Persisting Embryonal Infundibular Recess in Morning Glory Syndrome: Clinical Report of a Novel Association.
Publication Date: 07/03/2019, on AJNR. American journal of neuroradiology
by D'Amico A, Ugga L, Cuocolo R, Cirillo M, Grandone A, Conforti R
Morning glory syndrome is characterized by a congenital optic disc defect that resembles the eponymous flower. We present the MR imaging findings of 2 pediatric patients with morning glory disc anomaly and persisting embryonal infundibular recess, another rare malformative finding, a previously unreported association. Neuroradiologists should be aware of the possible presence of a persisting embryonal infundibular recess in patients with morning glory syndrome, to aid in the differential diagnosis including other pituitary malformations such as pituitary stalk duplication.
Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients.
Publication Date: 06/03/2019, on International journal of molecular sciences
by D'Onofrio N, Pieretti G, Ciccarelli F, Gambardella A, Passariello N, Rizzo MR, Barbieri M, Marfella R, Nicoletti G, Balestrieri ML, Sardu C
The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin ( < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.
Evolution of an insect immune barrier through horizontal gene transfer mediated by a parasitic wasp.
Publication Date: 05/03/2019, on PLoS genetics
by Di Lelio I, Illiano A, Astarita F, Gianfranceschi L, Horner D, Varricchio P, Amoresano A, Pucci P, Pennacchio F, Caccia S
Genome sequencing data have recently demonstrated that eukaryote evolution has been remarkably influenced by the acquisition of a large number of genes by horizontal gene transfer (HGT) across different kingdoms. However, in depth-studies on the physiological traits conferred by these accidental DNA acquisitions are largely lacking. Here we elucidate the functional role of Sl gasmin, a gene of a symbiotic virus of a parasitic wasp that has been transferred to an ancestor of the moth species Spodoptera littoralis and domesticated. This gene is highly expressed in circulating immune cells (haemocytes) of larval stages, where its transcription is rapidly boosted by injection of microorganisms into the body cavity. RNAi silencing of Sl gasmin generated a phenotype characterized by a precocious suppression of phagocytic activity by haemocytes, which was rescued when these immune cells were incubated in plasma samples of control larvae, containing high levels of the encoded protein. Proteomic analysis demonstrated that the protein Sl gasmin is released by haemocytes into the haemolymph, where it opsonizes the invading bacteria to promote their phagocytosis, both in vitro and in vivo. Our results show that important physiological traits do not necessarily originate from evolution of pre-existing genes, but can be acquired by HGT events, through unique pathways of symbiotic evolution. These findings indicate that insects can paradoxically acquire selective advantages with the help of their natural enemies.
A signalling cascade involving receptor-activated phospholipase A<sub>2</sub>, glycerophosphoinositol 4-phosphate, Shp1 and Src in the activation of cell motility.
Publication Date: 01/03/2019, on Cell communication and signaling : CCS
by Varone A, Mariggiò S, Patheja M, Maione V, Varriale A, Vessichelli M, Spano D, Formiggini F, Lo Monte M, Brancati N, Frucci M, Del Vecchio P, D'Auria S, Flagiello A, Iannuzzi C, Luini A, Pucci P, Banci L, Valente C, Corda D
Shp1, a tyrosine-phosphatase-1 containing the Src-homology 2 (SH2) domain, is involved in inflammatory and immune reactions, where it regulates diverse signalling pathways, usually by limiting cell responses through dephosphorylation of target molecules. Moreover, Shp1 regulates actin dynamics. One Shp1 target is Src, which controls many cellular functions including actin dynamics. Src has been previously shown to be activated by a signalling cascade initiated by the cytosolic-phospholipase A (cPLA) metabolite glycerophosphoinositol 4-phosphate (GroPIns4P), which enhances actin polymerisation and motility. While the signalling cascade downstream Src has been fully defined, the mechanism by which GroPIns4P activates Src remains unknown.
The complex CBX7-PRMT1 has a critical role in regulating E-cadherin gene expression and cell migration.
Publication Date: 28/02/2019, on Biochimica et biophysica acta. Gene regulatory mechanisms
by Federico A, Sepe R, Cozzolino F, Piccolo C, Iannone C, Iacobucci I, Pucci P, Monti M, Fusco A
The Chromobox protein homolog 7 (CBX7) belongs to the Polycomb Group (PcG) family, and, as part of the Polycomb repressive complex (PRC1), contributes to maintain transcriptional gene repression. Loss of CBX7 expression has been reported in several human malignant neoplasias, where it often correlates with an advanced cancer state and poor survival, proposing CBX7 as a candidate tumor-suppressor gene in cancer progression. Indeed, CBX7 is able to positively or negatively regulate the expression of genes involved in cell proliferation and cancer progression, such as E-cadherin, cyclin E, osteopontin, EGR1. To understand the molecular mechanisms that underlie the involvement of CBX7 in cancer progression, we designed a functional proteomic experiment based on CHIP-MS to identify novel CBX7 protein partners. Among the identified CBX7-interacting proteins we focused our attention on the Protein Arginine Methyltransferase 1 (PRMT1) whose critical role in epithelial-mesenchymal transition (EMT), cancer cell migration and invasion has been already reported. We confirmed the interaction between CBX7 and PRMT1 and demonstrated that this interaction is crucial for PRMT1 enzymatic activity both in vitro and in vivo and for the regulation of E-cadherin expression, an important hallmark of EMT. These results suggest a general mechanism by which CBX7 interacting with histone modification enzymes like HDAC2 and PRMT1 enhances E-cadherin expression. Therefore, disruption of this equilibrium may induce impairment of E-cadherin expression and increased cell migration eventually leading to EMT and, then, cancer progression.
Benzodifurans for biomedical applications: BZ4, a selective anti-proliferative and anti-amyloid lead compound.
Publication Date: 25/02/2019, on Future medicinal chemistry
by Vicidomini C, Cioffi F, Broersen K, Roviello V, Riccardi C, Montesarchio D, Capasso D, Gaetano SD, Musumeci D, Roviello GN
Our goal is to evaluate benzodifuran-based scaffolds for biomedical applications.
Effects of metformin therapy on COronary endothelial DYsfunction in prediabetic patients With stable angina and Non Obstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study.
Publication Date: 22/02/2019, on Diabetes care
by Sardu C, Paolisso P, Sacra C, Mauro C, Minicucci F, Portoghese M, Rizzo MR, Barbieri M, Sasso FC, D'Onofrio N, Balestrieri ML, Calabrò P, Paolisso G, Marfella R
To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS).
Platinum(II) <i>O</i>,<i>S</i> Complexes Inhibit the Aggregation of Amyloid Model Systems.
Publication Date: 14/02/2019, on International journal of molecular sciences
by Florio D, Malfitano AM, Di Somma S, Mügge C, Weigand W, Ferraro G, Iacobucci I, Monti M, Morelli G, Merlino A, Marasco D
Platinum(II) complexes with different cinnamic acid derivatives as ligands were investigated for their ability to inhibit the aggregation process of amyloid systems derived from Aβ, Yeast Prion Protein Sup35p and the C-terminal domain of nucleophosmin 1. Thioflavin T binding assays and circular dichroism data indicate that these compounds strongly inhibit the aggregation of investigated peptides exhibiting IC values in the micromolar range. MS analysis confirms the formation of adducts between peptides and Pt(II) complexes that are also able to reduce amyloid cytotoxicity in human SH-SY5Y neuroblastoma cells. Overall data suggests that bidentate ligands based on β-hydroxy dithiocinnamic esters can be used to develop platinum or platinoid compounds with anti-amyloid aggregation properties.
Does cognitive reserve play any role in multiple sclerosis? A meta-analytic study.
Publication Date: 14/02/2019, on Multiple sclerosis and related disorders
by Santangelo G, Altieri M, Gallo A, Trojano L
Inconsistent evidence is available about the possibility that cognitive reserve (CR) moderates the impact of disease progression, evaluated by MRI biomarkers (lesion load, white matter or gray matter volumes) or clinical proxies of physical disability (i.e. the Expanded Disability Status Scale, EDSS) on cognition in Multiple Sclerosis (MS). A meta-analytic study with a meta-regression approach was performed to investigate the possible role of CR as moderator of the impact of brain damage and physical disability on cognition.
Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment.
Publication Date: 13/02/2019, on Antiviral therapy
by Pisaturo M, Starace M, Minichini C, De Pascalis S, Macera M, Occhiello L, Messina V, Sangiovanni V, Claar E, Precone D, Stornaiuolo G, Stanzione M, Gentile I, Brancaccio G, Martini S, Masiello A, Megna AS, Coppola C, Federico A, Sagnelli E, Persico M, Lanza AG, Marrone A, Gaeta GB, Coppola N
This real-world clinical-setting study characterized the virological patterns in genotype-1 patients failing IFN-free regimens and evaluated the efficacy of re-treatment.
Thymomatous myasthenia gravis: novel association with HLA DQB1*05:01 and strengthened evidence of high clinical and serological severity.
Publication Date: 11/02/2019, on Journal of neurology
by Massa R, Greco G, Testi M, Rastelli E, Terracciano C, Frezza E, Garibaldi M, Marfia GA, Locatelli F, Mercuri NB, Pompeo E, Antonini G, Andreani M
The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood.
Apathy as a herald of cognitive changes in multiple sclerosis: A 2-year follow-up study.
Publication Date: 07/02/2019, on Multiple sclerosis (Houndmills, Basingstoke, England)
by Raimo S, Spitaleri D, Trojano L, Santangelo G
Behavioral symptoms, such as apathy and depression, are common in multiple sclerosis (MS) but their relationship with cognitive and clinical characteristics often remains underinvestigated and not monitored over time.
Thrombus Aspiration in Hyperglycemic Patients With High Inflammation Levels in Coronary Thrombus.
Publication Date: 05/02/2019, on Journal of the American College of Cardiology
by Sardu C, D'Onofrio N, Mauro C, Balestrieri ML, Marfella R
Neural plasticity and adult neurogenesis: the deep biology perspective.
Publication Date: 01/02/2019, on Neural regeneration research
by Colangelo AM, Cirillo G, Alberghina L, Papa M, Westerhoff HV
The recognition that neurogenesis does not stop with adolescence has spun off research towards the reduction of brain disorders by enhancing brain regeneration. Adult neurogenesis is one of the tougher problems of developmental biology as it requires the generation of complex intracellular and pericellular anatomies, amidst the danger of neuroinflammation. We here review how a multitude of regulatory pathways optimized for early neurogenesis has to be revamped into a new choreography of time dependencies. Distinct pathways need to be regulated, ranging from neural growth factor induced differentiation to mitochondrial bioenergetics, reactive oxygen metabolism, and apoptosis. Requiring much Gibbs energy consumption, brain depends on aerobic energy metabolism, hence on mitochondrial activity. Mitochondrial fission and fusion, movement and perhaps even mitoptosis, thereby come into play. All these network processes are interlinked and involve a plethora of molecules. We recommend a deep thinking approach to adult neurobiology.
Cognitive reserve and neuropsychological performance in multiple sclerosis: A meta-analysis.
Publication Date: 31/01/2019, on Neuropsychology
by Santangelo G, Altieri M, Enzinger C, Gallo A, Trojano L
Cognitive dysfunction is frequent in multiple sclerosis (MS), and its relationship with cognitive reserve (CR) has been investigated in several studies with conflicting results. In this meta-analysis, we here sought to determine the relationship between CR and cognition in MS patients and to ascertain whether demographic or clinical variables could moderate the above-mentioned relationship.