No abstract

Objective. CD8؉ T cells are abundant in rheumatoid arthritis (RA). However, their role in disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8؉ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA.Methods. CD8؉ T cell phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex-and age-matched healthy controls. Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines, and proteolytic enzymes in CD8؉ T cells was evaluated using flow cytometry.Results. PB CD8؉ T cells from RA patients with active disease exhibited an effector (CD27؊CD62L؊) phenotype (P ‫؍‬ 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor ␣ [TNF␣], interferon-␥ [IFN␥], interleukin-6 [IL-6], IL-17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 (P < 0.001), but lower cytokine production was observed. SF CD8؉ T cells from RA patients expressed more robust effector memory (CD27؉CD62L؊) and activated (CD69؉) profiles compared to the T cell subsets in paired PB samples.

Glioblastoma (GBM) is the most aggressive and malignant brain tumor. Recent studies indicated that glioma samples are characterized by increased expression of CXCR4, the CXCL12/SDF-1 chemokine receptor. To better understand the role of CXCR4 in GBM biology we performed an integrated study where we simultaneously evaluate the contribution of the CXCR4/CXCL12 signaling pathway to the proliferation, survival and motility of a human GBM cell line. Our results indicated that CXCR4/CXCL12 axis induced an increase in cell proliferation and in cell motility. The blockage of CXCR4 induced a significant increase of apoptosis. Together, our results indicated that CXCR4/CXCL12 signalling pathway may contribute to GBM development and emphasize the therapeutic potential of this pathway in patients with GBM.

Abstract. Glioblastomas (GBM) are the most lethal subtype of astrocytomas, with a mean patient survival rate of 12 months after diagnosis. The gold standard treatment of GBM, which includes surgery followed by the combination of radiotherapy and chemotherapy with temozolomide (TMZ), increases the survival rate to 14.6 months. The success of TMZ appears to be limited by the occurrence of chemoresistance that allows glioma cells to escape from death signaling pathways. However, the mechanism of TMZ action is yet to be clarified although some controversial results have been reported. Therefore, our aim was to evaluate the occurrence of apoptosis and autophagy in glioma cells treated with TMZ and to correlate TMZ action with the survival pathways Pi3K/ Akt and ERK1/2 MAP kinase. Cell proliferation was evaluated by incorporation of bromodeoxyuridine. Apoptosis was studied by flow cytometry as well as by fluorescence confocal microscopy in order to evaluate the sub G0/G1 percentage of cells and chromatin condensation. The expression of the autophagy-associated protein, LC3, as well as Akt and ERK1/2 was performed by Western blotting. In TMZ-treated GBM cells the expression of LC3, the autophagy-associated protein was increased and only a reduced percentage of cells underwent apoptosis. In addition, we showed that the phosphorylation status of Pi3K/Akt and ERK1/2 MAP kinase was maintained during the treatment with TMZ, suggesting that glioma cells escape from TMZ-induced cell death due to these signaling pathways. The chemoresistance of U-118 cells to TMZ was partially eradicated when cells were simultaneously treated with specific inhibitors of Pi3K/Akt and ERK1/2 MAP kinase signaling pathways and TMZ. Therefore, we hypothesized that in order to induce glioma cell death it is essential to evaluate the activation of the survival pathways and establish a combined therapy using TMZ and inhibitors of those signaling pathways.

Vitamin D deficiency is prevalent worldwide, but its prevalence is unknown in adult Portuguese population. In Portugal, 66% of adults present Vitamin D insufficiency/deficiency. Winter, living in Azores, older age, and obesity were the most important risk factors. It highlights the need of strategies to prevent vitamin D deficiency in Portugal. Objective To estimate the prevalence and risk factors of vitamin D deficiency in the adult Portuguese population. Methods Adults (≥ 18 years old) from the EpiReumaPt Study (2011-2013) were included. Standardized questionnaires on sociodemographic and lifestyle features were obtained. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated using