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基于转录组分析、炎症浸润和分子对接探索人类急性高原病的血液生物标志物和潜在治疗药物。

Exploring the Blood Biomarkers and Potential Therapeutic Agents for Human Acute Mountain Sickness Based on Transcriptomic Analysis, Inflammatory Infiltrates and Molecular Docking.

机构信息

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100080, China.

出版信息

Int J Mol Sci. 2024 Oct 21;25(20):11311. doi: 10.3390/ijms252011311.

Abstract

A high-altitude, low-pressure hypoxic environment has severe effects on the health and work efficiency of its residents, and inadequate preventive measures and adaptive training may lead to the occurrence of AMS. Acute exposure to hypoxia conditions can have a less-favorable physiological effect on the human immune system. However, the regulation of the immune system in high-altitude environments is extremely complex and remains elusive. This study integrated system bioinformatics methods to screen for changes in immune cell subtypes and their associated targets. It also sought potential therapeutically effective natural compound candidates. The present study observed that monocytes, M1 macrophages and NK cells play a crucial role in the inflammatory response in AMS. IL15RA, CD5, TNFSF13B, IL21R, JAK2 and CXCR3 were identified as hub genes, and JAK2 was positively correlated with monocytes; TNFSF13B was positively correlated with NK cells. The natural compound monomers of jasminoidin and isoliquiritigenin exhibited good binding affinity with JAK2, while dicumarol and artemotil exhibited good binding affinity with TNFSF13B, and all are expected to become a potential therapeutic agents.

摘要

高海拔、低气压缺氧环境对居民的健康和工作效率有严重影响,预防措施不足和适应性训练不当可能导致急性高原病的发生。急性暴露于缺氧环境对人体免疫系统的生理影响不太有利。然而,高海拔环境中免疫系统的调节极其复杂,目前仍难以捉摸。本研究综合系统生物信息学方法筛选免疫细胞亚型及其相关靶点的变化,并寻找潜在的治疗有效天然化合物候选物。本研究观察到,单核细胞、M1 巨噬细胞和 NK 细胞在 AMS 的炎症反应中起关键作用。IL15RA、CD5、TNFSF13B、IL21R、JAK2 和 CXCR3 被鉴定为枢纽基因,其中 JAK2 与单核细胞呈正相关;TNFSF13B 与 NK 细胞呈正相关。茉莉酮酸和异甘草素的天然化合物单体与 JAK2 具有良好的结合亲和力,而双香豆素和青蒿素与 TNFSF13B 具有良好的结合亲和力,均有望成为潜在的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73d9/11508554/dbe7836112fc/ijms-25-11311-g001.jpg

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