Latest PUBLICATIONS

  • Automatic classifier based on heart rate variability to identify fallers among hypertensive subjects.
    Publication Date: 02/07/2015, on Healthcare technology letters
    by Melillo P, Jovic A, De Luca N, Pecchia L
    DOI: 10.1049/htl.2015.0012

    Accidental falls are a major problem of later life. Different technologies to predict falls have been investigated, but with limited success, mainly because of low specificity due to a high false positive rate. This Letter presents an automatic classifier based on heart rate variability (HRV) analysis with the goal to identify fallers automatically. HRV was used in this study as it is considered a good estimator of autonomic nervous system (ANS) states, which are responsible, among other things, for human balance control. Nominal 24 h electrocardiogram recordings from 168 cardiac patients (age 72 ± 8 years, 60 female), of which 47 were fallers, were investigated. Linear and nonlinear HRV properties were analysed in 30 min excerpts. Different data mining approaches were adopted and their performances were compared with a subject-based receiver operating characteristic analysis. The best performance was achieved by a hybrid algorithm, RUSBoost, integrated with feature selection method based on principal component analysis, which achieved satisfactory specificity and accuracy (80 and 72%, respectively), but low sensitivity (51%). These results suggested that ANS states causing falls could be reliably detected, but also that not all the falls were due to ANS states.

  • Occurrence of Fusarium mycotoxins and their dietary intake through beer consumption by the European population.
    Publication Date: 01/07/2015, on Food chemistry
    by Rodríguez-Carrasco Y, Fattore M, Albrizio S, Berrada H, Mañes J
    DOI: 10.1016/j.foodchem.2015.01.092

    Since cereals are raw materials for production of beer and beer-based drinks, the occurrence mycotoxins in 154 beer samples was topic of investigation in this study. The analyses were conducted using QuEChERS extraction and gas chromatography-tandem mass spectrometry determination. The analytical method showed recoveries for vast majority of analytes ranged from 70% to 110%, relative standard deviations lower than 15% and limits of detection from 0.05 to 8 μg/L. A significant incidence of HT-2 toxin and deoxynivalenol (DON) were found in 9.1% and 59.7% of total samples, respectively. The exposure of European population to mycotoxins through beer consumption was assessed. No toxicological concern was associated to mycotoxins exposure for average beer consumers. Despite that, for heavy beer drinkers, the contribution of this commodity to the daily intake is not negligible, approaching or even exceeding the safety levels.

  • Sirtuins in vascular diseases: Emerging roles and therapeutic potential.
    Publication Date: 01/07/2015, on Biochimica et biophysica acta
    by D'Onofrio N, Vitiello M, Casale R, Servillo L, Giovane A, Balestrieri ML
    DOI: 10.1016/j.bbadis.2015.03.001

    Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly conserved protein family of histone deacetylases that promote longevity by mediating many of the beneficial effects of calorie restriction which extends life span and reduces the incidence of cancer, cardiovascular disease (CVD), and diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis and diseases by providing an update on the latest knowledge about their roles in endothelial damage and vascular repair mechanisms. Among all sirtuins, in the light of the numerous functions reported on SIRT1 in the vascular system, herein we discuss its roles not only in the control of endothelial cells (EC) functionality but also in other cell types beyond EC, including endothelial progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore, we also provide an update on the growing field of compounds under clinical evaluation for the modulation of SIRT1 which, at the state of the art, represents the most promising target for the development of novel drugs against CVD, especially when concomitant with type 2 diabetes.

  • The Potential for Plant Derivatives against Acrylamide Neurotoxicity.
    Publication Date: 01/07/2015, on Phytotherapy research : PTR
    by Adewale OO, Brimson JM, Odunola OA, Gbadegesin MA, Owumi SE, Isidoro C, Tencomnao T
    DOI: 10.1002/ptr.5353

    Certain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain-related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR-induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects.

  • The closing-in phenomenon in Parkinson's disease.
    Publication Date: 01/07/2015, on Parkinsonism & related disorders
    by De Lucia N, Trojano L, Vitale C, Grossi D, Barone P, Santangelo G
    DOI: 10.1016/j.parkreldis.2015.04.013

    Closing-in (CI) is a peculiar phenomenon consisting in the tendency to copy drawings close to or superimposed on a model. Recent findings showed that CI can be associated with frontal/executive dysfunctions, likely determining a failure in high-level monitoring of attention-action circuits. CI has been often observed in demented patients, but scarce data are available about CI in patients with Parkinson's disease (PD). In the present study, we detected occurrence of CI and investigated the cognitive processes associated to this phenomenon in a large sample of non-demented PD patients.

  • Probing the interaction of distamycin A with S100β: the "unexpected" ability of S100β to bind to DNA-binding ligands.
    Publication Date: 01/06/2015, on Journal of molecular recognition : JMR
    by Cerofolini L, Amato J, Borsi V, Pagano B, Randazzo A, Fragai M
    DOI: 10.1002/jmr.2452

    DNA-minor-groove-binding ligands are potent antineoplastic molecules. The antibiotic distamycin A is the prototype of one class of these DNA-interfering molecules that have been largely used in vitro. The affinity of distamycin A for DNA is well known, and the structural details of the complexes with some B-DNA and G-quadruplex-forming DNA sequences have been already elucidated. Here, we show that distamycin A binds S100β, a protein involved in the regulation of several cellular processes. The reported affinity of distamycin A for the calcium(II)-loaded S100β reinforces the idea that some biological activities of the DNA-minor-groove-binding ligands arise from the binding to cellular proteins.

  • Clinical and electroencephalographic on-off effect of amantadine in chronic non-traumatic minimally conscious state.
    Publication Date: 01/06/2015, on Journal of neurology
    by Estraneo A, Pascarella A, Moretta P, Loreto V, Trojano L
    DOI: 10.1007/s00415-015-7771-y

  • FBXW7 and USP7 regulate CCDC6 turnover during the cell cycle and affect cancer drugs susceptibility in NSCLC.
    Publication Date: 20/05/2015, on Oncotarget
    by Morra F, Luise C, Merolla F, Poser I, Visconti R, Ilardi G, Paladino S, Inuzuka H, Guggino G, Monaco R, Colecchia D, Monaco G, Cerrato A, Chiariello M, Denning K, Claudio PP, Staibano S, Celetti A
    DOI: 10.18632/oncotarget.3708

    CCDC6 gene product is a pro-apoptotic protein substrate of ATM, whose loss or inactivation enhances tumour progression. In primary tumours, the impaired function of CCDC6 protein has been ascribed to CCDC6 rearrangements and to somatic mutations in several neoplasia. Recently, low levels of CCDC6 protein, in NSCLC, have been correlated with tumor prognosis. However, the mechanisms responsible for the variable levels of CCDC6 in primary tumors have not been described yet.We show that CCDC6 turnover is regulated in a cell cycle dependent manner. CCDC6 undergoes a cyclic variation in the phosphorylated status and in protein levels that peak at G2 and decrease in mitosis. The reduced stability of CCDC6 in the M phase is dependent on mitotic kinases and on degron motifs that are present in CCDC6 and direct the recruitment of CCDC6 to the FBXW7 E3 Ubl. The de-ubiquitinase enzyme USP7 appears responsible of the fine tuning of the CCDC6 stability, affecting cells behaviour and drug response.Thus, we propose that the amount of CCDC6 protein in primary tumors, as reported in lung, may depend on the impairment of the CCDC6 turnover due to altered protein-protein interaction and post-translational modifications and may be critical in optimizing personalized therapy.

  • Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin-like growth factor-1 resistance in cardiomyocytes.
    Publication Date: 08/05/2015, on PloS one
    by Fabbi P, Spallarossa P, Garibaldi S, Barisione C, Mura M, Altieri P, Rebesco B, Monti MG, Canepa M, Ghigliotti G, Brunelli C, Ameri P
    DOI: 10.1371/journal.pone.0124643

    Insulin-like growth factor-1 (IGF-1) promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R). Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3), which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes.

  • Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.
    Publication Date: 07/05/2015, on PloS one
    by Conson M, Errico D, Mazzarella E, Giordano M, Grossi D, Trojano L
    DOI: 10.1371/journal.pone.0126448

    Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

  • New therapeutic perspectives in CCDC6 deficient lung cancer cells.
    Publication Date: 01/05/2015, on International journal of cancer
    by Morra F, Luise C, Visconti R, Staibano S, Merolla F, Ilardi G, Guggino G, Paladino S, Sarnataro D, Franco R, Monaco R, Zitomarino F, Pacelli R, Monaco G, Rocco G, Cerrato A, Linardopoulos S, Muller MT, Celetti A
    DOI: 10.1002/ijc.29263

    Non-small cell lung cancer (NSCLC) is the main cause of cancer-related death worldwide and new therapeutic strategies are urgently needed. In this study, we have characterized a panel of NSC lung cancer cell lines for the expression of coiled-coil-domain containing 6 (CCDC6), a tumor suppressor gene involved in apoptosis and DNA damage response. We show that low CCDC6 protein levels are associated with a weak response to DNA damage and a low number of Rad51 positive foci. Moreover, CCDC6 deficient lung cancer cells show defects in DNA repair via homologous recombination. In accordance with its role in the DNA damage response, CCDC6 attenuation confers resistance to cisplatinum, the current treatment of choice for NSCLC, but sensitizes the cells to olaparib, a small molecule inhibitor of the repair enzymes PARP1/2. Remarkably, the combination of the two drugs is more effective than each agent individually, as demonstrated by a combination index <1. Finally, CCDC6 is expressed at low levels in about 30% of the NSCL tumors we analyzed by TMA immunostaining. The weak CCDC6 protein staining is significatively correlated with the presence of lymph node metastasis (p ≤ 0.02) and negatively correlated to the disease free survival (p ≤ 0.01) and the overall survival (p ≤ 0.05). Collectively, the data indicate that CCDC6 levels provide valuable insight for OS. CCDC6 could represent a predictive biomarker of resistance to conventional single mode therapy and yield insight on tumor sensitivity to PARP inhibitors in NSCLC.

  • Response to comment on Balestrieri et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment. Diabetes 2015;64:1395-1406.
    Publication Date: 01/05/2015, on Diabetes
    by Balestrieri ML, Rizzo MR, Barbieri M, Paolisso P, D'Onofrio N, Giovane A, Servillo L, Paolisso G, Marfella R
    DOI: 10.2337/db14-1676

  • Platinated oligomers of bovine pancreatic ribonuclease: Structure and stability.
    Publication Date: 01/05/2015, on Journal of inorganic biochemistry
    by Picone D, Donnarumma F, Ferraro G, Russo Krauss I, Fagagnini A, Gotte G, Merlino A
    DOI: 10.1016/j.jinorgbio.2015.02.011

    The reaction between cis-diamminedichloroplatinum(II) (CDDP), cisplatin, a common anticancer drug, and bovine pancreatic ribonuclease (RNase A), induces extensive protein aggregation, leading to the formation of one dimer, one trimer and higher oligomers whose yields depend on cisplatin/protein ratio. Structural and functional properties of the purified platinated species, together with their spontaneous dissociation and thermally induced denaturation, have been characterized. Platinated species preserve a significant, although reduced, ribonuclease activity. The high resistance of the dimers against dissociation and the different thermal unfolding profiles suggest a quaternary structure different from those of the well-known swapped dimers of RNase A.

  • Serotonin 5-O-β-Glucoside and Its N-Methylated Forms in Citrus Genus Plants.
    Publication Date: 29/04/2015, on Journal of agricultural and food chemistry
    by Servillo L, Giovane A, Casale R, D'Onofrio N, Ferrari G, Cautela D, Balestrieri ML, Castaldo D
    DOI: 10.1021/acs.jafc.5b01031

    Citrus genus is characterized by a specific presence of indole metabolites deriving from the N-methylation of tryptamine and its hydroxylated form, 5-hydroxytryptamine (serotonin), which are likely involved in plant defense mechanisms. In this study, we identified for the first time the occurrence in Citrus plants of serotonin 5-O-β-glucoside and all its N-methylated derivatives, that is, N-methylserotonin 5-O-β-glucoside, N,N-dimethylserotonin (bufotenine) 5-O-β-glucoside, and N,N,N-trimethylserotonin (bufotenidine) 5-O-β-glucoside. The identification of the glucosylated compounds was based on mass spectrometric studies, hydrolysis by glucosidase, and in some cases, comparison to authentic compounds. Beside leaves, the distribution of the glucosylated forms and their aglycones in some Citrus species was evaluated in flavedo, albedo, juice, and seeds. The simultaneous presence of serotonin and its N-methylated derivatives, together with the corresponding glucosylated forms, is consistent with the occurrence of a metabolic pathway, specific for Citrus, aimed at potentiating the defensive response to biotic stress through the optimization of the production and use of the most toxic of such metabolites.

  • Design of sweet protein based sweeteners: hints from structure-function relationships.
    Publication Date: 15/04/2015, on Food chemistry
    by Rega MF, Di Monaco R, Leone S, Donnarumma F, Spadaccini R, Cavella S, Picone D
    DOI: 10.1016/j.foodchem.2014.10.151

    Sweet proteins represent a class of natural molecules, which are extremely interesting regarding their potential use as safe low-calories sweeteners for individuals who need to control sugar intake, such as obese or diabetic subjects. Punctual mutations of amino acid residues of MNEI, a single chain derivative of the natural sweet protein monellin, allow the modulation of its taste. In this study we present a structural and functional comparison between MNEI and a sweeter mutant Y65R, containing an extra positive charge on the protein surface, in conditions mimicking those of typical beverages. Y65R exhibits superior sweetness in all the experimental conditions tested, has a better solubility at mild acidic pH and preserves a significant thermal stability in a wide range of pH conditions, although slightly lower than MNEI. Our findings confirm the advantages of structure-guided protein engineering to design improved low-calorie sweeteners and excipients for food and pharmaceutical preparations.