Notum attenuates HBV-related liver fibrosis through inhibiting Wnt 5a mediated non-canonical pathways

BACKGROUND: Non-canonical Wnt pathways play important roles in liver fibrosis. Notum is a newly discovered inhibitor to Wnt proteins. This study was to investigate anti-fibrotic effects of Notum. METHODS: 53 patients with hepatitis B virus (HBV) infection as well as a cell co-culture system of LX-2 and Hep AD38 cells were engaged in this study. Clinical, biological and virological data of each patient were analyzed. Cell viability was detected at different time points. mRNA and protein levels of NFATc1 (Nuclear factor of activated T-cells), Jnk, α-SMA, Col1A1 and TIMP-1 were detected both in LX-2 and liver tissue. Protein levels of NFATc1 and Jnk in liver tissue and their correlations with fibrosis score were analyzed. RESULTS: Hepatitis B virus replication up-regulated Wnt5a induced NFATc1 and Jnk activity in Hep AD38. Notum suppressed NFATc1, Jnk and fibrosis genes expression, reduced cell viability in co-cultured LX-2 cells induced by HBV. Interestingly, Patients with HBV DNA > 5log copies/ml had higher mRNA levels of NFATc1 and fibrosis genes than patients with HBV DNA < 5log copies/ml. Most importantly, protein expressions of NFATc1 and pJnk have positive correlations with liver fibrosis scores in HBV-infected patients. CONCLUSIONS: Our data showed that Notum inhibited HBV-induced liver fibrosis through down-regulating Wnt 5a mediated non-canonical pathways. This study shed light on anti-fibrotic treatment.

Malation vs. Aedes aegypti (Linnaeus) (Diptera: Culicidae) de diferentes regiones de Venezuela / Malathion vs. Aedes aegypti (Linnaeus, Diptera: Culicidae) from different regions of Venezuela

En Venezuela, el malation ha sido ampliamente usado en forma continua en programas de control de aedes aegypti. Por tal motivo se realizó un estudio en mosquitos provenientes de zonas urbanas con alta casuística de dengue de los estados: Amazonas, Aragua, Bolívar, Lara, Mérida y Zulia, para determinar el status de susceptibilidad en este vector al malatión, en comparación con la cepa susceptible referencial, Rockefeller (Rock). Se hicieron bioensayos en botellas tratadas con el insecticida malatión evaluando la dosis diagnóstica 100ug/mL en 30 minutos y ensayos bioquímicos en microplacas para determinar mecanismos metabólicos asociados al status frente al insecticida. Los resultados de los bioensayos mostraron que existe susceptibilidad a malatión, lo cual fue confirmado por pruebas bioquímicas. Sin embargo, se encontraron diferencias significativas entre todas las cepas evaluadas con valores de P<0,005 para esterasas alfa (α), esterasas beta (β) y acetilcolinesterasa normal (Ache) y acetilcolinesterasa inhibida (Achei). La prueba de comparación de medias de Bonferroni encontró similitud entre la cepa Rock, mazonas y Lara para esterasas α y β. Se encontró similitud de la cepa Rock con las cepas de Bolívar y Zulia para las pruebas con Ache y Achei. Este estudio concluye que el malatión mostró su potencial de uso en el control del vector del dengue de las localidades evaluadas.

In Venezuela, malathion has been widely used continuously in control programs for Aedes aegypti. Therefore, a study in mosquitoes from urban areas with high dengue casuistry in the states of Amazonas, Aragua, Bolivar, Lara, Merida and Zulia was conducted to determine the status of this vector susceptibility to malathion, compared with the reference susceptible strain, Rockefeller. Bioassays were done on bottles treated with the insecticide malathion, 100ug/mL evaluating the diagnostic doses in 30 minutes and biochemical assays in microplates were performed to determine metabolic mechanisms associated with status against insecticide. The bioassay results showed that there is malathion susceptibility, which was confirmed by biochemical tests. However, significant differences were found among all strains assessed values of P<0.005 for esterases alpha (α), beta esterases (β) and standard acetylcholinesterase (AChe) and inhibited acetylcholinesterase (Achei). The mean comparison test of Bonferroni showed similarity between the strains Rock, Amazon and Lara for esterases α and β. Similarity was found between the strains Rock, Bolivar and Zulia for the Ache and Achei tests. This study concludes that malathion showed its potential use in controlling the dengue vector in the locations evaluated.