Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling.

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for prostaglandin synthesis during inflammation and immune responses. Our previous results show that NAD+ level decreased in activated macrophages while nicotinamide mononucleotide (NMN) supplementation suppressed the inflammatory responses via restoring NAD+ level and downregulating COX-2. However, whether NMN downregulates COX-2 in mouse model of inflammation, and its underlying mechanism needs to be further explored. In the present study, we established LPS- and alum-induced inflammation model and demonstrated that NMN suppressed the inflammatory responses in vivo. Quantitative proteomics in mouse peritoneal macrophages identified that NMN activated AhR signaling pathway in activated macrophages. Furthermore, we revealed that NMN supplementation led to IDO1 activation and kynurenine accumulation, which caused AhR nuclear translocation and activation. On the other hand, AhR or IDO1 knockout abolished the effects of NMN on suppressing COX-2 expression and inflammatory responses in macrophages. In summary, our results demonstrated that NMN suppresses inflammatory responses by activating IDO-kynurenine-AhR pathway, and suggested that administration of NMN in early-stage immuno-activation may cause an adverse health effect.

Intelligent Occlusion Stabilization Splint with Stress-Sensor System for Bruxism Diagnosis and Treatment.

Bruxism is a masticatory muscle activity characterized by high prevalence, widespread complications, and serious consequences but without specific guidelines for its diagnosis and treatment. Although occlusal force-based biofeedback therapy is proven to be safe, effective, and with few side effects in improving bruxism, its mechanism and key technologies remain unclear. The purpose of this study was to research a real-time, quantitative, intelligent, and precise force-based biofeedback detection device based on artificial intelligence (AI) algorithms for the diagnosis and treatment of bruxism. Stress sensors were integrated and embedded into a resin-based occlusion stabilization splint by using a layering technique (sandwich method). The sensor system mainly consisted of a pressure signal acquisition module, a main control module, and a server terminal. A machine learning algorithm was leveraged for occlusal force data processing and parameter configuration. This study implemented a sensor prototype system from scratch to fully evaluate each component of the intelligent splint. Experiment results showed reasonable parameter metrics for the sensors system and demonstrated the feasibility of the proposed scheme for bruxism treatment. The intelligent occlusion stabilization splint with a stress sensor system is a promising approach to bruxism diagnosis and treatment.