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 : 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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Liver ischemia reperfusion (IR) injury significantly impacts clinical outcomes by increasing the risk of hepatic dysfunction after liver surgery. Fatty livers are more susceptible to IR stress. Recent studies have demonstrated that S100A9 plays a crucial role in both IR injury and the progression of liver steatosis. ⋯ Intriguingly, S100A9 facilitated ATF4 nuclear translocation and enhanced NEK7/NLRP3 inflammasome activation in macrophages. In conclusion, our study identified S100A9 as a key regulator responsible for macrophage NLRP3 inflammasome activation and subsequent inflammatory injury in fatty liver IR process. Targeting TLR2/ATF4 signaling may offer a novel therapeutic strategy for mitigating S100A9-mediated liver injury.
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Background: Mechanical ventilation (MV) is a clinically important measure for respiratory support in critically ill patients. Although moderate tidal volume MV does not cause lung injury, it can further exacerbate lung injury in a pathological state such as sepsis. This pathological process is known as the "two-hit" theory, whereby an initial lung injury (e.g., infection, trauma, or sepsis) triggers an inflammatory response that activates immune cells, presenting the lung tissue in a fragile state and rendering it more susceptible to subsequent injury. ⋯ Different species of HMGB1 knockout mice have different lung-protective mechanisms in the two-hit model, and location is the key to function. Specifically, LysM HMGB1 -/- mice due to the deletion of HMGB1 in myeloid cells resulted in a pulmonary-protective mechanism that was associated with a downregulation of the inflammatory response. EC-HMGB1 -/- mice are deficient in HMGB1 owing to endothelial cells, resulting in a distinct pulmonary-protective mechanism independent of the inflammatory response and more relevant to the improvement of alveolar-capillary permeability. iHMGB1 -/- mice, which are systemically HMGB1-deficient, share both of these lung-protective mechanisms.
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Background: Eugenol has been found to inhibit a variety of disease processes, including abdominal aortic aneurysm (AAA) formation. However, the specific role and the underlying molecular mechanism of Eugenol in AAA progression need to be further revealed. Methods: Vascular smooth muscle cells (VSMCs) were pretreated with Eugenol, followed by treated with Angiotensin II (Ang-II). ⋯ Transcription factor STAT3 bound to HMGB2 promoter region to increase its expression. In addition, Eugenol decreased STAT3 expression to regulate HMGB2. Conclusion: Eugenol could slow down the development of AAA, which might be achieved by regulating STAT3/HMGB2 axis.
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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.