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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IL-33 and WNT1-inducible secreted protein (WISP1) play central roles in acute lung injury (ALI) induced by mechanical ventilation with moderate tidal volume (MTV) in the setting of sepsis. Here, we sought to determine the inter-relationship between IL-33 and WISP1 and the associated signaling pathways in this process. We used a two-hit model of cecal ligation puncture (CLP) followed by MTV ventilation (4 h 10 mL/kg) in wild-type, IL-33-/- or ST2-/- mice or wild-type mice treated with intratracheal antibodies to WISP1. ⋯ This WISP1 upregulation and WNT β-catenin activation were sensitive to inhibition of the β-catenin/TCF/CBP/P300 nuclear pathway. We show that IL-33 drives WISP1 upregulation and ALI during MTV in CLP sepsis. The identification of this relationship and the associated signaling pathways reveals a number of possible therapeutic targets to prevent ALI in ventilated sepsis patients.
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Ferroptosis has been found to play an important role in myocardial ischemia reperfusion (MIR) injury (MIRI). This study aimed to explore whether the improvement effect of Etomidate (Eto) on MIRI was related to ferroptosis. ⋯ Eto attenuated the myocardial injury by inhibiting IR-induced ferroptosis via Nrf2 pathway, which may provide a new idea for clinical reperfusion therapy.
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Host cells recognize molecules that signal danger using pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the most studied class of PRRs and detect pathogen-associated molecular patterns and danger-associated molecular patterns. ⋯ Here, we review the expression, regulation, and function of different TLRs, with an emphasis on TLR-4, and how TLR adaptor protein binding directs intracellular signaling resulting in activation or termination of an innate immune response. Finally, we highlight the recent progress of research on the involvement of S100 proteins as ligands for TLR-4 in inflammatory disease.
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Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. ⋯ Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.