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

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.

Keywords: AMS; bioinformatics; inflammatory infiltrates; molecular docking.

MeSH terms

  • Altitude Sickness* / blood
  • Altitude Sickness* / drug therapy
  • Altitude Sickness* / genetics
  • Biomarkers*
  • Gene Expression Profiling / methods
  • Humans
  • Inflammation / blood
  • Inflammation / genetics
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Molecular Docking Simulation*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Transcriptome

Substances

  • Biomarkers
  • Janus Kinase 2
  • JAK2 protein, human