31 results on '"Vascellari, Sarah"'
Search Results
2. Genetic Creutzfeldt-Jakob disease in Sardinia: a case series linked to the PRNP R208H mutation due to a single founder effect
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Melis, Marta, Molari, Andrea, Floris, Gianluca, Vascellari, Sarah, Balestrino, Luisa, Ladogana, Anna, Poleggi, Anna, Parchi, Piero, Cossu, Giovanni, Melis, Maurizio, Orrù, Sandro, and Defazio, Giovanni
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- 2020
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3. Synthesis, protonation constants and biological activity determination of amino acid–salicylaldehyde-derived Schiff bases
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Fattuoni, Claudia, Vascellari, Sarah, and Pivetta, Tiziana
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- 2020
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4. Gut microbiota markers associated with obesity and overweight in Italian adults
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Palmas, Vanessa, Pisanu, Silvia, Madau, Veronica, Casula, Emanuela, Deledda, Andrea, Cusano, Roberto, Uva, Paolo, Vascellari, Sarah, Loviselli, Andrea, Manzin, Aldo, and Velluzzi, Fernanda
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- 2021
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5. Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in vitro antiproliferative activity
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Pivetta, Tiziana, Valletta, Elisa, Ferino, Giulio, Isaia, Francesco, Pani, Alessandra, Vascellari, Sarah, Castellano, Carlo, Demartin, Francesco, Cabiddu, Maria Grazia, and Cadoni, Enzo
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- 2017
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6. Competitive reactions among glutathione, cisplatin and copper-phenanthroline complexes
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Cadoni, Enzo, Valletta, Elisa, Caddeo, Graziano, Isaia, Francesco, Cabiddu, Maria Grazia, Vascellari, Sarah, and Pivetta, Tiziana
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- 2017
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7. Physico-Chemical Investigation and Antimicrobial Efficacy of Ozonated Oils: The Case Study of Commercial Ozonated Olive and Sunflower Seed Refined Oils.
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Puxeddu, Silvia, Scano, Alessandra, Scorciapino, Mariano Andrea, Delogu, Ilenia, Vascellari, Sarah, Ennas, Guido, Manzin, Aldo, and Angius, Fabrizio
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SUNFLOWER seed oil ,SUNFLOWER seeds ,NUCLEAR magnetic resonance spectroscopy ,ESCHERICHIA coli ,ENTEROCOCCUS ,CANDIDA albicans ,PETROLEUM ,ENTEROCOCCUS faecalis - Abstract
Drug resistance represents one of the great plagues of our time worldwide. This largely limits the treatment of common infections and requires the development of new antibiotics or other alternative approaches. Noteworthy, the indiscriminate use of antibiotics is mostly responsible for the selection of mutations that confer drug resistance to microbes. In this regard, recently, ozone has been raising interest for its unique biological properties when dissolved in natural oils. Ozonated oils have been reported to act in a non-specific way on microorganisms hindering the acquisition of advantageous mutations that result in resistance. Here, we focused on the antimicrobial effect of two commercial olive (OOO) and sunflower seeds (OSO) oils. Nuclear magnetic resonance spectroscopy and thermal analysis showed the change in the chemical composition of the oils after ozonation treatment. Different ozonated oil concentrations were then used to evaluate their antimicrobial profile against Candida albicans, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli by agar diffusion and broth dilution methods. Cytotoxicity was also evaluated in keratinocytes and epithelial cells. Overall, our results revealed that both OOO and OSO showed a potent microbicidal effect, especially against C. albicans (IC50 = OOO: 0.3 mg/mL and OSO: 0.2 mg/mL) and E. faecalis (IC50 = OOO: 0.4 mg/mL and OSO: 2.8 mg/mL) albeit exerting a certain effect also against S. aureus and E. coli. Moreover, both OOO and OSO do not yield any relevant cytotoxic effect at the active concentrations in both cell lines. This indicates that the ozonated oils studied are not toxic for mammalian cells despite exerting a potent antimicrobial effect on specific microorganisms. Therefore, OOO and OSO may be considered to integrate standard therapies in the treatment of common infections, likely overcoming drug resistance issues. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Novel copper(II) complexes as new promising antitumour agents. A crystal structure of [Cu(1,10-phenanthroline-5,6-dione)2(OH2)(OClO3)](ClO4)
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Pivetta, Tiziana, Trudu, Federica, Valletta, Elisa, Isaia, Francesco, Castellano, Carlo, Demartin, Francesco, Tuveri, Rossana, Vascellari, Sarah, and Pani, Alessandra
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- 2014
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9. α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients.
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Vascellari, Sarah, Orrù, Christina D., Groveman, Bradley R., Parveen, Sabiha, Fenu, Giuseppe, Pisano, Giada, Piga, Giuseppe, Serra, Giulia, Oppo, Valentina, Murgia, Daniela, Perra, Andrea, Angius, Fabrizio, Hughson, Andrew G., Haigh, Cathryn L., Manzin, Aldo, Cossu, Giovanni, and Caughey, Byron
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PARKINSON'S disease , *ALPHA-synuclein , *DUODENUM , *SOWING , *ENDOSPERM , *GASTROINTESTINAL system - Abstract
Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies. Author summary: Misfolded α-Synuclein deposition is a hallmark of Parkinson's disease. The gastrointestinal tract may be an initial site of α-Synuclein aggregation, and its detection might be useful in the early diagnosis of Parkinson's disease. Here, we have used a rapid, ultrasensitive seed amplification assay (RT-QuICR) to show that pathologic α-Syn aggregates with prion-like self-propagating activity are in the upper intestine (duodenum) of Parkinson's disease patients. Our intra vitam detection of α-synuclein seeding activity in duodenum biopsies gave high diagnostic accuracy. Quantitation revealed high levels of seeds in duodenal tissue. Thus, our findings suggest that abnormal α-Synuclein seeds in the upper intestine might be both an early accurate biomarker for Parkinson's disease and cause of gut dysfunction. [ABSTRACT FROM AUTHOR]
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- 2023
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10. In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine
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Orrù Christina, Cannas M., Vascellari Sarah, Angius Fabrizio, Cocco Pier, Norfo Claudia, Mandas Antonella, La Colla Paolo, Diaz Giacomo, Dessì Sandra, and Pani Alessandra
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prions ,cholesterol metabolism ,cholesterol esters ,prion inhibitors ,drug combinations ,Biology (General) ,QH301-705.5 - Published
- 2010
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11. ACAT-1, Cav-1 and PrP expression in scrapie susceptible and resistant sheep
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Orrù Cristina, Abete Claudia, Dolores Cannas M., Mulas Claudia, Norfo Claudia, Mandas Antonella, Vascellari Sarah, Colla Paolo, Dessì Sandra, and Pani Alessandra
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scrapie ,prion diseases ,cholesterol homeostasis ,cholesterol esters ,Biology (General) ,QH301-705.5 - Published
- 2010
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12. Synthesis, structural characterization, formation constants and in vitro cytotoxicity of phenanthroline and imidazolidine-2-thione copper(II) complexes
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Pivetta, Tiziana, Cannas, Maria Dolores, Demartin, Francesco, Castellano, Carlo, Vascellari, Sarah, Verani, Gaetano, and Isaia, Francesco
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- 2011
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13. Real-Time Quaking- Induced Conversion Assays for Prion Diseases, Synucleinopathies, and Tauopathies.
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Vascellari, Sarah, Orrù, Christina D., and Caughey, Byron
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PRION disease diagnosis ,BIOMARKERS ,MEDICAL technology ,SYNUCLEINS ,CEREBROSPINAL fluid ,SENSITIVITY & specificity (Statistics) ,NEURODEGENERATION ,NEUROLOGIC examination - Abstract
Prion diseases, synucleinopathies and tauopathies are neurodegenerative disorders characterized by deposition of abnormal protein aggregates in brain and other tissues. These aggregates consist of misfolded forms of prion, α-synuclein (αSyn), or tau proteins that cause neurodegeneration and represent hallmarks of these disorders. A main challenge in the management of these diseases is the accurate detection and differentiation of these abnormal proteins during the early stages of disease before the onset of severe clinical symptoms. Unfortunately, many clinical manifestations may occur only after neuronal damage is already advanced and definite diagnoses typically require post-mortem neuropathological analysis. Over the last decade, several methods have been developed to increase the sensitivity of prion detection with the aim of finding reliable assays for the accurate diagnosis of prion disorders. Among these, the real-time quaking-induced conversion (RT–QuIC) assay now provides a validated diagnostic tool for human patients, with positive results being accepted as an official criterion for a diagnosis of probable prion disease in multiple countries. In recent years, applications of this approach to the diagnosis of other prion-like disorders, such as synucleinopathies and tauopathies, have been developed. In this review, we summarize the current knowledge on the use of the RT-QuIC assays for human proteopathies. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Antiproliferative and antiviral activity of methanolic extracts from Sardinian Maltese Mushroom (Cynomorium coccineum L.).
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Vascellari, Sarah, Zucca, Paolo, Perra, Daniela, Serra, Alessandra, Piras, Alessandra, and Rescigno, Antonio
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CELL lines ,DNA viruses ,EXTRACTS ,TRADITIONAL medicine ,MUSHROOMS - Abstract
Cynomorium coccineum is a non-photosynthetic plant that grows in Mediterranean countries and that is amply used in the traditional medicine. The aim of this study was to extend previous studies on the chemical and biological properties of C. coccineum, evaluating the potential antiviral and antiproliferative activity of the methanolic extract. The MTT assay was used for the in vitro cytotoxic studies against human cancer-derived cell lines, while both MTT and plaque reduction (PRT) methods were used to evaluate the potential inhibitory effect of the extract against a panel of mammal viruses. The results obtained showed no selective activity against any DNA and RNA virus but revealed an interesting antiproliferative activity against human leukaemia-derived cell lines. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains
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Di Bari Michele A, Cardone Franco, Vetrugno Vito, Vacca Claudia, Banni Sebastiano, Vascellari Sarah, La Colla Paolo, and Pani Alessandra
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Prions ,Cholesterol ,Cholesteryl esters ,Fatty acids ,Statins ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Objective Cholesterol changes have been described in prion-cell models and in experimental rodent scrapie; yet, the pattern of this association is still controversial. Methods To shed light on the matter, we analysed and compared cholesterol variations in ScN2a cells and in brains of Scrapie-infected C57Bl/6 mice, using two different methods: a fluorimetric-enzymatic cholesterol assay, and high performance liquid chromatography-mass spectroscopy (HPLC-MS). Results Compared to uninfected controls, similar cholesterol metabolism anomalies were observed in infected cells and brains by both methods; however, only HPLC-MS revealed statistically significant cholesterol variations, particularly in the cholesteryl esters (CE) fraction. HPLC-MS analyses also revealed different fatty acid composition of the CE fraction in cells and brains. In N2a cells, their profile reflected that of serum, while in normal brains cholesteryl-linoleate only was found at detectable levels. Following prion infection, most CE species were increased in the CE pool of ScN2a cells, whereas a conspicuous amount of cholesteryl-arachidonate only was found to contribute to the cerebral increase of CE. Of interest, oral pravastatin administration to Scrapie-infected mice, was associated with a significant reduction of cerebral free cholesterol (FC) along with a concomitant further increase of the CE pool, which included increased amounts of both cholesteryl-linoleate and cholesteryl-arachidonate. Conclusion Although mechanistic studies are needed to establish the pathophysiological relevance of changes in cerebral CE concentrations, to the best of our knowledge this is the first report to provide evidence of increased cholesterol esterification in brains of prion-infected mice, untreated and treated with pravastatin.
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- 2011
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16. Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa‐carbidopa intrajejunal gel.
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Melis, Marta, Vascellari, Sarah, Santoru, Maria Laura, Oppo, Valentina, Fabbri, Margherita, Sarchioto, Marianna, Murgia, Daniela, Zibetti, Maurizio, Lopiano, Leonardo, Serra, Alessandra, Palmas, Vanessa, Pisanu, Silvia, Perra, Daniela, Madau, Veronica, Cusano, Roberto, Uva, Paolo, Mereu, Alessandra, Contu, Paolo, Morelli, Micaela, and Atzori, Luigi
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GUT microbiome , *PARKINSON'S disease , *DOPA , *BACTERIAL metabolism , *MASS spectrometry - Abstract
Background and purpose: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD‐carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. Methods: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next‐generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. Results: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. Conclusions: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression. [ABSTRACT FROM AUTHOR]
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- 2021
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17. In vitro synergistic anti-prion effect of cholesterol ester modulators
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Orrù, Christina Doriana, Cannas, Maria Dolores, Vascellari, Sarah, Angius, Fabrizio, Cocco, Pier Luigi, Norfo, Claudia, Mandas, Antonella, La Colla, Paolo, Dessì, Sandra, and Pani, Alessandra
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- 2009
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18. Cisplatin, glutathione and the third wheel: a copper-(1,10-phenanthroline) complex modulates cisplatin–GSH interactions from antagonism to synergism in cancer cells resistant to cisplatin.
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Vascellari, Sarah, Valletta, Elisa, Perra, Daniela, Pinna, Elisabetta, Serra, Alessandra, Isaia, Francesco, Pani, Alessandra, and Pivetta, Tiziana
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- 2019
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19. Mass spectrometric discrimination of phospholipid patterns in cisplatin‐resistant and ‐sensitive cancer cells.
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Cadoni, Enzo, Vanhara, Petr, Valletta, Elisa, Pinna, Elisabetta, Vascellari, Sarah, Caddeo, Graziano, Isaia, Francesco, Pani, Alessandra, Havel, Josef, and Pivetta, Tiziana
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PHOSPHOLIPIDS ,CANCER cells ,MOLECULAR diagnosis of cancer ,BIOLOGICAL tags ,CELL membranes - Abstract
Rationale: Development of therapy‐resistant cancer is a major problem in clinical oncology, and there is an urgent need for novel markers identifying development of the resistant phenotype. Lipidomics represents a promising approach to discriminate lipid profiles of malignant phenotype cells. Alterations in phospholipid distribution or chemical composition have been reported in various pathologies including cancer. Here we were curious whether quantitative differences in phospholipid composition between cisplatin‐resistant and ‐sensitive model cancer cell lines could be revealed by mass spectrometric means. Methods: The phospholipid contents of cell membranes of the cancer cell lines CCRF‐CEM and A2780, both responsive and resistant to cisplatin, were analyzed by solid‐phase extraction (SPE) and electrospray ionization mass spectrometry (ESI‐MS and tandem mass spectrometry (MS/MS)). Extracts were obtained by disruption of cells with a dounce tissue grinder set followed by centrifugation. To minimize the enzymatic activity, phospholipids were extracted from cell extracts by SPE immediately after the cell lysis and analyzed by MS. Both supernatant and pellet fractions of cell extracts were analyzed. Results: A phospholipid profile specific for cell lines and their phenotypes was revealed. We have documented by quantitative analysis that phosphocholines PC P‐34:0, PC 34:1, PC 20:2_16:0, LPC 18:1 and LPC 16:0 PLs were present in the 200–400 μM concentration range in CCRF‐CEM cisplatin‐responsive cells, but absent in their cisplatin‐resistant cells. Similarly, PC 34:1, LPC 18:1 and LPC 16:0 were increased in cisplatin‐responsive A2780 cells, and PC 20:2_16:0 was downregulated in cisplatin‐resistant A2780 cells. Conclusions: In this work we showed that the ESI‐MS analysis of the lipid content of the therapy‐resistant and ‐sensitive cells can clearly distinguish the phenotypic pattern and determine the potential tumor response to cytotoxic therapy. Lipid entities revealed by mass spectrometry and associated with development of therapy resistance can thus support molecular diagnosis and provide a potential complementary cancer biomarker. [ABSTRACT FROM AUTHOR]
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- 2019
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20. 1H NMR brain metabonomics of scrapie exposed sheep.
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Scano, Paola, Rosa, Antonella, Incani, Alessandra, Maestrale, Caterina, Santucciu, Cinzia, Perra, Daniela, Vascellari, Sarah, Pani, Alessandra, and Ligios, Ciriaco
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- 2015
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21. Prion Seeding Activities of Mouse Scrapie Strains with Divergent PrPSc Protease Sensitivities and Amyloid Plaque Content Using RT-QuIC and eQuIC.
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Vascellari, Sarah, Orrù, Christina D., Hughson, Andrew G., King, Declan, Barron, Rona, Wilham, Jason M., Baron, Gerald S., Race, Brent, Pani, Alessandra, and Caughey, Byron
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AUTISM spectrum disorders , *HUMAN endogenous retroviruses , *GENETICS , *MESSENGER RNA , *PATIENTS , *DEVELOPMENTAL disabilities - Abstract
Different transmissible spongiform encephalopathy (TSE)-associated forms of prion protein (e.g. PrPSc) can vary markedly in ultrastructure and biochemical characteristics, but each is propagated in the host. PrPSc propagation involves conversion from its normal isoform, PrPC, by a seeded or templated polymerization mechanism. Such a mechanism is also the basis of the RT-QuIC and eQuIC prion assays which use recombinant PrP (rPrPSen) as a substrate. These ultrasensitive detection assays have been developed for TSE prions of several host species and sample tissues, but not for murine models which are central to TSE pathogenesis research. Here we have adapted RT-QuIC and eQuIC to various murine prions and evaluated how seeding activity depends on glycophosphatidylinositol (GPI) anchoring and the abundance of amyloid plaques and protease-resistant PrPSc (PrPRes). Scrapie brain dilutions up to 10¯8 and 10¯13 were detected by RT-QuIC and eQuIC, respectively. Comparisons of scrapie-affected wild-type mice and transgenic mice expressing GPI anchorless PrP showed that, although similar concentrations of seeding activity accumulated in brain, the heavily amyloid-laden anchorless mouse tissue seeded more rapid reactions. Next we compared seeding activities in the brains of mice with similar infectivity titers, but widely divergent PrPRes levels. For this purpose we compared the 263K and 139A scrapie strains in transgenic mice expressing P101L PrPC. Although the brains of 263K-affected mice had little immunoblot-detectable PrPRes, RT-QuIC indicated that seeding activity was comparable to that associated with a high-PrPRes strain, 139A. Thus, in this comparison, RT-QuIC seeding activity correlated more closely with infectivity than with PrPRes levels. We also found that eQuIC, which incorporates a PrPSc immunoprecipitation step, detected seeding activity in plasma from wild-type and anchorless PrP transgenic mice inoculated with 22L, 79A and/or RML scrapie strains. Overall, we conclude that these new mouse-adapted prion seeding assays detect diverse types of PrPSc. [ABSTRACT FROM AUTHOR]
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- 2012
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22. New generation QuIC assays for prion seeding activity.
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Orru, Christina D., Wilham, Jason M., Vascellari, Sarah, Hughson, Andrew G., and Caughey, Byron
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- 2012
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23. In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine.
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Orrù, Christina, Cannas, M., Vascellari, Sarah, Angius, Fabrizio, Cocco, Pier, Norfo, Claudia, Mandas, Antonella, La Colla, Paolo, Diaz, Giacomo, Dessì, Sandra, and Pani, Alessandra
- Abstract
Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral cells of sheep susceptible-to or suffering-from Scrapie were characterized by an altered cholesterol homeostasis, and that drugs affecting cholesterol ester pool were endowed with selective anti-prion activity in N2a cell lines infected with the 22L and RML prion strains. In these prion-infected N2a cell lines, we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors. Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. In addition, comparative lipid analyses in prion-infected vs. uninfected N2a cells, demonstrated a derangement of type and distribution of cholesterol ester, free cholesterol, and triglyceride pools in the infected cells. Single-drug treatments differently affected synthesis of the various lipid forms, whereas combined drug treatments appeared to restore a lipid profile similar to that of the untreated-uninfected cells. We conclude that the anti-prion synergistic effects of cholesterol ester modulators associated with the cholesterol-interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish lipid homeostasis in the prion-infected cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets. [ABSTRACT FROM AUTHOR]
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- 2010
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24. ACAT-1, Cav-1 and PrP expression in scrapie susceptible and resistant sheep.
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Orrù, Cristina, Abete, Claudia, Dolores Cannas, M., Mulas, Claudia, Norfo, Claudia, Mandas, Antonella, Vascellari, Sarah, Colla, Paolo, Dessì, Sandra, and Pani, Alessandra
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Scrapie is a prion disease for which no means of ante-mortem diagnosis is available. We recently found a relationship between cell susceptibility to scrapie and altered cholesterol homeostasis. In brains and in skin fibroblasts and peripheral blood mononuclear cells from healthy and scrapie-affected sheep carrying a scrapie-susceptible genotype, the levels of cholesterol esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant genotype. Here we show that intracellular accumulation of cholesterol esters (CE) in fibroblasts derived from scrapie-susceptible sheep was accompanied by parallel alterations in the expression level of acyl-coenzymeA: cholesterol-acyltransferase (ACAT1) and caveolin-1 (Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative analysis of cellular prion protein (PrPc) mRNA, showed an higher expression level in cells from animals carrying a susceptible genotype, with or without Scrapie. These data suggest that CE accumulation in peripheral cells, together with the altered expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid metabolic profile associated with increased susceptibility to develop prion disease following infection. [ABSTRACT FROM AUTHOR]
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- 2010
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25. Parkinson's Disease: A Prionopathy?
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Vascellari, Sarah and Manzin, Aldo
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PARKINSON'S disease , *PRION diseases , *PROTEIN structure , *NEUROLOGICAL disorders , *PRIONS - Abstract
The principal pathogenic event in Parkinson's disease is characterized by the conformational change of α-synuclein, which form pathological aggregates of misfolded proteins, and then accumulate in intraneuronal inclusions causing dopaminergic neuronal loss in specific brain regions. Over the last few years, a revolutionary theory has correlated Parkinson's disease and other neurological disorders with a shared mechanism, which determines α-synuclein aggregates and progresses in the host in a prion-like manner. In this review, the main characteristics shared between α-synuclein and prion protein are compared and the cofactors that influence the remodeling of native protein structures and pathogenetic mechanisms underlying neurodegeneration are discussed. [ABSTRACT FROM AUTHOR]
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- 2021
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26. Clinical Phenotypes of Parkinson's Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes.
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Vascellari, Sarah, Melis, Marta, Palmas, Vanessa, Pisanu, Silvia, Serra, Alessandra, Perra, Daniela, Santoru, Maria Laura, Oppo, Valentina, Cusano, Roberto, Uva, Paolo, Atzori, Luigi, Morelli, Micaela, Cossu, Giovanni, and Manzin, Aldo
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PARKINSON'S disease , *GUT microbiome , *ENTEROTYPES , *NIACIN , *GLUCURONIC acid , *MICROBIAL metabolites - Abstract
Parkinson's disease (PD) is a clinically heterogenic disorder characterized by distinct clinical entities. Most studies on motor deficits dichotomize PD into tremor dominant (TD) or non-tremor dominant (non-TD) with akinetic-rigid features (AR). Different pathophysiological mechanisms may affect the onset of motor manifestations. Recent studies have suggested that gut microbes may be involved in PD pathogenesis. The aim of this study was to investigate the gut microbiota and metabolome composition in PD patients in relation to TD and non-TD phenotypes. In order to address this issue, gut microbiota and the metabolome structure of PD patients were determined from faecal samples using 16S next generation sequencing and gas chromatography–mass spectrometry approaches. The results showed a reduction in the relative abundance of Lachnospiraceae, Blautia, Coprococcus, Lachnospira, and an increase in Enterobacteriaceae, Escherichia and Serratia linked to non-TD subtypes. Moreover, the levels of important molecules (i.e., nicotinic acid, cadaverine, glucuronic acid) were altered in relation to the severity of phenotype. We hypothesize that the microbiota/metabolome enterotypes associated to non-TD subtypes may favor the development of gut inflammatory environment and gastrointestinal dysfunctions and therefore a more severe α-synucleinopathy. This study adds important information to PD pathogenesis and emphasizes the potential pathophysiological link between gut microbiota/metabolites and PD motor subtypes. [ABSTRACT FROM AUTHOR]
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- 2021
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27. Impact of a Moderately Hypocaloric Mediterranean Diet on the Gut Microbiota Composition of Italian Obese Patients.
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Pisanu, Silvia, Palmas, Vanessa, Madau, Veronica, Casula, Emanuela, Deledda, Andrea, Cusano, Roberto, Uva, Paolo, Vascellari, Sarah, Boi, Francesco, Loviselli, Andrea, Manzin, Aldo, and Velluzzi, Fernanda
- Abstract
Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M = 20/3) was compared before (T0) and after 3 months (T3) of nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, GM characterization confirmed typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction in body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, an increase in the abundance of several Bacteroidetes taxa (i.e., Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and a depletion of many Firmicutes taxa (i.e., Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas) were observed. In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of moderate caloric restriction in counteracting the gut dysbiosis. [ABSTRACT FROM AUTHOR]
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- 2020
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28. High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD.
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Fiorini, Michele, Iselle, Giorgia, Perra, Daniela, Bongianni, Matilde, Capaldi, Stefano, Sacchetto, Luca, Ferrari, Sergio, Mombello, Aldo, Vascellari, Sarah, Testi, Silvia, Monaco, Salvatore, and Zanusso, Gianluigi
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CREUTZFELDT-Jakob disease ,CEREBROSPINAL fluid examination ,TAU proteins ,LONGITUDINAL method ,MAGNETIC resonance imaging ,CEREBROSPINAL fluid - Abstract
The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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29. Cover Image.
- Author
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Cadoni, Enzo, Vanhara, Petr, Valletta, Elisa, Pinna, Elisabetta, Vascellari, Sarah, Caddeo, Graziano, Isaia, Francesco, Pani, Alessandra, Havel, Josef, and Pivetta, Tiziana
- Abstract
The front cover image is based on the Research Article MASS SPECTROMETRY DISCRIMINATION OF PHOSPHOLIPID PATTERNS IN CISPLATIN‐RESISTANT AND SENSITIVE CANCER CELLS by Enzo Cadoni et al., https://doi.org/10.1002/rcm.8320. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
30. P.207: RT-QuIC detection of PrPsCJD spiked into human urine.
- Author
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Vascellari, Sarah, Hughson, Andrew G., Cardone, Franco, Pocchiari, Maurizio, Caughey, Byron, Orrù, Christina D., and Pani, Alessandra
- Published
- 2014
31. PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.
- Author
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Marshall, Karen E., Hughson, Andrew, Vascellari, Sarah, Priola, Suzette A., Akikazu Sakudo, Takashi Onodera, and Baron, Gerald S.
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GLYCOSYLPHOSPHATIDYLINOSITOL , *MEMBRANE proteins , *VIRAL proteins , *PRIONS , *VIRUS diseases , *NUCLEOTIDE sequence , *KNOCKOUT mice - Abstract
Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrPC) influences PrPC misfolding into the disease-associated isoform, PrPres, as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrPC away from rafts. Previous studies showed that nonraft transmembrane PrPC variants resist conversion to PrPres when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrPC and GPI-anchored PrPres in distinct membrane environments. Thus, it remained unclear whether transmembrane PrPC might convert to PrPres if seeded by an exogenous source of PrPres not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrPC. To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrPC supported persistent PrPres propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrPC is required for persistent PrPres propagation, implicating raft microdomains as a location for conversion. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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