Scientific evidences support the importance of an appropriate nutrition during pregnancy in promoting maternal and neonatal positive outcomes as well as in preventing gestational complications, such as hypertension, diabetes and fetal... more
Scientific evidences support the importance of an appropriate nutrition during pregnancy in promoting maternal and neonatal positive outcomes as well as in preventing gestational complications, such as hypertension, diabetes and fetal growth defects. According to \u201cDOHaD hypothesis\u201d (Developmental Origin of Health and Disease), the quantity and quality of nutrients assumed by the fetus during intra-uterine develoment could contribute in modulating the fetal metabolism, with long-term consequences on adult health. The "HuMAN-BB" project was conceived to investigate the impact of maternal nutrition on neonatal outcomes, in particular on newborn epigenome setting, through the \u201cEPIC-FFQ\u201d questionnaire on one side and the analysis of maternal/placental biological samples and related clinical data, on the other side. As part of \u201cHuMAN-BB\u201d project, this thesis evaluates the adequacy of maternal nutrition, compared to current guidelines (SIGO 2018). In...
Research Interests:
Research Interests:
Research Interests:
DNA methylation in the human genome is largely programmed and shaped by transcription factor binding and interaction between DNA methyltransferases and histone marks during gamete and embryo development. Normal methylation profiles can be... more
DNA methylation in the human genome is largely programmed and shaped by transcription factor binding and interaction between DNA methyltransferases and histone marks during gamete and embryo development. Normal methylation profiles can be modified at single or multiple loci, more frequently as consequences of genetic variants acting in cis or in trans, or in some cases stochastically or through interaction with environmental factors. For many developmental disorders, specific methylation patterns or signatures can be detected in blood DNA. The recent use of high-throughput assays investigating the whole genome has largely increased the number of diseases for which DNA methylation analysis provides information for their diagnosis. Here, we review the methylation abnormalities that have been associated with mono/oligogenic diseases, their relationship with genotype and phenotype and relevance for diagnosis, as well as the limitations in their use and interpretation of results.
Research Interests:
Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are... more
Several molecular markers drive diagnostic classification, prognostic stratification, and/or prediction of response to therapy in patients with gliomas. Among them, IDH gene mutations are valuable markers for defining subtypes and are strongly associated with epigenetic silencing of the methylguanine DNA methyltransferase (MGMT) gene. However, little is known about the percentage of MGMT-methylated alleles in IDH-mutated cells or the potential association between MGMT methylation and deletion of chromosome 10q, which encompasses the MGMT locus. Here, we quantitatively assessed MGMT methylation and IDH1 mutation in 208 primary glioma samples to explore possible differences associated with the IDH genotype. We also explored a potential association between MGMT methylation and loss of chromosome 10q. We observed that MGMT methylation was heterogeneously distributed within glioma samples irrespective of IDH status suggesting an incomplete overlap between IDH1-mutated and MGMT-methylated...
Research Interests:
Research Interests: Physiology, Diabetes, Stem Cell, Regenerative Medicine, Medicine, and 15 moreStem cell Therapy, Mesenchymal stem cells, Humans, Autoimmune diseases, Systemic sclerosis, Skin, Mesenchymal Stem Cell, Medical Physiology, Wound, Ulcer, Diabetes complications, Leg Ulcers, Organogenesis, Digital Ulcersin Systemic Sclerosis, and adipose stem cells
The coexistence of mesothelioma and other primary malignancies has been previously reported in literature, but the finding of a pleural mesothelioma with a synchronous peritoneal mesothelioma has not been reported so far. We report a case... more
The coexistence of mesothelioma and other primary malignancies has been previously reported in literature, but the finding of a pleural mesothelioma with a synchronous peritoneal mesothelioma has not been reported so far. We report a case of a 58-years-old woman that came to our attention for the incidental finding of an inguinal mass. Fine-needle biopsies of the mass and a thoracoscopy with pleural biopsies were performed, after imaging studies showed pleural thickenings suspicious for malignancy. Histological morphology and growth pattern were similar in both cases. Both tumors stained for calretinin, but only the pleural mesothelioma showed positivity for Wilms-Tumor 1 antibody. We tried to demonstrate with molecular biology techniques whether they were synchronous or one was the metastasis of the other, but our studies did not give informative results. The prognosis in this case is poor, and after 6 months the patient is still following a chemotherapy regimen, which is the only ...
Research Interests:
Research Interests:
Research Interests:
Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or... more
Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients. We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analys...
Research Interests: Genetics, Computational Biology, Biology, Medicine, Humans, and 15 moreFluorescence in situ hybridization, Mutation, Female, Phenotype, Clinical Sciences, Middle Aged, Base Sequence, Nose, Fingers, DNA binding proteins, Comparative Genomic Hybridization, Hand deformities, DNA mutational analysis, Hair Diseases, and Breakpoint
Research Interests: Engineering, Genetics, Chemistry, Genomics, Biology, and 15 moreMedicine, Gene expression, Colorectal cancer, Heterogeneity, Epigenomics, Humans, Fluorescence in situ hybridization, Glioma, DNA methylation, Fluorescent Antibody Technique, Malignant Glioma, Base Sequence, Brain Neoplasms, Comparative Genomic Hybridization, and clonal evolution
Research Interests: Endocrinology, Andrology, Biology, Immunohistochemistry, Medicine, and 15 morePregnancy, Humans, Placenta, Female, DNA methylation, Pediatric, Introns, Adult, Cesarean Section, Fetus, Gene Expression Regulation, real time polymerase chain reaction, Gene frequency, Paediatrics and reproductive medicine, and Fetal Growth Retardation
Research Interests:
Research Interests:
The Microtubule Affinity-Regulating Kinase 4 belongs to a kinases family that phosphorylates the Microtubule[MT]-Associated Proteins, causing their detachment and increasing MT dynamics. MARK4 encodes two alternative spliced isoforms, L... more
The Microtubule Affinity-Regulating Kinase 4 belongs to a kinases family that phosphorylates the Microtubule[MT]-Associated Proteins, causing their detachment and increasing MT dynamics. MARK4 encodes two alternative spliced isoforms, L and S, which expression is differentially regulated in human tissues. In normal brain the predominant expression of MARK4S has been related to a putative role in neuronal differentiation; the L isoform has been conversely found highly expressed in neural progenitors and in gliomas, as well as in hepatocarcinoma cell lines, highlighting a general role in neoplastic transformation. The current study aimed at better defining the role of MARK4 L and S in gliomagenesis. The expression levels of these isoforms were investigated by Q-PCR and WB on 50 gliomas (low and high grade tumors and cell lines) and 8 cancer stem cell lines (CSC), in addition to normal brain, neural stem cells (NSC) and neural progenitors. Array-CGH and mutation analysis failed to reve...
Research Interests:
The Microtubule Affinity-Regulating Kinase 4 belongs to a kinases family that phosphorylates the Microtubule[MT]-Associated Proteins, causing their detachment and increasing MT dynamics. MARK4 encodes two alternative spliced isoforms, L... more
The Microtubule Affinity-Regulating Kinase 4 belongs to a kinases family that phosphorylates the Microtubule[MT]-Associated Proteins, causing their detachment and increasing MT dynamics. MARK4 encodes two alternative spliced isoforms, L and S, which expression is differentially regulated in human tissues. In normal brain the predominant expression of MARK4S has been related to a putative role in neuronal differentiation; the L isoform has been conversely found highly expressed in neural progenitors and in gliomas, as well as in hepatocarcinoma cell lines, highlighting a general role in neoplastic transformation. The current study aimed at better defining the role of MARK4 L and S in gliomagenesis. The expression levels of these isoforms were investigated by Q-PCR and WB on 50 gliomas (low and high grade tumors and cell lines) and 8 cancer stem cell lines (CSC), in addition to normal brain, neural stem cells (NSC) and neural progenitors. Array-CGH and mutation analysis failed to reve...
Research Interests:
Research Interests:
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterised by the clonal proliferation of the haematopoietic precursors together with the progressive development of bone marrow fibrosis. This stromal alteration is an... more
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterised by the clonal proliferation of the haematopoietic precursors together with the progressive development of bone marrow fibrosis. This stromal alteration is an important clinical issue and specific prognostic markers are not currently available. In bone marrow biopsies from 58 PMF patients, we explored the methylation pattern of genes encoding cytokines involved in the stromal reaction, namely platelet-derived growth factor-beta (PDGFB), transforming growth factor-beta (TGFB) and basic fibroblast growth factor (FGF2). We also evaluated the methylation profile of the Long Interspersed Nucleotide Element 1 (LINE-1). PDGFB, FGF2 and LINE-1, but not TGFB, were significantly differently methylated in PMF compared to controls. Significantly, PDGFB hypomethylation (<16%) was correlated with a favourable PMF prognosis (grade of marrow fibrosis, p=0.03; International Prognostic Scoring Systems p=0.01 and Dynamic International Prognostic Scoring Systems, p=0.02). Although the basis of the association of PDGFB hypomethylation with favourable prognosis remains to be clarified, we speculate that hypomethylation in PMF could represent the effect of acquired somatic mutations in genes involved in epigenetic regulation of the genome.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Objective. The role of epigenetics in the modulation of longevity has not been studied in humans. We employed a new experimental model to identify epigenetically modulated genes involved in the process of ageing, healthy ageing and... more
Objective. The role of epigenetics in the modulation of longevity has not been studied in humans. We employed a new experimental model to identify epigenetically modulated genes involved in the process of ageing, healthy ageing and longevity. To this aim 1) we evaluated the DNA methylation from peripheral leukocyte of 21 female centenarians, their 21 female offspring, 21 offspring of both non long-lived parents and 21 young women.
Research Interests: Engineering, Physics, Chemistry, Genomics, Biology, and 13 moreMedicine, Multidisciplinary, Humans, Fluorescence in situ hybridization, Mutation, Glioma, PLoS one, Fluorescent Antibody Technique, Base Sequence, Hydrogen-Ion Concentration, Brain Neoplasms, Comparative Genomic Hybridization, and Neoplastic Stem Cells
Research Interests:
Background Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant ACADM (gene encoding MCAD enzyme)... more
Background Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant ACADM (gene encoding MCAD enzyme) genotypes that have never been identified in clinically ascertained patients. It could be hypothesised that residual MCAD enzyme activity can contribute in risk stratification of subjects with variant ACADM genotypes.
Research Interests:
Iron (Fe) deficiency in pregnancy is associated to low birth weight and premature delivery while in adults it can result in increased blood pressure and cardiovascular disease. Cellular Fe uptake is mediated by the Transferrin Receptor 1... more
Iron (Fe) deficiency in pregnancy is associated to low birth weight and premature delivery while in adults it can result in increased blood pressure and cardiovascular disease. Cellular Fe uptake is mediated by the Transferrin Receptor 1 (TFRC), located in the trophoblast membranes. Here, we measured TFRC mRNA expression (Real Time PCR) and TFRC protein expression and localization (Western Blotting
Research Interests: Biology, Immunohistochemistry, Intelligent Transport System, Cardiovascular disease, Gene expression, and 15 moreBirth Weight, Growth, Humans, Blood Pressure, Female, Iron, Clinical Sciences, Adult, Cesarean Section, Blood gas analysis, Intrauterine Growth Restriction, Case Control Studies, Fetal Heart Rate, In Utero, and Fetal Growth Retardation
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with... more
The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with preeclampsia (PE) and gestational hypertension (GH) is still controversial. We genotyped ACE I/D, ADD1 G460W, and ADD1 S586C polymorphisms in 672 unrelated pregnant women: 204 PE (81/204 mild PE), 56 GH, and 412 controls, evaluating both their single and combined effects on these pathologies. The genotype combination of the 3 polymorphisms was not statistically different in cases versus controls, nor were ACE and ADD1 polymorphisms in GH. Nevertheless, the distribution of ACE genotypes was different in PE. This was confirmed in mild PE, whereas no significance was found in severe PE. This could suggest that different factors may lead to mild and severe PE, with ACE polymorphism playing a more important role in the mild form.
Research Interests:
Background Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome... more
Background Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying the mutant ABCD1 allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD) carrier phenotype, but reported data so far are conflicting. Methods To shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs) of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify ABCD1 allele-specific expression. Moreover, very long...
Research Interests: Humans, Mutation, Female, Young Adult, Aged, and 4 moreMiddle Aged, Adult, Gene Expression Regulation, and alleles
Research Interests: Breast Cancer, Long Noncoding Rna, Multidisciplinary, RNA interference, Cell line, and 10 moreHumans, Fluorescence in situ hybridization, PLoS one, Genotype, Breast carcinoma, X chromosome, Breast Cancer Cells, X chromosome inactivation, Breast Neoplasms, and reverse transcriptase polymerase chain reaction
Research Interests:
Research Interests:
Among other factors, fetal growth requires maternal supply of cholesterol. Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and the scavenger receptor family. We hypothesized that expression levels of key... more
Among other factors, fetal growth requires maternal supply of cholesterol. Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and the scavenger receptor family. We hypothesized that expression levels of key receptors of these families were regulated differently in placentas from IUGR pregnancies with varying degrees of severity. Third-trimester placentas from IUGR pregnancies with (IUGR-S) and without (IUGR-M) fetal hemodynamic changes and from control (AGA) pregnancies were studied. LDL-R, LDL-R-related protein (LRP-1), and scavenger receptor class B type I (SR-BI) mRNA and protein levels were measured. Cholesterol concentration and composition of lipoproteins were analyzed enzymatically and by lipid electrophoresis, respectively, in maternal and umbilical cord blood. LDL-R mRNA levels in IUGR-M were similar to AGA but lower ( P < 0.05) in IUGR-S. In contrast, LDL-R protein was twofold (IUGR-M) and 1.8-fold (IUGR-S) higher ( P < 0.05) than in the AGA g...
Research Interests: Biological Sciences, Growth, Pregnancy, Humans, Placenta, and 15 moreCholesterol, Female, American, Newborn Infant, Middle Aged, Foetus, Adult, Lipoproteins, Fetus, Gestation, Lipoprotein a, Intrauterine Growth Restriction, Maternal-fetal exchange, Medical and Health Sciences, and Fetal Growth Retardation
Research Interests:
Research Interests:
Malignant peripheral nerve sheath tumor (MPNST) can arise sporadically or in association with neurofibromatosis type 1. Deletions at the 9p21 locus have been reported in these tumors. To additionally characterize the status of this... more
Malignant peripheral nerve sheath tumor (MPNST) can arise sporadically or in association with neurofibromatosis type 1. Deletions at the 9p21 locus have been reported in these tumors. To additionally characterize the status of this chromosomal region, in this study we performed a comprehensive, mostly PCR-based molecular analysis of the three tumor suppressor genes p15(INK4b), p14(ARF) and p16(INK4a) located at the 9p21 locus in 26 cryopreserved MPNSTs. Fourteen neurofibromatosis type 1-related and 12 sporadic cases were investigated for homozygous deletion coupled with fluorescent in situ hybridization, promoter methylation, and mutational analysis, as well as m-RNA expression. The results showed that an inactivation of one or more genes occurred in 77% of MPNSTs and was mainly achieved through homozygous deletion (46%), which, in turn, encompassed all of the three tandemly linked genes in 83% of the deleted cases. Promoter methylation was at a less extent involved in gene silencin...