Latest PUBLICATIONS

  • A clinical study on closing-in in focal brain-damaged individuals.
    Publication Date: 15/04/2016, on Journal of the neurological sciences
    by De Lucia N, Grossi D, Trojano L
    DOI: 10.1016/j.jns.2016.02.059

    In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual-task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain-damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis".

  • In Search of Alternative Antibiotic Drugs: Quorum-Quenching Activity in Sponges and their Bacterial Isolates.
    Publication Date: 05/04/2016, on Frontiers in microbiology
    by Saurav K, Bar-Shalom R, Haber M, Burgsdorf I, Oliviero G, Costantino V, Morgenstern D, Steindler L
    DOI: 10.3389/fmicb.2016.00416

    Owing to the extensive development of drug resistance in pathogens against the available antibiotic arsenal, antimicrobial resistance is now an emerging major threat to public healthcare. Anti-virulence drugs are a new type of therapeutic agent aiming at virulence factors rather than killing the pathogen, thus providing less selective pressure for evolution of resistance. One promising example of this therapeutic concept targets bacterial quorum sensing (QS), because QS controls many virulence factors responsible for bacterial infections. Marine sponges and their associated bacteria are considered a still untapped source for unique chemical leads with a wide range of biological activities. In the present study, we screened extracts of 14 sponge species collected from the Red and Mediterranean Sea for their quorum-quenching (QQ) potential. Half of the species showed QQ activity in at least 2 out of 3 replicates. Six out of the 14 species were selected for bacteria isolation, to test for QQ activity also in isolates, which, once cultured, represent an unlimited source of compounds. We show that ≈20% of the isolates showed QQ activity based on a Chromobacterium violaceum CV026 screen, and that the presence or absence of QQ activity in a sponge extract did not correlate with the abundance of isolates with the same activity from the same sponge species. This can be explained by the unknown source of QQ compounds in sponge-holobionts (host or symbionts), and further by the possible non-symbiotic nature of bacteria isolated from sponges. The potential symbiotic nature of the isolates showing QQ activity was tested according to the distribution and abundance of taxonomically close bacterial Operational Taxonomic Units (OTUs) in a dataset including 97 sponge species and 178 environmental samples (i.e., seawater, freshwater, and marine sediments). Most isolates were found not to be enriched in sponges and may simply have been trapped in the filtration channels of the sponge at the time of collection. Our results highlight potential for QQ-bioactive lead molecules for anti-virulence therapy both from sponges and the bacteria isolated thereof, independently on the symbiotic nature of the latter.

  • Efficient immobilization of a fungal laccase and its exploitation in fruit juice clarification.
    Publication Date: 01/04/2016, on Food chemistry
    by Lettera V, Pezzella C, Cicatiello P, Piscitelli A, Giacobelli VG, Galano E, Amoresano A, Sannia G
    DOI: 10.1016/j.foodchem.2015.10.074

    The clarification step represents, in fruit juices industries, a bottleneck process because residual phenols cause severe haze formation affecting juice quality and impairing customers acceptance. An enzymatic step can be efficiently integrated in the process, and use of immobilized enzymes entails an economical advantage. In this work, covalent immobilization of recombinant POXA1b laccase from Pleurotus ostreatus on epoxy activated poly(methacrylate) beads was optimized thanks to a Response Surface Methodologies approach. Through regression analysis the process was well fitted by a quadratic polynomial equation (R(2)=0.9367, adjusted R(2)=0.8226) under which laccase activity reached 2000 ± 100 Ug(-1) of beads, with an immobilization efficiency of 98%. The immobilized biocatalyst was characterized and then tested in fruit juice clarification reaching up to 45% phenol reduction, without affecting health-effective flavanones content. Furthermore, laccase treated juice displays an improved sensory profile, due to the reduction of vinyl guaiacol, a potent off-flavor possessing a peppery/spicy aroma.

  • Psychometric properties and validity of Beck Depression Inventory II in multiple sclerosis.
    Publication Date: 01/04/2016, on European journal of neurology
    by Sacco R, Santangelo G, Stamenova S, Bisecco A, Bonavita S, Lavorgna L, Trojano L, D'Ambrosio A, Tedeschi G, Gallo A
    DOI: 10.1111/ene.12932

    Depression is the most common psychiatric disorder in multiple sclerosis (MS). Self-report depression scales are frequently used as screening, diagnostic and grading instruments. This study investigated the psychometric properties of the Beck Depression Inventory second edition (BDI-II) for assessing depressive disorders in a sample of Italian MS patients.

  • Aging and the subjective experience of time.
    Publication Date: 01/04/2016, on Aging clinical and experimental research
    by Crisci C, Caccavale M, Trojano L
    DOI: 10.1007/s40520-015-0403-7

    The subjective experience of time involves several, not yet identified, mechanisms. Many cognitive and emotional factors, such as attention, memory and subjective mental states can influence time estimation.

  • Does pain relief influence recovery of consciousness? A case report of a patient treated with ziconotide.
    Publication Date: 01/04/2016, on European journal of physical and rehabilitation medicine
    by Lanzillo B, Loreto V, Calabrese C, Estraneo A, Moretta P, Trojano L
    DOI:

    For people with cervical spinal cord injury (SCI), access to computers can be difficult, thus several devices have been developed to facilitate their Disorders of consciousness (DOC) are difficult to classify. The degree of consciousness varies from coma to vegetative state or unresponsive wakefulness syndrome (UWS) and minimally conscious state. Correct diagnosis has important ethical and legal implications, and pain may be cause of misdiagnosis. We describe here a patient with traumatic brain injury, classified as UWS. His clinical picture was dominated by spasticity, and pain. He underwent intrathecal treatment of spasticity with baclofen. Improvement was not that expected. However, there was a dramatic improvement when ziconotide was added to relieve pain; the patient began to eat by mouth, talk, and his tracheal tube could be removed and he is currently classified as having severe disability. The suspension of ziconotide caused a clear re-worsening of clinical condition, reverted by his reintroduction. Pain is an important factor in patients with DOC. Anecdotal reports of improved consciousness with intrathecal baclofen therapy may be due to pain relief. Reduction of pain in DOC is important and drugs should not interfere with cognition, and must be effective and manageable. Ziconotide may be one of the possible candidate due to its synergistic antispastic action in combination with baclofen when an intratecal pump has been implanted.

  • Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?
    Publication Date: 01/04/2016, on Neuroscience research
    by La Marca V, Maresca B, Spagnuolo MS, Cigliano L, Dal Piaz F, Di Iorio G, Abrescia P
    DOI: 10.1016/j.neures.2015.09.008

    24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration.

  • Transferrin-Targeted Nanoparticles Containing Zoledronic Acid as a Potential Tool to Inhibit Glioblastoma Growth.
    Publication Date: 01/04/2016, on Journal of biomedical nanotechnology
    by Salzano G, Zappavigna S, Luce A, D'Onofrio N, Balestrieri ML, Grimaldi A, Lusa S, Ingrosso D, Artuso S, Porru M, Leonetti C, Caraglia M, De Rosa G
    DOI:

    The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted self-assembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors.

  • Betaines and related ammonium compounds in chestnut (Castanea sativa Mill.).
    Publication Date: 01/04/2016, on Food chemistry
    by Servillo L, Giovane A, Casale R, Balestrieri ML, Cautela D, Paolucci M, Siano F, Volpe MG, Castaldo D
    DOI: 10.1016/j.foodchem.2015.10.070

    Chestnut fruits, being poor of simple sugars and consisting mainly of fibers and starch, are among the constituents of Mediterranean diet. While numerous studies report on content of proteins and amino acids in chestnut, no one has appeared so far on betaines, an important class of nitrogen compounds ubiquitous in plants for their protective action in response to abiotic stress. In this study, we analyzed by HPLC-ESI-tandem mass spectrometry, in fruits and flours of varieties of chestnut cultivated in Italy, the composition of betaines and ammonium compounds intermediates of their biosynthesis. Besides the parent amino acids, the compounds quantified were choline, glycerophosphocholine, phosphocholine, glycine betaine, N-methylproline, proline betaine (stachydrine), β-alanine betaine, 4-guanidinobutyric acid, trigonelline, N,N,N-trimethyllysine. Interestingly, some uncommon derivatives of pipecolic acid, such as N-methylpipecolic acid, 4-hydroxypipecolic acid and 4-hydroxy-N-methylpipecolic acid were identified for the first time in chestnut samples and characterized by MS(n) tandem mass spectrometry.

  • Isolated unilateral ptosis due to neurovascular conflict.
    Publication Date: 01/04/2016, on Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
    by Piccirillo G, Trojsi F, Conforti R, Tedeschi G
    DOI: 10.1007/s10072-015-2440-6

  • Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation.
    Publication Date: 01/04/2016, on Muscle & nerve
    by Massa R, Pozzessere S, Rastelli E, Serra L, Terracciano C, Gibellini M, Bozzali M, Arca M
    DOI: 10.1002/mus.24983

    Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment.

  • The fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis.
    Publication Date: 31/03/2016, on Cell death & disease
    by Fortini P, Ferretti C, Iorio E, Cagnin M, Garribba L, Pietraforte D, Falchi M, Pascucci B, Baccarini S, Morani F, Phadngam S, De Luca G, Isidoro C, Dogliotti E
    DOI: 10.1038/cddis.2016.50

    Although the mechanisms controlling skeletal muscle homeostasis have been identified, there is a lack of knowledge of the integrated dynamic processes occurring during myogenesis and their regulation. Here, metabolism, autophagy and differentiation were concomitantly analyzed in mouse muscle satellite cell (MSC)-derived myoblasts and their cross-talk addressed by drug and genetic manipulation. We show that increased mitochondrial biogenesis and activation of mammalian target of rapamycin complex 1 inactivation-independent basal autophagy characterize the conversion of myoblasts into myotubes. Notably, inhibition of autophagic flux halts cell fusion in the latest stages of differentiation and, conversely, when the fusion step of myocytes is impaired the biogenesis of autophagosomes is also impaired. By using myoblasts derived from p53 null mice, we show that in the absence of p53 glycolysis prevails and mitochondrial biogenesis is strongly impaired. P53 null myoblasts show defective terminal differentiation and attenuated basal autophagy when switched into differentiating culture conditions. In conclusion, we demonstrate that basal autophagy contributes to a correct execution of myogenesis and that physiological p53 activity is required for muscle homeostasis by regulating metabolism and by affecting autophagy and differentiation.

  • Modulation of Matrix Metalloproteinases Activity in the Ventral Horn of the Spinal Cord Re-stores Neuroglial Synaptic Homeostasis and Neurotrophic Support following Peripheral Nerve Injury.
    Publication Date: 30/03/2016, on PloS one
    by Cirillo G, Colangelo AM, De Luca C, Savarese L, Barillari MR, Alberghina L, Papa M
    DOI: 10.1371/journal.pone.0152750

    Modulation of extracellular matrix (ECM) remodeling after peripheral nerve injury (PNI) could represent a valid therapeutic strategy to prevent maladaptive synaptic plasticity in central nervous system (CNS). Inhibition of matrix metalloproteinases (MMPs) and maintaining a neurotrophic support could represent two approaches to prevent or reduce the maladaptive plastic changes in the ventral horn of spinal cord following PNI. The purpose of our study was to analyze changes in the ventral horn produced by gliopathy determined by the suffering of motor neurons following spared nerve injury (SNI) of the sciatic nerve and how the intrathecal (i.t.) administration of GM6001 (a MMPs inhibitor) or the NGF mimetic peptide BB14 modulate these events. Immunohistochemical analysis of spinal cord sections revealed that motor neuron disease following SNI was associated with increased microglial (Iba1) and astrocytic (GFAP) response in the ventral horn of the spinal cord, indicative of reactive gliosis. These changes were paralleled by decreased glial aminoacid transporters (glutamate GLT1 and glycine GlyT1), increased levels of the neuronal glutamate transporter EAAC1, and a net increase of the Glutamate/GABA ratio, as measured by HPLC analysis. These molecular changes correlated to a significant reduction of mature NGF levels in the ventral horn. Continuous i.t. infusion of both GM6001 and BB14 reduced reactive astrogliosis, recovered the expression of neuronal and glial transporters, lowering the Glutamate/GABA ratio. Inhibition of MMPs by GM6001 significantly increased mature NGF levels, but it was absolutely ineffective in modifying the reactivity of microglia cells. Therefore, MMPs inhibition, although supplies neurotrophic support to ECM components and restores neuro-glial transporters expression, differently modulates astrocytic and microglial response after PNI.

  • Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.
    Publication Date: 28/03/2016, on PloS one
    by Foster GR, Coppola C, Derbala M, Ferenci P, Orlandini A, Reddy KR, Tallarico L, Shiffman ML, Ahlers S, Bakalos G, Hassanein T,
    DOI: 10.1371/journal.pone.0151703

    Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.

  • Cisplatin encapsulation within a ferritin nanocage: a high-resolution crystallographic study.
    Publication Date: 18/03/2016, on Chemical communications (Cambridge, England)
    by Pontillo N, Pane F, Messori L, Amoresano A, Merlino A
    DOI: 10.1039/c5cc10365g

    Cisplatin (CDDP) can be encapsulated within the central cavity of reconstituted (apo)ferritin, (A)Ft, to form a drug-loaded protein of potential great interest for targeted cancer treatments. In this study, the interactions occurring between cisplatin and native horse spleen Ft in CDDP-encapsulated AFt are investigated by high-resolution X-ray crystallography. A protein bound Pt center is unambiguously identified in AFt subunits by comparative analysis of difference Fourier electron density maps and of anomalous dispersion data. Indeed, a [Pt(NH3)2H2O](2+) fragment is found coordinated to the His132 residue located on the inner surface of the large AFt spherical cage. Remarkably, Pt binding does not alter the overall physicochemical features (shape, volume, polarity/hydrophobicity and electrostatic potential) of the outer surface of the AFt nanocage. CDDP-encapsulated AFt appears to be an ideal nanocarrier for CDDP delivery to target sites, as it possesses high biocompatibility and can be internalized by receptor mediated endocytosis, thus carrying the drug to tumor tissue with higher selectivity than free CDDP.