sirolimus and Periodontitis

A reduction in calorie intake [caloric restriction (CR)] appears to consistently decrease the biological rate of aging in a variety of organisms as well as protect against age-associated diseases including chronic inflammatory disorders such as cardiovascular disease and diabetes. Although the mechanisms behind this observation are not fully understood, identification of the main metabolic pathways affected by CR has generated interest in finding molecular targets that could be modulated by CR mimetics. This review describes the general concepts of CR and CR mimetics as well as discusses evidence related to their effects on inflammation and chronic inflammatory disorders. Additionally, emerging evidence related to the effects of CR on periodontal disease in non-human primates is presented. While the implementation of this type of dietary intervention appears to be challenging in our modern society where obesity is a major public health problem, CR mimetics could offer a promising alternative to control and perhaps prevent several chronic inflammatory disorders including periodontal disease.

Topics: Adaptive Immunity; Animals; Biomimetics; Caloric Restriction; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Humans; Immunity, Innate; Inflammation; Inflammation Mediators; Insulin-Like Growth Factor I; Metformin; Periodontitis; Resveratrol; Signal Transduction; Sirolimus; Sirtuins; Stilbenes; TOR Serine-Threonine Kinases

Metformin, a classical treatment for diabetes mellitus, has shown sound anti-inflammatory effects. Emerging studies have focused on the mechanism underlying inflammation-related diabetic complications, such as diabetic periodontitis. Herein, we investigated the anti-inflammatory effects of metformin on the NIMA-related kinase 7 (Nek7)/nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) pathway both in vivo and in vitro in experimental diabetic periodontitis.. All procedures were conducted in Porphyromonas gingivalis (Pg)-infected streptozotocin (STZ)-induced diabetic mice and in lipopolysaccharide (LPS)-treated RAW 264.7 cells under high-glucose conditions. A range of techniques were performed in this study: microcomputed tomography, western blotting, and immunofluorescence were used to analyze periodontal tissues. Enzyme-linked immunosorbent assay (ELISA) was for serum interleukin-1β (IL-1β) detection. Specific pharmacological inhibition was used to stimulate cells. Flow cytometry was implemented to analyze cell cycle.. We found that metformin treatment can robustly ameliorate periodontal infection and tissue destruction and reduce blood glucose and serum IL-1β levels in mice with diabetic periodontitis. Moreover, gingival tissue exhibited less macrophage infiltration and decreased expression of Nek7, NLRP3, caspase-1, and mammalian target of rapamycin (mTOR), which were simultaneously observed in RAW 264.7 cell models stimulated with metformin. Metformin also affected the cell cycle in a dose-dependent way. Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7/NLRP3.. Our research indicated that metformin significantly attenuated experimental diabetic periodontitis both in vivo and in vitro. Metformin suppressed the inflammatory state by inhibiting Nek7 expression to decrease NLRP3 inflammasome activity. Interestingly, mTOR inhibition was not involved in metformin-induced Nek7 downregulation. The observed Nek7 reduction could be related to metformin-mediated cell cycle arrest.

Topics: Animals; Diabetes Mellitus, Experimental; Interleukin-1beta; Metformin; Mice; NIMA-Related Kinases; NLR Family, Pyrin Domain-Containing 3 Protein; Periodontitis; Sirolimus; TOR Serine-Threonine Kinases; X-Ray Microtomography

To compare oral health status between renal transplant recipients (RTRs) receiving tacrolimus (Tac) or everolimus (ERL) as immunosuppressive therapy.. This study is a cross-sectional study.. Thirty-six RTRs receiving Tac and 22 RTRs receiving ERL were included in the study. Age, gender, time since transplant and pharmacological data were recorded for both groups. Oral health status was assessed through the evaluation of teeth, periodontal parameters as well as saliva flow rate and pH.. RTRs receiving ERL were older than those receiving Tac. No differences were found between groups concerning oral hygiene habits, oral symptoms, smoking habits, unstimulated and stimulated saliva flow rate and pH, clinical attachment level or the number of decayed, missing and filled teeth. However, RTRs receiving ERL presented lower visible plaque index and lower values for bleeding on probing when compared to RTRs receiving Tac. In addition, RTRs receiving ERL presented a gingival index varying from normal to moderate inflammation whereas RTRs receiving Tac presented a gingival index varying from mild to severe inflammation.. RTRs receiving ERL have lower periodontal inflammation when compared to RTRs receiving Tac.

Topics: Adolescent; Adult; Age Factors; Aged; Allografts; Cross-Sectional Studies; Dental Plaque Index; DMF Index; Everolimus; Female; Gingival Hemorrhage; Health Status; Humans; Hydrogen-Ion Concentration; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Oral Health; Oral Hygiene; Periodontal Attachment Loss; Periodontal Index; Periodontitis; Saliva; Secretory Rate; Sirolimus; Smoking; Tacrolimus; Young Adult