MEOX2 Regulates the Growth and Survival of Glioblastoma Stem Cells by Modulating Genes of the Glycolytic Pathway and Response to Hypoxia

The most widely accepted hypothesis for the development of glioblastoma suggests that glioblastoma stem-like cells (GSCs) are crucially involved in tumor initiation and recurrence as well as in the occurrence of chemo- and radio-resistance. Mesenchyme homeobox 2 (MEOX2) is a transcription factor overexpressed in glioblastoma, whose expression is negatively correlated with patient survival. Starting from our observation that MEOX2 expression is strongly enhanced in six GSC lines, we performed shRNA-mediated knock-down experiments in two different GSC lines and found that MEOX2 depletion resulted in the inhibition of cell growth and sphere-forming ability and an increase in apoptotic cell death. By a deep transcriptome analysis, we identified a core group of genes modulated in response to MEOX2 knock-down. Among these genes, the repressed ones are largely enriched in genes involved in the hypoxic response and glycolytic pathway, two strictly related pathways that contribute to the resistance of high-grade gliomas to therapies. An in silico study of the regulatory regions of genes differentially expressed by MEOX2 knock-down revealed that they mainly consisted of GC-rich regions enriched for Sp1 and Klf4 binding motifs, two main regulators of metabolism in glioblastoma. Our results show, for the first time, the involvement of MEOX2 in the regulation of genes of GSC metabolism, which is essential for the survival and growth of these cells

Profiling Individual Differences in Alcoholic Beverage Preference and Consumption: New Insights from a Large-Scale Study

Alcoholic beverage consumption plays an important role in European culture, and in many contexts drinking alcohol is socially acceptable and considered part of the diet. Understanding the determinants of alcohol preference and consumption is important not only for disease prevention, intervention, and policy management, but also for market segmentation, product development, and optimization. The aim of the study was to investigate the effect of individual responsiveness to various oral sensations on self-reported liking and intake of 14 alcoholic and non-alcoholic beverages (including beers, wines, spirits, and cocktails) considering gender, age, and oral responsiveness (measured through response to 6-n-propyl-2-thiouracil -PROP, basic tastes, astringency, and pungency) in a large sample of Italian consumers. Data were collected from 2388 respondents (age range 18\u201360 years; mean age = 37.6, SD = 13.1; 58.2% women). These results indicate that notwithstanding the strong gender difference, with women generally liking and consuming fewer alcoholic beverages than men, liking patterns in the two genders were similar. Three liking patterns for different alcoholic beverages largely driven by orosensory properties were identified in both genders. \u201cSpirit-lovers\u201d constituted the smallest group (12%), consumed alcoholic beverages of any kind (not only spirits) more than the other segments, and were mainly men aged 30\u201345. \u201cBeer/wine lovers\u201d (44%) were the oldest group with no difference by gender. \u201cMild-drink lovers\u201d (44%) liked alcoholic drinks with intense sweet taste and/or mixers that moderate ethanol perception. They were mainly women, aged 18\u201329, had a lower consumption of alcohol, and a higher orosensory responsiveness than the other two groups. The results also suggest the opportunity to develop personalized recommendations towards specific consumer segments based not only on socio-demographics but considering also perceptive variables. Finally, our data suggest that increased burning and bitterness from alcohol may act as a sensory hindrance to alcoholic beverage overconsumption