Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions th...Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.展开更多
Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as ...Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
目的近年来,静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)已成为无创研究多发性硬化症(multiple sclerosis,MS)脑功能异常的关键技术,但现有研究结论存在分歧。为此,需整合现有rs-fMRI研究证据...目的近年来,静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)已成为无创研究多发性硬化症(multiple sclerosis,MS)脑功能异常的关键技术,但现有研究结论存在分歧。为此,需整合现有rs-fMRI研究证据,明确MS患者脑功能的一致性改变。材料与方法截至2025年4月,系统检索PubMed、Web of Science、Embase、中国知网及万方数据库,筛选采用低频振幅(amplitude of low-frequency fluctuation,ALFF)、分数ALFF(fractional ALFF,fALFF)或局部一致性(regional homogeneity,ReHo)方法探究MS患者自发脑功能活动的研究,并运用各向异性效应量种子点d映射(anisotropic effect size seed-based d mapping,AES-SDM)软件进行数据分析。结果共纳入11项研究(12个数据集),涉及292例MS患者和278例健康对照(healthy controls,HCs)。与HCs相比,MS患者右岛叶、罗兰岛盖、赫氏回、缘上回、双侧丘脑及左侧额下回(眶部)自发性脑功能活动显著增强,而右舌回、楔叶皮层、距状裂/周围皮层、颞中回、纹状体(尾状核)活动显著降低。结论本研究揭示了MS患者一致性脑功能改变,涉及情绪调节、认知、感觉、视觉及运动控制等相关脑区。这些发现不仅深化了对MS神经病理机制的理解,还为疾病诊断、进展监测及治疗效果评估提供了潜在的生物标志物。展开更多
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金support held by JPA,Collaborative Network Award BRAVEinMS,Grant/Award Number:PA-1604-08492(MG)from the Multiple Sclerosis Society of Canada,Grant/Award Number:1038154(to TEK).
文摘Myelin,made by oligodendrocytes(OLs)in the central nervous system(CNS),is essential for neural transmission.In particular,myelin facilitates communication across the long connections between different brain regions that form the white matter.Myelinated segments also provide metabolic intermediates to axons,supporting their demanding energetic needs.Genetic disorders that disrupt myelin formation result in progressive neurologic degeneration.
基金supported by the National Natural Science Foundation of China,Nos.82372277(to ZW),82272361(to XS),82271395(to GL)Guangdong Province Basic and Applied Basic Research Fund Project,No.2024A1515010615(to XS)+1 种基金Guangdong Province Natural Youth Promotion Project,No.2314070000241(to GL)Guangzhou Science and Technology Project,No.2025A04J4740(to GL).
文摘Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
文摘目的近年来,静息态功能磁共振成像(resting-state functional magnetic resonance imaging,rs-fMRI)已成为无创研究多发性硬化症(multiple sclerosis,MS)脑功能异常的关键技术,但现有研究结论存在分歧。为此,需整合现有rs-fMRI研究证据,明确MS患者脑功能的一致性改变。材料与方法截至2025年4月,系统检索PubMed、Web of Science、Embase、中国知网及万方数据库,筛选采用低频振幅(amplitude of low-frequency fluctuation,ALFF)、分数ALFF(fractional ALFF,fALFF)或局部一致性(regional homogeneity,ReHo)方法探究MS患者自发脑功能活动的研究,并运用各向异性效应量种子点d映射(anisotropic effect size seed-based d mapping,AES-SDM)软件进行数据分析。结果共纳入11项研究(12个数据集),涉及292例MS患者和278例健康对照(healthy controls,HCs)。与HCs相比,MS患者右岛叶、罗兰岛盖、赫氏回、缘上回、双侧丘脑及左侧额下回(眶部)自发性脑功能活动显著增强,而右舌回、楔叶皮层、距状裂/周围皮层、颞中回、纹状体(尾状核)活动显著降低。结论本研究揭示了MS患者一致性脑功能改变,涉及情绪调节、认知、感觉、视觉及运动控制等相关脑区。这些发现不仅深化了对MS神经病理机制的理解,还为疾病诊断、进展监测及治疗效果评估提供了潜在的生物标志物。
