Articles: sepsis.
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Sepsis is a lethal clinical syndrome, and acute lung injury (ALI) is the earliest and most serious complication. We aimed to explore the role of growth differentiation factor 11 (GDF11) in sepsis-induced dysfunction of lung microvascular endothelial barrier in vivo and in vitro to elucidate its potential mechanism related to sirtuin 1 (SIRT1)/NADPH oxidase 4 (NOX4) signaling. Cecal ligation and puncture (CLP)-induced sepsis mice and lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial cells (PMECs) were used in this study. ⋯ Additionally, EX527 treatment relieved the impacts of GDF11 overexpression on ferroptosis and destruction of integrity of human pulmonary microvascular endothelial cells exposed to LPS. Taken together, GDF11 overexpression could alleviate sepsis-induced lung microvascular endothelial barrier damage by activating SIRT1/NOX4 signaling to inhibit ferroptosis. Our findings potentially provide new molecular target for clinical therapy of ALI.
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Liver and lung tissue damage caused by sepsis is still one of the causes of death. B-lymphocyte-induced maturation protein-1 (Blimp-1) has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. ⋯ In the LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Overexpression of Blimp-1 relieved LPS-induced cellular inflammatory damage and pyroptosis. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.
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Sepsis is a common, heterogeneous, and frequently lethal condition of organ dysfunction and immune dysregulation due to infection. The causes of its heterogeneity, including the contribution of the pathogen, remain unknown. Using cecal slurry, a widely used murine model of intraperitoneal polymicrobial sepsis, as well as 16S ribosomal RNA sequencing and measurement of immune markers, we performed a series of translational analyses to determine whether microbial variation in cecal slurry composition (representing intra-abdominal pathogens) mediated variation in septic response. ⋯ Likewise, in a human cohort of patients with intra-abdominal abscesses, Enterobacteriaceae was also associated with increased inflammatory markers. Taken together, these data demonstrate that intra-abdominal Enterobacteriaceae drives inflammation in sepsis both in animal models and human subjects. More broadly, our results demonstrate that pathogen identity is a major driver of the host response in polymicrobial sepsis and should not be overlooked as a major source of phenotypic heterogeneity.