A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.

Magnolol's Therapeutic Efficacy and Immunomodulatory Effects in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) presents a significant health challenge, requiring effective treatments. Magnolol, a compound with potential anticancer properties, warrants investigation in OSCC treatment. Here, we aimed to assess the efficacy of magnolol in inhibiting progression of OSCC and to explore the underlying mechanisms of its action. MATERIALS AND METHODS: We evaluated the effect of magnolol on tumor progression using the MOC1-bearing orthotopic model. We examined its impact on pathology and toxicity through hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and biochemical analysis. We also investigated the immunoregulatory effects of magnolol in the MOC1-bearing model using flow cytometry. RESULTS: At high doses, magnolol significantly reduced tumor volume (p<0.0001 for comparisons between treated with magnolol and untreated groups) and weight loss by 70% in vivo. It also induced caspase-dependent apoptosis, evidenced by 2.42-, 2-, and 2.2-fold increases in the expression of caspase-3, -8, and -9, respectively, in mouse tumors treated with high 60 mg/kg of magnolol compared to untreated (p<0.0001 for all comparisons). Magnolol demonstrated no toxicity, maintaining body weight and normal biochemical parameters, including liver and kidney function. Pathological evaluations showed no adverse effects on organs in all treatment groups. Moreover, high doses of magnolol enhanced natural killer cells (by 3%), dendritic cells (20-25%), and cytotoxic T cells (20-40%) while reducing myeloid-derived suppressor cells and regulatory T cells by 1.5 times. CONCLUSION: Magnolol demonstrates potential as a therapeutic agent for OSCC, offering antitumor efficacy and immunomodulatory benefits.

Court decisions in criminal proceedings for dental malpractice in Taiwan.

BACKGROUND/PURPOSE: Malpractice claims place heavy economic and emotional burdens on both dentists and patients. Recently, medical malpractice lawsuits are decreasing in prevalence but increasing in severity. The percentage of dental malpractice payments is also growing among the health profession. The present study aimed to explore criminal convictions in dental malpractice litigation and to analyze the factors affecting the judgment in dental disputes in Taiwan. METHODS: The keywords "dentist," "professional negligence," "medical malpractice," and "professional liability" were used to search Taiwan's Law and Regulations Retrieving System for criminal dental malpractice cases in all district courts from January 1, 2000 to June 30, 2021. The eligible judgments were summarized and analyzed. RESULTS: Overall, 425 cases were identified, with 28 dental disputes included in the final analysis. The dentists lost in 10 cases (35.7%). The average claim time was 36.75 ± 16.34 months. Taipei and Taichung dealt with more lawsuit cases (n = 8). Local clinics were the most common institution of the defendants (75%) and had the highest number of convictions (n = 9). Implant dentistry was the most common specialty involved. Expert testimony of the Medical Review Committee (MRC) had a high K coefficient of agreement with court judgments regarding professional negligence (p < 0.001). CONCLUSION: The overall criminal conviction rate was 35.7%. Implant therapy and local clinics had the highest rate of lawsuits and a considerably higher conviction rate. All guilty dentists were fined or given probation. The court judgments were highly consistent with the expert testimony of the MRC.

Association between Periodontal Disease and Subsequent Sjögren's Syndrome: A Nationwide Population-Based Cohort Study.

Xerostomia (dry mouth) is the cardinal symptom of Sjögren's syndrome (SS), which is an autoimmune disease involving the exocrine glands and other organs. Xerostomia may predispose patients to periodontal disease (PD) and an association between SS and PD has been reported. This association may be bidirectional; therefore, we conducted this study to investigate the risk of SS in patients with PD using data from the National Health Insurance Research Database of Taiwan. A total of 135,190 patients were enrolled in our analysis. In all, 27,041 patients with PD were matched by gender, age, insured region, urbanization and income, with cases and controls in a 1:4 ratio. Both groups were followed and the risks of SS were calculated by Cox proportional hazards regression. Finally, 3292 (2.4%) patients had newly diagnosed SS. Patients with PD had a significantly higher risk of subsequent SS (903 (3.3%) vs. 2389 (2.2%), adjusted hazard 1.47, 95% confidence interval: 1.36⁻1.59). In conclusion, patients with PD had an approximately 50% increased risk of subsequent SS. Physicians should be aware of the symptoms and signs of SS in patients with PD.

Reliability and validity of DS-ADHD: A decision support system on attention deficit hyperactivity disorders.

BACKGROUND AND OBJECTIVES: The purpose of this study is to examine the reliability of the clinical use of the self-built decision support system, diagnosis-supported attention deficit hyperactivity disorder (DS-ADHD), in an effort to develop the DS-ADHD system, by probing into the development of indicating patterns of past screening support systems for ADHD. METHODS: The study collected data based on 107 subjects, who were divided into two groups, non-ADHD and ADHD, based on the doctor's determination, using the DSM-IV diagnostic standards. The two groups then underwent Test of Variables of Attention (TOVA) and DS-ADHD testing. The survey and testing results underwent one-way ANOVA and split-half method statistical analysis, in order to further understand whether there were any differences between the DS-ADHD and the identification tools used in today's clinical trials. RESULTS: The results of the study are as follows: 1) The ROC area between the TOVA and the clinical identification rate is 0.787 (95% confidence interval: 0.701-0.872); 2) The ROC area between the DS-ADHD and the clinical identification rate is 0.867 (95% confidence interval: 0.801-0.933). CONCLUSIONS: The study results show that DS-ADHD has the characteristics of screening for ADHD, based on its reliability and validity. It does not display any statistical differences when compared with TOVA systems that are currently on the market. However, the system is more effective and the accuracy rate is better than TOVA. It is a good tool to screen ADHD not only in Chinese children, but also in western country.

Associations between dental anxiety and postoperative pain following extraction of horizontally impacted wisdom teeth: A prospective observational study.

The aim of the study is to identify associations between dental anxiety and postoperative pain in patients undergoing extraction of horizontally impacted wisdom teeth.A total of 119 volunteers provided demographic data, and completed questionnaires, the State-Trait Anxiety Inventory (STAI), Chinese Index of Dental Anxiety and Fear (C-IDAF)-4C, and the Numeric Rating Scale (NRS) for pain.Mean SAI, TAI, and C-IDAF-4C scores were 42.5 ±â€Š8.7, 46.4 ±â€Š10.9, and 16.9 ±â€Š7.2, respectively. Mean postoperative pain level score was 3.0 ±â€Š1.8 (range: 0.3-8.4). SAI scores increased as preoperative pain levels increased (ß = 1.30, 95% confidence interval [CI]: 0.62-1.98, P < .001); females had higher SAI scores than males (5.34; 95% CI: 1.74-8.95, P = .004). Multivariable analysis revealed that females, bad exodontic experience, and higher predicted pain levels were associated with higher IDAF-4C scores. SAI scores (γ = 0.611, P < .001) and TAI scores (γ = 0.305, P < .001) increased as C-IDAF-4C scores increased. Higher C-IDAF-4C scores and longer operative time were significantly associated with higher levels of postoperative pain.Specific factors are associated with anxiety and stress, and postoperative pain in patients undergoing wisdom teeth extraction. Addressing these factors preoperatively may reduce stress and anxiety, and lead to more favorable treatment outcomes.

Clinical effectiveness, toxicity, and failure patterns of helical tomotherapy for postoperative oral cavity cancer patients.

BACKGROUND: The outcome of postoperative high- and intermediate-risk oral cavity cancer (OCC) patients receiving helical tomotherapy (HT) remains limited. MATERIALS AND METHODS: Between November 2006 and November 2012, 53 postoperative high- and intermediate-risk OCC patients treated with HT were enrolled. RESULTS: The 4-year locoregional, local, and regional control rates were 66%, 76.4%, and 94.3%, respectively. The 4-year locoregional control rates of oral tongue and buccal mucosa cancer were 88.3% and 37.1%, respectively (P=0.012). Eleven (20.8%) patients experienced locoregional failure. In-field failure occurred in six of 53 (11.3%) in the primary area and three of 53 (5.7%) in the regional lymph-node area. No marginal failure was noted. Two of 53 (3.8%) experienced out-of-field failure. The rates of grade 3 dermatitis, mucositis, and dysphagia were 11%, 34%, and 13%, respectively. No grade 3 xerostomia was noted. Grade 2 xerostomia was 33% at month 6 and declined to 0 at month 48. A rate of 56% of grade 2 trismus at month 6 was noted, and declined to around 30% after 2 years. No grade 3 trismus was noted after 2 years. CONCLUSION: HT as a postoperative modality provided satisfying results, especially for xerostomia and trismus, and was impressive in high- and intermediate-risk OCC patients receiving postoperative HT.

Predicting the severity and prognosis of trismus after intensity-modulated radiation therapy for oral cancer patients by magnetic resonance imaging.

To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal-Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy.