琥珀酰辅酶A:3-酮酸辅酶A转移酶(Succinyl-CoA:3-ketoacid CoA transferase,SCOT),基因位点标记OXCT1,EC 2.8.3.5,存在于多个组织的线粒体内,能将乙酰乙酸转化为乙酰乙酰辅酶A,乙酰乙酰辅酶A在乙酰乙酰辅酶A硫解酶(T2)的作用下分解为乙...琥珀酰辅酶A:3-酮酸辅酶A转移酶(Succinyl-CoA:3-ketoacid CoA transferase,SCOT),基因位点标记OXCT1,EC 2.8.3.5,存在于多个组织的线粒体内,能将乙酰乙酸转化为乙酰乙酰辅酶A,乙酰乙酰辅酶A在乙酰乙酰辅酶A硫解酶(T2)的作用下分解为乙酰辅酶A后进入三羧酸循环。该酶是酮体代谢过程中的关键限速酶。先天性SCOT缺乏为常染色体隐性遗传病,1972年J.T.Tildon等首次进行了报道[1]。现对1例确诊的OXCT1基因突变导致的先天性SCOT缺乏病例进行分析总结,并通过复习相关文献归纳总结其特征,以便提高临床工作中对该病的认识,达到及时确诊、早期治疗的目的。展开更多
Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughp...Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughput gene expression data using weighted co-expression network analysis(WGCNA)to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus(GEO)database.Normalization,quality control,filtration,and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules.Furthermore,the correlation coefiidents between the modules and clinical traits were computed to identify the key modules.Gene ontology and pathway enrichment analyses were performed on the key module genes.The STRING database was used to construct the protein-protein interaction(PPI)networks,which were further analyzed by Cytoscape app(MCODE).Finally,validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules,among which 6 modules were identified as the key module relating to AD occurrence.These key modules are primarily involved in chemical synaptic transmission(G0:0007268),the tricarboxylic acid(TCA)cycle and respiratory electron transport(R-HSA-1428517).WDR47,OXCT1,C3orfl4,ATP6V1A,SLC25A14,NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses,we identified the hub genes of AD,including WDR47,0XCT1,C3orfl4i ATP6V1A,SLC25A14 and NAPB.Among them,three hub genes(ATP6V1A,SLC25A14,OXCT1)might contribute to AD pathogenesis through pathway of TCA cycle.展开更多
文摘琥珀酰辅酶A:3-酮酸辅酶A转移酶(Succinyl-CoA:3-ketoacid CoA transferase,SCOT),基因位点标记OXCT1,EC 2.8.3.5,存在于多个组织的线粒体内,能将乙酰乙酸转化为乙酰乙酰辅酶A,乙酰乙酰辅酶A在乙酰乙酰辅酶A硫解酶(T2)的作用下分解为乙酰辅酶A后进入三羧酸循环。该酶是酮体代谢过程中的关键限速酶。先天性SCOT缺乏为常染色体隐性遗传病,1972年J.T.Tildon等首次进行了报道[1]。现对1例确诊的OXCT1基因突变导致的先天性SCOT缺乏病例进行分析总结,并通过复习相关文献归纳总结其特征,以便提高临床工作中对该病的认识,达到及时确诊、早期治疗的目的。
基金Fund supported by the National Natural Science Foundation of China(81460598 and 81660644)the Natural Science Foundation of Jiangsu Province(BK20170267)Guangxi Special Fund for the First-Class Discipline Construction Project(05019038).
文摘Objective Alzheimer's disease(AD)is the most common cause of dementia.The pathophysiology of the disease mostly remains unearthed,thereby challenging drug development for AD.This study aims to screen high throughput gene expression data using weighted co-expression network analysis(WGCNA)to explore the potential therapeutic targets.Methods The dataset of GSE36980 was obtained from the Gene Expression Omnibus(GEO)database.Normalization,quality control,filtration,and soft-threshold calculation were carried out before clustering the co-expressed genes into different modules.Furthermore,the correlation coefiidents between the modules and clinical traits were computed to identify the key modules.Gene ontology and pathway enrichment analyses were performed on the key module genes.The STRING database was used to construct the protein-protein interaction(PPI)networks,which were further analyzed by Cytoscape app(MCODE).Finally,validation of hub genes was conducted by external GEO datasets of GSE 1297 and GSE 28146.Results Co-expressed genes were clustered into 27 modules,among which 6 modules were identified as the key module relating to AD occurrence.These key modules are primarily involved in chemical synaptic transmission(G0:0007268),the tricarboxylic acid(TCA)cycle and respiratory electron transport(R-HSA-1428517).WDR47,OXCT1,C3orfl4,ATP6V1A,SLC25A14,NAPB were found as the hub genes and their expression were validated by external datasets.Conclusions Through modules co-expression network analyses and PPI network analyses,we identified the hub genes of AD,including WDR47,0XCT1,C3orfl4i ATP6V1A,SLC25A14 and NAPB.Among them,three hub genes(ATP6V1A,SLC25A14,OXCT1)might contribute to AD pathogenesis through pathway of TCA cycle.
