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Matrix stiffening is ubiquitous in solid tumors and can direct epithelial-mesenchymal transition (EMT) and cancer cell migration. Stiffened niche can even cause poorly invasive oral squamous cell carcinoma (OSCC) cell lines to acquire a less adherent, more migratory phenotype, but mechanisms and durability of this acquired "mechanical memory" are unclear. Here, we observed that contractility and its downstream signals could underlie memory acquisition; invasive SSC25 cells overexpress myosin II (vs. noninvasive Cal27 cells) consistent with OSCC. However, prolonged exposure of Cal27 cells to a stiff niche or contractile agonists up-regulated myosin and EMT markers and enabled them to migrate as fast as SCC25 cells, which persisted even when the niche softened and indicated "memory" of their prior niche. Stiffness-mediated mesenchymal phenotype acquisition required AKT signaling and was also observed in patient samples, whereas phenotype recall on soft substrates required focal adhesion kinase (FAK) activity. Phenotype durability was further observed in transcriptomic differences between preconditioned Cal27 cells cultured without or with FAK or AKT antagonists, and such transcriptional differences corresponded to discrepant patient outcomes. These data suggest that mechanical memory, mediated by contractility via distinct kinase signaling, may be necessary for OSCC to disseminate.

Tumors are composed of heterogeneous phenotypes, each having different sensitivities to the microenvironment. One microenvironment characteristic - matrix stiffness - helps to regulate malignant transformation and invasion in mammary tumors, but its influence on oral squamous cell carcinoma (OSCC) is unclear. We observed that, on stiff matrices, a highly invasive OSCC cell line (SCC25) comprising a low E-cad to N-cad ratio (InvH/E:NL; SCC25) had increased migration velocity and decreased adhesion strength compared to a less invasive OSCC cell line (Cal27) with high E-cad to N-cad ratio (InvL/E:NH; Cal27). However, InvL/E:NH cells acquire a mesenchymal signature and begin to migrate faster when exposed to prolonged time on a stiff niche, suggesting that cells can be mechanically conditioned. Owing to increased focal adhesion assembly, InvL/E:NH cells migrated faster, which could be reduced when increasing integrin affinity with high divalent cation concentrations. Mirroring these data in human patients, we observed that collagen organization, an indicator of matrix stiffness, was increased with advanced disease and correlated with early recurrence. Consistent with epithelial tumors, our data suggest that OSCC cells are mechanically sensitive and that their contribution to tumor progression is mediated in part by this sensitivity.This article has an associated First Person interview with the first author of the paper.

Purpose: Distance learning appears to be an attractive approach to continuing education courses, but one barrier is maintaining learner engagement throughout the course. The primary aim of this research was to evaluate the operational efficacy of a private Facebook™ group (FG) in serving as a support mechanism for distance learning courses, and its impact on three fundamental dimensions: the attrition rates of participants who did not complete the course (commonly referred to as dropout rates), the rates of course completion and approval, and the overall performance of the participants. Methods: The participants of this quasi‐experimental study comprised 159 dental students and 565 dentists enrolled in an e‐learning course on oral mucosal lesion diagnosis. Prior to the initiation of the course, all participants were provided with the option to join a private FG. Within this group, moderators shared motivational messages and provided reminders concerning deadlines. Moreover, participants had the opportunity to engage in interactive discussions pertaining to topics related to the course. The course itself followed a self‐guided format, employing the flipped‐classroom methodology, spanning a total of 50 instructional hours. In order to assess the effectiveness of the course, participants were presented with photographs illustrating 30 oral lesions and were asked to propose diagnostic hypotheses both before and after the educational intervention (pre‐tests and post‐tests). Results: Dentists who participated in the FG exhibited a significantly lower rate of discontinuation. As for dental students, their involvement in the group was positively associated with better performance, as determined by the percentage of accurate diagnostic hypotheses (a minimum of 70% correct responses was required for their approval in the course). Conclusions: Facebook™ demonstrates promise as a supplementary pedagogical tool in distance education courses. The interactive nature of the platform has the potential to alleviate the inherent challenges of remote learning. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of titanium (Ti) particles on oral epithelial cell homeostasis and the potential of dental implants to release Ti debris upon insertion. Materials and Methods: Dental implants with varying surface treatments were employed to determine the feasibility of particle release during implant placement as well as the impact of free Ti debris on oral epithelial cells. Ti particles derived from implant surfaces were isolated and cultured in direct contact with normal oral epithelial cells for 48 hours. Further, cells were fixed and processed for immunofluorescence assay to detect the activation of the DNA damage response (DDR) using CHK2 and BRCA1 molecular markers. Positive cells demonstrating DNA damage were quantified and statistically analyzed. Results: Ti particles derived from implants containing phosphate-enriched titanium oxide (PETO), fluoride-modified (FM), and grit-blasted (GB) surface treatments were able to activate CHK2 and trigger the recruitment of BRCA1 in oral epithelial cells. Also, implants with GB surfaces were able to release Ti particles upon implant placement. Conclusion: The results indicate that Ti debris may be detached from the implant surface upon placement. Also, free Ti particles can trigger DDR signaling in oral epithelial cells. These findings suggest that Ti particles/debris released into a surgical wound may contribute to the disruption of epithelial homeostasis, and potentially compromise the oral epithelial barrier. [ABSTRACT FROM AUTHOR]

Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro‐inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates the clinical benefits of photobiomodulation therapy (PBMT) in the management of skin and mucosal wounds. Here, we decided to explore the effects of different regiments of PBMT on epithelial cells and stem cells, and the potential implications over the epigenetic circuitry during healing. Scratch‐wound migration, immunofluorescence (anti‐acetyl‐Histone H3, anti‐acetyl‐CBP/p300 and anti‐BMI1), nuclear morphometry and western blotting (anti‐Phospho‐S6, anti‐methyl‐CpG binding domain protein 2 [MBD2]) were performed. Epithelial stem cells were identified by the aldehyde dehydrogenase enzymatic levels and sphere‐forming assay. We observed that PBMT‐induced accelerated epithelial migration and chromatin relaxation along with increased levels of histones acetylation, the transcription cofactors CBP/p300 and mammalian target of rapamycin. We further observed a reduction of the transcription repression‐associated protein MBD2 and a reduced number of epithelial stem cells and spheres. In this study, we showed that PBMT could induce epigenetic modifications of epithelial cells and control stem cell fate, leading to an accelerated healing phenotype. [ABSTRACT FROM AUTHOR]

Objectives: This cross‐sectional study aims to evaluate whether Continuing Education Activities (CEA) influence dentists' behaviour in relation to oral lesions. The secondary aim is to assess the association between dentists' perception of learning adequacy and self‐efficacy for oral mucosal lesion management. Methods: A self‐administered online questionnaire was conducted on dentists working at the public health system of Rio Grande do Sul State, Brazil. The questionnaire included questions pertaining to perception of adequacy for oral diagnosis classes upon graduation, participation in oral cancer CEA and self‐efficacy in managing oral mucosal lesions. Results: 221 dentists from 91 municipalities answered the questionnaire. Most participants were female (71.5%) with a mean age of 38.3 years. Perception of learning as adequate during undergraduate coursework was associated with self‐efficacy to diagnose, biopsy, and treat oral mucosal lesions (P <.05, Chi‐squared test). However, 83.3% of dentists considered the time devoted to these topics prior to graduation insufficient. The frequency of oral lesion detection was related to self‐efficacy to treat oral lesions and detecting oral cancer (P <.05, Chi‐squared test). Among dentists who detected oral lesions frequently, 88.9% had attended CEA, whereas 11.1% of them had never attended these activities. Conclusions: CEA may improve awareness and efficacy of primary healthcare professional's detection of oral cancer. [ABSTRACT FROM AUTHOR]

The presence of the CRTC1-MAML2 translocation has been described in mucoepidermoid carcinoma (MEC) as a predictor of better survival rates. However, the real prognostic value of the translocation has been debated due to recent controversial findings. The aim of this study was to perform a systematic review to understand the prognostic potential of the CRTC1-MAML2 translocation in MEC. An electronic search was carried out using the MEDLINE/PubMed, EMBASE and Scopus databases. Articles that assessed the association between the CRTC1-MAML2 translocation and survival of MEC patients were selected for the systematic review. Ten published articles were included in the qualitative synthesis. The prevalence of the translocation varied from 33.7% to 69.7%. Seven studies observed a significant association between the presence of the CRTC1-MAML2 translocation and a favourable clinical outcome, which could improve disease-free, disease-specific or overall survival. Five studies were included in the quantitative synthesis. Fixed-effects model confirmed that translocation-positive patients have a decreased risk of death (combined odds ratio 0.08, 95% confidence interval - 0.03-0.23, P < .00001). The detection of the CRTC1-MAML2 translocation appears to be useful as a prognostic factor in MEC. However, the level of evidence is not as high as it could be once important limitations were found in the published studies. [ABSTRACT FROM AUTHOR]

Odontogenic lesions (OL) are an important group of oral and maxillofacial diseases represented by odontogenic cysts, benign, and malignant tumors. The brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrkB) signaling pathway has multiple biological actions and has been identified as an important pathway in the proliferation, invasion, and survival of different epithelial tumors. Its role in the development of OL, however, has so far been unexplored. Our aim was to evaluate the BDNF/TrkB/Akt/p-RPS6 signaling pathway in OL of epithelial origin. This cross-sectional study comprised 3 cases of tooth germs, 25 cases of odontogenic keratocyst (OK), 29 cases of ameloblastoma (Am), and 6 cases of ameloblastic carcinoma. Immunohistochemical staining for BDNF, TrkB, p-Akt, and p-RPS6 was performed. OLs were evaluated according to the pattern of immunohistochemical expression in epithelial cells and by semiquantitative scores that considered the intensity of staining and percentage of positive cells. BDNF stromal expression was also assessed. No significant differences were observed with respect to the percentage of positive cases for all markers. Regarding the immunoreactive scores, BDNF and p-RPS6 expressions were similar in the odontogenic epithelium of all OL. However, TrkB and p-Akt were overexpressed in OK compared with ameloblastic carcinoma. In Am, epithelial BDNF was significantly higher compared with stromal expression. In conclusion, BDNF seems to participate in the development of cystic, benign, and malignant odontogenic epithelium to similar degrees. The acquisition of the invasive or malignant phenotype in odontogenic neoplasms is not associated with alterations in the BDNF/TrkB/Akt/RPS6 axis, which could be implicated in the differentiation process., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Difficulties in diagnosis of oral mucosal lesions are a significant cause of delayed oral cancer diagnosis, and this difficulty may be due to gaps in knowledge. This study evaluated the diagnostic skills of primary healthcare professionals regarding oral cancer and presented them with an e-learning course., Materials and Methods: Forty-seven primary healthcare professionals (32 dentists and 15 nondentists) enrolled in a 24-h course on oral medicine delivered through an e-learning platform. A test, based on 33 clinical images of oral lesions, was used to evaluate the diagnostic skills of participants. The participants were requested to classify each lesion as benign, potentially malignant, or malignant as well as to inform their clinical impression. Three specialists also took the test as the gold standard., Results: Twenty-seven participants completed the test. Nondentists and dentists showed a comparable sensitivity of 68.8 ± 11.1 and 63.7 ± 15.8, respectively. Specialists performed somewhat better; however, the difference was not statistically significant (81.0% ± 4.1%, p = 0.16). Dentists and specialists (70.0% ± 16.6% and 95.5% ± 3.1%, respectively) showed higher specificity than nondentists (39.3 ± 20.6, p < 0.01). Nondentists had a higher number of unanswered questions (p < 0.01) for classification and clinical impression (50.0% ±45.1% and 72.0% ± 25.0%, respectively) than dentists (5.7% ±11.9% and 19.8% ± 20%, respectively). Both dentists and nondentists had low attendance in the course (44.57% ± 37.38% and 26.53% ± 26.53%, respectively, p = 0.26). To the best of our knowledge, this is the first study to assess the diagnostic skills of public health workers belonging to different professional categories., Conclusion: Both dentists and nondentists have a fairly good capacity for discriminating the nature of oral lesions. Early squamous cell carcinoma is the most challenging situation and remains an issue to be addressed.