Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for SLC25A13 transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring SLC25A13 gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC).

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of Garcinia cambogia, is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE2 in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (−50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE2 increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes.

The overproduction of reactive oxygen species and the exposure of the human body to free radicals contribute to the aetiology of many chronic health problems, such as cardiovascular disease and cancer. Supplementation with natural antioxidants could be helpful, preventing free-radical-induced tissue damage through the inhibition of the radicals’ formation. Quercetin derivatives have recently been shown to inhibit the production of inflammatory mediators and to reduce the proliferation of tumoral cells, thus being valid compounds to be promoted as dietary supplements. In this work, an HPLC-MS/MS investigation on the derivatives of quercetin in a methanolic extract of peppers deriving from an original crossing combination between Habanero white and Capsicum annuum revealed the occurrence of nine glycoconjugates, either monosaccharide, disaccharide or trisaccharide, as well as an acylated disaccharidic derivative (i.e., quercetin rhamnoside-(feruloyl-hexoside)). Due to the great variability in the quercetin derivatives’ profiles, the Habanero white hybrid pepper extract was subjected to in vitro cytotoxicity assays. The pepper extract under study was proved to have anti-inflammatory activity comparable to that shown by a Capsicum annuum pepper extract since it reduced ROS levels compared to activated cells. Due to its beneficial effects, it could be exploited as a natural constituent of nutraceutical formulations.

In recent years, there has been considerable interest in using microalgal lipids in the food, chemical, pharmaceutical, and cosmetic industries. Several microalgal species can accumulate appreciable lipid quantities and therefore are characterized as oleaginous. In cosmetic formulations, lipids and their derivatives are one of the main ingredients. Different lipid classes are great moisturizing, emollient, and softening agents, work as surfactants and emulsifiers, give consistence to products, are color and fragrance carriers, act as preservatives to maintain products integrity, and can be part of the molecules delivery system. In the past, chemicals have been widely used but today’s market and customers’ demands are oriented towards natural products. Microalgae are an extraordinary source of lipids and other many bioactive molecules. Scientists’ attention to microalgae cultivation for their industrial application is increasing. For the high costs associated, commercialization of microalgae and their products is still not very widespread. The possibility to use biomass for various industrial purposes could make microalgae more economically competitive.

Metabolic reprogramming is a hallmark of cancer cells required to ensure high energy needs and the maintenance of redox balance. A relevant metabolic change of cancer cell bioenergetics is the increase in glutamine metabolism. Hepatocellular carcinoma (HCC), one of the most lethal cancer and which requires the continuous development of new therapeutic strategies, shows an up-regulation of human glutamate dehydrogenase 1 (hGDH1). GDH1 function may be relevant in cancer cells (or HCC) to drive the glutamine catabolism from L-glutamate towards the synthesis of α-ketoglutarate (α-KG), thus supplying key tricarboxylic acid cycle (TCA cycle) metabolites. Here, the effects of hGLUD1 gene silencing (siGLUD1) and GDH1 inhibition were evaluated. Our results demonstrate that siGLUD1 in HepG2 cells induces a significant reduction in cell proliferation (58.8% ± 10.63%), a decrease in BCL2 expression levels, mitochondrial mass (75% ± 5.89%), mitochondrial membrane potential (30% ± 7.06%), and a significant increase in mitochondrial superoxide anion (25% ± 6.55%) compared to control/untreated cells. The inhibition strategy leads us to identify two possible inhibitors of hGDH1: quercetin and Permethylated Anigopreissin A (PAA). These findings suggest that hGDH1 could be a potential candidate target to impair the metabolic reprogramming of HCC cells.

The peppers of the Capsicum species are exploited in many fields, as flavoring agents in food industry, or as decorative and therapeutic plants. Peppers show a diversified phytochemical content responsible for different biological activities. Synergic activity exerted by high levels of antioxidant compounds is responsible for their important anti-inflammatory property. A methanolic extract was obtained from a new pepper genotype and tested for anti-inflammatory activity. The extract was incorporated into phospholipid vesicles to increase the bioavailability of its bioactive components. Two types of phospholipid vesicles were produced, conventional liposomes and Penetration Enhancer containing Vesicles (PEVs). They were tested in human monoblastic leukemia U937 cell line, showing no cytotoxic effect. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels were measured to value the in vitro efficacy of the vesicles in regulating inflammatory responses. Liposomal incorporation significantly reduced ROS levels in extract-treated LPS-activated cells. Furthermore, LC-MS/MS analyses demonstrated that liposomes facilitated the transport of the extract components across the cell membrane and their accumulation into the cytoplasm.

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Nowadays, the interest toward products containing probiotics is growing due to their potential health benefits to the host and the research is focusing on search of new probiotic microorganisms. The present work was focused on the characterization of indigenous Saccharomyces cerevisiae strains, isolated from different food matrixes, with the goal to select strains with probiotic or health-beneficial potential. A preliminary screening performed on fifty S. cerevisiae indigenous strains, in comparison to a commercial probiotic strain, allowed to individuate the most suitable ones for potential probiotic aptitude. Fourteen selected strains were tested for survival ability in the gastrointestinal tract and finally, the strains characterized for the most important probiotic features were analyzed for health-beneficial traits, such as the content of glucan, antioxidant and potential anti-inflammatory activities. Three strains, 4LBI-3, LL-1, TA4-10, showing better attributes compared to the commercial probiotic S.cerevisiae var. boulardii strain, were characterized by interesting health-beneficial traits, such as high content of glucan, high antioxidant and potential anti-inflammatory activities. Our results suggest that some of the tested S. cerevisiae strains have potential as probiotics and candidate for different applications, such as dietary supplements, and starter for the production of functional foods or as probiotic to be used therapeutically.