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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Septic cardiomyopathy is linked to a dysregulation in mitochondrial integrity and elevated mortality rates, for which an efficacious treatment remains elusive. PDS is a panaxadiol saponin extracted from ginseng stem and leaf. ⋯ DEX and PDS enhance antioxidant defense by degrading Keap1 to activate Nrf2; activate mitochondrial occurrence protein PGC-1α and fusion protein OPA1, Mfn1, and Mfn2 expression; and inhibit phosphorylation of mitochondrial fission protein Drp1, aiming to maintain normal structure and function of mitochondrial, thereby preserving oxidative phosphorylation capacity. In summary, our findings highlighted the protective efficacy of PDS and DEX in maintaining mitochondrial in LPS-induced cardiomyopathy, and mechanism improving mitochondrial quality control at least in part by promoting Nrf2 activation.
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Background: Acute lung injury (ALI) is a severe complication of sepsis, characterized by inflammation, edema, and injury to alveolar cells, leading to high mortality rates. Septic ALI is a complex disease involving multiple factors and signaling pathways. STEAP family member 1 (STEAP1) has been reported to be upregulated in a sepsis-induced ALI model. ⋯ Moreover, METTL14 silencing attenuated LPS-induced effects by decreasing STEAP1 expression in HPMECs, and STEAP1 silencing ameliorated cecal ligation and puncture-induced lung injury of mice. Conclusion: METTL14/IGF2BP2-mediated m6A modification of STEAP1 aggravated ALI induced by sepsis. These findings suggest potential therapeutic targets for the treatment of this disease.
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Objective : To evaluate if mechanical left ventricular unloading could reduce mortality in patients with cardiogenic shock undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods : We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials and propensity score-matched studies published until December 20, 2023. The primary outcome was mortality at the longest follow-up. ⋯ Mechanical left ventricular unloading was significantly associated with reduced mortality at the longest follow-up (RR, 0.89; 95% CI, 0.84-0.94; P = 0.0001; moderate certainty of evidence), which was confirmed in studies using intra-aortic balloon pump. Benefits of mechanical unloading were also observed in terms of successful VA-ECMO weaning (RR, 1.15; 95% CI, 1.02-1.29; P = 0.02; low certainty of evidence) and favorable neurological outcome (two studies; RR, 2.45; 95% CI, 1.62-3.69; P < 0.0001; low certainty of evidence), although we observed an increased incidence of major bleeding (RR, 1.27; 95% CI, 1.02-1.59; P = 0.03; low certainty of evidence) and hemolysis (RR, 1.49; 95% CI, 1.10-2.02; P = 0.01; moderate certainty of evidence). Conclusions : Among adult patients with cardiogenic shock treated with VA-ECMO, mechanical left ventricular unloading was associated with reduced mortality, which was confirmed in studies using intra-aortic balloon pump as an unloading device.
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Background : Extracorporeal membrane oxygenation (ECMO) is an effective technique for providing short-term mechanical support to the heart, lungs, or both. During ECMO treatment, the inflammatory response, particularly involving cytokines, plays a crucial role in pathophysiology. However, the potential effects of cytokines on patients receiving ECMO are not comprehensively understood. ⋯ Spearman correlation analyses and Mantel tests revealed that the expression of hub cytokines (IL1R2, CCL4, and IL7R) and pivotal molecular pathways scores (complement and coagulation cascades, IL6/JAK/STAT3 signaling, and para-inflammation) were closely related. Conclusion : A predictive model (CRG classifier) comprising nine CRGs based on multiple machine learning algorithms was constructed, potentially assisting clinicians in guiding individualized ECMO treatment. Additionally, elucidating the underlying mechanistic pathways of cytokines during ECMO will provide new insights into its treatment.
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Objective: The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. ⋯ In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. Conclusion: FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.