Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling

The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC 50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14+ human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK. © FASEB.

Tumor venéreo transmissível espontâneo canino: a inserção do transposon line-1 no gene C-MYC e os critérios de malignidade

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expressão de c-MYC, NKX3.1 e E-Caderina por Imuno-Histoquímica em Microarranjo de Tecido (TMA) de Lesões Pré- Neoplásicas e Neoplásicas na Próstata De Cães

Pós-graduação em Medicina Veterinária - FMVZ

Padrão de uso de alcool e outras drogas entre estudantes de Cascavel - PR

Pós-graduação em Educação - FFC

Perfil global de expressão de micro-RNAs no músculo esquelético de ratos com insuficiência cardíaca

Pós-graduação em Ciências Biológicas (Genética) - IBB

A saúde na roça: estudo hermenêutico de um serviço da saúde da família

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A metamorfose seniana: poesia e crítica na obra de Jorge de Sena

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo clínico e genético de uma família portadora de carcinoma medular de tireóide

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Alterações comportamentais, psicológicas, de higiene bucal e presença de microrganismos superinfectantes e viruses da família herpesviridae em pacientes mantidas em programa de desintoxicação para dependentes químicos

Pós-graduação em Odontologia - FOA

Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95%) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85%) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

Qualidade de vida de mulheres alcoolistas atendidas em serviço ambulatorial

Pós-graduação em Saúde Coletiva - FMB

Avaliação de características morfológicas e morfométricas dos pêlos de roedores da Mata Atlântica do estado de São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da pressão na obtenção e nas propriedades óticas e sensoras de filmes finos à base de 'SN''O IND. 2' com a adição de 'ZNO'

Pós-graduação em Química - IQ

Qualidade da aplicação de inseticida em amendoim (arachis hypogaea l.), com e sem adjuvantes na calda, sob chuva simulada

The present work aimed to evaluate the volumetric distribution profiles, droplet spectra, surface tension, contact angle of droplet and the spraying liquid deposition over the peanut leaves (Arachis hypogaea L.), under artificial rain, in comparison with deposition without rain, using two hydraulic nozzle models of plain fan and insecticide spraying liquids with and without adjuvants addition. It were used a patternator for volumetric distribution analysis, a laser particles analyzer to evaluate droplet spectra produced by SF 110015 and XR 110015 nozzles and tensiometer for droplet tension and contact angle. The spraying liquids evaluated were: water, lambda-cialotrina, lambda-cialotrina + nitrogen fertilizer and lambda-cialotrina + mineral oil. All experiments followed a completely randomized design. Data were submitted to variance analysis by F test and the means comparisons by Scott-Knott test at 5% of probability. According to the results, it must be considered the maximum spacing in spray boom usage of 50 and 90 cm between the nozzles SF110015 and XR110015, respectively. The adjuvants effects on droplet spectra have shown addicted to the nozzle and the product used, and the adjuvants addition to the spraying liquid affected the potential risk of drift; The Volumetric Median Diameter (VMD) of produced droplets by nozzles filled into thin class and were not influenced by the adjuvants. The nitrogen fertilizer adjuvant may be indicated to promote improvements on coverage and droplet deposition on target.

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)