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

被引:3
作者
Wu, Mingzheng [1 ]
Mi, Bobin [2 ]
Liu, Liu [3 ]
Ma, Haoli [4 ]
Jiang, Cheng [1 ]
Jiang, Shan [1 ]
Li, Yulin [1 ]
Zhao, Yan [1 ]
机构
[1] Wuhan Univ, Zhongnan Hosp, Emergency Med Ctr, 169 Donghu Rd, Wuhan 430061, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthoped, 1277 Jiefang Ave, Wuhan 430022, Peoples R China
[3] Hubei Univ, Coll Educ, 368 Youyi Ave, Wuhan 430062, Hubei, Peoples R China
[4] Wuhan Univ, Zhongnan Hosp, Dept Biol Repositories, 169 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
关键词
Septic shock; Sepsis; Gene polymorphism; Pathogenic gene; Biomarker; Signaling pathway; NF-KAPPA-B; ACUTE LUNG INJURY; CARDIAC DYSFUNCTION; BIOINFORMATICS ANALYSIS; RISK STRATIFICATION; EXPRESSION PROFILES; INCREASED MORTALITY; NITRIC-OXIDE; KEY GENES; SEPSIS;
D O I
10.1093/burnst/tkae006
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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-alpha, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor kappa B, 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.
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页数:19
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共 160 条
[1]  
Aggarwal BB, 2000, ANN RHEUM DIS, V59, P6
[2]   Potential Value of TNF-α (-376 G/A) Polymorphism and Cystatin C (CysC) in the Diagnosis of Sepsis Associated Acute Kidney Injury (S-AK I) and Prediction of Mortality in Critically Ill patients [J].
Al-Amodi, Hiba S. ;
Abdelsattar, Shimaa ;
Kasemy, Zeinab A. ;
Bedair, Hanan M. ;
Elbarbary, Hany S. ;
Kamel, Hala F. M. .
FRONTIERS IN MOLECULAR BIOSCIENCES, 2021, 8
[3]   Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial [J].
Alam, Nadia ;
Oskam, Erick ;
Stassen, Patricia M. ;
van Exter, Pieternel ;
van de Ven, Peter M. ;
Haak, Harm R. ;
Holleman, Frits ;
van Zanten, Arthur ;
van Leeuwen-Nguyen, Hien ;
Bon, Victor ;
Duineveld, Bart A. M. ;
Panday, Rishi S. Nannan ;
Kramer, Mark H. H. ;
Nanayakkara, Prabath W. B. .
LANCET RESPIRATORY MEDICINE, 2018, 6 (01) :40-50
[4]   Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity [J].
Andaluz-Ojeda, David ;
Bryant Nguyen, H. ;
Meunier-Beillard, Nicolas ;
Cicuendez, Ramon ;
Quenot, Jean-Pierre ;
Calvo, Dolores ;
Dargent, Auguste ;
Zarca, Esther ;
Andres, Cristina ;
Nogales, Leonor ;
Maria Eiros, Jose ;
Tamayo, Eduardo ;
Gandia, Francisco ;
Bermejo-Martin, Jesus F. ;
Emmanuel Charles, Pierre .
ANNALS OF INTENSIVE CARE, 2017, 7
[5]  
Arnalich F, 1996, REGUL PEPTIDES, V65, P115, DOI 10.1016/S0167-0115(96)00080-8
[6]   The Impact of Antibiotics Administration on Mortality for Time in Sepsis and Septic Shock Patients including Possible Reasons for Delayed Administration in Malaysia [J].
Arulappen, Ann L. ;
Danial, Monica ;
Ng, Ling Wei ;
Teoh, Jui Chang .
ANTIBIOTICS-BASEL, 2022, 11 (09)
[7]   mTOR pathway mediates endoplasmic reticulum stress-induced CD4+ T cell apoptosis in septic mice [J].
Bai, Guangxu ;
Wang, Hao ;
Cui, Na .
APOPTOSIS, 2022, 27 (9-10) :740-750
[8]   Procalcitonin Exerts a Mediator Role in Septic Shock Through the Calcitonin Gene-Related Peptide Receptor [J].
Baranowsky, Anke ;
Appelt, Jessika ;
Kleber, Christian ;
Lange, Tobias ;
Ludewig, Peter ;
Jahn, Denise ;
Pandey, Puja ;
Keller, Daniela ;
Rose, Thomas ;
Schetler, Daniela ;
Braumuller, Sonja ;
Huber-Lang, Markus ;
Tsitsilonis, Serafeim ;
Yorgan, Timur ;
Frosch, Karl-Heinz ;
Amling, Michael ;
Schinke, Thorsten ;
Keller, Johannes .
CRITICAL CARE MEDICINE, 2021, 49 (01) :E41-E52
[9]   Investigation of TLR2 and TLR4 Polymorphisms and Sepsis Susceptibility: Computational and Experimental Approaches [J].
Behairy, Mohammed Y. ;
Abdelrahman, Ali A. ;
Toraih, Eman A. ;
Ibrahim, Emad El-Deen A. ;
Azab, Marwa M. ;
Sayed, Anwar A. ;
Hashem, Hany R. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (18)
[10]   Inflammation, HIF-1, and the Epigenetics That Follows [J].
Brigati, Claudio ;
Banelli, Barbara ;
di Vinci, Angela ;
Casciano, Ida ;
Allemanni, Giorgio ;
Forlani, Alessandra ;
Borzi, Luana ;
Romani, Andmassimo .
MEDIATORS OF INFLAMMATION, 2010, 2010