Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyel...Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.展开更多
The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory ...The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.展开更多
目的探讨富含亮氨酸重复序列/Ⅲ型纤维连接蛋白4(leucine-rich repeat and fibronectin typeⅢdomain-containing protein 4,LRFN4)在胃癌组织中的表达情况,并分析LRFN4表达水平与胃癌患者临床病理参数和预后的关系。方法收集2017年1月...目的探讨富含亮氨酸重复序列/Ⅲ型纤维连接蛋白4(leucine-rich repeat and fibronectin typeⅢdomain-containing protein 4,LRFN4)在胃癌组织中的表达情况,并分析LRFN4表达水平与胃癌患者临床病理参数和预后的关系。方法收集2017年1月至12月于中山大学附属第一医院胃肠外科中心确诊并行手术治疗的胃癌患者组织标本8对(包含胃癌组织和癌旁正常组织),并选取2004年1月至2005年12月在同一中心行手术治疗的117例胃癌患者的术后组织标本制成胃癌组织芯片。分析LRFN4在癌症基因组图谱(the cancer genome atlas,TCGA)数据库胃癌数据集中的表达情况,应用蛋白质印迹法及实时荧光定量聚合酶链反应检测LRFN4在8对新鲜胃癌组织及癌旁正常组织中的表达,应用免疫组织化学检测LRFN4在胃癌组织芯片中的表达。分析不同LRFN4表达水平的胃癌患者其临床病理参数的差异。应用Kaplan-Meier法分析不同LRFN4表达水平的胃癌患者的预后情况。应用单因素和多因素Cox回归分析法分析胃癌患者预后的影响因素。结果LRFN4在TCGA数据库胃癌数据集的胃癌组织以及新鲜胃癌组织中呈高表达状态。LRFN4高表达的患者,表现出更大的肿瘤大小以及更为进展的T分期、N分期、M分期和TNM分期(均P<0.05),其预后也较差(P<0.001)。单因素和多因素Cox回归分析提示LRFN4在胃癌组织中的高表达是影响胃癌患者预后的独立危险因素(HR=3.898,95%CI 2.273~6.686,P<0.001)。结论胃癌组织中LRFN4高表达与患者较差的预后相关,可能成为预测胃癌患者预后的生物标志物之一。展开更多
Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting...Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome.Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation.However,this mutation was not found in her parents.She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82001282(to PW)and 81960232(to PW)Overseas Students’Innovation and Entrepreneurship Individual Project of Ningxia(2021)(to PW)+1 种基金Youth Talents Supporting Program of Ningxia Medical University and Ningxia,Nos.XT2019018(to PW),TJGC2019081(to PW)College Students’Innovation and En trepreneurship Training Program,No.X202210752038(to FYY)。
文摘Remyelination failure is one of the main characteristics of multiple sclerosis and is potentially correlated with disease progression.Previous research has shown that the extracellular matrix is associated with remyelination failure because remodeling of the matrix often fails in both chronic and progressive multiple sclerosis.Fibronectin aggregates are assembled and persistently exist in chronic multiple sclerosis,thus inhibiting remyelination.Although many advances have been made in the mechanisms and treatment of multiple sclerosis,it remains very difficult for drugs to reach pathological brain tissues;this is due to the complexity of brain structure and function,especially the existence of the blood-brain barrier.Therefore,herein,we review the effects of fibronectin aggregates on multiple sclerosis and the efficacy of different forms of drug delivery across the blood-brain barrier in the treatment of this disease.
基金supported by the National Nature Science Foundation of China,Nos.81371338(to HF)and 82071369(PPY)。
文摘The extracellular matrix surrounding oligodendrocytes plays an important role during myelination and remyelination in the brain.In many cases,the microenvironment surrounding demyelination lesions contains inhibitory molecules,which lead to repair failure.Accordingly,blocking the activity of these inhibitory factors in the extracellular matrix should lead to more successful remyelination.In the central nervous system,oligodendrocytes form the myelin sheath.We performed primary cell culture and found that a natural increase in fibronectin promoted the proliferation of oligodendrocyte progenitors during the initial stage of remyelination while inhibiting oligodendrocyte differentiation.Poly-L-ornithine blocked these inhibitory effects without compromising fibronectin’s pro-proliferation function.Experiments showed that poly-L-ornithine activated the Erk1/2 signaling pathway that is necessary in the early stages of differentiation,as well as PI3K signaling pathways that are needed in the mid-late stages.When poly-L-ornithine was tested in a lysolecithin-induced animal model of focal demyelination,it enhanced myelin regeneration and promoted motor function recovery.These findings suggest that poly-L-ornithine has the potential to be a treatment option for clinical myelin sheath injury.
文摘目的:探讨胎盘生长因子(placental growth factor,PLGF)、可溶性fms样酪氨酸激酶-1(soluble fms-like tyrosine kinase-1,SFLT-1)和糖基化纤连蛋白(glycosylated fibronectin,GLYFN)检测对子痫前期的预测价值。方法:选择在无锡市妇幼保健院就诊的188例孕妇,分154例正常孕妇(对照组)和34例子痫前期患者(子痫组),应用免疫荧光法分别检测其在孕16~18周血清中PLGF、SFLT-1和GLYFN的浓度,比较子痫前期组和对照组各标志物的水平,并使用受试者操作特征曲线(receiver operating characteristic,ROC)对3种标志物的预测价值进行效能评估。结果:在妊娠中期,子痫前期组血清PLGF浓度低于对照组,SFLT-1及GLYFN浓度均高于对照组,3种标志物的差异均有统计学意义(3指标P=0.000)。95%置信区间的ROC曲线下面积(areas under the ROC curve,AUC)为,PLGF为0.941(0.907~0.974),SFLT-1为0.881(0.800~0.962),GLYFN为0.951(0.918~0.985),联合指标SFLT-1和GLYFN、3项指标联合检测在ROC曲线下面积(areas under the ROC curve,AUC)分别为0.968、0.986。结论:PLGF、SFLT-1、GLYFN 3种标志物水平在对照组和子痫前期组均存在明显差异,对子痫前期的发病具有一定的预测价值,SFLT-1联合PLGF、SFLT-1联合GLYFN、3项指标联合检测对子痫前期的预测价值高于任一单项指标。
文摘目的探讨富含亮氨酸重复序列/Ⅲ型纤维连接蛋白4(leucine-rich repeat and fibronectin typeⅢdomain-containing protein 4,LRFN4)在胃癌组织中的表达情况,并分析LRFN4表达水平与胃癌患者临床病理参数和预后的关系。方法收集2017年1月至12月于中山大学附属第一医院胃肠外科中心确诊并行手术治疗的胃癌患者组织标本8对(包含胃癌组织和癌旁正常组织),并选取2004年1月至2005年12月在同一中心行手术治疗的117例胃癌患者的术后组织标本制成胃癌组织芯片。分析LRFN4在癌症基因组图谱(the cancer genome atlas,TCGA)数据库胃癌数据集中的表达情况,应用蛋白质印迹法及实时荧光定量聚合酶链反应检测LRFN4在8对新鲜胃癌组织及癌旁正常组织中的表达,应用免疫组织化学检测LRFN4在胃癌组织芯片中的表达。分析不同LRFN4表达水平的胃癌患者其临床病理参数的差异。应用Kaplan-Meier法分析不同LRFN4表达水平的胃癌患者的预后情况。应用单因素和多因素Cox回归分析法分析胃癌患者预后的影响因素。结果LRFN4在TCGA数据库胃癌数据集的胃癌组织以及新鲜胃癌组织中呈高表达状态。LRFN4高表达的患者,表现出更大的肿瘤大小以及更为进展的T分期、N分期、M分期和TNM分期(均P<0.05),其预后也较差(P<0.001)。单因素和多因素Cox回归分析提示LRFN4在胃癌组织中的高表达是影响胃癌患者预后的独立危险因素(HR=3.898,95%CI 2.273~6.686,P<0.001)。结论胃癌组织中LRFN4高表达与患者较差的预后相关,可能成为预测胃癌患者预后的生物标志物之一。
文摘Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome.Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation.However,this mutation was not found in her parents.She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.
