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
-
Severe burns are associated with massive tissue destruction and cell death where nucleus histones and other damage-associated molecular patterns are released into the circulation and contribute to the pathogenesis of multiple-organ dysfunction. Currently, there is limited information regarding the pathophysiology of extracellular histones after burns, and the mechanisms underlying histone-induced vascular injury are not fully understood. In this study, by comparing the blood samples from healthy donors and burn patients, we confirmed that burn injury promoted the release of extracellular histones into the circulation, evidenced by increased plasma levels of histones correlating with injury severity. ⋯ Functionally, in vivo administration of an anti-Clec2d antibody attenuated burn-induced plasma leakage across mesenteric microvessels. Consistently, Clec2d knockdown in endothelial cells partially inhibited histone-induced endothelial barrier dysfunction. Together, our data suggest that burn injury-induced increases in circulating histones contribute to microvascular leakage and endothelial barrier dysfunction via a mechanism involving the endothelial Clec2d receptor.
-
Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. There is currently no simple immune-imbalance-driven indicator for patients with sepsis. Methods: This study was conducted in Peking Union Medical College Hospital. ⋯ In trend analysis, as the trend of D1-D3-D7 IL-6/LY# decreases, the morality rate is lower than increase or fluctuate group (42.1% vs. 58.3%, 37.9% vs. 43.8%, 37.5% vs. 38.5% in high, moderate, and low D1 IL-6/LY# group separately). Conclusion: IL-6/LY# examined on first day in intensive care unit can be used as an immune-imbalance alert to identify sepsis patients with higher risk of 28-day mortality. Decreasing trend of IL-6/LY# suggests a lower 28-day mortality rate of sepsis patients.
-
Purpose: Cystatin C (CysC) has been linked to the prognosis of corona virus disease 2019 (COVID-19). The study aims to investigate a predictor correlated with CysC screening for poor prognosis in COVID-19 patients combined with skeletal muscle (SKM) impairment and rhabdomyolysis (RM). Methods: A single-center retrospective cohort analysis was carried out. ⋯ LDH*CysC and AST*CysC had better predictive values than CysC and the best prediction for RM, with an AUC of 0.880 (0.796,0.964) for LDH*CysC ( P < 0.05, vs CysC) and 0.925 (0.878,0.972) for AST*CysC ( P < 0.05, vs CysC). Conclusion: CysC is an essential evaluation indicator for COVID-19 patients' prognosis. AST*CysC and LDH*CysC have superior predictive value to CysC for SKM, RM, and death, and optimal classification for RM.
-
Escherichia coli and Staphylococcus aureus are two of the most common bacterial species responsible for sepsis. While it is observed that they have disparate clinical phenotypes, the signaling differences elicited by each bacteria that drive this variance remain unclear. Therefore, we used human whole blood exposed to heat-killed E. coli or S. aureus and measured the transcriptomic signatures. ⋯ Using Ingenuity Pathway Analysis, it was demonstrated that nuclear factor erythroid 2-related factor 2 signaling, a main transcription factor in antioxidant responses, was predominately upregulated in S. aureus exposed blood relative to E. coli. Furthermore, the use of pharmacologics that preferentially targeted the nuclear factor erythroid 2-related factor 2 pathway led to differential cytokine profiles depending on the type of bacterial exposure. These findings reveal significant inflammatory dysregulation between E. coli and S. aureus and provide insight into the targeting of unique pathways to curb bacteria-specific responses.
-
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Macrophages play important roles in the inflammatory process of sepsis by secreting chemokines. Chemokine (CC-motif) ligand 2 (CCL-2) is one of the main proinflammatory chemokines secreted by macrophages that plays a critical role in the recruitment of more monocytes and macrophages to the sites of injury in sepsis, but the mechanisms that regulate CCL-2 expression in macrophages during sepsis are still unknown. ⋯ We further confirmed miR-155 regulated SGK3 to increase LPS-induced CCL-2 by using miR-155 mimics and SGK3 overexpression. Thus, our study demonstrates that miR-155 targets SGK3 to increase LPS-induced CCL-2 expression in macrophages, which promotes macrophage chemotaxis and enhances organs injury during endotoxemia. Our study contributed to a better understanding of the mechanisms underlying the inflammatory response during sepsis.