Evaluation of Candida albicans adhesion and biofilm formation on a denture base acrylic resin containing silver nanoparticles

Aim: This study firstly evaluated the activity of a silver nanoparticle (AgNPs) solution against Candida albicans and then the effect of incorporation of AgNPs into a denture base acrylic resin on the material’s hydrophobicity, C. albicans adhesion and biofilm formation. Methods and Results: The AgNPs solution was synthesized by chemical reduction and characterized. Minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations for planktonic cells and sessile cells (MFCs) of the AgNPs solution against C. albicans were determined. Specimens (n = 360) of silver-incorporated acrylic resin at concentrations of 1000, 750, 500, 250 and 30 ppm were also prepared and stored in PBS for 0, 7, 90 and 180 days. Control was acrylic resin without AgNPs (0 ppm). After the storage periods, contact angles were measured and the specimens were used for C. albicans adherence ('37 GRAUS'; 90 min; n = 9) and biofilm formation ('37 GRAUS'; 48 h; n = 9) by XTT reduction assay. MIC, MFC and MFCs values were 3,98, 15,63 and 1000 ppm, respectively. Incorporation of AgNPs reduced the hydrophobicity of the resin. No effect on adherence and biofilm formation was observed. At 90 and 180 days of storage, there was significant increase in adherence and biofilm formation. Conclusions: Although the AgNPs solution had antifungal activity, no effect on C. albicans adherence and biofilm formation was observed after its incorporation into a denture base resin. Significance and Impact of the Study: The synthesized AgNPs solution is a promising antifungal agent, warranting investigations of more efficient methods of incorporation into denture base resins.FAPESP (08/11700-5; 08/07454-9

Multitarget CFTR Modulators Endowed with Multiple Beneficial Side Effects for Cystic Fibrosis Patients: Toward a Simplified Therapeutic Approach

Cystic fibrosis (CF) is a multiorgan disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR). In addition to respiratory impairment due to mucus accumulation, viruses and bacteria trigger acute pulmonary exacerbations, accelerating disease progression and mortality rate. Treatment complexity increases with patients’ age, and simplifying the therapeutic regimen represents one of the key priorities in CF. We have recently reported the discovery of multitarget compounds able to “kill two birds with one stone” by targeting F508del-CFTR and PI4KIIIβ and thus acting simultaneously as CFTR correctors and broad-spectrum enterovirus (EV) inhibitors. Starting from these preliminary results, we report herein a hit-to-lead optimization and multidimensional structure–activity relationship (SAR) study that led to compound 23a. This compound showed good antiviral and F508del-CFTR correction potency, additivity/synergy with lumacaftor, and a promising in vitro absorption, distribution, metabolism, and excretion (ADME) profile. It was well tolerated in vivo with no sign of acute toxicity and histological alterations in key biodistribution organs

A New Strategy for Glioblastoma Treatment: In Vitro and In Vivo Preclinical Characterization of Si306, a Pyrazolo[3,4-d]Pyrimidine Dual Src/P-Glycoprotein Inhibitor

20siopenOverexpression of P-glycoprotein (P-gp) and other ATP-binding cassette (ABC) transporters in multidrug resistant (MDR) cancer cells is responsible for the reduction of intracellular drug accumulation, thus decreasing the efficacy of chemotherapeutics. P-gp is also found at endothelial cells' membrane of the blood-brain barrier, where it limits drug delivery to central nervous system (CNS) tumors. We have previously developed a set of pyrazolo[3,4-d]pyrimidines and their prodrugs as novel Src tyrosine kinase inhibitors (TKIs), showing a significant activity against CNS tumors in in vivo. Here we investigated the interaction of the most promising pair of drug/prodrug with P-gp at the cellular level. The tested compounds were found to increase the intracellular accumulation of Rho 123, and to enhance the efficacy of paclitaxel in P-gp overexpressing cells. Encouraging pharmacokinetics properties and tolerability in vivo were also observed. Our findings revealed a novel role of pyrazolo[3,4-d]pyrimidines which may be useful for developing a new effective therapy in MDR cancer treatment, particularly against glioblastoma.openFallacara, Anna Lucia; Zamperini, Claudio; Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Stepanović, Marija; Mancini, Arianna; Rango, Enrico; Iovenitti, Giulia; Molinari, Alessio; Bugli, Francesca; Sanguinetti, Maurizio; Torelli, Riccardo; Martini, Maurizio; Maccari, Laura; Valoti, Massimo; Dreassi, Elena; Botta, Maurizio; Pešić, Milica; Schenone, SilviaFallacara, Anna Lucia; Zamperini, Claudio; Podolski-Renić, Ana; Dinić, Jelena; Stanković, Tijana; Stepanović, Marija; Mancini, Arianna; Rango, Enrico; Iovenitti, Giulia; Molinari, Alessio; Bugli, Francesca; Sanguinetti, Maurizio; Torelli, Riccardo; Martini, Maurizio; Maccari, Laura; Valoti, Massimo; Dreassi, Elena; Botta, Maurizio; Pešić, Milica; Schenone, Silvi

The Salmonella enterica Pan-genome

Salmonella enterica is divided into four subspecies containing a large number of different serovars, several of which are important zoonotic pathogens and some show a high degree of host specificity or host preference. We compare 45 sequenced S. enterica genomes that are publicly available (22 complete and 23 draft genome sequences). Of these, 35 were found to be of sufficiently good quality to allow a detailed analysis, along with two Escherichia coli strains (K-12 substr. DH10B and the avian pathogenic E. coli (APEC O1) strain). All genomes were subjected to standardized gene finding, and the core and pan-genome of Salmonella were estimated to be around 2,800 and 10,000 gene families, respectively. The constructed pan-genomic dendrograms suggest that gene content is often, but not uniformly correlated to serotype. Any given Salmonella strain has a large stable core, whilst there is an abundance of accessory genes, including the Salmonella pathogenicity islands (SPIs), transposable elements, phages, and plasmid DNA. We visualize conservation in the genomes in relation to chromosomal location and DNA structural features and find that variation in gene content is localized in a selection of variable genomic regions or islands. These include the SPIs but also encompass phage insertion sites and transposable elements. The islands were typically well conserved in several, but not all, isolates—a difference which may have implications in, e.g., host specificity

Lesbiche che scelgono la maternità: influenza delle minoranze e nuove tecnologie riproduttive

Il termine “nuove tecnologie riproduttive” è emerso nella metà degli anni Ottanta per descrivere l’insieme degli sviluppi clinici e scientifici in grado di aiutare uomini e donne con problemi di fertilità, affinché gli stessi potessero diventare genitori. Qui l’attenzione sarà riposta sul dibattito pubblico riguardante l’uso di queste tecnologie da parte di lesbiche, assumendo una prospettiva di analisi psicosociale

Lesbiche che scelgono la maternit\ue0: Influenza delle minoranze e nuove tecnologie riproduttive

Il termine \u201cnuove tecnologie riproduttive\u201d \ue8 emerso nella met\ue0 degli anni Ottanta per descrivere l\u2019insieme degli sviluppi clinici e scientifici in grado di aiutare uomini e donne con problemi di fertilit\ue0, affinch\ue9 gli stessi potessero diventare genitori. Qui l\u2019attenzione sar\ue0 riposta sul dibattito pubblico riguardante l\u2019uso di queste tecnologie da parte di lesbiche, assumendo una prospettiva di analisi psicosociale

Percorsi migratori, benessere sociale e incontri culturali

Il contributo metta a tema alcuni aspetti cruciali caratterizzanti il percorso migratorio e l\u2019incontro del migrante con la nuova realt\ue0, rileggendo e discutendo i contributi di ricerca raccolti in questo primo numero monografico. Il passaggio dall\u2019idea di \u201cmulticulturalismo\u201d a quella di \u201cintercultura\u201d, uno spazio di convivenza, sempre negoziata e scandita da una fitta rete di scambi sociali, accompagna i diversi contributi presentati, con l\u2019obiettivo di esplorare i percorsi di mutamento che, prima geografici, poi si fanno mentali ed emozionali. Molteplici i nodi tematici affrontati: il progetto migratorio e le numerose variabili ad esso connesse prima della migrazione, la fase iniziale di incontro del migrante con il paese di immigrazione (il sistema politico-normativo, mercato del lavoro, reti di supporto), la fase successiva di stabilizzazione dei migranti con le dinamiche sociali che la caratterizzano e le rilevanti sfide per le societ\ue0 occidentali (promozione del benessere sociale, riconoscimento dell\u2019altro e giustizia sociale)

Lotta per il riconoscimento: La vita quotidiana di madri lesbiche tra mancanza di leggi e presenza di un confronto sociale

Al fine di indagare la cultura relazionale che si genera all\u2019interno di nuove formazioni familiari, basate sull\u2019unione affettiva di due individui dello stesso sesso, e per comprenderne le specifiche dinamiche interne rispetto al mondo esterno, \ue8 stata realizzata una ricerca esplorativa con la partecipazione di un gruppo formato da 17 donne lesbiche, di cui 2 single e 8 coppie (per una coppia \ue8 stato possibile intervistare solo la madre biologica). I dati testuali raccolti con interviste semi-strutturate sono stati analizzati con lo strumento Atlas.ti. Pur essendo una ricerca esplorativa, la vastit\ue0 dei dati raccolti impone qui una breve presentazione generale e un approfondimento specifico legato al tema del riconoscimento giuridico e sociale come problema che caratterizza la vita quotidiana di tali madri