IDENTIFYING POTENTIAL KEY FERROPTOSIS-RELATED GENES AND THERAPEUTIC DRUGS IN SEPSIS-INDUCED ARDS BY BIOINFORMATICS AND EXPERIMENTAL VERIFICATION.

IF 2.7 3区 医学 Q2 CRITICAL CARE MEDICINE
SHOCK Pub Date : 2025-01-01 Epub Date: 2024-09-11 DOI:10.1097/SHK.0000000000002478
Man Li, Xiaojing Ren, Futai Lu, Shenyue Pang, Ling Ding, Lei Wang, Shuhua Xie, Licheng Geng, Jiangang Xu, Tao Yang
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引用次数: 0

Abstract

Abstract: Background: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine. Method: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus was analyzed to identify ferroptosis-related differentially expressed genes. Enrichment analysis and protein-protein interaction network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. Traditional Chinese medicine targeting hub genes was predicted via SymMap database and was verified. Results: Sixteen ferroptosis-related differentially expressed genes were obtained, among which the top four genes ( IL1B , TXN , MAPK3 , HSPB1 ) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The competitive endogenous RNA network showed 26 microRNAs and 38 long noncoding RNA. Ferroptosis occurred and the expressions of IL1B , MAPK3 , and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells. Sea buckthorn alleviated septic lung injury and affected hub genes expression. Conclusions: Ferroptosis-related genes of IL1B , MAPK 3, and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.

通过生物信息学和实验验证,确定脓毒症诱发 ARDS 的潜在关键铁变态反应相关基因和治疗药物。
背景:急性呼吸窘迫综合征(ARDS急性呼吸窘迫综合征(ARDS)是一种严重的病理过程,死亡率很高。铁蛋白沉积在脓毒症中起着关键作用,但其在脓毒症诱发的ARDS中的调控机制尚不清楚。我们的目的是确定脓毒症 ARDS 中与铁蛋白沉积相关的关键基因,并研究中医治疗方法:方法:分析从基因表达总库(Gene Expression Omnibus,GEO)获得的脓毒症诱导的ARDS数据集,以确定与铁中毒相关的差异表达基因(FRDEGs)。通过富集分析和蛋白质-蛋白质相互作用(PPI)网络构建来确定枢纽基因。分析了免疫细胞浸润并构建了竞争性内源性 RNA(ceRNA)网络。分析了中枢基因在脓毒症 ARDS 中的诊断价值,并检测了铁变态反应的发生和中枢基因的表达。通过 SymMap 数据库预测并验证了针对枢纽基因的中药:结果:得到了16个FRDEGs,其中前四个基因(IL1B、TXN、MAPK3、HSPB1)被选为中枢基因,它们可能是脓毒性ARDS的潜在诊断标志物。免疫测定显示,脓毒症诱发的ARDS和中枢基因与免疫细胞密切相关。ceRNA网络显示了26个microRNA和38个长非编码RNA(lncRNA)。在脓毒症ARDS小鼠和LPS挑战的人肺泡上皮细胞(HPAEpiCs)中,发生了铁变态反应,IL1B、MAPK3和TXN的表达增加。沙棘能缓解脓毒性肺损伤并影响枢纽基因的表达:结论:IL1B、MAPK3 和 TXN 等铁素体相关基因是脓毒症诱发 ARDS 的潜在诊断基因。沙棘可作为 ARDS 的治疗药物。这项研究为脓毒症 ARDS 的治疗提供了新的方向。
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来源期刊
SHOCK
SHOCK 医学-外科
CiteScore
6.20
自引率
3.20%
发文量
199
审稿时长
1 months
期刊介绍: SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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