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 , 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 ( < 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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563779 | PMC |
http://dx.doi.org/10.3389/fmed.2024.1501761 | DOI Listing |
Immune-mediated diseases are common in humans. The immune system is a complex host defense system that evolved to protect us from pathogens, but also plays an important role in homeostatic processes, removing dead or senescent cells, and participating in tumor surveillance. The human immune system has two arms: the older innate immune system, and the newer adaptive immune system.
View Article and Find Full Text PDFThe stress-induced keratin intermediate filament gene/protein (K16) is spatially restricted to the suprabasal compartment of the epidermis and extensively used as a biomarker for psoriasis, hidradenitis suppurativa, atopic dermatitis and other inflammatory disorders. However, its role in these conditions remains poorly defined. Here we show that K16 negatively regulates type-I interferon (IFN) signaling and innate immune responses.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
December 2024
Wuxi Medical College, Jiangnan University, Wuxi 214122, China. Electronic address:
The mitochondrial antiviral signaling protein (MAVS) is a pivotal adaptor in the antiviral innate immune signaling pathway and plays a crucial role in the activation of antiviral defences. This comprehensive review delves into the multifaceted functions of MAVS, spanning from its integral role in the RIG-I-like receptor (RLR) pathway to its emerging roles in tumor biology and autoimmune diseases. We discuss the structural and functional aspects of MAVS, its activation mechanisms, and the intricate regulatory networks that govern its activity.
View Article and Find Full Text PDFPol J Vet Sci
September 2024
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, No. 50 Zhongling Street, Nanjing City, Jiangsu Province, 210014, PR China.
The outbreak and prevalence of tembusu virus (TMUV) endanger the breeding industry of waterfowls. However, little is known about the molecular mechanism underlying TMUV infection. It was reported that heat shock protein 70 (HSP70) was a positive regulator of the infection of TMUV.
View Article and Find Full Text PDFCurr Res Microb Sci
November 2024
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology; CAS Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China.
RIG-I and MDA5 are members of RIG-I-like receptors (RLRs) that detect viral RNA within the cytoplasm and subsequently initiate antiviral immune responses. Necroptosis is a form of programmed cell death (PCD) executed by mixed lineage kinase domain-like (MLKL), which, upon phosphorylation by receptor-interacting protein kinase 3 (RIPK3), causes necrotic cell death. To date, no link between RLRs and necroptosis has been observed during bacterial infection.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!