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 : 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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Purpose: This study aimed to identify the association between hyperchloremia at intensive care unit (ICU) admission and/or the increase of blood chloride levels and the incidence of major adverse kidney events within 30 days (MAKE30) in critically ill adults. Methods: We conducted a retrospective study to analyze the data of all adult patients admitted to the ICU of a tertiary academic hospital in China between April 2020 and April 2022. Patients were categorized based on their admission chloride levels (hyperchloremia ≥110 mmol/L and nonhyperchloremia <110 mmol/L) and stratified on the increased chloride levels 48 h after ICU admission (∆Cl ≥5 mmol/L and ∆Cl <5 mmol/L). ⋯ After adjusted for confounders, it was found that ΔCl ≥5 mmol/L (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.096-1.93; P = 0.010), but not hyperchloremia (OR, 0.99; 95% CI, 0.77-1.28; P = 0.947), was associated with increased incidence of MAKE30. Conclusion: An increased chloride level in the first 48 h of ICU admission was an independent risk factor for MAKE30, whereas hyperchloremia at ICU admission was not associated with an increased incidence of MAKE30. Large-scale prospective studies are needed to verify our findings.
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Objective: The aim of the study is to screen transcription factor genes related to the prognosis of adult patients with sepsis. Methods: Twenty-three patients with sepsis and 10 healthy individuals admitted for RNA-seq. Differential factors were enriched by four transcription factor databases, and survival analysis was adopted for core factors. ⋯ Compared with those in the control group, FOXO3, SP1, SPI1, STAT3, and USF1 were highly expressed in the sepsis group, while PPARA had low expression. Conclusions: Transcription factors, such as FOXO3, PPARA, SP1, SPI1, STAT3, and USF1, are correlated with the prognosis of sepsis patients and thus may have a potential research value. Clinical Trial Registration: The clinical trial registration number is ChiCTR1900021261.
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Traumatic brain injury (TBI) is a kind of disease with high morbidity, mortality, and disability, and its pathogenesis is still unclear. Research shows that nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) activation in neurons and astrocytes is involved in neuroinflammatory cascades after TBI. What is more, polydatin (PD) has been shown to have a protective effect on TBI-induced neuroinflammation, but the mechanisms remain unclear. ⋯ More importantly, PD could inhibit the level of SOD2 Ac-K122, NLRP3, and cleaved caspase-1 and promote the expression of SOD2 after TBI both in vivo and in vitro. Polydatin also inhibited mtROS accumulation and MMP collapse after stretching injury. These results indicated that PD inhibited SOD2 acetylation to alleviate NLRP3 inflammasome activation, thus acting a protective role against TBI neuroinflammation.