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心脏发育及相关疾病的分子机制。

The molecular mechanisms of cardiac development and related diseases.

作者信息

Li Yingrui, Du Jianlin, Deng Songbai, Liu Bin, Jing Xiaodong, Yan Yuling, Liu Yajie, Wang Jing, Zhou Xiaobo, She Qiang

机构信息

Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Cardiology, Angiology, Haemostaseology, and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany; DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, Mannheim, Germany.

出版信息

Signal Transduct Target Ther. 2024 Dec 23;9(1):368. doi: 10.1038/s41392-024-02069-8.

Abstract

Cardiac development is a complex and intricate process involving numerous molecular signals and pathways. Researchers have explored cardiac development through a long journey, starting with early studies observing morphological changes and progressing to the exploration of molecular mechanisms using various molecular biology methods. Currently, advancements in stem cell technology and sequencing technology, such as the generation of human pluripotent stem cells and cardiac organoids, multi-omics sequencing, and artificial intelligence (AI) technology, have enabled researchers to understand the molecular mechanisms of cardiac development better. Many molecular signals regulate cardiac development, including various growth and transcription factors and signaling pathways, such as WNT signaling, retinoic acid signaling, and Notch signaling pathways. In addition, cilia, the extracellular matrix, epigenetic modifications, and hypoxia conditions also play important roles in cardiac development. These factors play crucial roles at one or even multiple stages of cardiac development. Recent studies have also identified roles for autophagy, metabolic transition, and macrophages in cardiac development. Deficiencies or abnormal expression of these factors can lead to various types of cardiac development abnormalities. Nowadays, congenital heart disease (CHD) management requires lifelong care, primarily involving surgical and pharmacological treatments. Advances in surgical techniques and the development of clinical genetic testing have enabled earlier diagnosis and treatment of CHD. However, these technologies still have significant limitations. The development of new technologies, such as sequencing and AI technologies, will help us better understand the molecular mechanisms of cardiac development and promote earlier prevention and treatment of CHD in the future.

摘要

心脏发育是一个复杂而精细的过程,涉及众多分子信号和信号通路。研究人员历经漫长历程探索心脏发育,最初的早期研究观察形态变化,随后发展到运用各种分子生物学方法探索分子机制。目前,干细胞技术和测序技术的进步,如人类多能干细胞和心脏类器官的生成、多组学测序以及人工智能(AI)技术,使研究人员能够更好地理解心脏发育的分子机制。许多分子信号调节心脏发育,包括各种生长因子、转录因子以及信号通路,如WNT信号通路、视黄酸信号通路和Notch信号通路。此外,纤毛、细胞外基质、表观遗传修饰和缺氧条件在心脏发育中也发挥着重要作用。这些因素在心脏发育的一个甚至多个阶段起着关键作用。最近的研究还确定了自噬、代谢转变和巨噬细胞在心脏发育中的作用。这些因素的缺陷或异常表达可导致各种类型的心脏发育异常。如今,先天性心脏病(CHD)的管理需要终身护理,主要涉及手术和药物治疗。手术技术的进步和临床基因检测的发展使得CHD能够更早地被诊断和治疗。然而,这些技术仍然存在显著局限性。测序和AI技术等新技术的发展将有助于我们更好地理解心脏发育的分子机制,并在未来促进CHD的早期预防和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdac/11666744/388ca449a210/41392_2024_2069_Fig1_HTML.jpg

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