The objective of this study was to explore salivary metabolite biomarkers by profiling both saliva and tumor tissue samples for oral cancer screening. Paired tumor and control tissues were obtained from oral cancer patients and whole unstimulated saliva samples were collected from patients and healthy controls. The comprehensive metabolomic analysis for profiling hydrophilic metabolites was conducted using capillary electrophoresis time-of-flight mass spectrometry. In total, 85 and 45 metabolites showed significant differences between tumor and matched control samples, and between salivary samples from oral cancer and controls, respectively (P < 0.05 correlated by false discovery rate); 17 metabolites showed consistent differences in both saliva and tissue-based comparisons. Of these, a combination of only two biomarkers yielded a high area under receiver operating characteristic curves (0.827; 95% confidence interval, 0.726–0.928, P < 0.0001) for discriminating oral cancers from controls. Various validation tests confirmed its high generalization ability. The demonstrated approach, integrating both saliva and tumor tissue metabolomics, helps eliminate pseudo-molecules that are coincidentally different between oral cancers and controls. These combined salivary metabolites could be the basis of a clinically feasible method of non-invasive oral cancer screening.

The aim of this study is to evaluate the effect of duration after meals for saliva collections for oral cancer detection using metabolomics. Saliva samples were collected from oral cancer patients (n = 22) and controls (n = 44). Saliva from cancer patients was collected 12 h after dinner, and 1.5 and 3.5 h after breakfast. Control subjects fasted >1.5 h prior to saliva collection. Hydrophilic metabolites were analyzed using capillary electrophoresis mass spectrometry. Levels of 51 metabolites differed significantly in controls vs. oral cancer patients at the 12-h fasting time point (P < 0.05). Fifteen and ten metabolites differed significantly at the 1.5- and 3.5-h time points, respectively. The area of under receiver operating characteristic curve for discriminating oral cancer patients from controls was greatest at the 12-h fasting time point. The collection time after meals affects levels of salivary metabolites for oral cancer screening. The 12-h fasting after dinner time point is optimal. This study contributes to design of saliva collection protocols for metabolomics-based biomarker discovery.

Zinc is an essential trace element that plays an important role in differentiation of osteoblasts and bone modeling. This in vitro study aimed to evaluate the osteoblast differentiation of human dental pulp stem cells (DPSCs) on zinc-modified titanium (Zn-Ti) that releases zinc ions from its surface. Based on real-time PCR, alkaline phosphatase (ALP) activity and Western blot analysis data, we investigated osteoblast differentiation of DPSCs cultured on Zn-Ti and controls. DPSCs cultured on Zn-Ti exhibited significantly up-regulated gene expression levels of osteoblast-related genes of type I collagen (Col I), bone morphogenetic protein 2 (BMP2), ALP, runt-related transcription factor 2 (Runx2), osteopontin (OPN), and vascular endothelial growth factor A (VEGF A), as compared with controls. We also investigated extracellular matrix (ECM) mineralization by Alizarin Red S (ARS) staining and found that Zn-Ti significantly promoted ECM mineralization when compared with controls. These findings suggest that the combination of Zn-Ti and DPSCs provides a novel approach for bone regeneration therapy.

Objective Dementia is a major cause of disruption for a healthy life expectancy in Japan. It has been suggested that the number of teeth is a modifiable risk factor for cognitive impairment and dementia. We therefore examined the possible association between the cognitive function and the number of natural and artificial teeth in community-dwelling Japanese elderly individuals. Methods Among the participants in our prospective, community-based study, 210 elderly individuals (103 men and 107 women; 78.1±4.9 years; mean age±standard deviation) underwent both dental examinations and a Mini-Mental State Examination (MMSE), as well as various medical checkups, in 2016 and 2017. Results The number of natural teeth was significantly associated with an individual's MMSE score. The percentage of cognitively normal subjects (MMSE scores: 27-30) decreased significantly with a decrease in the number of natural teeth. Among the MMSE items, the calculation ability was significantly and independently associated with the number of natural teeth. Regression was calculated as the predicted score of MMSE =21+0.3×(years of schooling)+0.1×(number of natural teeth). Among individuals with 19 or fewer natural teeth, those who had a total of 20 teeth or more, including both natural and artificial teeth, had significantly higher MMSE scores than those who had 19 or fewer natural and artificial teeth combined. Conclusion The number of natural teeth was significantly associated with the cognitive function, especially the calculation ability, and the use of artificial teeth was associated with the preservation of the cognitive function in community-dwelling elderly individuals.

Lipoma is relatively uncommon in the oral cavity. Among the intraoral regions, lipoma involving the gingiva or gingivobuccal fold is relatively infrequent. We report the case of a patient with lipoma extending superiorly from the mandibular gingivobuccal fold to the gingiva. In addition to the case report, we retrospectively reviewed 207 patients with intraoral lipoma reported in Japan from 1987 to 2004. The most frequent site of development was the buccal mucosa (40.6%), followed by the tongue (17.9%), lip (12.6%), gingiva (8.7%), oral floor (6.8%), gingivobuccal fold and palate (4.8%), and others (3.9%). Occurrence tended to be more frequent in males (57.5%) than in females (42.5%). Relative to age, frequency peaked among patients in the 7th (27.3%) and 6th decades (25.1%), respectively, followed in descending order by the 5th (14.8%) and 8th decades (13.1%). The majority of patients (86.3%) were at least 40 years. The most frequent size was 10-19 mm (37.5%), followed by 0-9 mm (27.8%) and 20-29 mm (14.6%), and tumors 30 mm or larger were relatively infrequent. Histopathological types in order of descending frequency were lipomas (69.0%), fibrolipomas (27.4%), and others (3.5%). The male:female ratio was 1.7:1 for lipoma and 1:1.6 for fibrolipoma.

Circulating microRNAs (miRNAs) have been detected in various types of cancer and have been proposed as novel biomarkers for diagnosis and treatment. Until recently, however, no studies had comprehensively examined circulating miRNAs in oral cancer. The current study used an ultra-sensitive genome-wide miRNA array to investigate changes in circulating miRNAs in plasma from five patients with oral cancer and ten healthy individuals. Results indicated that there were only a few circulating miRNAs, including miR-223, miR-26a, miR-126, and miR-21, that were up-regulated in patients with oral cancer. A subsequent validation test indicated that circulating miR-223 levels were significantly higher (~2-fold, P< 0.05) in patients with oral cancer (n = 31) than in those without cancer (n = 31). Moreover, miR-223 was found to be up-regulated in tumor-adjacent normal tissue compared to tumor tissue from patients with oral cancer. A gain-of-function assay was performed to explore the potential roles of circulating miR-223 in the development of oral cancer. Results revealed that miR-223 functions as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. In conclusion, this study suggested that circulating miR-223 may serve as a potential biomarker for diagnosis and that it may represent a novel therapeutic target for treatment of oral cancer.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

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