Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer / 生物医学工程学杂志

Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.

Updating the role of matrix metalloproteinases in mineralized tissue and related diseases

Abstract Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.

La singularidad de los maxilares dentro del sistema esquelético / Singularity of the jaws within the skeletal system

En la odontología es frecuente que se describa la peculiaridad de los huesos maxilares en cuanto a la resistencia a las infecciones en comparación con otros huesos de la economía. O que se plantée un desafío cuando es necesario tomar una decisión acerca de aplicar diferentes conductas terapéuticas en pacientes con patologías óseas sistémicas. Por ello, esta actualización tuvo como objetivo realizar una revisión de la bibliografía para integrar y evidenciar las diferencias y similitudes entre los diferentes huesos de la economía haciendo hincapié en los huesos maxilares. Si bien éstos poseen una gran cantidad de similitudes con el resto de los huesos, también presentan diferencias que los hacen entidades únicas dentro del sistema esquelético como el origen embriológico en las células de las crestas neurales, su alta tasa de remodelación, sin olvidar que estos huesos alojan a órganos que poseen una parte de su estructura en el medio interno y otra porción en medio externo de la cavidad bucal: las piezas dentarias (AU)

Evaluation of decellularized matrix and ß-tricalcium phosphate as biomaterials for bone neoformation: in vivo study / Evaluación de la matriz descelularizada y ß-fosfato tricálcico como biomateriales para neoformación ósea: estudio in vivo

The aim of this study was to evaluate histologically the effect of two biomaterials, a biomaterial derived from porcine Urinary submucosa Bladder Matrix (UBM) and beta-TriCalcium Phosphate (ß-TCP), on bone defects. Twenty male New Zealand rabbits were used; the models were divided in two groups: the UBM group; the ß-TCP group, and a Negative Control (NC) group. Five-mm defects were created in the femur of each model and then the different biomaterials were set in place depending on each group. At 4 and 8 weeks, the animals in the models were sacrificed and samples of the defect site were collected to perform a Hematoxylin and Eosin stain (H&E). Histologically, ß-TCP group at 4 and 8 weeks presented neoformation of bone-like and cartilage-like tissue, with the presence of inflammatory infiltrate; at 4 and 8 weeks, the UBM group presented neoformation of bone-like and cartilage-like tissue with a low presence of inflammatory infiltrate, and the NC group presented the formation of connective tissue and, in a low proportion, neoformation of bone tissue and cartilage. Both biomaterials, UBM and ß-TCP, exhibited the capacity to promote bone neoformation; however, the UBM-based biomaterial produced a better-organized tissue with a lower inflammatory response compared with the ß-TCP group.

El objetivo de este estudio fue evaluar histológicamente el efecto de dos biomateriales: derivado de matriz de submucosa de vejiga urinaria porcina (UBM) y b-fosfato tricálcico (ß-TCP) en defectos óseos. Veinte conejos macho de raza Nueva Zelanda fueron empleados para este estudio; los modelos fueron divididos en dos grupos: UBM, ß-TCP y un grupo control negativo. Se crearon defectos de 5 mm en el fémur de cada uno de los modelos y posteriormente se colocó el biomaterial correspondiente de acuerdo a cada uno de los grupos. A las 4 y 8 semanas los modelos fueron sacrificados y se tomaron muestras del sitio del defecto óseo para realizar una tinción de Hematoxilina y Eosina. Histológicamente el grupo de ß-TCP tanto a las 4 como a las 8 semanas mostró neoformación de tejido óseo y tejido cartilaginoso con presencia de infiltrado inflamatorio; el grupo de UBM a las 4 y 8 semanas presentó neoformación de tejido óseo, tejido cartilaginoso y un bajo infiltrado inflamatorio; el grupo control negativo presentó formación de tejido conectivo y en baja proporción neoformación de tejido óseo y cartílago. Ambos biomateriales, UBM y ß-TCP mostraron la capacidad de promover la neoformación de tejido óseo; sin embargo, el biomaterial basado en UBM produjo un tejido mejor organizado y un menor infiltrado inflamatorio en comparación con el ß-TCP.

A supramolecular look at microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny / Uma visão supramolecular sobre a regulação microambiental de células tronco epiteliais limbais e a diferenciação de sua progênie

ABSTRACT Various approaches have been taken to improve our knowledge of the microenvironmental regulation of limbal epithelial stem cells. Researchers have extensively investigated the roles of growth factors, survival factors, cytokines, enzymes, and permeable molecules secreted by the limbal cells. However, recent evidence suggests that stem cell fate (i.e., self-renewal or differentiation) can also be influenced by biophysical and mechanical cues related to the supramolecular organization and the liquid crystalline (mesophase) nature of the stromal extracellular matrix. These cues can be sensed by stem cells and transduced into intracellular biochemical and functional responses, a process known as mechanotransduction. The objective of this review is to offer perspectives on the supramolecular microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny.

RESUMO Muitas abordagens têm sido utilizadas para ampliar entendimentos sobre a regulação microambiental das células tronco epiteliais limbais. Neste contexto, pesquisadores têm exaustivamente investigado a participação de fatores de crescimento, fatores de sobrevida, citocinas, enzimas e moléculas permeáveis secretadas pelas células limbais. Entretanto, evidências recentes sugerem que o destino (ie. autorrenovação ou recrutamento para a via de diferenciação) das células tronco também sofre influência de estímulos biofísicos ou mecânicos relacionados à organização supramolecular e à natureza liquido-cristalina (mesofases) da matriz extracelular estromal. Esses estímulos podem ser percebidos e traduzidos pelas células tronco em sinais bioquímicos que geram respostas funcionais, através de um processo designado de mecanotransdução. Objetiva-se, com a presente revisão, oferecer ao leitor perspectivas supramoleculares sobre a regulação microambiental das células tronco epiteliais limbais e a diferenciação de sua progênie.

Acellular human glans extracellular matrix as a scaffold for tissue engineering: in vitro cell support and biocompatibility

ABSTRACT Objectives: Diseases of the genitourinary tract can lead to significant damage. Current reconstructive techniques are limited by tissue availability and compatibility. This study aims to assess if the decellularized human glans can be used as a biomaterial for penile reconstruction. Materials and Methods: Samples of the glans matrices were descellularized. We evaluate the presence of collagen type I and III, and elastic fibers. Biocompatibility assays were performed to assess the cytotoxic and non-cytotoxic interactions between the acellular matrix and 3T3 cells. The matrices were seeded with mesenchymal stem cells and were assessed for viability and integration of these cells. Biomechanical tests in native tissue, descellularized matrix and seeded matrix were performed to characterize their biomechanical properties. Results: The tissue architecture of the decellularized matrix of human glans was preserved as well as the maintenance of the biomechanical and biological properties. The analyzes of glans seeded with mesenchymal stem cells revealed the integration of these cells to the matrices, and its viability during two weeks "in vitro". Conclusion: The decellularization process did not alter the biological and biomechanical characteristics of the human glans. When these matrices were seeded they were able to maintain the cells integrity and vitality.

Cells involved in extracellular matrix remodeling after acute myocardial infarction / Células envolvidas no remodelamento da matriz extracelular após infarto agudo do miocárdio

Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation. Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct. .

Objetivo Avaliar os efeitos da transferência gênica do VEGF165 no processo de remodelamento da matriz extracelular após infarto agudo do miocárdio. Métodos Ratos Wistar foram submetidos ao infarto do miocárdio por ligação da artéria coronária descendente esquerda, e a fração de ejeção de ventrículo esquerdo foi utilizada para classificar os infartos em grandes e pequenos. Os animais foram divididos em grupos de dez animais, de acordo com o tamanho do infarto (grande ou pequeno), e receberam ou não tratamento com o VEGF165. A avaliação dos diferentes marcadores foi realizada por imuno-histoquímica e quantificação digital. Os anticorpos primários utilizados foram antifibronectina, antivimentina, anti- CD44, anti-E-caderina, anti-CD24, anti-alfa-1-actina e anti-PCNA. Os resultados foram representados como média e erro padrão, e analisados por ANOVA, sendo considerado estatisticamente significativo se p≤0,05. Resultados Houve aumento significativo da expressão de marcadores de células indiferenciadas, como fibronectina (proteína presente na matriz extracelular) e CD44 (glicoproteína presente nas células endoteliais). Entretanto, houve diminuição da expressão de vimentina e PCNA, indicando possível diminuição do processo de proliferação celular após o tratamento com VEGF165. Os marcadores de células diferenciadas, E-caderina (proteína de adesão entre as células do miocárdio), CD24 (proteína presente nos vasos sanguíneos) e alfa-1-actina (marcador especifico de miócitos) também apresentaram maior expressão nos grupos submetidos à terapia gênica, comparativamente com o grupo não tratado. O valor obtido pela relação entre alfa-1-actina e vimentina foi aproximadamente três vezes maior nos grupos tratados com VEGF165, indicando maior diferenciação tecidual. Conclusão O papel dos miócitos se mostrou importante no processo de remodelamento tecidual, confirmando que o VEGF165 parece conferir um efeito protetor no tratamento do infarto agudo do miocárdio. .

Integrin-ß1, not integrin-ß5, mediates osteoblastic differentiation and ECM formation promoted by mechanical tensile strain

BACKGROUND: Mechanical strain plays a great role in growth and differentiation of osteoblast. A previous study indicated that integrin-ß (ß1, ß5) mediated osteoblast proliferation promoted by mechanical tensile strain. However, the involvement of integrin-ß; in osteoblastic differentiation and extracellular matrix (ECM) formation induced by mechanical tensile strain, remains unclear. RESULTS: After transfection with integrin-ß1 siRNA or integrin-ß5 siRNA, mouse MC3T3-E1 preosteoblasts were cultured in cell culture dishes and stimulated with mechanical tensile strain of 2500 microstrain (µÎµ) at 0.5 Hz applied once a day for 1 h over 3 or 5 consecutive days. The cyclic tensile strain promoted osteoblastic differentiation of MC3T3-E1 cells. Transfection with integrin-ß1 siRNA attenuated the osteoblastic diffenentiation induced by the tensile strain. By contrast, transfection with integrin-ß5 siRNA had little effect on the osteoblastic differentiation induced by thestrain. At thesametime, theresultofECM formation promoted by the strain, was similar to the osteoblastic differentiation. CONCLUSION: Integrin-ß1 mediates osteoblast differentiation and osteoblastic ECM formation promoted by cyclic tensile strain, and integrin-ß5 is not involved in the osteoblasts response to the tensile strain.

Alterações da matriz extracelular causadas pelo diabetes: o impacto sobre a continência urinária / Changes in the extracellular matrix due to diabetes and their impact on urinary continence

A prevalência de incontinência urinária em gestantes diabéticas é significantemente elevada e persiste por até dois anos após o parto cesárea, podendo ser a sequela mais frequente da hiperglicemia gestacional comparada a outras complicações. Dessa forma, identificar os fatores de risco para o desenvolvimento da incontinência urinária em diabéticas é o principal objetivo na prevenção dessa condição tão comum. Pesquisas recentes apontam que não apenas o músculo uretral mas também a matriz extracelular uretral desempenham papel importante no mecanismo da continência urinária. Os trabalhos do nosso grupo de pesquisa evidenciaram que, em ratas, o diabetes durante a prenhez lesa a matriz extracelular e o músculo estriado uretral, o que pode explicar a alta prevalência de incontinência e disfunção do assoalho pélvico em mulheres com diabetes mellitus gestacional. O diabetes exerce efeito sobre a expressão, organização e alteração dos componentes da matriz extracelular em diversos órgãos, e a remodelação do tecido e a fibrose parecem ser uma consequência direta dele. Assim, a compreensão do impacto de fatores de risco modificáveis, como o diabetes, permitirá que, utilizando estratégias preventivas, reduzamos as taxas de incontinência urinária, bem como os custos de assistência à saúde, e melhoremos a qualidade de vida das mulheres, especialmente na gestação e no pós-parto.

The prevalence of urinary incontinence in diabetic pregnant women is significantly high two years after cesarean section. Incontinence can be the most common consequence of hyperglycemia compared to other complications. Thus, identifying the risk factors for the development of urinary incontinence in diabetes is the major aim in the prevention of this very common condition. Recent surveys have shown that not only muscle but also the urethral extracellular matrix play an important role in the mechanism of urinary continence. Translational work on rats by our research group showed that diabetes during pregnancy damages the extracellular matrix and urethral striated muscle, a fact that may explain the high prevalence of urinary incontinence and pelvic floor dysfunction in women with gestational diabetes mellitus. Diabetes affects the expression, organization and change in extracellular matrix components in different organs, and tissue remodeling and fibrosis appear to be a direct consequence of it. Therefore, understanding the impact of modifiable risk factors, such as diabetes, which involves using preventive strategies, can reduce the rates of urinary incontinence and the health care costs, and improve the quality of life of women, especially during pregnancy and postpartum.

Apicoformación en dientes permanentes jóvenes / Apexification in young permanent teeth

La endodoncia regenerativa desarrolla técnicas basadas en ingeniería de tejidos para reponer tejidos perdidos. Con el desarrollo del conocimiento actual de la biología molecular, la microbiología y la genética, entre otras disciplinas, estamos en condiciones de introducirnos en el conocimiento de las cascadas de señales intracelulares desencadenadas por los sistemas complejos autoorganizados en sus procesos de autoreparación. Esto nos permite definir los pasos que debemos efectuar para la regeneración ad integrum de los tejidos que conforman el sistema de inserción dental

Alteração precoce da matriz extracelular e parâmetros diastólicos na síndrome metabólica / Early change of extracellular matrix and diastolic parameters in metabolic syndrome

FUNDAMENTOS: Síndrome Metabólica (SM) está associada com maior risco cardiovascular, porém não está claro se as alterações miocárdicas presentes nessa condição, como a disfunção diastólica, são consequência de mecanismos sistêmicos ou de efeitos diretos no miocárdio. OBJETIVOS: Comparar função diastólica, biomarcadores de atividade da Matriz Extracelular (MEC), inflamação e estresse hemodinâmico, em pacientes com SM e controles saudáveis. MÉTODOS: Pacientes com SM (n = 76) e controles saudáveis (n = 30) foram avaliados clinicamente e submetidos a exame ecocardiográfico e mensuração dos níveis plasmáticos de metaloproteinase-9 (MMP9), inibidor tecidual da metaloproteinase-1 (TIMP1), proteína C reativa ultrassensível (PCR-us), resistência insulínica (HOMA-RI) e NT-proBNP. RESULTADOS: O grupo SM apresentou menor onda E' (10,1 ± 3,0 cm/s vs. 11,9 ± 2,6 cm/s, p = 0,005), maiores valores para onda A (63,4 ± 14,1 vs. 53,1 ± 8,9 cm/s, p < 0,001), razão E/E'(8,0 ± 2,2 vs. 6,3 ± 1,2; p < 0,001), MMP9 (502,9 ± 237,1 vs. 330,4 ± 162,7 ng/mL, p < 0,001), PCR-us (p = 0,001) e HOMA-RI (p < 0,001), sem diferença nos níveis de TIMP1 e NT-proBNP. Na análise multivariada, apenas MMP9 foi independentemente associada a SM. CONCLUSÃO: Pacientes com SM apresentaram diferenças em medidas ecocardiográficas de função diastólica, na atividade da MEC, PCR-us e HOMA-RI em relação aos controles. Porém, somente MMP9 foi independentemente associada com SM. Esses achados sugerem que os efeitos precoces da SM sobre a atividade da MEC podem não ser detectados nas medidas ecocardiográficas de função diastólica usuais.

BACKGROUND: Metabolic syndrome (MS) is associated with increased cardiovascular risk. It is not clear whether myocardial changes showed in this syndrome, such as diastolic dysfunction, are due to the systemic effects of the syndrome, or to specific myocardial effects. OBJECTIVES: Compare diastolic function, biomarkers representing extracellular matrix activity (ECM), inflammation and cardiac hemodynamic stress in patients with the MS and healthy controls. METHODS: MS patients (n=76) and healthy controls (n=30) were submitted to a clinical assessment, echocardiographic study, and measurement of plasma levels of metalloproteinase-9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), ultrasensitive-reactive-C-Protein (us-CRP), insulin resistance (HOMA-IR) and natriuretic peptide (NT-proBNP). RESULTS: MS group showed lower E' wave (10.1 ± 3.0 cm/s vs 11.9 ± 2.6 cm/s, p = 0.005), increased A wave (63.4 ± 14.1 cm/s vs. 53.1 ± 8.9 cm/s; p < 0.001), E/E' ratio (8.0 ± 2.2 vs. 6.3 ± 1.2; p < 0.001), MMP9 (502.9 ± 237.1 ng/mL vs. 330.4±162.7 ng/mL; p < 0.001), us-CRP (p = 0.001) and HOMA-IR (p < 0.001), but no difference for TIMP1 or NT-proBNP levels. In a multivariable analysis, only MMP9 was independently associated with MS. CONCLUSION: MS patients showed differences for echocardiographic measures of diastolic function, ECM activity, us-CRP and HOMA-IR when compared to controls. However, only MMP9 was independently associated with the MS. These findings suggest that there are early effects on ECM activity, which cannot be tracked by routine echocardiographic measures of diastolic function.

Desnutrição materna durante a lactação em ratos Wistar: efeitos sobre as fibras elásticas da matriz extracelular na traqueia dos filhotes / Maternal malnutrition during lactation in Wistar rats: effects on elastic fibers of the extracellular matrix in the trachea of offspring

OBJETIVO: Investigar os efeitos da desnutrição proteica materna durante a lactação sobre as fibras elásticas da traqueia de filhotes de ratos Wistar. MÉTODOS: Ao nascimento, 12 filhotes machos de duas ratas Wistar foram igualmente divididos em dois grupos: grupo controle, cuja mãe recebeu água e dieta padrão de laboratório ad libitum durante a lactação, e grupo restrição proteica (RP), cuja mãe recebeu água ad libitum e dieta isoenergética com RP (8% de proteína). Aos 21 dias de vida, os filhotes foram sacrificados, e suas traqueias foram ressecadas. As fibras elásticas foram coradas pelo método de resorcina-fucsina de Weigert (precedido de oxidação) e avaliadas sob microscopia óptica. As determinações morfométricas foram feitas por estereologia, utilizando o método de contagem de pontos, e expressas em densidade volumétrica. RESULTADOS: As fibras elásticas foram identificadas abaixo da mucosa traqueal, sendo a maioria em distribuição longitudinal. Além disso, camadas circulares bem definidas de fibras elásticas envolviam as superfícies interna e externa do anel cartilaginoso. Não houve diferenças entre os grupos quanto à organização e distribuição das fibras elásticas. A densidade volumétrica das fibras elásticas dos filhotes nos grupos controle e RP foi de, respectivamente, 2,46 ± 0,99% e 3,25 ± 1,13% (p < 0,01). CONCLUSÕES: Nossos resultados sugerem que a densidade volumétrica de fibras elásticas é maior em filhotes de ratos alimentados por fêmeas submetidas a dieta com RP do que naqueles de mães recebendo dieta normal.

OBJECTIVE: To investigate the effects of maternal protein malnutrition during lactation on the elastic fibers in the tracheas of Wistar rat pups. METHODS: At delivery, 12 male pups of two Wistar rat dams were equally divided into two groups: control, in which the dam received water and standard rat chow ad libitum during lactation; and protein-restricted (PR), in which the dam received water ad libitum and an isoenergetic PR diet (8% protein). At 21 days of age, the pups were killed and their tracheas were excised. The elastic fibers were stained with Weigert's resorcin-fuchsin (after oxidation) and evaluated under light microscopy. Morphometric determinations were performed by stereology, with the point-counting method, and expressed as volumetric densities. RESULTS: Elastic fibers, most having a longitudinal distribution, were identified beneath the tracheal mucosa. In addition, well-defined circular layers of elastic fibers were found around the inner and outer surfaces of the cartilaginous ring. There were no differences between the groups regarding the organization and distribution of the elastic fibers. The volumetric density of the elastic fibers of the pups in the control and PR groups was 2.46 ± 0.99% and 3.25 ± 1.13%, respectively (p < 0.01). CONCLUSIONS: The volumetric density of elastic fibers appears to be greater in rat pups breastfed by dams receiving a PR diet than in those breastfed by dams receiving a normal diet.

Elementos da matriz extracelular da cérvice uterina e trabalho de parto prematuro / Elements of extracellular matrix from uterine cervix and premature labor

As taxas de prematuridade não atingem quedas significativas, mesmo em países desenvolvidos, alertando os pesquisadores a buscarem alternativas clínico-farmacológicas na prevenção desta enfermidade obstétrica. A matriz extracelular ocupa espaço relevante na maturação cervical, e seu entendimento é fundamental para possíveis ações preventivas. Destaca-se a provável correlação dos níveis locais de glicosaminoglicanos na prevenção do parto prematuro por inibir processos inflamatórios na cérvice uterina

The preterm delivery rates do not decrease significantly, even in developed countries, prompting researchers to seek pharmacological and clinical alternatives to prevent this obstetrics disorder. The extracellular matrix is important in cervical length, and its understanding is essential for possible preventive actions. We emphasize the probable correlation of the local levels of glycosaminoglycans to prevent premature labor by inhibiting inflammatory processes from uterine cervix

Control of the skin scarring response

There comes a time when the understanding of the cutaneous healing process becomes essential due to the need for a precocious tissue repair to reduce the physical, social, and psychological morbidity. Advances in the knowledge on the control of interaction among cells, matrix and growth factors will provide more information on the Regenerative Medicine, an emerging area of research in medical bioengineering. However, considering the dynamism and complexity of the cutaneous healing response, it is fundamental to understand the control mechanism exerted by the interaction and synergism of both systems, cutaneous nervous and central nervous, via hypothalamus hypophysis-adrenal axis, a relevant subject, but hardly ever explored. The present study reviews the neuro-immune-endocrine physiology of the skin responsible for its multiple functions and the extreme disturbances of the healing process, like the excess and deficiency of the extracellular matrix deposition.

Aproxima-se uma época na qual é fundamental a compreensão do processo cicatricial cutâneo frente à necessidade da restauração tecidual precoce, visando a diminuição das morbidades física, social e psicológica. O avanço no conhecimento acerca do controle das interações entre as células, a matriz e os fatores de crescimento dará maiores informações à Medicina Regenerativa, área de pesquisa emergente da bioengenharia médica. Entretanto, diante do dinamismo e complexidade da resposta cicatricial cutânea torna-se indispensável o entendimento do mecanismo de controle exercido pela interação e sinergismo do sistema nervoso cutâneo e o sistema nervoso central, via eixo hipotálamo-hipófise-adrenal, tema relevante, porém, pouco abordado. O presente estudo revisa a fisiologia neuro-imuno-endócrina da pele, responsável por suas múltiplas funções, e os distúrbios extremos do processocicatricial, como o excesso e deficiência de deposição da matriz extracelular.

Aspectos celulares da cicatrização: [revisão] / Cellular aspects of wound healing: [review]

O processo cicatricial compreende uma sequência de eventos moleculares e celulares que interagem para que ocorra a restauração do tecido lesado. Desde o extravasamento de plasma, com a coagulação e agregação plaquetária até a reepitelização e remodelagem do tecido lesado o organismo age tentando restaurar a funcionalidade tecidual. Assim, este trabalho abrange os diversos aspectos celulares envolvidos no processo cicatricial, bem como os principais medicamentos utilizados no tratamento de patologias relacionadas às deficiências na cicatrização. São abordados também, os aspectos econômicos referentes, sobretudo, às feridas crônicas de pés diabéticos.

Wound healing is a dynamic interactive process that involves a sequence of molecular and cellular events. Recent advances in cellular and molecular biology have greatly expanded our understanding of the biological process involved in wound repair and tissue regeneration. From plasma extravasation, with coagulation and platelet aggregation, to reepithelialization and remodeling of injured tissue, the organism acts by trying to restore functionality tissue. Thus, the present study encompasses several cellular aspects involved in the wound healing process, as well as the main drugs used in treating the pathology related to wound healing complications. Economic aspects are also addressed, mainly related to chronic wounds of diabetic feet.

Las proteasas en la progresión neoplásica / Proteases in cancer progression

La invasión y la metástasis son los eventos más importantes en la progresión del cáncer, en los cuales están implicadas muchas moléculas, entre ellas, las proteasas. Éstas desempeñan un papel importante en etapas tempranas de la carcinogénesis, en la invasión, en fenómenos asociados como la angiogénesis y en la metástasis, principalmente por su capacidad para degradar componentes de la matriz extracelular, aunque sus sustratos son de naturaleza diversa: citocinas, quimiocinas, factores de crecimiento (b- FGF, HGF, VEGF) y de muerte celular, cistatina-C, galectina, procolágena y otras proteasas, que pueden favorecer o inhibir la progresión neoplásica. Las proteasas son también moléculas de señalización que modulan a otras moléculas; forman cascadas, circuitos e incluso redes, que en conjunto determinan parte del potencial maligno. Se sabe que tanto la célula tumoral como las del estroma secretan diversos factores que regulan directa e indirectamente la expresión de proteasas en el microambiente tumoral. Esta revisión proporciona un panorama breve y actualizado sobre la participación de las proteasas en la progresión neoplásica.

Invasion and metastasis are the most important events in cancer progression. In these two phases, several molecules are implicated and have been long associated with several forms of cancer. Proteases play a critical role not only in tumor cell invasion, but also in the earliest stages of carcinogenesis and its associated changes: angiogenesis and metastasis. Aside from their ability to degrade the extracellular matrix, facilitate invasion and metastasis, proteases target a great variety of substrates that favor or inhibit cancer progression: b-FGF, HGF, VEGF, cell death receptors, cistatin-C, galectin, procollagen, and other proteases. Proteases are also signaling molecules that modulate other molecules by underlying pathways in addition to their degradative role. Proteases form interconnected cascades, circuits and networks that bring about the tumor's potential for malignancy. Although, proteases are regulated by diverse molecules, it is known that tumoral and stromal cells secrete several biological molecules, including cytokines and chemokines that directly or indirectly regulate the protease-expression within the tumor's microenvironment. The present review briefly summarizes some of the major aspects associated with the role of proteases in cancer progression.

Análise do comportamento biológico de heteroenxertos descelularizados e homoenxertos criopreservados: estudo em ovinos / Decellularized heterografts versus cryopreserved homografts: experimental study in sheep model

OBJETIVO: Este estudo avalia o comportamento biológico dos heteroenxertos porcinos descelularizados (Grupo Desc) comparados com os homoenxertos criopreservados (Grupo Crio) implantados em carneiros jovens. MÉTODOS: Foram implantados em cinco animais heteroenxertos pulmonares porcinos descelularizados e em outros cinco, homoenxertos pulmonares criopreservados. Os animais apresentaram seguimento médio de 280 ± 14 dias. O diâmetro valvar foi medido por ecocardiografia, a qual foi realizada no 30º pós-operatório e antes do explante. As valvas foram também avaliadas macroscopicamente. A avaliação histológica foi realizada utilizando-se coloração de H.E., Gomori e Weigert e imunohistoquímica (Fator VIII, CD3, Vimentina e CD68). A quantificação de cálcio foi realizada utilizando-se espectrometria de absorção atômica. RESULTADOS: Houve um óbito no Grupo Desc por endocardite. As valvas do Grupo Crio apresentaram decréscimo na celularidade, enquanto que as valvas do Grupo Desc demonstraram repovoamento da matriz com células endoteliais e intersticiais. No grupo Crio, observou-se perda na densidade e desarranjo da arquitetura das fibras colágenas. A espectrometria de absorção atômica demonstrou maior calcificação no conduto e nas cúspides dos enxertos criopreservados quando comparados aos descelularizados (P=0,016). O diâmetro médio valvar no explante foi significantemente maior no Grupo Desc (P=0,025). CONCLUSÃO: Heteroenxertos descelularizados apresentam um comportamento biológico diferente quando comparados aos homoenxertos criopreservados, tornando-se repovoados por células com características de fibroblastos e células endoteliais. A matriz permaneceu bem preservada, o que possibilitou um processo de regeneração celular.

OBJECTIVES: The aim of this study is to assess the biological behaviour of porcine decellularized heterografts (Desc group) compared with cryopreserved homografts (Crio group) implanted in juvenile sheep. METHODS: Decellularized porcine pulmonary heterografts were implanted in five animals and cryopreserved pulmonary homografts in another five. The animals were followed-up for a mean of 280 ± 14 days. The valve diameter was measured by echocardiography, which was performed at the 30th postoperative day, and before the explantation. The valves were also assessed macroscopically. Histological evaluation was performed using H.E., Gomori and Weigert staining. Immunohistochemistry specified different cell types (Factor VIII, CD3, Vimentin and CD68). Calcium quantity was analyzed using atomic absortion spectometry. RESULTS: There was one death in the Desc group due to endocarditis. The valves of Crio group showed decrease in the cellularity whereas the valves of Desc group showed matrix repopulation with endothelial and interstitial cells. Loss of collagen density and disarrangement of the normal fiber architecture was observed in Crio group. Calcium content demonstrated higher levels on the cusps and conduits in Crio group comparatively with Desc group. (P=0.016). The mean valvular diameter at the explantation was significantly increased (P=0.025) in the Desc group. CONCLUSIONS: Decellularized heterografts had a different biological behaviour when compared to cryopreserved homografts and become repopulated by cells with fibroblasts and endothelial cells characteristics. The matrix was preserved and some regenerative potential was present

Alteração da matriz extracelular da cérvice uterina durante a gestação / Changes in the extracellular matrix of the uterine cervix during pregnancy

A matriz extracelular do colo uterino sofre importantes mudanças em sua composição no decorrer da gestação e principalmente no período peripartal. Tais mudanças são necessárias para transformar o colo uterino imaturo, uma estrutrura fibrosa, em um órgão complacente o bastante para a passagem do feto no trabalho de parto. Conhecer melhor todo o processo de amadurecimento cervical é de fundamental importância para obterem-se melhores resultados na indução do parto.