Objectives: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. Materials and Methods: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. Conclusions: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. Clinical relevance: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

The kynurenine pathway (KP), the primary route of tryptophan (TRP) metabolism, is influenced by inflammation and hypoxia and has been linked to immune dysregulation and oxidative stress. This study investigated the relationship between KP activity and hypoxia in periodontal inflammation, as well as their association with clinical periodontal parameters. A total of 23 systemically healthy patients with stage III, grade B periodontitis and 22 periodontally healthy individuals were included. Salivary and serum levels of tumor necrosis factor-alpha (TNF-α), hypoxia-inducible factor-1 alpha (HIF-1α), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured using ELISA. KP metabolites were analyzed via liquid chromatography-mass spectrometry. Results showed that salivary TNF-α, HIF-1α, and 8-OHdG levels were significantly higher in the periodontitis group ( P < .05). Both salivary and serum kynurenine/tryptophan (KYN/TRP) ratios and picolinic acid (PA), along with salivary 3-hydroxykynurenine (3OHKYN) and serum kynurenine (KYN), were elevated in periodontitis ( P < .05). In contrast, TRP levels in both saliva and serum were significantly reduced ( P < .001). Correlation analyses revealed that TRP levels were negatively associated with periodontal disease severity, whereas the salivary KYN/TRP ratio, 3OHKYN, HIF-1α, 8-OHdG, and TNF-α were positively associated ( P < .05). Strong correlations were observed between the saliva and serum compartments, with a strong positive relationship between salivary and serum TRP and a moderate correlation for the KYN/TRP ratios. Multivariate logistic regression identified salivary KYN/TRP ratio and HIF-1α as independent predictors of periodontitis after adjusting for age and gender, with male gender also emerging as a significant factor ( P < .05). Overall, the findings suggest that KP alterations, hypoxia, and oxidative stress are closely interconnected in periodontal inflammation. However, due to the cross-sectional design, these associations should not be interpreted as causal. The KP and hypoxia pathways may serve as potential non-invasive biomarkers for periodontitis.

ObjectiveThis study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-a (TNF-a), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking.BackgroundTight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown.MethodsThe study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-a levels in GCF.ResultsIn the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-a, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-a, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005).ConclusionsSmoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Background: The microbiome is a dynamic system that changes throughout life. Studies have revealed the relationship between periodontal disease and the oral microbiota; however, the impact of periodontal disease on the expression of senescence markers and on the inflammaging of the oral and systemic microbiome remains unclear. We hypothesized that aging increases the periodontitis‐induced changes in the oral and systemic microbiome and is accompanied by an altered inflammatory response. Methods: Experimental periodontitis was induced in 18‐month‐old (old) and 8‐month‐old (young) C57BL/6 mice by placing ligatures around the second maxillary molars. Bone morphometric analyses were conducted to assess bone loss. Senescence‐ and inflammatory‐related gene expression in the gingiva was measured by quantitative polymerase chain reaction (qPCR). Serum inflammatory markers were evaluated via immunoassay. Oral, brain, and gut microbial content were analyzed using next‐generation sequencing. Results: Maxillary bone loss was significantly higher in the old mice with periodontal disease than in young mice. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. The alpha diversity of the oral and brain microbial communities differed significantly between old and young mice. Treponema denticola , Fusobacterium nucleatum, Porphyromonas gingivalis, P. pasteri , and Prevotella nigrescens were only detected in the brains of old animals with periodontitis. Conclusion: Periodontopathogens and oral commensals are either only found in the brains of old animals with periodontal disease or are more prevalent in the brains of old animals, suggesting that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain. Plain language summary: Aging may increase the periodontitis‐induced changes in the oral and systemic microbiome, which an altered inflammatory response may accompany. Experimental periodontitis was created in old and young mouse models. Bone loss, senescence, and inflammatory gene expression and serum inflammatory markers were assessed in each model, and oral, brain, and gut microbial content was analyzed. Senescence and inflammatory markers were higher in old mice than in young ones, and periodontitis increased their expression. Our results suggested that aging and periodontitis may contribute to the dissemination of oral bacteria to the brain.