The MicroRNA network in sepsis: from biomarker discovery to novel targeted therapeutic strategies.

IF 5.5 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Jianyi Xie, Lingxuan Tang, Wangzheqi Zhang, Changli Wang
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引用次数: 0

Abstract

Sepsis is a life-threatening multiple-organ dysfunction syndrome triggered by infection and mediated by host immune dysregulation. Its complex pathophysiological mechanisms and the lack of effective diagnostic and therapeutic approaches make it a major challenge for the global healthcare system. As key molecules in post-transcriptional gene regulation, microRNAs (miRNAs) play crucial roles in immune dyshomeostasis, inflammatory storms, and organ damage during sepsis, and have emerged as a research focus in this field in recent years. This review summarizes the research progress of miRNAs in sepsis, with a focus on their expression characteristics, regulatory mechanisms, and clinical translational value. miRNAs regulate inflammatory responses by targeting core signaling pathways such as the Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) pathway. The specific mechanisms include: blocking upstream pathway activation by targeting TLR ligands or adaptor proteins; directly regulating NF-κB subunits to inhibit the transcription of pro-inflammatory genes; modulating negative feedback loops; and interacting with other signaling cascades. Furthermore, certain miRNAs act as both key regulators of immune responses and potential diagnostic/prognostic biomarkers. In terms of organ damage, miRNAs display organ-specific characteristics by working as specific regulatory molecules in sepsis-associated cardiac, hepatic, and cerebral injuries. They affect organ function by targeting pathways such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT). In terms of clinical translational value, miRNAs derived from human serum/plasma have shown significant potential in sepsis diagnosis, treatment guidance, and prognosis prediction. By dissecting the regulatory network of miRNAs in sepsis, this review not only provides a theoretical basis for understanding the complex pathophysiology of sepsis but also identifies key directions for developing miRNA-based precision diagnostic and therapeutic strategies (e.g. combined detection of multiple biomarkers and targeted delivery systems). It is anticipated to offer novel solutions for improving the prognosis of sepsis patients and reducing mortality.

脓毒症中的MicroRNA网络:从生物标志物发现到新的靶向治疗策略。
脓毒症是一种危及生命的多器官功能障碍综合征,由感染引发,由宿主免疫失调介导。其复杂的病理生理机制和缺乏有效的诊断和治疗方法使其成为全球卫生保健系统的主要挑战。microRNAs (miRNAs)作为转录后基因调控的关键分子,在脓毒症期间的免疫失衡、炎症风暴、器官损伤等过程中发挥着至关重要的作用,近年来成为该领域的研究热点。本文综述了mirna在脓毒症中的研究进展,重点介绍了其表达特征、调控机制和临床转化价值。mirna通过靶向toll样受体(TLR)/核因子κB (NF-κB)通路等核心信号通路调节炎症反应。具体机制包括:通过靶向TLR配体或接头蛋白阻断上游通路激活;直接调控NF-κB亚基抑制促炎基因的转录;调制负反馈回路;并与其他信号级联相互作用。此外,某些mirna既是免疫反应的关键调节因子,也是潜在的诊断/预后生物标志物。在器官损伤方面,mirna通过在败血症相关的心脏、肝脏和脑损伤中作为特异性调节分子发挥器官特异性特征。它们通过靶向磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B (AKT)和Janus激酶/信号转导和转录激活因子(JAK/STAT)等途径影响器官功能。在临床转化价值方面,来自人血清/血浆的mirna在脓毒症诊断、治疗指导和预后预测方面显示出巨大的潜力。通过剖析mirna在脓毒症中的调控网络,本综述不仅为理解脓毒症复杂的病理生理提供了理论基础,而且为开发基于mirna的精准诊断和治疗策略(如联合检测多种生物标志物和靶向递送系统)指明了关键方向。期望为改善脓毒症患者的预后和降低死亡率提供新的解决方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
20.00
自引率
0.00%
发文量
25
审稿时长
>12 weeks
期刊介绍: Critical Reviews in Clinical Laboratory Sciences publishes comprehensive and high quality review articles in all areas of clinical laboratory science, including clinical biochemistry, hematology, microbiology, pathology, transfusion medicine, genetics, immunology and molecular diagnostics. The reviews critically evaluate the status of current issues in the selected areas, with a focus on clinical laboratory diagnostics and latest advances. The adjective “critical” implies a balanced synthesis of results and conclusions that are frequently contradictory and controversial.
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