Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes.

Infection with high-risk human papillomaviruses like HPV-16 and HPV-18 is highly associated with the development of cervical and other cancers. Malignant transformation requires viral oncoproteins E5, E6 and E7, which promote cell proliferation and increase DNA damage. Oxidative stress and hypoxia are also key factors in cervical malignant transformation. Increased levels of reactive species of oxygen (ROS) and nitrogen (RNS) are found in the hypoxic tumor microenvironment, promoting genetic instability and invasiveness. In this work, we studied the combined effect of E5, E6 and E7 and hypoxia in increasing oxidative stress and promoting DNA damage and nuclear architecture alterations. HaCaT cells containing HPV-18 viral oncogenes (HaCaT E5/E6/E7-18) showed higher ROS levels in normoxia and higher levels of RNS in hypoxia compared to HaCaT parental cells, as well as higher genetic damage in hypoxia as measured by γH2AX and comet assays. In hypoxia, HaCaT E5/E6/E7-18 increased its nuclear dry mass and both cell types displayed marked heterogeneity in nuclear dry mass distribution and increased nuclear foci. Our results show contributions of both viral oncogenes and hypoxia to oxidative stress, DNA damage and altered nuclear architecture, exemplifying how an altered microenvironment combines with oncogenic transformation to promote tumor progression.

Artificial Intelligence for Image Analysis in Oral Squamous Cell Carcinoma: A Review.

Head and neck tumor differential diagnosis and prognosis have always been a challenge for oral pathologists due to their similarities and complexity. Artificial intelligence novel applications can function as an auxiliary tool for the objective interpretation of histomorphological digital slides. In this review, we present digital histopathological image analysis applications in oral squamous cell carcinoma. A literature search was performed in PubMed MEDLINE with the following keywords: "artificial intelligence" OR "deep learning" OR "machine learning" AND "oral squamous cell carcinoma". Artificial intelligence has proven to be a helpful tool in histopathological image analysis of tumors and other lesions, even though it is necessary to continue researching in this area, mainly for clinical validation.

Connexin 43 expression in tooth germ and benign odontogenic tumors.

OBJECTIVE: The aim of this study was to investigate and compare the immunohistochemical expression of connexin 43 (Cx43) in tooth germs (TGs), ameloblastic fibromas (AFs), ameloblastic fibro-odontomas (AFOs), and conventional ameloblastomas (AMs). STUDY DESIGN: Nine TGs, 12 AFs, 12 AFOs, and 27 AMs were evaluated for Cx43 expression by immunohistochemistry. RESULTS: Most of the TGs expressed Cx43 in the mesenchyme (77.6%) and in the late stages of odontogenesis. Cx43 was more highly expressed (P < .05) in the mesenchymal layer of all groups than in the epithelial layer except for the AFOs. When comparing the expression of Cx43 in the different layers of the analyzed groups, statistically significant differences were observed between AFO vs AM (*P = .0158) in the epithelial layer and between AF vs AFO (P** = .0046) in the mesenchymal layer. CONCLUSIONS: The results obtained in this study showed that Cx43 is a protein with important expression in the mesenchymal layer of the embryonic and odontogenic tissues studied. It could be speculated that Cx43 participates in mineralization events based on the relationship of the expression of this protein between the epithelial and mesenchymal layers of odontogenic tissues.

Spatial distribution of CD34 protein in primordial odontogenic tumour, ameloblastic fibroma and the tooth germ.

BACKGROUND: Primordial odontogenic tumour is a benign mixed neoplasm of recent description, which has histological similarities with other odontogenic tumours such as the ameloblastic fibroma. In this article, we investigate the architecture of the sub-epithelial layer of mesenchymal cells expressing the marker CD34 in primordial odontogenic tumour. OBJECTIVE: Analyse the spatial patterns of CD34 expression in primordial odontogenic tumour and compare them with those in ameloblastic fibroma and the normal tooth germ by means of objective imaging approaches, to better characterise these lesions. METHODS: Two cases of primordial odontogenic tumour, four cases of ameloblastic fibroma and two cases of tooth germ in cap and bell stages were used for morphological, structural and immunohistochemical analyses. RESULTS: CD34 expression was found in vascular endothelium of primordial odontogenic tumour, ameloblastic fibroma and tooth germ. In addition, a characteristic sub-epithelial expression was observed only in primordial odontogenic tumour, corresponding to 84%-86% of the sample boundaries. Moreover, the zone expressing CD34 corresponded with a higher cellularity, which was absent in ameloblastic fibroma and tooth germ. CONCLUSION: Image analysis of the primordial odontogenic tumour architecture revealed characteristics absent in other odontogenic tumours and tooth germs. This study provides additional information to support the idea that this neoplasm is a distinct entity from early stage AF or developing odontoma.

Ep-CAM (MOC-31) expression in tooth germ and ameloblastoma

Background: Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, hasdiverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regu-lation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, partic-ipating in theinitiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oralneoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ.Material and Methods: Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs(TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in theirtotality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% ofcells; + for staining of 5-50% of cells; ++ for staining >50% of cells.Results: Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epitheliumof the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression,the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases ofameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between proteinexpression and gender, age, clinical variants, or histological subtypes.Conclusions: Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies withdifferent experimental strategies are suggested to clarify the biological significance of this finding. (AU)

Decompression induces inflammation but do not modify cell proliferation and apoptosis in odontogenic keratocyst.

BACKGROUND: Odontogenic keratocyst (OKC) is a development cyst, of odontogenic origin, that differs from other entities by its infiltrating and aggressive biological behavior. Among conservative treatments for large lesions, surgical decompression stands out, with a variable recurrence rate. Aim: To evaluate the histological effects of decompression treatment on OKC, including cell proliferation and apoptosis of epithelial cyst. MATERIAL AND METHODS: 21 OKC cases were included. Samples were taken before and after surgical decompression for histological evaluation and immunohistochemical staining of Ki-67, MCM4/7, Bax and Bcl2. Data were analyzed and compared using Student's t and Wilcoxon tests for related samples, and p values <0,05 were considered statistically significant. RESULTS: After decompression treatment an increase in inflammation of the cystic wall (p=0,029), loss of parakeratinization of the epithelium (p=0,007) and absence of palisade cell distribution in the basal layer were observed (p=0,002). There were no statistically significant changes in the expression of Ki-67 (p=0,323), MCM4/7 (p=0,079), Bax (p=0,392) or Bcl-2 when compared before and after decompression. CONCLUSIONS: Surgical decompression generates histological structural changes in OKC both in the epithelium and connective wall, however, these findings do not seem to alter induction of the cell cycle or epithelial apoptosis. Key words:Odontogenic keratocyst, MCM, Bax, Bcl2, Ki-67, apoptosis, decompression.

Fisiopatología de la enfermedad COVID-19 / Pathophysiology of COVID-19 / Fisiopatologia da doença COVID-19

La enfermedad por coronavirus es una infección respiratoria causada por el virus SARS-CoV 2, el cual genera una cascada de eventos sistémicos, afectando diferentes órganos y tejidos. El entendimiento de la fisiopatología del COVID-19 es indispensable no solo al momento de brindar tratamiento a los pacientes, sino que también para comprender las causas de las complicaciones que presentan un número importante de pacientes recuperados. El objetivo de este trabajo es presentar una revisión actualizada de los efectos de la infección en diferentes órganos y sistemas principales que sea de utilidad como material de referencia para profesionales y estudiantes de la salud. Para ello se realizó una búsqueda bibliográfica en los portales PubMED, Scielo, Google Scholar, Cochrane y Springer Link, así como en las bases de repositorios científicos pre-publicación bioRxiv ("bioarchives") y medRxiv ("med-archives") y sobre un total de cerca de 200 mil artículos, se seleccionaron 100 artículos para esta revisión en base a su relevancia o sugerencias de parte de profesionales especializados.

Coronavirus disease is a respiratory infection caused by the SARS-CoV-2 virus, which causes a cascade of systemic events, affecting various organs and tissues. Understanding the pathophysiology of COVID-19 is essential to treat patients and understand the causes of the complications in a significant number of recovered patients. This article presents a review of the effects of infection on various organs and systems that will be useful as reference material for healthcare professionals and medical students. To this end, a literature search was conducted in PubMED, Scielo, Google Scholar, Cochrane, and Springer Link portals, as well as in the pre-publication scientific repositories bioRxiv ("bioarchives") and medRxiv ("med-archives") databases. From about 200,000 papers, 100 articles were selected for this review based on their relevance or suggestions from experts in the field.

A doença coronavírus é uma infecção respiratória causada pelo vírus SARS-CoV-2, que gera uma cascata de eventos sistêmicos, afetando diferentes órgãos e tecidos. Compreender a fisiopatologia da COVID-19 é essencial não apenas no tratamento de pacientes, mas também para compreender as causas das complicações que um número significativo de pacientes recuperados apresenta. O objetivo deste trabalho é apresentar uma revisão atualizada dos efeitos da infecção em diferentes órgãos e principais sistemas que seja útil como material de referência para profissionais de saúde e estudantes. Para isso, foi realizada uma pesquisa bibliográfica nos portais PubMED, Scielo, Google Scholar, Cochrane e Springer Link, bem como nos repositórios científicos de pré-publicação bioRxiv ("bioarquivos") e medRxiv ("arquivos med"). Num total de cerca de 200 mil artigos, 100 artigos foram selecionados para esta revisão por sua relevância ou sugestões de profissionais especializados.

Bases moleculares de los tumores odontogénicos benignos: revisión de la literatura en el contexto de la última clasificación de la Organización Mundial de la Salud

Resumen Los tumores odontogénicos (TOs) son un grupo heterogéneo de lesiones que incluyen hamartomas hasta neoplasias benignas o malignas. El presente estudio tuvo como objetivo revisar la literatura sobre los aspectos moleculares y genéticos de algunos TOs benignos. A partir de los estudios revisados, se apoya la idea de que las causas genéticas pueden tener un papel importante en la etiología y en la patogénesis de algunos TOs. Sin embargo, las investigaciones sobre el tema aún no permiten concluir de manera sólida los mecanismos definitivos involucrados en el desarrollo y en la progresión de los TOs. Se sugiere el desarrollo de más estudios moleculares y genéticos que evalúen muestras significativas de TOs para establecer su etiopatogenia, facilitar su proceso diagnóstico y enriquecer su abordaje terapéutico.

Resumo Os tumores odontogênicos (TOs) são um grupo heterogêneo de lesões que variam desde hamartomas até neoplasias benignas ou malignas. O presente estudo teve como objetivo revisar a literatura sobre os aspectos moleculares e genéticos de alguns TOs benignos. A partir dos estudos revisados, apoia-se que as causas genéticas podem desempenhar um papel importante na etiologia e patogênese de alguns TOs. No entanto, as pesquisas sobre o assunto ainda não permitem uma conclusão sólida sobre os mecanismos definitivos envolvidos no desenvolvimento e progressão dos TOs. Sugere-se o desenvolvimento de mais estudos moleculares e genéticos para avaliar amostras significativas de TOs para estabelecer sua etiopatogenia, facilitar seu processo diagnóstico e enriquecer sua abordagem terapêutica.

Abstract Odontogenic tumors (OTs) are a heterogeneous group of lesions that range from hamartomas to benign or malignant neoplasms. The present study aimed to review the literature regarding the molecular and genetic aspects from some benign OTs. Based on the review of the included studies, it is supported that genetic background may play an important role in the etiology and pathogenesis of OTs. However, the body of evidence on the subject still does not allow to conclude the definitive mechanisms involved in the development and progression of OTs. It is suggested the development of further molecular and genetic studies evaluating significant samples of OTs to establish its etiopathogenesis, facilitate its diagnostic process and enrich the therapeutic approaches.

Expression of caveolin-1 in tooth germ, ameloblastoma and ameloblastic carcinoma / Expresión de caveolina-1 en germen dental ameloblastoma y carcinoma ameloblástico

Background: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in sev-eral biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been as-sociated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear.Material and Methods: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium(n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) byimmunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot.Results: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemicalpositivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were signifi-cantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue,as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1immunoexpression patterns throughout the stages of TG show its importance during odontogenesis.Conclusions: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingivalepithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immu-noexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformationprocess. However, future studies are needed to clarify and confirm these hypotheses.(AU)

Mecanismos moleculares de la amelogénesis imperfecta. Una revisión de los genes ENAM, AMBN, FAM83H, MMP20 y KLK4 / Molecular mechanisms of amelogenesis imperfecta. A review of the ENAM, AMBN, FAM83H, MMP20 and KLK4 genes / Mecanismos moleculares da amelogênese imperfeita. Uma revisão dos genes ENAM, AMBN, FAM83H, MMP20 e KLK4

Resumen La amelogenesis imperfecta (AI) es un trastorno hereditario que afecta la estructura y apariencia clínica del esmalte dental. Hasta la fecha, se han asociado las mutaciones de 18 genes como la etiología de la AI no sindrómica. El objetivo de este trabajo es actualizar los conocimientos vigentes acerca de los genes ENAM, AMBN, FAM83H, MMP20 y KLK4 causantes de los diferentes tipos de AI. Metodología: Se realizó una búsqueda bibliográfica considerando artículos científicos desde el 2003 al 2021 sobre mutaciones en los genes mencionados en los siguientes portales: scielo, Pubmed/MEDLINE, Cochrane y Springer Link. Resultados: 37 artículos cumplieron los criterios de inclusión y fueron utilizados para esta revisión. Conclusiones: Dependiendo del gen implicado, las alteraciones del esmalte pueden mostrar una variedad de características. Los mecanismos biológicos que conducen a la enfermedad son múltiples y variados, sin embargo, muchos de ellos no están del todo claro aún, por lo que se requerirá de más investigaciones para mejorar nuestra comprensión del tema.

Amelogenesis imperfecta (AI) is an inherited disorder that affects the structure and clinical appearance of tooth enamel. Mutations of 18 genes have been associated as the etiology of AI. The objective of this work is to update the current knowledge about ENAM, AMBN, FAM83H, MMP20 and KLK4 genes that cause the different types of AI. Methodology: A bibliographic search was carried out considering scientific articles from 2003 to 2021 with regard to specific mutations in the aforementioned genes in the following portals: scielo, Pubmed / MEDLINE, Cochrane and Springer Link. Results: 37 articles met the inclusion criteria and were used for the development of this review. Conclusions: Depending on the gene involved, enamel alterations can show a variety of characteristics. The biological mechanisms that lead to the disease are multiple and varied, however many of them are not entirely clear yet, so more research will be required to improve our understanding of the subject.

A amelogênese imperfeita (AI) é uma doença hereditária que afeta a estrutura e aparência clínica do esmalte dentário. Mutações de 18 genes têm sido associadas como causa do AI. O objetivo deste trabalho é atualizar o conhecimento atual sobre genes ENAM, AMBN, FAM83H, MMP20 e KLK4 que causam os diferentes tipos de IA. Metodologia: Foi realizada uma busca bibliográfica considerando artigos científicos de 2003 até 2021 sobre mutações específicas nos genes citados nos seguintes portais: scielo, Pubmed / MEDLINE, Cochrane e Springer Link. Resultados: 37 artigos atenderam aos critérios de inclusão e foram utilizados para o desenvolvimento desta revisão. Conclusões: Dependendo do gene envolvido, as alterações do esmalte podem apresentar uma variedade de características. Os mecanismos biológicos que levam à doença são múltiplos e variados, porém muitos de les ainda não estão totalmente esclarecidos, portanto, mais pesquisas serão necessárias para melhorar nossa compreensão do assunto.

Perfil inmunohistoquímico del mixoma odontogénico, con énfasis en marcadores de agresividad tumoral y microdensidad vascular / Perfil imuno-histoquímico do mixoma odontogênico, com ênfase em marcadores de agressividade tumoral e microdensidade vascular / Immunohistochemical profile of odontogenic myxoma, with a focus on microvascular density and tumor aggressiveness markers

Con el fin de tener una mayor comprensión sobre el comportamiento biológico del mixoma odontogénico (MO), se realizó inmunohistoquímica en 31 muestras, utilizando marcadores relacionados con mecanismos de progresión tumoral (adhesión, angiogénesis, apoptosis, inflamación y proliferación celular). El epitelio odontogénico fue detectado en cuatro muestras mediante CK19 y CD138, este último, mostró expresión baja en matriz extracelular (MEC) y alta en las células tumorales. La microdensidad vascular (MDV) media fue de 7.51 y 5.35 vasos marcados con CD34 y VEGF-A respectivamente. Una alta expresión de Orosomucoide-1 y Mast Cell Tryptase se observó células tumorales y en MEC. El MO mostró negatividad para Calretinina. Este perfil inmunohistoquímico, la baja expresión para Ki-67, Bcl-2 y p53, y la relativamente baja MDV, sugieren que la actividad proliferativa, anti-apoptótica o angiogénica no representan los principales mecanismos de crecimiento del MO, los cuales podrían estar asociados a eventos como inmunomodulación y degradación de la MEC.

Immunohistochemistry tests were performed in 31 samples to elucidate the biological behavior of the odontogenic myxoma (OM), using markers related to mechanisms of tumor progression (adhesion, angiogenesis, apoptosis, inflammation and cell proliferation). Odontogenic epithelium was detected in four samples with CK19 and CD138; the latter had a low expression in the extracellular matrix (ECM) and a high expression in tumor cells. The mean microvascular density (MVD), assessed with CD34 and VEGF-A, was 7.51 and 5.35 blood vessels. A high expression of orosomucoid-1 and mast cell tryptase was observed in tumor cells and ECM, while calretinin was negative. The immunohistochemical profile mentioned above, as well as the low expression of Ki67, Bcl-2 and p53 and the relatively low MVD, suggest that the proliferative, antiapoptotic and angiogenic activities do not represent the main growing mechanisms of OM, which could be associated to other events, such as immunomodulation and ECM degradation.

Para melhor compreensão do comportamento biológico do mixoma odontogênico (MO), imuno-histoquímica foi realizada em 31 amostras, utilizando marcadores relacionados aos mecanismos de progressão tumoral (adesão, angiogênese, apoptose, inflamação e proliferação celular). Epitélio odontogênico foi detectado em quatro amostras por CK19 e CD138, o último mostrou baixa expressão na matriz extracelular (MEC) e alta em células tumorais. A microdensidade vascular (MDV) média foi de 7.51 e 5.35 vasos marcados com CD34 e VEGF-A, respectivamente. Uma alta expressão de Orosomucoide-1 e Mast Cell Tryptase foi observada nas células tumorais e na MEC. O MO mostrou negatividade para Calretinina. O perfil imuno-histoquímico mencionado acima, a baixa expressão de Ki-67, Bcl-2 e p53 e a relativamente baixa MDV, sugerem que a atividade proliferativa, anti-apoptótica ou angiogênica não representam os principais mecanismos de crescimento do MO, os quais poderiam estar associados com eventos como imunomodulação e degradação da MEC.

Primordial odontogenic tumor: A systematic review

BACKGROUND: The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis. AIM: To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features. MATERIAL AND METHODS: An electronic systematic review was performed up to September 2019 in multiple databases. RESULTS: A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for am-elogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm. CONCLUSION: POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently

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Regeneración ósea como un ejemplo de ingeniería tisular en odontología, con énfasis en el desarrollo de los andamios / Regeneração óssea como exemplo de engenharia de tecidos em odontologia, com ênfase no desenvolvimento de andaimes / Bone regeneration as an example of tissue engineering in dentistry, with an emphasis on the development of scaffolds

Resumen La ingeniería tisular es un área científica multidisciplinaria la cual tiene como finalidad terapéutica restaurar, sustituir o incrementar las actividades funcionales de los tejidos orgánicos. Objetivos: Realizar una revisión de la literatura sobre la ingeniería tisular a nivel del área bucomaxilofacial. Métodos: Se realizó una búsqueda bibliográfica mediante los portales PubMed MEDLINE, Google Scholar, y LILACS, usando los términos "células madre, regeneración ósea y factores de crecimiento tisular". Resultados: Se obtuvieron 193 resultados positivos, de los cuales 24 se utilizaron para el desarrollo del presente trabajo. Discusión: Han sido expuestos varios biomateriales capaces de propiciar la neoformación ósea, siendo esencial su correcta manipulación, la conformación de una arquitectura adecuada y la sinergia de las diversas propiedades. Conclusiones: Los andamios son los que brindan mayor oferta para su uso y la elección de cada uno de ellos no depende del material en sí mismo.

Resumo: A engenharia de tecidos é uma área científica multidisciplinar cujo objetivo é restaurar, substituir e aumentar as atividades funcionais dos tecidos orgânicos. Objetivos: O objetivo deste trabalho é revisar a literatura sobre engenharia de tecidos no nível da área bucomaxilofacial. Métodos: Foi realizada uma pesquisa bibliográfica no portals PubMed MEDLINE, Google Scholar, e LILACS, utilizando os termos "células-tronco, regeneração óssea e fatores de crescimento tecidual". Resultados: foram obtidos 193 resultados positivos, dos quais 24 foram utilizados para o desenvolvimento deste trabalho. Discussão: Vários biomateriais capazes de promover a neoformação óssea foram expostos, sendo sua manipulação correta, a conformação de uma arquitetura adequada e a sinergia das várias propriedades. Conclusões: são os andaimes que oferecem a melhor oferta para seu uso e a escolha de cada um não depende do material propriamente dito.

Abstract Tissue engineering is a multidisciplinary scientific area that has the therapeutic purpose of restoring, replacing, or increasing the functional activities of organic tissues. Objective: This work aims to review the literature on tissue engineering in oral and maxillofacial procedures. Methods: A bibliographic search was conducted in PubMed MEDLINE, Google Scholar, and LILACS, using the terms "stem cells," "bone regeneration," and "tissue growth factors." Results: In total, 193 positive results were obtained, of which 24 were used for this paper. Discussion: Several biomaterials capable of promoting bone neoformation have been described. They need to be adequately manipulated and have the right architecture and achieve the synergy of the various properties. Conclusions: Scaffolds have the widest uses, and selecting one does not depend on the material itself.

Inmunoexpresión de biomarcadores Bax, Bcl-2, CD138, H3, Ki-67, MCM3 y p53 en liquen plano oral / Immunoexpression of biomarkeres BAX, BCL-2, CD-138, H3, Ki-67, MCM3 AND p53 in oral lichen planus

El objetivo del presente trabajo fue determinar la expresión de diversos biomarcadores moleculares en liquen plano oral para ayudar a comprender su conducta biológica. Materiales y métodos: Se realizó un estudio inmunohistoquímico en 40 casos de liquen plano oral contra BAX, BCL-2, CD-138, Histona 3, Ki-67, MCM3 y p53, en el Área de Patología Molecular Estomatológica de la Facultad de Odontología, UDELAR, Uruguay. Resultados: Se observó mayor expresión de BAX en contraposición con BCL-2, sugiriendo un comportamiento proapoptótico, respaldado a su vez por la ausencia de expresión de p53. La expresión de los marcadores de proliferación celular fue en todo el tejido lesional observado, sugiriendo así alteraciones de la proliferación. CD-138 se expresó de manera intensa y uniforme, determinando una baja alteración de las uniones intercelulares para estos casos. Conclusiones: La alteración en la expresión de las proteínas estudiadas sugiere un trastorno en los mecanismos proliferativos y apoptóticos, los cuales se asocian con una conducta patológica de la mucosa oral.

This study aims to establish an association of the expression of specific biomarkers in oral lichen planus to understandits biological behavior. Materials and methods: An immunohistochemistry study was conducted in 40 cases of oral lichen planus against BAX, BCL-2, CD138, Histone 3, Ki-67, MCM3 and p53 at the Molecular Pathology Area of the School of Dentistry, UDELAR, Uruguay. Results: A greater expression of BAX was detected compared to BCL-2, suggesting a pro-apoptotic behavior, supported by the absence of p53 expression. MCM3 expression was more sensitive than Ki-67, considering proliferation alterations. CD-138 had a more intense and uniform expression, determining fewer intercellular adhesion alterations. Conclusions: The expression of the proteins studied suggests an alteration in proliferative and apoptotic mechanisms, associated with a pathological behavior of the oral mucosa.

O objetivo deste trabalho foi determinar a expressão de vários biomarcadores moleculares no líquen plano oral para ajudar a compreender seu comportamento biológico. Materiais emétodos: Foi realizado um estudo imunohistoquímico em 40 casos de líquen plano oral contra BAX, BCL-2, CD-138, Histona 3, Ki-67, MCM3 e p53, na área de Patologia Molecular Estomatológica da Faculdade de Odontologia , UDELAR, Uruguai. Resultados: Observou-se aumento da expressão de BAX em contraste com BCL-2, sugerindo um comportamento proapoptótico, apoiado por sua vez pela ausência da expressão de p53. A expressão de marcadores de proliferação celular foi observada em todo o tecido da lesão, sugerindo alterações na proliferação. CD-138 foi expressado de maneira intensa e uniforme, determinando uma baixa alteração das junções intercelulares para esses casos. Conclusões: A alteração na expressão das proteínas estudadas sugere um distúrbio nos mecanismos proliferativos e apoptóticos, os quais estão associados a um comportamento patológico da mucosa oral.

Estudio de apoptosis y adhesión intercelular en mucosa oral de pacientes con osteonecrosis inducida por bifosfonatos / Study of apoptosis and intercellular adhesion in oral mucosa of patients with osteonecrosis induced by biphosphonates

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Complejo mcm2-7. Revisión bibliográfica / MCM2-7 complex: a review

La formación de nuevas células se genera a partir de células preexistentes a través de una serie ordenada de eventos denominada ciclo celular. El control de este es fundamental para la integridad del genoma, por lo que hay múltiples proteínas regulando este proceso. Actualmente, se conoce que el complejo MCM2-7 tiene un rol esencial en la replicación del ADN, específicamente involucrado en la proliferación, durante el ciclo celular. La identificación inmunohistoquimica de las proteínas de este complejo a nivel tisular, podría ser una herramienta muy útil, para usarlos como biomarcadores y así comprender uno de los mecanismos biológicos que se ven afectados en el cáncer. Nuestro objetivo es realizar una revisión del complejo MCM2-7, ya que estas proteínas como se ha descrito, podrían comportarse como buenos marcadores biológicos de proliferación celular, y así poder realizar un buen diagnóstico, pronóstico y futuros blancos terapéuticos de aquellas lesiones principalmente neoplásicas , principalmente las que asientan a nivel de la mucosa bucal.

New cells are formed from preexisting cells through an ordered series of events called cell cycle. As the control of this cycle is fundamental for genome integrity, multiple proteins regulate this process. We currently know that the MCM2-7 complex has a major role in DNA replication in the cell cycle, in particular regarding proliferation. The immunohistochemical identification of the proteins in this complex on tissues may be useful, as they could be used as biomarkers and would help us understand one of the biological mechanisms affected in cancer processes. Our aim is to collect the existing evidence regarding the members of the MCM2-7 complex, since these proteins could be effective biological cell proliferation markers, which would help practitioners make accurate diagnosis, prognosis and future therapeutic targets of lesions that are mainly neoplastic, especially in the oral mucosa.

Estudio de la proliferación celular en gérmenes dentarios humanos / Cell proliferation study in human tooth germs

El objetivo de este estudio fue conocer la expresión de MCM4-5-6 en gérmenes dentarios humanos en estado de campana. Materiales y Métodos Se obtuvieron preparados histológicos de 4 maxilares fetales incluidos en parafina en el archivo de bloques de la cátedra de Histología de la Facultad de Odontología, UdelaR. Se procedió al corte de los mismos en secciones para técnica de rutina (HE) y de IHQ para MCM 4, 5 y 6. Resultados: Las diferentes regiones del órgano del esmalte mostraron 100 % de positividad en el estrato intermedio, una variación de 100 % a 0 % en el epitelio interno del órgano del esmalte, desde el sector cervical al sector incisal del mismo, y0% tanto en el retículo estrellado como en el epitelio externo del órgano del esmalte. Conclusiones: Los resultados obtenidos permitieron evidenciar y confirmar la acción proliferativa de las diferentes zonas del órgano del esmalte.

The aim of this study was to determine the expression of MCM4-5-6 in human tooth germs in the bell stage. Materials and methods: Histological samples were collected from four fetal maxillae placed in paraffin at the block archive of the Histology Department of the School of Dentistry, UdelaR. Sections were made for HE routine technique and for immunohistochemistry technique for MCM4-5-6. Results: Different regions of the enamel organ showed 100% positivity in the intermediate layer, a variation from 100% to 0% in the inner epithelium from the cervical loop to the incisal area, and 0% in the stellar reticulum as well as the outer epithelium. Conclusions: The results show and confirm the proliferative action of the different areas of the enamel organ.

JOSE VEROCAY - "Pragues pathologist". The history of a Latin-American doctor.

José Verocay (Paysandú 1876 - Eichwald/Dubí, Bohemia 1927) was a Uruguayan anatomopathologist, recognized worldwide as "Prague's pathologist" (Fig. 1). In 1910, he described, for the first time, the morphological structure later called Verocay's bodies, which are used for diagnosing schwannoma. He spent the end of the XIXth century and the beginning of XXth century in Charles-Ferdinand University in Prague. During the last years of his life, he tried unsuccessfully to reintegrate himself into the Uruguayan academic community. In 1927, he passed away in Eichwald, Teplitz district, Bohemia. Keywords: Prague's pathologist - Veroca y - Verocay's bodies.