miR-155 in the progression of lung fibrosis in systemic sclerosis

Background: MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD

Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle

Hepatitis C virus (HCV) is one of the main causes of liver disease and transplantation worldwide. Current therapy is expensive, presents additional side effects and viral resistance has been described. Therefore, studies for developing more efficient antivirals against HCV are needed. Compounds isolated from animal venoms have shown antiviral activity against some viruses such as Dengue virus, Yellow fever virus and Measles virus. In this study, we evaluated the effect of the complex crotoxin (CX) and its subunits crotapotin (CP) and phospholipase A2 (PLA2-CB) isolated from the venom of Crotalus durissus terrificus on HCV life cycle. Huh 7.5 cells were infected with HCVcc JFH-1 strain in the presence or absence of these toxins and virus was titrated by focus formation units assay or by qPCR. Toxins were added to the cells at different time points depending on the stage of virus life cycle to be evaluated. The results showed that treatment with PLA2-CB inhibited HCV entry and replication but no effect on HCV release was observed. CX reduced virus entry and release but not replication. By treating cells with CP, an antiviral effect was observed on HCV release, the only stage inhibited by this compound. Our data demonstrated the multiple antiviral effects of toxins from animal venoms on HCV life cycle

Anxiety and depression symptoms in women with and without binge eating disorder enrolled in weight loss programs

OBJECTIVES: 1) To investigate the association between binge eating scores, anxiety and depression symptoms, and body mass index (BMI), and 2) to assess the presence of differences in severity of anxiety symptoms, severity of depression symptoms, and BMI in women with and without binge eating disorder. METHOD: The sample comprised 113 women aged between 22 and 60 years (39.35±10.85) enrolled in weight loss programs in Porto Alegre, southern Brazil. The following instruments were used: structured interview, Brazilian Economic Classification Criteria, Beck Anxiety Inventory, Beck Depression Inventory, and Binge Eating Scale. Data were analyzed using descriptive and inferential statistics. RESULTS: A positive association was found between binge eating scores and the severity of anxiety symptoms (p OBJETIVOS: 1) Investigar a associação entre escores de compulsão alimentar, sintomas de ansiedade e de depressão e índice de massa corporal (IMC); e 2) verificar se existe diferença na intensidade dos sintomas de ansiedade, dos sintomas depressivos e no IMC em mulheres com e sem compulsão alimentar. MÉTODO: A amostra foi composta de 113 mulheres com idade entre 22 e 60 anos (39,35±10,85), participantes de programas de redução de peso na cidade de Porto Alegre, sul do Brasil. Foram aplicados os seguintes instrumentos: entrevista estruturada, Critérios de Classificação Econômica Brasil, Inventário de Ansiedade de Beck, Inventário de Depressão de Beck e Escala de Compulsão Alimentar Periódica. Os dados foram analisados utilizando-se estatística descritiva e inferencial. RESULTADOS: Houve associação positiva entre os escores de compulsão alimentar e a intensidade dos sintomas de ansiedade (p < 0,001) e de depressão (p < 0,001). Não foi observada associação significativa (p = 0,341) entre IMC e escores de compulsão alimentar. Houve diferença significativa entre mulheres com e sem compulsão alimentar com relação à intensidade dos sintomas de ansiedade (p < 0,001) e depressão (p < 0,001). Não foi encontrada diferença significativa entre os grupos com relação ao IMC (p = 0,103). CONCLUSÃO: Os achados deste estudo mostraram que a compulsão alimentar está associada a sintomas de ansiedade e de depressão, porém não está associada ao IMC