Stefania Di Mauro

Bio: Stefania Di Mauro is an academic researcher from University of Catania. The author has contributed to research in topics: Medicine & Diabetes mellitus. The author has an hindex of 9, co-authored 21 publications receiving 337 citations.

Identification of circulating microRNAs for the differential diagnosis of Parkinson's disease and Multiple System Atrophy

Abstract: Background. Parkinson's disease (PD) is a progressive neurodegenerative disorder which may be misdiagnosed with atypical conditions such as Multiple System Atrophy (MSA), due to overlapping clinical features. MicroRNAs (miRNAs) are small noncoding RNAs with a key role in post-transcriptional gene regulation. We hypothesized that identification of a distinct set of circulating miRNAs (cmiRNAs) could distinguish patients affected by PD from MSA and healthy individuals. Results. Using TaqMan Low Density Array technology, we analysed 754 miRNAs and found 9 cmiRNAs differentially expressed in PD and MSA patients compared to healthy controls. We also validated a set of 4 differentially expressed cmiRNAs in PD and MSA patients versus controls. More specifically, miR-339-5p was downregulated, whereas miR-223*, miR-324-3p and mir-24 were upregulated in both diseases. We found cmiRNAs specifically deregulated in PD (downregulation of miR-30c and miR-148b) and in MSA (upregulation of miR-148b). Finally, comparing MSA and PD, we identified 3 upregulated cmiRNAs in MSA serum (miR-24, miR-34b, miR-148b). Conclusions. Our results suggest that cmiRNA signatures discriminate PD from MSA patients and healthy controls and may be considered specific, non-invasive biomarkers for differential diagnosis.

Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress.

Abstract: Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins.

Serum coding and non-coding RNAs as biomarkers of NAFLD and fibrosis severity

Abstract: BACKGROUND & AIMS In patients with non-alcoholic fatty liver disease (NAFLD), liver biopsy is the gold standard to detect non-alcoholic steatohepatitis (NASH) and stage liver fibrosis. We aimed to identify differentially expressed mRNAs and non-coding RNAs in serum samples of biopsy-diagnosed mild and severe NAFLD patients with respect to controls and to each other. METHODS We first performed a whole transcriptome analysis through microarray (n = 12: four Control: CTRL; four mild NAFLD: NAS ≤ 4 F0; four severe NAFLD NAS ≥ 5 F3), followed by validation of selected transcripts through real-time PCRs in an independent internal cohort of 88 subjects (63 NAFLD, 25 CTRL) and in an external cohort of 50 NAFLD patients. A similar analysis was also performed on liver biopsies and HepG2 cells exposed to oleate:palmitate or only palmitate (cellular model of NAFL/NASH) at intracellular/extracellular levels. Transcript correlation with histological/clinical data was also analysed. RESULTS We identified several differentially expressed coding/non-coding RNAs in each group of the study cohort. We validated the up-regulation of UBE2V1, BNIP3L mRNAs, RP11-128N14.5 lncRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with NAS ≥ 5 (vs NAS ≤ 4) and the up-regulation of HBA2 mRNA, TGFB2/TGFB2-OT1 coding/lncRNA in patients with Fibrosis stages = 3-4 (vs F = 0-2). In in vitro models: UBE2V1, RP11-128N14.5 and TGFB2/TGFB2-OT1 had an increasing expression trend ranging from CTRL to oleate:palmitate or only palmitate-treated cells both at intracellular and extracellular level, while BNIP3L was up-regulated only at extracellular level. UBE2V1, RP11-128N14.5, TGFB2/TGFB2-OT1 and HBA2 up-regulation was also observed at histological level. UBE2V1, RP11-128N14.5, BNIP3L and TGFB2/TGFB2-OT1 correlated with histological/biochemical data. Combinations of TGFB2/TGFB2-OT1 + Fibrosis Index based on the four factors (FIB-4) showed an Area Under the Curve (AUC) of 0.891 (P = 3.00E-06) or TGFB2/TGFB2-OT1 + Fibroscan (AUC = 0.892, P = 2.00E-06) improved the detection of F = 3-4 with respect to F = 0-2 fibrosis stages. CONCLUSIONS We identified specific serum coding/non-coding RNA profiles in severe and mild NAFLD patients that possibly mirror the molecular mechanisms underlying NAFLD progression towards NASH/fibrosis. TGFB2/TGFB2-OT1 detection improves FIB-4/Fibroscan diagnostic performance for advanced fibrosis discrimination.

Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes

Abstract: Context: Prediabetes is associated with atherosclerotic vascular damage. Objective: We investigated the correlation of endogenous secretory receptor for advanced glycation end-products (esRAGE), total soluble RAGE (sRAGE) and markers of inflammation, with early cardiovascular disease in subjects with prediabetes. We particularly focused on individuals with prediabetes identified only by glycated hemoglobin A1c (HbA1c) (5.7–6.4%) who had normal fasting glucose and were normotolerant after oral glucose tolerance test. Design: This was a cross-sectional study. Setting: The study was conducted in the Department of Clinical and Molecular Medicine, University of Catania, Italy. Main Outcome Measure: sRAGE, esRAGE, carboxymethyl-lysine, S100A12, HbA1c, fasting glycemia, oral glucose tolerance test, pulse wave velocity, and intima-media thickness were evaluated in subjects with prediabetes. Patients: Three hundred eighty subjects without previous history of diabetes were stratified into three groups: controls (n ...

Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma.

Abstract: // Marco Maugeri 1, * , Davide Barbagallo 1, * , Cristina Barbagallo 1, * , Barbara Banelli 2, 5, * , Stefania Di Mauro 3 , Francesco Purrello 3 , Gaetano Magro 4 , Marco Ragusa 1, ** , Cinzia Di Pietro 1, ** , Massimo Romani 2, ** , Michele Purrello 1, ** 1 Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biologia e Genetica G Sichel, Unita di BioMedicina Molecolare, Genomica e dei Sistemi Complessi, Universita di Catania, Catania, Italy, EU 2 UOS Epigenetica dei Tumori, IRCCS A.O.U. San Martino-IST, Genova, Italy, EU 3 Dipartimento di Biomedicina Clinica e Molecolare, Universita di Catania, Ospedale Garibaldi, Catania, Italy, EU 4 Dipartimento di Scienze Mediche, Chirurgiche e Tecnologie Avanzate G.F. Ingrassia, Universita di Catania, Catania, Italy, EU 5 Department of HealthSciences, University of Genova, Genova, Italy, EU * These authors have contributed equally to this work ** Senior Corresponding Authors Correspondence to: Michele Purrello, email: purrello@unict.it Keywords: miRNAs encoding genes, promoter methylation profiles, neuroblastoma, gene expression, 5’-AZA Received: May 05, 2016 Accepted: October 21, 2016 Published: November 04, 2016 ABSTRACT Neuroblastoma is the most common human extracranial solid tumor during infancy. Involvement of several miRNAs in its pathogenesis has been ascertained. Interestingly, most of their encoding genes reside in hypermethylated genomic regions: thus, their tumor suppressor function is normally disallowed in these tumors. To date, the therapeutic role of the demethylating agent 5’-Aza-2 deoxycytidine (5’-AZA) and its effects on miRNAome modulation in neuroblastoma have not been satisfactorily explored. Starting from a high-throughput expression profiling of 754 miRNAs and based on a proper selection, we focused on miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p as candidate miRNAs for our analysis. They resulted downregulated in four neuroblastoma cell lines with respect to normal adrenal gland. MiRNAs 29a-3p and 34b-3p also resulted downregulated in vivo in a murine neuroblastoma progression model. Unlike the amount of methylation of their encoding gene promoters, all these miRNAs were significantly overexpressed following treatment with 5’-AZA. Transfection with candidate miRNAs mimics significantly decreased neuroblastoma cells proliferation rate. A lower expression of miR-181c was significantly associated to a worse overall survival in a public dataset of 498 neuroblastoma samples ( http://r2.amc.nl ). Our data strongly suggest that CDK6, DNMT3A, DNMT3B are targets of miR-29a-3p, while CCNE2 and E2F3 are targets of miR-34b-3p. Based on all these data, we propose that miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p are disallowed tumor suppressor genes in neuroblastoma and suggest them as new therapeutic targets in neuroblastoma.

An overview of microRNAs: Biology, functions, therapeutics, and analysis methods

Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs, which function in posttranscriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development, and apoptosis. They have been linked to many diseases, and currently miRNA-mediated clinical trial has shown promising results for treatment of cancer and viral infection. This review provides an overview and update on miRNAs biogenesis, regulation of miRNAs expression, their biological functions, and role of miRNAs in epigenetics and cell-cell communication. In addition, alteration of miRNAs following exercise, their association with diseases, and therapeutic potential will be explained. Finally, miRNA bioinformatics tools and conventional methods for miRNA detection and quantification will be discussed.

Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

Abstract: Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.