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
-
Observational Study
ENDOTHELIAL GLYCOCALYX SHEDDING IN INTRA-ABDOMINAL SEPSIS: A FEASIBILITY STUDY.
Background: The endothelial glycocalyx layer (EGL) is a complex meshwork of glycosaminoglycans and proteoglycans that protect the vascular endothelium. Cleavage or shedding of EGL-specific biomarkers, such as hyaluronic acid (HA) and syndecan-1 (SDC-1, CD138) in plasma, have been shown to be associated with poor clinical outcomes. However, it is unclear whether levels of circulating EGL biomarkers are representative of the EGL injury within the tissues. ⋯ Conclusions: Elevations in both circulating and tissue EGL biomarkers were positively correlated with postoperative SOFA scores at 24 hours, with resected pathologic tissue EGL levels displaying significant correlations with SOFA scores at all time points. Tissue and circulating EGL biomarkers were positively correlated at higher SOFA scores (SOFA > 6) and could be used as indicators of resuscitative needs within 24 hours of surgery. The present study demonstrates the feasibility of tissue and plasma procurement in the operating room, although larger studies are needed to evaluate the predictive value of these EGL biomarkers for patients with intra-abdominal sepsis.
-
Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. ⋯ This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.
-
Background: The importance of circular RNA (circRNA) in the progression of septic acute kidney injury (AKI) was gradually recognized. It has been confirmed that circ_0008882 expression was decreased in the blood of patients with AKI. However, the role of circ_0008882 in septic AKI progression remains unclear. ⋯ MiR-155-5p was a target of circ_0008882, and miR-155-5p mimic restored circ_0008882 overexpression-mediated effects on LPS-treated HK2 cells. PDE7A was identified as a target gene of miR-155-5p, and PDE7A downregulation almost reverted the improvement impacts induced by the miR-155-5p inhibitor. Conclusions: Overexpression of circ_0008882 impeded LPS-induced HK2 cell injury by modulating miR-155-5p/PDE7A pathway, implying that circ_0008882 might be a possible circRNA-targeted therapy for septic AKI.
-
Background: Lipopolysaccride-induced myocardial injury was characterized by frequent mitochondrial dysfunction. Our previous studies found that nucleolin (NCL) played important protective roles in myocardial ischemia-reperfusion injury. Recently, it has been found that NCL has a protective effect on LPS-induced myocardial injury in vivo. ⋯ In addition, the activation of PGC-1α diminished the detrimental effects of NCL knockdown on mitochondrial biogenesis in vitro and in vivo. Conclusions: Nucleolin upregulated the gene expression of PGC-1α by directly binding to the 5'-UTR of PGC-1α mRNA and increasing its mRNA stabilities, then promoted mitochondrial biogenesis, and played protective effect on cardiomyocytes during LPS-induced myocardial injury. Taken together, all these data showed that NCL activated PGC-1α to rescue cardiomyocytes from LPS-induced myocardial injury insult, suggesting that the cardioprotective role of NCL might be a promising prospect for clinical treatment of patients with endotoxemia.
-
This study aimed to explore the ameliorating effects of the platelet surface glycoprotein IIb/IIIa receptor antagonist tirofiban on coagulation and fibrinolytic abnormalities in a mouse model of antibody-mediated transfusion-associated acute lung injury (ALI). This is important because ALI is a major cause of death attributable to the occurrence of adverse transfusion reactions. No information on a definite diagnosis or pathological mechanism exists, and targeted treatment options are not available. ⋯ Compared with the TRALI model group, the lung injury indices in the tirofiban intervention group decreased significantly, and survival rates also improved. Furthermore, the level of coagulation and fibrinolytic abnormalities were obviously lower than those in the TRALI model group. In conclusion, our findings suggest that tirofiban might interfere with TRALI by inhibiting platelet activation and improving coagulation and fibrinolytic abnormalities.