Marx e i marxismi

No hi ha abstract

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

<div><p>Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in <i>Cftr^F508del</i> homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the <i>F508del-CFTR</i> mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from <i>F508del</i> homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both <i>in vivo</i>, in mice, and <i>in vitro</i>, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 <i>F508del-CFTR</i> homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells <i>in vivo</i>, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of <i>TNF/TNF-alpha (tumor necrosis factor)</i> and <i>CXCL8</i> (<i>chemokine [C-X-C motif] ligand 8</i>) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the <i>F508del-CFTR</i> mutation.</p></div

Libertà politica e virtù civile. Significati e percorsi del repubblicanesimo classico

Tra storia e filosofia della politica, il volume analizza il ruolo delle idee politiche repubblicane nella formazione delle repubbliche moderne e propone spunti di riflessione sul significato del repubblicanesimo per il futuro delle democrazie.- Indice #5- Introduzione, Maurizio Viroli #9- Il repubblicanesimo di Machiavelli, Maurizio Viroli #19- Declino e durata delle repubbliche e delle idee repubblicane nell’Italia del Cinquecento, Elena Fasano Guarini #49- Patriottismo e riforma politica, Rosario Villari #113- Le idee repubblicane e la Rivoluzione inglese, Blair Worden #127- Cittadini, clienti e creditori: la repubblica come critica del mutamento storico, John G. A. Pocock #151- Le trasformazioni del repubblicanesimo classico nella Francia del Settecento, Keith Michael Baker #167- Virtù e Vittorianesimo. I valori repubblicani del liberalismo inglese, 1860/1890, Eugenio F. Biagini #195- Tra virtù e libertà: percorsi dell’idea repubblicana nella Francia ottocentesca (1830/1875), Mirella Larizza #217- La tradizione repubblicana nell’Italia dell’Ottocento e del Novecento, Massimo L. Salvadori #245- Considerazioni sulla libertà repubblicana, Quentin Skinner #267- “Moderno repubblicanesimo”? La promessa della società civile, Benjamin R. Barber #279- La moderna repubblica: mito o realtà?, Jean Fabien Spitz #30