Sun Lichao, Li Xingliang, Hou Hailong, Yang John Zhiyong
Department of Emergency, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Emergency, Meihekou Central Hospital, Tonghua, Jilin, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Oct;1871(7):167905. doi: 10.1016/j.bbadis.2025.167905. Epub 2025 May 16.
Sepsis is a critical condition characterized by a dysregulated immune response to infection, leading to widespread inflammation, tissue damage, organ failure, and often death. It is a leading cause of morbidity and mortality, particularly in intensive care units, due to its complex pathophysiology involving immune dysregulation, coagulation abnormalities, and metabolic disturbances. Pyogenic liver abscess (PLA) is a significant cause, especially in developing countries where its incidence is rising. PLA, an infectious liver disease, can lead to sepsis, termed sepsis secondary to PLA (SLA). This study aimed to identify key genes and non-coding RNAs involved in the pathogenesis and treatment of SLA. We performed RNA sequencing on peripheral blood samples from healthy individuals, SLA patients, and SLA patients after seven days of therapy. Integrated bioinformatics analysis identified 4549 differentially expressed (DE) mRNAs, 9808 DE lncRNAs, 467 DE circRNAs, and 292 DE miRNAs between SLA patients and healthy controls. Additionally, 3199 mRNAs, 6018 lncRNAs, 161 circRNAs, and 132 miRNAs were differentially expressed between SLA patients before and after seven days of therapy. DE mRNAs in both comparisons were associated with immune responses; DE lncRNAs were linked to the B cell receptor signaling pathway and osteoclast differentiation; DE circRNAs were connected to Chagas disease and the B cell receptor signaling pathway; and DE miRNAs were implicated in the MAPK and estrogen signaling pathways. We constructed lncRNA/circRNA-miRNA-mRNA networks to explore regulatory relationships, validating 16 ceRNAs through RT-PCR. These findings provide new insights into SLA pathogenesis and treatment, potentially guiding the development of novel therapies.
脓毒症是一种危急病症，其特征是对感染的免疫反应失调，导致广泛的炎症、组织损伤、器官衰竭，且常导致死亡。由于其复杂的病理生理学涉及免疫失调、凝血异常和代谢紊乱，脓毒症是发病和死亡的主要原因，尤其是在重症监护病房。化脓性肝脓肿（PLA）是一个重要原因，特别是在发病率不断上升的发展中国家。PLA作为一种感染性肝病，可导致脓毒症，称为PLA继发脓毒症（SLA）。本研究旨在确定参与SLA发病机制和治疗的关键基因和非编码RNA。我们对健康个体、SLA患者以及治疗七天后的SLA患者的外周血样本进行了RNA测序。综合生物信息学分析确定了SLA患者与健康对照之间有4549个差异表达（DE）mRNA、9808个DE lncRNA、467个DE circRNA和292个DE miRNA。此外，治疗七天前后的SLA患者之间有3199个mRNA、6018个lncRNA、161个circRNA和132个miRNA差异表达。两个比较中的DE mRNA均与免疫反应相关；DE lncRNA与B细胞受体信号通路和破骨细胞分化有关；DE circRNA与恰加斯病和B细胞受体信号通路有关；DE miRNA与MAPK和雌激素信号通路有关。我们构建了lncRNA/circRNA-miRNA-mRNA网络以探索调控关系，并通过RT-PCR验证了16个ceRNA。这些发现为SLA的发病机制和治疗提供了新的见解，可能会指导新型疗法的开发。
