Fusobacterium nucleatum infection activates the noncanonical inflammasome and exacerbates inflammatory response in DSS-induced colitis.

Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F. nucleatum infection leads to NLRP3 activation and pyroptosis, but the precise activation process and disease association remain poorly understood. This study demonstrated that F. nucleatum infection exacerbates acute colitis in mice and activates pyroptosis through caspase-11-mediated gasdermin D cleavage in macrophages. Furthermore, F. nucleatum infection in colitis mice induces the enhancement of IL-1⍺ secretion from the colon, affecting weight loss and severe disease activities. Neutralization of IL-1⍺ protects F. nucleatum infected mice from severe colitis. Therefore, F. nucleatum infection facilitates inflammation in acute colitis with IL-1⍺ from colon tissue by activating noncanonical inflammasome through gasdermin D cleavage.

The elevation of fibroblast growth factor 21 is associated with generalized periodontitis in patients with treated metabolic syndrome.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is closely associated with metabolic syndrome (MetS). An alteration of FGF21 is possibly affected by periodontitis. The present study aimed to investigate the levels of serum FGF21 in MetS patients with generalized periodontitis and its association with periodontal and metabolic parameters. METHODS: One hundred forty-six MetS patients were recruited from the CORE (Cohort Of patients at a high Risk for Cardiovascular Events) Thailand registry. All participants received general data interviewing, periodontal examination and blood collection for measurement of FGF21 levels and biochemistry parameters. Periodontitis was defined according to the new classification and divided into two groups of localized periodontitis and generalized periodontitis. RESULTS: FGF21 was significantly higher in generalized periodontitis group when compared with localized periodontitis group (p <  0.05). The significant correlation was observed between FGF21 and variables including number of remaining teeth, mean clinical attachment loss, hypertriglyceridemia and low high-density lipoprotein cholesterol. The elevation of serum FGF21 was associated with presence of generalized periodontitis after adjusting of covariate factors (OR = 27.12, p = 0.012). CONCLUSIONS: The elevation of serum FGF21 might be a potential biomarker for MetS patients who have risk of generalized periodontitis.

Ozone ultrafine bubble water induces the cellular signaling involved in oxidative stress responses in human periodontal ligament fibroblasts.

Periodontitis is a chronic inflammatory disease caused by oral microorganisms in the subgingival biofilm. Stable aqueous ozone ultrafine bubble water (OUFBW) has recently begun to be used as an antiseptic in the treatment of periodontitis. The effectiveness of OUFBW is thought to depend on the bactericidal actions of dissolved ozone exerted via its oxidizing effect. On the other hand, the effects of ozone on the periodontal tissues are largely unknown. In this paper we examined the cellular responses after OUFBW treatment. Human primary periodontal ligament fibroblasts (hPDLFs) or Ca9-22 human gingival epithelial cells were treated with OUFBW or UV-inactivated OUFBW. The production of reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor-kappa B (NF-κB) activation were analyzed. The transcript profiles of hPDLFs after OUFBW treatment were also analyzed by RNA sequencing (RNA-seq). Our results showed that OUFBW induces oxidative stress by generating ROS, which, in turn, activated the MAPK pathway. OUFBW triggered activation of c-Fos, a major component of the transcription factor activator protein 1 (AP-1), and also nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), which possessed a high sensitivity to oxidative stress. The results of RNA-seq analysis revealed that the numerous genes involved in oxidative stress responses or MAPK signaling pathway were up-regulated after OUFBW treatment. Investigation of the signaling pathways activated by OUFBW highlights another aspect of the biological roles of OUFBW, in addition to its bactericidal activity, in the treatment of periodontitis.