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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Background: Multiple-organ dysfunction syndrome disproportionately contributes to pediatric sepsis morbidity. Humanin (HN) is a small peptide encoded by mitochondrial DNA and thought to exert cytoprotective effects in endothelial cells and platelets. We sought to test the association between serum HN (sHN) concentrations and multiple-organ dysfunction syndrome in a prospectively enrolled cohort of pediatric septic shock. ⋯ Furthermore, sHN was higher among those with high PERSEVERE-mortality risk strata and correlated with platelet counts and several markers of endothelial activation. Conclusion: Future investigation is necessary to validate the association between sHN and sepsis-associated acute kidney injury among children with septic shock. Furthermore, mechanistic studies that elucidate the role of HN may lead to therapies that promote organ recovery through restoration of mitochondrial homeostasis among those critically ill.
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Objective: This study aimed to test whether the prognostic value of tryptophanyl-tRNA synthetase 1 (WARS1) for 28-day mortality in patients with sepsis was affected by monocytopenia. Methods: A prospective analysis of retrospectively collected samples from 74 sepsis patients was performed. WARS1, C-reactive protein (CRP), and procalcitonin were measured at admission and 24 and 72 h after admission. ⋯ The AUROCs of WARS1 at admission and 24 h for mortality were significantly higher in patients without monocytopenia (0.830, 0.818) than in patients with monocytopenia (0.232, 0.196; P < 0.001, both). When patients without monocytopenia were analyzed, the AUROCs of WARS1 for mortality were 0.830 and 0.818 at admission and 24 h, respectively, which were significantly higher than those of CRP (0.586, 0.653) and procalcitonin (0.456, 0.453) at the same time points ( P = 0.024 and 0.034, respectively). Conclusion: WARS1 is a useful biomarker for prognosis in sepsis patients without monocytopenia.
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Background: Sepsis is a life-threatening systemic inflammatory disease that can cause many diseases, including acute kidney injury (AKI). Increasing evidence showed that a variety of circular RNAs were considered to be involved in the development of the disease. In this study, we aimed to elucidate the role and potential mechanism of circUSP42 in sepsis-induced AKI. ⋯ In addition, circUSP42 induced DUSP1 expression via sponging miR-182-5p to ameliorate LPS-induced HK2 cell damage. Conclusion : Our results showed that circUSP42 overexpression might attenuate LPS-induced HK2 cell injury by regulating miR-182-5p/DUSP1 axis. This might provide therapeutic strategy for the treatment of sepsis.
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Objective: To investigate whether pediatric sepsis phenotypes are stable in time. Methods: Retrospective cohort study examining children with suspected sepsis admitted to a Pediatric Intensive Care Unit at a large freestanding children's hospital during two distinct periods: 2010-2014 (early cohort) and 2018-2020 (late cohort). K-means consensus clustering was used to derive types separately in the cohorts. ⋯ Despite low mortality, this type had the longest PICU length of stay. Conclusions: This single center study identified four pediatric sepsis phenotypes in an earlier epoch but five in a later epoch, with the new type having a large proportion of characteristics associated with medical complexity, particularly technology dependence. Personalized sepsis therapies need to account for this expanding patient population.
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Background: Neonatal pneumonia is a common disease in the neonatal period with high mortality. The present work concentrated on the role and mechanism of circular RNA extra spindle pole bodies like 1, separase (circESPL1) in LPS-induced dysfunction of lung fibroblasts. Methods: Reverse transcription-quantitative polymerase chain reaction and Western blot assay were conducted to analyze RNA and protein expression, respectively. ⋯ CircESPL1 knockdown-mediated protective effects on LPS-induced lung fibroblasts were largely reversed by the silence of miR-146b-3p. miR-146b-3p directly interacted with the 3' untranslated region of TNF receptor associated factor 1 (TRAF1), and TRAF1 expression was regulated by the circESPL1/miR-146b-3p axis in lung fibroblasts. TRAF1 overexpression largely reversed miR-146b-3p accumulation-mediated protective effects on LPS-induced lung fibroblasts. Conclusion: CircESPL1 knockdown protected lung fibroblasts from LPS-induced injury partly by targeting the miR-146b-3p/TRAF1 axis.