Abstract

Sepsis-induced acute respiratory distress syndrome (ARDS) poses a grave danger to life, resulting from sepsis-induced multi-organ failure. Although ferroptosis, a form of iron-dependent lipid peroxidative cell death, has been associated with sepsis-induced ARDS, the specific mechanisms are not fully understood. In this study, we utilized WGCNA, PPI, friends analysis, and six machine learning techniques (Lasso, SVM, RFB, XGBoost, AdaBoost, and LightGBM) to pinpoint STAT3 as a potential diagnostic marker. A significant increase in monocyte and neutrophil levels was observed in patients with sepsis-induced ARDS, as revealed by immune infiltration analyses, when compared to controls. Moreover, there was a positive correlation between STAT3 expression and the level of infiltration. Single-cell analysis uncovered a notable disparity in B-cell expression between sepsis and sepsis-induced ARDS. Furthermore, in vitro experiments using LPS-treated human bronchial epithelial cells (BEAS-2B) and THP1 cells demonstrated a significant increase in STAT3 phosphorylation expression. Additionally, the inhibition of STAT3 phosphorylation by Stattic effectively prevented LPS-induced ferroptosis in both BEAS-2B and THP1 cells. This indicates that the activation of STAT3 phosphorylation promotes ferroptosis in human bronchial epithelial cells in response to LPS. In summary, this research has discovered and confirmed STAT3 as a potential biomarker for the diagnosis and treatment of sepsis-induced ARDS.

中文翻译：

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STAT3介导的铁死亡涉及脓毒症相关的急性呼吸窘迫综合征

摘要

脓毒症引起的急性呼吸窘迫综合征（ARDS）对生命造成严重威胁，是由脓毒症引起的多器官衰竭引起的。尽管铁死亡（铁依赖性脂质过氧化细胞死亡的一种形式）与脓毒症引起的ARDS有关，但其具体机​​制尚不完全清楚。在这项研究中，我们利用 WGCNA、PPI、朋友分析和六种机器学习技术（Lasso、SVM、RFB、XGBoost、AdaBoost 和 LightGBM）将 STAT3 确定为潜在的诊断标记。免疫浸润分析显示，与对照组相比，脓毒症引起的 ARDS 患者的单核细胞和中性粒细胞水平显着增加。此外，STAT3表达与浸润水平呈正相关。单细胞分析发现脓毒症和脓毒症诱导的 ARDS 之间 B 细胞表达存在显着差异。此外，使用 LPS 处理的人支气管上皮细胞 (BEAS-2B) 和 THP1 细胞进行的体外实验表明 STAT3 磷酸化表达显着增加。此外，Stattic 抑制 STAT3 磷酸化可有效防止 BEAS-2B 和 THP1 细胞中 LPS 诱导的铁死亡。这表明 STAT3 磷酸化的激活促进了人支气管上皮细胞响应 LPS 的铁死亡。总之，本研究发现并证实STAT3作为诊断和治疗脓毒症引起的ARDS的潜在生物标志物。