining more validation and momen-tum,especially in light of findings such as these.
基金National Natural Science Foundation of China,No.U20A20403This study was conducted in accordance with the Animal Ethics Committee of the Institute of Antler Science and Product Technology,Changchun Sci-Tech University(AEC No:CKARI202309).
文摘BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.
基金supported by the National Natural Science Foundation of China,Nos.31730031,32130060the National Natural Science Foundation of China,No.31971276(to JH)+1 种基金the Natural Science Foundation of Jiangsu Province,No.BK20202013(to XG)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(Major Program),No.19KJA320005(to JH)。
文摘Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.
文摘This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.
文摘BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.
文摘Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.
基金financially supported by the National Key Research and Development Program of China(2021YFD2100904)the National Natural Science Foundation of China(31871729,32172147)+2 种基金the Modern Agriculture key Project of Jiangsu Province of China(BE2022317)the Modern Agricultural Industrial Technology System Construction Project of Jiangsu Province of China(JATS[2021]522)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Active ingredients from highland barley have received considerable attention as natural products for developing treatments and dietary supplements against obesity.In practical application,the research of food combinations is more significant than a specific food component.This study investigated the lipid-lowering effect of highland barley polyphenols via lipase assay in vitro and HepG2 cells induced by oleic acid(OA).Five indexes,triglyceride(TG),total cholesterol(T-CHO),low density lipoprotein-cholesterol(LDL-C),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),were used to evaluate the lipidlowering effect of highland barley extract.We also preliminary studied the lipid-lowering mechanism by Realtime fluorescent quantitative polymerase chain reaction(q PCR).The results indicated that highland barley extract contains many components with lipid-lowering effects,such as hyperoside and scoparone.In vitro,the lipase assay showed an 18.4%lipase inhibition rate when the additive contents of highland barley extract were 100μg/m L.The intracellular lipid-lowering effect of highland barley extract was examined using 0.25 mmol/L OA-induced HepG2 cells.The results showed that intracellular TG,LDL-C,and T-CHO content decreased by 34.4%,51.2%,and 18.4%,respectively.ALT and AST decreased by 51.6%and 20.7%compared with the untreated hyperlipidemic HepG2 cells.q PCR results showed that highland barley polyphenols could up-regulation the expression of lipid metabolism-related genes such as PPARγand Fabp4.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金National Natural Science Foundation of China,No.82173359Basic Research and Frontier Exploration Project of Chongqing and Technology Commission,No.cstc2018jcyjAX0181Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University.
文摘BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金supported by NIH R01NS103981 and R01CA273586(to CW)。
文摘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 survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy 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 diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial 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 tissues.Thus,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 diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.