Periodontitis is a chronic non-communicable inflammatory disease in which oxidative stress plays an important role in tissue destruction and alveolar bone loss. Excessive production of reactive oxygen species disrupts redox homeostasis, activates inflammatory signaling pathways, and promotes regulated cell death processes such as pyroptosis and ferroptosis. The Nrf2/Keap1 pathway is a key regulator of antioxidant defense and cellular adaptation to redox imbalance. Impaired Nrf2 signaling has been associated with enhanced oxidative injury, NF-κB and NLRP3 inflammasome activation, osteoclast-driven bone resorption, and reduced regenerative capacity in periodontal tissues. Experimental studies suggest that Nrf2 activation can restore the redox balance and attenuate inflammation and bone destructive responses in a periodontal model. Moreover, therapeutic approaches involving phytochemicals, microbial-derived metabolites, and redox-responsive biomaterials have been reported to influence Nrf2-related signaling in experimental settings. However, the majority of the available evidence is derived from in vitro or animal studies, and the relevance of these findings to clinical periodontitis remains to be established. This review summarizes the current advances linking oxidative stress, redox signaling, cell death pathways, and bone remodeling with Nrf2 dysfunction in periodontitis and outlines the key mechanistic insights while highlighting the existing knowledge gaps.

Calcification plays a key role in biological processes, and breakdown of the regulatory mechanism results in a pathological state such as ectopic calcification. We hypothesized that ENPP1, the enzyme that produces the calcification inhibitor pyrophosphate, is transcriptionally regulated by Nrf2, and that Nrf2 activation augments ENPP1 expression to inhibit ectopic calcification. Cell culture experiments were performed using mouse osteoblastic cell line MC3T3-E1. Nrf2 was activated by 5-aminolevulinic acid and sodium ferrous citrate. Nrf2 overexpression was induced by the transient transfection of an Nrf2 expression plasmid. ENPP1 expression was monitored by real-time RT-PCR. Because the promoter region of ENPP1 contains several Nrf2-binding sites, chromatin immunoprecipitation using an anti-Nrf2 antibody followed by real-time PCR (ChIP-qPCR) was performed. The relationship between Nrf2 activation and osteoblastic differentiation was examined by alkaline phosphatase (ALP) and Alizarin red staining. We used mice with a hypomorphic mutation in ENPP1 (ttw mice) to analyze whether Nrf2 activation inhibits ectopic calcification. Nrf2 and Nrf2 overexpression augmented ENPP1 expression and inhibited osteoblastic differentiation, as indicated by ALP expression and calcium deposits. ChIP-qPCR showed that some putative Nrf2-binding sites in the ENPP1 promoter region were bound by Nrf2. Nrf2 activation inhibited ectopic calcification in mice. ENPP1 gene expression was transcriptionally regulated by Nrf2, and Nrf2 activation augmented ENPP1 expression, leading to the attenuation of osteoblastic differentiation and ectopic calcification in vitro and in vivo. Nrf2 activation has a therapeutic potential for preventing ectopic calcification.

Background: The Index of Orthodontic Treatment Need (IOTN) is widely used to assess the need for orthodontic treatment. IOTN consists of the Dental Health Component (DHC) and the Aesthetic Component (AC), evaluating malocclusion morphologically and aesthetically, respectively. However, the discriminatory power of individual DHC items and their relationship with AC grades remain unclear. Objective: This study aimed to evaluate the effectiveness of individual DHC items in school dental examinations and investigate their contribution to AC grades among junior high and high school students. Methods: A total of 726 students (443 males, 283 females; aged 12–18 years) from Tsurumi University Junior and Senior High School, excluding 168 students undergoing or having completed orthodontic treatment, were included. Nine calibrated orthodontists assessed DHC and AC using IOTN during standardized school examinations. The discriminatory power and information precision of DHC items were evaluated by Item Response Theory (IRT) analysis using three-, two-, or one-parameter logistic models depending on convergence. Correspondence analysis visualized the correlation between DHC and AC grades. Simple linear regression analyzed the contribution of each DHC item to AC grades. Results: Orthodontic treatment need was identified in 21.1% of students. Females showed a higher rate of treatment need than males. Correspondence analysis suggested that aesthetic evaluations were more lenient than morphological evaluations. IRT and regression analysis revealed that crowding (4.d), increased overjet (2.a), and increased overbite (2.f) demonstrated high discriminatory power and significant contributions to AC grades. Conclusions: Among the DHC items, crowding, increased overjet, and increased overbite had higher discriminatory power for malocclusion and contributed more significantly to AC evaluations compared to other items.

Mandibular retrognathism occurs by insufficient mandibular growth and causes several issues, such as respiratory difficulty and diminished masticatory function. At present, functional orthodontic appliances are used for stimulating mandibular growth in pediatric cases. However, the effectiveness of functional appliances is not always stable in daily practices. A more effective, reliable, and safer therapeutic method for mandibular growth promotion would be helpful for growing mandibular retrognathism patients. As we previously discovered that nutritional supplementation of myo-inositol in growing mice specifically increases mandibular endochondral growth, we performed preclinical animal experiments in rabbits in this study. Briefly, six-week-old male Japanese white rabbits were fed with or without myo-inositol supplementation in laboratory chow until 25 weeks old, and 3D image analysis using micro CT data and histological examinations was done. Myo-inositol had no systemic effect, such as femur length, though myo-inositol specifically augmented the mandibular growth. Myo-inositol increased the thickness of mandibular condylar cartilage. We discovered that the nutritional supplementation of myo-inositol during the growth period specifically augmented mandibular growth without any systemic influence, even in rabbits. Our results suggest the possibility of clinical use of myo-inositol for augmentation of the mandibular growth in growing mandibular retrognathism patients in the future.

Oral mucositis is a frequent adverse effect of cancer therapy and is often complicated by pain, oral dryness, and secondary infection. Freeze-dried hyaluronic acid (HA) sheets can protect and moisturize the oral mucosa, but their intrinsic antibacterial activity is limited. We developed freeze-dried HA sheets containing the commercial persimmon tannin product PANCIL^® PS-M and evaluated their release behavior, pH profile, antimicrobial activity, and in vitro cytocompatibility. Persimmon tannin release into phosphate-buffered saline was quantified over 8 h using the Folin–Ciocalteu method. Antimicrobial activity against Streptococcus mitis, Prevotella intermedia, and Candida albicans was assessed by colony counting, and cytocompatibility was evaluated using the human oral cell line T3M-1. Approximately 95% of the incorporated persimmon tannin was released within 8 h, while the surrounding pH remained near neutral to mildly alkaline. The antibacterial HA sheets markedly reduced viable counts of S. mitis and P. intermedia, whereas no inhibitory effect was observed against C. albicans. Neither HA sheet nor antibacterial HA sheet solutions significantly reduced T3M-1 cell viability at concentrations up to 100 µg/mL after 24 h. These findings suggest that persimmon tannin-containing HA sheets may provide sustained antibacterial activity without detectable cytotoxicity under the tested conditions and may serve as a topical adjunct for cancer treatment-related oral mucositis.

Background: Older inpatients in acute care hospitals often have impaired swallowing, which adversely affects nutrition and prognosis. However, limited research has ex-amined how dietary form, oral health, and functional independence interact in this population. Methods: We conducted a cross-sectional study of 74 patients (mean age, 87.1 ± 6.0 years) admitted to the Department of Geriatric Medicine, Kanazawa Medical Univer-sity Hospital. Dietary form was determined by swallowing specialists using videoen-doscopic (VE) and videofluoroscopic (VF) evaluations. Oral health was assessed with the Japanese Oral Health Assessment Tool (OHAT-J), and functional independence was measured with the Functional Independence Measure (FIM). Logistic regression, including stepwise selection, identified predictors of dietary form. Receiver operating characteristic (ROC) curve analysis evaluated model discrimination. Results: Higher OHAT scores were linked to a lower likelihood of receiving a regu-lar/soft diet (adjusted OR, 0.69; 95% CI, 0.54–0.89; p = 0.003), while higher FIM scores were linked to a greater likelihood (adjusted OR, 1.04; 95% CI, 1.01–1.07; p = 0.003). Age, serum albumin, and remaining teeth were not predictors. In stepwise regression, only OHAT and FIM remained significant. Model discrimination was strong, with AUC 0.85 for the full model and 0.82 for the simplified model. Conclusions: Poor oral health and low functional independence were associated with restricted dietary forms. Combined use of OHAT-J and FIM offers a practical and reli-able method for predicting dietary form in acute care, supporting integrated oral health and functional assessments for older inpatients.