Co-delivery of antigen and dual adjuvants by aluminum hydroxide nanoparticles for enhanced immune responses.

Adjuvants that contain pathogen-associated molecular patterns (PAMPs) can enhance vaccination efficacy by binding to pattern recognition receptors (PRRs), thereby stimulating immune responses. Particularly effective may be the combination of multiple PAMPs that activate different PRRs, which occurs with natural pathogens. Here we hypothesized the enhanced effects would occur in two adjuvants that stimulate different PRRs: CpG oligodeoxynucleotide (CpG-ODN), which is Toll-like receptor 9 agonist; and 5'-triphosphate, short, double-stranded RNA (3pRNA), which activates retinoic acid-inducible gene I (RIG-I). The model antigen ovalbumin (OVA) was loaded and adjuvants were surface-adsorbed to aluminum hydroxide nanoparticles (hereafter NP-3pRNA-CpG) by electrostatic interaction with an average size of 120 nm and a negative surface charge for targeting lymph nodes. These nanoparticles were efficiently internalized by antigen-presenting cells (APCs) in the lymph nodes, and the resulting APC activation and antigen cross-presentation generated strong humoral immunity and cytotoxic T lymphocyte responses and IFN-γ secretion. NP-3pRNA-CpG significantly suppressed B16-OVA tumor growth and prolonged survival of tumor-bearing mice in therapeutic and prophylactic models, illustrating the enhanced effects of CpG-ODN and 3pRNA. Our study highlights the potential of combining multiple adjuvants for effective vaccine design.

Selenium concentration, dietary intake and risk of hepatocellular carcinoma - A systematic review with meta-analysis.

INTRODUCTION: Aim: this study was performed to investigate the association between selenium concentrations, dietary intake, and the risk of hepatocellular carcinoma (HCC). Methods: we identified eligible studies in PubMed and EMBASE databases, in addition to the reference lists of original studies and review articles on this topic, up to 1 Feb 2019. A summary of standardized mean differences (SMD) with 95% confidence intervals (CI) was calculated using a random-effects model. Heterogeneity between studies was assessed using Cochran Q and I2 statistics. Results: finally, a meta-analysis showed that dietary intake of selenium and tissue selenium concentration were not associated with HCC risk (dietary SMD = -0.11, 95% CI: -0.26 to 0.03; tissue SMD = -0.12, 95% CI: -0.56 to 0.33). However, samples from toenail, whole blood, and serum all showed an inverse association with HCC risk (toenail SMD = -0.53, 95% CI: -0.72 to -0.35; whole blood SMD = -2.21, 95% CI: -2.67 to -1.76; tissue SMD = -1.26, 95% CI: -1.71 to -0.81). Dose-response data from few studies showed that an extra increase in serum selenium was dramatically related with a lower risk of HCC (adjusted p-trend < 0.05). This study showed that selenium concentration in toenail, whole blood and serum was inversely associated with HCC risk. Conclusion: increased concentration in serum selenium was related to a lower risk of HCC. However, these results based on dietary intake and tissue samples, which included few studies, did not reach statistical significance.

INTRODUCCIÓN: Objetivo: este estudio se realizó para investigar la asociación entre las concentraciones de selenio, la ingesta dietética y el riesgo de carcinoma hepatocelular (CHC). Métodos: identificamos estudios elegibles en las bases de datos PubMed y EMBASE, además de las listas de referencias de los estudios originales y artículos de revisión sobre este tema hasta el 1 de febrero de 2019. Se realizó un resumen de las diferencias medias estandarizadas (SMD) con intervalos de confianza (CI) del 95% utilizando un modelo de efectos aleatorios. La heterogeneidad entre estudios se evaluó utilizando las estadísticas de Cochran Q e I2. Resultados: por último, el metaanálisis mostró que la concentración de selenio en la ingesta dietética y de selenio tisular no estaban asociadas al riesgo de HCC (SMD dietética -0,11, IC 95%: -0,26 a 0,03; SMD tisular -0,12, IC 95%: -0,56 a 0,33). Sin embargo, las muestras de uña del pie, sangre entera y suero mostraron todas ellas una asociación inversa con el riesgo de CHC (SMD ungueal -0.53, IC 95%: -0.72 a -0.35; SMD de sangre entera -2.21, IC 95%: -2.67 a -1.76; SMD tisular -1.26, IC 95%: -1.71 a -0.81). Los datos de dosis-respuesta de pocos estudios mostraron que los incrementos del selenio sérico se relacionaban fuertemente con un menor riesgo de CHC (tendencia de p ajustada < 0.05). Este estudio demostró que la concentración de selenio en las uñas del pie, en sangre entera y en suero se asocian inversamente al riesgo de CHC. Conclusión: El aumento de la concentración de selenio sérico se relacionó con menor riesgo de CHC. Sin embargo, los resultados de la ingesta dietética y los tejidos, que incluían pocos estudios, no alcanzaron la significación estadística.