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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Introduction: Gut microbiota dysbiosis is associated with susceptibility to sepsis and poor outcomes. However, changes to the intestinal microbiota during sepsis and their value as biomarkers are unclear. In this study, we compared the intestinal microbiota of patients with sepsis and healthy controls. ⋯ The genus Blautia was more abundant in controls than in the sepsis group, and Faecalibacterium less abundant in the nonsurvivor than in the other groups. Regression analysis associated low Shannon index with 6-month mortality. Conclusions: Survivors of sepsis, nonsurvivors, and healthy controls have different gut microbiomes, and a low Shannon index is a risk factor for 6-month mortality.
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Background: Neonatal pneumonia is a common disease in the neonatal period with high mortality. The present work concentrated on the role and mechanism of circular RNA extra spindle pole bodies like 1, separase (circESPL1) in LPS-induced dysfunction of lung fibroblasts. Methods: Reverse transcription-quantitative polymerase chain reaction and Western blot assay were conducted to analyze RNA and protein expression, respectively. ⋯ CircESPL1 knockdown-mediated protective effects on LPS-induced lung fibroblasts were largely reversed by the silence of miR-146b-3p. miR-146b-3p directly interacted with the 3' untranslated region of TNF receptor associated factor 1 (TRAF1), and TRAF1 expression was regulated by the circESPL1/miR-146b-3p axis in lung fibroblasts. TRAF1 overexpression largely reversed miR-146b-3p accumulation-mediated protective effects on LPS-induced lung fibroblasts. Conclusion: CircESPL1 knockdown protected lung fibroblasts from LPS-induced injury partly by targeting the miR-146b-3p/TRAF1 axis.
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Introduction: Extracellular histones have been determined as significant mediators of sepsis, which can induce endothelial cell injury and promote coagulation activation, and ultimately contribute to multiorgan failure. Evidence suggests that magnesium sulfate (MgSO 4 ) exerts a potential coagulation-modulating activity; however, whether MgSO 4 ameliorates histone-induced coagulation dysfunction and organ damage remains unclear. Methods: To measure circulating histone levels, blood specimens were collected from septic patients and mice, and the relationship between circulating histone levels, coagulation parameters, and Mg 2+ levels in sepsis was investigated. ⋯ Interestingly, we also observed a positive link between histones and Mg 2+ levels, suggesting that Mg 2+ with anticoagulant activity is involved in histone-mediated coagulation alterations in sepsis. Further animal experiments confirmed that MgSO 4 administration significantly improved survival and attenuated histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage in mice. Conclusion: These results suggest that therapeutic targeting of histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage, for example, with MgSO 4 , may be protective in septic individuals with elevated circulating histone levels.
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Background: After severe injury, optical measures of microvascular blood flow (MBF) decrease and do not normalize with resuscitation to normal blood pressure. These changes are associated with organ dysfunction, coagulopathy, and death. However, the pathophysiology is not well understood. ⋯ Conclusion: We present a rat model of MBF derangement in uninjured skeletal muscle and coagulopathy after polytrauma that persists after resuscitation with whole blood to normal macrohemodynamics. Parametric CEUS analysis shows that this change is primarily due to microvascular obstruction. This platform can be used to develop a deeper understanding of this important process.