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: Protein kinase ataxia telangiectasia mutated (ATM) regulates the function of endothelial cells and responds quickly to endotoxin. However, the function of ATM in lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) disruption remains unknown. This study aimed to investigate the role and underlying mechanism of ATM in the regulation of the BBB function in sepsis. ⋯ By activating ATM, doxorubicin increased the protein binding between ATM and AKT and promoted the phosphorylated activation of AKT at S473, which could directly phosphorylate DRP1 at S637 to repress excessive mitochondrial fission. Consistently, the protective role of ATM was abolished by the AKT inhibitor MK-2206. Conclusions: Ataxia telangiectasia mutated protects against LPS-induced BBB disruption by regulating mitochondrial homeostasis, at least in part, through the AKT/DRP1 pathway.
-
Background : Accurate prediction of fluid responsiveness is important for postoperative critically ill elderly patients. The objective of this study was to evaluate the predictive values of peak velocity variation (ΔVpeak) and passive leg raising (PLR)-induced changes in ΔVpeak (ΔVpeak PLR ) of the left ventricular outflow tract to predict fluid responsiveness in postoperative critically ill elderly patients. Method : Seventy-two postoperative elderly patients with acute circulatory failure who were mechanically ventilated with sinus rhythm were enrolled in our study. ⋯ Results : Thirty-two patients were fluid responders. The area under the receiver operating characteristic curves (AUC) for baseline PPV and ΔVpeak to predict fluid responsiveness was 0.768 (95% confidence interval [CI], 0.653-0.859; P < 0.001) and 0.899 (95% CI, 0.805-0.958; P < 0.001) with gray zones of 7.63% to 12.66% that included 41 patients (56.9%) and 9.92% to 13.46% that included 28 patients (38.9%). ΔPPV PLR predicted fluid responsiveness with an AUC of 0.909 (95% CI, 0.818-0.964; P < 0.001), and the gray zone was 1.49% to 2.93% and included 20 patients (27.8%). ΔVpeak PLR predicted fluid responsiveness with an AUC of 0.944 (95% CI, 0.863-0.984; P < 0.001), and the gray zone was 1.48% to 2.46% and included six patients (8.3%). Conclusions : Passive leg raising-induced changes in peak velocity variation of blood flow in the left ventricular outflow tract accurately predicted fluid responsiveness with a small gray zone in postoperative critically ill elderly patients.
-
Introduction: Acute respiratory distress syndrome (ARDS) is a severe hypoxemic respiratory failure with a high in-hospital mortality. However, the molecular mechanisms underlying ARDS remain unclear. Recent findings have indicated that the onset of severe inflammatory diseases, such as sepsis, is regulated by epigenetic changes. ⋯ Conclusion: Acute respiratory distress syndrome elevates Setdb2 , apoptosis of VECs, and vascular permeability. Elevation of histone methyltransferase Setdb2 suggests the possibility to histone change and epigenetic modification. Thus, Setdb2 may be a novel therapeutic target for controlling the pathogenesis of ARDS.
-
Background: Numerous studies have shown that pyroptosis is associated with sepsis progression, which can lead to dysregulated host immune responses and organ dysfunction. Therefore, investigating the potential prognostic and diagnostic values of pyroptosis in patients with sepsis is essential. Methods: We conducted a study using bulk and single-cell RNA sequencing (scRNA-seq) from the Gene Expression Omnibus database to examine the role of pyroptosis in sepsis. ⋯ The single-cell analysis identified a macrophage subpopulation characterized by gasdermin D (GSDMD) expression that may be involved in pyroptosis regulation, which was associated with the prognosis of sepsis. Conclusion: We developed and validated a risk score for sepsis identification based on 10 PRGs, four of which also have potential value in the prognosis of sepsis. We identified a subset of gasdermin D macrophages associated with poor prognosis, providing new insights into the role of pyroptosis in sepsis.