Beta vulgaris L. (beetroot) contains high amounts of biologically active substances including betalains and inorganic nitrate. We determined the amounts of various compounds (minerals, betalains, oxalic acid, phenolic acids, and sugars) in juice prepared from seven different beetroot varieties cultivated in Upper Austria. Large differences were found between the varieties for some substances (such as nitrate), whereas others showed only minor variation (certain minerals and sugars). The total betalain content was found to range between 0.8 and 1.3g/L fresh juice (about 60% betacyanins and 40% betaxanthins) that accounted for 70–100% of the total phenolics content. Other detected phenolics were hydroxycinnamic acids, which accounted for up to 2.6% of total phenolics. Nitrate content varied 10-fold between single varieties. Sugar composition was similar in all varieties with an average total content of about 7.7%, consisting of 95% sucrose. Only minor differences in the concentration of oxalic acid (0.3–0.5g/L fresh juice) were found between the varieties. In addition, 16 commercial juices and four powders were analyzed for their nitrate contents, as its metabolic product nitric oxide has been reported to provide cardiovascular benefits. Large variations of the nitrate levels, ranging from 0.01 to 2.4g/L, were found

Essential oils (EOs) have attracted increased interest for different applications such as food preservatives, feed additives and ingredients in cosmetics. Due to their reported variable composition of components, they might be acutely toxic to humans and animals in small amounts. Despite the necessity, rigorous toxicity testing in terms of safety evaluation has not been reported so far, especially using alternatives to animal models. Here, we provide a strategy by use of alternative in vitro (cell cultures) and in vivo (Caenorhabditis elegans, hen’s egg test) approaches for detailed investigation of the impact of commonly used rosemary, citrus and eucalyptus essential oil on acute, developmental and reproductive toxicity as well as on mucous membrane irritation. In general, all EOs under study exhibited a comparable impact on measured parameters, with a slightly increased toxic potential of rosemary oil. In vitro cell culture results indicated a concentration-dependent decrease of cell viability for all EOs, with mean IC₅₀ values ranging from 0.08 to 0.17% [v/v]. Similar results were obtained for the C. elegans model when using a sensitized bus-5 mutant strain, with a mean LC₅₀ value of 0.42% [v/v]. In wild-type nematodes, approximately tenfold higher LC₅₀ values were detected. C. elegans development and reproduction was already significantly inhibited at concentrations of 0.5% (wild-type) and 0.1% (bus-5) [v/v] of EO, respectively. Gene expression analysis revealed a significant upregulation of xenobiotic and oxidative stress genes such as cyp-14a3, gst-4, gpx-6 and sod-3. Furthermore, all three EOs under study showed an increased short-time mucous membrane irritation potential, already at 0.5% [v/v] of EO. Finally, GC–MS analysis was performed to quantitate the relative concentration of the most prominent EO compounds. In conclusion, our results demonstrate that EOs can exhibit severe toxic properties, already at low concentrations. Therefore, a detailed toxicological assessment is highly recommended for each EO and single intended application.

Insulin-like growth factor-I receptor (IGF-IR) preferentially regulates the long-term IGF activities including growth and metabolism. Kinetics of ligand-dependent IGF-IR endocytosis determines how IGF induces such downstream signaling outputs. Here, we find that the insulin receptor substrate (IRS)−1 modulates how long ligand-activated IGF-IR remains at the cell surface before undergoing endocytosis in mammalian cells. IRS-1 interacts with the clathrin adaptor complex AP2. IRS-1, but not an AP2-binding-deficient mutant, delays AP2-mediated IGF-IR endocytosis after the ligand stimulation. Mechanistically, IRS-1 inhibits the recruitment of IGF-IR into clathrin-coated structures; for this reason, IGF-IR avoids rapid endocytosis and prolongs its activity on the cell surface. Accelerating IGF-IR endocytosis via IRS-1 depletion induces the shift from sustained to transient Akt activation and augments FoxO-mediated transcription. Our study establishes a new role for IRS-1 as an endocytic regulator of IGF-IR that ensures sustained IGF bioactivity, independent of its classic role as an adaptor in IGF-IR signaling.

Dietary inorganic nitrate (NO3-) and its reduced forms nitrite (NO2-) and nitric oxide (NO), respectively, are of critical importance for host defense in the oral cavity. High concentrations of salivary nitrate are linked to a lower prevalence of caries due to growth inhibition of cariogenic bacteria. In-vitro studies suggest that the formation of antimicrobial NO results in an increase of the pH preventing erosion of tooth enamel. The purpose of this study was to prove this effect in-vivo. In a randomized clinical study with 46 subjects we investigated whether NO3- rich beetroot juice exhibits a protective effect against caries by an increase of salivary pH. Our results show that, in comparison to a placebo group, consumption of beetroot juice that contains 4000 mg/L NO3- results in elevated levels of salivary NO2-, nitrite NO3-, and NO. Furthermore, we determined an increase of the mean pH of saliva from 7.0 to 7.5, confirming the anti-cariogenic effect of the used NO3--rich beetroot juice. Taken together, we have found that NO3--rich beetroot juice holds potential effects against dental caries by preventing acidification of human saliva. C-87-15 (Ethics Commissions of Upper Austria).

Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells Multi-level suppression of receptor-PI3K-mTORC1 by fatty acid synthase inhibitors is crucial for their efficacy against ovarian cancer cells