Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Intestinal ischemia-reperfusion (I/R) injury is a severe disease associated with high mortality. Stimulator of interferon genes (STING) is an intracellular protein that is activated by cytosolic DNA and is implicated in I/R injury, resulting in transcription of type I interferons (IFN-α and IFN-β) and other proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, induces STING activation. ⋯ Finally, H151 improved the survival rate from 41% to 81% after intestinal I/R. Conclusions: H151, a novel STING inhibitor, attenuates the inflammatory response and reduces tissue injury and mortality in a murine model of intestinal I/R. H151 shows promise as a potential therapeutic in the treatment of this disease.
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Observational Study
Time from hospital admission to onset of septic shock is associated with higher in-hospital mortality.
Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. ⋯ The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.
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Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. ⋯ Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre- and post-septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.
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Idiopathic pulmonary fibrosis is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. Interleukin (IL)-11 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. In this study, we explore whether a potential antifibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and antifibrotic effects through suppressing activation of the IL-11/MEK/ERK signaling pathway in vivo and in vitro. ⋯ Results showed that FD markedly reduced the expressions of IL-8, IL-18, IL-11, monocyte chemotactic protein-1, α-SMA, fibronectin, and collagen I in mice lung tissues. In addition, FD attenuated IL-11-induced expressions of α-SMA, fibronectin, and collagen I and inhibited IL-11RA, gp130, and phosphorylation of the ERK and MEK protein expression, as well as reduced the expressions of IL-8, IL-18, and monocyte chemotactic protein-1 in vitro. This study demonstrated that FD attenuated bleomycin-induced pulmonary inflammation and fibrosis in mice by inhibiting the IL-11/MEK/ERK signaling pathway.
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Sex-related outcome differences in trauma remain controversial. The mechanisms causing sex-biased outcomes are likely to have hormonal and genetic components, in which X-linked genetic polymorphisms may play distinct roles because of X-linked inheritance, hemizygosity in males, and X chromosome mosaicism in females. The study aimed to elucidate the contribution of biological sex and the common X-linked IRAK1 haplotype to posttrauma clinical complications, inflammatory cytokine and chemokine production, and polymorphonuclear cell and monocyte activation. ⋯ Variant IRAK1 decreased IL-6, IL-8, and interferon gamma-induced protein 10 production in male trauma subjects compared to WT, whereas cytokine/chemokine responses were similar in variant IRAK1 and WT female trauma subjects. Trauma-induced and lipopolysaccharide-stimulated polymorphonuclear cell and monocyte activation determined by using a set of cluster of differentiation markers and flow cytometry were not influenced by sex or variant IRAK1. These findings suggest that variant IRAK1 is a potential contributor to sex-based outcome differences, but its immunomodulatory impacts are modulated by biological sex.