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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Chronic kidney disease (CKD)-related vascular calcification (VC) is a common degenerative phenomenon of the vessel wall and its pathological basis is the phenotypic transformation of vascular smooth muscle cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have been reported to be expressed in the aortic tissues in a rat model of VC. This work is conducted to reveal the functions of ZBTB16 on VC in CKD and to probe its involved reaction mechanisms. ⋯ Moreover, silencing with ZBTB16 inactivated Wingless-related integration site (Wnt)/β-catenin pathway. LiCl (Wnt/β-catenin agonist) reversed the protective effects of ZBTB16 knockdown on the calcification and osteoblastic transformation in vitro. Together, ZBTB16 silencing may downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.
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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.