Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic He...Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.展开更多
Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its...Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its six EF-hand domains,including endocrine granule secretion,synaptic vesicle release,and plays crucial roles in neurodevelopment and neurological disorders.This review systematically summarizes Scgn’s structural characteristics,expression patterns,and multifaceted roles within the nervous system,while exploring its potential pathological significance and therapeutic value in neuropsychiatric disorders.Existing studies indicate that Scgn is specifically distributed in brain regions such as the olfactory bulb and hippocampus.It engages in Ca^(2+)-dependent interactions with key synaptic secretion molecules like SNAP-25 and Doc2α,thereby regulating neurotransmission and synaptic plasticity.Furthermore,pathological alterations in Scgn observed in diseases like Alzheimer’s disease,Parkinson’s disease,and epilepsy suggest its potential as an early biomarker and therapeutic target,offering significant prospects for translational research.展开更多
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease i...Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.展开更多
The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achie...The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achieved notable success in hematological malignancies,their broader application is hindered by the high cost and delays of autologous manufacturing,as well as the critical risk of graft-vs-host disease(GvHD).In addition,their efficacy against solid tumors is often compromised by the immunosuppressive tumor microenvironment(TME).As a promising solution,γδT cells are being developed as an alternative CAR platform.Their intrinsic ability to recognize transformed cells in a major histocompatibility complex(MHC)-independent manner minimizes the risk of GvHD and supports the creation of safe,effective allogeneic therapies.Building on this unique biology,the therapeutic efficacy of CARγδT cells is being enhanced through advanced engineering strategies.Key innovations include“armoring”technologies,such as cytokine secretion,checkpoint blockade,and metabolic rewiring,to overcome local immunosuppression and improve persistence,as well as the use of induced pluripotent stem cells(iPSCs)to generate standardized products from a renewable and consistent source.This expanding technological toolbox is also enabling novel applications beyond oncology.For example,chimeric autoantibody receptor(CAAR)constructs built onγδT cells integrate both classical and emerging insights into CARγδT cell therapy,highlighting innovations that are driving the field toward safer,more versatile,and longer-lasting treatments for cancer and autoimmunity.In light of these advancements,this review provides an overview of the current understanding ofγδT cell biology and highlights emerging engineering strategies that enhance the efficacy and durability of CARγδT cells across oncologic and autoimmune contexts.展开更多
Summary： IgG4-related disease （IgG4-RD） is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 eleva tion commonly occ...Summary： IgG4-related disease （IgG4-RD） is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 eleva tion commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay （ELISA） in a variety of autoimmune diseases including systemic lupus erythematosus （SLE）, Sjogren＇s syndrome （SS）, polymyositis or dermatomy- ositis （PM/DM） and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric as-say. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups （P〉0.05）. The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.展开更多
Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phen...Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes;these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.展开更多
Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work throug...Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.展开更多
Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protei...Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.展开更多
Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transc...Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transcriptional regulation. Indeed, evidence shows that microRNAs are one of the most important regulators mediating microglial activation, polarization, and autophagy, and subsequently affecting neuroinflammation and the outcome of central nervous system disease. In this review, we provide insight into the function of microRNAs, which may be an attractive strategy and influential treatment for microglia-related central nervous system dysfunction. Moreover, we comprehensively describe how microglia fight against central nervous system disease via multiple functional microRNAs.展开更多
Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training i...Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.展开更多
Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy （HDIT） and autolognus hemopoietic stem cell transplantation （HSCT） with CD^34＋ cell selection in patients with se...Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy （HDIT） and autolognus hemopoietic stem cell transplantation （HSCT） with CD^34＋ cell selection in patients with severe, refractory autoim mune diseases. Methods Twenty-six patients with persistent systemic lupus erythematosus （SLE）, rheumatoid arthritis （RA）, primary Sjogren＇s syndrome （pSS）, or systemic sclerosis （SSc） who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease acti- vity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored. Overall treatment related mortality was 7.7% （2/26） with 1 patient died of cytomegalovirus infection and an other of severe pneumonia. Relapse occurred in 3 SLE patients （17.6%） in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index （SLEDAI） scores of SLE survivors decreased significantly （P 〈 0.01）. RA patients recorded a drop of Disease Activity Score 28 （DAS 28）. The pSS patient remained symptoms free up to now, more than 50 months aider the transplantation. Conclusion HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,...Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.展开更多
Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We compre...Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.展开更多
Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional org...Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional organic conditions.The present invited Editorial discusses the application of FR in autoimmune diseases(AD),highlighting a few successful studies demonstrating symptomatic relief and objective improvements.Despite promising results,the FR domain remains under-investigated and an urgent need to confirm and understand the effect of FR in chronic diseases,including AD,is highly recommended.展开更多
Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family （Olig family） is known to be an important factor in regulating neura...Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family （Olig family） is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.展开更多
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China,No.82474468the Science and Technology Innovation Program of Hunan Province,No.2024RC3200+3 种基金the Health Commission Talent Project of Hunan Province,No.20240304118the Scientific Research Project of Hunan Department of Education,No.23A0281the Open Fund for Chinese Medicine Powder and Innovative Drugs in the Cultivation Base of the Provincial-Ministry Jointly Established State Key Laboratory of Chinese Medicine,No.23PTKF1013the Training Plan of Outstanding Innovative Youth of Changsha,No.kq2009018(all to PM)。
文摘Over the past few decades,the Sonic Hedgehog protein has become a pivotal player in many biological processes,including tumourigenesis,embryonic development,and protective mechanisms after cerebral damage.The Sonic Hedgehog signaling pathway is crucial in the central nervous system,with implications in a diverse range of diseases,including Parkinson's disease,Alzheimer's disease,spinal cord injury,traumatic brain injury,depression,Sonic Hedgehog medulloblastoma,and stroke.In this comprehensive review,we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways,elucidating their complex connections to the central nervous system.Subsequently,we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein.Finally,we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field,with the aim of providing new research ideas and methods.
基金supported by the National Natural Science Foundation of China(Grant No.32170699,32200560)the Hubei Provincial Natural Science Foundation of China(Grant No.2022CFB906,2025AFA009)。
文摘Scgn is an EF-hand calcium-binding protein occupying a unique position within the family of neuron-specific calcium sensors.As a key participant in calcium signaling,Scgn regulates diverse neural processes through its six EF-hand domains,including endocrine granule secretion,synaptic vesicle release,and plays crucial roles in neurodevelopment and neurological disorders.This review systematically summarizes Scgn’s structural characteristics,expression patterns,and multifaceted roles within the nervous system,while exploring its potential pathological significance and therapeutic value in neuropsychiatric disorders.Existing studies indicate that Scgn is specifically distributed in brain regions such as the olfactory bulb and hippocampus.It engages in Ca^(2+)-dependent interactions with key synaptic secretion molecules like SNAP-25 and Doc2α,thereby regulating neurotransmission and synaptic plasticity.Furthermore,pathological alterations in Scgn observed in diseases like Alzheimer’s disease,Parkinson’s disease,and epilepsy suggest its potential as an early biomarker and therapeutic target,offering significant prospects for translational research.
基金supported by the National Research Foundation of South Korea(2023R1A2C2004516,RS-2023-00219399 to SPY,and 2022R1I1A1A01063513 to MGJ)。
文摘Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
基金supported by the National Research Foundation of Korea(NRF)through the Ministry of Education(2021R1I1A3059820)(to Jea-Hyun Baek).
文摘The paradigm of cancer treatment has been reshaped by chimeric antigen receptor(CAR)αβT cell therapy,yet its full potential remains constrained by fundamental limitations.While conventional CARαβT cells have achieved notable success in hematological malignancies,their broader application is hindered by the high cost and delays of autologous manufacturing,as well as the critical risk of graft-vs-host disease(GvHD).In addition,their efficacy against solid tumors is often compromised by the immunosuppressive tumor microenvironment(TME).As a promising solution,γδT cells are being developed as an alternative CAR platform.Their intrinsic ability to recognize transformed cells in a major histocompatibility complex(MHC)-independent manner minimizes the risk of GvHD and supports the creation of safe,effective allogeneic therapies.Building on this unique biology,the therapeutic efficacy of CARγδT cells is being enhanced through advanced engineering strategies.Key innovations include“armoring”technologies,such as cytokine secretion,checkpoint blockade,and metabolic rewiring,to overcome local immunosuppression and improve persistence,as well as the use of induced pluripotent stem cells(iPSCs)to generate standardized products from a renewable and consistent source.This expanding technological toolbox is also enabling novel applications beyond oncology.For example,chimeric autoantibody receptor(CAAR)constructs built onγδT cells integrate both classical and emerging insights into CARγδT cell therapy,highlighting innovations that are driving the field toward safer,more versatile,and longer-lasting treatments for cancer and autoimmunity.In light of these advancements,this review provides an overview of the current understanding ofγδT cell biology and highlights emerging engineering strategies that enhance the efficacy and durability of CARγδT cells across oncologic and autoimmune contexts.
基金supported by the National Natural Science Foundation of China(Nos.30972706 and 31270965)
文摘Summary： IgG4-related disease （IgG4-RD） is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 eleva tion commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay （ELISA） in a variety of autoimmune diseases including systemic lupus erythematosus （SLE）, Sjogren＇s syndrome （SS）, polymyositis or dermatomy- ositis （PM/DM） and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric as-say. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups （P〉0.05）. The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.
基金supported by the National Natural Science Foundation of China,Nos. 82004028 (to LJS) and 81473577 (to CGM)China Postdoctoral Science Foundation,No. 2020M680912 (to LJS)+4 种基金Shanxi Applied Basic Research Project,No. 201901D211538 (to LJS)Leading Team of Medical Science and Technology of Shanxi Province,No. 2020TD05 (to CGM)Funds for Construction of Key Disciplines from Shanxi University of Chinese Medicine,Young Scientists Cultivation Project of Shanxi University of Chinese Medicine No. 2021PYQN-09 (to LJS)Basic Research Project of the Cultivation Plan of Scientific and Technological Innovation Ability of Shanxi University of Chinese Medicine,No. 2020PY-JC-02 (to LJS)Cardiovascular Special Fund Project of National Regional Traditional Chinese Medicine Medical Center of Affiliated Hospital of Shanxi University of Chinese Medicine in 2021, No. XGZX202115 (to LJS)。
文摘Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes;these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.
基金Supported by the Oman Ministry of Higher Education,Research,and Innovation,No.BFP/RGP/HSS/24/015.
文摘Chloroquine(CQ)and hydroxychloroquine(HCQ),originally developed as anti-malarial drugs,have found a new purpose in treating various autoimmune dis-eases due to their immunomodulatory properties.These drugs work through mu-ltiple mechanisms,including inhibiting Toll-like receptor signaling,suppressing antigen presentation,and modulating autophagy.This review article provides a comprehensive analysis of the immunomodulatory effects of CQ and HCQ in several autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,systemic sclerosis,and others.We delve into the intricate mechanisms of action,highlighting the key immune cells involved and discussing the clinical implications of these drugs in managing autoimmune conditions.Our review covers the latest research and clinical trials,offering a comprehensive under-standing of the therapeutic potential of CQ and HCQ in autoimmune diseases.We also discuss the challenges and controversies surrounding the use of these drugs,such as their long-term side effects and the need for personalized treatment approaches.By synthesizing current knowledge and identifying areas for future research,this review aims to provide a valuable resource for healthcare profes-sionals and researchers involved in the management of autoimmune diseases.
基金supported by the National Natural Science Foundation of China,No. 82071374Discipline Construction Project of Guangdong Medical University,Nos. 1.13 and 4.1.19+1 种基金College Students Innovative Experimental Project in Guangdong Medical University,Nos. FYDB015, ZCDS001, ZYDB004, ZYDB016, and ZZDI001College Students’ Science and Technology Innovation Training Project,Nos. GDMU2020194, GDMU2020195, GDMU2021021, GDMU2021023, GDMU2021091, GDMU2021111 (all to HFW)。
文摘Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.
基金supported by the National Natural Science Foundation of China,No.81401084(to XHW)Beijing Municipal Administration of Hospital Ascent Plan,No.DFL20150802(to TLW)+2 种基金Beijing 215 High Level Healthcare Talent Plan Academic Leader,No.008-0027(to TLW)Beijing Municipal Commission of Health and Family Planning,No.PXM2017_026283_000002(to TLW)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,No.ZYLX201706(to TLW)
文摘Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transcriptional regulation. Indeed, evidence shows that microRNAs are one of the most important regulators mediating microglial activation, polarization, and autophagy, and subsequently affecting neuroinflammation and the outcome of central nervous system disease. In this review, we provide insight into the function of microRNAs, which may be an attractive strategy and influential treatment for microglia-related central nervous system dysfunction. Moreover, we comprehensively describe how microglia fight against central nervous system disease via multiple functional microRNAs.
基金supported by the National Natural Science Foundation of China(NO.31801003 for DX,NO.31701040 for BL)Shanghai Key Lab of Human Performance(Shanghai University of Sport)(NO.11DZ2261100)。
文摘Background:The anti-inflammatory effect of exercise may be an underlying factor in improving several autoimmune diseases.The aim of this systematic review was to examine the evidence on the role of exercise training in mitigating inflammation in adolescents and adults with autoimmune disease.Methods:PubMed,Web of Science,and Embase databases were systematically reviewed for related studies published between January 1,2003,and August 31,2023.All randomized and non-randomized controlled trials of exercise interventions with autoimmune disease study participants that evaluated inflammation-related biomarkers were included.The quality of evidence was assessed using the Tool for the assEssment of Study qualiTy and reporting in EXercise scale and Cochrane bias risk tool.Results:A total of 14,565 records were identified.After screening the titles,abstracts,and full texts,87 were eligible for the systematic review.These studies were conducted in 25 different countries and included a total of 2779 participants(patients with autoimmune disease,in exercise or control groups).Overall,the evidence suggests that inflammation-related markers such as C-reactive protein,interleukin 6,and tumor necrosis factor a were reduced by regular exercise interventions.Regular exercise interventions combined with multiple exercise modes were associated with greater benefits.Conclusion:Regular exercise training by patients with autoimmune disease exerts an anti-inflammatory influence.This systematic review provides support for the promotion and development of clinical exercise intervention programs for patients with autoimmune disease.Most patients with autoimmune disease can safely adopt moderate exercise training protocols,but changes in inflammation biomarkers will be modest at best.Acute exercise interventions are ineffective or even modestly but transiently pro-inflammatory.
基金Supported by Ministry of Health for ClinicalIntensiveSubjects(2001-2003 ).
文摘Objective To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy （HDIT） and autolognus hemopoietic stem cell transplantation （HSCT） with CD^34＋ cell selection in patients with severe, refractory autoim mune diseases. Methods Twenty-six patients with persistent systemic lupus erythematosus （SLE）, rheumatoid arthritis （RA）, primary Sjogren＇s syndrome （pSS）, or systemic sclerosis （SSc） who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease acti- vity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored. Overall treatment related mortality was 7.7% （2/26） with 1 patient died of cytomegalovirus infection and an other of severe pneumonia. Relapse occurred in 3 SLE patients （17.6%） in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index （SLEDAI） scores of SLE survivors decreased significantly （P 〈 0.01）. RA patients recorded a drop of Disease Activity Score 28 （DAS 28）. The pSS patient remained symptoms free up to now, more than 50 months aider the transplantation. Conclusion HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金supported by KAKENHI under grant number 23K08535,22K09274(to MK)。
文摘Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular communication.These nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive molecules.Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders.These exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic effects.Furthermore,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug encapsulation.Consequently,researchers have turned their attention to exosomes as a novel therapeutic avenue.Nonetheless,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application.To overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system.By exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier.Notably,exosomes,owing to their small size,can readily access the nerve pathways using this method.As a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments.In this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases.Furthermore,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.
文摘Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.
文摘Foot reflexology(FR)is a Chinese-originated and non-invasive complementary therapy increasingly used by functional,alternative and para-medical professionals.Enhance attempts are made to study FR in non-functional organic conditions.The present invited Editorial discusses the application of FR in autoimmune diseases(AD),highlighting a few successful studies demonstrating symptomatic relief and objective improvements.Despite promising results,the FR domain remains under-investigated and an urgent need to confirm and understand the effect of FR in chronic diseases,including AD,is highly recommended.
基金the National Natural Science Foundation of China,No.81171859the Natural Science Foundation of Chongqing,No.cstc2012jjA10058the Chongqing Health Bureau Project,No.2011-2-172
文摘Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family （Olig family） is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.
