• Standard, transepithelial and iontophoresis corneal cross-linking: clinical analysis of three surgical techniques.

    Publication Date: 28/11/2017, on International ophthalmology
    by Rossi S, Santamaria C, Boccia R, De Rosa L, D'Alterio FM, Simonelli F, De Rosa G
    DOI: 10.1007/s10792-017-0772-3

    To evaluate the clinical results of standard, transepithelial (TE) and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive keratoconus.

  • Bisphenol A and Bisphenol S release in milk under household conditions from baby bottles marketed in Italy.

    Publication Date: 27/11/2017, on Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes
    by Russo G, Barbato F, Cardone E, Fattore M, Albrizio S, Grumetto L
    DOI: 10.1080/03601234.2017.1388662

    A simple and sensitive validated analytical method based on liquid chromatography coupled to tandem fluorescence (FD) and ultraviolet (UV) spectrophotometry was applied to monitor the presence of bisphenol A and bisphenol S in plastic baby bottles marketed in Italy. The limits of detection (LOD) were 3.75 ng mL-1 and 80.00 ng mL-1, and those of quantification (LOQ) were 12.51 ng mL-1 and 260.00 ng mL-1 for BPA (FD detection) and for BPS (UV detection), respectively. BPA was found in only four samples, two samples undergone to microwave heating and two samples undergone to bottle warmer heating either at 40°C or at 80°C. Although the quantities of leached BPA were well below the reference dose for daily intake established by the European Food Safety Authority (EFSA) (4.0 µg kg-1 bw/day), the release of BPA and BPS from these plastic materials should be carefully considered by the government authorities to increase people's awareness on this issue and to protect the most vulnerable population group.

  • Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.

    Publication Date: 03/11/2017, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Cardinale A, Fusco FR, Paldino E, Giampà C, Marino M, Nuzzo MT, D'Angelo V, Laurenti D, Straccia G, Fasano D, Sarnataro D, Squillaro T, Paladino S, Melone MAB
    DOI: 10.1007/s10072-017-3168-2

    Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

  • Probing the Eumelanin-Silica Interface in Chemically Engineered Bulk Hybrid Nanoparticles for Targeted Subcellular Antioxidant Protection.

    Publication Date: 01/11/2017, on ACS applied materials & interfaces
    by Silvestri B, Vitiello G, Luciani G, Calcagno V, Costantini A, Gallo M, Parisi S, Paladino S, Iacomino M, D'Errico G, Caso MF, Pezzella A, d'Ischia M
    DOI: 10.1021/acsami.7b11839

    We disclose herein the first example of stable monodispersed hybrid nanoparticles (termed MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a silica nanoscaffold matrix and endowed with high antioxidant and cytoprotective effects associated with a specific subcellular localization. MelaSil-NPs have been fabricated by an optimized sol-gel methodology involving ammonia-induced oxidative polymerization of a covalent conjugate of the eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA) with 3-aminopropyltriethoxysilanes (APTS). They displayed a round-shaped (ca. 50-80 nm) morphology, exhibited the typical electron paramagnetic resonance signal of eumelanin biopolymers, and proved effective in promoting decomposition of hydrogen peroxide under physiologically relevant conditions. When administered to human ovarian cancer cells (A2780) or cervical cancer cells (HeLa), MelaSil-NPs were rapidly internalized and colocalized with lysosomes and exerted efficient protecting effects against hydrogen peroxide-induced oxidative stress and cytotoxicity.

  • Antitumour activity of resveratrol on human melanoma cells: A possible mechanism related to its interaction with malignant cell telomerase.

    Publication Date: 01/11/2017, on Biochimica et biophysica acta
    by Platella C, Guida S, Bonmassar L, Aquino A, Bonmassar E, Ravagnan G, Montesarchio D, Roviello GN, Musumeci D, Fuggetta MP
    DOI: 10.1016/j.bbagen.2017.08.001

    trans-Resveratrol (tRES) is a polyphenolic stilbene found in plant products which has attracted great attention because of its antioxidant, anti-inflammatory and anticancer properties.

  • Binding of Harmine Derivatives to DNA: A Spectroscopic Investigation.

    Publication Date: 27/10/2017, on Molecules (Basel, Switzerland)
    by Pagano B, Caterino M, Filosa R, Giancola C
    DOI: 10.3390/molecules22111831

    Harmine belongs to a group of β-carboline alkaloids endowed with antitumor properties. Harmine and its derivatives are thought to bind to DNA and interfere with topoisomerase activities. We investigated the base-dependent binding of harmine, and three of its synthetic anticancer-active derivatives to the genomic DNA from calf thymus and two synthetic 20-mer double helices, the poly(dG-dC)·poly(dG-dC) and the poly(dA-dT)·poly(dA-dT), by means of UV-Vis and circular dichroism (CD) spectroscopies. The data show that the DNA binding and stabilising properties of the investigated derivatives are base pair-dependent. These results could be used as a guide to design and develop further bioactive analogues.

  • Deregulation of MicroRNAs mediated control of carnitine cycle in prostate cancer: molecular basis and pathophysiological consequences.

    Publication Date: 26/10/2017, on Oncogene
    by Valentino A, Calarco A, Di Salle A, Finicelli M, Crispi S, Calogero RA, Riccardo F, Sciarra A, Gentilucci A, Galderisi U, Margarucci S, Peluso G
    DOI: 10.1038/onc.2017.216

    Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. Moreover, the analysis of human prostate cancer and prostate control specimens confirmed the aberrant expression of miR-124-3p, miR-129-5p and miR-378 in primary tumors. Forced expression of the miRNAs mentioned above affected tumorigenic properties, such as proliferation, migration and invasion, in PC3 and LNCaP cells regardless of their hormone sensitivity. CPT1A, CACT and CrAT overexpression allow PCCs to be more prone on FA utilization than normal prostate cells, also in the presence of high pyruvate concentration. Finally, the simultaneous increase of CPT1A, CACT and CrAT is fundamental for PCCs to sustain FA oxidation in the presence of heavy lipid load on prostate cancer mitochondria. Indeed, the downregulation of only one of these proteins reduces PCCs metabolic flexibility with the accumulation of FA-intermediate metabolites in the mitochondria. Together, our data implicate carnitine cycle as a primary regulator of adaptive metabolic reprogramming in PCCs and suggest new potential druggable pathways for prevention and treatment of prostate cancer.

  • Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe Inherited Retinal Dystrophies.

    Publication Date: 20/10/2017, on Genes
    by Di Iorio V, Karali M, Brunetti-Pierri R, Filippelli M, Di Fruscio G, Pizzo M, Mutarelli M, Nigro V, Testa F, Banfi S, Simonelli F
    DOI: 10.3390/genes8100280

    We performed a clinical and genetic characterization of a pediatric cohort of patients with inherited retinal dystrophy (IRD) to identify the most suitable cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18 years, with severe isolated IRD at the time of presentation. The ophthalmological characterization also included assessment of the photoreceptor layer integrity in the macular region (ellipsoid zone (EZ) band). In parallel, we carried out a targeted, next-generation sequencing (NGS)-based analysis using a panel that covers over 150 genes with either an established or a candidate role in IRD pathogenesis. Based on the ophthalmological assessment, the cohort was composed of 24 Leber congenital amaurosis, 14 early onset retinitis pigmentosa, and 5 achromatopsia patients. We identified causative mutations in 58.1% of the cases. We also found novel genotype-phenotype correlations in patients harboring mutations in the CEP290 and CNGB3 genes. The EZ band was detectable in 40% of the analyzed cases, also in patients with genotypes usually associated with severe clinical manifestations. This study provides the first detailed clinical-genetic assessment of severe IRDs with infantile onset and lays the foundation of a standardized protocol for the selection of patients that are more likely to benefit from gene replacement therapeutic approaches.

  • Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

    Publication Date: 12/10/2017, on International journal of molecular sciences
    by De Luca C, Virtuoso A, Maggio N, Papa M
    DOI: 10.3390/ijms18102128

    Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

  • Adherence to Barcelona Clinic Liver Cancer guidelines in field-practice: results of Progetto Epatocarcinoma Campania.

    Publication Date: 10/10/2017, on Journal of gastroenterology and hepatology
    by Guarino M, Tortora R, de Stefano G, Coppola C, Morisco F, Megna AS, Izzo F, Nardone G, Piai G, Adinolfi LE, D'Adamo G, Gaeta GB, Messina V, Francica G, De Girolamo V, Coppola N, Persico M, Di Costanzo GG,
    DOI: 10.1111/jgh.14013

    The BCLC algorithm is the standard system for clinical management of HCC. Data on adherence to this therapeutic paradigm are scarce.

  • Evaluating the Effects of an Organic Extract from the Mediterranean Sponge Geodia cydonium on Human Breast Cancer Cell Lines.

    Publication Date: 09/10/2017, on International journal of molecular sciences
    by Costantini S, Guerriero E, Teta R, Capone F, Caso A, Sorice A, Romano G, Ianora A, Ruocco N, Budillon A, Costantino V, Costantini M
    DOI: 10.3390/ijms18102112

    Marine sponges are an excellent source of bioactive secondary metabolites for pharmacological applications. In the present study, we evaluated the chemistry, cytotoxicity and metabolomics of an organic extract from the Mediterranean marine sponge Geodia cydonium, collected in coastal waters of the Gulf of Naples. We identified an active fraction able to block proliferation of breast cancer cell lines MCF-7, MDA-MB231, and MDA-MB468 and to induce cellular apoptosis, whereas it was inactive on normal breast cells (MCF-10A). Metabolomic studies showed that this active fraction was able to interfere with amino acid metabolism, as well as to modulate glycolysis and glycosphingolipid metabolic pathways. In addition, the evaluation of the cytokinome profile on the polar fractions of three treated breast cancer cell lines (compared to untreated cells) demonstrated that this fraction induced a slight anti-inflammatory effect. Finally, the chemical entities present in this fraction were analyzed by liquid chromatography high resolution mass spectrometry combined with molecular networking.

  • Identification of novel direct protein-protein interactions by irradiating living cells with femtosecond UV laser pulses.

    Publication Date: 07/10/2017, on Biochemical and biophysical research communications
    by Itri F, Monti DM, Chino M, Vinciguerra R, Altucci C, Lombardi A, Piccoli R, Birolo L, Arciello A
    DOI: 10.1016/j.bbrc.2017.08.037

    The identification of protein-protein interaction networks in living cells is becoming increasingly fundamental to elucidate main biological processes and to understand disease molecular bases on a system-wide level. We recently described a method (LUCK, Laser UV Cross-linKing) to cross-link interacting protein surfaces in living cells by UV laser irradiation. By using this innovative methodology, that does not require any protein modification or cell engineering, here we demonstrate that, upon UV laser irradiation of HeLa cells, a direct interaction between GAPDH and alpha-enolase was "frozen" by a cross-linking event. We validated the occurrence of this direct interaction by co-immunoprecipitation and Immuno-FRET analyses. This represents a proof of principle of the LUCK capability to reveal direct protein interactions in their physiological environment.

  • Fluorescent Thrombin Binding Aptamer-Tagged Nanoparticles for an Efficient and Reversible Control of Thrombin Activity.

    Publication Date: 05/10/2017, on ACS applied materials & interfaces
    by Riccardi C, Russo Krauss I, Musumeci D, Morvan F, Meyer A, Vasseur JJ, Paduano L, Montesarchio D
    DOI: 10.1021/acsami.7b11195

    Progress in understanding and treatment of thrombotic diseases requires new effective methods for the easy, rapid, and reversible control of coagulation processes. In this framework, the use of aptamers, and particularly of the thrombin binding aptamer (TBA), has aroused strong interest, due to its enormous therapeutic potential, associated with a large number of possible applications in biotechnological and bioanalytical fields. Here, we describe a new TBA analogue (named tris-mTBA), carrying three different pendant groups: a dansyl residue at the 3'- and a β-cyclodextrin moiety at the 5'-end-providing a host-guest system which exhibits a marked fluorescence enhancement upon TBA G-quadruplex folding-and a biotin tag, allowing the attachment of the aptamer onto biocompatible streptavidin-coated silica nanoparticles (NPs) of 50 nm hydrodynamic diameter (Sicastar). The use of nanoparticles for the in vivo delivery of TBA, expected to induce per se increased nuclease resistance and improved pharmacokinetic properties of this oligonucleotide, offers as an additional advantage the possibility to exploit multivalency effects, due to the presence of multiple copies of TBA on a single scaffold. In addition, the selected fluorescent system allows monitoring both the presence of TBA on the functionalized NPs and its correct folding upon immobilization, also conferring enhanced enzymatic resistance and bioactivity. The anticoagulant activity of the new tris-mTBA, free or conjugated to Sicastar NPs, was evaluated by dynamic light scattering experiments. Highly effective and reversible inhibition of thrombin activity toward fibrinogen was found for the free tris-mTBA and especially for the tris-mTBA-conjugated NPs, demonstrating great potential for the biomedical control of blood clotting.

  • Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network.

    Publication Date: 04/10/2017, on PloS one
    by Kondili LA, Gaeta GB, Brunetto MR, Di Leo A, Iannone A, Santantonio TA, Giammario A, Raimondo G, Filomia R, Coppola C, Amoruso DC, Blanc P, Del Pin B, Chemello L, Cavalletto L, Morisco F, Donnarumma L, Rumi MG, Gasbarrini A, Siciliano M, Massari M, Corsini R, Coco B, Madonia S, Cannizzaro M, Zignego AL, Monti M, Russo FP, Zanetto A, Persico M, Masarone M, Villa E, Bernabucci V, Taliani G, Biliotti E, Chessa L, Pasetto MC, Andreone P, Margotti M, Brancaccio G, Ieluzzi D, Borgia G, Zappulo E, Calvaruso V, Petta S, Falzano L, Quaranta MG, Weimer LE, Rosato S, Vella S, Giannini EG
    DOI: 10.1371/journal.pone.0185728

    Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.

  • New Perspectives in Cancer: Modulation of Lipid Metabolism and Inflammation Resolution.

    Publication Date: 03/10/2017, on Pharmacological research
    by Prevete N, Liotti F, Amoresano A, Pucci P, de Paulis A, Melillo RM
    DOI: 10.1016/j.phrs.2017.09.024

    Inflammation is considered an enabling feature of cancer. Besides the persistence of inflammatory stimuli, also defective mechanisms of resolution can lead to chronic inflammation. Inflammation resolution is an active process controlled by lipidic specialized pro-resolving mediators (SPMs), derived from ω-3 or ω-6 essential polyunsaturated fatty acids (PUFA) through the activity of lipoxygenases (ALOX5 and 15). Thus, a lack or defect in resolution mechanisms may affect cancer development and progression by prolonging inflammation. Components of pro-resolving pathways (PUFA, enzymes, or SPMs) have been reported to modulate various cancer features by affecting both epithelial cells and cancer-associated stroma. Here, we will review the most important mechanisms by which SPMs, ω-3/6 PUFA, and ALOXs affect cancer biology, paying particular attention to their role in the inhibition of inflammation and angiogenesis, two of the most important hallmarks of cancer. The collection of these results may suggest novel perspectives in cancer management based on the modulation of lipid metabolism and the production of SPMs.