Cardiovascular diseases(CVDs) remain the leading cause of mortality worldwide,spurring extensive research endeavors to improve understanding and combat these ***,the intricate connections between exposure factors and ...
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Cardiovascular diseases(CVDs) remain the leading cause of mortality worldwide,spurring extensive research endeavors to improve understanding and combat these ***,the intricate connections between exposure factors and CVDs pose a challenge due to the vast number of unstandardized *** objective of our study is to develop a cardiovascular knowledge graph that offers comprehensive and novel insights on a macroscopic *** research commences by introducing a rule-based approach for retrieving cardiovascular *** this study we acquired and integrated more than 2 million biomedical literatures,databases and ontologies pertaining to cardiovascular *** structured dataset of the cardiovascular knowledge graph was constructed using the Resource Description ***,we propose the development of a disease centered schema and sematic layers for cardiovascular knowledge graph,which define the various entity types within the ***,we demonstrate the practical application of predefined queries and the inference of intermediate paths through graph-based knowledge *** summary,we have developed a comprehensive cardiovascular knowledge graph that extends disease associations by integrating various *** knowledge graph not only offers valuable insights for cardiovascular research but also facilitates personalized medicine and improves clinical decision-making in the field of cardiovascular healthcare.
糖基化修饰（O-GlcNAcylation）是一种类似磷酸化的调节性蛋白质翻译后修饰,在糖尿病时,高血糖导致体内O-GlcNAc水平升高。最近研究显示,O-GlcNAc参与糖尿病心血管并发症的发生发展,能通过代谢调控疾病进程,加重心血管损伤。YAP是Hippo通路中参与促进细胞增殖、维持器官大小和组织内稳态的转录共激活因子,YAP与心血管疾病的相关性、重要性已有较多研究报道~。在课题组前期研究中发现YAP在糖尿病心脏中活化,但其活化的具体原因与其经典上游Hippo通路关系不十分密切,提示糖尿病时存在特殊的活化机制。最新的研究表明,YAP活化可能与O-GlcNAc相关,但其在糖尿病及糖尿病心肌病中的具体作用和分子机制尚不清楚。本研究利用2型糖尿病小鼠模型,明确在糖尿病小鼠心脏中,YAP表达增多,促进心肌细胞肥大;抑制YAP可以减轻糖尿病心肌细胞肥大。本研究在不同2型糖尿病病程的小鼠心脏中发现O-GlcNAc水平较正常组高,同时发现O-GlcNAc的表达水平和YAP的表达水平呈线性正相关。利用大鼠乳鼠心肌细胞模型模拟糖尿病代谢环境变化,发现O-GlcNAc水平的上升是引起YAP活化增多的原因。研究进一步在体外实验中利用OGT抑制剂OSMI-1和OGT siRNA证明YAP在O-GlcNAc水平上升时受到OGT的修饰,活化增多。同时,构建in vivo OGT siRNA,在2型糖尿病小鼠上验证OGT对YAP的影响。结果发现在OGT受到抑制的2型糖尿病小鼠的心脏中,YAP活化受到抑制,改善糖尿病心脏功能受损。
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