Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line.

BACKGROUND: Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process. METHODS: Cholesterol depletion was induced on SCC-9 cells by methyl-ß-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence. RESULTS: Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-ß-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-ß-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-ß-cyclodextrin (p = 0.02, Kruskal-Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1. CONCLUSION: These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.

Mechanisms of immune evasion by head and neck cancer stem cells.

Different mechanisms are involved in immune escape surveillance driven by Oral and Head and Neck Cancer Stem Cells (HNCSCs). The purpose of this review is to show the most current knowledge regarding the main impact of HNCSCs on tumor evasion through immunosuppression, CSCs phenotypes and environmental signals, highlighting strategies to overcome immune evasion. The main results drive the participation of cell surface receptors and secreted products and ligands, the crosstalk between cells, and genetic regulation. The reduction in CD8+ T cell recruitment and decreased effector of anti-PD-1 therapy by cells expressing BMI1 is a key event; Natural Killer cell ligands and cytokines needed for its activation and expansion are crucial to control tumor growth and to target CSCs by immunotherapy; CSCs expressing ALDH1 are related to increased expression of PD-L1, with a positive link between DNMT3b expression; CD276 expression in CSCs can act as a checkpoint inhibitor and together with Activator Protein 1 (AP-1) activation, they create continuous positive feedback that enables immune evasion by suppressing CD8+ T cells and prevent immune cell infiltration in head and neck cancer. These data demonstrate the relevance of the better understanding of the interaction between HNCSCs and immune cells in the tumor microenvironment. The ultimate clinical implication is to ground the choice of optimized targets and improve immune recognition for ongoing treatments as well as the response to approved immunotherapies.

Oral manifestations of multisystemic inflammatory syndrome in children (MIS-C) and Kawasaki disease associated to COVID-19: A systematic review.

AIMS: Multisystemic inflammatory syndrome in children (MIS-C) is a condition noted in some children asymptomatic but positive to Sars-cov-2 antibody and it presents clinical and laboratory changes similar to Kawasaki disease (KD). Oral changes have also been observed. This systematic review evaluated oral manifestations detected in children with MIS-C and KD associated to COVID-19. METHODS AND RESULTS: This work was registered at PROSPERO (#CRD42020225909), following PRISMA guidelines. A comprehensive research was conducted in MEDLINE, Web of Science, EMBASE, LILACS, Scopus, and Grey Literature through August 2021, based on original research evaluating children diagnosed with MIS-C or KD related to COVID-19. Two authors independently screened all retrieved references. Twenty five selected studies evaluated 624 children, mean age 8.78 years. The assessment of the risk of bias (ROB) showed that most of them presented low ROB. Oral manifestations were erythematous mucous membrane, oral ulcers lesions, dry, swollen and cracked lips, and strawberry tongue. CONCLUSION: MIS-C and KD share the same oral manifestations and their identification may lead to an early diagnosis.

Diagnóstico de reabsorção radicular: influência da resolução espacial de captura de imagens digitais periapicais / Root resorption diagnostic: influence of periapical digital image scanning

Introdução: a detecção da reabsorção da raiz dentária é realizada por meio de exames de imagens, pois frequentemente não apresenta sinal e sintoma clínicos. Dentre os exames de imagem disponíveis, o exame radiográfico periapical, é indicado para diagnóstico, prognóstico e acompanhamento da reabsorção radicular. Objetivo: o estudo tem como objetivo investigar a relação de diferentes resoluções espaciais com o diagnóstico de reabsorção radicular. Metodologia: foram realizados desgastes simulando reabsorção externa no terço apical e vestibular de 15 (quinze) incisivos inferiores, radiografados em crânio seco, antes e depois do desgaste. A técnica radiográfica foi realizada utilizando o sistema VistaScan (Durr Dental, Bietigheim-Bissingen, Germany), aparelho CS 2200 (Carestream Dental LLC, Atlanta-GA, USA) usando tempo de exposição de 0,15 segundos e escaneadas sob diferentes protocolos de resolução espacial, a saber, 20 pares de linhas por milímetro (pl/mm) e 40 pl/mm. Posteriormente dois avaliadores experientes fizeram análises das referidas imagens sem conhecimento prévio da resolução de escaneamento. Resultados: 75% das radiografias realizadas com 20 pl/mm foram classificadas como excelentes pelos avaliadores, contra 33% com 40 pl/mm, estatisticamente significativa. Discussão: ao avaliar a reabsorção radicular, obteve-se uma acurácia diagnóstica igual para os dois protocolos sem distinção, estatisticamente significativa, entre localização ou profundidade. Conclusão: tendo em vista que para os examinadores imagens com 20 pl/mm foram satisfatórias, com percentual de qualidade maior quando comparado a imagens obtidas com 40 pl/ mm, este estudo indica o emprego de imagens com 20 pl/mm para avaliação inicial de suspeita de reabsorções nas raízes dentárias.

Introduction: the detection of tooth root resorption is carried out by means of imaging tests, as it often does not present a clinical sign and symptom. Among the imaging tests available, the periapical radiographic examination is indicated for diagnosis, prognosis and monitoring of root resorption. Objective: the study aims to investigate the relationship of different spatial resolutions in the diagnosis of root resorption. Methods: Artificial external root resorptions were simulated using burs by drilling to the entire depth in different locations at the apical and buccal thirds of 15 (fifteen) lower incisors were worn, radiographed on a dry skull, before and after wear. The radiographic technique was performed using the VistaScan system (Durr Dental, Bietigheim-Bissingen, Germany), CS 2200 device (Carestream Dental LLC, Atlanta-GA, USA) using an exposure time of 0.15 seconds and scanned under different resolutions protocols, namely, 20 pairs of lines per millimeters (pl/mm) and 40 pl/mm. Subsequently, two experienced evaluators performed analyzes of these images without prior knowledge of the scanning resolution. Results: seventy-five percent of the radiographs taken at 20 pl/mm were rated as excellent by the evaluators, against 33% at 40 pl/mm, a statistically significant difference. Discussion: When assessing root resorption, a similar diagnostic accuracy was obtained for the two protocols without a statistically significant distinction between location or depth. Conclusions: Considering that for examiners images with 20 pl/mm were satisfactory, with a percentage of quality greater than 40 pl/mm, this study indicates the use of 20 pl/mm for initial evaluation of suspected root resorption.