Multidrug resistance (MDR) is a serious obstacle to efficient cancer treatment. Overexpression of P-glycoprotein (P-gp) plays a significant role in MDR. Recent studies proved that targeting cellular metabolism could sensitize MDR cells. In addition, metabolic alterations could affect the extracellular vesicles (EVs) cargo and release. This study aimed to: i) identify metabolic alterations in P-gp overexpressing cells that could be involved in the development of MDR and, ii) identify a potential role for the EVs in the acquisition of the MDR. Two different pairs of MDR and their drug-sensitive counterpart cancer cell lines were used. Our results showed that MDR (P-gp overexpressing) cells have a different metabolic profile from their drug-sensitive counterparts, demonstrating decreases in the pentose phosphate pathway and oxidative phosphorylation rate; increases in glutathione metabolism and glycolysis; and alterations in the methionine/S-adenosylmethionine pathway. Remarkably, EVs from MDR cells were capable of stimulating a metabolic switch in the drug-sensitive cancer cells, towards a MDR phenotype. In conclusion, obtained results contribute to the growing knowledge about metabolic alterations in MDR cells and the role of EVs in the intercellular transfer of MDR. The specific metabolic alterations identified in this study may be further developed as targets for overcoming MDR.

Several hallmarks of metabolic syndrome, such as dysregulation in the glucose and lipid metabolism, endothelial dysfunction, insulin resistance, low-to-medium systemic inflammation, and intestinal microbiota dysbiosis, represent a pathological bridge between metabolic syndrome and diabesity, cardiovascular, and neurodegenerative disorders. This review aims to highlight some therapeutic strategies against metabolic syndrome involving integrative approaches to improve lifestyle and daily diet. The beneficial effects of foods containing antioxidant polyphenols, intestinal microbiota control, and physical activity were also considered. We comprehensively examined a large body of published articles involving basic, animal, and human studie, as well as recent guidelines. As a result, dietary polyphenols from natural plant-based antioxidants and adherence to the Mediterranean diet, along with physical exercise, are promising complementary therapies to delay or prevent the onset of metabolic syndrome and counteract diabesity and cardiovascular diseases, as well as to protect against neurodegenerative disorders and cognitive decline. Modulation of the intestinal microbiota reduces the risks associated with MS, improves diabetes and cardiovascular diseases (CVD), and exerts neuroprotective action. Despite several studies, the estimation of dietary polyphenol intake is inconclusive and requires further evidence. Lifestyle interventions involving physical activity and reduced calorie intake can improve metabolic outcomes.

Grape pomace (GP) represents the main solid by-product deriving from grape processing. The aim of this study was to evaluate the effect of dietary GP intake on nutritional quality, lipid oxidation and volatile profile of chicken meat. A total of 112 Ross 508 broilers were randomly divided into 4 groups and fed for 21 days with a standard diet. For the remaining 28 days of the trial, the control group (CG) continued to receive a standard diet, while the experimental groups (EGs) were fed with diets containing different GP concentrations: 2.5% (EG1), 5% (EG2) and 7% (EG3). Following the slaughtering, samples of breast meat were collected from each group. No significant differences were observed for pH, cooking loss and meat brightness, whereas the GP intake showed effectiveness in inducing variations in drip loss, meat yellowness and redness. The experimental feeding strategy also induced changes in the fatty acid profile, with an overall increase in polyunsaturated fatty acids (PUFA), mainly due to the increase in concentration of linoleic acid. The dietary supplementation also induced a decrease in lipid oxidation in meat, a finding also confirmed by the reduction in volatile aldehydes in 7 days stored raw meat. The feeding strategy based on the use of GP did not induce detrimental effects on the quality of broiler meat and showed the potential to lengthen the shelf-life as a direct consequence of the improvement in the oxidative stability. Overall, the present study showed a viable way for the recovery and the valorization of an agro-industrial by-product, with potential benefits also from an environmental point of view.