Stabilized oral lichen planus does not compromise dental implants survival: A systematic review and meta-analysis.

BACKGROUND: This study aimed to evaluate the incidence of implant failure in patients with oral lichen planus (OLP) and investigate the potential association between OLP and peri-implant diseases. MATERIALS AND METHODS: Embase, Web of Science, PubMed, and Scopus databases were searched for studies with no time restrictions. Meta-analysis was performed calculating pooled proportion of peri-implantitis (PI), peri-implant mucositis (PIM), and bleeding on probing (BOP) prevalence using fixed-effects model. Odds ratio and corresponding 95% CI were calculated to assess the potential risk of PI, PIM, and BOP in dental implant patients with OLP compared to healthy controls. RESULTS: Implant failure rate was 4.38% at the patient level and 4.37% at the implant level. Six patients (3.92%) from five studies were diagnosed with oral cancer after receiving implant. The prevalence of PI, PIM, and BOP at the implant level were 14.00%, 20.00%, and 40.00%, respectively. There was no significant difference in the occurrence of PI and PIM between OLP patients and healthy controls. CONCLUSIONS: Stabilized OLP is not considered a significant risk factor for peri-implant diseases. It is advised against placing implants or prostheses during the acute phase of the disease. Histopathological investigation to differentiate OLP from oral lichenoid dysplasia is crucial.

Performance of a simplified scoring system for risk stratification in oral cancer and oral potentially malignant disorders screening.

BACKGROUND: Impact and efficiency of oral cancer and oral potentially malignant disorders screening are most realized in "at-risk" individuals. However, tools that can provide essential knowledge on individuals' risks are not applied in risk-based screening. This study aims to optimize a simplified risk scoring system for risk stratification in organized oral cancer and oral potentially malignant disorders screening. METHODS: Participants were invited to attend a community-based oral cancer and oral potentially malignant disorders screening program in Hong Kong. Visual oral examination was performed for all attendees and information on sociodemographic characteristics as well as habitual, lifestyle, familial, and comorbidity risk factors were obtained. Individuals' status of those found to have suspicious lesions following biopsy and histopathology were classified as positive/negative and this outcome was used in a multiple logistic regression analysis with variables collected during screening. Odds ratio weightings were then used to develop a simplified risk scoring system which was validated in an external cohort. RESULTS: Of 979 participants, 4.5% had positive status following confirmatory diagnosis. A 12-variable simplified risk scoring system with weightings was generated with an AUC, sensitivity, and specificity of 0.82, 0.71, and 0.78 for delineating high-risk cases. Further optimization on the validation cohort of 491 participants yielded a sensitivity and specificity of 0.75 and 0.87 respectively. CONCLUSIONS: The simplified risk scoring system was able to stratify oral cancer and oral potentially malignant disorders risk with satisfactory sensitivity and specificity and can be applied in risk-based disease screening.

Simultaneous Management of Condylar Osteochondroma and Secondary Malformation With a New Intraoral Approach.

PURPOSE: The present study aimed to investigate the clinical efficacy of simultaneous management of condylar osteochondroma and its secondary dentofacial deformities using an intraoral surgical approach. METHODS: Six patients with condylar osteochondroma were treated with intraoral vertical ramus osteotomies and condylar resection. The free rising branch was used for reconstructing the temporomandibular joint. The simultaneous orthognathic surgery and plastic surgery were performed sequentially to correct the secondary dentofacial deformities. The indexes of aesthetic symmetry, occlusion relationship, temporomandibular joint function, condylar height, and volume change were assessed in the subsequential follow up. RESULTS: The mean follow up period was 31 months. All patients had no tumor recurrence. The ipsilateral joint function, occlusal relationship, and facial symmetry were satisfied. The ipsilateral condylar reconstruction had no obvious bone resorption and the ramus height was maintained well. Postoperative assessment showed the preoperative design was accurately fulfilled. CONCLUSIONS: The simultaneous condylar osteochondroma resection and temporomandibular joint reconstruction using intraoral approach avoids extraoral scars and correct facial asymmetry without compromising the long-term joint function and occlusal relationship.

Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma.

YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.

The influence of locally applied granulocyte-colony stimulating factor on osteoporotic bone.

OBJECTIVES: The compromised capacity of bone healing in osteoporotic population renders a serious concern of patients and clinicians. This study aimed to investigate the influence of G-CSF on bone reconstruction using an osteoporotic animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were surgically created on all the animals. The defects were left unfilled, filled with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G-CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week 1 to week 8, the histomorphometric and micro-CT analysis demonstrated more advanced bone formation in femur in the control group; by week 12, all groups achieved cortical closure. In cranial bone, more advanced bone formation was exhibited in G-CSF-treated group at both early and late stages, although this observation was not statistically significant. CONCLUSIONS: The results indicated that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where spontaneous bone formation was insufficient.

Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats.

OBJECTIVE: This study aimed to investigate the role of progressive periodontal disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ) using an ovariectomized (OVX) rat model mimicking human intracortical remodeling process. MATERIALS AND METHODS: Thirty 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature was placed subgingivally around the first left lower molar to induce periodontitis. All animals were sacrificed 12 weeks after injection. The entire mandibles were harvested for micro-computed tomography (micro-CT) and histological examinations. RESULTS: Micro-CT examination showed that ligature placement caused significant alveolar bone loss both in ZA (0.63 ± 0.13 vs. 0.38 ± 0.06 mm, P < 0.001) and in control (0.88 ± 0.19 vs. 0.40 ± 0.06 mm, P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared with the control group (P < 0.01); the bone mineral density in the ZA group (1.00 ± 0.02 g/cm(3)) was significantly higher than that in vehicle control group (0.96 ± 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none of the control group. CONCLUSION: Bisphosphonates inhibit alveolar bone resorption in progressive periodontal disease, which might benefit the management of periodontitis, but increase the risk of developing BRONJ.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES: Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS: Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS: Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS: This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

Influence of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants in rabbit calvaria.

AIM: Until recently, adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants were unknown. Hence, this study investigated the short- and long-term effects of a 7-day regimen of parecoxib and diclofenac sodium on osseointegration of dental implants in calvarial bone. MATERIAL AND METHODS: Eighteen New Zealand White rabbits were randomly allocated into three groups (each n = 6): Control group with no postoperative pain killers (Group A), diclofenac group (Group B) and parecoxib group (Group C). In each animal, one dental implant was placed into the calvarial bone (total n = 18). Three rabbits from each group were sacrificed in Week 4. The other three rabbits from each group were sacrificed in Week 12 postoperatively. The implant together with the calvarial bone and dura mater was harvested and subjected to micro-computed tomography (micro-CT) and histomorphometric analysis. RESULTS: Quantitative analysis of micro-CT data and histomorphometric data neither revealed any statistically significant (P ≤ 0.05) differences between the three different groups related to osseointegration nor between different time points of observation. CONCLUSION: In rabbits, a 7-day regimen of appropriate doses of diclofenac sodium and parecoxib did not adversely affect osseointegration of dental implants and bone healing in calvaria, neither short nor long term (12 weeks).

Quantitative analysis of titanium-induced artifacts and correlated factors during micro-CT scanning.

OBJECTIVES: To investigate the impact of cover screw, resin embedment, and implant angulation on artifact of microcomputed tomography (micro-CT) scanning for implant. MATERIALS AND METHODS: A total of twelve implants were randomly divided into 4 groups: (i) implant only; (ii) implant with cover screw; (iii) implant with resin embedment; and (iv) implants with cover screw and resin embedment. Implants angulation at 0°, 45°, and 90° were scanned by micro-CT. Images were assessed, and the ratio of artifact volume to total volume (AV/TV) was calculated. A multiple regression analysis in stepwise model was used to determine the significance of different factors. One-way ANOVA was performed to identify which combination of factors could minimize the artifact. RESULTS: In the regression analysis, implant angulation was identified as the best predictor for artifact among the factors (P < 0.001). Resin embedment also had significant effect on artifact volume (P = 0.028), while cover screw had not (P > 0.05). Non-embedded implants with the axis parallel to X-ray source of micro-CT produced minimal artifact. CONCLUSIONS: Implant angulation and resin embedment affected the artifact volume of micro-CT scanning for implant, while cover screw did not.

Dose-dependent effect of radiation on titanium implants: a quantitative study in rabbits.

OBJECTIVES: The aim of the study was to investigate the dose-dependent effect of radiation on dental implant stability and osseointegration using a series of quantitative analyses. MATERIAL AND METHODS: Six rabbits were randomly assigned to 15 and 30 Gy radiation groups. Each rabbit received radiation at the tibial and femoral metaphyseal region of left hind leg. The right leg was used as control. Implant surgery was performed on tibial and femoral metaphyses after 1 week. Totally 24 implants were inserted. The animals were killed at postoperative week four. Implant stability was measured using resonance frequency analysis. Ratio of bone volume to total volume (BV/TV), rate of bone growth, and bone-to-implant contact (BIC) were assessed using micro-computed tomography (micro-CT), fluorochrome labeling analysis, and histomorphometric analysis, respectively. RESULTS: After 4 weeks of healing, all implants were integrated (n = 6). Implant stability was significantly compromised by 15 Gy (P = 0.010) and 30 Gy (P = 0.025) of radiation. Radiation decreased BV/TV, and the significant effect was detected at the dose of 15 Gy (P = 0.008) and 30 Gy (P < 0.001). Bone growth in osseointegration was impaired by radiation. In 15 Gy group, the radiation side showed significant lower rate of bone growth than the control side at week 3 (P = 0.001), while the undistinguishable signals on 30 Gy radiation side suggested the low rate of new bone formation at each time point. Histomorphological BIC had no significant difference between 15 Gy control side and 15 Gy radiation side. 30 Gy radiation side showed a significantly lower BIC than 30 Gy control side (P < 0.001) as well as 15 Gy radiation side (P < 0.001). CONCLUSIONS: Implant stability and osseointegration were compromised by radiation. Radiation compromised osseointegration in a dose-dependent manner.

Diagnostic accuracy of artificial intelligence assisted clinical imaging in the detection of oral potentially malignant disorders and oral cancer: A systematic review and meta-analysis.

BACKGROUND: The objective of this study is to examine the application of AI algorithms in detecting OPMD and oral cancerous lesions, and to evaluate the accuracy variations among different imaging tools employed in these diagnostic processes. MATERIALS AND METHODS: A systematic search was conducted in four databases: Embase, Web of Science, PubMed, and Scopus. The inclusion criteria included studies using machine learning algorithms to provide diagnostic information on specific oral lesions, prospective or retrospective design, and inclusion of OPMD. Sensitivity and specificity analyses were also required. Forest plots were generated to display overall diagnostic odds ratio (DOR), sensitivity, specificity, negative predictive values, and summary receiver operating characteristic (SROC) curves. Meta-regression analysis was conducted to examine potential differences among different imaging tools. RESULTS: The overall DOR for AI-based screening of OPMD and oral mucosal cancerous lesions from normal mucosa was 68.438 (95%CI= [39.484, 118.623], I2 = 86%). The area under the SROC curve was 0.938, indicating excellent diagnostic performance. AI-assisted screening showed a sensitivity of 89.9% (95%CI= [0.866,0.925]; I2 = 81%), specificity of 89.2% (95%CI= [0.851,0.922], I2 = 79%), and a high negative predictive value of 89.5% (95%CI= [0.851; 0.927], I2 = 96%). Meta-regression analysis revealed no significant difference among the three image tools. After generating a GOSH plot, the DOR was calculated to be 49.30, and the area under the SROC curve was 0.877. Additionally, sensitivity, specificity, and negative predictive value were 90.5% (95%CI [0.873,0.929], I2=4%), 87.0% (95%CI [0.813,0.912], I2=49%) and 90.1% (95%CI [0.860,0.931], I2=57%), respectively. Subgroup analysis showed that clinical photography had the highest diagnostic accuracy. CONCLUSIONS: AI-based detection using clinical photography shows a high diagnostic odds ratio and is easily accessible in the current era with billions of phone subscribers globally. This indicates that there is significant potential for AI to enhance the diagnostic capabilities of general practitioners to the level of specialists by utilizing clinical photographs, without the need for expensive specialized imaging equipment.

Multifunctional Nanofibrous Scaffolds Capable of Localized Delivery of Theranostic Nanoparticles for Postoperative Cancer Management.

Postoperative recovery of cancer patients can be affected by complications, such as tissue dysfunction or disability caused by tissue resection, and also cancer recurrence resulting from residual cancer cells. Despite impressive progress made for tissue engineering scaffolds that assist tissue regeneration for postoperative cancer patients, the majority of existing tissue engineering scaffolds still lack functions for monitoring and killing residual cancer cells, if there are any, upon their detection. In this study, multifunctional scaffolds that comprise biodegradable nanofibers and core-shell structured microspheres encapsulated with theranostic nanoparticles (NPs) are developed. The multifunctional scaffolds possess an extracellular matrix-like nanofibrous architecture and soft tissue-like mechanical properties, making them excellent tissue engineering patch candidates for assisting in the repair and regeneration of tissues at the cancerous sites after surgery. Furthermore, they are capable of localized delivery of theranostic NPs upon quick degradation of core-shell structured microspheres that contain theranostic NPs. Leveraging on folic acid-mediated ligand-receptor binding, surface-enhanced Raman scattering activity, and near-infrared-responsive photothermal effect of the theranostic gold NPs (AuNPs) delivered locally, the multifunctional scaffolds display excellent active targeting, diagnosis, and photothermal therapy functions for cancer cells, showing great promise for adaptive postoperative cancer management.

Explainable ensemble learning model improves identification of candidates for oral cancer screening.

OBJECTIVES: Artificial intelligence could enhance the use of disparate risk factors (crude method) for better stratification of patients to be screened for oral cancer. This study aims to construct a meta-classifier that considers diverse risk factors to identify patients at risk of oral cancer and other suspicious oral diseases for targeted screening. MATERIALS AND METHODS: A retrospective dataset from a community oral cancer screening program was used to construct and train the novel voting meta-classifier. Comprehensive risk factor information from this dataset was used as input features for eleven supervised learning algorithms which served as base learners and provided predicted probabilities that are weighted and aggregated by the meta-classifier. Training dataset was augmented using SMOTE-ENN. Additionally, Shapley additive explanations (SHAP) values were generated to implement the explainability of the model and display the important risk factors. RESULTS: Our meta-classifier had an internal validation recall, specificity, and AUROC of 0.83, 0.86, and 0.85 for identifying the risk of oral cancer and 0.92, 0.60, and 0.76 for identifying suspicious oral mucosal disease respectively. Upon external validation, the meta-classifier had a significantly higher AUROC than the crude/current method used for identifying the risk of oral cancer (0.78 vs 0.46; p = 0.001) Also, the meta-classifier had better recall than the crude method for predicting the risk of suspicious oral mucosal diseases (0.78 vs 0.47). CONCLUSION: Overall, these findings showcase that our approach optimizes the use of risk factors in identifying patients for oral screening which suggests potential clinical application.

Rate of Malignant Transformation Differs Based on Diagnostic Criteria for Oral Lichenoid Conditions: A Systematic Review and Meta-Analysis of 24,277 Patients.

OBJECTIVES: This systematic review and meta-analysis aims to evaluate the evidence on the malignant potential of oral lichenoid conditions (OLCs) including oral lichen planus (OLP), oral lichenoid lesions (OLL), and lichenoid mucositis dysplasia (LMD). In addition, it aims to compare the rate of malignant transformation (MT) in OLP patients diagnosed according to different diagnostic criteria, and to investigate the possible risk factors for OLP MT into OSCC. MATERIALS AND METHODS: A standardized search strategy was applied across four databases (PubMed, Embase, Web of Science, and Scopus). Screening, identification and reporting followed the PRISMA framework. Data on MT were calculated as a pooled proportion (PP), subgroup analyses and possible risk factors for MT were pooled as odds ratios (ORs). RESULTS: Among 54 studies with 24,277 patients, the PP for OLCs MT was 1.07% (95% CI [0.82, 1.32]). The estimated MT rate for OLP, OLL and LMD was 0.94%, 1.95% and 6.31%, respectively. The PP OLP MT rate using the 2003 modified WHO criteria group was lower than that using the non-2003 criteria (0.86%; 95% CI [0.51, 1.22] versus 1.01%; 95% CI [0.67, 1.35]). A higher odds ratio of MT was observed for red OLP lesions (OR = 3.52; 95% CI [2.20, 5.64]), smokers (OR = 1.79; 95% CI [1.02, 3.03]), alcohol consumers (OR = 3.27, 95% CI [1.11, 9.64]) and those infected with HCV (OR = 2.55, 95% CI [1.58, 4.13]), compared to those without these risk factors. CONCLUSIONS: OLP and OLL carry a low risk of developing OSCC. MT rates differed based on diagnostic criteria. A higher odds ratio of MT was observed among red OLP lesions, smokers, alcohol consumers, and HCV-positive patients. These findings have implications for practice and policies.

A reflection on COVID-19 and oral mucosal lesion: a systematic review.

Introduction: The aim of this systematic review is to provide a clinical update of the current knowledge on COVID-19 and oral mucosal lesions, to analyze the types and prevalence of oral mucosal lesions in patients with COVID-19, and to clarify the potential association between COVID-19 and oral mucosal lesions. Methods: The literature search was conducted using PubMed, Web of Science, Scopus and the Cochrane Library, as well as literatures via manual searches of the reference lists of included studies. Studies published in English that mentioned oral mucosal lesions in patients with COVID-19 were included, resulting in a total of 31 studies. Results: Most of the included studies were considered to have a moderate to high risk of bias according to the Joanna Briggs Institute bias assessment tools. Based on COVID-19 severity, the characteristics and patterns of oral mucosal lesions in COVID-19 patients were described, analyzed and synthesized. Overall, ulcers without specific diagnosis had the highest prevalence in COVID-19 patients, followed by traumatic ulcers, candidiasis, petechiae and aphthous-like lesions. Homogeneity of data cannot be achieved in statical analysis, indicating randomness of outcome (ulcers without specific diagnosis, 95% CI: 28%-96%, I2 = 98.7%). Discussion: Given the limited evidence from currently available studies, the association between COVID-19 and oral mucosal lesions remains difficult to clarify. Healthcare professionals should be aware of the possible association between COVID-19 and oral mucosal lesions, and we hereby discuss our findings.

Treatment of irradiated mandibles with mesenchymal stem cells transfected with bone morphogenetic protein 2/7.

PURPOSE: The study aimed to evaluate whether mesenchymal stem cells transfected with bone morphogenetic protein (BMP) 2/7 could increase bone regeneration after radiotherapy using a rabbit model of mandibular distraction osteogenesis. MATERIALS AND METHODS: Twelve rabbits were randomly assigned to the sham control, radiotherapy control, nontransfected mesenchymal stem cells (MSCs), and MSCs transfected with BMP-2/7 groups. All rabbits, except those in the sham control group, received preoperative radiation of 9 Gy for 5 fractions. One month after radiotherapy, all rabbits underwent unilateral mandibular distraction at a rate of 0.9 mm/d for 11 days. At the end of active distraction, MSCs combined with bovine collagen were injected into the distraction zone. After 4 weeks of consolidation, the mandibular samples were collected and subjected to radiographic, microcomputed tomographic, and histologic examinations. RESULTS: By radiographic examination, animals injected with nontransfected MSCs or MSCs encoding BMP-2/7 exhibited more bone formation than the control groups. Histologic examination showed that the group with MSCs encoding BMP-2/7 had a more mature medullary cavity than the nontransfected MSCs group. CONCLUSIONS: MSCs encoding BMP-2/7 can increase bone healing in irradiated mandibular bone.

Expression of angiogenic markers in jawbones and femur in a rat model treated with zoledronic acid.

OBJECTIVES: This study aimed to investigate the gene expression of angiogenic marker in surgically treated jawbones and femur on a rat model administrated with zoledronic acid. RESULTS: No soft tissue fenestration or bone exposure was found in femur. Delayed soft tissue healing was found in both ZA group (3 in mandible, 4 in maxilla) and control group (1 in mandible, 2 in maxilla), while exposed bone was found only in the ZA group (1 in maxilla, 2 in mandible). RT-PCR analysis demonstrated no significant difference in gene expression of angiogenetic markers between ZA-treated and control groups in femur and mandible. In the maxilla, the expression of VEGFA and VEGFR-2 in medium-term ZA group was significantly down-regulated compared with that in the control. The ZA treatment does not change significantly the expression of the angiogenic factors in femur and mandible, but significantly downregulates the expression in maxilla in this rat model. The angiogenesis inhibition may contribute to the development of MRONJ but does not play a key role.

Machine Learning-Based Genome-Wide Salivary DNA Methylation Analysis for Identification of Noninvasive Biomarkers in Oral Cancer Diagnosis.

This study aims to examine the feasibility of ML-assisted salivary-liquid-biopsy platforms using genome-wide methylation analysis at the base-pair and regional resolution for delineating oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A nested cohort of patients with OSCC and OPMDs was randomly selected from among patients with oral mucosal diseases. Saliva samples were collected, and DNA extracted from cell pellets was processed for reduced-representation bisulfite sequencing. Reads with a minimum of 10× coverage were used to identify differentially methylated CpG sites (DMCs) and 100 bp regions (DMRs). The performance of eight ML models and three feature-selection methods (ANOVA, MRMR, and LASSO) were then compared to determine the optimal biomarker models based on DMCs and DMRs. A total of 1745 DMCs and 105 DMRs were identified for detecting OSCC. The proportion of hypomethylated and hypermethylated DMCs was similar (51% vs. 49%), while most DMRs were hypermethylated (62.9%). Furthermore, more DMRs than DMCs were annotated to promoter regions (36% vs. 16%) and more DMCs than DMRs were annotated to intergenic regions (50% vs. 36%). Of all the ML models compared, the linear SVM model based on 11 optimal DMRs selected by LASSO had a perfect AUC, recall, specificity, and calibration (1.00) for OSCC detection. Overall, genome-wide DNA methylation techniques can be applied directly to saliva samples for biomarker discovery and ML-based platforms may be useful in stratifying OSCC during disease screening and monitoring.

Influence of nicotine on the biological activity of rabbit osteoblasts.

OBJECTIVES: To assess the influence of nicotine on the proliferation and gene expression of osteogenic and angiogenic mediators of osteoblasts. MATERIAL AND METHODS: Rabbit primary osteoblasts were exposed to various concentrations of nicotine (0.001, 0.1 and 10 µmol/l). The cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The gene expression of transforming growth factor (TGF)-ß(1), bone morphogenetic protein (BMP)-2, platelet-derived growth factor (PDGF)-AA and vascular endothelial growth factor (VEGF) was evaluated using real-time reverse transcription - polymerase chain reaction. RESULTS: The osteoblast proliferation was inhibited by nicotine at the concentration of 0.001-10 µM at 48 and 72 h of culture, but with no significant effect at 24 h. The expression of TGF-ß(1), BMP-2, PDGF-AA and VEGF was inhibited by nicotine at the concentrations of 0.1 and 10 µM, but with no significant difference at the low concentration of 0.001 µM. CONCLUSIONS: Nicotine suppresses osteoblast proliferation and inhibits the expression of some key osteogenic and angiogenic mediators in the in vitro experimental model. These inhibitory effects of nicotine on the osteoblast activity may reflect, to a certain degree, the overall detrimental effects of tobacco use on the survival rate of dental implants.

Influence of low-dose nicotine on bone healing.

BACKGROUND: Nicotine at a low concentration was suggested as a new topical drug for clinical application. It has been reported to be capable of enhancing skin wound healing. This study was designed to assess the effect of nicotine administration at a low dose on bone regeneration using a rabbit model of mandibular distraction osteogenesis. METHODS: Twenty New Zealand white rabbits were randomly assigned to nicotine group and control group. A total of 0.75 g, 60-day time release, nicotine pellets or placebos were implanted in the neck subcutaneous tissue of the rabbits. The nicotine or placebo exposure time for all the animals was 7 weeks. Unilateral mandibular distraction osteogenesis was performed. Five animals in each group were killed on week 2 and week 4 of consolidation, respectively. The mandibular samples were subjected to radiographic, histologic, and immunohistochemical analysis. RESULTS: Nicotine at low dose showed no significant effect on the expression of bone morphogenetic protein-2 and on the radiodensity of bone regeneration. However, the delayed bone healing was detected in the nicotine group by histologic examination. CONCLUSIONS: These findings imply a potential risk of compromised bone healing in patients taking nicotine medication. Further clinical studies are necessary to assess the risk of nicotine medication on reconstructive surgery.