Exploring the potential of graphene oxide nanosheets for porous media decontamination from cationic dyes

Graphene oxide (GO) nanosheets, often embedded in nano-composites, have been studied as promising materials for waste water purification, in particular to adsorb heavy metals and cationic organic contaminants. However, a broader range of potential applications of GO is still unexplored. This work investigated the potential applicability of GO for enhanced in-situ soil washing of secondary sources of groundwater contamination (i.e. the controlled recirculation of a washing GO suspension via injection/extraction wells). The laboratory study aimed at quantifying the capability of GO to effectively remove adsorbed methylene blue (MB) from contaminated sand. The tests were conducted in simplified conditions (synthetic groundwater at NaCl concentration of 20 mM, silica sand) to better highlight the key mechanisms under study. The results indicated a maximum sorption capacity of 1.6 mgMB/mgGO in moderately alkaline conditions. Even though the adsorption of MB onto GO slightly reduced the GO mobility in the porous medium, a breakthrough higher than 95% was obtained for MB/GO mass ratios up to 0.5. This suggests that a very high recovery of the injected particles should be also expected in the field

TAS2R38 is a novel modifer gene in patients with cystic fbrosis

The clinical manifestation of cystic fbrosis (CF) is heterogeneous also in patients with the same cystic fbrosis transmembrane regulator (CFTR) genotype and in afected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was signifcantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifer gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF

A Creatine Transporter Is Operative at the Brush Border Level of the Rat Jejunal Enterocyte

Abstract Although ergogenic effects and health benefits have been reported for creatine used as nutritional supplement, to date little is known about the mechanism of creatine absorption in the small intestine. Thus the current study was undertaken to elucidate the mechanism of creatine intake in rat jejunum with the use of well-purified brush border membrane vesicles, isolated from jejunal enterocyte. Creatine uptake was found markedly stimulated by inwardly directed Na(+) and Cl(- )gradients, potential-sensitive, strongly reduced by the substitution of Na(+) and Cl(-) with various cations and anions and positively affected by intravesicular K(+). Moreover, creatine uptake is: 1) significantly inhibited by creatine structural analogs, 2) abolished by low concentrations of 2-aminoethyl methanethiosulfonate hydrobromide (MTSEA), 3) saturable as a function of creatine concentration with an apparent Michaelis-Menten constant of 24.08 +/- 0.80 muM and a maximal velocity of 391.30 +/- 6.19 pmoles mg protein(-1) 30 s(-1). The transport is electrogenic since at least two Na(+) and one Cl(-) are required to transport one creatine molecule. Western blot analysis showed the same amount of creatine transport protein in the jejunal apical membrane when compared to ileum. Thus, these data demonstrate the existence of a Na(+)- and Cl(-)-dependent, membrane potential-sensitive, electrogenic carrier-mediated mechanism for creatine absorption in rat jejunal apical membrane vesicles, which is biochemically and pharmacologically similar to those observed in other tissues. However, in other cell types the stimulatory effect of intravesicular K(+) was never detected

Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors

Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC

Estensione dell'analisi di rischio sanitario ambientale a contaminazioni di nanomateriali in sistemi acquiferi

Il largo impiego dei nanomateriali in numerosi processi industriali ha sollevato particolare attenzione attorno alle questioni sanitarie connesse ad una loro potenziale diffusione in ambiente. Tuttavia, a causa della natura polidispersa dei nanomateriali, il rischio sanitario ambientale associato ad una contaminazione da nanoparticelle (NP) non può essere quantificato tramite la procedura ASTM comunemente applicata per le altre sostanze chimiche. NP di dimensione diverse sono infatti caratterizzate da differente tossicità e mobilità nei comparti ambientali. In questo studio viene proposto un approccio per l’adattamento della procedura ASTM al caso di acquiferi contaminati da NP. Le soluzioni analitiche usate per l’analisi di rischio di Livello 2 di sostanze disciolte sono qui adattate ed estese per tenere conto dei meccanismi di trasporto propri delle NP. Vengono infine presentati due casi applicativi della procedura proposta, uno teorico ed uno sperimentale-modellistico, facendo particolare riferimento al ruolo dell’eterogeneità granulometrica delle NP nella quantificazione del rischio sanitario ambientale

Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis

Background: To date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in children and young adults affected by Cystic Fibrosis (CF). Methods: In this study, 21 CF patients aged 10–25 underwent oral glucose tolerance test (OGTT) before and after 12–18 months of treatment with Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor. β-cell function (i.e., first and second phase of insulin secretion measured as derivative and proportional control, respectively) and insulin clearance were estimated by OGTT mathematical modelling. Insulin sensitivity was estimated by the Oral Glucose Sensitivity Index (OGIS). The dynamic interplay between β-cell function, insulin clearance and insulin sensitivity was analysed by vector plots of glucose-stimulated insulin bioavailability vs. insulin sensitivity. Results: No changes in glucose tolerance occurred after either treatment, whereas a significant improvement in pulmonary function and chronic bacterial infection was observed. Beta cell function and insulin clearance did not change in both treatment groups. Insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. The analysis of vector plots confirmed that glucose regulation was stable in both groups. Conclusions: Treatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants

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