生物标志物和分子信号通路在急性肺损伤中的作用。

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-01-26 DOI:10.1111/fcp.12987
Pakter Niri, Achintya Saha, Subramanyam Polopalli, Mohit Kumar, Sanghita Das, Pronobesh Chattopadhyay
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引用次数: 0

摘要

背景:急性肺损伤(ALI)是由细菌、真菌和病毒感染引起的。当病原体侵入肺部时,免疫系统会产生细胞因子、趋化因子和干扰素,以促进吞噬细胞的浸润。细胞因子、趋化因子和干扰素的过量产生会导致过度活跃的免疫反应和病理性高炎症状态,从而引发 ALI。迄今为止,尽管已知有中性粒细胞胞外捕获物(NETs)和活性氧(ROS)等炎症介质,但仍没有治疗 ALI 的特效药物:因此,本综述的主要目的是提供关于控制中性粒细胞胞外捕获物(NETs)、活性氧(ROS)形成的机制以及 ALI 发病过程中其他相关过程的清晰概述。此外,我们还讨论了上皮和内皮损伤指标的重要性以及与 ALI 相关的几种分子信号通路:方法:我们从 Web of Science、Scopus、PubMed 和 Google Scholar 上查阅了有关 ALI、NETs、ROS、炎症、生物标志物、Toll 和核苷酸结合寡聚域(NOD)样受体、肺泡损伤、促炎细胞因子以及上皮/内皮损伤的单独或组合的文献:本综述总结了 ALI 的主要临床表现,包括上皮和内皮生物标志物、NETs、ROS 和模式识别受体(PRRs)的调节和不同功能:然而,目前还没有针对 ALI 的特定药物(包括疫苗)。此外,目前还缺乏有效的诊断工具,现有治疗生物标志物的预测合理性也很差。因此,需要开展广泛而精确的研究,通过应用人工智能技术、基于结构的药物设计、硅内方法和药物再利用,加快药物测试和开发进程。
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Role of biomarkers and molecular signaling pathways in acute lung injury

Background

Acute lung injury (ALI) is caused by bacterial, fungal, and viral infections. When pathogens invade the lungs, the immune system responds by producing cytokines, chemokines, and interferons to promote the infiltration of phagocytic cells, which are essential for pathogen clearance. Their excess production causes an overactive immune response and a pathological hyper-inflammatory state, which leads to ALI. Until now, there is no particular pharmaceutical treatment available for ALI despite known inflammatory mediators like neutrophil extracellular traps (NETs) and reactive oxygen species (ROS).

Objectives

Therefore, the primary objective of this review is to provide the clear overview on the mechanisms controlling NETs, ROS formation, and other relevant processes during the pathogenesis of ALI. In addition, we have discussed the significance of epithelial and endothelial damage indicators and several molecular signaling pathways associated with ALI.

Methods

The literature review was done from Web of Science, Scopus, PubMed, and Google Scholar for ALI, NETs, ROS, inflammation, biomarkers, Toll- and nucleotide-binding oligomerization domain (NOD)-like receptors, alveolar damage, pro-inflammatory cytokines, and epithelial/endothelial damage alone or in combination.

Results

This review summarized the main clinical signs of ALI, including the regulation and distinct function of epithelial and endothelial biomarkers, NETs, ROS, and pattern recognition receptors (PRRs).

Conclusion

However, no particular drugs including vaccine for ALI has been established. Furthermore, there is a lack of validated diagnostic tools and a poor predictive rationality of current therapeutic biomarkers. Hence, extensive and precise research is required to speed up the process of drug testing and development by the application of artificial intelligence technologies, structure-based drug design, in-silico approaches, and drug repurposing.

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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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Issue Information The synergy between alkylating agents and ERCC1-XPF inhibitors is p53 dependent. Capivasertib augments chemotherapy via Akt inhibition in preclinical small cell lung cancer models. New ways to repurpose salmeterol in an animal model of fibromyalgia. Induction of Ca2+ signaling and cytotoxic responses of human lung fibroblasts upon an antihistamine drug oxatomide treatment and evaluating the protective effects of Ca2+ chelating.
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