Perspectivas atuais da engenharia de tecidos da articulação temporomandibular / Perspectivas Actuales de la Ingeniería de Tejidos para la Articulación Temporomandibular / Current Perspectives of Tissue Engineering for the Temporomandibular Joint

Introdução: As limitações das terapias atuais para doenças degenerativas da articulação temporomandibular (ATM) levaram ao aumento do interesse em estratégias regenerativas. A engenharia de tecidos (ET), combinando células-tronco, arcabouços e fatores de crescimento, pode fornecer uma substituição biológica funcional e permanente das estruturas da ATM, além de prevenir o avanço de doenças degenerativas. Objetivo: Este artigo descreve as perspectivas atuais da ET das estruturas da ATM em modelos animais. Metodologia: As abordagens da ET foram categorizadas de acordo com as estruturas primárias da ATM: 1) o disco articular, 2) o côndilo mandibular e 3) a fossa glenóide e eminência articular. Resultados: As áreas com a maior quantidade de estudos são o côndilo mandibular e disco articular, em estudos que abordam o uso de arcabouços tridimensionais, de origem sintética e/ou natural, podendo ou não estar associados a células tronco (diferenciadas ou não) e a fatores de crescimento. Conclusão: A ET da ATM ainda é uma área relativamente nova, em desenvolvimento e em constante avanço. Os avanços tecnológicos desenvolvidos nessa área têm o potencial de auxiliar no desenvolvimento de terapias mais eficientes e menos invasivos... (AU)

Introducción: Las limitaciones de las terapias actuales para las enfermedades degenerativas de la articulación temporomandibular (ATM) han llevado a un mayor interés en las estrategias regenerativas. La ingeniería de tejidos, que combina células, andamios y factores de crecimiento, puede proporcionar un reemplazo biológico funcional y permanente de las estructuras de la ATM, además de prevenir el avance de enfermedades degenerativas. Objetivo: Este artículo describe las perspectivas actuales de la ingeniería de tecidos de las estructuras de la ATM en modelos animales. Metodología: Los enfoques de ingeniería de tejidos se clasificaron según las estructuras primarias de la ATM: 1) el disco articular, 2) el cóndilo mandibular y 3) la fosa glenoidea y la eminencia articular. Resultados: Las áreas con mayor número de estudios son el cóndilo mandibular y el disco articular, en estudios que abordan el uso de estructuras tridimensionales, de origen sintético y/o natural, que pueden o no estar asociadas a células (diferenciadas o no) y con factores de crecimiento. Conclusión: La ingeniería de tejidos de la ATM es todavía un área relativamente nueva, en desarrollo y en constante avance. Los avances tecnológicos desarrollados en esta área tienen el potencial de ayudar en el desarrollo de terapias más eficientes y menos invasivas... (AU)

Introduction: The limitations of current therapies for degenerative diseases of the temporomandibular joint (TMJ) have led to increased interest in regenerative strategies. Tissue engineering (TE), combining stem cells, scaffolds, and growth factors, can provide a functional and permanent biological replacement of TMJ structures, in addition to preventing the advancement of degenerative diseases. Aim: This article describes current TE perspectives of TMJ structures in animal models. Methods: TE approaches were categorized according to the primary TMJ structures: 1) the articular disc, 2) the mandibular condyle, and 3) the glenoid fossa and articular eminence. Results: The areas with the greatest number of studies are the mandibular condyle and articular disc, in studies that address the use of three-dimensional scaffolds, of synthetic and/ or natural origin, which may or may not be associated with stem cells (differentiated or not) and with growth factors. Conclusion: TE of the TMJ is still a relatively new, developing, and constantly advancing area. The technological advances developed in this area have the potential to assist in the development of more efficient and less invasive therapies... (AU)

Research advances on biomaterials for the delivery of growth factors to regulate wound repair / 中华烧伤杂志

Wound repair is a highly coordinated and mutually regulated complex process involving various kinds of cells, extracellular matrices and cytokines. A variety of growth factors play an important regulatory role in wound healing, and it is critical to achieve effective delivery and sustained function of growth factors. In recent years, the application of biomaterials in tissue engineering has shown great potential, and the effective delivery of growth factors by biomaterials has attracted increasing attention. Based on this, this paper introduces the mechanism of related growth factors in the process of wound healing, focusing on the recent progress of biomaterial delivery of growth factors to accelerate wound healing, in order to provide new enlightenment for clinical wound treatment.

Progress and thoughts on the regulation of wound repair by growth factors / 中华烧伤杂志

Growth factors play an important role in wound healing, and they mainly accelerate wound healing by activating the related signal pathways. Chinese scientists have been conducting basic and clinical researches on growth factors for 30 years, with a series of growth factor drugs being developed and widely used in the treatment of burns and trauma and chronic refractory ulcers. This paper expounds the frontier progress of growth factors on wound healing from the perspectives of immunity, nerve, fat, and so on, and puts forward the further thoughts of the research team on the regulation of wound healing by growth factors.

Efecto del factor de crecimiento fibroblástico dos (FGF-2), en la reducción de la senescencia en células madre mesenquimales aisladas de gelatina de Wharton / Fibroblastic growth factor two (FGF-2), in reducing the senescent effect on mesenchymal stem cell isolated from Wharton ́s jelly

Resumen Introducción. Las células madre mesenquimales han generado interés en la ingeniería de tejidos, debido a sus propiedades proliferativas y capacidad de reparación de tejidos, sin embargo, para un trasplante exitoso, es necesario aumentar el número de células mediante un cultivo in-vitro. Durante este proceso la capacidad proliferativa disminuye, provocando cambios en la morfología y funcionalidad celular y afectando la viabilidad del cultivo, este estado se conoce como senescencia celular y como posibles causales, se ha considerado el estrés oxidativo y la falta de factores de crecimiento. Objetivos: Evaluar el efecto de FGF-2 sobre la senescencia de un cultivo de células madre mesenquimales aisladas de gelatina de Wharton y su papel en la regulación del estrés oxidativo. Metodología. Se añadieron dosis de 3,5 y 7,5 ng de FGF-2 al cultivo. Durante los pasajes 5 y 7, se estimó tanto la senescencia celular como la presencia de ROS (especies reactivas de oxígeno). Resultados.Se obtuvo en el pasaje 5, una diferencia significativa del 99,5% entre el control (+) con respecto a los tratamientos con FGF-2, sin embargo, en el pasaje 7 se observó un aumento en la producción de la enzima ß-galactosidasa y cambios morfológicos, confirmando un estado senescente en el cultivo en todos los tratamientos evaluados. Conclusión. Las dosis utilizadas en este estudio contribuyeron positivamente a disminuir el proceso senescente en el cultivo celular, además se determinó, que el FGF-2 puede prolongar el tiempo de cultivo, retardando parcialmente la concentración de especies reactivas de oxígeno

AbstractIntroduction. Mesenchymal stem cells have been generated interest in tissue engineering, due to their proliferative properties and tissue repair capacity, however, for a successful transplant process, it is necessary to increase the number of cells in a culture expansion process. During this process the proliferative capacity is limited, causing changes in cell morphology and functionality affecting the viability of the culture, this state is known as cell senescence. Oxidative stress and deregulation of growth factors are considered as reasons. Aims. To evaluate the effect of FGF-2 on the senescence of a mesenchymal stem cells culture isolated from Wharton ́s jelly and its role in the regulation of oxidative stress. Methodology: 3,5 and 7,5 ng doses of FGF-2 were added to the culture medium from passage 2, then the senescence of the culture was evaluated and the presence of reactive oxygen species was determined during passages 5 and 7. Results. We observed that in passage 5, there is a significant difference 99.5% between the control (+) concerning the FGF-2 treatments, however, in passage 7, an increase in the production of the enzyme ß-galactosidase was observed and changes in morphology such as: increase in size and elongated shape of the cell, confirming a senescent state on the culture in all the treatments evaluated. Conclusion. The doses used in this study contributed positively to decrease this process in a cell culture, also, the FGF- 2 can prolong the cultivation time, partially decreasing the concentration of reactive oxygen species

Novo Efeito Cardioprotetor da L-Carnitina em Camundongos Obesos Diabéticos: Regulação da Expressão de Quemerina e CMKLRI no Coração e Tecidos Adiposos / Novel Cardioprotective Effect of L-Carnitine on Obese Diabetic Mice: Regulation of Chemerin and CMKLRI Expression in Heart and Adipose Tissues

Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Limitations and advances in new treatments and future perspectives of corneal blindness / Limitações e avanços em novos tratamentos e perspectivas futuras na cegueira corneal

ABSTRACT This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.(AU)

RESUMO O presente trabalho traz uma revisão das abordagens terapêuticas para a cegueira da córnea. O estudo detalha as etapas e os elementos envolvidos na cicatrização da córnea. Ele mostra as limitações das estratégias cirúrgicas e farmacológicas usadas para restaurar e manter a transparência da córnea em termos de sobrevida a longo prazo e alcance geográfico. As perspectivas dos agentes anabólicos, incluindo vitamina A, hormônios, fatores de crescimento e novos moduladores pró-mitóticos e anti-inflamatórios para auxiliar a cicatrização da ferida na córnea, são revisadas criticamente. Aqui, apresentamos estudos envolvendo nanotecnologia, terapia gênica e reengenharia de tecidos como possíveis estratégias futuras para atuar de maneira isolada ou combinada com a cirurgia da córnea para prevenir ou reverter a cegueira corneana.(AU)

Avaliação do tratamento de alterações estéticas faciais com uso de um protocolo operacional desenvolvido para a aplicação de plasma rico em plaquetas / Evaluation of the treatment of changes aesthetic facial with the use of an operational protocol developed for the application of platelet rich plasm

Introdução: o plasma rico em plaquetas é definido como um concentrado de plaquetas autólogas, obtido por centrifugação de sangue total. Trata-se de uma técnica inovadora, simples e de baixo custo, que apresenta muitos benefícios, podendo ser aplicada em diferentes áreas da saúde. Objetivo: a presente pesquisa buscou desenvolver um protocolo operacional padrão para obtenção e aplicação do plasma sanguíneo rico em plaquetas para o tratamento de alterações estéticas faciais. Metodologia: o estudo tratou de uma pesquisa de campo experimental, de caráter qualitativo e quantitativo. Um processo seletivo foi realizado para recrutar pacientes voluntários para o estudo, que foram selecionados de acordo com os critérios de inclusão e exclusão. Através de testes foi possível chegar ao tempo de centrifugação e velocidade ideais para a produção do plasma rico em plaquetas e testá-lo no tratamento de alterações estéticas faciais. Resultados e discussão: as principais mudanças que foram notadas pelos pacientes durante e após o tratamento foram a redução das cicatrizes de acne e aumento da hidratação e viscosidade da pele. A melhora das alterações estéticas tratadas foi notada por 100% dos pacientes, não havendo piora em nenhum paciente. Conclusão: com base nos testes e resultados obtidos, foi possível padronizar um protocolo operacional padrão ideal para a obtenção e aplicação do plasma rico em plaquetas, comprovando sua eficácia no tratamento de alterações estéticas faciais como rugas, flacidez, linhas de expressões acentuadas, acne, cicatrizes de acne, além de ter-se observado uma melhora significativa na hidratação da pele e redução de poros dilatados.

Introduction: platelet-rich plasma is defined as a concentrate of autologous platelets, obtained by centrifuging whole blood. It is an innovative, simple and low-cost technique that has many benefits, and can be applied in different areas of health. Objective: the present research sought to develop a standard operating protocol for obtaining and applying platelet-rich blood plasma for the treatment of facial aesthetic changes. Metodology: the study was a qualitative and quantitative field research. A selection process was carried out to recruit volunteer patients for the study, who were selected according to the inclusion and exclusion criteria. Through tests it was possible to reach the ideal centrifugation time and speed for the production of platelet-rich plasma and to test it in the treatment of facial aesthetic changes. Results and discussion: the main changes that were noted by patients during and after treatment were the reduction of acne scars and increased hydration and skin viscosity. The improvement of the aesthetic changes treated was noticed by 100% of the patients, with no worsening in any patient. Conclusion: based on the tests and results obtained, it was possible to standardize an ideal standard operating protocol for obtaining and applying platelet-rich plasma, proving its effectiveness in the treatment of facial aesthetic changes such as wrinkles, sagging, accentuated expression lines, acne, scars from acne, in addition to a significant improvement in skin hydration and reduction of enlarged pores.

Expressão do RNAm e metilação do DNA do gene DKK2 em câncer colorretal / Rnam expression and dna methylation of dkk2 gene in colorectal câncer

ABSTRACT BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.

RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.

Proteína moduladora de la actividad del receptor de aril hidrocarburos (AIP): genética, bioquímica e impacto clínico / Aryl hydrocarbon receptor interacting protein (AIP): genetics, biochemistry and clinical impact

El gen AIP (proteína moduladora de la actividad del receptor de aril hidrocarburos) se localiza en la región 11q13.2 y codifica para una proteína de 330 aminoácidos que interactúa con el factor de transcripción AhR (receptor para aril hidrocarburos). Las mutaciones en este gen se han asociado con adenomas pituitarios aislados de tipo familiar (APAF). Se caracterizan por una presentación temprana (alrededor de 20 años), por lo regular producen hormona de crecimiento y/o prolactina, tienen un comportamiento clínico agresivo y poca respuesta a análogos de somatostatina.

The AIP gene (aryl hydrocarbon receptor interacting protein) is located on chromosome 11q13.2 and encodes a 330 amino acid protein which interacts with the aryl hydrocarbon receptor (AHR) transcription factor. Mutations in the AIP gene have been associated with familial isolated pituitary adenomas (FIPA). They characterize by an early-onset (around the age of 20 years old) and for being aggressive, growth hormone and/or prolactin-secreting tumors, with poor response to somatostatin analogues.

Identification and verification of key cancer genes associated with prognosis of colorectal cancer based on bioinformatics analysis / 中南大学学报(医学版)

OBJECTIVES@#The biomarkers targeting colorectal cancer (CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC.@*METHODS@#GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa (CRM) tissues from the NCBI-GEO database, and the differentially expressed genes (DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC.@*RESULTS@#For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets (|log@*CONCLUSIONS@#The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.

Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer / 中国医学科学院学报

Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ

Análisis de microdensidad vascular y factores de crecimiento en carcinoma oral de células escamosas / Analysis of vascular microdensity and growth factors in oral squamous cell carcinoma

Introducción: El carcinoma oral de células escamosas (COCE) es una neoplasia epitelial maligna que se presenta frecuentemente entre la quinta y sexta década de la vida. Su compleja patogénesis incluye el proceso de angiogénesis y la regulación del microambiente tumoral como mecanismos de progresión tumoral. Objetivo: Determinar la relación entre las variables clínicas e histológicas del COCE con la inmunoexpresión de VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II y CD105. Material y métodos: Nueve casos de COCE; tres bien (BD), tres moderado (MD) y tres pobremente diferenciados (PD) obtenidos del Departamento de Patología y Medicina Bucal, División de Estudios de Postgrado e Investigación. Se aplicó la técnica de inmunohistoquímica por peroxidasa para identificar la expresión de VEGF, FGF-1, FGFR- 1, TGFB-1, TGFBR-II y CD105. El análisis de inmunoexpresión se realizó con el programa ImageJ. Se aplicó la prueba de Kruskal-Wallis y correlación de Spearman (p < 0.05). Resultados: La inmunoexpresión de VEGF fue mayor en los COCE PD, FGFR-1 fue positivo en los BD, mientras que FGF, TGFB-1 y TGFBR-II fueron negativos. El análisis de microdensidad vascular (MVD) indicó mayor número de vasos CD105 positivos en los carcinomas BD, seguidos de los PD y MD. Conclusión: Considerando los resultados obtenidos podemos concluir que la angiogénesis es un fenómeno constante independiente del grado de diferenciación que durante el proceso de transformación de una neoplasia requerirá la formación de vasos sanguíneos y que este proceso puede ser modulado por factores de crecimiento tales como los analizados en este trabajo (AU)

Introduction: Oral squamous cell carcinoma (OSCC) is a malignant epithelial neoplasm that frequently occurs between the fifth and sixth decade of life. Its complex pathogenesis includes the angiogenesis process and the regulation of the tumor microenvironment as mechanisms of tumor progression. Objective: To determine the relationship between the clinical and histological variables of OSCC with the immunoexpression of VEGF, FGF-1, FGFR-1, TGFB- 1, TGFBR-II and CD105. Material and methods: Nine cases of OSCC; three well (WD), three moderate (MD) and three poorly differentiated (PD) obtained from the Oral Medicine and Pathology Department, Division of Graduate Studies and Research. The peroxidase immunohistochemistry technique was performed to identify the expression of VEGF, FGF-1, FGFR-1, TGFB-1, TGFBR-II and CD105. The immunoexpression analysis was performed with the ImageJ software. The Kruskal-Wallis and Spearman correlation test were performed (p < 0.05). Results: VEGF immunoexpression was higher in PD OSCC, while FGFR-1 was predominantly positive in WD; FGF, TGFB-1 and TGFBR-II were negative. Vascular microdensity analysis (MVD) indicated a greater number of CD105 positive vessels in WD carcinomas, followed by PD and MD. Conclusion: Considering the results obtained, we can conclude that angiogenesis is a constant phenomenon independent of the degree of differentiation; that during the transformation process of a neoplasm it will require the formation of blood vessels and that this process can be modulated by growth factors such as those analyzed in this work (AU)

La aplicación de factores de crecimiento en el desarrollo de la Ingeniería de tejidos óseos / Application of growth factors in the development of bone tissue engineering

RESUMEN Introducción: los avances científico-técnicos en el campo de la Biología celular y molecular han permitido restaurar y mejorar la función de órganos y tejidos lesionados por ciertas enfermedades y traumatismos. La Ingeniería de tejido se define como el uso de los principios y métodos de la Ingeniería, la Biología y la Bioquímica, los cuales están orientados a la comprensión de la estructura y la función de los tejidos normales y patológicos, y al consecuente desarrollo de sustitutos biológicos para restaurar, mantener o mejorar su función. Objetivo: realizar un acercamiento a algunos aspectos de la Biología celular y molecular vinculada con la Ingeniería tisular ósea. Métodos: se realizó una búsqueda bibliográfica en SciELO Cuba y en Google académico durante el período de 1 de marzo al 28 de abril de 2018. Se evaluaron 134 artículos y el estudio se circunscribió a los 25 artículos que se enfocaban en estas temáticas de manera integral. Conclusiones: se ofreció una visión general de los avances que se han obtenido en la Biología celular y molecular, y en particular a: la aplicación de los factores de crecimiento en la Ingeniería del tejido óseo, así como sus futuras perspectivas. Se concluyó que es fundamental consolidar una base apropiada de conocimientos sobre la Biología celular y molecular y el desarrollo actual de la Ingeniería del tejido óseo.

ABSTRACT Introduction: scientific and technical advances in the field of cellular and molecular biology have allowed restoring and improving the function of organs and tissues injured by certain diseases and trauma. Tissue engineering is defined as the use of the principles and methods of Engineering, Biology and Biochemistry, which are aimed at understanding the structure and function of normal and pathological tissues, and the consequent development of biological substitutes to restore, maintain or improve their function. Objective: to carry out an approach to some aspects of cellular and molecular biology related to bone tissue engineering. Methods: a bibliographic review was carried out in SciELO Cuba and Google Scholar from March 1 to April 28, 2018. A number of 134 articles were evaluated and the study was limited to 25 articles that focused on these topics in an integral way. Conclusions: an overview of the advances that have been obtained in cellular and molecular biology was offered, particularly to the application of growth factors in bone tissue engineering, as well as its future perspectives. We concluded that it is essential to consolidate an appropriate knowledge base on cellular and molecular biology and the current development of bone tissue engineering.

In vivo and in vitro study of co-expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma / Estudo in vivo e in vitro da coexpressão de LMP1 e Cripto-1 em carcinoma nasofaríngeo

Abstract Introduction: Nasopharyngeal carcinoma, an epithelial-derived malignant tumor which because of its anatomical location and atypical early symptoms, when diagnosed invasion and metastasis often have occurred. This requires a better understanding of the development mechanism, identifying diagnostic markers, and developing new treatment strategies. Objective: To study the relationship of LMP1 and Cripto-1 in nasopharyngeal carcinoma. Methods: The expression of LMP1 and Cripto-1 in specimens obtained from nasopharyngeal carcinoma patients (n = 42) and nasopharyngitis patients (n = 22) were examined. The expression of LMP1 and Cripto-1 in LMP1-negative and LMP1-positive (CNE1-LMP1) cells were also examined. Results: The expression of LMP1 and Cripto-1 was significantly higher in nasopharyngeal carcinoma than in nasopharyngitis (p < 0.05). Their expression in nasopharyngeal carcinoma with metastasis were significantly higher than that without metastasis (p < 0.05), which was correlated with TNM staging (p < 0.05). High Cripto-1 expression and high proliferation rate were seen in CNE1-LMP1 cells. Conclusions: The expression of LMP1 and Cripto-1 in nasopharyngeal carcinoma is positively related. Their co-expression might contribute to the proliferation and metastasis of nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é um tumor maligno derivado do epitélio de localização anatômica recôndita e sintomas iniciais atípicos; quando diagnosticado, frequentemente invasão e metástases já ocorreram. Isso requer uma melhor compreensão do seu mecanismo de desenvolvimento, identificação dos marcadores diagnósticos e desenvolvimento de novas estratégias de tratamento. Objetivo: Estudar a relação de LMP1 e Cripto-1 no carcinoma nasofaríngeo. Método: A expressão de LMP1 e Cripto-1 em espécimes obtidos de pacientes com carcinoma de nasofaringe (n = 42) e pacientes com nasofaringite (n = 22) foi analisada. A expressão de LMP1 e Cripto-1 em células LMP1-negativas e LMP1-positivas (CNE1-LMP1) também foi analisada. Resultados: A expressão de LMP1 e Cripto-1 foi significantemente maior na presença de carcinoma nasofaríngeo do que na nasofaringite (p < 0,05). Sua expressão em carcinomas com metástase foi significantemente maior do que em casos sem metástase (p < 0,05), o que se correlacionou com o estadiamento TNM (p < 0,05). Uma alta expressão de Cripto-1 e alta taxa de proliferação foram observadas nas células CNE1-LMP1. Conclusões: A expressão de LMP1 e Cripto-1 é positivamente relacionada com carcinoma nasofaríngeo. Sua coexpressão pode ser atribuída à proliferação e metástase do tumor.

Level of Evidence and Industry Sponsorship Associated with Favorable Outcomes in Publications on Platelet-Rich-Plasma Therapy in Musculoskeletal Disorders / Nível de evidência e patrocínio industrial associado a desfechos favoráveis nas publicações sobre terapia com plasma rico em plaquetas nas doenças osteomusculares

Abstract Platelet-rich plasma is derived from centrifuging whole blood. There is increasing interest in the sports medicine and athlete community about providing endogenous growth factors directly to the injury site, using autologous blood products such as platelet-rich plasma. The aim of the present study is to evaluate the association between research financing, conflict of interests, level of evidence and author affiliation with the interpretation of results in articles published on platelet-rich plasma therapy in musculoskeletal ailments. A review of the current literature was performed. The outcome was classified as favorable or unfavorable. The declaration of conflict of interests and the type of funding was extracted from each article. The financing was classified as industry-sponsored; not industry-sponsored; or unidentifiable. The level of evidence was categorized from I to IV. Higher positive outcomes were observed in 134 studies with industry sponsorship compared with not industry-sponsored studies (odds ratio [OR]: 0.26; 95% confidence interval [95%CI]: 0.08-0.85; p < 0.05). Compared with level of evidence I, levels II and IV increase the probability of positive outcomes by 12.42 times (p < 0.01) and 10.97 times (p < 0.01) respectively. Proportionally, industry-sponsored studies are more likely to present positive results, as well as articles with a lower quality of evidence.

Resumo O plasma rico em plaquetas é derivado da centrifugação do sangue total. Há um interesse crescente, na medicina esportiva e na comunidade atlética, no fornecimento de fatores de crescimento endógeno diretamente ao sítio da lesão, usando componentes sanguíneos autólogos, como o plasma rico em plaquetas. O objetivo deste estudo é avaliar a associação entre financiamento de pesquisa, conflito de interesses, nível de evidência e afiliação dos autores com a interpretação dos resultados em publicações sobre terapia com plasma rico em plaquetas nas doenças osteomusculares. Foi realizada uma revisão da literatura atual. O desfecho foi classificado como favorável ou desfavorável. A declaração de conflito de interesses e o tipo de financiamento foram extraídos de cada artigo. O financiamento foi qualificado em patrocínio industrial; não patrocinado pela indústria; ou não identificável. O nível de evidência foi categorizado de I a IV. Foram obtidos os resultados positivos mais altos com 134 estudos financiados pelo setor industrial, em comparação com estudos não financiados pela indústria (razão de probabilidades [RP]: 0,26; intervalo de confiança de 95% [95%IC]: 0,08-0,85; p < 0,05). Em comparação com o nível de evidência I, os níveis II e IV aumentam a probabilidade de resultado positivo em 12,42 vezes (p < 0,01) e 10,97 vezes (p < 0,01), respectivamente. Demonstrou-se que, proporcionalmente, estudos patrocinados pela indústria têm maior probabilidade de apresentar resultados positivos, bem como artigos com menor qualidade de evidência.

Analysis of the chemerin and resistin adipokines in children and adolescents

SUMMARY OBJECTIVES To compare the serum concentrations of adipokines resistin and chemerin in children and adolescents with eutrophic and overweight and to evaluate their relationship with anthropometric, biochemical, and blood pressure variables. METHODS a cross-sectional epidemiological study was conducted with 234 students enrolled in public elementary schools in the city of Juiz de Fora / MG. Anthropometric evaluation, biochemistry, and blood pressure measurement were performed. Statistical analyzes included the Student-t or Mann-Whitney tests, Pearson or Spearman correlation, used according to the distribution of the variables, and linear regression analysis, by means of the evaluation of the effect of the independent variables on the serum levels of chemerin and resistin, adjusted for age and sex. For the data analysis, SPSS® software version 21.0 and STATA® version 10.1 were used, assuming a significance level of 5%. RESULTS the concentrations of chemerin were higher in eutrophic individuals than in those with excess weight (p> 0.05). In contrast, levels of resistin were higher in the young with excess weight than in the eutrophic ones (p <0.05). In the multiple linear regression analysis, the levels of chemerin were associated with the values of resistin, systolic, and diastolic blood pressure. Resistance levels maintained association only with BMI and chemerin values. CONCLUSION the adipokines analyzed presented a distinct profile in the groups of children and adolescents with eutrophic and overweight.

RESUMO OBJETIVOS Comparar as concentrações séricas das adipocinas resistina e quemerina em crianças e adolescentes com eutrofia e excesso de peso e avaliar sua relação com as variáveis antropométricas, bioquímicas e a pressão arterial. MÉTODOS Estudo epidemiológico transversal realizado com 234 estudantes matriculados em escolas públicas do ensino fundamental no município de Juiz de Fora/MG. Realizou-se avaliação antropométrica, bioquímica e aferição da pressão arterial. As análises estatísticas compreenderam os testes t de Student ou Mann-Whitney, correlação de Pearson ou Spearman, utilizados de acordo com a distribuição das variáveis, e análise de regressão linear, realizada por meio da avaliação do efeito das variáveis independentes nos níveis séricos de quemerina e resistina, ajustado por idade e sexo. Para a análise dos dados foram utilizados os softwares SPSS® versão 21.0 e Stata® versão 10.1, admitindo-se nível de significância de 5%. RESULTADOS As concentrações de quemerina foram maiores nos indivíduos eutróficos do que nos com excesso de peso (p>0,05). Em contrapartida, os níveis de resistina estiveram maiores nos jovens com excesso ponderal do que nos eutróficos (p<0,05). Na análise de regressão linear múltipla, os níveis de quemerina apresentaram associação com os valores de resistina, pressão arterial sistólica e diastólica. Os níveis de resistina mantiveram associação apenas com os valores de IMC e quemerina. CONCLUSÃO As adipocinas analisadas apresentaram perfil distinto nos grupos de crianças e adolescentes com eutrofia e com excesso de peso.

Comparação dos meios de preparação e preservação de membrana amniótica humana para uso no tratamento de doenças da superfície ocular / Comparison of the preparation and preservation techniques of amniotic membrane used in the treatment of ocular surface diseases

Resumo Atualmente a membra amniótica (MA) tem obtido importância devido à comprovada capacidade de reduzir inflamação, auxiliar a cicatrização e epitelização, possuindo propriedades antimicrobianas e antivirais, além de baixa imunogenicidade. As indicações de seu uso na oftalmologia têm aumentado muito nas duas últimas décadas. Objetivo: Descrever a estrutura básica e as propriedades biológicas da MA em relação aos componentes da sua matriz extracelular e fatores de crescimento, as consequências de diferentes técnicas empregadas na sua preservação e esterilização, métodos para remoção do epitélio e a comparação dos custos dos diferentes meios de conservação atualmente empregados. Métodos: Pesquisa nas bases de dados do Portal da Biblioteca Virtual em Saúde (BVS), Pubmed, Cochrane, Scielo e Lilacs com as palavras-chave: membrana amniótica, transplante, reconstrução da córnea, doenças da conjuntiva. Resultados: A literatura é vasta na descrição dos efeitos de diversos agentes e técnicas na preparação da MA, dentre elas sua preservação, esterilização e desepitelização. A membrana desnuda tem sido a escolha para a reconstrução da superfície ocular, pois facilita a cicatrização. Em relação aos agentes conservantes, o glicerol é o meio mais utilizado mundialmente pelo baixo custo e facilidade de manuseio. Conclusão: A comparação das diversas técnicas nos guia na elaboração de protocolos de preparo da MA para uso oftalmológico. A membrana desnuda facilita a cicatrização em relação a com células epiteliais. O glicerol é o meio de conservação mais utilizado pelo baixo custo e facilidade de manuseio.

Abstract Currently, the amniotic membrane (AM) has obtained importance due to its ability to reduce inflammation, helping in the healing and epithelialization processes, having antimicrobial and antiviral properties and low immunogenicity. Its indications in ophthalmology have increased considerably in the past two decades. Objective: To describe the basic structure and biological properties of the AM, the components of the extracellular matrix and growth factors, the consequences of different techniques used in its preservation, and sterilization methods for the epithelium removal. To compare the costs of the different preservation solutions currently employed. Study design: literature review. Methods: Research in BVS databases, PubMed, Cochrane, Scielo and Lilacs with keywords: amniotic membrane transplantation, corneal reconstruction, conjunctival diseases. Results: The literature is vast in describing the effects of different agents and techniques used in the preparation of MA, including its preservation, sterilization and desepithelization. The naked membrane is the choice to reconstruct the ocular surface, as it facilitates the healing course. Regarding the preservatives, glycerol is the most used worldwide due its low cost and easy handling. Conclusion: Comparing different techniques guides us in developing a MA preparation protocol for ophthalmic use. The naked membrane facilitates the healing process compared with the presence of epithelial cells. The glycerol is the most used preservation method because of its low cost and easy handling.

Anti-inflammation and anti-apoptosis effects of growth arrest-specific protein 6 in acute liver injury induced by LPS/D-GalN in mice

Abstract Purpose To investigate the effect of growth arrest-specific protein 6 (Gas6) on acute liver injury in mice and related mechanisms. Methods Thirty C57BL/6 (6-8 weeks old) mice were randomly divided into control, LPS/D-GalN, and LPS/D-GalN+Gas6 groups (10 mice in each group). The LPS/D-GalN group was intraperitoneally administered with LPS (0.25 mg/Kg) and D-GalN (400 mg/Kg) for 5h. The LPS/D-GalN+Gas6 group was intraperitoneally administered with rmGas6 one hour before intraperitoneal application of LPS/D-GalN. All subjects were sacrificed at 5 h for blood and tissue analysis. The expression of protein and mRNA was assessed by western blotting and RT-PCR, respectively. Results Compared with the control group, AST, ALT, IL-1β, TNF-α, IL-6 IL-10, MPO activity were increased in the LPS/D-GalN group. However, they were significantly inhibited by Gas6. Gas6 markedly suppressed the expression of apoptosis-related protein induced by LPS/D-GalN. Moreover, Gas6 attenuated the activation of the NF-κB signaling pathway in acute liver injury induced by LPS/D-GalN. Conclusions Gas6 alleviates acute liver injury in mice through regulating NF-κB signaling pathways. Gas6 can be a potential therapeutic agent in treating LPS/D-GalN-induced acute liver injury in the future.

Plasma rich in growth factors (PRGF) in non-surgical periodontal therapy: a randomized clinical trial

Abstract The aim of this split mouth, double blinded, randomized clinical trial was to evaluate the clinical efficacy of use of Plasma rich in growth factors (PRGF) as an adjunct to scaling and root planing (SRP) in the treatment of periodontal pockets. Twenty six patients (15 males, 11 females) diagnosed with generalized periodontitis with Pocket Depth > 5mm and plaque index score < 1.5, were randomly allocated by using computer generated random sequence, into two groups, one treated with intra-pocket application of PRGF adjunct to SRP and other with SRP alone. The clinical outcomes like pocket depth (PD), relative attachment level (RAL) and sulcus bleeding index (SBI) were assessed at baseline, 3 months and 6 months. Twenty two patients (44 sites) were analyzed at the end of 6 month follow-up, using SPSS 20.0v software. There was a significant statistical difference observed between both the groups favouring SRP +PRGF group in terms of PD (p = 0.007) and RAL (p = 0.021) at the end of 6 month follow-up. Also there was a statistical significant difference (< 0.001) at all time points compared to baseline, for all parameters in intra-group comparison. Moreover, the sites with PD>4mm necessitating further treatment after 6-month follow-up were significantly lesser for SRP+PRGF group. The use of PRGF technology in non-surgical periodontal therapy, by single intra-pocket application in to periodontal pockets as an adjunct to SRP, in chronic periodontitis patients, was found to be effective in reduction of pocket depth and gain in clinical attachment level.

Gingival recession treatment with concentrated growth factor membrane: a comparative clinical trial

Abstract Objective This clinical trial sought to evaluate the clinical effectiveness of concentrated growth factor (CGF) and compare it with connective tissue graft (CTG) with coronally advanced flap (CAF) in the treatment of Miller Class I gingival recessions (GR). Methodology This split-mouth study included 74 Miller Class I isolated (24 teeth) or multiple (50 teeth) GRs in 23 jaws of 19 patients. GRs were randomly treated using CGF (test group: 37 teeth; 12 teeth in isolated GRs, 25 teeth in multiple GRs) or CTG with CAF (control group: 37 teeth;12 teeth isolated GRs, 25 teeth in multiple GRs). Clinical variables, plaque index (PI), gingival index (GI), probing depth (PD), recession depth (RD), recession width (RW), clinical attachment level (CAL), keratinized tissue thickness (KTT), keratinized tissue width (KTW), and root coverage (RC) were assessed at the baseline as well as at three and six months post-surgery. Healing index (HI) were obtained in the second and third weeks post-surgery. Postoperative pain was assessed for the first seven days using a horizontal visual analog scale (VAS). Results No significant change was observed in PI, GI, or PD values in either the intergroup or the intragroup comparisons. A statistically significant decrease was observed in CAL, RD, and RW, and KTT increased in all groups at three and six months compared with the baseline. The control group had greater increases in KTW, KTT, and RC at three and six months. No significant difference was found in CAL or RD at the third and sixth months between the two groups. Healing was found to be similar for both groups in the second and third weeks post-surgery. The VAS values in the control group were higher than in the test group, especially at the second, fourth, fifth, and seventh days postoperatively. Conclusions CTG is superior to CGF with CAF for increasing KTT, KTW, and RC. CGF may be preferable due to decreased postoperative pain.