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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Septic acute kidney injury (SAKI) represents a clinical challenge with high morbidity and mortality. The current study aimed to analyze the effects and molecular mechanism of Krüppel-like factor 6 (KLF6) on SAKI. First, SAKI mouse models were established by cecum ligation and puncture, while in vivo cell models were established using lipopolysaccharide (LPS). ⋯ Mechanistic results confirmed that KLF6 inhibited miR-223-3p via binding to the miR-223-3p promoter and promoted NLRP3. On the other hand, downregulation of miR-223-3p activated the NLRP3/Caspase-1/IL-1β pathway and aggravated OS and pyroptosis. Overall, our findings indicated that KLF6 inhibited miR-223-3p via binding to the miR-223-3p promoter and promoted NLRP3, and activated the NLRP3/Caspase-1/IL-1β pathway, thereby aggravating pyroptosis and SAKI.
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Observational Study
Factors Associated with Mortality Among Patients Managed For Large Volume Hemorrhage In A Medical Intensive Care Unit.
Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes. ⋯ In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.
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Recent studies have demonstrated that alterations in mitochondrial dynamics can impact innate immune function. However, the upstream mechanisms that link mitochondrial dynamics to innate immune phenotypes have not been completely elucidated. This study asks if Protein Kinase C, subunit delta (δPKC)-mediated phosphorylation of dynamin-related protein 1 (Drp1), a key driver of mitochondrial fission, impacts macrophage pro-inflammatory response following bacterial-derived lipopolysaccharide (LPS) stimulation. ⋯ These data suggest that inhibiting Drp1 phosphorylation by δPKC abates the excessive mitochondrial fragmentation and mitochondrial dysfunction that is seen following LPS treatment. Furthermore, these data suggest that limiting δPKC-dependent Drp1 activation decreases the pro-inflammatory response following LPS treatment. Altogether, δPKC-dependent Drp1 phosphorylation might be an upstream mechanistic link between alterations in mitochondrial dynamics and innate immune phenotypes, and may have therapeutic potential.
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Omeprazole (OMZ) is a proton pump inhibitor that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of LPS-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury. ⋯ OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.