Latest PUBLICATIONS

  • Sphenoidal pneumosinus dilatans due to anterior skull base meningiomas - CT and MRI aspects: Report of two new cases and literature review.
    Publication Date: 01/08/2016, on The neuroradiology journal
    by Scuotto A, Saracino D, Rotondo M, Izzo A, Urraro F, Cappabianca S, Sampaolo S
    DOI: 10.1177/1971400916648336

    We report on two patients disclosing a pneumosinus dilatans (PSD) and an anterior skull base meningioma. Our findings, together with those from the pertinent literature, support the thought that this infrequent anomaly of paranasal sinuses is a useful clue to suspect a concomitant meningioma. Moreover, hypotheses concerning the pathophysiology of PSD are discussed.

  • Mapping the protein-binding sites for iridium(iii)-based CO-releasing molecules.
    Publication Date: 26/07/2016, on Dalton transactions (Cambridge, England : 2003)
    by Caterino M, Petruk AA, Vergara A, Ferraro G, Marasco D, Doctorovich F, Estrin DA, Merlino A
    DOI: 10.1039/c6dt01685e

    A combination of mass spectrometry, Raman microspectroscopy, circular dichroism and X-ray crystallography has been used to obtain detailed information on the reaction of an iridium-based CO-releasing molecule (Ir-CORM), Cs2IrCl5CO, with a model protein, bovine pancreatic ribonuclease. The results show that Ir-compound fragments bind to the N-terminal amine and close to histidine and methionine side chains, and the CO ligand is retained for a long time. The data provide helpful information for identifying protein targets for Ir-CORMs and for studying the mechanism that allows them to exhibit their interesting biological properties.

  • Gold-based drug encapsulation within a ferritin nanocage: X-ray structure and biological evaluation as a potential anticancer agent of the Auoxo3-loaded protein.
    Publication Date: 21/07/2016, on Chemical communications (Cambridge, England)
    by Ferraro G, Monti DM, Amoresano A, Pontillo N, Petruk G, Pane F, Cinellu MA, Merlino A
    DOI: 10.1039/c6cc02516a

    Auoxo3, a cytotoxic gold(iii) compound, was encapsulated within a ferritin nanocage. Inductively coupled plasma mass spectrometry, circular dichroism, UV-Vis absorption spectroscopy and X-ray crystallography confirm the potential-drug encapsulation. The structure shows that naked Au(i) ions bind to the side chains of Cys48, His49, His114, His114 and Cys126, Cys126, His132, His147. The gold-encapsulated nanocarrier has a cytotoxic effect on different aggressive human cancer cells, whereas it is significantly less cytotoxic for non-tumorigenic cells.

  • Functional improvement assessed by multifocal electroretinogram after Ocriplasmin treatment for vitreomacular traction.
    Publication Date: 18/07/2016, on BMC ophthalmology
    by Rossi S, Testa F, Melillo P, Orrico A, Della Corte M, Simonelli F
    DOI: 10.1186/s12886-016-0284-3

    To evaluate the functional recovery of patients with symptomatic vitreomacular traction (VMT) after Ocriplasmin treatment.

  • The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients.
    Publication Date: 05/07/2016, on Neurology
    by Savarese M, Di Fruscio G, Torella A, Fiorillo C, Magri F, Fanin M, Ruggiero L, Ricci G, Astrea G, Passamano L, Ruggieri A, Ronchi D, Tasca G, D'Amico A, Janssens S, Farina O, Mutarelli M, Marwah VS, Garofalo A, Giugliano T, Sanpaolo S, Del Vecchio Blanco F, Esposito G, Piluso G, D'Ambrosio P, Petillo R, Musumeci O, Rodolico C, Messina S, Evilä A, Hackman P, Filosto M, Di Iorio G, Siciliano G, Mora M, Maggi L, Minetti C, Sacconi S, Santoro L, Claes K, Vercelli L, Mongini T, Ricci E, Gualandi F, Tupler R, De Bleecker J, Udd B, Toscano A, Moggio M, Pegoraro E, Bertini E, Mercuri E, Angelini C, Santorelli FM, Politano L, Bruno C, Comi GP, Nigro V
    DOI: 10.1212/WNL.0000000000002800

    To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients.

  • Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses.
    Publication Date: 01/07/2016, on Aging
    by Özcan S, Alessio N, Acar MB, Mert E, Omerli F, Peluso G, Galderisi U
    DOI: 10.18632/aging.100971

    Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions, such as sensitizing surrounding cells to senesce; immunomodulation; impairing or fostering cancer growth; and promoting tissue development. Identifying secreted factors that achieve such tasks is a challenging issue since the profile of secreted proteins depends on genotoxic stress and cell type. Currently, researchers are trying to identify common markers for SASP. The present investigation compared the secretome composition of five different senescent phenotypes in two different cell types: bone marrow and adipose mesenchymal stromal cells (MSC). We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation, and replicative exhaustion. We took advantage of LC-MS/MS proteome identification and subsequent gene ontology (GO) evaluation to perform an unbiased analysis (hypothesis free manner) of senescent secretomes. GO analysis allowed us to distribute SASP components into four classes: extracellular matrix/cytoskeleton/cell junctions; metabolic processes; ox-redox factors; and regulators of gene expression. We used Ingenuity Pathway Analysis (IPA) to determine common pathways among the different senescent phenotypes. This investigation, along with identification of eleven proteins that were exclusively expressed in all the analyzed senescent phenotypes, permitted the identification of three key signaling paths: MMP2 - TIMP2; IGFBP3 - PAI-1; and Peroxiredoxin 6 - ERP46 - PARK7 - Cathepsin D - Major vault protein. We suggest that these paths could be involved in the paracrine circuit that induces senescence in neighboring cells and may confer apoptosis resistance to senescent cells.

  • Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients.
    Publication Date: 01/07/2016, on Biochimie
    by Perna AF, Di Nunzio A, Amoresano A, Pane F, Fontanarosa C, Pucci P, Vigorito C, Cirillo G, Zacchia M, Trepiccione F, Ingrosso D
    DOI: 10.1016/j.biochi.2016.04.018

    Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses. In uremia, we have demonstrated low plasma total hydrogen sulfide levels, due to reduced cystathionine γ-lyase expression. Plasma hydrogen sulfide levels were measured in hemodialysis patients and healthy controls with three different techniques in comparison, allowing to discern the different pools of this gas. The protein-bound (the one thought to be the most active) and acid-labile forms are significantly decreased, while homolanthionine, but especially lanthionine, accumulate in the blood of uremic patients. The hemodialysis regimen plays a role in determining sulfur compounds levels, and lanthionine is partially removed by a single dialysis session. Lanthionine inhibits hydrogen sulfide production in cell cultures under conditions comparable to in vivo ones. We therefore propose that lanthionine is a novel uremic toxin. The possible role of high lanthionine as a contributor to the genesis of hyperhomocysteinemia in uremia is discussed.

  • Effect of temperature on the interaction of cisplatin with the model protein hen egg white lysozyme.
    Publication Date: 01/07/2016, on Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
    by Ferraro G, Pica A, Russo Krauss I, Pane F, Amoresano A, Merlino A
    DOI: 10.1007/s00775-016-1352-0

    The products of the reaction between cisplatin (CDDP) and the model protein hen egg white lysozyme (HEWL) at 20, 37 and 55 °C in pure water were studied by UV-Vis absorption spectroscopy, intrinsic fluorescence and circular dichroism, dynamic and electrophoretic light scattering and inductively coupled plasma mass spectrometry. X-ray structures were also solved for the adducts formed at 20 and 55 °C. Data demonstrate that high temperature facilitates the formation of CDDP-HEWL adducts, where Pt atoms bind ND1 atom of His15 or NE2 atom of His15 and NH1 atom of Arg14. Our study suggests that high human body temperature (fever) could increase the rate of drug binding to proteins thus enhancing possible toxic side effects related to CDDP administration.

  • An interdomain network: the endobacterium of a mycorrhizal fungus promotes antioxidative responses in both fungal and plant hosts.
    Publication Date: 01/07/2016, on The New phytologist
    by Vannini C, Carpentieri A, Salvioli A, Novero M, Marsoni M, Testa L, de Pinto MC, Amoresano A, Ortolani F, Bracale M, Bonfante P
    DOI: 10.1111/nph.13895

    Arbuscular mycorrhizal fungi (AMF) are obligate plant biotrophs that may contain endobacteria in their cytoplasm. Genome sequencing of Candidatus Glomeribacter gigasporarum revealed a reduced genome and dependence on the fungal host. RNA-seq analysis of the AMF Gigaspora margarita in the presence and absence of the endobacterium indicated that endobacteria have an important role in the fungal pre-symbiotic phase by enhancing fungal bioenergetic capacity. To improve the understanding of fungal-endobacterial interactions, iTRAQ (isobaric tags for relative and absolute quantification) quantitative proteomics was used to identify differentially expressed proteins in G. margarita germinating spores with endobacteria (B+), without endobacteria in the cured line (B-) and after application of the synthetic strigolactone GR24. Proteomic, transcriptomic and biochemical data identified several fungal and bacterial proteins involved in interspecies interactions. Endobacteria influenced fungal growth, calcium signalling and metabolism. The greatest effects were on fungal primary metabolism and respiration, which was 50% higher in B+ than in B-. A shift towards pentose phosphate metabolism was detected in B-. Quantification of carbonylated proteins indicated that the B- line had higher oxidative stress levels, which were also observed in two host plants. This study shows that endobacteria generate a complex interdomain network that affects AMF and fungal-plant interactions.

  • Looking Inside the Matrix: Perineuronal Nets in Plasticity, Maladaptive Plasticity and Neurological Disorders.
    Publication Date: 01/07/2016, on Neurochemical research
    by De Luca C, Papa M
    DOI: 10.1007/s11064-016-1876-2

    The integrity of the central nervous system (CNS) matrix is crucial for its proper function. Loss of the lattice-like structure compromise synaptic stability and can lead to the disruption of the excitatory/inhibitory balance, astrocytosis, maladaptive plasticity and neuronal death. Perineuronal nets (PNNs) in the extracellular matrix (ECM) provide synaptic integration and control the functional wiring between neurons. These nets are significantly modified during CNS disorders, such as neurodegenerative, cerebrovascular and inflammatory diseases. The breakdown or the modification of PNNs could be due to the activity of matrix metalloproteinases (MMPs) or to the deposition of proteoglycans, glycoproteins, and hyaluronic acid. The expression and the activity of ECM-degrading enzymes can be regulated with tissue inhibitors of MMPs or via transcriptional and epigenetic silencing or enhancement (i.e. via histone deacetylases). The identification of molecules and mechanisms able to modify these processes will be essential for a new perspective on brain functioning in health and disease, leading to a target-directed approach with drugs directly interfering with the molecular mechanism underlying neurological disorders.

  • Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6.
    Publication Date: 01/07/2016, on Free radical biology & medicine
    by D'Onofrio N, Servillo L, Giovane A, Casale R, Vitiello M, Marfella R, Paolisso G, Balestrieri ML
    DOI: 10.1016/j.freeradbiomed.2016.04.013

    Ergothioneine (Egt), the betaine of 2-mercapto-L-histidine, is a dietary antioxidant protecting against many diseases, including cardiovascular disease (CVD), through a redox mechanism different from alkylthiols. Here, experiments were designed to evaluate the mechanisms underlying the beneficial effect of Egt against hyperglycaemia-induced senescence in endothelial cells. To this end, cells were incubated with increasing concentrations of Egt (0.01-1.00mM) for 12h followed by incubation for 48h with high-glucose (25mM). Cell evaluation indicated that viability was not affected by mM concentrations of Egt and that the high-glucose cytotoxicity was prevented with the highest efficacy at 0.5mM Egt. The cytoprotective effect of Egt was paralleled by reduced ROS production, cell senescence, and, interestingly, the formation of hercynine (EH), a betaine we recently found to be produced during the Egt oxidation pathway. Notably, the Egt beneficial effect was exerted through the upregulation of sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) expression and the downregulation of p66Shc and NF-κB. SIRT1 activity inhibition and SIRT6 gene silencing by small interfering RNA abolished the protective effect of Egt against the high-glucose-induced endothelial senescence. These data provide the first evidence of the Egt ability to interfere with endothelial senescence linked to hyperglycaemia through the regulation of SIRT1 and SIRT6 signaling, thus further strengthening the already assessed role of these two histone deacetylases in type 2 diabetes.

  • Elucidating the reactivity of Pt(II) complexes with (O,S) bidentate ligands towards DNA model systems.
    Publication Date: 01/07/2016, on Journal of inorganic biochemistry
    by Mügge C, Musumeci D, Michelucci E, Porru F, Marzo T, Massai L, Messori L, Weigand W, Montesarchio D
    DOI: 10.1016/j.jinorgbio.2016.02.013

    In the search for novel platinum-based anticancer therapeutic agents, we have recently established a structural motif of (O,S) bidentate ligands bound to a Pt(II) metal center which is effective against various cancer cell lines. Aiming at further enhancing the cytotoxicity of metal-based drugs, the identification of potential biological targets and elucidation of the mode of action of selected lead compounds is of utmost importance. Here we report our studies on the DNA interaction of three representative Pt(II) complexes of the investigated series, using various model systems and analytical techniques. In detail, CD spectroscopy as well as ESI-MS and MS(2) techniques were applied to gain an overall picture of the binding properties of this class of (O,S) bidentate Pt(II) compounds with defined oligonucleotide sequences in single strand, duplex or G-quadruplex form, as well as with the nucleobase 9-methylguanine. On the whole, it was demonstrated that the tested compounds interact with DNA and produce conformational changes of different extents depending on the sequence and structure of the examined oligonucleotide. Guanine was established as the preferential target within the DNA sequence, but in the absence or unavailability of guanines, alternative binding sites can be addressed. The implications of these results are thoroughly discussed.

  • Erratum to: The treatment with pasireotide in Cushing's disease: effects of long-term treatment on tumor mass in the experience of a single center.
    Publication Date: 01/07/2016, on Endocrine
    by Simeoli C, Auriemma RS, Tortora F, De Leo M, Iacuaniello D, Cozzolino A, De Martino MC, Pivonello C, Mainolfi CG, Rossi R, Cirillo S, Colao A, Pivonello R
    DOI: 10.1007/s12020-016-0924-7

  • Human prion diseases: surgical lessons learned from iatrogenic prion transmission.
    Publication Date: 01/07/2016, on Neurosurgical focus
    by Bonda DJ, Manjila S, Mehndiratta P, Khan F, Miller BR, Onwuzulike K, Puoti G, Cohen ML, Schonberger LB, Cali I
    DOI: 10.3171/2016.5.FOCUS15126

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

  • En Face Spectral-Domain Optical Coherence Tomography for the Monitoring of Lesion Area Progression in Stargardt Disease.
    Publication Date: 01/07/2016, on Investigative ophthalmology & visual science
    by Melillo P, Testa F, Rossi S, Di Iorio V, Orrico A, Auricchio A, Simonelli F
    DOI: 10.1167/iovs.15-18751

    We investigated the progression of Stargardt disease (STGD1) over a multiyear follow-up by evaluating the macular lesion area as computed by an automatic algorithm from spectral-domain optical coherence tomography (SD-OCT).