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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Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance In early Human Sepsis.
Limited studies have functionally evaluated the heterogeneity in early ex vivo immune responses during sepsis. Our aim was to characterize early sepsis ex vivo functional immune response heterogeneity by studying whole blood endotoxin responses and derive a transcriptional metric of ex vivo endotoxin response. ⋯ An attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome.
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Randomized Controlled Trial
Modulation of LTCC Pathways by A Melusin Mimetic Increases Ventricular Contractility During LPS-Induced Cardiomyopathy.
Sepsis-induced cardiomyopathy is commonplace and carries an increased risk of death. Melusin, a cardiac muscle-specific chaperone, exerts cardioprotective function under varied stressful conditions through activation of the AKT pathway. The objective of this study was to determine the role of melusin in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction and to explore its signaling pathway for the identification of putative therapeutic targets. ⋯ This study identifies AKT / Melusin as a key pathway for preserving cardiac function following LPS challenge. The cell-permeable mimetic peptide (R7W-MP) represents a putative therapeutic for sepsis-induced cardiomyopathy.
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Observational Study
GROWTH DIFFERENTIATION FACTOR-15 CORRELATES WITH MORTALITY AND SEVERITY IN SEVERE BURNS.
Growth differentiation factor-15 (GDF-15) is expressed in almost all tissues of the body and is necessary for the body's defense response to stress such as inflammation. It has been reported to be associated with incidence and mortality in many diseases, including systemic inflammatory response syndromes. There are no reports on GDF-15 in burns. The purpose of this study was to investigate the trend of GDF-15 in blood in patients with severe burns and to determine its relationship with severity and mortality. ⋯ In the acute phase of severe burn, GDF-15 levels were associated with mortality and SOFA scores.
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Hepcidin Alleviates LPS-Induced ARDS by Regulating The Ferritin-Mediated Suppression of Ferroptosis.
The effects of ferroptosis, an iron-dependent cell death, on acute respiratory distress syndrome (ARDS) remain largely elusive. Hepcidin, encoded by the HAMP gene, affects inflammation, and iron homeostasis. The present study aimed to investigate whether hepcidin protects against ferroptosis in lipopolysaccharide (LPS)-induced ARDS. ⋯ The effects of hepcidin on the A549 cell line were in line with the in vivo results. In addition, we used si-FTH to knock down FTH expression and found that this suppressed the ability of hepcidin to protect against ferroptosis. Collectively, our data suggest that hepcidin inhibits ferroptosis by increasing FTH expression in LPS-induced ARDS; thus, hepcidin may represent a possible treatment targeting ferroptosis.
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Nitrosative stress is widely involved in cell injury via inducing the nitration modification of a variety of proteins. This study aimed to investigate whether inhibition of nitrosative stress attenuated myocardial injury and improved outcomes in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). ⋯ Inhibition of nitrosative stress is a novel molecular target to alleviate myocardial injury and improve outcomes in a rat model of CA/CPR.