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: Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASCs) have therapeutic potential in multiple disease states; however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. ⋯ However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect seems to be mediated by HAS1. Level of Evidence : Basic science study.
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Introduction: Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. We previously showed that the α1 subunit of AMP-activated protein kinase (AMPK), a crucial regulator of mitochondrial function, exerts a protective role in hemorrhagic shock. Humanin is a mitochondrial peptide with cytoprotective properties against cellular stress. ⋯ Humanin-G also ameliorated cardiac mitochondrial damage and increased adenosine triphosphate levels in KO mice. Beneficial effects of humanin-G were associated with lung cytoplasmic and nuclear activation of the signal transducer and activator of transcription-3 (STAT3) in AMPKα1-independent manner with marginal or no effects on mitochondrial STAT3 and complex I subunit GRIM-19. Conclusions: Our data indicate that circulating levels of humanin increase during hemorrhagic shock in AMPKα1-independent fashion as a defense mechanism to counteract metabolic derangement and that administration of humanin-G affords beneficial effects through STAT3 activation even in the absence of a functional AMPKα1.
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Objective: Our study aims to evaluate the association between heart rate variability (HRV) and short- and long-term prognosis in patients admitted to intensive care unit (ICU). Methods and Results: Adult patients continuously monitored for over 24 h in ICUs from the the American Medical Information Mart for Intensive Care (MIMIC)-IV Waveform Database were recruited in our study. Twenty HRV-related variables (8 time domain, 6 frequency domain, and 6 nonlinear variables) were calculated based on RR intervals. ⋯ All the time domain, frequency domain, and nonlinear HRV parameters did not differ significantly between survivors and nonsurvivors with or without AF (all P > 0.05). Presence of renal failure, malignancy, and elevated blood urea nitrogen level were associated with increased 30-day all-cause mortality in SR patients, while presence of sepsis, infection, higher platelet count, and magnesium level were associated with increased 30-day all-cause mortality in AF patients. Conclusions: Heart rate variability variables were not associated with increased 30-day all-cause mortality in ICU patients with or without AF.
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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.
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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.