Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh ...Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.展开更多
Duchenne muscular dystrophy (DMD) is X-linked muscular disorder, with an incidence of approximately 1 in 3500 newborn males. The patient is characterised by progressive wasting of the skeletal muscles and usually dies...Duchenne muscular dystrophy (DMD) is X-linked muscular disorder, with an incidence of approximately 1 in 3500 newborn males. The patient is characterised by progressive wasting of the skeletal muscles and usually dies of respiratory difficul-展开更多
Demyelination of axons plays an important role in the pathology of many spinal cord diseases and injuries.Remyelination in demyelinated lesions is primarily performed by oligodendrocyte progenitor cells(OPCs),which ge...Demyelination of axons plays an important role in the pathology of many spinal cord diseases and injuries.Remyelination in demyelinated lesions is primarily performed by oligodendrocyte progenitor cells(OPCs),which generate oligodendrocytes in the developing and mature central nervous system.The efficiency of remyelination decreases with age.Many reports suggest that this decline in remyelination results from impaired OPC recruitment and differentiation during aging.Of the various molecular mechanisms involved in aging,changes in epigenetic modifications have received particular attention.Global DNA methylation is a major epigenetic modification that plays important roles in cellular senescence and organismal aging.Thus,we aimed to evaluate the dynamic changes in the global DNA methylation profiles of OPCs derived from rat spinal cords during the aging process.We separated and cultured OPCs from the spinal cords of neonatal,4-month-old,and 16-month-old rats and investigated the age-related alterations of genomic DNA methylation levels by using quantitative colorimetric analysis.To determine the potential cause of dynamic changes in global DNA methylation,we further analyzed the activity of DNA methyltransferases(DNMTs)and the expression of DNMT1,DNMT3a,DNMT3b,TET1,TET2,TET3,MBD2,and MeCP2 in the OPCs from each group.Our results showed the genomic DNA methylation level and the activity of DNMTs from OPCs derived from rat spinal cords decreased gradually during aging,and OPCs from 16-month-old rats were characterized by global hypomethylation.During OPC aging,the mRNA and protein expression levels of DNMT3a,DNMT3b,and MeCP2 were significantly elevated;those of DNMT1 were significantly down-regulated;and no significant changes were observed in those for TET1,TET2,TET3,or MBD2.Our results indicated that global DNA hypomethylation in aged OPCs is correlated with DNMT1 downregulation.Together,these data provide important evidence for partly elucidating the mechanism of age-related impaired OPC recruitment and differentiation and assist in the development of new treatments for promoting efficient remyelination.展开更多
Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs are then regulated by RNA binding p...Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs are then regulated by RNA binding proteins(RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs(half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts(MBs) or myotubes(MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.展开更多
文摘Quantitative magnetic resonance image(MRI)in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy(DMD).The purpose of this study w批to measure丁2 relaxation time of thigh muscles in children with DMD and healthy boys,and to correlate the T2 relaxation time of muscles with the fat fraction(FF)at quantitative magnetic resonance and results of clinical assessment.Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI.Age,body mass index(BMI),muscle strength assessment,timed functional tests(time to walk or run 10 metres,rise from the floor and ascend four stairs),and the North Star Ambulatory Assessment(NSAA)were evaluated.Spearman’s correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time.The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group(P<0.05),except for the gracilis(P=0.952).The gracilis,sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients.The T2 relaxation time was correlated significantly with the mean FF in all muscles.Age,BMI,total muscle strength score,timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time.T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.
文摘Duchenne muscular dystrophy (DMD) is X-linked muscular disorder, with an incidence of approximately 1 in 3500 newborn males. The patient is characterised by progressive wasting of the skeletal muscles and usually dies of respiratory difficul-
基金grants from the National Natural Science Foundation of China(No.81000520 and No.81702650)the Natural Science Foundation of Hubei Province of China(No.02.07.17040039)+1 种基金Innovation Foundation of Huazhong University of Science and Technology(No.2016YXMS229)the Innovation Foundation of Wuhan Union Hospital(No.02.03.2017-54).
文摘Demyelination of axons plays an important role in the pathology of many spinal cord diseases and injuries.Remyelination in demyelinated lesions is primarily performed by oligodendrocyte progenitor cells(OPCs),which generate oligodendrocytes in the developing and mature central nervous system.The efficiency of remyelination decreases with age.Many reports suggest that this decline in remyelination results from impaired OPC recruitment and differentiation during aging.Of the various molecular mechanisms involved in aging,changes in epigenetic modifications have received particular attention.Global DNA methylation is a major epigenetic modification that plays important roles in cellular senescence and organismal aging.Thus,we aimed to evaluate the dynamic changes in the global DNA methylation profiles of OPCs derived from rat spinal cords during the aging process.We separated and cultured OPCs from the spinal cords of neonatal,4-month-old,and 16-month-old rats and investigated the age-related alterations of genomic DNA methylation levels by using quantitative colorimetric analysis.To determine the potential cause of dynamic changes in global DNA methylation,we further analyzed the activity of DNA methyltransferases(DNMTs)and the expression of DNMT1,DNMT3a,DNMT3b,TET1,TET2,TET3,MBD2,and MeCP2 in the OPCs from each group.Our results showed the genomic DNA methylation level and the activity of DNMTs from OPCs derived from rat spinal cords decreased gradually during aging,and OPCs from 16-month-old rats were characterized by global hypomethylation.During OPC aging,the mRNA and protein expression levels of DNMT3a,DNMT3b,and MeCP2 were significantly elevated;those of DNMT1 were significantly down-regulated;and no significant changes were observed in those for TET1,TET2,TET3,or MBD2.Our results indicated that global DNA hypomethylation in aged OPCs is correlated with DNMT1 downregulation.Together,these data provide important evidence for partly elucidating the mechanism of age-related impaired OPC recruitment and differentiation and assist in the development of new treatments for promoting efficient remyelination.
基金Prinses Beatrix Spierfonds in the Netherlands(Grant No.W.OR.14-13)
文摘Muscle formation is a coordinated process driven by extensive gene expression changes where single cells fuse together to form multinucleated muscle fibers. Newly synthesized m RNAs are then regulated by RNA binding proteins(RBPs), affecting post-transcriptional transcript metabolism. Here, we determined how large-scale gene expression changes affect the catalog of RBPs by studying proliferating and differentiated muscle cells in healthy and dystrophic conditions. Transcriptomic analysis showed that the expression of more than 7000 genes was affected during myogenesis. We identified 769 RBPs, of which 294 were muscle-specific and 49 were uniquely shared with cardiomyocytes. A subset of 32 RBPs(half of which were muscle-specific) was found to be preferentially associated with target mRNAs in either myoblasts(MBs) or myotubes(MTs). A large proportion of catalytic proteins were bound to mRNAs even though they lack classical RNA binding domains. Finally, we showed how the identification of cell-specific RBPs enabled the identification of biomarkers that can separate healthy individuals from dystrophic patients. Our data show how interactome data can shed light on new basic RNA biology as well as provide cell-specific data that can be used for diagnostic purposes.
