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Mariana Campos da Paz,1 Maria de Fátima M Almeida Santos,1 Camila MB Santos,2 Sebastião W da Silva,2 Lincoln Bernardo de Souza,3 Emília CD Lima,3 Renata C Silva,1 Carolina M Lucci,1 Paulo César Morais,2 Ricardo B Azevedo,1 Zulmira GM Lacava11Instituto de Ciências Biológicas; 2Instituto de Física, Universidade de Brasília, Brasília, DF, Brazil; 3Instituto de Química, Universidade Federal de Goiás, Goiânia, GO, BrazilAbstract: Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid) and surface-functionalized with anticarcinoembryonic antigen (anti-CEA) and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC) cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF) sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T) and a low-CEA expressing cell line (HCT116). Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter), dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm) and the zeta-potential (−38 mV) of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS) was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm−1, absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116) confirm that the as-prepared MF-anti-CEA is highly specific for CEA-expressing cells. Finally, transmission electron microscopy analyses show that the association with anti-CEA seems to increase the number of LS174T cells with internalized maghemite nanoparticles, whereas no such increase seems to occur in the HCT116 cell line. In conclusion, the MF-anti-CEA sample is a biocompatible device that can specifically target CEA, suggesting its potential use as a theragnostic tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.Keywords: magnetic nanoparticles, anti-CEA antibody, targeted delivery, diagnostic, Raman, biocompatible device

Regional odontodysplasia is a rare developmental anomaly of the teeth that affects enamel and dentin. Its etiology is unknown, but the most accepted theory refers to circulatory disorders associated with vascular nevi. An uncommon case of regional odontodysplasia involving three quadrants of the jaws is reported. An 8-year-old boy was referred to the authors' institution with lack of teeth as a major symptom. There was no hereditary anomaly in the family. Extraoral examination revealed a brown discoloration on the skin on the right side of the face, neck, and chest. Detailed intraoral examination showed hypoplastic and carious teeth. Fistulae and gingival overgrowth were also observed. Radiographically, the affected teeth presented the pathognomonic image of 'ghost teeth.' Conservative treatment was instituted. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to compare the immunohistochemical expression of nuclear factor [kappa]B (NF-[kappa]B), matrix metalloproteinase 9 (MMP-9), and CD105 in odontogenic keratocysts (OKCs), dentigerous cysts (DCs), and radicular cysts (RCs). STUDY DESIGN: Twenty cases of OKCs, 20 DCs, and 20 RCs were analyzed. A labeling index (LI), which expresses the percentage of NF-[kappa]B-stained nuclei, was calculated for the analysis of NF-[kappa]B expression. Expression of MMP-9 in the epithelium and in the capsule of each lesion was scored as 0 (<10% stained cells), 1 (10%-50% stained cells), or 2 (>50% stained cells). In addition, MMP-9 immunostaining was analyzed in endothelial cells of vessels with a conspicuous lumen. The angiogenic index was determined based on the number of anti-CD105 antibody-stained microvessels. RESULTS: In the epithelial component, the NF-[kappa]B LI was higher in OKCs than in DCs and RCs (P < .001). Analysis of MMP-9 expression in the epithelial component showed a predominance of score 2 in OKCs (90%), DCs (70%), and RCs (65%; P = .159). Evaluation of the NF-[kappa]B LI according to the expression of MMP-9 in the epithelial lining revealed no significant difference between lesions (P = .282). In the fibrous capsule, the highest percentage of MMP-9-stained cells (score 2) was observed in OKCs (P = .100). Analysis of the expression of MMP-9 in the vessels of odontogenic cysts showed a predominance of score 2 in OKCs (80%) and RCs (50%) and of score 1 in DCs (75%; P = .002). Mean microvessel count was high in RCs (16.9), followed by DCs (12.1) and OKCs (10.0; P = .163). No significant difference in microvessel count according to the expression of MMP-9 was observed between groups (P = .689). CONCLUSIONS: The results suggest that the more aggressive biologic behavior of OKCs is related to the higher expression of MMP-9 and NF-[kappa]B in those lesions. The differences in the biologic behavior of the lesions studied do not seem to be associated with the angiogenic index. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of this study was to evaluate mast cell (MC) density and migration and their association with matrix metalloproteinase (MMP) 9 expression in squamous cell carcinoma (SCC) and actinic cheilitis (AC). STUDY DESIGN: Tryptase, c-Kit, and MMP-9 expression was evaluated in 20 cases of SCC, 20 cases of AC, and 7 cases of normal lip (control samples) by immunohistochemistry techniques. RESULTS: Tryptase(+) and c-Kit(+) MC densities were significantly higher in SCCs than in ACs and control samples (P < .001). However, no significant difference was found when comparing tryptase(+) and c-Kit(+) MC densities between ACs and control samples (P values .185 and .516, respectively). MMP-9 was strongly expressed in SCCs and moderately expressed in ACs and control samples. A highly significant association was found between tryptase(+) MC density and the expression of MMP-9 (P < .001). CONCLUSIONS: The increase in MC density associated with the strong expression of MMP-9 may favor SCC progression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim was to analyze the expression of E-cadherin and beta-catenin in ameloblastomas and tooth germs to determine their roles in cell differentiation processes and invasiveness compared with odontogenesis. STUDY DESIGN: Twenty-one ameloblastoma cases (16 solid and 5 unicystic tumors) and 5 tooth germs were submitted to the immunohistochemical detection of E-cadherin and beta-catenin. Immunoreactivity was evaluated using descriptive and semiquantitative analysis, investigating the location and intensity of staining. The Fisher exact test was performed, and P values of <.05 were considered to indicate statistical significance. RESULTS: There was no statistically significant difference in the expression of E-cadherin and beta-catenin between solid and unicystic ameloblastomas (P = .59; P = .63; respectively). The same was found when comparing solid and unicystic ameloblastomas with the tooth germs for both E-cadherin (P = .53; P = .44; respectively) and beta-catenin (P = .12; P = .16; respectively). Nuclear staining of beta-catenin was observed in only 4 cases (3 solid and 1 unicystic tumor). CONCLUSION: The results showed no differences in the expression of E-cadherin or beta-catenin between tooth germs and solid and unicystic ameloblastomas. The expression of these molecules seems mainly to be related to the process of cell differentiation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and compare the expression of E-cadherin, Snail1 and Twist1 in pleomorphic adenomas (PAs), adenoid cystic carcinomas (AdCCa) and carcinoma ex-pleomorphic adenomas (CaexPA) of salivary glands, as well as investigate possible associations with clinicopathological parameters., Study Design: E-cadherin, Snail1 and Twist1 antibody immunostaining were analyzed semiquantitatively in 20 PAs, 20 AdCCas and 10 CaexPAs. Cases were classified as low and high expression for analysis of the association with clinicopathological parameters., Results: Compared to PAs, AdCCas and CaexPAs exhibited higher nuclear expression of Snail1 (p = 0.021 and p = 0.028, respectively) and Twist1 (p = 0.009 and p = 0.001). Membranous and cytoplasmic expression of E-cadherin were positively correlated in PAs, AdCCas and CaexPAs (r = 0.645, p = 0.002; r = 0.824, p < 0.001; r = 0.677, p = 0.031). In PAs, positive correlation was found between nuclear expression of Snail1 and membrane expression of E-cadherin (r = 0.634; p = 0.003), as well as between nuclear expression of Snail1 and Twist1 (r = 0.580; p = 0.007). Negative correlations were detected between membrane expression of E-cadherin and cytoplasmic expression of Snail1 in AdCCas (r = - 0.489; p = 0.029)., Conclusions: E-cadherin, Twist1, and Snail1 may participate in modulating events related to cell differentiation and adhesion in PAs and to biological behavior in AdCCas and CaexPAs, which indicates the involvement of EMT in these processes. Furthermore, the expression of these proteins in these carcinomas may reflect the plasticity feature of EMT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Lower lip squamous cell carcinomas (LLSCCs) exhibit lower levels of aggressiveness, low relations with metastases and better prognosis when compared with intraoral squamous cell carcinomas. Differently from the oral tongue squamous cell carcinomas (OTSCCs) have a high tendency towards local invasion and lymph nodal dissemination. Our aim was to evaluate tumor thickness in cases of oral squamous cell carcinoma and correlate it with histological grade of malignancy and GATA3 immunoreactivity., Methods: Sixty specimens (30 LLSCCs and 30 OTSCCs) were scanned and digitized for the subsequent measurement of tumor thickness, histopathological examination, and quantitative analysis of GATA3 in the parenchyma and stroma of the tumors., Results: Tumor thickness was lower in LLSCC compared to OTSCCs. Immunohistochemical analysis of GATA3 in parenchyma, stroma and both compartments showed higher immunoreactivity in LLSCCs compared to OTSCCs. We observed a negative correlation between tumor thickness and GATA3 expression in parenchyma, stroma, and both compartments. Our results revealed the presence of GATA3 in all cases both in the parenchyma and in the stroma. Higher expression was more related to LLSCCs, which are known to be less aggressive tumors than OTSCCs., Conclusions: A greater tumor thickness was found in OTSCCs, which was correlated with lower expression of GATA3, suggesting that this protein is involved in the inhibition of proliferative, migratory, and invasive capacity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear., Methods: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well., Results: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes., Conclusion: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 C. Bergeron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Changes in the expression of nuclear β-catenin are responsible for tumorigenesis. Beta-catenin acts synergistically with the TGF-β/BMPs pathway. This interaction leads to greater dentin deposition and may explain the differences between distinct tooth morphologies and hamartomas. The aim of this study was to investigate the role of β-catenin, BMP4 and TGF-β in the development of odontomas. This cross-sectional, retrospective, immunohistochemical study evaluated 30 compound odontomas, 30 complex odontomas and 17 tooth germs. The results showed that BMP4 and TGF-β were more immunoexpressed in the ectomesenchyme of complex odontomas (median = 33.7, p < 0.001; median = 76.4, p = 0.002, respectively). Higher immunoexpression of BMP4 and TGF-β was also observed in the epithelium of tooth germs (median = 2.0, p < 0.001; median = 120.3, p < 0.001, respectively). TGF-β and BMP4 showed a positive and significant correlation (p < 0.001). Both TGF-β and BMP4 were positively correlated with nuclear β-catenin in ectomesenchyme (p = 0.047 and p = 0.023, respectively). Developing teeth exhibited higher concentrations of the proteins studied in odontogenic epithelium, especially during the bud and cap stages. Higher immunoexpression in odontomas occurred mainly in the ectomesenchyme. We therefore suggest that changes in the ectomesenchyme can lead to the development of odontomas., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Prospective cohort study from Brazil to evaluate glaucoma treatment adherence using a medication event monitoring system (MEMS) device and correlate with glaucoma progression and loss to follow-up (LTF) after one year of follow up. We included primary open glaucoma (POAG) patients treated with at least one ocular hypotensive eye drop. MEMS devices was used to monitor adherence for 60 days and evaluate the percentage of doses prescribed taken within the 60-day period. We classified patients according to rates of adherence: low adherence (less than 75% from MEMS measurements) and high adherence (more than 75% from MEMS measurements). We applied a questionnaire to investigated self-reported behavior towards treatment behaviors (glaucoma treatment compliance assessment tool, GTCAT). We also correlated rates of treatment adherence with clinical, demographical variables and the occurrence of glaucoma progression or LTF after one year of observation. We included 110 POAG patients and found that 28.18% of them were considered low adherent. We identify several variables associated with poor adherence such as glaucoma progression, LTF, younger age, low educational and income levels, absence of health insurance, years of disease and peak intraocular pressure. Several constructs from the self-reported GTCAT were also correlated with the rates of treatment adherence. To date, this is the first study in Latin America to evaluate glaucoma treatment adherence with MEMS devices and correlate adherence rates with glaucoma progression and LTF. We found a low-adherence rate of 28.18% and several additional risk factors were statistically associated with poor adherence., (© 2024. The Author(s).)

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

The aim was to evaluate the effect of different energy diets available in adulthood on the longevity, dispersal capacity and sexual performance of Aedes aegypti produced under a mass-rearing system. To evaluate the effects of diets in relation to the survival of the adult male insects of Ae. aegypti , six treatments were used: sucrose at a concentration of 10%, as a positive control (sack10); starvation, as a negative control (starvation); sucrose at a concentration of 20% associated with 1 g/l of ascorbic acid (sac20vitC); wild honey in a concentration of 10% (honey10); demerara sugar in a 10% concentration (demerara10); and sucrose at a concentration of 20% associated with 1 g/l of ascorbic acid and 0.5 g/l of amino acid proline (sac20vitCPr). Each treatment had 16 cages containing 50 adult males. For the tests of flight ability and propensity to copulation, five treatments were used (saca10; sac20vitC; mel10; demerara10; and sac20vitCPr), with males each for flight ability and females copulated by a single male for copulation propensity. The diet composed of sucrose at a concentration of 20% associated with ascorbic acid, as an antioxidant, improved the survival, flight ability and propensity to copulate in Ae. aegypti males under mass-rearing conditions, and may be useful to enhance the performance of sterile males, thus improving the success of sterile insect technique programmes.

Researchers have concentrated efforts in the search for natural-based reversible inhibitors for cholinesterase enzymes as they may play a key role in the treatment of degenerative diseases. Diverse plant alkaloids can inhibit the action of acetylcholinesterase and, among them, berberine is a promising bioactive. However, berberine has poor water solubility and low bioavailability, which makes it difficult to use in treatment. The solid dispersion technique can improve the water affinity of hydrophobic substances, but berberine solid dispersions have not been extensively studied. Safety testing is also essential to ensure that the berberine-loaded solid dispersions are safe for use. This study investigated the effectiveness of berberine-loaded solid dispersions (SD) as inhibitors of acetylcholinesterase enzyme (AChE). Docking simulation was used to investigate the influence of berberine on AChE, and in vitro assays were conducted to confirm the enzymatic kinetics of AChE in the presence of berberine. Berberine SD also showed improved cytotoxic effects on tumoral cells when dispersed in aqueous media. In vivo assays using Allium cepa were implemented, and no cytotoxicity/genotoxicity was found for the berberine solid dispersion. These results suggest that berberine SD could be a significant step towards safe nanostructures for use in the treatment of neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: About half of cancer deaths in Brazil occur among individuals of working-age (under 65 years for men, under 60 for women), resulting in a substantial economic impact for the country. We aimed to estimate the years of potential productive life lost (YPPLL) and value the productivity lost due to premature deaths from cancer between 2001 and 2015 and the projected to 2030., Methods: We used the Human Capital Approach to estimate the productivity losses corresponding to YPPLL for cancer deaths in working age people (15-64 years). Mortality data were obtained from the Mortality Information System from 2001 to 2015 and projected between 2016 and 2030. Economic data were obtained from the Continuous National Household Sample Survey and forecasted to 2030. Productivity lost was calculated as the monetary value arising from YPPLL in Int$(2016)., Results: Between 2001 and 2030, a total of 2.3 million premature deaths from all cancers combined were observed and forecasted in Brazil (57% men, 43% women), corresponding to 32 million YPPLL and Int$141.3 billion in productivity losses (men: Int$102.5 billion, women: Int$38.8 billion). Between 2001 and 2030, among men, lung (Int$ 12.6 billion), stomach (Int$ 10.6 billion) and colorectal (Int$ 9.4 billion) cancers were expected to contribute to the greatest productivity losses; and among women, it will be for breast (Int$ 10.0 billion), cervical (Int$ 6.4 billion) and colorectal (Int$ 3.2 billion) cancers., Conclusions: Many preventable cancers result in high lost productivity, suggesting measure to reduce smoking prevalence, alcohol consumption, physical inactivity and inadequate diet, improving screening programs and increasing vaccination coverage for human papillomavirus and hepatitis B would have a positive impact on the economy, as well as reducing morbidity and mortality from cancer., Competing Interests: Declaration of Competing Interest This study was funded by the MSD Independent Oncology Policy Grant Program. The sponsor was not involved in the study design, in collection, analysis and interpretation of data; in the writing of the manuscript and in the decision to submit the manuscript for publication. IARC disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization., (Copyright © 2023. Published by Elsevier Ltd.)

The normal-weight obesity (NWO) is highly associated with an increased risk for chronic non-communicable diseases and intricately linked to diet quality. Therefore, we assessed the consumption of ultra-processed and non-ultraprocessed foods of 224 Brazilian adults with NWO ( n 159) and without NWO ( n 65, non-NWO) in a cross-sectional study. For that, three dietary recalls were applied and categorised according to the NOVA classification. Individuals with NWO showed lower energy intake from the 'fresh or minimally processed food' group, specifically for rice ( P = 0⋅037), beans ( P = 0⋅002) and fruits ( P = 0⋅026), as well as lower consumption of dietary fibre ( P < 0⋅05) compared with non-NWO subjects. Total consumption of ultra-processed foods did not differ between groups; however, individuals with NWO had a higher energy intake from processed meats compared with the non-NWO group (54⋅1 ± 73⋅5 × 32⋅5 ± 50⋅8 kcal; P = 0⋅023). Energy and added sugar from ultra-processed foods (OR 1⋅02, CI 95 % 1⋅00-1⋅04, P = 0⋅0100) and total fat from non-ultra-processed foods (OR 1⋅09, CI 95 % 1⋅01-1⋅18; P = 0⋅0100) were associated with the presence of NWO. In conclusion, non-NWO individuals consumed more non-ultra-processed foods compared with the NWO group. Overall, there were no differences in the consumption of ultra-processed foods between the two groups. Important associations between food compounds and the presence of NWO were observed, emphasising the importance of fresh and minimally processed foods as the basis of the diet., (© The Author(s) 2023.)

Objective: This study aimed to compare the immunoexpression profile of tumor stem cell (TSC) biomarkers CD44, aldehyde dehydrogenase 1 (ALDH1), OCT4, and SOX2 in salivary gland tumors (SGTs)., Study Design: Sixty tissue specimens of SGTs, including 20 pleomorphic adenomas, 20 adenoid cystic carcinomas (ACCs), and 20 mucoepidermoid carcinomas, in addition to 4 samples of normal glandular tissue, were subjected to immunohistochemistry. The expression of the biomarkers in the parenchyma and stroma was evaluated. Data were analyzed statistically by nonparametric tests (P < .05)., Results: Higher parenchymal expression of ALDH1, OCT4, and SOX2 was observed in pleomorphic adenomas, ACCs, and mucoepidermoid carcinomas, respectively. Most ACCs did not express ALDH1. Higher immunoexpression of ALDH1 in major SGTs (P = .021) and of OCT4 in minor SGTs (P = .011) was found. Immunoexpression of SOX2 was related to lesions without myoepithelial differentiation (P < .001) and malignant behavior (P = .002). Furthermore, OCT4 was related to myoepithelial differentiation (P = .009). CD44 expression was related to a better prognosis. Stromal immunoexpressions of CD44, ALDH1, and OCT4 were higher in malignant SGTs., Conclusions: Our findings suggest the participation of TSCs in the pathogenesis of SGTs. We emphasize the need for further investigations into the presence and role of TSCs in the stroma of these lesions., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC) exhibit epithelial alterations mainly associated with chronic ultraviolet ray exposure. Currently, it is impossible to predict which AC cases will progress to LLSCC; thus, biomolecular markers have been studied. The aim of this study was to evaluate the immunoexpression of IMP-3 and KI-67 in AC and LLSCC. Forty AC and 40 LLSCC cases were submitted to peroxidase method and quantitatively analyzed, using the following scores: 0 (0% positive cells), + 1(≤ 30%), + 2 (> 30% to ≤ 60%), and + 3 (> 60%). Results were submitted to non-parametric Mann-Whitney (U) test. A p value < 0.05 was considered to indicate statistical significance. IMP-3 immunoexpression was observed in 26 AC cases, with predominance of the score 1 (35% of cases). This protein was also positive in 22 LLSCC cases, with predominance of the score 3 (37.5% of cases). Immunoexpression of KI-67 was observed in all studied cases, with predominance of the score 2 (70% of AC cases and 57.5% LLSCC cases). The association between IMP-3 and Ki-67 immunoexpression, AC dysplastic severity and LLSCC tumoral grade revealed no significant differences. The present results demonstrate that IMP-3 and Ki-67 immunoexpression are frequent in AC and in LLSCC. Moreover, these proteins could be involved in lower lip carcinogenesis process., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the impact of the COVID-19 pandemic on the number of diagnoses of oral and maxillofacial lesions in public laboratories after one year of COVID-19 outbreak in Brazil., Material and Methods: This is a cross-sectional study. Biopsies submitted to histopathologic examination from March 2019 to February 2020 (pre-pandemic period) and from April 2020 to March 2021 (pandemic period) in nine Brazilian public oral pathology laboratories were retrieved and the number of diagnoses, types of lesion, and percentage changes during both periods were analyzed., Results: There were 7389 diagnoses in the pre-pandemic period and 2728 in the pandemic era, indicating a reduction of 63.08%. The reduction was 64.23% for benign lesions and 49.48% for malignant lesions, with a 50.64% reduction in squamous cell carcinoma. The largest decreases were observed in April 2020 and January 2021., Conclusion: An important reduction in the diagnoses of benign and malignant lesions was noted in the Brazilian public oral pathology laboratories during the first year of the COVID-19 pandemic., (© 2022 Wiley Periodicals LLC.)

Aims: To investigate the effects of endurance training on stress-induced cardiometabolic perturbations given the elevated release of stress hormones and subsequent glucose homeostasis perturbations., Materials and Methods: Rats were randomized into non-trained rats, rats submitted to endurance training, non-trained rats submitted to stress, and trained rats submitted to stress. Endurance training was applied for 8 weeks, while chronic stress was applied at the 4th, 5th, and 6th weeks of the training period. Two weeks after the last stressor stimuli, rats were euthanized, and blood and heart were collected for biochemical tests., Key Findings: Exacerbated corticosterone levels were observed in both stressed groups, and chronic stress per se impaired glucose tolerance and insulin sensitivity. Training reduced circulating adrenaline, even though noradrenaline levels were elevated in the blood and heart of trained rats. While stress-induced high circulating serotonin levels were further increased by endurance training, cardiac serotonin levels were attenuated in trained rats. Endurance training mitigated the stress-induced higher circulating lipids. Cardiac TBARs and GPx activity increased in trained rats while CAT and GPx were reduced in response to chronic stress. Endurance training not only attenuated the stress-induced higher circulating ACE/ACE2 ratio but also reduced ACE/ACE2 balance in the heart. Glucose intolerance, insulin resistance, and altered stress hormones release were linked to impairment of cardiometabolic responses, elevated oxidative stress, and dysregulation of ACE/ACE2 ratio., Significance: Endurance training mitigated the stress-related pathophysiological responses, which could be related to improvements in the antioxidant capacity and the balance of ACE/ACE2 activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The morphological diversity and different biological behaviors of human lesions has been attributed to the presence of cells with stem cell (SC) characteristics. Among SC markers, ALDH1 has been used in studies investigating different neoplasms and high expression of this marker was associated with clinicopathological features and prognosis in some groups. The aim of this study was to analyze the presence and distribution of SCs based on the expression of ALDH1 in epithelial odontogenic cysts and tumors. The sample consisted of 80 cases (20 dentigerous cysts (DCs), 20 odontogenic keratocysts (OKCs), 20 ameloblastomas (AMs), and 20 adenomatoid odontogenic tumors (AOTs). An immunoreactivity score was obtained from the percentage of positive cells and intensity of immunostaining. A level of 5% (p < 0.05) was adopted for the statistical tests. Immunoexpression of ALDH1 was observed in cytoplasm and nucleus-cytoplasm. The median scores indicated significantly higher expression in OKCs and DCs compared to AMs (p < 0.0001) and AOTs (p < 0.0001). In the tumor stroma and cystic capsule, immunoreactivity was detected in all odontogenic cysts studied and in 85% and 90% of AMs and AOTs, respectively. The expression of ALDH1 suggests the presence of SCs in the odontogenic lesions studied. Epithelial immunoexpression was higher in odontogenic cysts than in odontogenic tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: We aimed to investigate whether Saccharomyces boulardii strain might exert renoprotective effects by modulating renal renin angiotensin system, oxidative stress and intestinal microbiota in streptozotocin-diabetic mice., Main Methods: Thirty-six C57BL/6 male mice were divided into four groups: control (C), control + probiotic (CP), diabetes (D), diabetes + probiotic (DP). Diabetes was induced by one intraperitoneal injection of streptozotocin and Saccharomyces boulardii was administered by oral gavage for 8 weeks. Blood glucose, albuminuria and urinary volume were measured. Renal levels of angiotensin peptides (angiotensin I, II and 1-7) and the activities of angiotensin-converting enzyme (ACE) and ACE2 were determined, besides that, renal morphology, serotonin and dopamine levels and also microbiota composition were analyzed., Key Findings: Probiotics significantly increased C-peptide secretion and reduced blood glucose of diabetic animals. Saccharomyces boulardii also improved renal antioxidant defense, restored serotonin and dopamine concentration, and activated the renin-angiotensin system (RAS) vasodilator and antifibrotic axis. The modulation of these markers was associated with a beneficial impact on glomerular structure and renal function of diabetic treated animals. The phenotypic changes induced by Saccharomyces boulardii were also related to modulation of intestinal microbiota, evidenced by the decreased abundance of Proteus and Escherichia-Shigella, considered diabetic nephropathy biomarkers., Significance: Therefore, probiotic administration to streptozotocin-induced diabetic mice improves kidney structure and function in a murine model and might represent a reasonable strategy to counteract nephropathy-associated maladaptive responses in diabetes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bearing in mind the several medicinal properties of Mentha genus, this work aimed to evaluate the anti-proliferative potential of the ethanolic extract (EE) and fractions from M. aquatica L aerial parts. Using the anti-proliferative protocol developed by the NCI/USA, four fractions (F2 - F4 and F6) obtained from EE showed promising anti-proliferative profile against a panel of human tumor and non-tumor cell lines. After 24-h exposure, F2 (0.25 µg/mL) showed potent and irreversible anti-proliferative effect without inducing cell cycle arrest in both NCI-H460 and MCF-7 cells, without (anti) estrogenic activity. These effects were lost after storage of F2 diluted in dimethyl sulfoxide at -80 °C during 2 weeks. Analysis by gas chromatography coupled to mass detection evidenced some chemical changes induced by F2 storage in solution. The present study demonstrated the anti-proliferative effect of M. aquatica . Further studies are necessary to determine better storage conditions to enhance F2 stability.

Objective: To evaluate the influence of plasminogen activator inhibitor-1 (PAI-1) on the biological behavior and prognosis of oral tongue squamous cell carcinoma (OTSCC)., Methods: Immunoexpression of PAI-1 was analyzed in 60 OTSCC specimens and classified as low-expression (≤50% of positive cells) or high-expression (>50%). In vitro effects of recombinant human PAI-1 (rhPAI-1) were assessed through functional assays on the OTSCC-derived cell line SCC-25. Three cell groups were evaluated: G0 (control), G10 (10 nM rhPAI-1), and G20 (20 nM rhPAI-1)., Results: High membrane expression of PAI-1 was associated with tumor budding (p = 0.046) and high-risk cases (p = 0.043). Cytoplasmic and membrane expression of PAI-1 was not associated with patient survival. Cell viability (p = 0.020) and progression to the S-phase of the cell cycle (p = 0.024) were higher in G10 and G20 at 24 h. The percentages of apoptotic/necrotic cells were not affected by rhPAI-1. The presence of rhPAI-1 increased cell migration (p = 0.039) and invasion (p = 0.039) after 24 and 72 h, respectively., Conclusion: Our findings indicate the involvement of PAI-1 in the biological behavior of OTSCC, although its expression may not predict patient survival. The in vitro results suggest that PAI-1 stimulates cell proliferation, migration and invasion and may contribute to the aggressive phenotype of OTSCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Store-operated calcium entry (SOCE) is triggered by assembly of Orai1 with STIM proteins in ER-PM junctions. Plasma membrane PIP 2 as well as PIP 2 -binding protein, SEPT4, significantly impact Orai1-STIM1 interaction. While septins and PIP 2 can organize the actin cytoskeleton, it is unclear whether the status of actin within the junctions contributes to SOCE. We report herein that actin remodeling modulates STIM1 clustering. Our findings show that a PIP 2 - and SEPT4-dependent mechanism involving CDC42, WASP/WAVE, and ARP2 regulates actin remodeling into a ring-like structure around STIM1 puncta. CDC42 localization in the ER-plasma membrane region is enhanced following ER-Ca 2+ store depletion. PIP 2 depletion or knockdown of SEPT4 attenuate the recruitment of CDC42 to the ER-PM region. Importantly, knockdown of SEPT4, or CDC42+ARP2, disrupts the organization of actin as well as STIM1 clustering. Consequently, Orai1 recruitment to STIM1 puncta, SOCE, and NFAT translocation to the nucleus are all attenuated. Ca 2+ influx induced by STIM1-C terminus is not affected by CDC42 knockdown. In aggregate, our findings reveal that PIP 2 and SEPT4 affect Orai1/STIM1 clustering by coordinating actin remodeling within ER-PM junctions. This dynamic reorganization of actin has an important role in regulation of SOCE and downstream Ca 2+ -dependent effector functions., (Copyright © 2021. Published by Elsevier Ltd.)

We investigated elastofibromas (EF) and elastofibroma-like structures (EFL) in 95 cases that had been diagnosed as oral fibromas (OF). Histological sections were stained with Verhoeff-Van Gieson, Congo red and hematoxylin and eosin to enable possible reclassification to EF or EFL, or to retain the diagnosis of OF. To do this, we identified amyloid and used histopathological descriptions and epidemiological clinical profiles. We found 56 EF and 21 EFL cases, while 18 diagnoses of OF were retained. We observed a predilection for EF in females. Also, the most common site for OF was the cheek mucosa. We also found a longer time course for lesion development for OF compared to the other lesions. We found a relation between elastic fibers and amyloid material in EF. We also observed perivascular fibrotic lesions (PVFL) in EF. Most cases of EF exhibited more elastic fibers, thicker fibers, stronger relation with amyloid material deposition, rare evidence of PVFL and a longer time course for development compared to the other lesions. We suggest that EFL may give rise to oral EF.

Adenoid cystic carcinoma (AdCC) is a rare malignancy that accounts for approximately 1% of all head and neck cancers. This neoplasm is characterized by slow but often relentless growth and dissemination. Our aim was to retrospectively evaluate the clinical-pathological features of patients diagnosed with head and neck AdCC and to identify possible prognostic factors. This retrospective observational study analyzed 87 cases of AdCC of the head and neck. Clinical parameters (tumor size, lymph node and distant metastasis, clinical stage, and survival) were obtained from the records. Survival curves were constructed using the Kaplan-Meier method. A p value ≤ 0.05 was considered significant. There was a slight predominance of cases diagnosed in female patients (54%). The mean age at diagnosis was 51.5 years. Analysis using Cox's proportional hazards model considering 10-year disease-specific survival identified histologic pattern and presence of perineural invasion as independent prognostic variables. Primary tumor size and distant metastasis were prognostic predictors of 5- and 10-year disease-free survival. Detailed analysis of the association between clinical-pathological parameters and prognosis can assist professionals with cancer treatment planning and adequate patient management. Considering the long-term aggressive behavior of AdCC, rigorous patient follow-up is important to identify possible locoregional or distant recurrences.

Objective: To analyze the immunohistochemical expression of the base excision repair (BER) proteins apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing protein 1 (XRCC1) and nucleotide excision repair (NER) protein xeroderma pigmentosum group F (XPF) in malignant salivary gland tumors (MSGTs)., Design: Sixty-two cases of MSGTs were selected, including 14 acinic cell carcinomas (AcCC), 15 polymorphous adenocarcinomas (PAC), 16 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). The specimens were submitted to quantitative immunohistochemical analysis., Results: All MSGTs exhibited nuclear or nucleo-cytoplasmic immunostaining of APE1, XRCC1 and XPF, with a high percentage of positive cells (median = 78.31, 70.48 and 75.46, respectively). XRCC1 expression was higher in PAC compared to MEC (p = 0.032). Nuclear APE1 immunostaining was significantly higher than nucleo-cytoplasmic expression in the selected MSGTs (p < 0.0001). APE1 expression was significantly associated with T1-T2 tumors in ACC (p = 0.006). Increased expression of XPF was associated with age older than 60 years in MEC (p = 0.015) and with ACC involving the minor salivary gland (p = 0.012), while a lower expression was found in AcCC and ACC patients treated by surgery combined with adjuvant therapy (p = 0.036 and p = 0.020, respectively). Low expression of XRCC1 in the nucleus (p = 0.028) and concomitant expression of this protein in the nucleus/cytoplasm were associated with a lower overall 5-year survival rate (p = 0.017)., Conclusions: This study showed that BER and NER proteins evaluated are highly expressed in the MSGTs studied, indicating mechanisms of genotoxic control in these tumors. In addition, the dysregulation of XRCC1 expression was a prognostic predictor in MSGTs analyzed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions from each anal sac in 15 healthy dogs. DNA was extracted from swabs and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced with Illumina MiSeq. Overall, 14 different bacterial phyla were identified in the rectum and in both anal sacs, the 5 main ones being Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria. The rectum had higher microbial diversity and richness than the left and right anal sacs. Community membership and structure significantly differed between the rectum and both anal sacs, but not between the right and the left anal sacs. This study showed that the diversity and richness of the bacterial microbiota of the anal sacs in dogs is greater than what has been reported in previous studies with culture-based methods. In conclusion, the bacterial microbiota of the anal sacs in dogs varies between individuals and differs from the rectal bacterial microbiota., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Purpose: Cripto-1 also known as teratoma-derived growth factor 1 (TDGF-1) belongs to the EGF-CFC family of growth factor-like molecules. Cripto-1 is involved with embryonic development and not expressed in adult tissue, but some tumours are accompanied by reactivation., Methods: The aim of this study was to evaluate the immunohistochemical expression of Cripto-1 in most common odontogenic cysts and tumours. Thirty ameloblastomas, 30 keratocysts, 30 dentigerous cysts and two ameloblastic carcinomas were evaluated using the polymeric immunoperoxidase technique. Immunohistochemical expressions were analysed by the IRS (immunoreactive score). Statistical analyses were performed by the Kruskal-Wallis and Mann-Whitney tests (p ≤ 0.05)., Results: Age ranged from 9 to 75 years old, with a prevalence of females (n = 49/53.3%). The mandible was the most affected anatomical site (n = 69/75.0%). Cripto-1 immunoexpression was observed in all ameloblastoma, keratocyst and ameloblastic carcinoma cases, although nine dentigerous cyst cases (30%) were negative. Expression scores were higher in ameloblastoma, keratocyst and ameloblastic carcinoma cases (median ranging from 8 to 11) when compared with dentigerous cyst cases (median of 2), with a statistically significant difference (p < 0.001)., Conclusions: Cripto-1 is critically important in the progression of several tumours since it is related to significant cell survival and differentiation pathways. The high expression of Cripto-1 in more aggressive odontogenic lesions suggests that this molecule may be involved in the activation of important pathways related to the etiopathogenesis of these lesions.

The enzyme aldehyde dehydrogenase-1 (ALDH-1) is a known putative tumour stem cells (TSC) marker, and these cells are implicated in carcinogenesis and progression of human neoplasms. We aimed to evaluate ALDH-1 expression in benign and malignant salivary gland neoplasms and its clinicopathological and prognostic significance. Expression of ALDH-1 was investigated by immunohistochemistry and confirmed by Western Blot analysis in 154 salivary gland neoplasms (103 malignant and 51 benign neoplasms). The expression was identified in the parenchyma of malignant (n = 88; 85.6%) and benign (100%) neoplasms. Overall, expression in the parenchyma varied considerably and was not associated with clinical parameters in most malignant neoplasms, however, a high expression in mucoepidermoid carcinomas (MEC) was associated with advanced pathological TNM stage (p = 0.047). The presence of ALDH-1 in stromal cells of malignant neoplasms (n = 67; 65.0%) was associated with lymph node metastasis (p = 0.032), tumour recurrence (p = 0.006) and death (p = 0.013). Overall and disease-free survival in 5 and 10 years was lower in patients with diagnosis of adenoid cystic carcinoma, tumour recurrence, advanced staging, and presence of ALDH-1 in the stroma. When adjusted by multivariate analysis, advanced staging and stromal expression were independent prognostic factors affecting disease-free survival. Our findings provide evidence that cells characterized as TSC in the parenchyma and stroma are differentially present among the different types of neoplasms studied and may be related to tumourigenesis, biological behaviour and persistence capacity of malignant tumours of the salivary gland., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Data on the occurrence and clinicopathological characteristics of actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC) are well studied; however, they are based on studies limited to a single centre. Herein, we described the frequency of AC and LSCC submitted to microscopic examination from representative geographic regions of Brazil. A retrospective multicentre study was performed on biopsies obtained from 1953 to 2018 at 10 Brazilian oral and maxillofacial pathology centres. A total of 198,709 biopsy specimens were surveyed. Sociodemographic data and clinicopathologic characteristics were analysed. A total of 2017 cases of ACs (1.0%) and 850 cases of LSCCs (0.4%) were recorded. A strong fair-skinned (> 87%) male (> 70%) predilection was observed in both conditions. The mean age was 54.8 ± 18.7 for individuals with AC and 57.8 ± 19.0 for individuals with LSCC. The most commonly affected site was the lower lip (> 90%). This is a large multicentre study of AC and LSCC from Brazil. The frequency and clinicopathological features of AC and LSCC were similar to those described worldwide. This study provides robust and representative epidemiological data of these conditions for the scientific community.

Objective: The aim of this systematic review was to explore the biological functions and mechanisms of epithelial-mesenchymal transition-inducing transcription factors in head and neck squamous cell carcinoma-derived cell lines. In addition, we analyzed the possible usefulness of epithelial-mesenchymal transition-inducing transcription factors as a future therapeutic target., Design: An electronic search was performed in EMBASE, Medline/PubMed, Chinese BioMedical Literature Databases, and Cochrane Collaboration Library. Articles evaluating the relationship between epithelial-mesenchymal transition-inducing transcription factors and the biological behavior of head and neck squamous cell carcinoma cell lines were selected for this systematic review. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria., Results: After application of the previously established inclusion/exclusion criteria, 23 articles were included in the qualitative synthesis. Our study showed that epithelial-mesenchymal transition-inducing transcription factors are essential components during the progression of head and neck squamous cell carcinomas and their overexpression is associated with a greater capacity of dissemination and survival of the tumor and resistance to cancer treatment. The inhibition of epithelial-mesenchymal transition-inducing transcription factors is able to reverse the epithelial-mesenchymal transition process and to increase the sensitivity of head and neck squamous cell carcinoma cell lines to radio/chemotherapy., Conclusions: Analysis of the expression of epithelial-mesenchymal transition-inducing transcription factors for the prediction of prognosis and response to cancer treatment may have a significant clinical impact., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The initial stimulation of photosynthesis under elevated CO 2 concentrations (eCO 2 ) is often followed by a decline in photosynthesis, known as CO 2 acclimation. Changes in N levels under eCO 2 can have different effects in plants fertilized with nitrate (NO 3 - ) or ammonium (NH 4 + ) as the N source. NO 3 - assimilation consumes approximately 25% of the energy produced by an expanded leaf, whereas NH 4 + requires less energy to be incorporated into organic compounds. Although plant-N interactions are important for the productivity and nutritional value of food crops worldwide, most studies have not compared the performance of plants supplied with different forms of N. Therefore, this study aims to go beyond treating N as the total N in the soil or the plant because the specific N compounds formed from the available N forms become highly engaged in all aspects of plant metabolism. To this end, plant N metabolism was analyzed through an experiment with eCO 2 and fertigation with NO 3 - and/or NH 4 + as N sources for tobacco (Nicotiana tabacum) plants. The results showed that the plants that received only NO 3 - as a source of N grew more slowly when exposed to a CO 2 concentration of 760 μmol mol -1 than when they were exposed to ambient CO 2 conditions. On the other hand, in plants fertigated with only NH 4 + , eCO 2 enhanced photosynthesis. This was essential for the maintenance of the metabolic pathways responsible for N assimilation and distribution in growing tissues. These data show that the physiological performance of tobacco plants exposed to eCO 2 depends on the form of inorganic N that is absorbed and assimilated.

Purpose: This study aimed to analyze the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas diagnosed in a reference center in the Brazilian Northeast., Materials and Methods: This retrospective cohort study reviewed the clinical records of patients with head and neck sarcomas. Epidemiologic data consisted in clinical location, age, gender, histopathological diagnosis, clinical TNM staging and treatment. Outcome variables were local recurrence and survival. The statistical analyses were performed by a binary logistic regression analysis. The survival analysis was assessed through the Kaplan-Meier curve., Results: Sixty-nine patients with head and neck sarcomas (male 39; female 30) were analyzed. The most common histologic subtypes were rhabdomyosarcoma, dermatofibrosarcoma, and pleomorphic sarcoma. The mean age of the patients at the time of diagnosis was 38.1 years old. A total of 31 patient died (sarcoma-related death) up to the end of the follow-up, with a mean follow-up rate of 1.63 years. A multivariate analysis revealed that anatomical site, treatment modality, histopathological diagnosis, and clinical stage of the disease were associated with specific survival, reaching statistical significance., Conclusion: This study demonstrates the impact of important clinical-pathological parameters on the overall prognosis of head and neck sarcomas.

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: The skin is the largest organ of the human body. Upon injury, the skin triggers a sequence of signaling pathways that induce epithelial proliferation, migration, and ultimately, the re-establishment of the epithelial barrier. Our study explores the unknown epigenetic regulations of wound healing from a histone perspective. Posttranslational modifications of histones enhance chromatin accessibility and modify gene transcription., Methods: Full-thickness wounds were made in the dorsal skin of twenty-four C57/B6 mice (C57BL/6J), followed by the use of ring-shaped silicone splints to prevent wound contraction. Tissue samples were collected at three time points (post-operatory day 1, 4, and 9), and processed for histology. Immunofluorescence was performed in all-time points using markers for histone H4 acetylation at lysines K5, K8, K12, and K16., Results: We found well-defined histone modifications associated with the stages of healing. Most exciting, we showed that the epidermis located at a distance from the wound demonstrated changes in histone acetylation, particularly the deacetylation of histone H4K5, H4K8, and H4K16, and hyperacetylation of H4K12. The epidermis adjacent to the wound revealed the deacetylation of H4K5 and H4K8 and hyperacetylation of H4K12. Conversely, the migratory epithelium (epithelial tongue) displayed significant acetylation of H4K5 and H4K12. The H4K5 and H4K8 were decreased in the newly formed epidermis, which continued to display high levels of H4K12 and H4K16., Conclusions: This study profiles the changes in histone H4 acetylation in response to injury. In addition to the epigenetic changes found in the healing tissue, these changes also took place in tissues adjacent and distant to the wound. Furthermore, not only deacetylation but also hyperacetylation occurred during tissue repair and regeneration.

Actinic cheilitis (AC) is a potentially malignant lesion caused by chronic sun exposure. This study aimed to evaluate the relationship between the degree of epithelial dysplasia and morphometric findings in AC. Sixty-eight slides of AC cases were selected and classified according to the grade of epithelial dysplasia, following morphologic criteria of World Health Organization. For morphometric analysis, the slides were scanned and images were analyzed using Pannoramic Viewer software. We obtained vertical measurements of the parameters: thicknesses of the keratin layer, lamina propria and zone of solar elastosis in three selected fields. Thirty-seven (54.4%) of the analyzed cases were classified as none/mild dysplasia and 31 (45.6%) as moderate/severe epithelial dysplasia. Cases with a moderate/severe dysplasia exhibited a thicker layer of keratin (median = 0.055 mm) than none/mild dysplasia (median = 0.045 mm) (p = 0.033). No significant differences in the thicknesses of lamina propria and zone of solar elastosis were observed according to the grade of epithelial dysplasia. A positive significant correlation between keratin layer and lamina propria thicknesses was found (p = 0.019). Based on our findings, rigorous clinical follow-up should be recommended for patients whose histopathological examination shows a greater thickness of the keratin layer., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Objectives: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil., Materials and Methods: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods., Results: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits., Conclusions: Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: This study aimed to evaluate tryptase and E-cadherin protein expression in odontogenic keratocysts (OKCs) and radicular cysts (RCs) and their relationship with lesion size., Materials and Methods: Thirty OKC and 30 RC cases were analyzed by immunohistochemistry. Tryptase expression was quantitatively assessed using the quantification of mast cells, and expression of E-cadherin was semi-quantitatively analyzed estimating the proportion of positive cells: 1 = less than 25% of immunopositive cells; 2 = 26 to 50% of immunopositive cells; 3 = 51 to 75% of immunopositive cells; 4 = more than 75% of immunopositive cells. Data on cystic lesion sizes were obtained from patients' clinical files, based on previous radiographic exams, and the lesions were categorized into three groups: group 1 (< 2 to 2 cm); group 2 (> 2 to 4 cm), and group 3 (> 4 cm)., Results: Higher mast cell means were found for RCs, with the predominance of degranulated mast cells in both OKCs and RCs (p = 0.082). Concerning the epithelial component, a higher concentration of degranulated mast cells was detected in RCs (p = 0.000). Regarding connective tissue, degranulated mast cells were more evident in OKCs (p = 0.762). A negative correlation was observed between E-cadherin expression and total number of mast cells (p = 0.011), degranulated mast cells (p = 0.040), and degranulated mast cells in both superficial (p = 0.035) and deep connective tissues (p = 0.009). Concerning lesion size, a negative correlation with total number of mast cells (p = 0.016) and number of degranulated mast cells (p = 0.049) was observed, both in the epithelial components. Herein, the larger the lesion size, the lower the number of degranulated mast cells in the epithelium (r = - 0.271; p = 0.49), suggesting that these cells play a role in the initial cystic expansion phase., Conclusion: The higher expression of tryptase in degranulated mast cells was linked to a lower expression of E-cadherin, which may be related to a change in the epithelial permeability in these lesions, contributing to increased cystic content and lesion growth., Clinical Relevance: Evidence of the relationship between mast cells and E-cadherin in the growth of odontogenic cysts was studied.

Purpose: To investigate the contribution of MMP-13 in tumor aggressiveness, by acting on the reorganization of the extracellular matrix, regulating the biological activity of cytokines in odontogenic epithelial lesions, as well as to evaluate the role of EMMPRIN as an inducer of MMP-13., Methods: Twenty solid ameloblastomas (SAs), 10 unicystic ameloblastomas (UAs), 20 odontogenic keratocysts (OKCs), and 20 adenomatoid odontogenic tumors (OATs) were selected. The expression of MMP-13 and EMMPRIN was evaluated in epithelial/connective tissue by determining the score of immunoreactive cells., Results: Higher concentration of MMP-13 was observed in epithelium of SAs and OKCs (p = 0.316), while in connective, MMP-13 was more expressed in OKCs and UAs (p = 0.213). OKCs exhibited the highest immunoreactivity score for EMMPRIN in the epithelium (p = 0.091). In connective tissue, a larger number of immunoreactive cells were observed in OKCs and UACs (p = 0.357). There was a moderate correlation (r = 0.343/p = 0.004) between MMP-13/EMMPRIN in epithelium and strong correlation (r = 0.474/p < 0.001) in connective tissue., Conclusion: We suggest that the OKCs, SAs and UAs presented greater immunoexpression for MMP-13 and EMMPRIN, since they were lesions of more aggressive behavior, with smaller expressions in the AOTs that are admittedly indolent. However, we did not find a statistically significant difference between the expression of MMP-13 and EMMPRIN in lesions studied. The positive correlation found between MMP-13 and EMMPRIN in the epithelial and connective tissue of odontogenic lesions analyzed, seems to be related to the role of EMMPRIN as an inducer of MMP-13 expression.