Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.

IF 6.3 1区 医学 Q1 DERMATOLOGY
Burns & Trauma Pub Date : 2024-05-06 eCollection Date: 2024-01-01 DOI:10.1093/burnst/tkae006
Mingzheng Wu, Bobin Mi, Liu Liu, Haoli Ma, Cheng Jiang, Shan Jiang, Yulin Li, Yan Zhao
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引用次数: 0

Abstract

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

与脓毒性休克相关的基因多态性、生物标志物和信号通路:从诊断到治疗目标。
脓毒性休克是脓毒症的一种严重形式,其特点是全球死亡率高且遗传性显著。长期以来,临床医生一直对基因的差异表达感到困惑,这给脓毒性休克的早期诊断和及时治疗带来了挑战。基因多态性在决定脓毒性休克的易感性、死亡率和预后方面起着至关重要的作用。研究表明,致病基因可通过特定等位基因导致脓毒性休克,而保护基因则可对受影响的个体产生有益影响。尽管存在许多与脓毒性休克相关的生物标志物,但其临床应用仍然有限。因此,需要进一步研究以确定有助于早期预防、诊断和风险分层的特定生物标志物。脓毒性休克与多种信号通路密切相关,包括toll样受体2/toll样受体4、肿瘤坏死因子-α、磷脂酰肌醇3-激酶/蛋白激酶B、丝裂原活化蛋白激酶、核因子κB、Janus激酶/信号转导和转录激活因子、哺乳动物雷帕霉素靶标、NOD样受体热蛋白结构域相关蛋白3和缺氧诱导因子-1通路。了解了这些信号通路的调控,就可能找到治疗靶点,从而开发出治疗败血症或脓毒性休克的新型药物。总之,识别脓毒性休克发生过程中的不同基因表达可让医生在早期根据风险对患者进行分层。此外,辅助检查还能帮助医生确定相关信号通路中的治疗靶点,促进早期诊断和治疗,降低死亡率,改善脓毒性休克患者的预后。虽然脓毒性休克的基因多态性、特异性生物标志物和信号通路的研究已经取得了重大进展,但其临床应用和普及仍任重道远。
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
Burns & Trauma
Burns & Trauma 医学-皮肤病学
CiteScore
8.40
自引率
9.40%
发文量
186
审稿时长
6 weeks
期刊介绍: The first open access journal in the field of burns and trauma injury in the Asia-Pacific region, Burns & Trauma publishes the latest developments in basic, clinical and translational research in the field. With a special focus on prevention, clinical treatment and basic research, the journal welcomes submissions in various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, and the prevention and regeneration of burns and trauma injuries. With an expert Editorial Board and a team of dedicated scientific editors, the journal enjoys a large readership and is supported by Southwest Hospital, which covers authors'' article processing charges.
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