Applying Machine Learning for Enhanced MicroRNA Analysis: A Companion Risk Tool for Oral Squamous Cell Carcinoma in Standard Care Incisional Biopsy.

Machine learning analyses within the realm of oral cancer outcomes are relatively underexplored compared to other cancer types. This study aimed to assess the performance of machine learning algorithms in identifying oral cancer patients, utilizing microRNA expression data. In this study, we implemented this approach using a panel of oral cancer-associated microRNAs sourced from standard incisional biopsy specimens to identify cases of oral squamous cell carcinomas (OSCC). For the model development process, we used a dataset comprising 30 OSCC and 30 histologically normal epithelium (HNE) cases. We initially trained a logistic regression prediction model using 70 percent of the dataset, while reserving the remaining 30 percent for testing. Subsequently, the model underwent hyperparameter tuning resulting in enhanced performance metrics. The hyperparameter-tuned model exhibited high accuracy (0.894) and ROC AUC (0.898) in predicting OSCC. Testing the model on cases of potentially malignant disorders (OPMDs) revealed that leukoplakia with mild dysplasia was predicted as having a high risk of progressing to OSCC, emphasizing machine learning's advantage over histopathology in detecting early molecular changes. These findings underscore the necessity for further refinement, incorporating a broader set of variables to enhance the model's predictive capabilities in assessing the risk of oral potentially malignant disorders.

Assessment of Oxidative Stress-Induced Oral Epithelial Toxicity.

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H2O2) at concentrations of 100 µM up to 1200 µM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 µM, 800 µM, and 400 µM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

Acquisition and annotation in high resolution in vivo digital biopsy by confocal microscopy for diagnosis in oral precancer and cancer.

Introduction: Scanned fibre endomicroscopes are full point-scanning confocal microscopes with submicron lateral resolution with an optical slice thickness thin enough to isolate individual cell layers, allow active positioning of the optical slice in the z-axis and collection of megapixel images. Here we present descriptive findings and a brief atlas of an acquisition and annotation protocol high resolution in vivo capture of oral mucosal pathology including oral squamous cell carcinoma and dysplasia using a fluorescence scanned fibre endomicroscope with 3 topical fluorescent imaging agents: fluorescein, acriflavine and PARPi-FL. Methods: Digital biopsy was successfully performed via an acquisition protocol in seventy-one patients presenting for investigation of oral mucosal abnormalities using a miniaturized, handheld scanned fibre endoscope. Multiple imaging agents were utilized and multiple time points sampled. Fifty-nine patients had a matched histopathology correlating in location with imaging. The images were annotated back to macrographic location using a purpose-built software, MouthMap™. Results: Acquisition and annotation of cellular level resolved images was demonstrated with all 3 topical agents. Descriptive observations between clinically or histologically normal oral mucosa showed regular intranuclear distance, a regular nuclear profile and fluorescent homogeneity. This was dependent on the intraoral location and type of epithelium being observed. Key features of malignancy were a loss of intranuclear distance, disordered nuclear clustering and irregular nuclear fluorescence intensity and size. Perinuclear fluorescent granules were seen in the absence of irregular nuclear features in lichenoid inflammation. Discussion: High resolution oral biopsy allows for painless and rapid capture of multiple mucosal sites, resulting in more data points to increase diagnostic precision. High resolution digital micrographs can be easily compared serially across multiple time points utilizing an annotation software. In the present study we have demonstrated realization of a high-resolution digital biopsy protocol of the oral mucosa for utility in the diagnosis of oral cancer and precancer..

Characterization of a novel dual murine model of chemotherapy-induced oral and intestinal mucositis.

Oral and intestinal mucositis are debilitating inflammatory diseases observed in cancer patients undergoing chemo-radiotherapy. These are devastating clinical conditions which often lead to treatment disruption affecting underlying malignancy management. Although alimentary tract mucositis involves the entire gastrointestinal tract, oral and intestinal mucositis are often studied independently utilizing distinct organ-specific pre-clinical models. This approach has however hindered the development of potentially effective whole-patient treatment strategies. We now characterize a murine model of alimentary tract mucositis using 5-Fluorouracil (5-FU). Mice were given 5-FU intravenously (50 mg/kg) or saline every 48 h for 2 weeks. Post initial injection, mice were monitored clinically for weight loss and diarrhea. The incidence and extent of oral mucositis was assessed macroscopically. Microscopical and histomorphometric analyses of the tongue and intestinal tissues were conducted at 3 interim time points during the experimental period. Repeated 5-FU treatment caused severe oral and intestinal atrophy, including morphological damage, accompanied by body weight loss and mild to moderate diarrhea in up to 77.8% of mice. Oral mucositis was clinically evident throughout the observation period in 88.98% of mice. Toluidine blue staining of the tongue revealed that the ulcer size peaked at day-14. In summary, we have developed a model reproducing the clinical and histologic features of both oral and intestinal mucositis, which may represent a useful in vivo pre-clinical model for the study of chemotherapy-induced alimentary tract mucositis and the development of preventative therapies.

Metabolomic Profile of Indonesian Betel Quids.

Consumption of areca nut alone, or in the form of betel quid (BQ), has negative health effects and is carcinogenic to humans. Indonesia is one of the largest producers of areca nuts worldwide, yet little is known about the biomolecular composition of Indonesian areca nuts and BQs. We have recently shown that phenolic and alkaloid content of Indonesian BQs exhibits distinct geographical differences. Here, we profiled for the first time the metabolomics of BQ constituents from four regions of Indonesia using non-targeted gas chromatography-mass spectrometry (GC-MS) analysis. In addition to well-known alkaloids, the analysis of small-molecule profiles tentatively identified 92 phytochemicals in BQ. These included mainly benzenoids and terpenes, as well as acids, aldehydes, alcohols, and esters. Safrole, a potentially genotoxic benzenoid, was found abundantly in betel (Piper betle) inflorescence from West Papua and was not detected in areca nut samples from any Indonesian region except West Papua. Terpenes were mostly detected in betel leaves and inflorescence/stem. Areca nut, husk, betel leaf, the inflorescence stem, and BQ mixture expressed distinctive metabolite patterns, and a significant variation in the content and concentration of metabolites was found across different geographical regions. In summary, this was the first metabolomic study of BQs using GC-MS. The results demonstrate that the molecular constituents of BQs vary geographically and suggest that the differential disease-inducing capacity of BQs may reflect their distinct chemical composition.

Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords "betel quid" and "oral submucous fibrosis", and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers.

Risk Factors Associated With Poor Outcomes Following Temporomandibular Joint Discectomy and Fat Graft.

PURPOSE: Temporomandibular joint (TMJ) discectomy is performed for patients with degenerative joint disease with an unsalvageable disc, but with a salvageable condylar head and glenoid fossa. The purpose of this study was to estimate the incidence and risk factors associated with poor postoperative outcomes following TMJ discectomy and abdominal fat grafting. METHODS: A retrospective cohort study was conducted on patients who underwent TMJ discectomy. Included in this study were patients who had complete data sets with a minimum of 1-year follow-up. Potential risk factors included demographics, preoperative findings (mouth opening, pain levels, previous TMJ surgery), operative findings (disc degeneration, state of TMJ components), and postoperative outcomes (pain levels, mouth opening). Failed outcomes were those who had return of pain postoperatively, no improvement in mouth opening following TMJ discectomy, and/or those who progressed to TMJ total joint replacement (TJR). Statistical methods included Kaplan-Meier curves and Cox proportional hazards regression time to event analyses. RESULTS: This study included 129 patients who had undergone 132 TMJ discectomies. Most patients were female (89.9%), with a mean age of 43.2 years, standard deviation 14.2. The success rate for discectomy was 75.2% and the conversion rate of TMJ discectomy to TJR was 11.7%. A total of 32 patients (24.8%) experienced return of pain. The median time to return of pain or second surgery was 94.4 months (95% CI = 88.3 to 101.8). No risk factors were statistically significant, although mouth opening improvement of less than 10% was associated with higher risk of poor outcome (P = .77). CONCLUSION: The findings of this study suggest that lower improvement in mouth opening at 1 year following surgery is likely to result in failure of the TMJ discectomy procedure although the result was not statistically significant. This outcome may ultimately necessitate a TJR.

Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients.

Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, TP53 (60%) and CDKN2A (24%) were most frequently mutated, and the most common CNVs were EGFR amplifications (9%) and deletions of BRCA2 (5%) and CDKN2A (4%). Significant associations were found for TP53 mutation and nodal disease, lymphovascular invasion and extracapsular spread, CDKN2A mutation or deletion with advanced tumour stage, and EGFR amplification with perineural invasion and extracapsular spread. PIK3CA mutation, CDKN2A deletion, and EGFR amplification were associated with worse survival in univariate analyses (p < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of CDKN2A mutations, EGFR amplifications, and BRCA2 deletions (p < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.

Oral Antibiotic for Empirical Management of Acute Dentoalveolar Infections-A Systematic Review.

Concerns regarding increasing antibiotic resistance raise the question of the most appropriate oral antibiotic for empirical therapy in dentistry. The aim of this systematic review was to investigate the antibiotic choices and regimens used to manage acute dentoalveolar infections and their clinical outcomes. A systematic review was undertaken across three databases. Two authors independently screened and quality-assessed the included studies and extracted the antibiotic regimens used and the clinical outcomes. Searches identified 2994 studies, and after screening and quality assessment, 8 studies were included. In addition to incision and drainage, the antibiotics used to manage dentoalveolar infections included amoxicillin, amoxicillin/clavulanic acid, cefalexin, clindamycin, erythromycin, metronidazole, moxifloxacin, ornidazole and phenoxymethylpenicillin. Regimens varied in dose, frequency and duration. The vast majority of regimens showed clinical success. One study showed that patients who did not receive any antibiotics had the same clinical outcomes as patients who received broad-spectrum antibiotics. The ideal choice, regimen and spectrum of empirical oral antibiotics as adjunctive management of acute dentoalveolar infections are unclear. Given that all regimens showed clinical success, broad-spectrum antibiotics as first-line empirical therapy are unnecessary. Narrow-spectrum agents appear to be as effective in an otherwise healthy individual. This review highlights the effectiveness of dental treatment to address the source of infection as being the primary factor in the successful management of dentoalveolar abscesses. Furthermore, the role of antibiotics is questioned in primary space odontogenic infections, if drainage can be established.

Improvement of dental prescribing practices using education and a prescribing tool: A pilot intervention study.

AIMS: Antibiotic resistance is a global public health problem. Around 55% of dental antibiotic prescribing is deemed inappropriate. The aim of this multimodal interventional pilot study was to assess the effect on prescribing of education and a dentally designed prescribing website. METHODS: Twenty-six dentists were recruited for the 12-week study using a pre-post design. Dentists self-recorded their prescribing of antibiotics, analgesics and anxiolytics for 6 weeks. After dentists were provided education and website access, they recorded their prescribing for a further 6 weeks. Four outcomes were measured comparing the prescribing before and after the intervention: (i) the number of inappropriate indications for which antibiotics were prescribed; (ii) the number of prescriptions; (iii) accuracy of the prescriptions according to the Australian therapeutic guidelines; and (iv) the confidence of practitioners towards the prescribing website. Participants were interviewed for feedback. RESULTS: There was a substantial reduction of 44.6% in the number of inappropriate indications for which antibiotics were prescribed after the intervention and a decrease of 40.5% in the total number of antibiotics. Paracetamol with codeine substantially reduced by 56.8%. For the 3 most commonly prescribed antibiotics (amoxicillin, phenoxymethylpenicillin and metronidazole), there was the improvement in the accuracy of the prescriptions ranging from 0-64.7 to 74.2-100%. CONCLUSION: This pilot study showed the intervention of targeted education and the prescribing tool was effective in improving dental prescribing, knowledge and confidence of practitioners, as well as providing an effective antibiotic stewardship tool. This context-specific intervention shows substantial promise for implementation into dental practice.

Medication-related osteonecrosis of the jaw: Analysing the range of implicated drugs from the Australian database of adverse event notifications.

AIMS: Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon but potentially debilitating condition, characterised by nonhealing jawbone, with or without mucosal exposure, in the presence of certain drugs. Those already strongly associated with MRONJ include antiresorptives denosumab and bisphosphonates; however, a growing range of other non-antiresorptive drugs is implicated. The aim of this study was to analyse all case reports of MRONJ submitted to the publicly available Database of Adverse Event Notification from the Therapeutic Goods Administration in Australia. METHODS: The Therapeutic Goods Administration was contacted on 6 January 2020 and asked for all reports containing the words "osteonecrosis of the jaw". This was provided in a spreadsheet of de-identified reports received from commencement of the database in 1971 until 1 October 2019. RESULTS: The drugs implicated in the 419 cases were divided by established drugs with MRONJ and secondary drugs that possibly contribute to MRONJ development. While the majority of cases were associated with denosumab or bisphosphonates (n = 405), there were 14 reports where secondary agents that directly or indirectly affect bone turnover, were also implicated. Some of these secondary drugs, including adalimumab, etanercept, methotrexate and rituximab have previously been associated with MRONJ in published case reports. CONCLUSIONS: This study contributes to the sparse but growing literature associating an increasing number of drugs with MRONJ, and underscores the importance of considering all possible drugs that elevate a patient's MRONJ risk.

Odontoblast markers and dentine reactions in carious primary molars with and without hypomineralised enamel defects.

BACKGROUND: Wnt/ß-Catenin signalling and DMP1 have key roles in tertiary dentinogenesis. AIM: To compare the relationship between remaining dentine thickness (RDT), tertiary dentine thickness (TDT), ß-catenin and dentine matrix protein 1 (DMP1) in carious second primary molar teeth with normal (SPM) and hypomineralised enamel (HSPM). DESIGN: Extracted carious SPM and HSPM were fixed, sectioned (5 µm) and stained with haematoxylin and eosin or with indirect immunofluorescence for ß-catenin and DMP1. Image analysis was performed to determine RDT, TDT, ß-catenin and DMP1 intensity in the odontoblast layer and dentine-pulp complex. RESULTS: Carious SPM (n = 11; mean RDT = 1536.1 µm) and HSPM (n = 12; mean RDT = 1179.9 µm) had mean TDT 248.6 µm and 518.1 µm, respectively (P = .02). There were no significant differences in intensity values in the odontoblast layer and dentine-pulp complex for ß-catenin and DMP1 for both groups. CONCLUSION: There was no observable variation in Wnt/ß-catenin and DMP1 expression between HSPM and SPM despite a statistically significant twofold increased TDT in HSPM compared with SPM that had similar RDT. Thus, the observed increased TDT in HSPM is more likely due to an earlier onset of repair processes rather than an amplified response to caries.

Intraoral human herpes viruses detectable by PCR in majority of patients.

OBJECTIVES: To identify factors which influence the intraoral prevalence of human herpes viruses (HHVs) using mucosal swabs, saliva samples and qPCR analysis. METHODOLOGY: In this cross-sectional observational study, matched saliva and oral swabs were collected from a total of 115 subjects: 70 immunocompetent subjects with no mucosal abnormalities, 22 with mucosal abnormalities and 23 therapeutically immunocompromised individuals. Extracted DNA was analysed by multiplex qPCR for detection and quantification of HHVs 1-6. RESULTS: At least one human herpes virus was detected in 77.1% of immunocompetent individuals with no mucosal abnormalities, with EBV the most commonly detected at 61.4%. HHV-6 was detected in 17.1%, HSV-1 in 4.3% and CMV in 1.1%. Detection was higher in saliva than in oral swabs. There was no detection of HSV-2 or VZV. Neither presence of oral mucosal abnormality nor therapeutic immunocompromise was related to increased detection of human herpes virus. CONCLUSION: Commensal detection rates of EBV are high, and caution in clinical correlation of positive detection is warranted. Commensal CMV rates are low, and detection is likely to be clinically relevant. This study presents a comprehensive commensal detection rate of HHVs 1-6 by qPCR in saliva and swabs.

Measuring Antibiotic Stewardship Programmes and Initiatives: An Umbrella Review in Primary Care Medicine and a Systematic Review of Dentistry.

Antibiotic stewardship aims to tackle the global problem of drug-resistant infections by promoting the responsible use of antibiotics. Most antibiotics are prescribed in primary care and widespread overprescribing has been reported, including 80% in dentistry. This review aimed to identify outcomes measured in studies evaluating antibiotic stewardship across primary healthcare. An umbrella review was undertaken across medicine and a systematic review in dentistry. Systematic searches of Ovid Medline, Ovid Embase and Web of Science were undertaken. Two authors independently selected and quality assessed the included studies (using Critical Appraisal Skills Programme for the umbrella review and Quality Assessment Tool for Studies with Diverse Designs for the systematic review). Metrics used to evaluate antibiotic stewardship programmes and interventions were extracted and categorized. Comparisons between medical and dental settings were made. Searches identified 2355 medical and 2704 dental studies. After screening and quality assessment, ten and five studies, respectively, were included. Three outcomes were identified across both medical and dental studies: All focused on antibiotic usage. Four more outcomes were found only in medical studies: these measured patient outcomes, such as adverse effects. To evaluate antibiotic stewardship programmes and interventions across primary healthcare settings, measures of antibiotic use and patient outcomes are recommended.

Molecular diagnostics in oral cancer and oral potentially malignant disorders-A clinician's guide.

Current risk stratification of individuals for the development of oral squamous cell carcinoma (OSCC), including those with oral potentially malignant disorders (OPMD), remains based on clinical detection of visibly abnormal mucosa and tissue biopsy with histological assessment for the presence of OSCC or oral epithelial dysplasia (OED). In OPMD, the presence of OED remains the only prognostic tool used in standard care for the development of future OSCC, despite its ample limitations. There is assured potential that the analysis of the genome, transcripts and proteome can provide insight into what is occurring at a cellular level preceding the appearance of clinically observable change. The landscape of the role of the genome and its transcriptome on the development of OSCC and relationships with OPMDs are immense with exploration occurring on several fronts. For clinicians involved in the diagnosis and care of patients with OSCC and OPMD, understanding of commonly used molecular diagnostic techniques is imperative to gain useful insight from the expanding literature investigating the development of OSCC and the relationship with the clinical presentations which encompass OPMDs. Here we present an introduction to molecular diagnostic methods used in the study of OSCC and OPMD.

The MarrowMiner: A Novel Minimally Invasive and Effective Device for the Harvest of Bone Marrow.

Bone marrow (BM) is a rich source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and other important stem/progenitor cells. It is the traditional source of cells used in hematopoietic cell transplantation, which is a proven curative treatment for many blood and immune diseases. BM-derived cells have also been shown to have other diverse clinical uses and are increasingly being used in orthopedic medicine, regenerative medicine, and gene therapy applications. Traditional methods for harvesting BM are crude, tedious, time-consuming, and expensive, requiring multiple bone punctures under general anesthesia with serial small-volume aspirates often diluted with peripheral blood. The MarrowMiner (MM) is a novel device designed for rapid and minimally invasive BM harvest. Here we show the safety and efficacy of the MM in both preclinical and clinical settings. In a large-animal porcine model, the MM enabled effective BM collection with similar total nucleated cell collection and increased colony formation compared with standard methods. The MM was subsequently evaluated in a clinical study showing effective and complication-free anterior and posterior BM collection of 20 patients under only local anesthesia or light sedation. Increased total nucleated and mononucleated cell collection was achieved with the MM compared with standard methods in the same patients. Importantly, stem cell content was high with trends toward increased HSC, MSC, and endothelial progenitor cells with similar T cell content. Given the MM is a novel device approved by the US Food and Drug Administration, enabling safe, effective, and minimally invasive harvest of BM, we anticipate rapid adoption for various applications.

A review and guide to drug-associated oral adverse effects-Oral mucosal and lichenoid reactions. Part 2.

Dental practitioners and other health professionals commonly encounter and manage adverse medicine effects that manifest in the orofacial region. Numerous medicines are associated with a variety of oral adverse effects. However, due to lack of awareness and training, these side effects are not always associated with medicine use and are underreported to pharmacovigilance agencies by dentists and other health professionals. This article aims to inform health professionals about the various oral adverse effects that can occur and the most commonly implicated drugs to improve the management, recognition and reporting of adverse drug effects. This article follows on from Part 1; however, the focus here is on lichenoid reactions and oral mucosal disorders including oral aphthous-like ulceration, mucositis and bullous disorders such as drug-induced pemphigus, pemphigoid, Stevens-Johnson syndrome and toxic epidermal necrolysis.

The immunopathogenesis of oral lichen planus-Is there a role for mucosal associated invariant T cells?

Oral lichen planus (OLP) is a chronic, T-cell-mediated, immune condition of unknown cause. OLP may present with painful symptoms requiring treatment, as well as lesions outside the oral cavity. It is likely that what initiates the OLP disease process is a complex interaction of host susceptibility and environmental triggers. While it is possible that OLP represents a true autoimmune condition against an epithelial autoantigen, the mechanisms that lead to this immune dysregulation are still poorly understood. In this review article, we discuss current concepts relating to the immunopathogenesis of OLP, as well as the potential contributory roles the oral microbiota and mucosal-associated invariant T (MAIT) cells.

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review.

BACKGROUND: Kava is a beverage made from the ground roots of the plant Piper Methysticum and has long-held a significant place within Pacific island communities. Active compounds were extracted from kava, and secondary metabolites include kavalactones, chalcones, cinnamic acid derivatives and flavanones. It is thought that components of kava may exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. METHODS: We conducted a systematic review to summarize available evidence of the anticancer effects of kava components and investigate their potential use for oral squamous cell carcinoma (OSCC) treatment. Eligible studies were identified through a comprehensive search of OVID EMBASE, OVID MEDLINE and Web of Science, as at April 2018. RESULTS: Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins. Further, they were associated with a dose-dependent reduction of angiogenesis. CONCLUSION: There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma.