Papers by Federica Boraldi
The aim of this study was to assess the cytotoxicity of tow types of impression dental materials:... more The aim of this study was to assess the cytotoxicity of tow types of impression dental materials: polyethers (Impregum Penta, Permadyne Penta Heavy and Light) and vinyl polysiloxanes (Elite Mono Tray, Medium, Low viscosity and Elite H-D Putty). Their cytotoxic effects were studied by indirect and direct tests. The indirect tests were performed by incubating impression materials in serum free cell culture medium to prepare the soluble extracts. Balb/c 3T3 cells were incubated with extract dilutions (25, 50, 75 and 100%) for 24 h. The extracts of polyether materials caused a decrease of cellular viability, evaluated by light microscopy, by cell counting and by MTT test. The extracts of vinyl polysiloxanes materials induced a slight effect on cellular number and viability. The direct tests were performed by placing the impression materials in the centre of Petri dishes while Balb/c 3T3 were settling. The cellular proliferation was drastically reduced by polyethers and it was unaffected...
Journal of Investigative Dermatology, 2022
Pseudoxanthoma elasticum (PXE) is a heritable ectopic calcification disorder with multi-organ cli... more Pseudoxanthoma elasticum (PXE) is a heritable ectopic calcification disorder with multi-organ clinical manifestations. The gene at default, ABCC6, encodes an efflux transporter, ABCC6, which is a new player regulating the homeostasis of inorganic pyrophosphate (PPi), a potent endogenous anti-calcification factor. Previous studies suggested that systemic PPi deficiency is the major, but not the exclusive, cause of ectopic calcification in PXE. In this study, we demonstrate that the DNA damage response (DDR) and poly(ADP-ribose) (PAR) pathways are involved locally in PXE at sites of ectopic calcification. Genetic inhibition of PARP1, the predominant PAR-producing enzyme, showed a 54% reduction of calcification in the muzzle skin in Abcc6-/-Parp1-/- mice, as compared to age-matched Abcc6-/-Parp1+/+ littermates. Subsequently, oral administration of minocycline, an inhibitor of DDR/PAR signaling, resulted in an 86% reduction of calcification in the muzzle skin of Abcc6-/- mice. Minocycline treatment also attenuated the DDR/PAR signaling and reduced calcification of dermal fibroblasts derived from PXE patients. The anti-calcification effect of DDR/PAR inhibition was not accompanied by alterations in plasma PPi concentrations. These results suggest that local DDR/PAR signaling in calcification-prone tissues contributes to PXE pathogenesis, and its inhibition might provide a promising treatment strategy for ectopic calcification in PXE, a currently intractable disease.
International Journal of Molecular Sciences, 2022
Elastin represents the structural component of the extracellular matrix providing elastic recoil ... more Elastin represents the structural component of the extracellular matrix providing elastic recoil to tissues such as skin, blood vessels and lungs. Elastogenic cells secrete soluble tropoelastin monomers into the extracellular space where these monomers associate with other matrix proteins (e.g., microfibrils and glycoproteins) and are crosslinked by lysyl oxidase to form insoluble fibres. Once elastic fibres are formed, they are very stable, highly resistant to degradation and have an almost negligible turnover. However, there are circumstances, mainly related to inflammatory conditions, where increased proteolytic degradation of elastic fibres may lead to consequences of major clinical relevance. In severely affected COVID-19 patients, for instance, the massive recruitment and activation of neutrophils is responsible for the profuse release of elastases and other proteolytic enzymes which cause the irreversible degradation of elastic fibres. Within the lungs, destruction of the ela...
Fibroblast involvement in soft connective tissue calcification
Brain Sciences, 2021
Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregu... more Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption...
Cells, 2021
Extraosseous calcification is a pathologic mineralization process occurring in soft connective ti... more Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.
The FASEB Journal, 2013
A surprisingly high percentage of clinical complications affecting beta-thalassemia (beta-thal) p... more A surprisingly high percentage of clinical complications affecting beta-thalassemia (beta-thal) patients is due to ectopic calcification. In these patients, elastic fiber calcification is associated with accumulation of anion superoxide and to increased levels of oxidized proteins and lipids. As a consequence, carboxylation of the calcification inhibitor Matrix Gla Protein (MGP) might be impaired. Independently from the gene defect, common pathogenic pathways are associated with ectopic calcification in PXE and in a number of beta-thal patients
Pseudoxanthoma elasticum (PXE) is a rare inherited multisystem disorder that mainly affects skin,... more Pseudoxanthoma elasticum (PXE) is a rare inherited multisystem disorder that mainly affects skin, eyes and cardiovascular system. The associated clinical signs are due to progressive calcification of elastic fibres and blood vessels, despite normal levels of calcium and phosphorus in blood and urine. The first clinical description of the disease was done in 1881 by Rigal, and in 1896 it was named PXE by Darier. Transmission of the disease is autosomal recessive. PXE is caused by homozygous or compound heterozygous mutations in the ATP-binding cassette subfamily C member 6 ( ABCC6 ) gene, which encodes a transmembrane transport ADP-dependent protein (MRP6). The gene is expressed predominantly in the liver and kidney, and found in low level in the tissue involved by PXE. The clinical expression of PXE is heterogeneous with considerable variation in age of onset, progression and severity of the disease, even in individuals of the same family with identical mutations. We present the cas...
Universidad de Malaga. Campus de Excelencia Internacional Andalucia Tech. PS13/14: Study of the n... more Universidad de Malaga. Campus de Excelencia Internacional Andalucia Tech. PS13/14: Study of the non-immunological mechanisms of action of Gilenya (Fingolimod) as therapeutic tool in Multiple Sclerosis and/or other neurodegenerative diseases. Novartis Farmaceutica S.A.
Journal of Clinical Medicine, 2020
LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations of... more LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations of LONP1 have been associated with Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome. To clarify the role of LONP1 in vivo, we generated a mouse model in which Lonp1 was ablated. The homozygous Lonp−/− mouse was not vital, while the heterozygous Lonp1wt/− showed similar growth rate, weight, length, life-span and histologic features as wild type. Conversely, ultrastructural analysis of heterozygous enterocytes evidenced profound morphological alterations of mitochondria, which appeared increased in number, swollen and larger, with a lower complexity. Embryonic fibroblasts (MEFs) from Lonp1wt/− mice showed a reduced expression of Lonp1 and Tfam, whose expression is regulated by LONP1. Mitochondrial DNA was also reduced, and mitochondria were swollen and larger, albeit at a lesser extent than enterocytes, with a perinuclear distribution. From the functional point of...
Redox Biology, 2021
Oxidative distress and mitochondrial dysfunction, are key factors involved in the pathophysiology... more Oxidative distress and mitochondrial dysfunction, are key factors involved in the pathophysiology of Parkinson's disease (PD). The pleiotropic hormone insulin-like growth factor II (IGF-II) has shown neuroprotective and antioxidant effects in some neurodegenerative diseases. In this work, we demonstrate the protective effect of IGF-II against the damage induced by 1-methyl-4-phenylpyridinium (MPP+) in neuronal dopaminergic cell cultures and a mouse model of progressive PD. In the neuronal model, IGF-II counteracts the oxidative distress produced by MPP + protecting dopaminergic neurons. Improved mitochondrial function, increased nuclear factor (erythroid-derived 2)-like2 (NRF2) nuclear translocation along with NRF2-dependent upregulation of antioxidative enzymes, and modulation of mammalian target of rapamycin (mTOR) signalling pathway were identified as mechanisms leading to neuroprotection and the survival of dopaminergic cells. The neuroprotective effect of IGF-II against MPP + -neurotoxicity on dopaminergic neurons depends on the specific IGF-II receptor (IGF-IIr). In the mouse model, IGF-II prevents behavioural dysfunction and dopaminergic nigrostriatal pathway degeneration and mitigates neuroinflammation induced by MPP+. Our work demonstrates that hampering oxidative stress and normalising mitochondrial function through the interaction of IGF-II with its specific IGF-IIr are neuroprotective in both neuronal and mouse models. Thus, the modulation of the IGF-II/IGF-IIr signalling pathway may be a useful therapeutic approach for the prevention and treatment of PD.
American Journal of Ophthalmology, 2021
PURPOSE To describe the retinal findings of patients affected by Pseudoxanthoma Elasticum (PXE) u... more PURPOSE To describe the retinal findings of patients affected by Pseudoxanthoma Elasticum (PXE) using a multimodal imaging approach including flood-illumination adaptive optics ophthalmoscopy (AO). DESIGN Retrospective case series MATERIALS AND METHODS: Patients affected by PXE were retrospectively studied. Clinical data, color, infrared and autofluorescence fundus imaging, OCT scans and AO examinations were collected. Furthermore, the photoreceptor count was assessed. PXE diagnosis was confirmed by a positive skin biopsy and/or genetic testing. RESULTS Twenty-one eyes of 18 patients (11 females and 7 males) were included in the study. In 3 patients, both eyes were studied. The mean age at examination was 37 ± 16.4 years (range 11-66) and the mean best-corrected visual acuity (BCVA) was 0.1 ± 0.2 LogMAR (range 0-1). We identified 3 types of angioid streaks (AS) using AO: "crack", "band" and "hypopigmented". The first 2 were very similar and they differed in size; the third type showed specific clinical features. Comet lesions appeared as hyper-reflective round lesions on AO imaging. In all eyes the cone mosaic appeared reduced inside the streaks compared to the neighboring areas (13532.8 ± 1366.5 cones/mm2 vs 16817.1 ± 1263.0 cones/mm2 respectively). CONCLUSION Using AO imaging in PXE-related retinopathy we were able to observe the presence of the photoreceptors within the angioid streaks, differentiate 3 types of angioid streaks, based on size and reflective features, and identify the very small crystalline bodies not identifiable using other retinal imaging techniques.
Ophthalmic Genetics, 2019
Purposes: To describe the long-term follow-up of a patient affected by Pseudoxanthoma Elasticum (... more Purposes: To describe the long-term follow-up of a patient affected by Pseudoxanthoma Elasticum (PXE) and acquired macular vitelliform lesions in both eyes. Material and methods: Case report Results: We reported the 9-year follow-up of a patient affected by PXE. We described the onset and the resolution of the vitelliform macular lesions which lasted 5 years. The vitelliform lesion appeared almost simultaneously in both eyes with an initial increase in size, even though asymmetrical. We detected the intraretinal migration of hyper-reflective foci in both eyes during the follow-up. Choroidal neovascularization (CNV) occurred in her right eye during the follow-up. Visual acuity decreased from 20/20 to 20/32 in left eye; from 20/20 to 20/100 in her right eye. Conclusions: we reported the natural history of acquired vitelliform lesion in PXE-related retinopathy describing the Intraretinal hyperreflective foci migration.
Analytical and Bioanalytical Chemistry, 2018
This investigation was undertaken to explore the mutual recognition of the pentapeptide (ValGlyGl... more This investigation was undertaken to explore the mutual recognition of the pentapeptide (ValGlyGlyValGly) n , a hydrophobic elastin-like peptide (ELP), suspended in deionized water in monomer (n = 1) and trimer (n = 3) forms and the outer surface of a very thin, insulating polymer, poly(ortho-aminophenol) (PoAP), electrochemically grown on a platinum foil by cyclic voltammetry in a neutral medium (phosphate-buffered saline, I = 0.1M) immersed in the suspension. As a prior task, the proved propensity of the ValGlyGlyValGly sequence, at the given minimal length (three or more repeats), to self-assemble into amyloid-like fibrils when solubilized in an aqueous environment was considered within the framework of testing PoAP surfaces for the specific detection of amyloid precursors. From our knowledge of the chemical structure and physical properties of both biomacromolecule families obtained in previous studies, we focused on the efficacy of the binding sites offered to ELP fibrils by PoAP in its as-prepared form or properly modified either by postsynthesis oxidation or by adsorption/entrapping of ELP monomer(s) with or without protecting terminal groups. Consistent with all methods of preparation, the best surfaces, recognizable by the trimer fibrils, are those modified to carry a larger number of carbonyls, particularly by entrapment of ELP monomer(s) during PoAP electrosynthesis using an imprinting-inspired method. The degree of attachment of fibrillar aggregates, detected by atomic force microscopy and X-ray photoelectron spectroscopy, provides unequivocal evidence of the cooperative forces involving PoAP-ELP interactions. The results obtained suggest the prospect of using the proposed Pt/PoAP/ELP systems as biodetectors in Alzheimer disease.
The Faseb Journal, Apr 1, 2011
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 1999
Skin biopsies of 18 healthy relatives of patients with pseudoxanthoma elasticum (PXE), belonging ... more Skin biopsies of 18 healthy relatives of patients with pseudoxanthoma elasticum (PXE), belonging to six different recessive families, have been examined by optical and electron microscopy in order to determine morphologic alterations potentially useful for the identification of carriers of this genetic disorder. These morphologic features have been compared with those observed in the same tissue areas of eight PXE patients belonging to the same families, with six normal subjects, and to the carrier status of these apparently unaffected relatives as determined by haplotype analysis using informative markers surrounding the locus of the PXE gene on chromosome 16p. The dermis of all the relatives of PXE patients, established by haplotype analysis to be heterozygote carriers of a mutation in the PXE gene, exhibited several alterations very similar, although less severe, to those typical in PXE patients. Alterations were present in the reticular dermis and consisted of irregular-sized co...
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Papers by Federica Boraldi