Sdccag3 Promotes Implant Osseointegration during Experimental Hyperlipidemia

Hyperlipidemia adversely affects bone metabolism, often resulting in compromised osseointegration and implant loss. In addition, genetic networks associated with osseointegration have been proposed. Serologically defined colon cancer antigen 3 (Sdccag3) is a novel endosomal protein that functions in actin cytoskeleton remodeling, protein trafficking and secretion, cytokinesis, and apoptosis, but its roles in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and in implant osseointegration under hyperlipidemic conditions have not been uncovered. Here, we performed microarray and RNA sequencing analysis to determine the differential expression of the Sdccag3 gene and related noncoding RNAs (ncRNAs) and to assess the long noncoding RNA (lncRNA) MSTRG.97162.4-miR-193a-3p-Sdccag3 coexpression network in bone tissues within the region 0.5 mm around implants in hyperlipidemic rats. In this experiment, we found that Sdccag3 and the previously uncharacterized lncRNA-MSTRG.97162.4 were downregulated during hyperlipidemia, while miR-193a-3p was upregulated. Sdccag3 overexpression increased new trabecular formation, the bone volume/total volume (BV/TV) (1.24-fold), and bone-implant combination ratio (BIC%) (1.26-fold). An RNA pulldown experiment revealed that Sdccag3 protein targeted lncRNA-MSTRG.97162.4 nucleotides 361 to 389. In addition, lncRNA-MSTRG.97162.4 overexpression significantly enhanced Sdccag3 (2.78-fold) expression and increased BV/TV (1.45-fold) and BIC% (1.07-fold) at the bone-implant interface. Taken together, these findings indicate that Sdccag3 overexpression enhances implant osseointegration under hyperlipidemic conditions by binding to lncRNA-MSTRG.97162.4. Furthermore, miR-193a-3p overexpression inhibited lncRNA-MSTRG.97162.4 (0.63-fold) and Sdccag3 (0.88-fold) expression and induced poor implant osseointegration (BV/TV, 0.86-fold; BIC%, 0.82-fold), while miR-193a-3p downregulation produced the opposite results (lncRNA-MSTRG.97162.4, 10.69-fold; Sdccag3, 6.96-fold; BV/TV, 1.20-fold; BIC%, 1.26-fold). Therefore, our findings show that Sdccag3 promotes implant osseointegration, and its related lncRNA-MSTRG.97162.4 and miR-193a-3p play an important role in osseointegration during hyperlipidemia, which might be a promising therapeutic target for improving dental implantation success rates.

Dronedarone: the effect of diet-induced obesity on its metabolism and experimental hyperlipidemia on its metabolism and tissue distribution in the rat

Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague–Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.

Effects of сramizol on expression of the ApoA1 gene in rats with experimental hyperlipidemia

An imidazole derivative cramizol, has lipid-lowering and anti-atherogenic effects. Cramizol reduces blood levels of cholesterol and triglycerides, and also reduces the atherogenic index in animals with acute hyperlipidemia induced by Triton WR-1339. Cramizol and the lipid-lowering drug fenofibrate exhibited similar effectiveness as hypolipidemic agents. Cramizol also restores the expression of the Apoa1 gene in rats with experimentally induced hyperlipidemia to normal values. This may be a basis of its hypolipidemic and anti-atherogenic action.

The effect of hyperlipidemia on the local content of cytokines in the zone of implantation of synthetic materials

Relevance. Abdominal plastic with the use of synthetic materials is a universally recognized method of treating ventral hernias. However, using implants, surgeons have faced the problem of tissue biocompatibility. The aim of the study was to evaluate the effect of synthetic implants from polypropylene mesh ("Esfil") and polytetrafluoroethylene ("Ecoflon") on local production of cytokines in experimental hyperlipidemia. Materials and methods. The work was performed on male Wistar rats weighing 250 ± 50 grams (n=54). The method of Meshcherskaya K.A. (1966) was used for the development of hyperlipidemia. The diet consisted of adding to the food of cholesterol powder 1%, 20% margarine and 2.5 IU of vitamin D per kg of body weight of rats for 6 months. The plastic of the anterior abdominal wall was performed by 8 month old animals using the Onlay method using the implants "Esfil" and "Ecoflon". The control group was rats with prosthetics of the abdominal wall on a normal diet. The material of the study was blood plasma and biopsy specimens of the muscle-aponeurotic rumen of the anterior abdominal wall of rats. Results. It was noticed in the course of the experimental study that the implants used in the reconstruction of the anterior abdominal wall have individual features of the effect on the local production of cytokines. "Ecoflon" has a more pronounced reactogenicity, manifested by hyperproduction of pro-inflammatory cytokines from 10 to 30 days. "Esfil" is characterized by less pronounced influence on local pro-inflammatory activity of cells in dynamics after alloplasty, in comparison with the use of "Ecoflon". Hyperlipidemia leads to a decrease in local production, both of pro-inflammatory and anti-inflammatory cytokines.