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
-
Background : Increased plasma lactate levels in patients with sepsis may be due to insufficient oxygen delivery, but mitochondrial dysfunction or accelerated glycolysis may also contribute. We studied the effect of the latter on muscle metabolism by using microdialysis in a sepsis model with sustained oxygen delivery and decreased energy consumption or mitochondrial blockade. Methods : Pigs were subjected to continuous Escherichia coli infusion (sepsis group, n = 12) or saline infusion (sham group, n = 4) for 3 h. ⋯ Muscle lactate, LPR, and glutamate levels were higher in the sepsis group than in the sham group in the cyanide catheters ( P < 0.001, all comparisons) and did not normalize in the former group. Conclusions: In this experimental study on resuscitated sepsis, we observed increased aerobic metabolism and preserved mitochondrial function. Sepsis and electron transport chain inhibition led to increased LPR, suggesting a decreased mitochondrial reserve capacity in early sepsis.
-
Background: Sepsis reduces neutrophil apoptosis. As the result, neutrophils may become aged, exacerbating inflammation and tissue injury. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a damage-associated molecular pattern to promote inflammation and tissue injury in sepsis. ⋯ We also found that aged neutrophils expressed significantly higher levels of SerpinB2 compared with non-aged neutrophils. Conclusions: eCIRP inhibits neutrophil apoptosis to increase aged phenotype by increasing SerpinB2 expression in sepsis. Thus, targeting eCIRP could be a new therapeutic strategy to ameliorate inflammation caused by neutrophil aging in sepsis.
-
Background: Pneumonia is a frequent complication after polytrauma. This study aims to evaluate the ability of different serum markers to identify patients at risk of developing pneumonia after polytrauma. Methods: A retrospective analysis of prospectively collected data in polytraumatized patients with concomitant thoracic trauma (Injury Severity Score ≥16, Abbreviated Injury Scale Thorax ≥ 3) was performed. ⋯ No statistically significant difference could be observed for serum levels of CYFRA 21-1, Ang-2, PTX-3, sRAGE, IL-6, and IL-10 between the groups (pneumonia vs. no pneumonia) on all days. Logistic regression revealed a combination of IL-6, IL-10, sRAGE, and PTX-3 to be eventually helpful to identify patients at risk of developing pneumonia and our newly developed score was significantly higher on day 0 in patients developing pneumonia ( P < 0.05). Conclusion: The investigated serum markers alone are not helpful to identify polytraumatized patients at risk of developing pneumonia, while a combination of IL-6, IL-10, PTX-3, and sRAGE might be.
-
Background: Exosome from adipose-derived stem cells (ADSCs-Exo) has been shown to inhibit the progression of human diseases, including sepsis-related acute kidney injury (AKI). CircVMA21 is considered to be an important regulator for sepsis-related AKI. However, whether ADSCs-Exo affected sepsis-induced AKI by delivering circVMA21 is not clear. ⋯ Besides, miR-16-5p inhibitor reversed the promotion effect of Exo-sh-circVMA21 on LPS-induced cell injury. In addition, ADSCs-Exo protected LPS-induced AKI in mice by increasing circVMA21 expression and decreasing miR-16-5p expression. Conclusion: Exosomal circVMA21 derived by ADSCs relieved LPS-induced AKI through targeting miR-16-5p, which provided a potential molecular target for treating sepsis-related AKI.
-
Nonantibody-mediated transfusion-related acute lung injury (TRALI) may account for up to 25% of TRALI cases. This indicates the need for further research to understand the pathophysiological mechanisms involved beyond antibody mediation fully. During this research, a TRALI rat model was developed using the trauma-blood loss-massive transfusion method. ⋯ In addition, HMGB1 and RIP3 promoted the inflammatory response by stimulating the toll-like receptor 44/nuclear factor kappa B and mitogen-activated protein kinase signaling pathways in the lung tissue of rats. Identifying efficient agents from inflammatory mediators such as alarmin can be an innovative scheme for diagnosing and preventing TRALI. These findings give HMGB1 and RIP3 a strong theoretical and experimental foundation for clinical use.