ABSTRACT
BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. CONCLUSION: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.
ABSTRACT
A series of novel thiazolidine-2,4-dione or rhodanine derivatives (5a-5k, 6a-6k) were synthesized and evaluated for their α-glucosidase inhibitory activity. The majority of compounds exhibited potent inhibitory activity in the range of 5.44 ± 0.13 to 50.45 ± 0.39 µM, when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 µM). Among the compounds in the series, compounds 5k, 6a, 6b, 6e, 6h and 6k showed potent inhibitory potential with IC50 values of 20.95 ± 0.21, 16.11 ± 0.19, 7.72 ± 0.16, 7.91 ± 0.17, 6.59 ± 0.15 and 5.44 ± 0.13 µM, respectively. Compound 6k (IC50 = 5.44 ± 0.13 µM), containing chloro and rhodanine groups at the 2- and 4-positions of the phenyl ring respectively, was found to be the most active compound that inhibits α-glucosidase activity. Furthermore, molecular docking studies were performed to understand the binding interactions between the molecule and enzyme.
ABSTRACT
AIM: To investigate a new technique of the anorectal fistula treatment with acellular extracellular matrix (AEM). METHODS: Thirty patients with anorectal fistula were treated with AEM. All fistula tracts and primary openings were identified using conventional fistula probe. All tracts were curetted with curet and irrigated with hydrogen peroxide and metronidazole. The AEM was pulled into the fistula tract from secondary to primary opening. The material was secured at the level of the primary opening. The excess AEM was trimmed at skin level at the secondary opening. RESULTS: All of the 30 patients had successful closure of their fistula after a 7-14 d follow-up. The healing rate of anal fistula in treatment group was 100%. The ache time, healing time and anal deformation of treatment group were obviously superior to traditional surgical methods. CONCLUSION: Using AEM anal fistula plug in treatment that causes the anorectal fistula is safe and successful in 100% of patients. It can reduce pain, shorten disease course and protect anal function.
