1,078 results on '"Oliviero O"'
Search Results
2. Functional porous hydrogels to study angiogenesis under the effect of controlled release of vascular endothelial growth factor
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Oliviero, O., Ventre, M., and Netti, P.A.
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- 2012
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3. Additive manufacturing and tissue engineering to improve outcomes in breast reconstructive surgery
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Rocco N., Nava M. B., Catanuto G., Accurso A., Martorelli M., Oliviero O., Improta G., Papallo I., De Santis R., Gloria A., Speranza D., IMPROTA, Giovanni, Rocco, N., Nava, M. B., Catanuto, G., Accurso, A., Martorelli, M., Oliviero, O., Improta, G., Papallo, I., De Santis, R., Gloria, A., Speranza, D., and Improta, Giovanni
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medicine.medical_specialty ,Reconstructive surgery ,Mass transport ,Breast conservation ,business.industry ,medicine.medical_treatment ,design ,Porous scaffold ,scaffold design ,reverse engineering ,Tissue engineering ,breast reconstructive surgery ,Medicine ,Medical physics ,skin and connective tissue diseases ,business ,Breast reconstruction ,additive manufacturing ,fat grafting ,Mastectomy ,Early breast cancer - Abstract
Many women with early breast cancer undergo mastectomy as a consequence of an unfavorable tumor/breast ratio or because they prefer this option to breast conservation. As reported, breast reconstruction offers significant psychological advantages. Several techniques are currently available for the breast oncoplastic surgeon and offer interesting results in terms of aesthetic and patient-reported outcomes, using both breast implants and autologous tissues. On the other hand, advanced methodologies and technologies, such as reverse engineering and additive manufacturing, allow the development of customized porous scaffolds with tailored architectures, biological, mechanical and mass transport properties. Accordingly, the current research dealt with challenges, design methods and principles to develop 3D additively manufactured structures in breast reconstructive surgery.
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- 2019
4. Unveiling a hotspot of genetic diversity in southern Italy for the endangered Hermann’s tortoise Testudo hermanni
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Andrea Chiocchio, Mauro Zampiglia, Marta Biaggini, Roberto Biello, Luciano Di Tizio, Francesco Luigi Leonetti, Oliviero Olivieri, Emilio Sperone, Massimo Trabalza-Marinucci, Claudia Corti, and Daniele Canestrelli
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Biodiversity hotspots ,Conservation genetics ,Italian Peninsula ,Genetic structure ,Phylogeography ,Threatened species ,Ecology ,QH540-549.5 ,Evolution ,QH359-425 - Abstract
Abstract Background Hotspots of intraspecific genetic diversity represent invaluable resources for species to cope with environmental changes, and their identification is increasingly recognized as a major goal of conservation ecology research. However, even for iconic and endangered species, conservation strategies are often planned without thorough information on the geographic patterns of genetic variation. Here, we investigated the spatial patterns of genetic variation of the endangered Hermann’s tortoise Testudo hermanni in the Italian Peninsula by genotyping 174 individuals at 7 microsatellite loci, with the aim to contribute to planning effective conservation strategies. Results Ordination-based and Bayesian clustering analyses consistently identified three main genetic clusters, one spread in the central and northern part of the peninsula, and two restricted to southern Italy and Sicily, respectively. The highest levels of genetic diversity were found in populations of the southern cluster and, in particular, at the northern edges of its distribution (He > 0.6, Ar > 2.8 ), that correspond to areas of putative secondary contact and admixture between distinct lineages. Our results clearly identify a hotspot of genetic diversity for the Hermann’s tortoise in southern Italy. Conclusion We inferred the evolutionary history and the spatial patterns of genetic variation of the Hermann’s tortoise in the Italian Peninsula. We identified three main genetic clusters along the peninsula and a hotspot of intraspecific diversity in southern Italy. Our results underline the urgent need for conservation actions to warrant the long-term persistence of viable tortoise populations in this area. Furthrmore, these data add further evidence to the role of southern Italy as a biodiversity hotspot for temperate fauna, claiming for higher consideration of this area in large scale conservation programs.
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- 2022
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5. Novel protein-truncating variant in the APOB gene may protect from coronary artery disease and adverse cardiovascular events
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Gabriele Mango, Nicola Osti, Silvia Udali, Anna Vareschi, Giovanni Malerba, Alejandro Giorgetti, Francesca Pizzolo, Simonetta Friso, Domenico Girelli, Oliviero Olivieri, Annalisa Castagna, and Nicola Martinelli
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Dyslipidemia ,Apolipoprotein B ,Coronary Artery Disease ,Next Generation Sequencing ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background and aims: Genetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon. Methods: Starting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol. Results: APOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-100 (ApoB-51), with a truncation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-48, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation. Conclusions: Our data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes.
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- 2022
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6. Effect of topical antiinflammatory drugs on mechanical behavior of rabbit cornea
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Lepore, D., De Santis, R., Pagliara, M. M., Gloria, A., Oliviero, O., Nucci, C., Improta, G., Triassi, M., Ambrosio, L., Lepore D. (ORCID:0000-0002-2104-9239), Lepore, D., De Santis, R., Pagliara, M. M., Gloria, A., Oliviero, O., Nucci, C., Improta, G., Triassi, M., Ambrosio, L., and Lepore D. (ORCID:0000-0002-2104-9239)
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Background: A variety of antiinflammatory therapies are employed to promote corneal wound healing. The effects of steroidal and nonsteroidal antiinflammatory drugs on the biomechanical properties of rabbit cornea were investigated over time using tensile tests. Methods: Full-thickness incisions were made and used to analyze the effects of dexamethasone sodium phosphate 0.1% and diclofenac sodium 0.1% on corneal biomechanical properties during wound healing at 7, 14 and 21 days after surgery. Results: The full-thickness incision deeply modified all of the mechanical properties. At 3 weeks after incision, regardless of the drug therapy, the tensile modulus was about 70% of the value for the intact cornea. Conclusions: Topical treatment with dexamethasone was particularly effective during the first week after surgery; the second week after surgery, a similar result was observed in the corneas treated with diclofenac. Low doses of steroidal and nonsteroidal antiinflammatory drugs would seem to have the potential to improve biomechanical properties only during the early stage of the healing process of the cornea.
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- 2017
7. Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism
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Lorenzo Bertolone, Annalisa Castagna, Marcello Manfredi, Domenica De Santis, Francesca Ambrosani, Elisa Antinori, Paolo Mulatero, Elisa Danese, Emilio Marengo, Elettra Barberis, Mariangela Veneri, Nicola Martinelli, Simonetta Friso, Francesca Pizzolo, and Oliviero Olivieri
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urinary extracellular vesicles (UEVs) ,primary aldosteronism ,essential hypertension ,proteomics ,aquaporin 1 (AQP1) ,aquaporin 2 (AQP2) ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundUrinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information “in vivo” without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).MethodsPatients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.ResultsMS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH vs PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH vs PA, as well as A1AG1 (AGP1).ConclusionThrough this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH.
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- 2023
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8. Urinary extracellular vesicles carry valuable hints through mRNA for the understanding of endocrine hypertension
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Simonetta Friso, Annalisa Castagna, Gabriele Mango, Oliviero Olivieri, and Francesca Pizzolo
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11-beta hydroxysteroid dehydrogenase 2 ,HSD11B2 ,endocrine hypertension ,gene expression ,mRNA ,exosomes ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Urinary extracellular vesicles (uEVs), released from cells of the urogenital tract organs, carry precious information about originating tissues. The study of molecules transported through uEVs such as proteins, lipids and nucleic acids provides a deeper understanding of the function of the kidney, an organ involved in the pathogenesis of hypertension and a target of hypertension-mediated organ damage. Molecules derived from uEVs are often proposed for the study of disease pathophysiology or as possible disease diagnostic and prognostic biomarkers. Analysis of mRNA loading within uEVs may be a unique and readily obtainable way to assess gene expression patterns of renal cells, otherwise achievable only by an invasive biopsy procedure. Interestingly, the only few studies investigating transcriptomics of hypertension-related genes through the analysis of mRNA from uEVs are inherent to mineralocorticoid hypertension. More specifically, it has been observed that perturbation in human endocrine signalling through mineralcorticoid receptors (MR) activation parallels changes of mRNA transcripts in urine supernatant. Furthermore, an increased copy number of uEVs-extracted mRNA transcripts of the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene were detected among subjects affected by apparent mineralocorticoid excess (AME), a hypertension-inducing autosomal recessive disorder due to a defective enzyme function. Moreover, by studying uEVs mRNA, it was observed that the renal sodium chloride cotransporter (NCC) gene expression is modulated under different conditions related to hypertension. Following this perspective, we illustrate here the state of the art and the possible future of uEVs transcriptomics towards a deeper knowledge of hypertension pathophysiology and ultimately more tailored investigational, diagnostic-prognostic approaches.
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- 2023
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9. Spatial and temporal variability of throughfall at the plot scale in the Italian pre-Alps
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Zuecco, Giulia, Oliviero, O., Penna, Daniele, van Meerveld, H. J., Hopp, L., DALLA FONTANA, Giancarlo, and Borga, Marco
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- 2014
10. Atypical hemolytic uremic syndrome: Unique clinical presentation linked to rare CFHR5 mutation
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Sofia Menotti, Martino Donini, Giuseppina Pessolano, Livia Tiro, Maurizio Cantini, Jacopo Croce, Matteo Morandi, Filippo Mazzi, Katia Donadello, Oliviero Olivieri, Francesco Dima, Sergio De Marchi, Giovanni Gambaro, Enrico Polati, and Lucia De Franceschi
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complement ,eculizumab ,microangiopathy ,plasmapheresis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2021
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11. Detection of Testudinid alphaherpesvirus, Chlamydia spp., Mycoplasma spp., and Salmonella spp. in free‑ranging and rescued Italian Testudo hermanni hermanni
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Maria Luisa Marenzoni, Valentina Stefanetti, Emilia Del Rossi, Alessia Zicavo, Stefania Scuota, Francesco Carlo Origgi, Gianluca Deli, Claudia Corti, Massimo Trabalza Marinucci, and Oliviero Olivieri
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Mycoplasma agassizii ,Reintroduction ,Salmonella ,Testudinid alphaherpesvirus ,Testudo hermanni ,Free‑ranging ,Animal culture ,SF1-1100 ,Veterinary medicine ,SF600-1100 - Abstract
Testudo hermanni is included as near‑threatened in the Red List of the International Union for Conservation of Nature, while T. hermanni hermanni is considered endangered in the Italian Red List. Appropriate management of smuggled or seized wild individuals is recommended before their reintroduction into the wild. Accordingly, a health monitoring study was carried out. During 2014‑2016, 133 oral swabs and 121 cloacal swabs were collected from a total of approximately 180 free‑ranging and rescued T. hermanni hermanni from eight different Italian regions to investigate the presence of DNA of Testudinid alphaherpesvirus (TeAHV), Chlamydia spp. and Mycoplasma spp. in the oral cavity, and Salmonella spp. isolates in the cloaca. Mycoplasma spp. was detected in 52 out of 87 (59.77%) of rescued and in 1 out of 46 free‑ranging (2.17%) individuals; 33 out of 53 (62.26%) Mycoplasma spp. positive samples were typed as M. agassizii by PCR. Salmonella spp. was isolated from 45 out of 121 (37.19%) cloacal swabs, typed into 14 serovars, and characterized for complete antimicrobial susceptibility. A significantly different distribution of Salmonella spp. isolates was found in 2016 in comparison with 2014 and 2015, without any difference between free‑ranging and rescued tortoises. All the tested tortoises were negative for TeAHV and Chlamydia spp. These results are considered a baseline information critical to monitor the dynamics of these microorganisms in free‑ranging and rescued populations of T. h. hermanni, and to correctly approach the management of rescued animals and possible relocation programs.
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- 2022
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12. Controls on rainfall-runoff response of a forested mountain catchment
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Penna, D., Oliviero, O., Giulia Zuecco, Meerveld, H. J., marco borga, and Giancarlo Dalla Fontana
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- 2013
13. Effects of rainfall amount and antecedent moisture conditions on the rainfall-runoff response of a forested mountain catchment
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Penna, Daniele, Oliviero, O., Zuecco, Giulia, Assendelft, R., van Meerveld, H. J., Borga, Marco, and DALLA FONTANA, Giancarlo
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- 2013
14. Macro-porous PEG-crosslinked heparin for the sustained release of VEGF
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Oliviero, O., Capua, A., PAOLO NETTI, Oliviero, Olimpia, De Capua, Antonia, and Netti, PAOLO ANTONIO
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Biomaterials - Published
- 2008
15. Antiangiogenetic activity of the endocannabinoid anandamide.Correlation to its tumour-suppressor efficacy
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M Pisanti S, Borselli C., Gazzerro P, Laezza C, Bifulco. Pisanti S, Borselli C, Oliviero O, and Bifulco M.
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- 2007
16. The spatial distribution and the temporal evolution of the matrix regulate cell function
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Borselli C, Oliviero O., De Rosa E., Battista S., Ambrosio L., and Netti P.A
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collagen ,vascularization ,tissue engineering ,hyaluronic acid ,composite - Published
- 2006
17. High Plasma Concentration of Apolipoprotein C-III Confers an Increased Risk of Cerebral Ischemic Events on Cardiovascular Patients Anticoagulated With Warfarin
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Oliviero Olivieri, Gianni Turcato, Manuel Cappellari, Filippo Stefanoni, Nicola Osti, Francesca Pizzolo, Simonetta Friso, Antonella Bassi, Annalisa Castagna, and Nicola Martinelli
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apolipoprotein C-III ,cerebral ischemic events ,anticoagulant therapy ,warfarin ,atrial fibrillation ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
IntroductionApolipoprotein C-III (Apo CIII) is a crucial regulator of triglyceride-rich lipoproteins (TRLs) and influences the risk of cardiovascular diseases. High levels of Apo CIII have been also associated with cerebrovascular events and earlier works showed procoagulant effects of Apo CIII. The main aim was to assess whether the plasma concentration of Apo CIII could confer an increased risk of cerebral ischemic events in anticoagulated patients at high-risk of cardioembolism.MethodsWe systematically checked medical records and quantified cerebral ischemic events in a selected cohort of 118 subjects [median age 68 with interquartile range (IQR) 59–75 years, 66.9% males, 52.5% with coronary artery disease (CAD)], taking anticoagulant therapy with warfarin because of atrial fibrillation (AF) and/or mechanical prosthetic heart valves. All the subjects, enrolled between May 1999 and December 2006, were prospectively followed until death or July 31, 2018. Assessments of complete plasma lipid and apolipoprotein profiles, including Apo A-I, B, CIII, and E, were available for all subjects at enrollment.ResultsAfter a median follow-up of 109 months (IQR, 58–187), 24 subjects (20.3%) had cerebral ischemic events: stroke (n = 15) and TIA (n = 9). Subjects with plasma concentration of Apo CIII above the median value (10.3 mg/dL) had an about three-fold increased risk of stroke/TIA than those with lower levels of Apo C-III [hazard ratio 3.08 (95%CI, 1.22–7.77)]. This result was confirmed in multiple Cox regression models adjusted for gender, age, CAD, AF, diabetes, hypertension, plasma lipids, and CHA2DS2-VASc score. By stratifying the sample on the basis of Apo CIII level and CHA2DS2-VASc score, an additive effect was observed with the highest risk in subjects with both high Apo C-III concentration and CHA2DS2-VASc score.ConclusionHigh Apo CIII plasma levels may be associated with an increased risk of ischemic stroke/TIA in high-risk cardiovascular patients anticoagulated with warfarin.
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- 2022
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18. The Impact of the COVID-19 Pandemic on Head and Neck Cancer Diagnosis in the Piedmont Region, Italy: Interrupted Time-Series Analysis
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Maja Popovic, Valentina Fiano, Giovenale Moirano, Luigi Chiusa, David I. Conway, Paolo Garzino Demo, Marco Gilardetti, Giuseppe Carlo Iorio, Chiara Moccia, Oliviero Ostellino, Giancarlo Pecorari, Guglielmo Ramieri, Umberto Ricardi, Giuseppe Riva, Shama Virani, and Lorenzo Richiardi
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COVID-19 ,head and neck ,cancer detection ,Italy ,interrupted time-series analysis (ITSA) ,time trend analyses ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundThe COVID-19 pandemic has likely affected the most vulnerable groups of patients and those requiring time-critical access to healthcare services, such as patients with cancer. The aim of this study was to use time trend data to assess the impact of COVID-19 on timely diagnosis and treatment of head and neck cancer (HNC) in the Italian Piedmont region.MethodsThis study was based on two different data sources. First, regional hospital discharge register data were used to identify incident HNC in patients ≥18 years old during the period from January 1, 2015, to December 31, 2020. Interrupted time-series analysis was used to model the long-time trends in monthly incident HNC before COVID-19 while accounting for holiday-related seasonal fluctuations in the HNC admissions. Second, in a population of incident HNC patients eligible for recruitment in an ongoing clinical cohort study (HEADSpAcE) that started before the COVID-19 pandemic, we compared the distribution of early-stage and late-stage diagnoses between the pre-COVID-19 and the COVID-19 period.ResultsThere were 4,811 incident HNC admissions in the 5-year period before the COVID-19 outbreak and 832 admissions in 2020, of which 689 occurred after the COVID-19 outbreak in Italy. An initial reduction of 28% in admissions during the first wave of the COVID-19 pandemic (RR 0.72, 95% CI 0.62–0.84) was largely addressed by the end of 2020 (RR 0.96, 95% CI 0.89–1.03) when considering the whole population, although there were some heterogeneities. The gap between observed and expected admissions was particularly evident and had not completely recovered by the end of the year in older (≥75 years) patients (RR: 0.88, 0.76–1.01), patients with a Romano-Charlson comorbidity index below 2 (RR 0.91, 95% CI: 0.84–1.00), and primary surgically treated patients (RR 0.88, 95% CI 0.80–0.97). In the subgroup of patients eligible for the ongoing active recruitment, we observed no evidence of a shift toward a more advanced stage at diagnosis in the periods following the first pandemic wave.ConclusionsThe COVID-19 pandemic has affected differentially the management of certain groups of incident HNC patients, with more pronounced impact on older patients, those treated primarily surgically, and those with less comorbidities. The missed and delayed diagnoses may translate into worser oncological outcomes in these patients.
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- 2022
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19. Matrix-bound angiogenic factors enhance the angiogenic response within 3D biopolymers
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Borselli C, Oliviero O., Battista S., Ambrosio L., and Netti P.A.
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collagen ,angiogenesis ,tissue engineering ,hyaluronic acid ,VEGF - Published
- 2005
20. Gradients of ECM control directional sprouting angiogenesis
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Borselli C., Oliviero O., Battista S., Ambrosio L., and Netti P.A
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collagen ,angiogenesis ,tissue engineering ,extracellular matrix ,hyaluronic acid - Published
- 2005
21. Seasonal changes in runoff generation in a small forested mountain catchment
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Penna, D., primary, van Meerveld, H. J., additional, Oliviero, O., additional, Zuecco, G., additional, Assendelft, R. S., additional, Dalla Fontana, G., additional, and Borga, M., additional
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- 2014
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22. CD14+-Monocytes Exposed to Apolipoprotein CIII Express Tissue Factor
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Oliviero Olivieri, Sara Gasperini, Federica Calzetti, Elisa Gardiman, Annalisa Castagna, Nicola Martinelli, Nicola Tamassia, and Marco A. Cassatella
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apolipoprotein CIII ,tissue factor ,monocytes ,thrombosis ,atherosclerosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Apolipoprotein CIII (ApoCIII) represents a key regulator of plasma lipid metabolism and a recognized risk factor for atherosclerosis and cardiovascular diseases. Beyond the regulation of lipoprotein trafficking, ApoCIII is also involved in endothelial dysfunction and monocyte recruitment related to atherothrombosis. With tissue factor (TF) being the primary initiator of the blood coagulation cascade, we hypothesized that ApoCIII-treated monocytes could express it. Hence, human CD14+-monocytes and autologous neutrophils were incubated with ApoCIII and sera from human subjects containing previously measured ApoCIII amounts. By RT-qPCR and ELISA, CD14+-monocytes, but not neutrophils, were found to show increased mRNA expression and production of TNFα, IL-1β and IL-6 as well as TF mRNA once exposed to ultra-purified ApoCIII. By flow cytometry, CD14+-monocytes were found to rapidly express TF on their cell surface membrane when incubated with either ApoCIII or sera with known concentrations of ApoCIII. Finally, preincubation with specific ApoCIII-neutralizing antibodies significantly reduced the ability of most sera with known concentrations of ApoCIII to upregulate TF protein, other than partially inhibiting cytokine release, in CD14+-monocytes. In sum, herein we demonstrate that ApoCIII activates CD14+-monocytes to express TF. The data identify a potential mechanism which links circulating apolipoproteins with inflammation and atherothrombosis-related processes underlying cardiovascular risk.
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- 2023
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23. High Plasma Levels of Activated Factor VII-Antithrombin Complex Point to Increased Tissue Factor Expression in Patients with SARS-CoV-2 Pneumonia: A Potential Link with COVID-19 Prothrombotic Diathesis
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Nicola Martinelli, Anna Maria Rigoni, Sergio De Marchi, Nicola Osti, Martino Donini, Martina Montagnana, Annalisa Castagna, Patrizia Pattini, Silvia Udali, Lucia De Franceschi, Elisa Tinazzi, Filippo Mazzi, Sara Moruzzi, Giuseppe Argentino, Lorenzo Delfino, Giulia Sartori, Anna Maria Azzini, Evelina Tacconelli, Patrick Van Dreden, Giuseppe Lippi, Domenico Girelli, Oliviero Olivieri, Simonetta Friso, and Francesca Pizzolo
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severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,coronavirus disease 2019 (COVID-19) ,coagulation ,tissue factor (TF) ,activated factor VII-antithrombin (FVIIa-AT) ,Medicine (General) ,R5-920 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.
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- 2022
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24. Detection of Urinary Exosomal HSD11B2 mRNA Expression: A Useful Novel Tool for the Diagnostic Approach of Dysfunctional 11β-HSD2-Related Hypertension
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Domenica De Santis, Annalisa Castagna, Elisa Danese, Silvia Udali, Nicola Martinelli, Francesca Morandini, Mariangela Veneri, Lorenzo Bertolone, Oliviero Olivieri, Simonetta Friso, and Francesca Pizzolo
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apparent mineralocorticoid excess ,11β-hydroxysteroid dehydrogenase type 2 ,urinary cortisol metabolites ratio ,urinary exosomal mRNA ,Droplet Digital PCR ,HSD11B2 ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
ObjectiveApparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C>G genotype (corresponding to a 221 A>G substitution) in patients with AME and essential hypertension (EH).Aim of the StudyTo detect and quantify HSD11B2 mRNA from urinary exosomes in samples from family members affected by AME and EH, and to evaluate the relationship between exosomal HSD11B2 mRNA, steroid ratio, 662C>G genotype, and hypertension.MethodsIn this observational case–control study, urinary steroid ratios and biochemical parameters were measured. Urinary exosomes were extracted from urine and exosomal HSD11B2 mRNA was quantified by Droplet Digital PCR (ddPCR). B2M (β-2 microglobulin) gene was selected as the reference housekeeping gene.ResultsAmong family members affected by AME, exosomal urinary HSD11B2 mRNA expression was strictly related to genotypes. The two homozygous mutant probands showed the highest HSD11B2 mRNA levels (median 169, range 118–220 copies/µl) that progressively decreased in 221 AG heterozygous with hypertension (108, range 92–124 copies/µl), 221 AG heterozygous normotensives (23.35, range 8–38.7 copies/µl), and wild-type 221 AA subjects (5.5, range 4.5–14 copies/µl). Heterozygous hypertensive subjects had more HSD11B2 mRNA than heterozygous normotensive subjects. The F/E urinary ratio correlated with HSD11B2 mRNA copy number (p < 0.05); HSD11B2 mRNA strongly decreased while THF+5αTHF/THE increased in the two probands after therapy. In the AME family, HSD11B2 copy number correlated with both F/E and THF+5αTHF/THE ratios, whereas in EH patients, a high F/E ratio reflected a reduced HSD11B2 mRNA expression.ConclusionsHSD11B2 mRNA is detectable and quantifiable in urinary exosomes; its expression varies according to the 662 C>G genotype with the highest levels in homozygous mutant subjects. The HSD11B2 mRNA overexpression in AME could be due to a compensatory mechanism of the enzyme impairment. Exosomal mRNA is a useful tool to investigate HSD11B2 dysregulation in hypertension.
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- 2021
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25. Profibrotic Effects of Endothelin-1 on Fibroblasts Are Mediated by Aldosterone In Vitro: Relevance to the Pathogenesis and Therapy of Systemic Sclerosis and Pulmonary Arterial Hypertension
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Giuseppe Argentino, Alessandro Barbieri, Ruggero Beri, Caterina Bason, Andrea Ruzzenente, Oliviero Olivieri, Elisa Tinazzi, Antonio Puccetti, Claudio Vitali, Nicoletta Del Papa, Simonetta Friso, and Claudio Lunardi
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endothelin-1 ,aldosterone ,reactive oxygen species ,systemic sclerosis ,pulmonary arterial hypertension ,fibroblasts ,Biology (General) ,QH301-705.5 - Abstract
Endothelin-1 (ET-1) is a vasoactive and profibrotic peptide that plays a pivotal role in diseases such as systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH), by inducing fibrosis and vascular remodeling. Such effects may be sustained by the induction of aldosterone production and reactive oxygen species (ROS). We have used fibroblasts obtained from skin of healthy donors and SSc patients and commercial fibroblasts from lung to evaluate whether ET-1 is able to stimulate ROS production directly or indirectly through aldosterone induction. We found that ET-1 receptors are present in all types of fibroblasts analyzed, whereas the expression of mineralocorticoid receptor (MCR) is lower in dermal fibroblasts from healthy donors (HDFs) compared to fibroblasts derived from lung (HPFs) or from skin of SSc patients (SScHDFs). ET-1 induces ROS production in HDFs and SScHDFs after 24 h of incubation involving its receptor B (ETB), whereas aldosterone exerts its effects after 40 min of incubation. Moreover, ROS production was inhibited by the pre-incubation of cells with MCR inhibitor. Our results indicate that ET-1 induces ROS indirectly through aldosterone production suggesting that aldosterone may play a pivotal role in the pathogenesis of SSc and PAH.
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- 2022
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26. M276 TREATMENT IN OUTPATIENT DEPARTMENT BY EXCISION WITH RADIOFREQUENCY IN PATIENTS WITH DYSPLASIA OF HIGH DEGREE (HSIL) OF THE CERVIX, IN THE PERIOD FROM 1/1/2008 TO 31/12/2011: ADVANTAGES AND CRITICAL PROBLEMS
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Oliviero, O., primary, Canino, T., additional, Marino, K., additional, Mantenuto, L., additional, Pontani, G., additional, Cappiello, G., additional, Tedeschi, D., additional, and Giovannini, M., additional
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- 2012
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27. M338 REVIEW OF CASES OF ASCUS, LSIL, HSIL HPV-CORRELATED: EXPERIENCE OF S.PERTINI HOSPITAL'S SERVICE OF COLPOSCOPY FROM 1/1/2008 TO 31/12/2011: TREATMENT AND FOLLOW UP
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Oliviero, O., primary, Canino, T., additional, Marino, K., additional, Mantenuto, L., additional, Pontani, G., additional, Longo, R., additional, Tedeschi, D., additional, and Giovannini, M., additional
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- 2012
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28. Whole-genome sequencing analysis of semi-supercentenarians
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Paolo Garagnani, Julien Marquis, Massimo Delledonne, Chiara Pirazzini, Elena Marasco, Katarzyna Malgorzata Kwiatkowska, Vincenzo Iannuzzi, Maria Giulia Bacalini, Armand Valsesia, Jerome Carayol, Frederic Raymond, Alberto Ferrarini, Luciano Xumerle, Sebastiano Collino, Daniela Mari, Beatrice Arosio, Martina Casati, Evelyn Ferri, Daniela Monti, Benedetta Nacmias, Sandro Sorbi, Donata Luiselli, Davide Pettener, Gastone Castellani, Claudia Sala, Giuseppe Passarino, Francesco De Rango, Patrizia D'Aquila, Luca Bertamini, Nicola Martinelli, Domenico Girelli, Oliviero Olivieri, Cristina Giuliani, Patrick Descombes, and Claudio Franceschi
- Subjects
longevity ,ageing ,clonal hematopoiesis ,sequencing ,geroscience ,semi-supercentenarians ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.
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- 2021
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29. Case Report: Microangiopathic Hemolytic Anemia With Normal ADAMTS13 Activity
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Nicola Osti, Greta Beschin, Marzia Goldin, Lucia Guidolin, Enrico Panero, Alice Sartori, Alice Parisi, Maurizio Cantini, Francesca Pizzolo, Oliviero Olivieri, and Simonetta Friso
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thrombotic microangiopathy ,breast cancer ,ADAMTS13 ,thrombotic thrombocytopenic purpura ,disseminated intravascular coagulation ,hemolytic anemia ,Medicine (General) ,R5-920 - Abstract
Thrombotic microangiopathies (TMAs) include a heterogeneous group of diseases characterized by abnormalities in the vessel walls of arterioles and capillaries resulting in microvascular thrombosis that typically presents with a microangiopathic hemolytic anemia (MAHA) and severe thrombocytopenia. We describe here the case of an 82-year-old woman, who came to our attention for a clinical condition consistent with thrombotic microangiopathy. Even if initially highly suggestive for a thrombotic thrombocytopenic purpura (TTP), the elevated ADAMTS13 activity together with the alteration of the main coagulation parameters (D-dimer elevation, fibrinogen consumption, slightly prolonged prothrombin time), induced us to consider several other diseases in the differential diagnostic process. The case evolved toward a suspected overlapped secondary hemophagocytic syndrome, though the hyperferritinemia was finally interpreted within the frame of a cytokine storm. After a complex diagnostic workup, the clinical and biochemical parameters guided us toward the diagnosis of a cancer-related microangiopathic hemolytic anemia (CR-MAHA) secondary to a relapsing breast cancer with multiple metastatic localizations. Prednisone 1 mg/kg body weight was started, and several units of fresh frozen plasma were infused, obtaining a good control of the hemolysis. No specific oncological therapies were, however, possible, due to the older age and the critically compromised general condition of the patient; therefore, after clinical stabilization, the patient was discharged for treatment in a palliative care Hospital.
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- 2021
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30. Basophil Blood Cell Count Is Associated With Enhanced Factor II Plasma Coagulant Activity and Increased Risk of Mortality in Patients With Stable Coronary Artery Disease: Not Only Neutrophils as Prognostic Marker in Ischemic Heart Disease
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Francesca Pizzolo, Annalisa Castagna, Oliviero Olivieri, Domenico Girelli, Simonetta Friso, Filippo Stefanoni, Silvia Udali, Veronica Munerotto, Marcello Baroni, Vera Cetera, Giovanni Battista Luciani, Giuseppe Faggian, Francesco Bernardi, and Nicola Martinelli
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basophils ,factor II plasma coagulant activity ,neutrophils ,secondary prevention of coronary artery disease ,white blood cell count ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background White blood cell count, which is inexpensive and widely available in clinical practice, has been proposed to provide prognostic information in coronary artery disease (CAD). Elevated levels of white blood cell subtypes may play different roles in atherothrombosis and predict cardiovascular outcomes. Methods and Results The association between white blood cell counts and mortality was evaluated in 823 subjects with angiographically demonstrated and clinically stable CAD in an observational–longitudinal study. The correlation among white blood cell counts and factor II plasma coagulant activity was analyzed in 750 subjects (554 CAD and 196 CAD‐free) not taking anticoagulant drugs. Subjects with overt leukocytosis or leukopenia were excluded. In the longitudinal study after a median follow‐up of 61 months, 160 (19.4%) subjects died, 107 (13.0%) of whom from cardiovascular causes. High levels of neutrophils, monocytes, eosinophils, and basophils were associated with an increased mortality rate. In multiadjusted Cox regression models, only neutrophils and basophils remained predictors of total and cardiovascular mortality. The associations remained significant after adjustment for traditional cardiovascular risk factors and by including D‐dimer and the chemokine CXCL12 in the regression models. Neutrophils and basophils were also significant predictors of factor II plasma coagulant activity variability after adjustment for blood cell counts, age, sex, inflammatory markers, CAD diagnosis, and prothrombin G20210A polymorphism. Factor II plasma coagulant activity was similarly increased in subjects with high neutrophil and basophil counts and in carriers of the prothrombin 20210A allele. Conclusions Both high neutrophil and basophil blood counts may predict mortality in patients with clinically stable CAD and are associated with enhanced factor II plasma coagulant activity, thereby suggesting underlying prothrombotic mechanisms.
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- 2021
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31. Seasonal changes in runoff generation in a small forested mountain catchment.
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Penna, D., Meerveld, H. J., Oliviero, O., Zuecco, G., Assendelft, R. S., Dalla Fontana, G., and Borga, M.
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RUNOFF ,ELECTRIC conductivity research ,WATERSHEDS ,EXPERIMENTAL forests ,PRECIPITATION (Chemistry) - Abstract
This study aimed to investigate the seasonal variability of runoff generation processes, the sources of stream water, and the controls on the contribution of event water to streamflow for a small forested catchment in the Italian pre-Alps. Hydrometric, isotopic, and electrical conductivity data collected between August 2012 and August 2013 revealed a marked seasonal variability in runoff responses. Noticeable differences in runoff coefficients and hydrological dynamics between summer and fall/spring rainfall events were related to antecedent moisture conditions and event size. Two-component and three-component hydrograph separation and end-member mixing analysis showed an increase in event water contributions to streamflow with event size and average rainfall intensity. Event water fractions were larger during dry conditions in the summer, suggesting that stormflow generation in the summer consisted predominantly of direct channel precipitation and some saturated overland flow from the riparian zone. On the contrary, groundwater and hillslope soil water contributions dominated the streamflow response during wet conditions in fall. Seasonal differences were also noted between event water fractions computed based on isotopic and electrical conductivity data, likely because of the dilution effect during the wetter months. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2015
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32. Trace Elements Status and Metallothioneins DNA Methylation Influence Human Hepatocellular Carcinoma Survival Rate
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Silvia Udali, Domenica De Santis, Filippo Mazzi, Sara Moruzzi, Andrea Ruzzenente, Annalisa Castagna, Patrizia Pattini, Greta Beschin, Antonia Franceschi, Alfredo Guglielmi, Nicola Martinelli, Francesca Pizzolo, Francesca Ambrosani, Oliviero Olivieri, Sang-Woon Choi, and Simonetta Friso
- Subjects
copper ,DNA methylation ,epigenetics ,hepatocellular carcinoma ,MT1G ,MT1H ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundMechanisms underlying hepatocellular carcinoma (HCC) development are largely unknown. The role of trace elements and proteins regulating metal ions homeostasis, i.e. metallothioneins (MTs), recently gained an increased interest. Object of the study was to investigate the role of promoter DNA methylation in MTs transcriptional regulation and the possible prognostic significance of serum trace elements in HCC.MethodsForty-nine HCC patients were enrolled and clinically characterized. Cu, Se, and Zn contents were measured by Inductively Coupled Plasma Mass Spectrometry in the serum and, for a subset of 27 patients, in HCC and homologous non-neoplastic liver (N) tissues. MT1G and MT1H gene expression in hepatic tissues was assessed by Real-Time RT-PCR and the specific promoter DNA methylation by Bisulfite-Amplicon Sequencing.ResultsPatients with Cu serum concentration above the 80th percentile had a significantly decreased survival rate (P < 0.001) with a marked increased hazard ratio for mortality (HR 6.88 with 95% CI 2.60–18.23, P < 0.001). Se and Zn levels were significantly lower in HCC as compared to N tissues (P
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- 2021
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33. A Novel ALAS2 Missense Mutation in Two Brothers With Iron Overload and Associated Alterations in Serum Hepcidin/Erythroferrone Levels
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Acaynne Lira Zidanes, Giacomo Marchi, Fabiana Busti, Alessandro Marchetto, Elisa Fermo, Alejandro Giorgetti, Alice Vianello, Annalisa Castagna, Oliviero Olivieri, Paola Bianchi, and Domenico Girelli
- Subjects
XLSA ,ERFE ,hepcidin ,ALAS2 gene ,next-generation sequencing ,in silico modeling ,Physiology ,QP1-981 - Abstract
Iron loading anemias are characterized by ineffective erythropoiesis and iron overload. The prototype is non-transfusion dependent ß-thalassemia (NTDT), with other entities including congenital sideroblastic anemias, congenital dyserythropoietic anemias, some hemolytic anemias, and myelodysplastic syndromes. Differential diagnosis of iron loading anemias may be challenging due to heterogeneous genotype and phenotype. Notwithstanding the recent advances in linking ineffective erythropoiesis to iron overload, many pathophysiologic aspects are still unclear. Moreover, measurement of hepcidin and erythroferrone (ERFE), two key molecules in iron homeostasis and erythropoiesis, is scarcely used in clinical practice and of uncertain utility. Here, we describe a comprehensive diagnostic approach, including next-generation sequencing (NGS), in silico modeling, and measurement of hepcidin and erythroferrone (ERFE), in two brothers eventually diagnosed as X-linked sideroblastic anemia (XLSA). A novel pathogenic ALAS2 missense mutation (c.1382T>A, p.Leu461His) is described. Hyperferritinemia with high hepcidin-25 levels (but decreased hepcidin:ferritin ratio) and mild-to-moderate iron overload were detected in both patients. ERFE levels were markedly elevated in both patients, especially in the proband, who had a more expressed phenotype. Our study illustrates how new technologies, such as NGS, in silico modeling, and measurement of serum hepcidin-25 and ERFE, may help in diagnosing and studying iron loading anemias. Further studies on the hepcidin-25/ERFE axis in additional patients with XLSA and other iron loading anemias may help in establishing its usefulness in differential diagnosis, and it may also aid our understanding of the pathophysiology of these genetically and phenotypically heterogeneous entities.
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- 2020
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34. Rare variants lowering the levels of coagulation factor X are protective against ischemic heart disease
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Elvezia Maria Paraboschi, Amit Vikram Khera, Piera Angelica Merlini, Laura Gigante, Flora Peyvandi, Mark Chaffin, Marzia Menegatti, Fabiana Busti, Domenico Girelli, Nicola Martinelli, Oliviero Olivieri, Sekar Kathiresan, Diego Ardissino, Rosanna Asselta, and Stefano Duga
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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35. NEW THERAPEUTIC OPTIONS FOR THE TREATMENT OF SICKLE CELL DISEASE
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Alessandro Matte, Filippo Mazzi, Enrica Federti, Oliviero Olivieri, and Lucia De Franceschi
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Sickle cell disease ,hemoglobinopathy ,pathological hemoglobin ,vaso-occlusive events ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Sickle cell disease (SCD; ORPHA232; OMIM # 603903) is a chronic and invalidating disorder distributed worldwide, with high morbidity and mortality. Given the disease complexity and the multiplicity of pathophysiological targets, development of new therapeutic options is critical, despite the positive effects of hydroxyurea (HU), for many years the only approved drug for SCD. New therapeutic strategies might be divided into (1) pathophysiology-related novel therapies and (2) innovations in curative therapeutic options such as hematopoietic stem cell transplantation and gene therapy. The pathophysiology related novel therapies are: a) Agents which reduce sickling or prevent sickle red cell dehydration; b) Agents targeting SCD vasculopathy and sickle cell-endothelial adhesive events; c) Anti-oxidant agents. This review highlights new therapeutic strategies in SCD and discusses future developments, research implications, and possible innovative clinical trials.
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- 2019
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36. Not Just Arterial Damage: Increased Incidence of Venous Thromboembolic Events in Cardiovascular Patients With Elevated Plasma Levels of Apolipoprotein CIII
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Oliviero Olivieri, Gianni Turcato, Sara Moruzzi, Annalisa Castagna, Domenico Girelli, Francesca Pizzolo, Simonetta Friso, Marco Sandri, Antonella Bassi, and Nicola Martinelli
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apolipoprotein CIII ,plasma lipids ,triglyceride ,venous thromboembolism ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Apolipoprotein CIII (apo CIII) is a crucial player in triglyceride‐rich lipoprotein metabolism, but may also act pleiotropically, provoking inflammatory responses and stimulating coagulation. Elevated apoCIII plasma levels have been associated with increased activity of coagulation factors. Since these features of prothrombotic diathesis are linked with venous thromboembolism (VTE), we hypothesized that apo CIII plays a role in VTE. Methods and Results We recorded nonfatal VTE events in 1020 patients (age 63.3±11.4 years; 29.1% women) with or without coronary artery disease (79.1% with coronary artery disease and 20.9% without coronary artery disease) during a long follow‐up. Complete plasma lipid and apolipoproteins were available for all patients. Forty‐five patients (4.4%) experienced nonfatal VTE events during a median follow‐up period of 144 months. Apo CIII plasma concentration at enrollment was higher in patients with VTE compared with patients without VTE (12.2 [95% CI, 11.10–13.5] mg/dL vs 10.6 [95% CI, 10.4–10.9] mg/dL, respectively; P=0.011). Patients with apo CIII levels above the median value (10.6 mg/dL) exhibited an increased risk of VTE (incidence rate, 6.0 [95% CI, 4.0–8.0] vs 1.8 [95% CI, 0.7–2.9] VTE events/1000 person‐years; unadjusted hazard ratio [HR], 3.42 [95% CI, 1.73–6.75]; P
- Published
- 2019
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37. DNA Methylation and Hydroxymethylation in Primary Colon Cancer and Synchronous Hepatic Metastasis
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Silvia Udali, Domenica De Santis, Andrea Ruzzenente, Sara Moruzzi, Filippo Mazzi, Greta Beschin, Stephanie A. Tammen, Tommaso Campagnaro, Patrizia Pattini, Oliviero Olivieri, Alfredo Guglielmi, Sang-Woon Choi, and Simonetta Friso
- Subjects
epigenetics ,methylcytosine ,hydroxymethylcytosine ,primary colon cancer ,synchronous hepatic metastasis ,Genetics ,QH426-470 - Abstract
Colon cancer is one of the most frequent solid tumor and simultaneous diagnosis of primary colon cancer and liver metastases occurs in about one fourth of cases. The current knowledge on epigenetic signatures, especially those related to hydroxymethylation in primary cancer tissue, synchronous metastasis, and blood circulating cells is lacking. This study aimed to investigate both methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) status in the DNA of individual patients from colon cancer tissue, synchronous liver metastases, and in cancer-free colon and liver tissues and leukocytes. Patients undergoing curative surgery (n = 16) were enrolled and their laboratory and clinical history data collected. The contents of mCyt and hmCyt were determined by a liquid chromatography/mass spectrometry (LC/MS/MS) method in DNA extracted from primary colon cancer, synchronous hepatic metastatic tissues and homologous cancer-free tissues, i.e., colon and liver tissues as well as leukocytes. The mCyt and hmCyt levels were compared between cancerous and cancer-free tissues, and correlations between leukocytes and colon/liver tissues for both the mCyt and hmCyt levels were evaluated. The mCyt levels were similar in primary colon cancer and liver metastasis tissues (4.69 ± 0.37% vs. 4.77 ± 0.38%, respectively, p = 0.535), and both primary and metastatic tissues were hypomethylated compared to cancer-free colon (4.98 ± 0.26%). The difference in the mCyt content between cancerous and cancer-free colon tissues was significantly lower in primary colon cancer (p = 0.004), but not in liver metastasis (p = 0.148). The hmCyt content was similar in primary colon cancer compared to liver metastasis (0.035%, C.I. 0.024–0.052% versus 0.035%, C.I. 0.021–0.058%, respectively, p = 0.905) and markedly depleted compared to the cancer-free colon (0.081%, C.I. 0.055–0.119%) with a statistically significant difference (p < 0.05) for both comparisons. The mCyt levels showed a borderline correlation between leukocytes and colon cancer tissue (Pearson’s correlation coefficient = 0.51, p = 0.052) while no correlations were detected for the hmCyt levels. In conclusion, primary colon cancer and synchronous liver metastasis tissues showed a similar epigenetic status but were significantly hypomethylated and hypohydroxymethylated as compared to homologous cancer-free colon tissues.
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- 2018
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38. One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation.
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Sara Moruzzi, Patrizia Guarini, Silvia Udali, Andrea Ruzzenente, Alfredo Guglielmi, Simone Conci, Patrizia Pattini, Nicola Martinelli, Oliviero Olivieri, Stephanie A Tammen, Sang-Woon Choi, and Simonetta Friso
- Subjects
Medicine ,Science - Abstract
Several polymorphic gene variants within one-carbon metabolism, an essential pathway for nucleotide synthesis and methylation reactions, are related to cancer risk. An aberrant DNA methylation is a common feature in cancer but whether the link between one-carbon metabolism variants and cancer occurs through an altered DNA methylation is yet unclear. Aims of the study were to evaluate the frequency of one-carbon metabolism gene variants in hepatocellular-carcinoma, cholangiocarcinoma and colon cancer, and their relationship to cancer risk together with global DNA methylation status. Genotyping for BHMT 716A>G, DHFR 19bp ins/del, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, TCII 776C>G and TS 2rpt-3rpt was performed in 102 cancer patients and 363 cancer-free subjects. Methylcytosine (mCyt) content was measured by LC/MS/MS in peripheral blood mononuclear cells (PBMCs) DNA. The MTHFD1 1958AA genotype was significantly less frequent among cancer patients as compared to controls (p = 0.007) and related to 63% reduction of overall cancer risk (p = 0.003) and 75% of colon cancer risk (p = 0.006). When considering PBMCs mCyt content, carriers of the MTHFD1 1958GG genotype showed a lower DNA methylation as compared to carriers of the A allele (p = 0.048). No differences were highlighted by evaluating a possible relationship between the other polymorphisms analyzed with cancer risk and DNA methylation. The MTHFD1 1958AA genotype is linked to a significantly reduced cancer risk. The 1958GG genotype is associated to PBMCs DNA hypomethylation as compared to the A allele carriership that may exert a protective effect for cancer risk by preserving from DNA hypomethylation.
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- 2017
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39. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers.
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Sara Moruzzi, Silvia Udali, Andrea Ruzzenente, Alfredo Guglielmi, Patrizia Guarini, Nicola Martinelli, Simone Conci, Filippo Mazzi, Patrizia Pattini, Stephanie A Tammen, Oliviero Olivieri, Francesca Pizzolo, Sang-Woon Choi, and Simonetta Friso
- Subjects
Medicine ,Science - Abstract
Polymorphisms within one-carbon metabolism genes have been largely studied in relation to cancer risk for the function of this pathway in nucleotide synthesis and DNA methylation. Aims of this study were to explore the possible link among several common functional gene polymorphisms within one-carbon metabolism and survival rate in primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma, and to assess the additional effect of global DNA methylation on survival rate and mortality risk. Forty-seven primary liver cancer patients were genotyped for ten polymorphisms: DHFR 19bp ins/del, TS 2rpt-3rpt, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, BHMT 716 A>G, TC II 776C>G. Methylation was determined in peripheral blood mononuclear cells (PBMCs) DNA as methylcytosine (mCyt) content using LC/MS/MS. Among the polymorphisms analysed, the RFC1 80G>A (rs1051266) influenced the survival rate in primary liver cancers. The RFC1 80AA was associated to a significantly reduced survival rate (22.2%) as compared to both GG and GA genotypes (61.5% and 76% respectively, p = 0.005). When the cancer patients were stratified according to the mCyt median value as high (>5.34%) or low (≤5.34%), the concomitant presence of AA genotype and low mCyt level led to a significantly worse survival rate as compared to the G allele carriership (pA polymorphism influenced the survival rate, and the presence of RFC1 80AA genotype with low global methylation in PBMCs DNA was associated with poorer prognosis and higher mortality risk, therefore highlighting novel molecular signatures potentially helpful to define prognostic markers for primary liver cancers.
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- 2016
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40. Influence of Maternal and Postweaning Linseed Dietary Supplementation on Growth Rate, Lipid Profile, and Meat Quality Traits of Light Sarda Lambs
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Massimo Trabalza-Marinucci, Laura Mughetti, David Ranucci, Gabriele Acuti, Oliviero Olivieri, Dino Miraglia, and Raffaella Branciari
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Technology ,Medicine ,Science - Abstract
The effects of dietary extruded linseed (EL) on growth performance, meat quality, and lipid profile of Semimembranosus and Longissimus lumborum muscles of 81 Sarda lambs were studied in a 3 × 3 design: EL content (0%, 10%, and 20%) of maternal dietary concentrate fed from 20 d to parturition to 60 d of lactation and EL content (0%, 10%, 20%) of lamb concentrate fed after weaning for 30 d. The basal diet was composed of alfalfa and meadow hay during pregnancy and alfalfa hay during lactation. At slaughter, carcass and meat quality were evaluated. Sensory quality of Semimembranosus from 0% and 20% EL lambs was assessed. Both maternal and postweaning diets affected growth performance, with higher body weights recorded with the 10% EL concentrate. Carcass and meat quality were not affected by diet. Saturated and monounsaturated FA decreased and n-3 polyunsaturated FA increased with increasing EL content in lamb diet. An increase in vaccenic and rumenic acid was associated with the EL content of the maternal diet. Both diets increased the n-6/n-3 FA ratio. No differences in acceptability were detected by consumers among groups. It is concluded that EL supplementation and early life nutrition can influence performance and FA metabolism in growing lambs.
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- 2016
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41. Spatio-temporal variability of throughfall and soil moisture at the plot scale in the Italian pre-Alps
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Penna, D., Giulia Zuecco, Oliviero, O., Meerveld, H. J., Hopp, L., Giancarlo Dalla Fontana, and marco borga
42. Material guidance for cell metabolism in 3D in vitro cultures
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Guaccio, A., Borselli, C., Oliviero, O., PAOLO NETTI, Guaccio, Angela, Borselli, Cristina, Oliviero, Olimpia, and Netti, PAOLO ANTONIO
- Subjects
Biomaterials
43. Do trees and streams have the same source of water? Isotopic evidence from a small pre-alpine catchment
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Penna, Daniele, Oliviero, O., Assendelft, R., Giulia Zuecco, Mantese, Nicola, Vinicio Carraro, Tommaso ANFODILLO, Meerveld, H. J., marco borga, and Giancarlo Dalla Fontana
44. Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease
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Oliviero Olivieri, Antonella Bassi, Chiara Stranieri, Elisabetta Trabetti, Nicola Martinelli, Francesca Pizzolo, Domenico Girelli, Simonetta Friso, Pier Franco Pignatti, and Roberto Corrocher
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apolipoproteins ,apoC-III ,coronary disease ,genes ,lipids ,Biochemistry ,QD415-436 - Abstract
Apolipoprotein C-III (apoC-III) is a marker of triglyceride (TG)-rich lipoproteins, which are often increased in metabolic syndrome (MS). The T−455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apoC-III levels. To evaluate the contribution of apoC-III levels and T−455C polymorphisms in the coronary artery disease (CAD) risk of MS patients, we studied 873 patients, 549 with CAD and 251 with normal coronary arteries. Patients were classified also as having or not having MS (MS, n = 270; MS-free, n = 603). Lipids, insulin, apolipoprotein levels, and APOC3 T−455C genotypes were evaluated. ApoC-III levels were significantly increased in MS patients, and the probability of having MS was correlated with increasing quartiles of apoC-III levels. MS patients with CAD had significantly higher apoC-III levels than did CAD-free MS patients. The carriership for the −455C variant multiplied the probability of CAD in MS in an allele-specific way and was associated with increased apoC-III and TG levels. Obesity was less frequent in MS carriers of the −455C allele than in MS noncarriers (21.6% vs. 34.8%, P < 0.05).In conclusion, apoC-III-rich lipoprotein metabolism and the APOC3 polymorphism have relevant impacts on the CAD risk of MS patents.
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- 2003
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45. ApoC-III gene polymorphisms and risk of coronary artery disease
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Oliviero Olivieri, Chiara Stranieri, Antonella Bassi, Barbara Zaia, Domenico Girelli, Francesca Pizzolo, Elisabetta Trabetti, Suzanne Cheng, Michael A. Grow, Pier Franco Pignatti, and Roberto Corrocher
- Subjects
lipids ,risk factors ,insulin ,Biochemistry ,QD415-436 - Abstract
Several polymorphisms in the apolipoprotein C-III (apoC-III) gene have been associated with hypertriglyceridemia, but the link with coronary artery disease risk is still controversial. In particular, apoC-III promoter sequence variants in the insulin responsive element (IRE), constitutively resistant to downregulation by insulin, have never been investigated in this connection. We studied a total of 800 patients, 549 of whom had angiographically documented coronary atherosclerosis, whereas 251 had normal coronary arteriograms. We measured plasma lipids, insulin, apoA-I, apoB, and apoC-III and assessed three polymorphisms in the apoC-III gene, namely, T-455C in the IRE promoter region, C1100T in exon 3, and Sst1 polymorphic site (S1/S2) in the 3′ untranslated region. Each variant influenced triglyceride levels, but only the T-455C (in homozygosity) and S2 alleles influenced apoC-III levels. In coronary artery disease (CAD) patients, 18.6% were homozygous for the −455C variant compared with only 9.2% in CAD-free group (P < 0.001).In logistic regression models, homozygosity for −455C variant was associated with a significantly increased risk of CAD (OR = 2.5 and 2.18 for unadjusted and adjusted models, respectively) suggesting that it represents an independent genetic susceptibility factor for CAD.
- Published
- 2002
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46. Correction: Increased Serum Hepcidin Levels in Subjects with the Metabolic Syndrome: A Population Study.
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Nicola Martinelli, Michela Traglia, Natascia Campostrini, Ginevra Biino, Michela Corbella, Cinzia Sala, Fabiana Busti, Corrado Masciullo, Daniele Manna, Sara Previtali, Annalisa Castagna, Giorgio Pistis, Oliviero Olivieri, Daniela Toniolo, Clara Camaschella, and Domenico Girelli
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Medicine ,Science - Abstract
[This corrects the article on p. e48250 in vol. 7.].
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- 2013
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47. Access rate to the emergency department for venous thromboembolism in relationship with coarse and fine particulate matter air pollution.
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Nicola Martinelli, Domenico Girelli, Davide Cigolini, Marco Sandri, Giorgio Ricci, Giampaolo Rocca, and Oliviero Olivieri
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Medicine ,Science - Abstract
Particulate matter (PM) air pollution has been associated with cardiovascular and respiratory disease. Recent studies have proposed also a link with venous thromboembolism (VTE) risk. This study was aimed to evaluate the possible influence of air pollution-related changes on the daily flux of patients referring to the Emergency Department (ED) for VTE, dissecting the different effects of coarse and fine PM. From July 1(st), 2007, to June 30(th), 2009, data about ED accesses for VTE and about daily concentrations of PM air pollution in Verona district (Italy) were collected. Coarse PM (PM(10-2.5)) was calculated by subtracting the finest PM(2.5) from the whole PM(10). During the index period a total of 302 accesses for VTE were observed (135 males and 167 females; mean age 68.3 ± 16.7 years). In multiple regression models adjusted for other atmospheric parameters PM(10-2.5), but not PM(2.5), concentrations were positively correlated with VTE (beta-coefficient = 0.237; P = 0.020). During the days with high levels of PM(10-2.5) (≥ 75(th) percentile) there was an increased risk of ED accesses for VTE (OR 1.69 with 95%CI 1.13-2.53). By analysing days of exposure using distributed lag non-linear models, the increase of VTE risk was limited to PM(10-2.5) peaks in the short-term period. Consistently with these results, in another cohort of subjects without active thrombosis (n = 102) an inverse correlation between PM(10-2.5) and prothrombin time was found (R = -0.247; P = 0.012). Our results suggest that short-time exposure to high concentrations of PM(10-2.5) may favour an increased rate of ED accesses for VTE through the induction of a prothrombotic state.
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- 2012
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48. Increased serum hepcidin levels in subjects with the metabolic syndrome: a population study.
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Nicola Martinelli, Michela Traglia, Natascia Campostrini, Ginevra Biino, Michela Corbella, Cinzia Sala, Fabiana Busti, Corrado Masciullo, Daniele Manna, Sara Previtali, Annalisa Castagna, Giorgio Pistis, Oliviero Olivieri, Daniela Toniolo, Clara Camaschella, and Domenico Girelli
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Medicine ,Science - Abstract
The recent discovery of hepcidin, the key iron regulatory hormone, has changed our view of iron metabolism, which in turn is long known to be linked with insulin resistant states, including type 2 diabetes mellitus and the Metabolic Syndrome (MetS). Serum ferritin levels are often elevated in MetS (Dysmetabolic hyperferritinemia--DHF), and are sometimes associated with a true mild-to-moderate hepatic iron overload (dysmetabolic iron overload syndrome--DIOS). However, the pathophysiological link between iron and MetS remains unclear. This study was aimed to investigate, for the first time, the relationship between MetS and hepcidin at population level. We measured serum hepcidin levels by Mass Spectrometry in 1,391 subjects from the Val Borbera population, and evaluated their relationship with classical MetS features. Hepcidin levels increased significantly and linearly with increasing number of MetS features, paralleling the trend of serum ferritin. In multivariate models adjusted for relevant variables including age, C-Reactive Protein, and the HFE C282Y mutation, ferritin was the only significant independent predictor of hepcidin in males, while in females MetS was also independently associated with hepcidin. Overall, these data indicate that the fundamental iron regulatory feedback is preserved in MetS, i.e. that hepcidin tends to progressively increase in response to the increase of iron stores. Due to recently discovered pleiotropic effects of hepcidin, this may worsen insulin resistance and contribute to the cardiovascular complications of MetS.
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- 2012
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49. Abnormal modulation of cell protective systems in response to ischemic/reperfusion injury is important in the development of mouse sickle cell hepatopathy
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Angela Siciliano, Giorgio Malpeli, Orah S. Platt, Christophe Lebouef, Anne Janin, Aldo Scarpa, Oliviero Olivieri, Eliana Amato, Roberto Corrocher, Yves Beuzard, and Lucia De Franceschi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Sickle cell disease, a genetic red cell disorder inherited in an autosomal recessive manner, occurs throughout the world. Hepatic dysfunction and liver damage may be present in sickle cell disease, but the pathogenesis of these conditions is only partially understood.Design and Methods Transgenic mice with sickle cell disease (SAD mice) and wild-type mice were exposed to an ischemic/reperfusion stress. The following parameters were evaluated: hematologic profile, transaminase and bilirubin levels, liver histopathology, and mRNA levels of nuclear factor-κB p65, endothelial nitric oxide synthase, inducible nitric oxide synthase, heme oxygenase-1 and phosphodiesterase-1, -2, -3, and -4 genes in hepatocytes obtained by laser-capture microdissection. Immunoblotting was used to analyze the expression of the following proteins: nuclear factor-κB p65 and phospho-nuclear factor-κB p65, heme oxygenase-1, biliverdin reductase, heat shock protein-70, heat shock protein-27 and peroxiredoxin-6. A subgroup of SAD mice was treated with the phosphodiesterase-4 inhibitor rolipram (30 mg/Kg/day by gavage) during the ischemic/reperfusion protocol.Results In SAD mice the ischemic/reperfusion stress induced liver damage compatible with sickle cell disease hepatopathy, which was associated with: (i) lack of hypoxia-induced nuclear factor-κB p65 activation; (ii) imbalance in the endothelial/inducible nitric oxide synthase response to ischemic/reperfusion stress; (iii) lack of hypoxia-induced increased expression of heme oxygenase-1/biliverdin reductase paralleled by a compensatory increased expression of heat shock proteins 70 and 27 and peroxiredoxin-6; and (iv) up-regulation of the phosphodiesterase-1, -2, -3, and -4 genes. In SAD mice the phosphodiesterase-4 inhibitor rolipram attenuated the ischemic/reperfusion-related microcirculatory dysfunction, reduced the inflammatory cell infiltration and induced the heme oxygenase-1/biliverdin reductase cytoprotective systems.Conclusions In SAD mice, sickle cell hepatopathy is associated with perturbed nuclear factor-κB p65 signaling with an imbalance of endothelial/inducible nitric oxide synthase levels, lack of heme oxygenase-1/biliverdin reductase expression and up-regulation of two novel cytoprotective systems: heat shock protein-27 and peroxiredoxin-6.
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- 2011
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50. Hepcidin levels and their determinants in different types of myelodysplastic syndromes.
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Valeria Santini, Domenico Girelli, Alessandro Sanna, Nicola Martinelli, Lorena Duca, Natascia Campostrini, Agostino Cortelezzi, Michela Corbella, Alberto Bosi, Gianluigi Reda, Oliviero Olivieri, and Maria Domenica Cappellini
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Medicine ,Science - Abstract
Iron overload may represent an additional clinical problem in patients with Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the key iron hormone, may play a role, but studies until now have been hampered by technical problems. Using a recently validated assay, we measured serum hepcidin in 113 patients with different MDS subtypes. Mean hepcidin levels were consistently heterogeneous across different MDS subtypes, with the lowest levels in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant predictors of hepcidin in multivariate analyses adjusted for ferritin and transfusion history. Consistently with current knowledge on hepcidin action/regulation, RARS patients had the highest levels of toxic non-transferrin-bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive Protein as compared to other MDS subtypes, and showed lost of homeostatic regulation by iron. Growth differentiation factor 15 did not appear as a primary hepcidin regulator in this series. If confirmed, these results may help to calibrate future treatments with chelating agents and/or hepcidin modulators in MDS patients.
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- 2011
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