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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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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Hepatic ischemia/reperfusion (I/R) injury is a major concern in liver surgery settings. Mitochondria are critical targets or the origin of tissue injury, particularly I/R injury. Mitophagy, a selective form of autophagy, is a fundamental process that removes damaged or unwanted mitochondria for mitochondrial quality control, but its role in hepatic I/R remains unclear. ⋯ No significant change is in PINK1 but it translocated to MAMs region to initiate mitophagy. The silencing PINK1 by shRNA in cultured primary hepatocytes reduced the level of H/R-induced mitophagy, leading to the accumulation of dysfunctional mitochondria during H/R, increased production of ROS, mitochondria-induced apoptosis, and eventually hepatocyte death. Taken together, these findings indicate that PINK1-mediated mitophagy plays a key role in mitochondrial quality control and liver cell survival during I/R.
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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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Septic patients are often anemic, requiring red blood cell (RBC) transfusions. However, RBC transfusions are associated with organ injury. The mechanisms of RBC-induced organ injury are unknown, but increased clearance of donor RBCs from the circulation with trapping in the organs could play a role. We hypothesized that washing of RBCs prior to transfusion may reduce clearance and trapping of donor cells and thereby reduce organ injury. ⋯ In healthy recipients, washing increased 24h-PTR of donor RBCs and decreased trapping in organs. In pneumoseptic rats, washing reduced bacterial outgrowth and lung injury, but did not improve PTR.
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Multicenter Study Clinical Trial
Prehospital Point of Care Testing for the Early Detection of Shock and Prediction of Lifesaving Interventions.
Early diagnosis and treatment are essential for enhancing outcomes for the traumatically injured. In this prospective prehospital observational study, we hypothesized that a variety of laboratory results measured in the prehospital environment would predict both the presence of early shock and the need for lifesaving interventions (LSIs) for adult patients with traumatic injuries. ⋯ In this prospective observational trial, lactate outperformed static vital signs, including shock index, for detecting shock and predicting the need for LSIs. A lactate level > 4 mmol/L was found to be highly associated with the need for LSIs.