Modulation of Sirt1/NF-κB interaction of evogliptin is attributed to inhibition of vascular inflammatory response leading to attenuation of atherosclerotic plaque formation.

Evogliptin is a novel, potent and selective dipeptidyl peptidase 4 inhibitor that has received approval for use in the treatment of type 2 diabetes in South Korea. In the management of diabetes, it is important to reduce cardiovascular risk factors, as this can decrease the complication and mortality rate. However, the effect of evogliptin on the atherosclerotic progression has not been evaluated. In this study, we examined the effects of evogliptin on the progression of atherosclerosis and its possible mechanism of action. The anti-atherosclerotic effect of evogliptin was evaluated in ApoE-knockout mice fed high-fat diet analysed by plaque lesion formation, lipid profiles and vascular inflammatory response in the atherosclerotic progression. The in vitro effects of evogliptin were verified in endothelial cells analysed by immunoblotting, siRNA gene knockdown, promoter-luciferase assay, immunoprecipitation and adhesion assay. Evogliptin reduced the high-fat diet-induced atherosclerotic plaque area in the ApoE-/- mouse model. Macrophage infiltration into lesions was suppressed in the evogliptin group. In the endothelial cells, evogliptin inhibited inflammatory responses via suppression of adhesion molecules induced by TNF-α. TNF-α-mediated activation of NF-κB was ameliorated by evogliptin via the interaction of NF-κB with SIRT1 (Sirtuin-1). TNF-α-mediated adhesion between endothelial cells and monocytes was inhibited by evogliptin, but this inhibitory effect was reversed by Sirt1 gene knockdown. This study demonstrates that the protective effect of evogliptin on atherosclerotic progression via inhibition of vascular inflammation. The findings imply that evogliptin has potential for anti-atherosclerosis therapy that targets arterial inflammation.

Periodontal status of anterior teeth following clinical crown lengthening by minimally traumatic controlled surgical extrusion.

BACKGROUND/AIMS: The number of fractured anterior teeth following trauma has been increasing while not every patient is able to afford a dental implant instead of maintaining the injured tooth. Thus, a tooth conservation solution is required to place an aesthetic and functional restoration without biologic width violation. The aim of this study was to evaluate the effectiveness of minimally traumatic controlled surgical extrusion in fractured anterior teeth crown lengthening by assessing the periodontal status through clinical examination and radiographs. METHODS: This longitudinal observational study investigated a group of 18 patients (six males and 12 females) at the Department of Periodontology, National Hospital of Odonto-stomatology, Ho Chi Minh City, Vietnam. Following pre-surgery procedures and examination, minimally traumatic controlled surgical extrusion was carried out using a periotome. Patients were examined at four follow-up appointments after 1 week, 1, 3 and 6 months to record the following experimental variables: periodontal parameters including the gingival index (GI), pocket depth (PD), bleeding on probing (BOP), mobility, marginal gingiva position, alveolar ridge resorption, periapical osteogenesis, tooth resorption and ankylosis. RESULTS: All periodontal parameters were significantly decreased at 3 and 6 months post-procedure (P < 0.001). Tooth mobility decreased gradually following surgery, and at 6 months, all teeth became normal at level 0. Periapical osteogenesis changes were significantly increased at 1, 3 and 6 months in comparison with pre-surgery (P < 0.001). Marginal gingiva position and alveolar ridge resorption were not significantly different between pre-surgery and 1, 3 and 6 months post-surgery. No cases of root resorption or ankylosis were observed at 6 months post-surgery. CONCLUSION: A minimally traumatic controlled surgical extrusion technique for clinical crown lengthening yielded highly successful results in both aesthetic and functional aspects, and no cases had unfavourable outcomes during the 6-month follow-up period.

Effects of platelet-rich plasma on human gingival fibroblast proliferation and migration in vitro

Abstract Objective This study evaluated the influence of platelet-rich plasma (PRP) on the behaviour of human gingival fibroblasts (hGFs), including fibroblast proliferation, migration and colony formation. Methods PRP was obtained from the human peripheral blood of a healthy volunteer and then was diluted into platelet concentrations of 1%, 2% and 5%. The proliferation of hGFs was determined by two methods: (1) Cell-number counting with a haemocytometer method at days 1, 3, 5 and 7; (2) Colony-forming unit-fibroblast (CFU-F) assay at 2 weeks. The migration of hGFs was evaluated with scratch assay, then recorded digital images were analysed by Image-Analysis J 1.51j8 software to compare the remaining artificial wound areas between PRP groups at 0, 24 and 48 hours. Results All hGFs that were cultivated in media with 1%, 2% and 5% PRP showed their ability to proliferate and migrate. Cell numbers incubated with 1% PRP increased significantly during the first three days and peaked at day 5, tending to be similar to their proliferation in complete medium. With concentrations of 2% and 5% PRP, hGFs outgrew and peaked at day 3, which was faster than with those in medium with 1% PRP. Especially, hGFs in the group 5% PRP proliferated with higher cell numbers than those in the other remaining groups at day 3. The hGF colony number that was formed in the group 5% PRP was significantly higher than those in the groups 1% and 2% PRP. Scratch assay showed hGFs in the groups 2% and 5% PRP almost filled the artificial wound and migrated more effectively than in the group 1% PRP at 24 hours, which was significant. Conclusion In this study, perhaps the medium with 5% PRP is the dominant option, promoting the abilities of hGFs to heal wounds, because of its fast and effective impact on cell proliferation, colony formation and migration.

The physico-chemical alteration of lovastatin and enhanced antioxidant effect of Bacillus subtilis fermented-red yeast rice product.

Red yeast rice product (RYP) has been used as a food supplement because of its lipid lowering, and in food additives as a natural colorant. Lovastatin of RYP is a hypolipidemic commercial drug. To enhance the beneficial effects of RYP, we performed a bioconversion with Bacillus subtilis. This B. subtilis-fermentation process of RYP increased the ratio of the active open-hydroxyl acid form and the prodrug lactone form of lovastatin, which is a potent cholesterol synthesis inhibitor. 3(2H)-benzofuranone was newly produced in the fermented red yeast rice product (FRYP) as analyzed by GC-MS. FRYP increased the free radical scavenging activity compared with RYP. FRYP blocked xanthine oxidase (XO)-induced oxidative cytotoxicity and inhibited the H2O2-induced intracellular ROS in cells. This is the first study to illustrate that B. subtilis-fermented FRYP is useful for facilitating the alteration in the physico-chemical property of lovastatin and enhancing antioxidant activity, which may have greater pharmacological activity.