集成的多omics的菌相关的分子亚型表征和生物标志物鉴定在败血症
1Department of Emergency Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
Scientific reports
|December 1, 2025
概括
这项研究确定了四个关键的菌相关基因 (MAG) 作为诊断败血症和分层患者的生物标志物. 据证明,NUP93可以恢复髓,为败血症治疗提供新的途径.
科学领域:
- 生物化学 生物化学
- 遗传学 是一个遗传学.
- 免疫学 免疫学 免疫学
背景情况:
- 败血症是一种危及生命的疾病,死亡率和异质性很高.
- 线粒体,去除受损的线粒体,可以减轻与败血症相关的损伤.
- 对于败血症的诊断和治疗,关键的菌因相关基因 (MAG) 尚未得到很好的定义.
研究的目的:
- 系统地识别和验证用于败血症诊断,分层和免疫调节的MAG.
- 探索NUP93在败血症诱导的线粒菌中的作用.
- 根据MAG表达来定义毒症的分子亚型.
主要方法:
- 集成批量和单细胞RNA-seq数据用于差异表达分析,WGCNA和机器学习.
- 进行了免疫透分析 (ESTIMATE,ssGSEA) 和共识聚类.
- 在LPS刺激的RAW264.7细胞中功能验证NUP93.
主要成果:
- 确定了四种MAG生物标志物 (RPL18,PRPF8,NUP93,CUL1),具有高诊断功率 (AUC为0.957-0.990).
- 将败血症患者分层分为不同的分子亚型,具有不同的免疫格局.
- 通过影响PINK1和LC3B水平,NUP93的过度表达在体外恢复了线粒.
结论:
- RPL18,PRPF8,NUP93和CUL1都是强大的诊断性MAG生物标志物用于败血症.
- 这些MAG定义了具有不同免疫微环境的分子亚型.
- NUP93促进了败血症中的线粒,提供了潜在的治疗点.
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