Association between periodontitis and systemic lupus erythematosus: a meta-analysis.

OBJECTIVE: The objective of this study was to explore the association between periodontitis and systemic lupus erythematosus (SLE). METHODS: To identify eligible studies, the PubMed, EMBASE and Web of Science databases were searched from inception to 19 September 2019. Associations of periodontitis, and other periodontal parameters, with SLE were assessed. RESULTS: Ten studies involving 80,633 subjects were included in this meta-analysis. Pooled data showed a significant association between periodontitis and SLE (odds ratio=5.32, 95% confidence interval (CI) 1.69-16.78, p = 0.004). In addition, SLE patients had a higher prevalence of bleeding on probing (mean difference = 0.03, 95% CI 0.00-0.06, p = 0.02) and higher mean clinical attachment loss (mean difference = 0.69, 95% CI 0.39-1.00, p < 0.001). However, there were no significant differences between SLE and reference subjects in mean plaque index, gingival index, pocket depth or decayed, missing or filled teeth. CONCLUSIONS: This study demonstrates a significant association between periodontitis and SLE, which indicates that avoidance of periodontitis by maintaining oral health may be a simple and economical way to prevent SLE.

Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening.

Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3Cpro in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3Cpro inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3Cpro. The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21.72 ± 0.95 µM without apparent toxicity (CC50 > 200 µM). To explore structure-activity relationship of DC07090, 15 new derivatives were designed, synthesized and evaluated in vitro enzyme assay accordingly. Interestingly, four compounds showed inhibitory activities against EV71 3Cpro and only DC07090 inhibited EV71 replication with an EC50 value of 22.09 ± 1.07 µM. Enzyme inhibition kinetic experiments showed that the compound was a reversible and competitive inhibitor. The Ki value was determined to be 23.29 ± 12.08 µM. Further molecular docking, MD simulation and mutagenesis studies confirmed the binding mode of DC07090 and EV71 3Cpro. Besides, DC07090 could also inhibit coxsackievirus A16 (CVA16) replication with an EC50 value of 27.76 ± 0.88 µM. Therefore, DC07090 represents a new non-peptidyl small molecule inhibitor for further development of antiviral therapy against EV71 or other picornaviruses.