PDA-Based Glyconanomicelles for Hepatocellular Carcinoma Cells Active Targeting Via Mannose and Asialoglycoprotein Receptors.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugar-coated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).

Prevalence of Suicidality in the European General Population: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the prevalence and variability in suicidality in the general adult population of Europe between 2008 and 2017. METHODS: Studies containing original data on suicidality were identified in five electronic databases. Point, 12-month and lifetime prevalences were calculated for various types of suicidality. Pooled prevalence rates were calculated using a random effects model. Subgroup analysis and multivariate meta-regression were also performed. RESULTS: We identified 24 papers containing original data, which provided 97 prevalence rates for suicidality. The pooled point prevalence rate was 3.96% (2.37-5.56), pooled 12-month prevalence 2.9% (1.49-4.32), and pooled lifetime prevalence 5.55% (4.31-6.79). The subgroup analysis showed that lifetime prevalence figures for wishing to be dead and suicidal ideation were higher in areas with a population of less than 3,849 inhabitants and in Eastern Europe. Finally, the multivariate meta-regression showed differences with respect to the period and type of suicidality, lower and upper age thresholds, population size, and study area. CONCLUSION: Our data showed that approximately 21% of European individuals have wished to be dead at some point during their lifetime. Studies like this are necessary to highlight the need for efforts to prevent and intervene in suicidality.