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Regenerative endodontics aims to restore pulp tissues, thus preserving the vitality of the tooth. One promising approach involves the utilization of decellularized human dental pulp (DHDP) as a scaffold repopulated with Wharton's Jelly mesenchymal stem cells (WJMSCs). This study aimed to regenerate pulp tissues using DHDP and WJMSCs following pulpectomy in mature canine teeth of a feline animal model and to investigate the histological features of the regenerated pulp. A 12-month-old male domestic shorthaired felines were used as subjects. Teeth were categorized into untreated (Group 1), pulpectomy with mineral trioxide aggregate (MTA) (Group 2), and pulpectomy with DHDP-repopulated scaffold and MTA (Group 3). The animals were sacrificed six weeks post-intervention. H&E and immunohistochemistry using anti-collagen type 1 and laminin antibodies were used to stain the tissue sections. Histological examinations presented pulp-like tissues in Group 3, with tissue components similar to the structures found in Group 1. Immunohistochemical analysis demonstrated the presence of collagen type I and laminin within the regenerated tissues. The root canals of teeth in Group 2 were devoid of pulpal tissue. DHDP with WJMSCs can potentially be used for pulp regeneration, supporting the modality for developing new clinical protocols in stem cell therapy., Competing Interests: Declaration of Competing Interest The authors deny any conflicts of interest related to this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study evaluated the effectiveness of face-to-face (F2F) and online OralDETECT training programme in enhancing early detection skills for oral cancer., Methods: A total of 328 final-year dental students were trained across six cohorts. Three cohorts (175 students) received F2F training from the academic years 2016/2017 to 2018/2019, and the remaining three (153 students) underwent online training during the Covid-19 pandemic from 2019/2020 to 2021/2022. Participant scores were analysed using the Wilcoxon signed rank test, the Mann-Whitney test, Cohen's d effect size, and multiple linear regression., Results: Both F2F and online training showed increases in mean scores from pre-test to post-test 3: from 67.66 ± 11.81 to 92.06 ± 5.27 and 75.89 ± 11.03 to 90.95 ± 5.22, respectively. Comparison between F2F and online methods revealed significant differences in mean scores with large effect sizes at the pre-test stage (p < 0.001), while significant differences with small effect sizes were noted for post-test 1 (p = 0.002) and post-test 3 (p = 0.041). Regression analysis indicated that the delivery method is associated with the participants' final scores., Conclusion: F2F and online versions of the OralDETECT training programme significantly enhance participants' knowledge and skills in oral cancer detection. Although F2F appeared to be more effective, the difference was not substantial enough to be considered educationally meaningful., (© 2024 Wiley Periodicals LLC.)

Objectives: The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC)., Materials and Methods: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg's funnel plot., Results: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI - 0.25-0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group., Conclusion: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC., Clinical Relevance: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Homeobox genes play crucial roles in tooth morphogenesis and development and thus mutations in homeobox genes cause developmental disorders such as odontogenic lesions. The aim of this scoping review is to identify and compile available data from the literatures on the topic of homeobox gene expression in odontogenic lesions., Method: An electronic search to collate all the information on studies on homeobox gene expression in odontogenic lesions was carried out in four databases (PubMed, EBSCO host, Web of Science and Cochrane Library) with selected keywords. All papers which reported expression of homeobox genes in odontogenic lesions were considered., Results: A total of eleven (11) papers describing expression of homeobox genes in odontogenic lesions were identified. Methods of studies included next generation sequencing, microarray analysis, RT-PCR, Western blotting, in situ hybridization, and immunohistochemistry. The homeobox reported in odontogenic lesions includes LHX8 and DLX3 in odontoma; PITX2, MSX1, MSX2, DLX, DLX2, DLX3, DLX4, DLX5, DLX6, ISL1, OCT4 and HOX C in ameloblastoma; OCT4 in adenomatoid odontogenic tumour; PITX2 and MSX2 in primordial odontogenic tumour; PAX9 and BARX1 in odontogenic keratocyst; PITX2, ZEB1 and MEIS2 in ameloblastic carcinoma while there is absence of DLX2, DLX3 and MSX2 in clear cell odontogenic carcinoma., Conclusions: This paper summarized and reviews the possible link between homeobox gene expression in odontogenic lesions. Based on the current available data, there are insufficient evidence to support any definite role of homeobox gene in odontogenic lesions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral., Subjects and Methods: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions., Results: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®., Conclusion: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management., (© 2021 Wiley Periodicals LLC.)

Introduction: Dental education involves performing clinical procedures on patients under expert supervision. The COVID-19 pandemic has disrupted routine face-to-face teaching-learning-assessment dynamics world over. This study assessed the self-perceived preparedness of dental undergraduate students for practice, whose clinical training was interrupted by the COVID-19 pandemic from dental schools across Malaysia., Materials and Methods: This cross-sectional web-based questionnaire survey was done among new dental graduates of the academic year 2019-2020 and the final year undergraduate students (academic year 2020-2021) from dental schools in Malaysia, using the Dental Undergraduates Preparedness Assessment Scale (DU-PAS), from 6th to 26th April 2021. The questionnaire addressed clinical skill competence, and cognitive and behavioral attributes. The number of respondents needed to achieve a confidence level of 95% with margin of error of 5% was 306., Results: A total of 453 (243 final year students and 210 new graduates) responded from dental schools nationwide, with a response rate of 30.6%. The overall mean score for preparedness for dental practice was 76.3±14.7, for clinical skills 39.7±7.3, and behavioral and cognitive attributes 36.5±9.1. New graduates had significantly higher mean preparedness score (78.6±14.4) as compared to students in their final year (74.2±14.7). Performing endodontic treatment on multi-rooted teeth had the lowest perceived competency (29.8%), followed by assessing treatment needs of patients requiring orthodontics (37.1%), prescribing drugs (46.6%) and providing crowns using principles of tooth preservation (48.1%)., Conclusions: Satisfactory scores were obtained for most attributes. The final-year cohort was significantly less prepared for dental practice compared to the newly graduated cohort., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives: Studies examining the importance of inflammatory markers before treatment as prognosticators of OSCC are available, but information on post-therapy inflammatory markers and their prognostic significance is limited. This study aimed to evaluate the prognostic abilities of pre- and post-treatment inflammatory markers in patients with OSCC. Materials and Methods: In this retrospective analysis, information on 151 OSCC patients' socio-demographic, clinico-pathological, recurrence, metastasis, and survival data were gathered from clinical records. A multivariable Cox proportional hazards regression (stepwise model) was conducted to identify the prognostic predictors of OS and DFS. The multivariable models' performances were evaluated using Harrell's concordance statistics. Results: For OS, high pre-treatment LMR (HR 3.06, 95%CI 1.56, 5.99), and high post-treatment PLC (HR 3.35, 95%CI 1.71, 6.54) and PLR (HR 5.26, 95%CI 2.62, 10.58) were indicative of a poor prognosis. For DFS, high pre-treatment SII (HR 2.59, 95%CI 1.50, 4.48) and high post-treatment PLC (HR 1.92, 95%CI 1.11, 3.32) and PLR (HR 3.44, 95%CI 1.98, 5.07) were associated with increased mortality. The fitness of the OS and DFS stepwise Cox regression models were proven with a time-dependent AUC of 0.8787 and 0.8502, respectively. Conclusions: High pre-treatment levels of LMR and SII and high post-treatment levels of PLC and PLR are independent predictors of a poor prognosis for patients with OSCC.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4′s involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. Materials and Methods: Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT2 Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. Results: RT2 profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; p < 0.05) and Tie-2 (4.5-fold change; p < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (p < 0.01) and significantly increased the percentage of microvessels covered with pericytes (p < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (p < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. Conclusions: The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.

Lactate dehydrogenase enzyme (LDH) helps in the conversion of glucose into pyruvic acid during aerobic glycolysis and is found in the cytoplasm of most cells in the human body. When oxidative stress occurs in the body, LDH may be released extracellularly and its level is usually indicative of the severity of tissue damage. LDH has proved to be an inestimably resourceful marker in early prediction of serious diseases involving extensive tissue or cellular damage. This short communication explores the potential of LDH as a salivary biomarker of cell injury and death., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer., (© 2020. American Association for Cancer Education.)

Autophagy, first described by the Belgian biochemist Christian De Duve in 1963, is derived from the Greek word "autóphagos," which means "self-devouring." It is a cellular homeostatic process in which the body rids itself of flawed or damaged cells and other defective cellular organelles. 1 The implication of defective autophagy in various human diseases has been well documented. The vital importance of autophagy is underscored by the fact that robust cellular health and function are intricately linked with it.

Background: We examined the lactate dehydrogenase (LDH) enzyme levels in the saliva of vapers (e-cigarette users) and compared the data with cigarette smokers and a control group of non-smokers and non-vapers., Methods: Subjects were recruited among those responding to a social media announcement or patients attending the SEGi Oral Health Care Centre between May and December 2019, and among some staff at the centre. Five ml of unstimulated   whole saliva was collected and salivary LDH enzyme activity levels were measured with a LDH colorimetric assay kit. Salivary LDH activity level was determined for each group and compared statistically., Results: Eighty-eight subjects were categorized into three groups (control n=30, smokers n=29, and vapers n=29). The mean ± standard deviation (SD) values for salivary LDH activity levels for vapers, smokers, and control groups were 35.15 ± 24.34 mU/ml, 30.82 ± 20.73 mU/ml, and 21.45 ± 15.30 mU/ml, respectively. The salivary LDH activity levels of smoker and vaper groups were significantly higher than in the control group (p = 0.031; 0.017). There was no significant difference of salivary LDH activity level in vapers when compared with smokers (p= 0.234)., Conclusion: Our findings showed higher LDH levels in the saliva of vapers when compared with controls, confirming cytotoxic and harmful effects of e-cigarettes on the oral mucosa.

Objective: This study aims to examine the ability of optical coherence tomography (OCT) to differentiate ex vivo epithelial structure of benign disorders, dysplastic, and oral squamous cell carcinoma (OSCC) in comparison with the structure of normal marginal mucosa of oral biopsies. As a secondary objective, we examined the inter- and intra-observer variations of OCT measurements of two calibrated assessors., Materials and Methods: Oral biopsies (n = 44) were scanned using the swept source OCT (SSOCT) and grouped by pathology diagnosis to benign, dysplasia or carcinoma. Two trained and calibrated assessors scored on the five OCT variables: thickness of keratin layer (KL), epithelial layer (EL), homogeneity of lamina propria (LP), basement membrane integrity (BMI), and the degree of reflection of the epithelial layer (Ep Re). Chi-square tests and Fischer's exact method were used to compare the data., Results: The OCT images showed breached BM status in all the OSCC samples (100%). Epithelial reflection was noted to be hyper-reflective in all the OSCC and oral dysplasia samples (100%). An increase in KL in 66.67% of the OSCC and 100% of the oral dysplasia samples was found. EL was increased in all the OSCC samples (100%) and 85.72% of the oral dysplasias. Kappa values showed that there was very good agreement (over 0.7) when scoring individual parameters between the two assessors., Conclusion: The study showed that the BM status was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders., Clinical Relevance: OCT is a non-invasive and non-radioactive adjunct diagnostic tool that can provide immediate results on the structure of oral mucosa. The BM status measured ex vivo was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC)., Methods: Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) ( n  = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) ( n  = 120) and immunohistochemistry (IHC) ( n  = 70) were used to confirm our findings., Results: The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC ( p  < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues., Conclusion: Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation., Competing Interests: The authors declared that they have no competing interests., (©2021 Wong et al.)

Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche-Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia.

Background and Objectives: In cancer therapy optimization, an optimal amount of drug is determined to not only reduce the tumor size but also to maintain the level of chemo toxicity in the patient's body. The increase in the number of objectives and constraints further burdens the optimization problem. The objective of the present work is to solve a Constrained Multi- Objective Optimization Problem (CMOOP) of the Cancer-Chemotherapy. This optimization results in optimal drug schedule through the minimization of the tumor size and the drug concentration by ensuring the patient's health level during dosing within an acceptable level., Methods: This paper presents two hybrid methodologies that combines optimal control theory with multi-objective swarm and evolutionary algorithms and compares the performance of these methodologies with multi-objective swarm intelligence algorithms such as MOEAD, MODE, MOPSO and M-MOPSO. The hybrid and conventional methodologies are compared by addressing CMOOP., Results: The minimized tumor and drug concentration results obtained by the hybrid methodologies demonstrate that they are not only superior to pure swarm intelligence or evolutionary algorithm methodologies but also consumes far less computational time. Further, Second Order Sufficient Condition (SSC) is also used to verify and validate the optimality condition of the constrained multi-objective problem., Conclusion: The proposed methodologies reduce chemo-medicine administration while maintaining effective tumor killing. This will be helpful for oncologist to discover and find the optimum dose schedule of the chemotherapy that reduces the tumor cells while maintaining the patients' health at a safe level., Competing Interests: Declaration of Competing Interest The authors of this paper entitled “The Combined Effect of Optimal Control and Swarm Intelligence on Optimization of Cancer Chemotherapy” would like state there is no conflict of interest in submitting this work to the journal of Computer Methods and Programs in Biomedicine., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Up to 86% of oral cancer (OC) patients present at the late stage where survival is dismal. Limited access to specialist diagnosis is a significant factor for late presentation. The increasing use of smartphones presents an opportunity to use digital technology to facilitate early detection of OC. Aim: To evaluate the feasibility of using Mobile Mouth Screening Anywhere (MeMoSA ® ) to facilitate early detection of OC. Methods: A mobile phone app named MeMoSA was developed and the feasibility of integrating this for documentation of oral lesions, and communication between dentists and specialists for management decisions were evaluated. The experience of dentists and specialists in using MeMoSA was determined using qualitative questionnaires. Results: Communication between specialist and dentists using MeMoSA stratified cases and streamlined referral of patients. Twelve of 48 patients were found to have oral lesions or signs suspicious of cancer and 3 required referrals. The patient's compliance for referral was tracked with MeMoSA. All dentists agreed that MeMoSA could facilitate early detection of OC and believed that MeMoSA could assist in the identification of oral mucosal lesions through direct communication with specialists and continuous learning in the recognition of high-risk lesions. Conclusions: MeMoSA has the potential to be used to promote equitable health care and streamline patient management that could result in early detection of OC.

Conventionally, the batch type reactors were used for the production of biodiesel. However, in recent years, the usage of microreactors has started emerging as a significant substitute for biodiesel production due to its higher conversion rate at a short duration. These microreactors have a significantly high surface to volume ratio and high heat-mass transfer rate. The disadvantage of this type of reactors is its low mixing rate of the reagents. This can be overcome with the assistance of ultrasonic mixing. The main objective of this paper is to study the interlaced effect of a continuous flow microreactor and ultrasonic mixing on trans-esterification of Aegle Marmelos Correa seed oil using sodium methoxide catalyst. Results of microreactors with 0.3 mm and 0.8 mm diameter were compared. The effects of process parameters namely, flow rate (2-10 mL/min), reaction temperature (45-65 °C), catalyst amount (0.5-2.5 wt%), oil to methanol molar ratio (1:6-1:18) and ultrasonic mixing time (30-150 s) were studied using response surface methodology (RSM). The biodiesel yield of 98% and 91.8% were obtained for 0.3 mm and 0.8 mm microreactors, respectively. The maximum biodiesel yield observed in 0.3 mm reactor under following optimum conditions: 6.8 mL/min flow rate, 48 °C reaction temperature, 1.3 wt% catalyst, 1:9 oil to methanol molar ratio and 83 s ultrasonic mixing time. The predictive and generalization abilities of RSM and artificial neural network (ANN) models were evaluated and compared. The study showed that ANN and RSM models could predict the yield with an R 2 value of 0.9955 and 0.9900 respectively. However, the ANN model predicted the yield with the least mean square error value of 0.00001294, which is much lower than RSM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.

Objectives: To evaluate the efficacy of mouth self-examination (MSE) as a self-screening tool for detection of oral mucosal lesions among an Indigenous population in Malaysia at high risk for oral premalignant and malignant disorders., Methods: Two villages were selected as the sampling frame based on prevalence of tobacco and betel quid chewing habit. Respondents were asked to check their mouth for presence of lesion or abnormalities. Education on oral cancer, including MSE, was provided. Subsequently, respondents were asked to perform MSE. Finally, a clinical oral examination (COE) was done by a specialist and the presence of oral mucosal lesions was recorded., Results: Almost 64.5 percent of respondents exhibited high levels of difficulty and low mucosal visualization and retracting ability, whereas 3.0 percent demonstrated high attention level when performing MSE. Prevalence of oral mucosal lesions was 59.0 percent, whereas the prevalence of oral potentially malignant disorders (OPMDs) was 9.0 percent. Detection of oral lesions by respondents using MSE was lower than detection by the gold standard. Sensitivity and specificity of MSE for detection of all types of lesions were 8.6 and 95.0 percent respectively. When analyzing each lesion type separately, MSE was found to be most sensitive in detection of swellings (10.0 percent), and most specific in identifying white lesions (97.8 percent). For detection of OPMDs, although specificity was high (98.9 percent), sensitivity (0 percent), and +LR (0) was poor., Conclusion: MSE is not an effective self-screening tool for early detection of potentially malignant lesions for this population., (© 2019 American Association of Public Health Dentistry.)

Objective: To study the potential for apoptosis induction of Dracaena cinnabari Balf. f methanolic extract (DCBME) on tongue squamous cell carcinoma cell line, H103. We evaluated the chemopreventive activity of DCBME against 4-nitroquinolone-1-oxide (4NQO)-induced tongue carcinogenesis in rat., Design: Phase contrast microscope, acridine orange/propidium iodide (AO/PI) analysis of cells under fluorescence microscope, annexin-V flow-cytometry, DNA fragmentation, mitochondrial membrane potential, and caspase 3/7, 8 and 9 assays were performed. In vivo study, the rats were given 4NQO in their drinking water. The tongue was subjected to histopathological study to evaluate the incidence of squamous cell carcinoma (SCC)., Results: DCBME showed cytotoxic effect on H103 cells in a dose- and time-dependent manner. Furthermore, DCBME showed low cytotoxic effect on a normal cell line. In H103 cells, it caused cell morphology changes, S and G2/M-phase cell cycle arrest, significant reduction of cell migration and induced apoptosis through the intrinsic (mitochondrial) pathway. The incidence of SCC was 85.7% in the induced cancer and vehicle groups while in rats treated with DCBME at 100, 500 and 1000 mg/kg was 57.1%, 28.6% and 14.3%, respectively., Conclusions: (DCBME)-apoptosis induction reported in this work can be exploited as a potential antitumor agent with applications in medicinal treatments of tongue SCC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Alopecia is a clinical condition caused by excessive hair loss which may result in baldness, the causes of which still remain elusive. Conditioned media (CM) from stem cells shows promise in regenerative medicine. Our aim was to evaluate the potential CM of dental pulp stem cells obtained from human deciduous teeth (SHED-CM) to stimulate hair growth under in vitro and in vivo conditions. SHED and hair follicle stem cells (HFSCs) (n = 3) were cultured in media combinations; i) STK2, ii) DMEM-KO+10% FBS, iii) STK2+2% FBS and profiled for the presence of positive hair growth-regulatory paracrine factors; SDF-1, HGF, VEGF-A, PDGF-BB and negative hair growth-regulatory paracrine factors; IL-1α, IL-1β, TGF-β, bFGF, TNF-α, and BDNF. The potential of CM from both cell sources to stimulate hair growth was evaluated based on the paracrine profile and measured dynamics of hair growth under in vitro conditions. The administration of CM media to telogen-staged synchronized 7-week old C3H/HeN female mice was carried out to study the potential of the CM to stimulate hair growth in vivo. SHED and HFSCs cultured in STK2 based media showed a shorter population doubling time, higher viability and better maintenance of MSC characteristics in comparison to cells cultured in DMEM-KO media. STK2 based CM contained only two negative hair growth-regulatory factors; TNF-α, IL-1 while DMEM-KO CM contained all negative hair growth-regulatory factors. The in vitro study confirmed that treatment with STK2 based media CM from passage 3 SHED and HFSCs resulted in a significantly higher number of anagen-staged hair follicles (p<0.05) and a significantly lower number of telogen-staged hair follicles (p<0.05). Administration of SHED-CM to C3H/HeN mice resulted in a significantly faster stimulation of hair growth in comparison to HFSC-CM (p<0.05), while the duration taken for complete hair coverage was similar for both CM sources. Thus, SHED-CM carries the potential to stimulate hair growth which can be used as a treatment tool for alopecia., Competing Interests: The authors have declared that no competing interests exist.

Objectives: In vivo study was performed to determine the chemopreventive efficacy of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer animal model., Materials and Methods: This study involves administration of 4NQO solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC) extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week before exposure until 1 week after the carcinogen exposure was stopped. All rats were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumor marker antibodies were analyzed using an image analyzer computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT 2 -PCR., Results: The incidence of OSCC decreased with the administration of DC extract at 100, 500, and 1000 mg/kg compared to the induced cancer group. The developed tumor was also observed to be smaller when compared to the induced cancer group. The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2, Cyclin D1, and EGFR genes when compared to the induced cancer group., Conclusions: The data indicated that systemic administration of the DC resin methanol extract has anticarcinogenic potency on oral carcinogenesis., Clinical Relevance: Chemoprevention with DC resin methanol extract may significantly reduce morbidity and possibly mortality from OSCC.

Goniothalamin (GTN) is an isolated compound from several plants of the genus Goniothalamus , and its anticancer effect against several cancers was reported. However, there is no scientific data about effects of its higher doses on internal organs. Accordingly, this study aimed to evaluate the acute and subacute effects of higher doses of GTN on the hematology, biochemistry, and histology of selected internal organs of male Sprague-Dawley rats. In acute study, 35 rats were distributed in 5 groups (n=7) which were intraperitoneally (IP) injected with a single dose of either 100, 200, 300, 400, or 500 mg/kg of GTN, while extra 7 rats serve as a normal control. In subacute study, 7 rats were IP-injected with a daily dose of 42 mg/kg of GTN for 14 days, while another 7 rats serve as a normal control group. The normal controls in both studies were IP-injected simultaneously with 2 ml/kg of 10% DMSO in PBS. At the end of both tests, rats were sacrificed to collect blood for hematology and biochemistry and harvest livers, kidneys, lungs, hearts, spleens, and brains for histology. During acute and subacute exposure, no abnormal changes were observed in the hematology, biochemistry, and histology of the internal organs. However, the 300, 400, and 500 mg/kg of GTN during acute exposure were associated with morbidities and mortalities. Ultimately, GTN could be safe up to the dose of 200 mg/kg, and the dose of 42 mg/kg of GTN was tolerated well.

Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10 A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48 healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival. The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion. Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence to support the lack of association of IL10 A1082G polymorphism in oral cancer., (Creative Commons Attribution License)

Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.

The authors wish to make the following change to their paper [1].[...].

Background: Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations., Methods: In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology., Results: In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control., Conclusion: This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.

A relatively new class of three-dimensional ordered mesoporous silicates, KIT-6, incorporated with Earth-abundant metals such as Zr, Nb, and W (termed as M-KIT-6), show remarkable tunability of acidity and metal dispersion depending on the metal content, type, and synthetic method. The metal-incorporation is carried out using one-pot synthesis procedures that are amenable to easy scale-up. By such tuning, M-KIT-6 catalysts are shown to provide remarkable activity and selectivity in industrially-significant reactions, such as alcohol dehydration, ethylene epoxidation, and metathesis of 2-butene and ethylene. We review how the catalytic properties of M-KIT-6 materials may be tailored depending on the application to optimize performance., Competing Interests: The authors declare no conflict of interest.

Objectives: Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis., Materials and Methods: An electronic search was undertaken using combination of keywords e.g. Homeobox genes, tooth development, dental diseases, stem cells, induced pluripotent stem cells, gene control region was used as search terms in PubMed and Web of Science and relevant full text articles and abstract were retrieved that were written in English. A manual hand search in text books were also carried out. Articles related to homeobox genes in dentistry and tissue engineering and regenerative medicine of odontogenesis were selected., Results: The possible perspective of stem cells technology in odontogenesis and subsequent analysis of gene correction pertaining to dental disorders through the possibility of induced pluripotent stem cells technology is also inferred., Conclusions: We demonstrate the promising role of tissue engineering and regenerative medicine on odontogenesis, which can generate a new ray of hope in the field of dental science., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To obtain data on the prevalence of oral mucosal lesions (OMLs) among Cambodians, and to assess the relationship between known risk habits of oral diseases with prevalence of oral potentially malignant disorders (OPMDs)., Design: This was a population-based, cross-sectional study whereby subjects were adults aged 18 years old and above. A workshop on the identification of OML was held to train and calibrate dental officers prior to data collection in the field. Sociodemographic and risk habits data were collected via face-to-face interview, whilst presence of OML and clinical details of lesions such as type and site were collected following clinical oral examination by the examiners. Data analysis was carried out using the Statistical Package for Social Science (SPSS) version 12.0. The association between risk habits and risk of OPMD was explored using logistic regression analysis., Results: A total of 1634 subjects were recruited. Prevalence of OML for this population was 54.1%. Linea alba was the most common lesion seen (28.7%). This study showed an overall OPMD prevalence of 5.6%. The most common type of OPMD was leukoplakia (64.8%), followed by lichen planus (30.8%). Subjects who only smoked were found to have an increased risk for OPMD of almost four-fold (RR 3.74, 95%CI 1.89-7.41). The highest risk was found for betel quid chewers, where the increased risk observed was more than six times (RR 6.75, 95%CI 3.32-13.72). Alcohol consumption on its own did not seem to confer an increased risk for OPMD, however when practiced concurrently with smoking, a significant risk of more than five times was noted (RR 5.69 95%CI 3.14-10.29)., Conclusion: The prevalence of OML was 54.1%, with linea alba being the most commonly occurring lesion. Smoking, alcohol consumption and betel quid chewing were found to be associated with the prevalence of OPMD, which was 5.6%.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.

Sweet syndrome (SS) is a prototypical neutrophilic dermatosis, a class of inflammatory diseases marked by elevated levels of tumor necrosis factor (TNF)-α and IL-17A, pathologic neutrophil recruitment, and microvascular remodeling. Histologic analyses of four matrix proteins-collagen I and IV, laminin, and fibronectin-in skin biopsies of patients with SS reveal that the basement membrane of dermal postcapillary venules undergoes changes in structure and composition. Increased neutrophil recruitment in vivo was associated with increases in collagen IV, decreases in laminin, and varied changes in fibronectin. In vitro studies using TNF-α and IL-17A were conducted to dissect basement membrane remodeling. Prolonged dual activation of cultured human pericytes with TNF-α and IL-17A augmented collagen IV production, similar to in vivo remodeling. Co-activation of pericytes with TNF-α and IL-17A also elevated fibronectin levels with little direct effect on laminin. However, the expression of fibronectin- and laminin-specific matrix metalloproteinases (MMPs), particularly MMP-3, was significantly up-regulated. Interactions between pericytes and neutrophils in culture yielded even higher levels of active MMPs, facilitating fibronectin and laminin degradation, and likely contributing to the varied levels of detectable fibronectin and the decreases in laminin observed in vivo. These data indicate that pericyte-neutrophil interactions play a role in mediating microvascular changes in SS and suggest that targeting MMP-3 may be effective in protecting vascular wall integrity., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy., Objectives: The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes., Materials and Methods: Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software., Results: Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC., Conclusion: Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways.

Introduction: This study examined the concordance in clinical diagnosis of high-risk lesions in the oral cavity and referral decisions between clinical oral examination (COE) and teledentistry., Materials and Methods: Sixteen individuals with a range of oral potentially malignant disorders (OPMD) and normal oral mucosa were included. Five areas of the oral cavity were photographed by three dentists using mobile phone cameras with 5 MP-13 MP resolutions. On the same day, the patients were given COE by two oral medicine specialists (OMS) and 3 weeks later, they reviewed the images taken using the phone, and concordance was examined between the two by Kappa statistics. The sensitivity and specificity of clinical diagnosis using the phone images were also measured. Pre- and post-program questionnaires were answered by both the dentists and the OMS to determine the feasibility of integrating teledentistry in their clinical practice., Results: The Kappa values in determining the presence of lesion, category of lesion (OPMD or not), and making referral decision were moderate to strong (0.64-1.00). The overall sensitivity was more than 70% and specificity was 100%. The false negative rate decreased as the camera resolution increased. All dentists agreed that the process could facilitate early detection of oral mucosal lesion, and was easy to use in the clinic., Conclusions: This study provides evidence that teledentistry can be used for communication between primary care and OMS and could be readily integrated into clinical setting for patient management.

The 5' m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2'O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Turnaround time (TAT) is the benchmark to assess the performance of a laboratory, pathologists, and pathology services, but there are few articles on TAT of surgical pathology, particularly in relation to oral or head and neck specimens. This study investigates the TAT for oral histopathology reporting in an academic institution's training laboratory and offers recommendations to achieve better overall quality of diagnostic services., Methods: This study examined data obtained from biopsy request forms for specimens received from the Oro-Maxillofacial Surgery Department of Hospital Tengku Ampuan Rahimah Klang in the Oral Pathology Diagnostic Laboratory of the Faculty of Dentistry, University of Malaya, over a period of 3 years between January 2012 and October 2014., Results: TAT for surgical and decalcified specimens were increased significantly compared to biopsies. Additional special handling did not influence TAT, but increased specimen volume resulted in greater TAT. Slide interpretation was the most time-consuming stage during histopathology reporting. Overall, mean TAT was acceptable for most specimens, but the TAT goals were less than satisfactory., Conclusion: A TAT goal appropriate for this laboratory may hence be established based on this study. Collective efforts to improve the TAT for various specimens are essential for better laboratory performance in the future., (© The Author(s) 2016.)

Caveolin-1 (Cav-1) and Actin-Related Protein 2/3 Complex, Subunit 1B (ARPC1B) have been implicated in various human cancers, yet its role in tumorigenesis remains controversial. Therefore, this study aims to determine the protein expression of these two genes in oral squamous cell carcinomas (OSCCs) and to evaluate the clinical and prognostic impact of these genes in OSCC. Protein expressions of these two genes were determined by immunohistochemistry technique. The association between Cav-1 and ARPC1B with clinico-pathological parameters was evaluated by Chi-square test (or Fisher exact test where appropriate). Correlation between the protein expressions of these 2 genes with survival was analyzed using Kaplan-Meier and Cox regression models. Cav-1 and ARPC1B were found to be significantly over-expressed in OSCC compared to normal oral mucosa (p = 0.002 and p = 0.033, respectively). Low level of ARPC1B protein expression showed a significant correlation with lymph node metastasis (LNM) (p = 0.010) and advanced tumor staging (p = 0.003). Kaplan-Meier survival analyses demonstrated that patients with over-expression of Cav-1 protein were associated with poor prognosis (p = 0.030). Adjusted multivariate Cox regression model revealed that over-expression of Cav-1 remained as an independent significant prognostic factor for OSCC (HRR = 2.700, 95 % CI 1.013-7.198, p = 0.047). This study demonstrated that low-expression of ARPC1B is significantly associated with LNM and advanced tumor staging whereas high expression of Cav-1 can be a prognostic indicator for poor prognosis in OSCC patients.

RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

RNAs with 5'-triphosphate (ppp) are detected in the cytoplasm principally by the innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I), whose activation triggers a Type I IFN response. It is thought that self RNAs like mRNAs are not recognized by RIG-I because 5'ppp is capped by the addition of a 7-methyl guanosine (m7G) (Cap-0) and a 2'-O-methyl (2'-OMe) group to the 5'-end nucleotide ribose (Cap-1). Here we provide structural and mechanistic basis for exact roles of capping and 2'-O-methylation in evading RIG-I recognition. Surprisingly, Cap-0 and 5'ppp double-stranded (ds) RNAs bind to RIG-I with nearly identical Kd values and activate RIG-I's ATPase and cellular signaling response to similar extents. On the other hand, Cap-0 and 5'ppp single-stranded RNAs did not bind RIG-I and are signaling inactive. Three crystal structures of RIG-I complexes with dsRNAs bearing 5'OH, 5'ppp, and Cap-0 show that RIG-I can accommodate the m7G cap in a cavity created through conformational changes in the helicase-motif IVa without perturbing the ppp interactions. In contrast, Cap-1 modifications abrogate RIG-I signaling through a mechanism involving the H830 residue, which we show is crucial for discriminating between Cap-0 and Cap-1 RNAs. Furthermore, m7G capping works synergistically with 2'-O-methylation to weaken RNA affinity by 200-fold and lower ATPase activity. Interestingly, a single H830A mutation restores both high-affinity binding and signaling activity with 2'-O-methylated dsRNAs. Our work provides new structural insights into the mechanisms of host and viral immune evasion from RIG-I, explaining the complexity of cap structures over evolution.

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named ‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’ variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’ as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential., (Creative Commons Attribution License)

Objectives: This study includes the direct sequencing of cornulin (CRNN) gene to elucidate the possible mechanism of CRNN downregulation and explore the genetic imbalances at 1q21.3 across oral squamous cell carcinoma (OSCC) samples., Materials and Methods: In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples., Results: No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044)., Conclusion: This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC., Clinical Relevance: Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.

Background: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC., Methods: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models., Results: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC., Conclusion: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC.

A novel chemosensor based on pyrazole biscoumarin molecule "4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methyl)-2H-chromen-2-one" (PBC) was synthesized by a simple method. The chemosensing properties of PBC towards transition metal ions like Cu(2+) and Zn(2+) by naked eye, UV-Visible and fluorescence spectroscopic methods were described. The PBC solution with Cu(2+) and Zn(2+) ion showed brown and blue colour respectively. The UV-Visible spectra of PBC with Cu(2+) and Zn(2+) ions exposed their corresponding absorption maxima. Further, the Job's plot method confirmed the 1:1 and 2:1 stoichiometry of the complex formation between the PBC with Cu(2+) and Zn(2+) ions respectively. The fluorescence enhancement of PBC on binding with Cu(2+) and Zn(2+) is due to the inhibition of photo induced electron transfer mechanism., (Copyright © 2015 Elsevier B.V. All rights reserved.)