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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Sex-related outcome differences in trauma remain controversial. The mechanisms causing sex-biased outcomes are likely to have hormonal and genetic components, in which X-linked genetic polymorphisms may play distinct roles because of X-linked inheritance, hemizygosity in males, and X chromosome mosaicism in females. The study aimed to elucidate the contribution of biological sex and the common X-linked IRAK1 haplotype to posttrauma clinical complications, inflammatory cytokine and chemokine production, and polymorphonuclear cell and monocyte activation. ⋯ Variant IRAK1 decreased IL-6, IL-8, and interferon gamma-induced protein 10 production in male trauma subjects compared to WT, whereas cytokine/chemokine responses were similar in variant IRAK1 and WT female trauma subjects. Trauma-induced and lipopolysaccharide-stimulated polymorphonuclear cell and monocyte activation determined by using a set of cluster of differentiation markers and flow cytometry were not influenced by sex or variant IRAK1. These findings suggest that variant IRAK1 is a potential contributor to sex-based outcome differences, but its immunomodulatory impacts are modulated by biological sex.
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Background: Optimal ventilation during cardio-pulmonary resuscitation (CPR) is still controversial. Ventilation is expected to provide sufficient arterial oxygen content and adequate carbon dioxide removal, while minimizing the risk of circulatory impairment. The objective of the present study was to compare three ventilation strategies in a porcine model during mechanical continuous chest compressions (CCC) according to arterial oxygenation and hemodynamic impact. ⋯ There was no difference between groups concerning hemodynamic parameters, cerebral perfusion and microcirculation. Conclusion: Ventilation modalities in this porcine model of prolonged CPR influence oxygenation and decarboxylation without impairing circulation and cerebral perfusion. Synchronized bi-level pressure-controlled ventilation' use avoid hyperoxia and was as efficient as asynchronized volume ventilation to maintain alveolar ventilation and systemic perfusion during prolonged CPR.
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Severe burns develop a catecholamine surge, inducing severe damage to the organism, raising the possibility of multisystem organ failure, and even death. The mechanisms of catecholamine surge have not been fully elucidated, and few strategies are generally acceptable to reduce catecholamine surge postburn. Thus, it is valuable to investigate the underlying mechanisms of catecholamine surge postburn to develop targeted interventions to attenuate it. ⋯ We find that histamine can amplify the catecholamine surge by elevating tyrosine hydroxylase expression and catecholamine synthesis in chromaffin cells through the histamine H1 receptor/Protein Kinase A /cAMP-response element binding protein signaling pathway. In summary, for the first time, we find that histamine plays a vital role in catecholamine surge postburn. We also confirm that the lytic cocktail effectively alleviates catecholamine surge and organ injury postburn through promethazine.
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Purpose: Sepsis-associated encephalopathy (SAE) induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation. Yin Yang 1 (YY1) is an important transcription factor that acts as a key role in sepsis and neuroepithelium development. However, the function of YY1 in SAE remains unclear. ⋯ Besides, TREM-2 was identified as the target of miR-130a-3p. TREM-2 silencing could reverse the effects of miR-130a-3p inhibition on LPS-treated BV-2 cells. Conclusion: Taken together, YY1 promoted microglia M2 polarization via upregulating TREM-2 by interacting with miR-130a-3p promoter, suggesting YY1 overexpression might be a novel therapeutic strategy of SAE.
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Hypoxia/reoxygenation (H/R) induces pyroptosis in the setting of acute myocardial infarction (AMI). Previous studies have shown that the expression of the miR-15 family is stimulated in myocardial ischemia-reperfusion injury or H/R-induced cardiomyocyte injury, and miR-15 is a promoter of cardiac ischemia-reperfusion or H/R injury. However, whether miR-15b-5p regulates H/R injury and cardiomyocyte pyroptosis and its mechanism still need to be further clarified. ⋯ NLRP3 inhibitor MCC950 annulled the previously mentioned antagonistic effect of silencing SIRT3 on the protection of miR-15b-5p downregulation against pyroptosis. We then used a rat AMI model to analyze myocardial infarction area by triphenyl tetrazolium chloride staining and assess serum cardiac troponin T level by ELISA and found that miR-15b-5p silencing reduced AMI injury in rats. Collectively, these results suggest that miR-15b-5p increase H/R-induced pyroptosis in cardiomyocytes by targeting SIRT3 and activating the NLRP3 inflammasome.