Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot ...Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot firstdescribed its clinical and pathologicalcharacteristics.Its incidence is very high,especially in Europe and America.Thereis no epidemic data of this展开更多
PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of P...PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-γ mRNA activates PKR through a structure in its 5＇- region harboring a pseudoknot which is critical for PKR activation. Mutations that impair pseudoknot stability reduce the ability of IFN-γ mRNA to activate PKR and strongly increase its translation efficiency. The cis-acting RNA element in IFN-γ mRNA functions as a biological sensor of intracellular PKR levels. During an immune response, as IFN-γ and other inflammatory cytokines build up in the cell＇s microenvironment, they act to induce higher levels of PKR in the cell, resulting in a more extensive activation of PKR by IFN-γ mRNA. With the resulting phosphorylation of eIF2α, a negative feedback loop is created and the production of IFN-γ is progressively attenuated. We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.展开更多
A 43-year-old woman with multiple sclerosis （MS） was treated with pulsed methylprednisolone and interferon 13 at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and...A 43-year-old woman with multiple sclerosis （MS） was treated with pulsed methylprednisolone and interferon 13 at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis （AIH）. She was successfully treated with corticosteroids. As ataxia developed after i year, she was treated with pulsed methylprednisolone for 3 days, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.展开更多
From December of 1998 to August of 2002, the author treated 95 cases of multiple sclerosis with acupuncture. The observation has confirmed that acupuncture is a very effective method for treating this disease, especia...From December of 1998 to August of 2002, the author treated 95 cases of multiple sclerosis with acupuncture. The observation has confirmed that acupuncture is a very effective method for treating this disease, especially to sclerosis patients in the early stage; and furthermore it can slow down the development of the pathological conditions of the patients. Thus it is an important therapeutic method worthy of the choice by European and American clinical doctors.展开更多
Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and th...Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.展开更多
文摘Multiple sclerosis(MS),a diseaseaffecting the central nervous system,ischaracterized by patches of demyelinationand sclerosis of gliosis desseminatedthroughout the white matter of brain andspinal cord.In 1968,Charcot firstdescribed its clinical and pathologicalcharacteristics.Its incidence is very high,especially in Europe and America.Thereis no epidemic data of this
基金Acknowledgements Research in the author＇s laboratory was supported by grants from the Israel Science Foundation （537/03） and the Deutsche Forschungsgemeinschaft （H0- 1116）,
文摘PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-γ mRNA activates PKR through a structure in its 5＇- region harboring a pseudoknot which is critical for PKR activation. Mutations that impair pseudoknot stability reduce the ability of IFN-γ mRNA to activate PKR and strongly increase its translation efficiency. The cis-acting RNA element in IFN-γ mRNA functions as a biological sensor of intracellular PKR levels. During an immune response, as IFN-γ and other inflammatory cytokines build up in the cell＇s microenvironment, they act to induce higher levels of PKR in the cell, resulting in a more extensive activation of PKR by IFN-γ mRNA. With the resulting phosphorylation of eIF2α, a negative feedback loop is created and the production of IFN-γ is progressively attenuated. We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.
文摘A 43-year-old woman with multiple sclerosis （MS） was treated with pulsed methylprednisolone and interferon 13 at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis （AIH）. She was successfully treated with corticosteroids. As ataxia developed after i year, she was treated with pulsed methylprednisolone for 3 days, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS.
文摘From December of 1998 to August of 2002, the author treated 95 cases of multiple sclerosis with acupuncture. The observation has confirmed that acupuncture is a very effective method for treating this disease, especially to sclerosis patients in the early stage; and furthermore it can slow down the development of the pathological conditions of the patients. Thus it is an important therapeutic method worthy of the choice by European and American clinical doctors.
基金supported by the China National Basic Research Program(2013CB966901,2012CBA01303)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01040108)+1 种基金National Thousand Young Talents Program to Tongbiao Zhaothe National Natural Science Foundation of China Program((31271592,31570995)to Tongbiao Zhao,(31400831)to Jiani Cao)
文摘Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.
