Nonalcoholic fatty liver disease (NAFLD) is a major cause of morbidity and mortality worldwide. Additional therapies using functional foods and dietary supplements have been investigated and used in clinical practice, showing them to be beneficial. Honeybee pollen from Chile has shown a large concentration of phenolic compounds and high antioxidant activity. In this work, we characterized twenty-eight bee pollen extracts from the central zone of Chile according to botanical origin, phenolic profile, quercetin concentration, and antioxidant activity (FRAP and ORAC-FL). Our results show a statistically significant positive correlation between total phenolic content and antioxidant capacity. Selected samples were evaluated on the ability to reverse the steatosis in an in vitro cell model using Hepa1-6 cells. The pollen extracts protected Hepa1-6 cells against oxidative damage triggered by 2,2′-azo-bis(2-amidinopropane) dihydrochloride (AAPH)derived free radicals. This effect can be credited to the ability of the phenolic compounds present in the extract to protect the liver cells from chemical-induced injury, which might be correlated to their free radical scavenging potential. Additionally, bee pollen extracts reduce lipid accumulation in a cellular model of steatosis. In summary, our results support the antioxidant, hepatoprotective, and anti-steatosis effect of bee pollen in an in vitro model.

A mounting body of evidence indicates that adolescents are specially more susceptible to alcohol influence than adults. However, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity and recently, the opening of hemichannels and pannexons has been found to participate in both processes. Here, we evaluated whether adolescent rats exposed to ethanol exhibit changes in the activity of astrocyte hemichannels and pannexons in the hippocampus, as well as alterations in astrocyte arborization and cytokine levels. Adolescent rats were subjected to ethanol (3.0 g/kg) for two successive days at 48-h periods over 14 days. The opening of hemichannels and pannexons was examined in hippocampal slices by dye uptake, whereas hippocampal cytokine levels and astroglial arborization were determined by ELISA and Sholl analysis, respectively. We found that adolescent ethanol exposure increased the opening of connexin 43 (Cx43) hemichannels and pannexin-1 (Panx1) channels in astrocytes. Blockade of p38 mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS) and cyclooxygenases (COXs), as well as chelation of intracellular Ca²⁺, drastically reduced the ethanol-induced channel opening in astrocytes. Importantly, ethanol-induced Cx43 hemichannel and Panx1 channel activity was correlated with increased levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 in the hippocampus, as well as with profound alterations in astrocyte arbor complexity. Thus, we propose that uncontrolled opening of astrocyte hemichannels and pannexons may contribute not only to the glial dysfunction and neurotoxicity caused by adolescent alcohol consumption, but also to the pathogenesis of alcohol use disorders in the adulthood.

Chickpeas are rich sources of bioactive compounds such as phenolic acids, flavonoids, and isoflavonoids. However, the contribution of insoluble-bound phenolics to their antioxidant properties remains unclear. Four varieties of chickpeas were evaluated for the presence of soluble (free and esterified) and insoluble-bound phenolics as well as their antiradical activity, reducing power and inhibition of peroxyl-induced cytotoxicity in human HuH-7 cells. In general, the insoluble-bound fraction showed a higher total phenolic content. Phenolic acids, flavonoids, and isoflavonoids were identified and quantified by UPLC-MS/MS. Taxifolin was identified for the first time in chickpeas. However, m-hydroxybenzoic acid, taxifolin, and biochanin A were the main phenolics found. Biochanin A was mostly found in the free fraction, while m-hydroxybenzoic acid was present mainly in the insoluble-bound form. The insoluble-bound fraction made a significant contribution to the reducing power and antiradical activity towards peroxyl radical. Furthermore, all extracts decreased the oxidative damage of human HuH-7 cells induced by peroxyl radicals, thus indicating their hepatoprotective potential. This study demonstrates that the antioxidant properties and bioactive potential of insoluble-bound phenolics of chickpeas should not be neglected.

Teneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer.