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
-
Background: Lipopolysaccride-induced myocardial injury was characterized by frequent mitochondrial dysfunction. Our previous studies found that nucleolin (NCL) played important protective roles in myocardial ischemia-reperfusion injury. Recently, it has been found that NCL has a protective effect on LPS-induced myocardial injury in vivo. ⋯ In addition, the activation of PGC-1α diminished the detrimental effects of NCL knockdown on mitochondrial biogenesis in vitro and in vivo. Conclusions: Nucleolin upregulated the gene expression of PGC-1α by directly binding to the 5'-UTR of PGC-1α mRNA and increasing its mRNA stabilities, then promoted mitochondrial biogenesis, and played protective effect on cardiomyocytes during LPS-induced myocardial injury. Taken together, all these data showed that NCL activated PGC-1α to rescue cardiomyocytes from LPS-induced myocardial injury insult, suggesting that the cardioprotective role of NCL might be a promising prospect for clinical treatment of patients with endotoxemia.
-
Purpose : Sepsis is the leading cause of death in patients with severe acute pancreatitis (SAP) in the intensive care unit (ICU). Early prediction of sepsis secondary to SAP developed in the late phase and of related mortality can enable appropriate treatment and improve outcomes. This study was conducted to evaluate the predictive value of presepsin in ICU patients with SAP at the early stage and compared it with established blood markers and scoring systems. ⋯ Among the analyzed biomarkers, presepsin was the only blood marker independently associated with sepsis secondary to SAP on days 3 and 7, and presepsin on day 3 was independently associated with mortality at ICU discharge and on days 28 and 90. It showed similar or even better predictive accuracy for both secondary sepsis and mortality than procalcitonin and Sequential Organ Failure Assessment score. Conclusion : Presepsin could be a valuable early predictor of secondary sepsis and mortality in patients admitted to the ICU with SAP and may serve as an indicator for early risk stratification.
-
Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. ⋯ This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.
-
Background: Severe trauma disrupts bone marrow function resulting in persistent anemia and immunosuppression. Exosomes are extracellular vesicles implicated in disease, cellular functions, and immunomodulation. The effects of trauma plasma-derived exosomes on bone marrow hematopoiesis are unstudied; we hypothesized that trauma plasma-derived exosomes suppress bone marrow hematopoietic progenitor cell (HPC) growth and contribute to increased inflammatory cytokines and HPC mobilization. ⋯ Culture of trauma exosomal protein with bone marrow stromal cells resulted in increased expression of IFN-γ, IL-1α, TNF-α, G-CSF, CXCR4, SDF-1, and VCAM-1 in bone marrow stroma. Conclusions: Both plasma and plasma-derived exosomes from trauma patients adversely affect bone marrow function. Plasma-derived exosomes may contribute to altered hematopoiesis after severe trauma; analysis of exosomal content may improve our understanding of altered bone marrow function.
-
Background: Sepsis-associated encephalopathy (SAE) is a dysfunction of the central nervous system experienced during sepsis with variable clinical and pathophysiologic features. We sought to identify distinct SAE phenotypes in relation to clinical outcomes. Methods: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU database were used to conduct a retrospective cohort study. ⋯ Conclusions: Four SAE phenotypes had different clinical outcomes. The mixed phenotype had the worst outcomes. Further understanding of these phenotypes in sepsis may improve trial design and targeted SAE management.