Effect of microbial fermentation on functional traits and volatiloma profile of pâté olive cake.

In this study, the pâté olive cake (POC), a by-product of the olive oil industry, was subjected to fermentation in a bioreactor using three microbial strains, Lactiplantibacillus plantarum, Wickerhamomyces anomalus and Candida boidinii, previously isolated from fermented table olive brines. Chemical, microbiological and molecular analyses were carried out at the beginning and at the end of fermentation. The lowest pH value (4.09) was reached after 10 days in sample inoculated with C. boidinii. Microbiological analyses exhibited the dominance of yeasts throughout the whole process (from 5.5 to 7.80 Log10 CFU/g), as confirmed by PCR-DGGE analysis. The microbial cultures affected both phenolic and volatile organic compound profiles. Moreover, the POC samples treated with different microbial strains were investigated for biological assays. The sample fermented with W. anomalus showed the greatest diffusion speed of transepithelial transport through Caco-2 cell, the highest inhibitory activity towards the tested cyclooxygenases and the highest antioxidant activity.

ß(3)-Adrenoceptor agonists and (antagonists as) inverse agonists history, perspective, constitutive activity, and stereospecific binding.

ß(3)-Adrenergic receptor (ß(3)-AR) is expressed in several tissues and is considered a drug target for the treatment of several pathologies such as obesity, type 2 diabetes, cachexia, metabolic syndrome, heart failure, anxiety and depressive disorders, preterm labor, overactive bladder, control colon motility, and of coadjuvants in colon cancer therapy. It is a seven-transmembrane domain (7TD) G-protein coupled receptor and is usually coupled to a Gs-protein (Gi-protein in very few cases), and its stimulation increases the production of cAMP. A lot of ß(3)-AR agonists have been uncovered and extensively characterized. Conversely, very little is known about ß(3)-AR inverse agonists that would suppress the agonist-independent activity (constitutive activity) of the receptor by stabilizing it in its inactive state. This chapter attempts to outline (a) the importance of the ß(3)-AR as a therapeutic target through the disquisition of its role in human health (physiology) and disease (pathology); (b) the description of ß(3)-AR structure [amino acid sequence and 7TD organization]; (c) the medicinal chemistry of ß(3)-AR: 7TD amino acid-ligand specific interactions, ß-adrenoreceptor subtype selectivity, stereospecific interactions and biological activity relationships, inverse agonism and blockage of ß(3)-adrenoceptor constitutive activity; and (d) ß(3)-AR inverse agonists. The detailed procedure to prepare and assess the biological activity/selectivity of the more potent and selective ß(3)-AR inverse agonists (SP-1e and SP-1g) up to now known is also described.

Receptor-drug interaction: europium employment for studying the biochemical pathway of g-protein-coupled receptor activation.

In medicinal chemistry field, the biochemical pathways, involved in 7-transmembrane domains G-protein coupled receptors (GPCRs) activation, are commonly studied to establish the activity of ligands towards GPCRs. The most studied steps are the measurement of activated GTP-alpha subunit and stimulated intracellular cAMP. At the present, many researchers defined agonist or antagonist activity of potential GPCRs drugs employing [(35)S]GTPgammaS or [(3)H]cAMP as probes. Recently, the corresponding lanthanide labels Eu-GTP and Eu-cAMP as alternative to radiochemicals have been developed because they are highly sensitive, easy to automate, easily synthesized, they display a much longer shelf-life and they can be used in multilabel experiments. In the present review, the receptor-drug interaction by europium employment for studying the biochemical pathway of GPCR activation has been focused. Moreover, comparative studies between lanthanide label probes and the corresponding radiolabeled compounds have been carried out.