Causal effects of denture wearing on epigenetic age acceleration and the mediating pathways: a mendelian randomization study.

BACKGROUND: The epigenetic-age acceleration (EAA) represents the difference between chronological age and epigenetic age, reflecting accelerated biological aging. Observational studies suggested that oral disorders may impact DNA methylation patterns and aging, but their causal relationship remains largely unexplored. This study aimed to investigate potential causal associations between dental traits and EAA, as well as to identify possible mediators. METHODS: Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate the overall and independent effects of ten dental traits (dentures, bleeding gums, painful gums, loose teeth, toothache, ulcers, periodontitis, number of teeth, and two measures of caries) on four EAA subtypes (GrimAge acceleration [GrimAA], PhenoAge acceleration [PhenoAA], HannumAge acceleration [HannumAA] and intrinsic EAA [IEAA]), and used two-step Mendelian randomization to evaluate twelve potential mediators of the associations. Comprehensive sensitivity analyses were used to verity the robustness, heterogeneity, and pleiotropy. RESULTS: Univariable inverse variance weighted MR analyses revealed a causal effect of dentures on greater GrimAA (ß: 2.47, 95% CI: 0.93-4.01, p = 0.002), PhenoAA (ß: 3.00, 95% CI: 1.15-4.85, p = 0.001), and HannumAA (ß: 1.96, 95% CI: 0.58-3.33, p = 0.005). In multivariable MR, the associations remained significant after adjusting for periodontitis, caries, number of teeth and bleeding gums. Three out of 12 aging risk factors were identified as mediators of the association between dentures and EAA, including body mass index, body fat percentage, and waist circumference. No evidence for reverse causality and pleiotropy were detected (p > 0.05). CONCLUSIONS: Our findings supported the causal effects of genetic liability for denture wearing on epigenetic aging, with partial mediation by obesity. More attention should be paid to the obesity-monitoring and management for slowing EAA among denture wearers.

Assessment of the cancerization risk for oral potentially malignant disorders by clinical risk model combined with autofluorescence and brush biopsy with DNA-image cytometry.

PURPOSE: To explore the feasibility of assessing the cancerization risk of oral potentially malignant disorders (OPMD) through a clinical risk model combined with autofluorescence and brush biopsy with DNA-image cytometry. METHODS: We collected the baseline clinical data of 269 patients; then, performed autofluorescence, brush biopsy with DNA-image cytometry and histopathological examination. Then, we obtained the significant factors by univariate logistic analysis, constructed the clinical risk model by multiple logistic regression and selected the optimal cutoff value according to the maximum Youden index. Finally, we calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the clinical risk score ≥ cutoff value, autofluorescence and brush biopsy with DNA-image cytometry, and plotted the receiver-operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: The clinical risk model is represented by the formula: 1 × gender + 1.6 × age group + 1 × lesion site + 1.4 × local stimulus + 1.5 × drink. The area under the curve (AUC) was 0.83, and the optimal cutoff score was 3. The AUC indicated that the clinical risk score ≥ 3 (0.74) and autofluorescence (0.77) had a certain diagnostic values, while brush biopsy with DNA-image cytometry (0.92) displayed a good value. Besides, the DCA showed that all three tests had clinical significance. CONCLUSIONS: The cancerization risk of patients can be assessed by the clinical risk model combined with sequence application of autofluorescence and brush biopsy with DNA-image cytometry, to decide whether histopathological examination or other intervention measures should be selected.

Systematic Review and Meta-Analysis of Oxidative Stress and Antioxidant Markers in Oral Lichen Planus.

BACKGROUND: Oral lichen planus (OLP) is a relatively common chronic inflammatory disease of unknown etiology, which might be caused by oxidative stress and impaired antioxidant defense. OBJECTIVE: To systematically investigate the markers of oxidative stress and antioxidant systems in the saliva and blood from OLP patients and healthy controls. METHODS: The PubMed, Cochrane Library, and Embase were systematically queried to collect data from studies in which oxidative stress/antioxidant markers from OLP and healthy subjects had been evaluated until March 10, 2021. RESULTS: A total of 28 studies fulfilled inclusion criteria, and 25 of them, having 849 OLP patients and 1,052 control subjects and analyzing 12 oxidative stress and antioxidant state marker levels, were subjected to meta-analysis. We found a significant decrease in total antioxidant capacity (TAC) and uric acid (UA) and a significant increase in malondialdehyde (MDA) and nitric oxide (NO) levels in the saliva and serum/plasma of OLP patients. Moreover, a significant elevation of 8-hydroxy-deoxyguanosine (8-OHdG) and advanced oxidation protein product (AOOP) level and a decrease in vitamin C were also observed in the saliva of the OLP group. In contrast, salivary vitamin A, zinc, glutathione peroxidase (GPx), vitamin E, and nitrite were not significantly different between the two groups. In single studies, markers of oxidative stresses such as superoxide dismutase (SOD) and 8-isoprostanelevels were elevated in OLP, and antioxidant parameters such as glutathione (GSH) and total protein (TP) levels were dysregulated. CONCLUSION: This meta-analysis helps to clarify the profile of oxidative stress and antioxidant state markers in OLP patients although existing evidence is rather heterogeneous and many studies are affected by several limitations. Larger and more standardized studies are warranted to ascertain whether these markers are potential causes or effects of OLP and whether antioxidant therapy improving oxidative stress will be useful.