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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The purpose of this study was to reveal possible consequences of long-bone fracture on cardiac tissue and to analyze the role of systemically elevated danger associated molecular patterns, complement anaphylatoxins and cytokines. Blood samples of mice, pigs, and humans after a fracture were analyzed by ELISAs for complement component 5a (C5a), tumor necrosis factor (TNF), and extracellular histones. In vivo results were completed by in vitro experiments with human cardiomyocytes treated with TNF and extracellular histones. ⋯ Further, the presence of TNF leads to elevation of reactive oxygen species, troponin I release, and histone appearance in supernatant of human cardiomyocytes. Incubation of human PMNs with histones and plasma of patients after fracture lead to formation of neutrophil extracellular traps. Present results suggest that structural alterations in the heart might be consequences of the complement activation, the release of extracellular histones, and the systemic TNF elevation in the context of a long bone fracture.
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Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. ⋯ Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.
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Na/H exchanger 1 (NHE1) is a ubiquitously expressed protein on mammalian plasma membranes and involved in cell apoptosis and tissue injury. Our previous study found that NHE1 inhibition prevents burn-induced acute lung injury (ALI). However, the potential mechanism of NHE1 in burn-induced ALI is still unclear. ⋯ The data demonstrate that NHE1 activation facilitates burn-induced endothelial cell apoptosis, mediated by Ca-dependent pathway. PI3K-Akt and p38 MAPK were found to be upstream regulators of NHE1. This study provides new mechanisms underlying burn-induced ALI.
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Clinical Trial Observational Study
Association between doppler snuffbox resistive index and tissue perfusion in septic patients.
Peripheral vascular disorders leading to tissue hypoperfusion play a central role in the pathophysiology of organ failure in septic shock. The Doppler snuffbox resistive index (SBRI) can be an accurate parameter to evaluate the status of peripheral vasculature at the bedside. We evaluated whether the SBRI is related to lactate levels or the peripheral perfusion index (PI) and its ability to predict lactate clearance in septic patients. ⋯ The Doppler SBRI is correlated with tissue perfusion parameters in critically ill patients. An abnormal SBRI may be better than the PI for predicting poor lactate clearance in septic patients. Further investigations are required to determine whether correcting an abnormal SBRI and PI may improve the success rate of septic shock resuscitation.
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Myocardial ischemia reperfusion (IR) injury is a serious issue in the treatment of myocardial infarction. MiR-433 is upregulated in myocardial IR injury, but its specific effects remain unclear. In this study, we explored the effect and mechanism of miR-433 in myocardial IR injury. ⋯ MiR-433 regulated myocardial IR injury by targeting NDRG4 and modulating PI3K/Akt signal pathway.