Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase

One of the most prominent alterations in cancer cells is their strict dependence on the glycolytic pathway for ATP generation. This observation led to the evaluation of glycolysis inhibitors as potential anticancer agents. The inhibition of lactate dehydrogenase (LDH) is a promising way to inhibit tumor cell glucose metabolism without affecting the energetic balance of normal tissues. However, the success of this approach depends chiefly on the availability of inhibitors that display good selectivity. We identified a compound (galloflavin, CAS 568‐80‐9) which, in contrast to other inhibitors of human LDH, hinders both the A and B isoforms of the enzyme. To determine the mechanism of action, we collected LDH‐A and ‐B inhibition data in competition reactions with pyruvate or NADH and evaluated the results using software for enzyme kinetics analysis. We found that galloflavin inhibits both human LDH isoforms by preferentially binding the free enzyme, without competing with the substrate or cofactor. The calculated K_i values for pyruvate were 5.46 μM (LDH‐A) and 15.06 μM (LDH‐B). In cultured tumor cells, galloflavin blocked aerobic glycolysis at micromolar concentrations, did not interfere with cell respiration, and induced cell death by triggering apoptosis. To our knowledge, the inhibition of LDH is, to date, the only biochemical effect described for galloflavin. Because galloflavin is not commercially available, we also describe herein a procedure for its synthesis and report its first full chemical characterization.     

Survival of Lactobacillus rhamnosus strains inoculated in cheese matrix during simulated human digestion

Survival of probiotic bacteria during transit through the gastrointestinal (GI) tract is influenced by a number of environmental variables including stomach acidity, bile salts, digestive enzymes and food matrix. This study assessed survival of seven selected Lactobacillus rhamnosus strains delivered within a model cheese system to the human upper GI tract using a dynamic gastric model (DGM). Good survival rates for all tested strains were recorded during both simulated gastric and duodenal digestion. Strains H12, H25 and N24 demonstrated higher survival capacities during gastric digestion than L. rhamnosus GG strain used as control, with H12 and N24 continuing to grow during duodenal digestion. Strains L. rhamnosus F17, N24 and R61 showed adhesion properties to both HT-29 and Caco-2 cells. The ability to attach to the cheese matrix during digestion was confirmed by scanning electron microscopy, also indicating production of extracellular polysaccharides as a response to acid stress.     

Effect of micro-oxygenation on sensory characteristics and consumer preference of Cabernet Sauvignon wine

BACKGROUND: The main objective of this study was to improve the structure of a Cabernet Sauvignon red wine in a short period of time by micro‐oxygenation (MOX) at high rates (25 and 50 mL L^?1 month^?1), the effects of which were evaluated based on sensory characteristics and consumer preference. Sensory data were analysed by principal component analysis, discriminant analysis and ordinal logistic regression (OLR). RESULTS: MOX led to significant differences in the colour, colour stability and phenolic compounds of wine. Sensory characteristics also changed through MOX treatment, and wine experts were able to discriminate between MOX‐treated and untreated samples, with olfactory intensity, complexity, astringency and roundness being the main discriminating characteristics. Ordinal logistic regression enabled identification of the sensory characteristics that drove consumer preference. CONCLUSION: MOX at high rates improved the sensory characteristics of wine and may therefore be considered a valid technique for obtaining structured wines in a short period of time, i.e. within just a few months after the vintage. The results highlight the need for (i) careful selection of the MOX dosage rate and duration (the 25 mL L^?1 month^?1 dose for 6 days provided the best result) and (ii) continuous monitoring of the MOX treatment. Copyright © 2011 Society of Chemical Industry     

A criterion for the assessment of the reliability of ASHRAE conduction transfer function coefficients

This paper presents a new mathematical approach, which, when applied to conduction transfer functions (CTFs) of a multi-layered wall, is able to predict the reliability of building simulations. This new procedure can be used to identify the best set of CTF coefficients, which are a critical point at the core of the ASHRAE calculation methodology founded on the transfer function method. To evaluate the performance of different CTF coefficient sets, the authors performed a large number of thermal simulations on the multi-layered walls included in the ASHRAE Handbook, volume fundamentals, and on other walls typical of Mediterranean building heritage. Those data were employed to test an algorithm able to assess the reliability of the simulations. The numerical results show that it is possible to select the optimal number of coefficients on the basis of the size of the poles of a CTF. The proposed criterion, which employs a pole threshold value, is highly accurate, fast and easy to integrate in the most diffuse building simulation tools.     

A comparison of analytical methods for measuring the color components of red wines

The monomeric and polymeric pigments of 20 young red wines were analysed using most recent of the approaches available for phenolics measurements in wine, including: (i) HPLC with silica-based reversed-phase, (ii) HPLC with polymeric-based reversed-phase columns, (iii) the spectrophotometric Adams’ tannin and polymeric pigments assay, (iv) the Boulton’s copigmentation assay, and (v) the Somers’ unbleached polymeric color assay. Moreover, a modification of an existing HPLC method, i.e. the addition of SO₂ to the mobile phases, allowed the unbleached polymeric pigments to be analysed by HPLC for the first time. The wines displayed a variation in their color density at 520 nm that ranged by 10-fold, and included wines made from Pinot noir, Merlot, Cabernet sauvignon, Cabernet franc, Sangiovese, Cagnulari and Cannonau grapes. The total color of wines was an aggregate number of three components: copigmentation (8–30%), total free anthocyanins (24–35%), and polymeric pigment (35–63%). Cross-comparison between the selected method was performed and discussed. In particular, the polymeric pigments estimated by HPLC with polymeric-based reversed-phase column were in good agreement with the result of the reversed-phase C₁₈ column (R² = 0.9703) and the sum of small and large polymeric pigments estimated by the Adams’ assay (R² = 0.9511). The level of copigmentation can be almost completely described by the levels of monomeric pigments (R² = 0.9464) and not by the tannin content as has often been suggested (copigmentation vs tannin: R² = 0.4827).     

Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.     

How Important Are Genes to Achieve Longevity?

Several studies on the genetics of longevity have been reviewed in this paper. The results show that, despite efforts and new technologies, only two genes, APOE and FOXO3A, involved in the protection of cardiovascular diseases, have been shown to be associated with longevity in nearly all studies. This happens because the genetic determinants of longevity are dynamic and depend on the environmental history of a given population. In fact, population-specific genes are thought to play a greater role in the attainment of longevity than those shared between different populations. Hence, it is not surprising that GWAS replicated associations of common variants with longevity have been few, if any, as these studies pool together different populations. An alternative way might be the study of long-life families. This type of approach is proving to be an ideal resource for uncovering protective alleles and associated biological signatures for healthy aging phenotypes and exceptional longevity.     

MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis

We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets.     

Modelling the evolution of oxidative browning during storage of white wines: effects of packaging and closures

Shelf life of products is a key parameter for any company at local and international level that wish to improve their competitiveness; thus, there is a need to search for methods that allow one to predict the shelf life of bottled wines. In this view, the progress of chemical oxidative reactions of six Italian white wines during storage (10 months after bottling), in different packaging, was monitored by means of selected oenological parameters. The optical density at 420 nm, an index of browning, showed a progressive increase that fitted the zero‐order kinetic rate. The onset of wine browning was further tested by means of accelerated ageing in controlled temperature conditions which results, modelled using the rate constants approach, showed an Arrhenius‐like dependence from temperature, allowing to estimate apparent activation energies of oxidative chemical browning (range: 46.8–88.3 kJ mol^?1). Kinetic and thermodynamic approach provided a useful tool to predict quality changes of white wines during storage with respect to packaging conditions.