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: 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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Loss of function of the phospholipid scramblase (PLS) TMEM16F results in Scott Syndrome, a hereditary bleeding disorder generally attributed to intrinsic platelet dysfunction. The role of TMEM16F in endothelial cells, however, is not well understood. We sought to test the hypothesis that endothelial TMEM16F contributes to hemostasis by measuring bleeding time and venous clotting in endothelial-specific knockout (ECKO) mice. ⋯ Endothelial TMEM16F function is essential for normal hemostasis. ECKO of TMEM16F is sufficient to produce a coagulopathic phenotype, as shown by the prolonged bleeding time after tail transection and decreased thrombus generation in response to IVC stenosis. Because endothelial calcium events are pathologically amplified in response to trauma factors, these results suggest that TMEM16F may play a role in trauma-induced coagulopathy.
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The global prevalence of heart failure is still growing, which imposes a heavy economic burden. The role of microRNA-146b (miR-146b) in HF remain largely unknown. This study aims to explore the role and mechanism of miR-146b in HF. ⋯ MiR-146b knockout mice showed a more pronounced decrease in cardiac function and more severe myocardial fibrosis and apoptosis than wild type. Meanwhile, over expression or repression of miR-146b in primary neonatal mouse cardiomyocytes could inhibit or upregulate HIF-1α mRNA and protein expression. Conclusion: Our study shows that miR-146b may be a protective factor for cardiomyocytes by modulating HIF-1α.