899 resultados para Synovial lining cells, Hyaluronan, HAS, IL-1 beta, TMJ
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Pós-graduação em Odontologia Restauradora - ICT
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Species of the genus Qualea are used by the Brazilian public as a natural anti-inflammatory. Based on this evidence, we evaluated the effects of terpene fractions (βF and TF) obtained from Qualea multiflora on nitric oxide production (Griess assay), cytokines (IL-1, IL-10, IL-12, and TNF-a) and the transcription factor NF-κB by peritoneal macrophages. Since there is a relationship between inflammation and cancer, the cytotoxicity of βF and TF against mammary tumoural cell lineage, and macrophages was evaluated. Inhibition levels close to 90% of the production of NO, IL-1, IL-12 and TNF-a; about 32% of NF-κB; and a large stimulation of IL-10 production (close to the positive control) by peritoneal macrophages were observed in response to βF and TF which are correlated with anti-inflammatory activity. Additionally, the samples showed exceptional cytotoxic activity against tumoural cells but not against macrophages. Since anti-inflammatory activity is important in tumour inhibition, further examination of potential anti-cancerous activity of Qualea multiflora is warranted.
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Pós-graduação em Odontologia - FOA
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P = 0.003) in precursor B-cell Ph(-) ALL patients (n = 147) treated with a contemporary polychemotherapy protocol.
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Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense. Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN. Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. In the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO. Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated. (C) 2012 Elsevier Inc. All rights reserved.
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Nicotinic acetylcholine receptors (nAChRs) have been studied in detail with regard to their interaction with therapeutic and drug addiction-related compounds. Using a structureactivity approach, we have examined the relationship among the molecular features of a set of eight para-R-substituted N,N-[(dimethylamino)ethyl] benzoate hydrochlorides, structurally related to procaine and their affinity for the a3 beta 4 nAChR heterologously expressed in KXa3 beta 4R2 cells. Affinity values (log[1/IC50]) of these compounds for the a3 beta 4 nAChR were determined by their competition with [3H]TCP binding. Log(1/IC50) values were analyzed considering different hydrophobic and electronic parameters and those related to molar refractivity. These have been experimentally determined or were taken from published literature. In accordance with literature observations, the generated cross-validated quantitative structureactivity relationship (QSAR) equations indicated a significant contribution of hydrophobic term to binding affinity of procaine analogs to the receptor and predicted affinity values for several local anesthetics (LAs) sets taken from the literature. The predicted values by using the QSAR model correlated well with the published values both for neuronal and for electroplaque nAChRs. Our work also reveals the general structure features of LAs that are important for interaction with nAChRs as well as the structural modifications that could be made to enhance binding affinity. (c) 2012 Wiley Periodicals, Inc.
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Galectin-3 has been implicated in the tumor development via its mediation of the Wnt signaling pathway. Likewise, glycogen synthase kinase-3beta (GSK3 beta) also plays a role in the Wnt signaling pathway by controlling the levels of cytoplasmic beta-catenin. Altered GSK3 beta expression has been described in various tumors, but to date, there are no studies evaluating its expression in models of oral carcinogenesis. Additionally, it is unknown whether the absence of galectin-3 regulates the expression of GSK3 beta. To this end, Gal3-deficient (Gal3(-/-)) and wild-type (Gal3(+/+)) male mice were treated with 4NQO for 16 weeks and sacrificed at week 16 and 32. The tongues were removed, processed, and stained with H&E to detect dysplasias and carcinomas. An immunohistochemical assay was performed to determine the level of P-GSK3 beta-Ser9 expression in both groups. Carcinomas were more prevalent in Gal3(+/+) than Gal3(-/-) mice (55.5% vs. 28.5%), but no statistical difference was reached. In the dysplasias, the proportion of cells positive for P-GSK3 beta-Ser9 was slightly higher in Gal3(+/+) than Gal3(-/-) mice (63% vs. 61%). In the carcinomas, a significant difference between Gal3(+/+) and Gal3(-/-) mice was found (74% vs. 59%; p=0.02). P-GSK3 beta-Ser9-positive cells slightly decreased from the progression of dysplasias to carcinomas in Gal3(-/-) mice (61% vs. 59%; p>0.05). However, a significant increase in P-GSK3 beta-Ser9 expression was observed from dysplasias to carcinomas in Gal3(+/+) mice (63% vs. 74%; p=0.01). In conclusion, these findings suggest that fully malignant transformation of the tongue epithelium is associated with increased P-GSK3 beta-Ser9 expression in Gal3(+/+) mice, but not in Gal3(-/-) mice.