Search

Herein, a highly efficient, scalable, and cascade [1,5] hydride transfer/cyclization method for constructing unique spirocyclic pyrazolone-pyrrolo[4,3,2- de ]quinoline structures via C(sp 3 )-H functionalization is achieved, using pyrazolones and oxindoles attached to C4 amines. This strategy represents a limited approach utilizing C-H activation to construct spirocyclic pyrazolone scaffolds with moderate to excellent reaction performance.

The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation. The patients were then divided into VIC and VMC groups. There were plaques in all anterior tibial arteries, while the enrichment of galectin-3 in arterial plaques in the VIC group was significantly higher than that in the VMC group. Furthermore, a macrophage/vascular smooth muscle cell (VSMC) coculture system was constructed. VSMC-derived extracellular vesicles (EVs) was labeled with fluorescent probe. After macrophages were pretreated with recombinant galectin-3 protein, the migration of VSMC-derived EVs and VSMC-derived calcification was more pronounced. And anti-galectin-3 antibody can inhibit this process of EVs and calcification translocation. Then, lentivirus (LV)-treated bone marrow cells (BMCs) were transplanted into apolipoprotein E-deficient (ApoE -/- ) mice, and a diabetic atherosclerosis mouse model was constructed. After 15 wk of high-fat diet, ApoE -/- mice transplanted with LV-shgalectin-3 BMCs exhibited medial calcification and a concentrated distribution of EVs in the media. In conclusion, upregulation of galectin-3 in macrophages promotes the migration of VSMC-derived EVs to the intima and induces diabetic vascular intimal calcification. NEW & NOTEWORTHY The clinical risk and prognosis of vascular intimal and medial calcification are different. Macrophage galectin-3 regulates the migration of vascular smooth muscle cell-derived extracellular vesicles and mediates diabetic vascular intimal/medial calcification translocation. This study may provide insights into the early intervention in diabetic vascular calcification.

Background: Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N ε -Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown., Methods and Results: In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE -/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE -/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia., Conclusion: CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Zhengyang Bao et al.)