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Tetrahydroquinoline derivatives are interesting structures exhib-iting a wide range of biological activities, including antitumor effects. In this investigation, the effect of the synthesized tetrahydroquinolines JS-56 and JS-92on apoptosis, intracellular Ca2+ concentration ([Ca2+]i),and the sarco(endo)plas-mic reticulum Ca2+-ATPase (SERCA) activity was determined on MCF-7 breast cancer cells.Colorimetric assays were used to assess MCF-7 cells viability and SERCA activity. Fura-2 and rhodamine 123 were used to measure the intracellu-lar Ca2+ concentration and the mitochondrial electrochemical potential, respectively. TUNEL assay was used to analyze DNA fragmentation, while caspase activi-ty and NF-κB-dependent gene expression were assessed by luminescence. In silicomodels were used for molecular docking analysis. These compounds increase intracellular Ca2+ concentration; the main contribution is the Ca2+ entry from the extracellular milieu. Both JS-56 and JS-92 inhibit the activity of SERCA and dissipate the mitochondrial electrochemical potentialthrough processes depen-dent and independent of the Ca2+ uptake by this organelle. Furthermore, JS-56 and JS-92 generate cytotoxicity in MCF-7 cells. The effect of JS-92 is higher than JS-56. Both compounds activate caspases 7 and 9, cause DNA fragmentation, and potentiate the effect of phorbol 12-myristate-13-acetate on NF-κB-dependent gene expression. Molecular docking analysis suggests that both compounds have a high interaction for SERCA, similar to thapsigargin. Both tetrahydroquinoline derivatives induced cell death through a combination of apoptotic events, in-crease [Ca2+]i, and inhibit SERCA activity by direct interaction.

ADAM33 is a metalloproteinase important in the extracellular matrix for tissue remodeling, and, consequently, in asthma and chronic obstructive pulmonary disease (COPD). Several polymorphisms of the ADAM33 gene have been associated with enzyme activity. One of the most studied polymorphisms is V4, cytosine for guanine in the 3 'UTR region, and T1, adenine for guanine in the exon 19 of the gen. The aim of this study was to ascertain the possible association among single polymorphisms of ADAM33, V4 and T1, in Venezuelan patients with asthma or COPD. The polymorphisms V4 and T1 were analyzed in 303 individuals (103 asth- matic, 100 COPD and 100 controls) by PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphisms). There was a significant difference (P0.05) in the frequency of ADAM33 V4 polymorphism in both, asthmatic and COPD patients groups, as compared to controls. No significant differences (P=0.4) were found for T1 polymorphism. However, there were significant differences (PO.05) when haplotypes and diplotypes of ADAM33 V4/T1 were compared in all three groups. It can be concluded that the polymorphism V4 of ADAM33 is associated with asthma or COPD in Venezuelan patients.

Autophagy is a complex process in which cell homeostasis of proteins, organelles, exocitic and endocitic vacuoles are controlled. There is a direct link between autophagy and cell death with antigen processing, generation of inflammatory response and immune response. In different diseases, deficiencies in autophagy have been reported. It has been proposed that in early stages of cancer, autophagy is capable of inducing cell death; however, in agresive tumors and metastasis, the process is responsible for pharmacologic resistance and tumor survival. More research has to be done in order to allow us to understand the process and generate therapeutic options in different pathologies important for the human being.

The immune response represents a fundamental element in the control of Hepatitis C virus (HCV) infection. Viral and cellular host factors may modulate this response. In the present study, we characterized immune complexes (cryoprecipitates) isolated form HCV-infected patients and evaluated the expression of Fc receptors for IgG (FcgammaR) in peripheral blood leucocytes of these patients. Twelve HCV (+) patients and 12 healthy control individuals were selected for this study. For each group, sera samples were collected for cryoglobulins isolation and characterization and EDTA-anticoagulated venous blood samples were collected for flow cytometry analysis of FcgammaR, CD64 (FcgammaRI), CD32 (FcgammaRII) and CD16 (FcgammaRIII) expression. Presence of HCV RNA in serum and cryoprecipitates was analysed by RT-PCR. Results show that 50% of HCV-infected patients present high levels of cryoglobulins mainly constituted by IgG. Three out of 5 cryoglobulins analyzed by RT-PCR were positive for HCV-RNA. Expression of CD64 was observed mainly in monocytes (80%), CD32 in monocytes, B lymphocytes and neutrophils (90%) and CD16 in NK cells and neutrophils (85% and 95% respectively). No differences were observed in the percentage of FcgammaR expression when comparing HCV-infected patients with healthy controls. On the contrary, density of expression of CD32 in monocytes and neutrophils cell populations of HCV patients was significantly lower than that observed in healthy controls (p0.05). We concluded that low density expression of FcgammaRII in HCV-infected patients may have implications in the physiopatholgy of HCV infection.