Magda Gioia - Academia.edu (original) (raw)

Papers by Magda Gioia

International Journal of Environmental Research and Public Health

Background: Obstructive sleep apnea syndrome (OSAS) may be associated with and activates the stre... more Background: Obstructive sleep apnea syndrome (OSAS) may be associated with and activates the stress response system, and variation in the physiological antioxidant capacity of body fluids. Our aim was to evaluate the variation of pH and antioxidant capacity on the saliva of obstructive sleep apnea subjects (OG) compared to a control group (CG). Method: Fifty subjects with moderate/severe OSAS were recruited in Tor Vergata Hospital and compared with 20 healthy subjects CG. The buffer and the antioxidant capacity of the samples were quantified measuring the pH and the percentage of total salivary antioxidant capacity (%TAC), which refers to the reduced glutathione salivary concentration (GSH). Moreover, the protein concentration and the gelatinolytic activity of metalloproteinases were quantified. Results: The data showed that the pH value is slightly more alkaline in OSAS subjects; however, it is not directly related to the severity of OSAS. The %TAC was found to be significantly red...

Biochemical Pharmacology, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space f... more Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry "-omics" and histochemical and ultrastructural approaches have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Sμg) on human primary osteoblasts (hpOB) induces an alteration of proosteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYα-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Sμg can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., preosteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Sμg environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Sμg can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.

The response of human primary osteoblasts exposed to simulated microgravity has been investigated... more The response of human primary osteoblasts exposed to simulated microgravity has been investigated and analysis of metabolomic and proteomic profiles demonstrated a prominent dysregulation of mitochondrion homeostasis. Gravitational unloading treatment induced a decrease in mitochondrial proteins, mainly affecting efficiency of the respiratory chain. Metabolomic analysis revealed that microgravity influenced several metabolic pathways; stimulating glycolysis and the pentose phosphate pathways, while the Krebs cycle was interrupted at succinate-fumarate transformation. Interestingly, proteomic analysis revealed that Complex II of the mitochondrial respiratory chain, which catalyses the biotransformation of this step, was under-represented by 50%. Accordingly, down-regulation of quinones 9 and 10 was measured. Complex III resulted in up-regulation by 60%, while Complex IV was down-regulated by 14%, accompanied by a reduction in proton transport synthesis of ATP. Finally, microgravity treatment induced an oxidative stress response, indicated by significant decreases in oxidised glutathione and antioxidant enzymes. Decrease in malate dehydrogenase induced a reverse in the malate-aspartate shuttle, contributing to dysregulation of ATP synthesis. Beta-oxidation of fatty acids was inhibited, promoting triglyceride production along with a reduction in the glycerol shuttle. Taken together, our findings suggest that microgravity may suppress bone cell functions, impairing mitochondrial energy potential and the energy state of the cell.

Nephrology Dialysis Transplantation, 2005

Objective: Doppler sonographic evaluation of hemodynamic changes in the course of time in radioce... more Objective: Doppler sonographic evaluation of hemodynamic changes in the course of time in radiocephalic and brachiocephalic arteriovenous fistula (AVF). Material and Methods: 20-72 years aged (mean 42,6) thirty-one (14 male, 17 female) chronic dialysis patients were enrolled into the study. Patients were grouped into two according type of fistula; 21 patients had brachiocephalic and 10 had radiocephalic fistulas. In both groups cephalic vein color Doppler sonographic examinations were done. Cephalic vein flow volume, peak systolic velocity (PSV) end diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) were measured. Results: In chronic hemodialysis patients with radiocephalic fistula, cephalic vein volume was 871±322mL/min, PSV:96.8±62cm/s, EDV:59.8±35.5cm/s, RI:0.38±07, PI:0.48±13 and cephalic vein cross sectional area was 21±7.8mm 2. In brachiocephalic fistula cephalic vein flow volume was 1789±1228mL/min, PSV:93.7±53cm/s, EDV:54.2±23cm/s, RI:0.39±12, PI:0.49±21and cephalic vein cross sectional area was 51.9±43mm 2. In brachiocephalic fistulas both cephalic vein flow volume and cross sectional area measurements were higher than in radiocephalic fistula (P= 0.042 and P=0.048, respectively). There was no statistically significant difference in PSV, EDV, RI and PI values between two fistula types (P>0.005). Conclusion: Color Doppler sonographic examination of fistula in hemodialysis patient is done to evaluate the sufficiency of fistula and determination of fistula complications. In this study, the hemodynamic changes in cephalic vein after opening the AVF have been investigated. The Doppler sonographic findings of hemodynamic changes in cephalic vein in radiocephalic and brachiocephalic AVF have been discussed. It is known that increased venous volume in patients with fistula increases cardiac output especially it is more significant in brachiocephalic fistulas. Despite this, longer duration of patency than radiocephalic fistulas may be due to larger cross sectional area of vein and increased venous volume.

International Journal of Molecular Sciences

Recently, there has been an increasing focus on cellular morphology and mechanical behavior in or... more Recently, there has been an increasing focus on cellular morphology and mechanical behavior in order to gain a better understanding of the modulation of cell malignancy. This study used uniaxial-stretching technology to select a mechanical regimen able to elevate SAOS-2 cell migration, which is crucial in osteosarcoma cell pathology. Using confocal and atomic force microscopy, we demonstrated that a 24 h 0.5% cyclic elongation applied at 1 Hz induces morphological changes in cells. Following mechanical stimulation, the cell area enlarged, developing a more elongated shape, which disrupted the initial nuclear-to-cytoplasm ratio. The peripheral cell surface also increased its roughness. Cell-based biochemical assays and real-time PCR quantification showed that these morphologically induced changes are unrelated to the osteoblastic differentiative grade. Interestingly, two essential cell-motility properties in the modulation of the metastatic process changed following the 24 h 1 Hz mec...

Mini-Reviews in Medicinal Chemistry, 2014

Tendons play a crucial role in musculoskeletal functioning because they physically connect bones ... more Tendons play a crucial role in musculoskeletal functioning because they physically connect bones and muscles making the movement of articular joints possible. The molecular composition of tendons mostly include collagen I fibrils, which aggregate together to form fibers to form a fascicle. A complex network composed of resident cells (i.e., tenocytes) and extracellular matrix macromolecules (glycosaminoglycans, proteoglycans, glycoproteins and other non collagenous proteins) interact and define the structure of tendons and their properties. Development, renewal and remodeling of tendons composition occur at all ages of living organisms so the homeostasis of proteolytic systems is a critical issue. A major role is played by Metalloproteinases, a family of Zn 2+-dependent endopeptidases involved in the catabolism of several components of the extracellular matrix, such as collagens, proteoglycans, fibronectin and many others. Among these, two main classes are mostly involved in tendon pathophysiology, namely the Matrix Metalloproteinases (MMPs) and a Disintegrin-like and Metalloproteinase domain with Thrombospondin motifs (ADAMTSs). This study analyses the various aspects of the roles played by Metalloproteinases in the physiological and pathological processes of tendons.

Molecular Aspects of Medicine, 2012

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases.... more Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

Biochemical Journal, 2007

The proteolytic processing of bovine fibrinogen by MMP-2 (gelatinase A), which brings about the f... more The proteolytic processing of bovine fibrinogen by MMP-2 (gelatinase A), which brings about the formation of a product unable to form fibrin clots, has been studied at 37 °C. Catalytic parameters, although showing a somewhat lower catalytic efficiency with respect to thrombin and plasmin, indeed display values indicating a pathophysiological significance of this process. A parallel molecular modelling study predicts preferential binding of MMP-2 to the β-chain of fibrinogen through its haemopexin-like domain, which has been directly demonstrated by the inhibitory effect in the presence of the exogenous haemopexin-like domain. However, the removal of this domain does not impair the interaction between MMP-2 and fibrinogen, but it dramatically alters the proteolytic mechanism, producing different fragmentation intermediates. The investigation at various pH values between 6.0 and 9.3 indicates a proton-linked behaviour, which is relevant for interpreting the influence on the process by...

MS/MS spectra of the (608–621) peptide (A) and (608–627) peptide (B) deriving from LysC ... more MS/MS spectra of the (608–621) peptide (A) and (608–627) peptide (B) deriving from LysC digestion of lower and upper band of the gel shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.g002" target="_blank">Fig 2</a>, respectively. Matched b and y ions are colored in red and blue, respectively.</p

Anti-Cancer Drugs, 2011

We investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcino... more We investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four doses (5, 10, 20, and 40 lmol/l) for 24 and 48 h. The epithelial-tomesenchymal transition markers E-cadherin, b-catenin, and vimentin were analyzed by immunofluorescence as well as actin and tubulin; matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was analyzed by SDS-zymography, intracellular and secreted SPARC levels by western blot, and cell cycle by flow cytometry. Ukrain did not induce E-cadherin/b-catenin immunoreactivity at the cell-cell boundary, although it determined the actin cortical expression in Caki-2 and ACHN, and did not affect vimentin organization; however, in some Caki-1 and ACHN cells the perinuclear concentration of vimentin was consistent with its downregulation. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was significantly downregulated 48 h after 20 lmol/l Ukrain administration. At this time point, Ukrain significantly decreased migration and invasion, and downregulated SPARC levels in cell supernatants at all doses in Caki-2, and at 20 lmol/l in Caki-1 and ACHN cells. Concomitantly, SPARC was upregulated in all ccRCC cells, suggesting that Ukrain could also affect cell proliferation by cell cycle inhibition, as supported by the cell cycle analysis, as SPARC also acts as a cell cycle inhibitor. Our results suggest that Ukrain may switch the epithelial-to-mesenchymal transition-related phenotype of ccRCC cells, and targets the two major aspects involved in RCC progression, such as tumor invasion/microenvironment remodeling and cell proliferation. Anti-Cancer Drugs 22:749-762 c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Lineweaver-Burk plot of the enzymatic activity of 60 nM MMP-2 at 37°C at pH 7.3 as a fun... more Lineweaver-Burk plot of the enzymatic activity of 60 nM MMP-2 at 37°C at pH 7.3 as a function of the fluorogenic substrate concentration at different concentrations of α-DG(613–651) peptide, namely (panel A) 0 (o), 23 nM (x), 125 nM (*), 200 nM (Δ) and 0.4,μM (25CA), and (panel B) 0.4 μM (o), 1 μM (x), 2 μM (*) and 4 μM (◊). Continuous lines have been obtained by applying Eqs. (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.e001" target="_blank">1</a>)–(<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.e003" target="_blank">3</a>), employing parameters reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.t002" target="_blank">Table 2</a>. (Panel C): namely 0 (o), 23 nM (x), 60 nM (*) and 0.2 μM (◊), and, (panel D) 0.2 μM (o), 0.6 μM (x) and 2 μM (*) and, (panel D) 0.2 μM (o), 0.6 μM (x) and 2 μM (*). Continuous lines have been obtained by applying Eqs. (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.e001" target="_blank">1</a>)–(<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.e003" target="_blank">3</a>), employing parameters reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0192651#pone.0192651.t002" target="_blank">Table 2</a>. Dashed line corresponds to the Lineweaver-Burk plot of the enzymatic activity of whole MMP-2 in the absence. Dashed-dotted lines corresponds to the Lineweaver-Burk plot in the presence of the α-DG(613–651) peptide 0.2 μM and 2 μM α-DG(613–651) peptide in panel C and panel D, respectively. Where not shown, standard deviation is smaller than symbol.</p

Cells, 2021

The complex multidimensional skeletal organization can adapt its structure in accordance with ext... more The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note that the microstructure of bone depends not only on genetic determinants (which control the bone remodeling loop through autocrine and paracrine signals) but also, more importantly, on the continuous response of cells to external mechanical cues. In particular, bone cells sense mechanical signals such as shear, tensile, loading and vibration, and once activated, they react by regulating bone anabolism. Although several specific surrounding conditions needed for osteoblast cells to specifically augment bone formation have been empirically discovered, most of the underlying biomechanical cellular processes underneath remain largely unknown. Nev...

Journal of Inorganic Biochemistry

PloS one, 2018

Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin-glycoprotein complex (DGC) ... more Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin-glycoprotein complex (DGC) and formed by two subunits, α-dystroglycan (α-DG) and β-dystroglycan (β -DG). The C-terminal domain of α-DG and the N-terminal extracellular domain of β -DG are connected, providing a link between the extracellular matrix and the cytosol. Under pathological conditions, such as cancer and muscular dystrophies, DG may be the target of metalloproteinases MMP-2 and MMP-9, contributing to disease progression. Previously, we reported that the C-terminal domain α-DG (483-628) domain is particularly susceptible to the catalytic activity of MMP-2; here we show that the α-DG 621-628 region is required to carry out its complete digestion, suggesting that this portion may represent a MMP-2 anchoring site. Following this observation, we synthesized an α-DG based-peptide, spanning the (613-651) C-terminal region. The analysis of the kinetic and thermodynamic parameters of the whole and the isolated ca...