The extraction of yellow gentian root (Gentiana lutea L .)

 Several solvents have been investigated for the preparation of bitter compounds of gentian roots (Gentiana lutea L.) for food applications. The highest concentrations of the bitter compounds, amarogentin and gentiopicroside, were obtained with ethanol : water 55 : 45 (v/v), propylene glycol: water 30 : 70 (v/v) and ethanol: propylene glycol: water 20 : 20 : 60 (v/v/v). Enzyme treatment prior to solvent extraction gave a greater extract yield (3.5%) but the amarogentin and gentiopicroside concentrations remained the same. The volatile fraction was affected by the solvent used through the formation of esters of organic acids from the plant. Received: 22 January 1997 / Revised version: 18 March 1997     

Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis

Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS.     

Bis-(thio)ethers as Chelating Ligands for the Pd-Catalyzed Alternating CO/tert-Butylstyrene Copolymerization

We synthesized and characterized new neutral and cationic palladium(II) complexes containing bis-(thio)ether ligands. The cationic compounds catalyzed the alternating CO/tert-butylstyrene copolymerization leading to polyketones with different degrees of stereoregularity depending on the nature of the S-S ligand.     

Galectin‐3‐Binding Glycomimetics that Strongly Reduce Bleomycin‐Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition

Discovery of glycan‐competitive galectin‐3‐binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin‐3 accumulation at damaged vesicles, hence revealing galectin‐3–glycan interactions involved in fibrosis progression and in intracellular galectin‐3 activities, is reported. 3,3′‐Bis‐(4‐aryltriazol‐1‐yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin‐1, ‐2, ‐3, and ‐4 N‐terminal, ‐4 C‐terminal, ‐7 and ‐8 N‐terminal, ‐9 N‐terminal, and ‐9 C‐terminal domains. Compounds displaying low‐nanomolar affinities for galectins‐1 and ‐3 were identified in a competitive fluorescence anisotropy assay. X‐ray structural analysis of selected compounds in complex with galectin‐3, together with galectin‐3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin‐3. The most potent galectin‐3 antagonist was demonstrated to act in an assay monitoring galectin‐3 accumulation upon amitriptyline‐induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin–carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin‐induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.     

Highly sensitive PCR-based detection method specific for Aspergillus flavus in wheat flour

Aspergillus flavus is frequently found in food, producing a wide variety of toxins, aflatoxins being the most relevant in food safety. A specific PCR-based protocol for this species is described which allowed discrimination from other closely related species having different profiles of secondary metabolites from the Aspergillus Section Flavi, particularly A. parasiticus. The specific primers were designed on the multi-copy internal transcribed region of the rDNA unit (ITS1-5.8S-ITS2 rDNA) and were tested in a wide sample of related species and other fungal species commonly found in food. The PCR assay was coupled with a fungal enrichment and a DNA extraction method for wheat flour to enhance the sensitivity of the diagnostic protocol. The results indicated that the critical PCR amplification product was clearly observed for wheat flour contaminated by 10² spores after 16 h of incubation.     

Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease

Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valve has not been investigated. We aim to explore IL-33 as a possible inductor of myxomatous degeneration in human mitral valves. We enrolled 103 patients suffering from severe mitral regurgitation due to myxomatous degeneration undergoing mitral valve replacement. Immunohistochemistry of the resected leaflets showed IL-33 and ST2 expression in both valve interstitial cells (VICs) and valve endothelial cells (VECs). Positive correlations were found between the levels of IL-33 and molecules implicated in the development of myxomatous MVD, such as proteoglycans, extracellular matrix remodeling enzymes (matrix metalloproteinases and their tissue inhibitors), inflammatory and fibrotic markers. Stimulation of single cell cultures of VICs and VECs with recombinant human IL-33 induced the expression of activated VIC markers, endothelial–mesenchymal transition of VECs, proteoglycan synthesis, inflammatory molecules and extracellular matrix turnover. Our findings suggest that the IL-33/ST2 system may be involved in the development of myxomatous MVD by enhancing extracellular matrix remodeling.     

Definition of requirements for accessing multilingual information opinions

Multimedia Tools and Applications - In this paper, we will present a study concerning the understanding of the needs of people using Internet in order to access to multilingual information. In...