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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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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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 After 90 minutes of HS, fluid resuscitation with withdrawn blood and 0.9% NaCl was performed.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.
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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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Observational Study
Identification of Subphenotypes of Sepsis-Associated Liver Dysfunction Using Cluster Analysis.
Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. ⋯ In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.
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Background: Cardiac arrest (CA) is one of the leading causes of death worldwide. Endoplasmic reticulum (ER) stress and ferroptosis are proven pathological mechanisms implicated in neuronal damage. Baicalein, a ferroptosis Inhibitor, improved outcomes after traumatic brain injury. ⋯ Conclusion: Ferroptosis and ER stress are both involved in brain injury after ROSC. Baicalein alleviates brain injury via suppressing the ferroptosis and ER stress, and reduces ROS partly through inhibiting ER stress. Baicalein is a potential drug to relieve brain injury after ROSC.