La comunidad de los otros. A partir de Jean-Luc Nancy

El tema de la "comunidad" es central desde el punto de vista antropológico, ético y filosófico-político. A partir de los años 80 se despliega un debate en el pensamiento francés, y ya en los 90 son autores italianos los que participan en él. La posible-imThe topic of the "community" has a fundamental relevance from the anthropological, ethical and political point of view. Starting from the years 80 in france, and then during the 90 in italy, the debate has been developed in a very vivid manner. The possi

Cardioprotective Effects of Grapefruit IntegroPectin Extracted via Hydrodynamic Cavitation from By-Products of <i>Citrus</i> Fruits Industry: Role of Mitochondrial Potassium Channels

Citrus flavonoids are well-known for their beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; in addition, the clinical trials are also inconsistent. Their limited bioavailability can be, at least in part, the reason for these discrepancies. Therefore, many efforts have been made towards the improvement of their bioavailability. Hydrodynamic cavitation methods were successfully applied to the extraction of byproducts of the Citrus fruits industry, showing high process yields and affording stable phytocomplexes, known as IntegroPectin, endowed with great amounts of bioactive compounds and high water solubility. The cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. Further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of the flavonoids, showed anti-ischemic cardioprotective activity, which was better than pure naringenin (the bioactive aglycone of naringin). On cardiac-isolated mitochondria, this extract confirmed that naringenin/naringin were involved in the activation of mitochondrial potassium channels. The hydrodynamic cavitation-based extraction confirmed a valuable opportunity for the exploitation of Citrus fruits waste, with the end product presenting high levels of Citrus flavonoids and improved bioaccessibility that enhances its nutraceutical and economic value

Design and Synthesis of New Oligopeptidic Parvulin Inhibitors

: Pin1 catalyzes the cis-trans isomerization of pThr-Pro or pSer-Pro amide bonds of different proteins involved in several physio/pathological processes. In this framework, recent research activity is directed towards the identification of new selective Pin1 inhibitors. Here, we developed a set ( 5a - p ) of peptide-based Pin1 inhibitors. Direct-binding experiments allowed the identification of the peptide-based inhibitor 5k as a potent ligand of Pin1. Notably, 5k binds Pin1 with a higher affinity compared to Pin4. The comparative analysis of molecular models of Pin1 and Pin4 with the selected compound, gave a rational explanation of the biochemical activity, and pinpointed the chemical elements that, if opportunely modified, may further improve inhibitory potency, pharmacological properties and selectivity of future peptide-based Parvulin inhibitors. Since 5k showed a limited cell penetration and no antiproliferative activity, it was conjugated to a polyarginine stretch, known to promote cell penetration of peptides, to obtain R8-5k derivative, which displayed an anti-proliferative effect on cancer cell lines compared to non-tumor cells. The effect of R8 on cell proliferation was also investigated. This work doubts the application of the R8 strategy for the development of cell penetrating antiproliferative peptides since it is not inert

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities