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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Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of sepsis, yet the pathophysiologic mechanisms of SA-AKI are incompletely understood. PERSEVERE is a clinically validated serum biomarker panel with high sensitivity in predicting mortality from sepsis, and recent evidence suggests it can also predict severe, persistent SA-AKI at day 3 of hospitalization among septic children. We developed a murine model of PERSEVERE (mPERSEVERE) to further interrogate the sepsis-related biological underpinnings of SA-AKI using candidate biomarkers within mPERSEVERE. ⋯ The combination of plasma CCL3+KC can predict SA-AKI development in mice at 24-hours following CLP Of these two biomarkers, only renal expression of KC is increased in mice with SA-AKI. Further studies are required to determine if KC directly contributes to the underlying pathobiology of SA-AKI.
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Interleukin-38 (IL-38), a new type of cytokine, is involved in processes such as tissue repair, inflammatory response, and immune response. However, its function in pneumonia caused by Pseudomonas aeruginosa (P. aeruginosa) is still unclear. ⋯ To summarize, the above findings provide additional insights into the mechanism of IL-38 in the treatment of P. aeruginosa pneumonia.
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Intratracheal (IT) lipopolysaccharide (LPS) causes severe acute lung injury (ALI) and systemic inflammation. CMT-3 has pleiotropic anti-inflammatory effects including matrix metalloproteinase (MMP) inhibition, attenuation of neutrophil (PMN) activation, and elastase release. CMT-3's poor water solubility limits its bioavailability when administered orally for treating ALI. We developed a nano-formulation of CMT-3 (nCMT-3) to test the hypothesis that the pleiotropic anti-inflammatory activities of IT nCMT-3 can attenuate LPS-induced ALI. ⋯ Pre-treatment with nCMT3 significantly attenuates LPS-induced lung injury/inflammation by multiple mechanisms including: MMP activation, PMN elastase, sTREM-1 release, and NLRP3 inflammasome/caspase-1 activation.