Effects of APOE, APOB and LDLR variants on serum lipids and lack of association with xanthelasma in individuals from Southeastern Brazil

Xanthelasma might be a clinical manifestation of dyslipidemia, a recognized risk factor for coronary artery disease. We investigated the association of apolipoprotein E (APOE HhaI), apolipoprotein B (APOB XbaI and Ins/Del) and LDL receptor (LDLR AvaII and HincII) gene polymorphisms with lipid profiles in 100 Brazilians with xanthelasma and 100 controls. Allele frequencies were similar in both groups. APOE, APOB and LDLR genotypes were not correlated with differences in the serum lipid profile. In individuals with xanthelasma, the APOB D allele was associated with less chance of having increased LDL-cholesterol (O.R. = 0.16, CI95% = 0.03-0.94, p = 0.042). In the control group, the APOB X+ allele was associated with less chance of having both increased total cholesterol (O.R. = 0.16, CI95% = 0.03-0.78, p = 0.023) and increased LDL-cholesterol (O.R. = 0.10, CI95% = 0.02-0.60, p = 0.012). Moreover, there was a significantly higher frequency of control individuals (68%) with elevated serum triglyceride levels, compared to patients (48%, p = 0.008). On the other hand, triglyceride levels in controls also seemed to be influenced by all other gene polymorphisms studied, an effect that might be enhanced by environmental factors

Atorvastatin attenuation of ABCB1 expression is mediated by microRNA miR-491-3p in Caco-2 cells

AimAtorvastatin, a HMG-CoA reductase inhibitor, used in the treatment of hypercholesterolemia, has been previously shown to regulate ABCB1 expression in vivo and in vitro. We hypothesized that the statin could regulate gene expression of ABCB1 transporter via microRNAs.MethodsExpression of microRNAs and ABCB1 mRNA was examined in atorvastatin-treated and control cells using real-time PCR. miR-491-3P mimic and inhibitor were transfected in Caco-2 and ABCB1 expression was monitored by western blot and real-time PCR.ResultsIn HepG2 cells, none of the microRNAs predicted to target ABCB1 3'UTR was regulated by atorvastatin treatment. In agreement with this, ABCB1 3'UTR activity was not modulated in HepG-2 cells after 48h-treatment as measured by luciferase assay. In Caco-2 cells, atorvastatin treatment provoked a decrease in luciferase activity and, accordingly, miR-491-3p was upregulated about 2.7 times after 48h-statin treatment. Luciferase analysis of miR-491-3p with a mimetic or inhibitor of miR-491-3p revealed that this microRNA could target ABCB1 3'UTR, as after miR-491-3p inhibition, ABCB1 levels were increased by two-fold, and miR-491-3p superexpression decreased ABCB1 3'UTR activity. Finally, functional analysis revealed that treatment with miR-491-3p inhibitor could reverses atorvastatin attenuation of ABCB1 (Pg-p) protein levels.ConclusionOur results suggest atorvastatin control ABCB1 expression via miR-491-3p in Caco-2 cells. This finding may be an important mechanism of statin drug-drug interaction, since common concomitant drugs used in the prevention of cardiovascular diseases are ABCB1 substrates

Bacteriophage: laboratorial diagnosis and phage therapy Bacteriofagos: diagnóstico laboratorial e terapia fágica

Bacteriophages have been researched as a new alternative to antibiotics. These viruses inject their genetic material into bacteria and use their host machinery to multiply themselves. The research of bacteriophages in Brazil will certainly provide low-cost treatment of multidrug resistant bacteria, new microbiological diagnosis and advantages for the Brazilian food industry.<br>Bacteriófagos têm sido pesquisados como uma alternativa ao uso de antibióticos. Estes vírus infectam as bactérias e utilizam a maquinaria celular para multiplicar o próprio material genético. O estudo de bacteriófagos no Brasil levará ao desenvolvimento de tratamentos de baixo custo, novos testes diagnósticos e vantagens para a industria alimentícia