RIG012 assists in the treatment of pneumonia by inhibiting the RIG-I-like receptor signaling pathway.

IF 3.1 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

Frontiers in Medicine Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI:10.3389/fmed.2024.1501761

Shi Zhang, Hanbing Chen, Jianfeng Xie, Lili Huang

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引用次数: 0

Abstract

Objective: Pneumonia is a common clinical condition primarily treated with antibiotics and organ support. Exploring the pathogenesis to identify therapeutic targets may aid in the adjunct treatment of pneumonia and improve survival rates.

Methods: Transcriptomic data from peripheral blood of 183 pneumonia patients were analyzed using Gene Set Variation Analysis (GSVA) and univariate Cox regression analysis to identify signaling pathways associated with pneumonia mortality. A pneumonia mouse model was established via airway injection of Klebsiella pneumoniae, and pathway-specific blockers were administered via tail vein infusion to assess whether the identified signaling pathways impact the mortality in pneumonia.

Results: The combination of GSVA and Cox analysis revealed 17 signaling pathways significantly associated with 28-day mortality in pneumonia patients (P < 0.05). Notably, the RIG-I-like receptor signaling pathway exhibited the highest hazard ratio of 2.501 with a 95% confidence interval of [1.223-5.114]. Infusion of RIG012 via the tail vein effectively inhibited the RIG-I-like receptor signaling pathway, significantly ameliorated lung injury in pneumonia mice, reduced pulmonary inflammatory responses, and showed a trend toward improved survival rates.

Conclusion: RIG012 may represent a novel adjunctive therapeutic agent for pneumonia.

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RIG012 通过抑制 RIG-I 样受体信号通路来辅助治疗肺炎。

目的：肺炎是一种常见的临床病症，主要通过抗生素和器官支持治疗。探索发病机制以确定治疗靶点可能有助于肺炎的辅助治疗并提高存活率：方法：使用基因组变异分析（Gene Set Variation Analysis，GSVA）和单变量考克斯回归分析法分析了 183 名肺炎患者外周血的转录组数据，以确定与肺炎死亡率相关的信号通路。通过气道注射肺炎克雷伯氏菌建立了肺炎小鼠模型，并通过尾静脉输注途径特异性阻断剂来评估所发现的信号通路是否会影响肺炎死亡率：结果：结合 GSVA 和 Cox 分析发现，17 条信号通路与肺炎患者 28 天的死亡率显著相关（P < 0.05）。值得注意的是，RIG-I 样受体信号通路的危险比最高，为 2.501，95% 置信区间为[1.223-5.114]。通过尾静脉输注 RIG012 能有效抑制 RIG-I 样受体信号通路，显著改善肺炎小鼠的肺损伤，减轻肺部炎症反应，并显示出改善存活率的趋势：结论：RIG012 可能是一种新型的肺炎辅助治疗药物。

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

Frontiers in Medicine Medicine-General Medicine

CiteScore

5.10

自引率

5.10%

发文量

3710

审稿时长

12 weeks

期刊介绍： Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate - the use of patient-reported outcomes under real world conditions - the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines - the scientific bases for guidelines and decisions from regulatory authorities - access to medicinal products and medical devices worldwide - addressing the grand health challenges around the world