1H‐NMR metabolomic profiling of the crayfish Astacus leptodactylus subjected to polyphenol‐enriched diets

1H-NMR analysis of the hepatopancreas, muscle and haemolymph of Astacus leptodactylus after feeding with polyphenol-enriched diet is reported. 1H-NMR spectra of lipophilic extracts showed the presence of cholesterol, fatty acid residues, phospholipids and triglycerides. 1H-NMR spectra of aqueous extracts identified 35 metabolites in the hepatopancreas, 31 in the muscle and 22 in the haemolymph. A total of 20 metabolites (amino acids and their derivatives) were present in the hepatopancreas, the muscle and the haemolymph. A total of 10 metabolites were present in both the hepatopancreas and the muscle (five amino acids, 2-hydroxybutyrate, choline, myo-inositol, glycogen and uracil). 2-Hydroxyisobutyrate and creatine were present in both the hepatopancreas and the haemolymph. Phosphorylethanolamine, phosphocholine and fumarate were present only in the hepatopancreas and isoleucine only in the muscle. Statistical analysis showed that the percentage of weight gain was statistically higher in polyphenol-enriched diet groups compared to the control and that polyphenols had a stimulating effect on the general metabolism. No stress-related metabolites were higher in crayfish fed with polyphenol-enriched diet. Conversely, phosphatidylcholine, cholesterol and DHA, linked to resistance to environmental stress and diseases, were higher compared to the control diet. This study indicates that 1H-NMR is a useful tool to study the metabolomics in relation to diet differences

Lipophilic phytotoxins produced by Neofusicoccum parvum, a grapevine canker agent

Lipophilic phytotoxins produced by Neofusicoccum parvum, a Botryosphaeriaceae species pathogenic to grapevine, were isolated and identified by spectroscopic methods as (3R,4R)-(-)-4-hydroxymellein, (3R,4S)-(-)-4-hydroxymellein, isosclerone and tyrosol. When assayed for phytotoxicity on tomato plants, all four metabolites showed phytotoxic activity, with (3R,4R)-(-)-4-hydroxymellein and isosclerone the most active. Isosclerone is reported for the first time as produced by a Botryosphaeriaceae specie

Exploring Airway Diseases by NMR-Based Metabonomics: A Review of Application to Exhaled Breath Condensate

There is increasing evidence that biomarkers of exhaled gases or exhaled breath condensate (EBC) may help in detecting abnormalities in respiratory diseases mirroring increased, oxidative stress, airways inflammation and endothelial dysfunction. Beside the traditional techniques to investigate biomarker profiles, “omics” sciences have raised interest in the clinical field as potentially improving disease phenotyping. In particular, metabonomics appears to be an important tool to gain qualitative and quantitative information on low-molecular weight metabolites present in cells, tissues, and fluids. Here, we review the potential use of EBC as a suitable matrix for metabonomic studies using nuclear magnetic resonance (NMR) spectroscopy. By using this approach in airway diseases, it is now possible to separate specific EBC profiles, with implication in disease phenotyping and personalized therapy

Modeling acquired resistance to the second-generation androgen receptor antagonist enzalutamide in the TRAMP model of prostate cancer

Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-naïve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate the mechanisms of resistance and to assess therapeutic settings that may delay or prevent the onset of resistance. In this study, the prostate cancer multistage murine model TRAMP and TRAMP-derived cells have been used to extensively characterize in vitro and in vivo the response and resistance to enzalutamide. The therapeutic profile as well as the resistance onset were characterized and a multiscale stochastic mathematical model was proposed to link the in vitro and in vivo evolution of prostate cancer. The model showed that all therapeutic strategies that use enzalutamide result in the onset of resistance. The model also showed that combination therapies can delay the onset of resistance to enzalutamide, and in the best scenario, can eliminate the disease. These results set the basis for the exploitation of this "TRAMP-based platform" to test novel therapeutic approaches and build further mathematical models of combination therapies to treat prostate cancer and CRPC.Significance: Merging mathematical modeling with experimental data, this study presents the "TRAMP-based platform" as a novel experimental tool to study the in vitro and in vivo evolution of prostate cancer resistance to enzalutamide

Interactions between synthetic vanilloids and the endogenous cannabinoid system

Abstract The chemical similarity between some synthetic agonists of vanilloid receptors, such as olvanil (N-vanillyl-cis-9-octadecenoamide), and the`endocannabinoid' anandamide (arachidonoyl-ethanolamide, AEA), suggests possible interactions between the cannabinoid and vanilloid signalling systems. Here we report that olvanil is a stable and potent inhibitor of AEA facilitated transport into rat basophilic leukemia (RBL-2H3) cells. Olvanil blocked both the uptake and the hydrolysis of (ii) inhibited forskolin-induced cAMP formation in intact N18TG2 cells (IC SH = 1.60 W WM), this effect being reversed by the selective CB1 antagonist SR141716A. Pseudocapsaicin, but not capsaicin, also selectively bound to CB1 receptor-containing membranes. These data suggest that some of the analgesic actions of olvanil may be due to its interactions with the endogenous cannabinoid system, and may lead to the design of a novel class of cannabimimetics with potential therapeutic applications as analgesics. z 1998 Federation of European Biochemical Societies

Lipophilic phytotoxins produced by <I>Neofusicoccum parvum</I>, a grapevine canker agent

Lipophilic phytotoxins produced by Neofusicoccum parvum, a Botryosphaeriaceae species pathogenic to grapevine, were isolated and identified by spectroscopic methods as (3R,4R)-(-)-4-hydroxymellein, (3R,4S)-(-)-4-hydroxymellein, isosclerone and tyrosol. When assayed for phytotoxicity on tomato plants, all four metabolites showed phytotoxic activity, with (3R,4R)-(-)-4-hydroxymellein and isosclerone the most active. Isosclerone is reported for the first time as produced by a Botryosphaeriaceae specie