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: CircRNA regulates sepsis-induced acute kidney injury (AKI). CircNRIP1 is overexpressed in the blood of AKI patients, but its role in septic AKI occurrence remains unknown. Methods: Human kidney 2 (HK2) cells were stimulated using lipopolysaccharide (LPS) to generate a septic AKI cell model. ⋯ MiR-339-5p bound to OXSR1, and circNRIP1 modulated OXSR1 expression by interacting with miR-339-5p. Further, ectopic expression of OXSR1 relieved circNRIP1 knockdown-mediated effects in LPS-induced HK2 cells. Conclusion: CircNRIP1 depletion ameliorated LPS-induced HK2 cell damage by regulating the miR-339-5p/OXSR1 pathway.
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Background : Our previous studies have shown that ameliorating mitochondrial damage in renal tubular epithelial cells (RTECs) can alleviate septic acute kidney injury (SAKI). It is reported that AMPK phosphorylation (p-AMPK) could ameliorate mitochondrial damage in renal tissue and Sirtuin 5 (SIRT5) overexpression significantly enhanced the level of p-AMPK in bovine preadipocytes. However, the role of SIRT5-mediated phosphorylation of AMPK in SAKI needs to be clarified. ⋯ Notably, an AMPK activator alleviated SAKI. Sirtuin 5 gene knockout significantly aggravated SAKI, while SIRT5 overexpression alleviated mitochondrial dysfunction after LPS stimulation, as manifested by the increase of p-AMPK level, the alleviation of mitochondrial structure damage, the restoration of ATP content, the decrease of proapoptotic protein expression, as well as the reduction of reactive oxygen species generation. Conclusions : Upregulation of SIRT5 expression can attenuate mitochondrial dysfunction in RTECs and alleviate SAKI by enhancing the phosphorylation of AMPK.
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Aim: The purpose of this study was to investigate the effect of esmolol (ES) on LPS-induced cardiac injury and the possible mechanism. Methods: Sepsis was induced by i.p. injection of LPS (10 mg/kg) in male Sprague-Dawley rats pretreated with ES, 3-methyladenine or rapamycin. The severity of myocardial damage was analyzed by hematoxylin-eosin staining, and myocardial damage scores were calculated. ⋯ Pretreatment of LPS-treated rats with ES or rapamycin reduced myocardial injury (release of cardiac troponin, myocardial damage score) and increased autophagy (LC3-II, beclin-1, p-AMPK, and p-ULK1 levels and autophagosome numbers) at 12 and 24 h. In contrast, 3-methyladenine showed no effect. Conclusion: Esmolol alleviates LPS-induced myocardial damage through activating the AMPK/mTOR/ULK1 signal pathway-regulated autophagy.
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Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. ⋯ In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients.
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Objective : The purpose of this study was to investigate the immunomodulatory effects of sulforaphane (SFN), a nuclear factor erythroid 2-related factor (Nrf2) pathway activator, on splenic macrophages' immunocompetence after hemorrhagic shock/resuscitation (HS/R). Methods : Male C57/BL6 wild-type mice (n = 6 per group) were subjected to either pressure-controlled HS (MAP, 35-45 mm Hg) or a sham procedure surgery (without HS). After 90 minutes of HS, fluid resuscitation with withdrawn blood and 0.9% NaCl was performed. ⋯ HS/R + SFN group: 20.54 ± 5.35 [at 6 h] and 8.60 ± 2.37 [at 24 h], P < 0.05). Furthermore, SFN improved in vitro splenic macrophage immunocompetence after HS/R, as evidenced by the increased secretion of inflammatory cytokines in response to LPS stimulation in vitro. Conclusions : Our study shows that SFN can reduce inflammatory cytokines secreted by splenic macrophages after HS/R and increase their immunocompetence toward a more anti-inflammatory profile.