Latest PUBLICATIONS

  • Single-access laparoscopic rectal resection versus the multiport technique: a retrospective study with cost analysis.
    Publication Date: 01/02/2015, on Surgical innovation
    by Bracale U, Melillo P, Lazzara F, Andreuccetti J, Stabilini C, Corcione F, Pignata G
    DOI: 10.1177/1553350614529668

    Single-access laparoscopic surgery is not used routinely for the treatment of colorectal disease. The aim of this retrospective cohort study is to compare the results of single-access laparoscopic rectal resection (SALR) versus multiaccess laparoscopic rectal resection with a mean follow-up of 24 months.

  • Synthetic Aβ peptides acquire prion-like properties in the brain.
    Publication Date: 20/01/2015, on Oncotarget
    by Xiao X, Cali I, Yuan J, Cracco L, Curtiss P, Zeng L, Abouelsaad M, Gazgalis D, Wang GX, Kong Q, Fujioka H, Puoti G, Zou WQ
    DOI: 10.18632/oncotarget.2819

    In transmission studies with Alzheimer's disease (AD) animal models, the formation of Aβ plaques is proposed to be initiated by seeding the inoculated amyloid β (Aβ) peptides in the brain. Like the misfolded scrapie prion protein (PrPSc) in prion diseases, Aβ in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aβ remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aβ peptides and Aβ isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aβ species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aβ immunoreactivity after digestion with PK. In contrast, synthetic Aβ40 and Aβ42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aβ40 and Aβ42 synthetic peptides shows that both species of Aβ form mature fibrils. Those generated from Aβ40 are longer but less numerous than those made of Aβ42. When spiked into human brain homogenates, both Aβ40 and Aβ42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aβ peptides PrPSc-like physicochemical properties.

  • Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole-containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea.
    Publication Date: 16/01/2015, on Marine drugs
    by Esposito G, Teta R, Miceli R, Ceccarelli LS, Della Sala G, Camerlingo R, Irollo E, Mangoni A, Pirozzi G, Costantino V
    DOI: 10.3390/md13010444

    The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

  • Relationships between Environmental Dependency and Closing-in in Patients with Fronto-temporal Dementia.
    Publication Date: 01/01/2015, on Journal of the International Neuropsychological Society : JINS
    by Grossi D, De Lucia N, Milan G, Trojano L
    DOI: 10.1017/S135561771400099X

    Environmental dependency (ED) phenomena, including utilization behavior and imitation behavior, are clinical manifestations typically observed in patients with the behavioral variant of fronto-temporal dementia (bvFTD), who may also show the closing-in (CI) phenomenon. Here, we explored the neuropsychological correlates of ED and CI in bvFTD, and the association of ED with CI to clarify the mechanisms underlying these clinical manifestations. Thirty-one bvFTD patients underwent a wide cognitive assessment in addition to special tasks to detect occurrence of CI and ED phenomena. Both ED and CI phenomena were present in more than half of the sample. Logistic regression analyses revealed that both ED and CI phenomena were significantly associated with poor scores on frontal neuropsychological tests. Although ED and CI often co-occurred, 3/12 patients with CI did not show ED, and 5/18 patients with ED did not show CI. A logistic regression model showed that the presence of ED was not significantly associated to CI. CI and ED are associated to progressive derangement of frontal functions in bvFTD. However, specific frontal dysfunctions might explain the occurrence of either phenomenon in isolation.

  • Closing-in is related to apathy in Alzheimer's disease patients.
    Publication Date: 01/01/2015, on Journal of Alzheimer's disease : JAD
    by Grossi D, de Lucia N, Trojano L
    DOI: 10.3233/JAD-141257

    Apathy and depression are behavioral manifestations that may occur often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in (CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that apathetic symptoms are related to frontal dysfunctions in AD patients, whereas the cognitive bases of depressive symptoms in AD are still unclear. Recent studies demonstrated that frontal dysfunctions are also involved in the genesis of CI in AD patients.

  • Trafficking and Membrane Organization of GPI-Anchored Proteins in Health and Diseases.
    Publication Date: 01/01/2015, on Current topics in membranes
    by Paladino S, Lebreton S, Zurzolo C
    DOI: 10.1016/bs.ctm.2015.03.006

    Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of lipid-anchored proteins attached to the membranes by a glycolipid anchor that is added, as posttranslation modification, in the endoplasmic reticulum. GPI-APs are expressed at the cell surface of eukaryotes where they play diverse vital functions. Like all plasma membrane proteins, GPI-APs must be correctly sorted along the different steps of the secretory pathway to their final destination. The presence of both a glycolipid anchor and a protein portion confers special trafficking features to GPI-APs. Here, we discuss the recent advances in the field of GPI-AP trafficking, focusing on the mechanisms regulating their biosynthetic pathway and plasma membrane organization. We also discuss how alterations of these mechanisms can result in different diseases. Finally, we will examine the strict relationship between the trafficking and function of GPI-APs in epithelial cells.

  • Symptomatic Heterozygosity due to Definite GAA Mutations in Late-Onset Pompe Disease.
    Publication Date: 01/01/2015, on Journal of neuromuscular diseases
    by Sampaolo S, Farina O, Cipullo F, Napolitano F, Esposito T, Lombardi L, Di Iorio G
    DOI:

  • A Unique Myopathy Syndrome in a Patient Disclosing Clinical, Laboratory, and Genetic Findings of Late-Onset Pompe Disease, Together with a Lack of Dysferlin on Muscle Biopsy.
    Publication Date: 01/01/2015, on Journal of neuromuscular diseases
    by Sampaolo S, Lombardi L, Pascarella A, Picillo E, Farina O, Esposito T, Politano L, Di Iorio G
    DOI:

  • Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection.
    Publication Date: 01/01/2015, on Autophagy
    by Janda E, Lascala A, Carresi C, Parafati M, Aprigliano S, Russo V, Savoia C, Ziviani E, Musolino V, Morani F, Isidoro C, Mollace V
    DOI: 10.1080/15548627.2015.1058683

    Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular target of neurotoxins in the brain. PQ decreased the basal levels of LC3-II and LC3-positive vesicles, and its colocalization with lysosomal markers, both in the absence and presence of chloroquine. This was paralleled by increased number and size of SQSTM1/p62 aggregates. Downregulation of autophagy was also observed in cells chronically exposed to hydrogen peroxide or nonlethal concentrations of PQ, and it was associated with a reduced astrocyte capability to protect dopaminergic cells from OS in co-cultures. Surprisingly, PQ treatment led to inhibition of MTOR, activation of MAPK8/JNK1 and MAPK1/ERK2-MAPK3/ERK1 and upregulation of BECN1/Beclin 1 expression, all signals typically correlating with induction of autophagy. Reduction of OS by NMDPEF, a specific NQO2 inhibitor, but not by N-acetylcysteine, abrogated the inhibitory effect of PQ and restored autophagic flux. Activation of NQO2 by PQ or menadione and genetic manipulation of its expression confirmed the role of this enzyme in the inhibitory action of PQ on autophagy. PQ did not induce NFE2L2/NRF2, but when it was co-administered with NMDPEF NFE2L2 activity was enhanced in a SQSTM1-independent fashion. Thus, a prolonged OS in astrocytes inhibits LC3 lipidation and impairs autophagosome formation and autophagic flux, in spite of concomitant activation of several pro-autophagic signals. These findings outline an unanticipated neuroprotective role of astrocyte autophagy and identify in NQO2 a novel pharmacological target for its positive modulation.

  • Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.
    Publication Date: 01/01/2015, on Journal of neurology
    by Bonavita S, Sacco R, Della Corte M, Esposito S, Sparaco M, d'Ambrosio A, Docimo R, Bisecco A, Lavorgna L, Corbo D, Cirillo S, Gallo A, Esposito F, Tedeschi G
    DOI: 10.1007/s00415-014-7528-z

    To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p < 0.01), PASAT 3" (p < 0.00), PASAT 2" (p < 0.03), SRT-D (p < 0.02), and 10/36 SPART-D (p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

  • De-regulated expression of the BRG1 chromatin remodeling factor in bone marrow mesenchymal stromal cells induces senescence associated with the silencing of NANOG and changes in the levels of chromatin proteins.
    Publication Date: 01/01/2015, on Cell cycle (Georgetown, Tex.)
    by Squillaro T, Severino V, Alessio N, Farina A, Di Bernardo G, Cipollaro M, Peluso G, Chambery A, Galderisi U
    DOI: 10.4161/15384101.2014.995053

    Stem cells have a peculiar chromatin architecture that contributes to their unique properties, including uncommitted status, multi/pluripotency and self-renewal. We analyzed the effect of the de-regulation of the SWI/SNF chromatin remodeling complex in mesenchymal stromal cells (MSC) through the silencing and up-regulation of BRG1, which is the ATPase subunit of the complex. The altered expression of BRG1 promoted the senescence of MSC with suppression of the NANOG transcription, which is part of the transcriptional circuitry governing stem cell functions. To gain insight on the way NANOG was silenced, we evaluated how the de-regulated BRG1 expression affect the binding of activators and repressors on the NANOG promoter. We found 4 E2F binding motifs on NANOG promoter, which can be occupied by RB1 and RB2/P130. These are members of the retinoblastoma gene family. In MSC with a silenced BRG1, the relative binding of the 2 retinoblastoma proteins increased, and this was associated with the recruitment of DNMT1. This induced the methylation of CpG on the NANOG promoter. Opposingly, when a high level of BRG1 was present, the same E2F binding motifs were docking sites for BRG1, which induced chromatin compaction without CpG methylation but with increased histone deacetylation, associated with the presence of HDAC1 on E2F binding sites. Besides the sharp regulation of the NANOG expression, we evidenced, through proteomic analysis, that the de-regulation of the SWI/SNF function affected the expression of histones and other nuclear proteins involved in "nuclear architecture," suggesting that BRG1 may act as global regulator of gene expression.

  • Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats.
    Publication Date: 01/01/2015, on Mediators of inflammation
    by Rossi S, Di Filippo C, Gesualdo C, Testa F, Trotta MC, Maisto R, Ferraro B, Ferraraccio F, Accardo M, Simonelli F, D'Amico M
    DOI: 10.1155/2015/126408

    Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10-100-1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 μg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2, N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

  • Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.
    Publication Date: 01/01/2015, on Mediators of inflammation
    by Rossi S, Di Filippo C, Gesualdo C, Potenza N, Russo A, Trotta MC, Zippo MV, Maisto R, Ferraraccio F, Simonelli F, D'Amico M
    DOI: 10.1155/2015/149381

    This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 μL volume containing 10-100-1000 ng/kg RvD1 1 h post-LPS injection (200 μg, Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-α and NF-κB were reduced.

  • Wearable technology and ECG processing for fall risk assessment, prevention and detection.
    Publication Date: 01/01/2015, on Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
    by Melillo P, Castaldo R, Sannino G, Orrico A, de Pietro G, Pecchia L
    DOI: 10.1109/EMBC.2015.7320186

    Falls represent one of the most common causes of injury-related morbidity and mortality in later life. Subjects with cardiovascular disorders (e.g., related to autonomic dysfunctions and postural hypotension) are at higher risk of falling. Autonomic dysfunctions increasing the risk of falling in the short and mid-term could be assessed by Heart Rate Variability (HRV) extracted by electrocardiograph (ECG). We developed three trials for assessing the usefulness of ECG monitoring using wearable devices for: risk assessment of falling in the next few weeks; prevention of imminent falls due to standing hypotension; and fall detection. Statistical and data-mining methods are adopted to develop classification and regression models, validated with the cross-validation approach. The first classifier based on HRV features enabled to identify future fallers among hypertensive patients with an accuracy of 72% (sensitivity: 51.1%, specificity: 80.2%). The regression model to predict falls due to orthostatic dropdown from HRV recorded before standing achieved an overall accuracy of 80% (sensitivity: 92%, specificity: 90%). Finally, the classifier to detect simulated falls using ECG achieved an accuracy of 77.3% (sensitivity: 81.8%, specificity: 72.7%). The evidence from these three studies showed that ECG monitoring and processing could achieve satisfactory performances compared to other system for risk assessment, fall prevention and detection. This is interesting as differently from other technologies actually employed to prevent falls, ECG is recommended for many other pathologies of later life and is more accepted by senior citizens.

  • Photorefractive keratectomy on purely refractive accommodative esotropia.
    Publication Date: 01/01/2015, on Seminars in ophthalmology
    by Rossi S, Testa F, Santamaria C, Orrico A, Attanasio M, Simonelli F, De Rosa G
    DOI: 10.3109/08820538.2013.810286

    Results on refractive keratectomy of the treatment of young patients with purely refractive accommodative esotropia.