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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Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. ⋯ This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol + burn Tregs compared with sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues 1 day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn-injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.
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Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms. ⋯ GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.
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Multicenter Study
Incidence, Clinical Characteristics and Outcomes of Early Hyperbilirubinemia in Critically ill Patients - Insights From The Mars Study.
To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients. ⋯ Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.
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Innate immune dysregulation may contribute to age-related differences in outcomes among critically ill adults. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an important innate immune marker with prognostic value in sepsis, but age-related differences have not been studied. ⋯ sTREM-1 was elevated among critically ill older adults, and strongly associated with both death and persistent organ dysfunction. Immune responses associated with sTREM-1 may contribute to age-related differences in ICU outcomes, warranting further study as a potential therapeutic target in older adults.
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Nuclear factor erythroid 2-related factor (Nrf2) is a redox-sensitive transcription factor that responds to oxidative stress by activating expressions of key antioxidant and cytoprotective enzymes via the Nrf2-antioxidant response element (ARE) signaling pathway. Our objective was to characterize hyperoxia-induced acute lung injury (HALI) in Nrf2 knock-out (KO) rats to elucidate the role of this pathway in HALI. Adult Nrf2 wildtype (WT), and KO rats were exposed to room air (normoxia) or >95% O2 (hyperoxia) for 48 h, after which selected injury and functional endpoints were measured in vivo and ex vivo. ⋯ Hyperoxia had no effect on expression of Bcl-2 (anti-apoptotic protein) or peroxiredoxin-1. These results suggest that the protection offered by the Nrf2-ARE pathway against HALI is in part via its regulation of the GSH redox pathway. To the best of our knowledge, this is the first study to assess the role of the Nrf2-ARE signaling pathway in protection against HALI using a rat Nrf2 knockout model.