186 results on '"Maffia, M"'
Search Results
2. SERS based optical sensor to detect prion protein in neurodegenerate living cells
- Author
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Serra, A., Manno, D., Filippo, E., Buccolieri, A., Urso, E., Rizzello, A., and Maffia, M.
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- 2011
- Full Text
- View/download PDF
3. PBMCs protein expression profile in relapsing IFN-treated multiple sclerosis: A pilot study on relation to clinical findings and brain atrophy
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De Masi, R., Vergara, D., Pasca, S., Acierno, R., Greco, M., Spagnolo, L., Blasi, E., Sanapo, F., Trianni, G., and Maffia, M.
- Published
- 2009
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4. The MC1R single nucleotide polymorphisms identification by DNA-microarray on miniaturized silicon chip
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Petralia, S, Vigilanza, A, Sciuto, E, Maffia, M, Romanini, A, and Conoci, S
- Published
- 2021
5. Atlantic salmon ( Salmo salar L.) parr fed genetically modified soybeans and maize: Histological, digestive, metabolic, and immunological investigations
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Bakke-McKellep, A.M., Sanden, M., Danieli, A., Acierno, R., Hemre, G.-I., Maffia, M., and Krogdahl, Å.
- Published
- 2008
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6. Formation and characterization of glutamate dehydrogenase monolayers on silicon supports
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Blasi, L., Longo, L., Pompa, P.P., Manna, L., Ciccarella, G., Vasapollo, G., Cingolani, R., Rinaldi, R., Rizzello, A., Acierno, R., Storelli, C., and Maffia, M.
- Published
- 2005
- Full Text
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7. Characterization of glutamate dehydrogenase immobilization on silica surface by atomic force microscopy and kinetic analyses
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Blasi, L., Longo, L., Vasapollo, G., Cingolani, R., Rinaldi, R., Rizzello, T., Acierno, R., and Maffia, M.
- Published
- 2005
- Full Text
- View/download PDF
8. Adaptation of intestinal cell membrane enzymes to low temperatures in the Antarctic teleost Pagothenia bernacchii
- Author
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Maffia, M., Acierno, R., Deceglie, G., Vilella, S., and Storelli, C.
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- 1993
- Full Text
- View/download PDF
9. Physiological role of prion protein in copper homeostasis and angiogenic mechanisms of endothelial cells
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Rizzo, F., De Riccardis, L., Garzarelli, V., Intini, C., Greco, M., Maffia, M., and Urso, E.
- Published
- 2019
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10. Spatio-temporal analysis of rat peripheral nerve regeneration
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Maffia, M., Vergara, D., Romano, A., Corricciati, C., Damato, M., Frank, J., Fournier, I., Salzet, M., and Quattrini, A.
- Published
- 2019
- Full Text
- View/download PDF
11. Exposure to Electromagnetic Fields in UHF Band of an Insulin Preparation: Biological Effects
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Acierno, R., Riccardis, L., Maffia, M., Luca Mainetti, Patrono, L., Urso, E., Acierno, Raffaele, DE RICCARDIS, L., Maffia, Michele, Mainetti, Luca, Patrono, Luigi, and Urso, Emanuela
- Subjects
Insulin Preparation ,Biological Effect ,Evaluation of Exposure Risk ,Reverse Phase-High Pressure Liquid Chromatography ,Radio Frequency Identification (RFID) - Abstract
The item-level tracing and tracking requirements are growing more and more in the pharmaceutical sector, where the counterfeiting problem and the significant fragmentation of the market contribute significantly to complicate the scenario. The Radio Frequency Identification (RFID) technology holds the promise to eliminate many of the previous problems. Unfortunately, there are still some barriers limiting the largescale deployment of these innovative technologies. Currently, it is not easy finding an exhaustive analysis about potential effects of exposure to electromagnetic fields of the RFID systems on drugs. This work aimed to evaluate the effects of RFID systems on the molecular structure and potency of a biological drug. In particular, some samples of a commercial human insulin preparation (ActrapidTM) were exposed for different periods to electromagnetic fields generated by RFID devices in UHF band. In order to evaluate both possible alterations of the molecular structure and possible adverse effects on drug performance, the following techniques have been used: Reverse Phase-High Pressure Liquid Chromatography and in vitro cell proliferation assays. The experimental results have shown that the electromagnetic field generated by UHF RFID devices does not cause significant biological effects on ActrapidTM insulin.
- Published
- 2010
12. Lipid and Fatty Acid Compositions of Mytilus galloprovincialis Cultured in the Mar Grande of Taranto (Southern Italy): Feeding Strategies and Trophic Relationships
- Author
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Prato, E., Danieli, A., Maffia, M., FRANCESCA BIANDOLINO, E., Prato, Danieli, Antonio, Maffia, Michele, and F., Biandolino
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Seasonal variation ,Lipid composition ,Trophic markers ,Mussel - Abstract
Lipid and fatty acid compositions of Mytilus galloprovincialis cultured in the Mar Grande of Taranto (southern Italy): feeding strategies and trophic relationships. Zoological Studies 49(2): 211-219. Lipid and fatty acid (FA) compositions were determined in the mussel Mytilus galloprovincialis collected from June 2006 to May 2007 in the Mar Grande of Taranto, southern Italy. Total lipids significantly differed throughout the study period (ANOVA, p < 0.05), with higher values in summer (24.7% dry weight (DW)) and the lowest values in winter (3.5% DW). Triacylglycerols (TAGs) were the dominant lipid class in spring and summer accounting for 55.28% and 60.3% of total lipids, respectively, while in the autumn and winter phospholipids (PLs) were considerably greater than TAGs, comprising 55.16% and 47.5% of total lipids, respectively. Cholesterol did not show large variations over the seasons. Predominant FAs were saturated FAs (SAFAs) followed by monounsaturated FAs (MUFAs). The amount of polyunsaturated FAs (PUFAs) was low. The 14:0, 16:0, 18:0, and 22:0 SAFAs, together with 14:1, 16:1 omega 7, 18:1 omega 9, 18:1 omega 7, 20:1 omega 9, and 24:1 omega 9 MUFAs, and the PUFA, non-methylene interrupted dienoic (NMID), were the most abundant FAs. FA biomarkers are frequently used to identify trophic relationships among marine invertebrates. In order to obtain indications on food sources of M. galloprovincialis, a variety of FA ratios and the sum of some FAs were determined. The sum of 18:1 omega 7 + odd-branched FAs indicated a moderate bacterial contribution to the mussel diet. A high 18:1 omega 9/18:1 omega 7 ratio together with a high level of 20:1w9 indicated an animal dietary input. Trophic markers suggested lows contribution of diatoms and dinoflagellates to the diet of M. galloprovincialis.
- Published
- 2010
13. Structural and functional characterisation of gill carbonic anhydrase of the Antarctic icefish Chionodraco hamatus
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Rizzello A., Ciardiello M.A., Acierno R., Carratore V., Verri T., di Prisco G., Storelli C., and Maffia M.
- Published
- 2006
14. Structural properties of branchial carbonic anhydrase of icefish Chionodraco hamatus
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Maffia M., Rizzello A., Ciardiello M.A., Acierno R., Carratore V., di Prisco G., and Storelli C.
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- 2003
15. NA+/H+ exchange in the kidneys of eels adapted to sea-water or to fresh water environments: Studies with brush border membrane vesicles
- Author
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VILELLA, Sebastiano, ZONNO V, CASSANO G, MAFFIA M. AND STORELLI C., Vilella, Sebastiano, Zonno, V, Cassano, G, and Maffia, M. AND STORELLI C.
- Published
- 1991
16. Lysine transport by brush border membrane vesicles of eel intestine: interaction with neutral amino acids. Am. J. Physiol. 259: R1181-R1188
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VILELLA, Sebastiano, AHEARN G, CASSANO G, MAFFIA M. AND STORELLI C., Vilella, Sebastiano, Ahearn, G, Cassano, G, and Maffia, M. AND STORELLI C.
- Published
- 1990
17. Comparative proteomic profiling of Hodgkin lymphoma cell lines.
- Author
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Vergara, D., Simeone, P., De Matteis, S., Carloni, S., Lanuti, P., Marchisio, M., Miscia, S., Rizzello, A., Napolitano, R., Agostinelli, C., and Maffia, M.
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- 2016
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18. RFID-based tracing systems for drugs: Technological aspects and potential exposure risks.
- Author
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Acierno, R., Maffia, M., Mainetti, L., Patrono, L., and Urso, E.
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- 2011
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19. Potential effects of RFID systems on biotechnology insulin preparation: A study using HPLC and NMR spectroscopy.
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Acierno, R., Carata, E., De Pascali, S.A., Fanizzi, F.P., Maffia, M., Mainetti, L., and Patrono, L.
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- 2010
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20. Investigating potential effects of RFID systems on the molecular structure of the human insulin.
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Acierno, R., De Pascali, S.A., Fanizzi, F.P., Maffia, M., Mainetti, L., Patrono, L., and Urso, E.
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- 2010
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21. Effects Evaluation of UHF RFID Systems on the Molecular Structure of Biological Drugs.
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Acierno, R., Carata, E., Maffia, M., Mainetti, L., and Patrono, L.
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- 2010
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22. A multidisciplinary approach to investigate potential exposure risks on drugs of RFID systems.
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Acierno, R., Maffia, M., Mainetti, L., Patrono, L., and Urso, E.
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- 2010
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23. Nanostructures for SERS in living cell.
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Manno, D., Filippo, E., Buccolieri, A., Fiore, R., Serra, A., Urso, E., Rizzello, A., and Maffia, M.
- Published
- 2009
24. Network P2P for exploring and visualization of proteomic data produced by two dimensional electrophoresis.
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Mercurio, G., Maglio, S., Agrusti, A., DeNunzio, G., Cataldo, R., DeMitri, I., Favetta, M., Massafra, A., Marsella, G., Vergara, D., and Maffia, M.
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- 2008
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25. Network P2P for Exploring and Visualization of Proteomic Data: Possibility of Handling Data and Analysing Them under Different Perspectives.
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Mercurio, G., Maglio, S., Agrusti, A., De Nunzio, G., Cataldo, R., De Mitri, I., Favetta, M., Massafra, A., Marsella, G., Vergara, D., Maffia, M., Vasilateanu, A., and Serbanati, L.D.
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- 2008
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26. A rapid and inexpensive method to assay transport of short chain peptides across intestinal brush-border membrane vesicles from the European eel ( Anguilla anguilla).
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VERRI, T., DANIELI, A., BAKKE, S., ROMANO, A., BARCA, A., RØNNESTAD, I., MAFFIA, M., and STORELLI, C.
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ANGUILLA anguilla ,PEPTIDES ,BRUSH border membrane ,CELL membranes ,IODIDES ,FLUORESCENCE - Abstract
Membrane potential depolarization due to electrogenic peptide transport activity was examined in eel ( Anguilla anguilla) intestinal brush-border membrane vesicles (BBMV) by monitoring the fluorescence quenching of the voltage-sensitive dye 3,3′-diethylthiadicarbocyanine iodide. Our experimental approach consisted of generating an internal negative membrane potential mimicking in vivo conditions and measuring membrane potential depolarization due to different extravesicular dipeptides. Peptide-dependent membrane potential depolarization was observed in both the presence and absence of extravesicular Na
+ and was inhibited by diethylpyrocarbonate, which is consistent with the involvement of electrogenic, Na+ -independent, H+ -dependent peptide transport activity. Kinetic analysis indicated that peptide-dependent membrane potential depolarization is a saturable process ( Km,app ∼ 1.5 mmol L−1 ) and that within the 0.1–10 mmol L−1 peptide range a single carrier system is involved in the transport process. Our results suggest that a peptide transport activity, kinetically resembling the PepT1(Slc15A1)-type-mediated H+ /peptide cotransport action, can be monitored in eel intestinal BBMV using an easy and inexpensive fluorescence assay. [ABSTRACT FROM AUTHOR]- Published
- 2008
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27. Nutritional, physiological, and histological responses in Atlantic salmon, Salmo salar L. fed diets with genetically modified maize.
- Author
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HEMRE, G.-I., SAGSTAD, A., BAKKE-MCKELLEP, A.M., DANIELI, A., ACIERNO, R., MAFFIA, M., FRØYSTAD, M., KROGDAHL, Å., and SANDEN, M.
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ANIMAL feeding ,ATLANTIC salmon ,FISH physiology ,BODY composition of fish ,WEIGHT gain ,ANTHROPOMETRY ,PHYSIOLOGY - Abstract
The objective of this study was to evaluate whether standard fish meal diets prepared with increasing levels of genetically modified (GM; 150 and 300 g kg
−1 ) maize (event MON810® ) as a starch source, showed any nutritional or physiological adverse effects on Atlantic salmon, Salmo salar L. postsmolt. The diets with low or high inclusions of GM maize and its near-isogenic parental line (nongenetically modified; nGM maize), were balanced with Suprex maize (Reference) to obtain compositional equivalency of diet starch, sugars and all other nutrients. Total starch level in all diets was 160 g kg−1 . After 82 days of feeding, fish growth was high in all groups, however fish fed the GM maize showed slight but significant lower feed intake, which was followed by slight but significant lower specific growth rate and final body weights, compared with fish fed nGM maize, none of the groups varied significantly from fish fed the Reference diet. There was no variation in feed conversion ratios (FCR), protein and lipid efficiency ratios (PER and LER), or protein- and lipid-productive values (PPV and LPV) in this study. No significant effect of maize type was detected on apparent digestibility coefficients (ADC) of dry matter, protein or lipid. Hematological analysis and plasma nutrients varied within normal ranges for Atlantic salmon in all diet groups, except for somewhat elevated aspartate aminotransferase (ASAT) values in all groups. Hepatosomatic index (HSI) with values ranging from 1.37 to 1.60, was significantly higher for the high GM maize group compared with the high nGM maize group but not when compared with the Reference diet group. Lowered spleen (SSI) and head-kidney somatic indices (H-KSI) were registered when fed GM compared with nGM maize, the Reference treatment was however, equal to both. Distal intestine somatic index (DISI) was significantly higher for GM maize-fed fish compared with nGM maize-fed fish, but not significantly different from the Reference diet group. Histological evaluation of the mid- and distal intestine, liver, spleen and head-kidney did not reveal any diet-related morphological changes. Maltase activities in the mid- and distal intestinal tissue homogenates were affected by diet, the fish fed high GM maize having higher activities compared with high nGM maize-fed fish. Leucine aminopeptidase (LAP) and alkaline phosphatase (AP) activities were not affected by diet. Sodium-dependentd-glucose uptake in brush border membrane vesicles (BBMV) isolated from pyloric caeca of fish fed high GM maize was significantly higher than that found in fish fed the analogous diet with high nGM maize. Based on the present findings, the conclusions made are: Atlantic salmon smolts fed GM maize (event MON810® ), its near-isogenic parental line and suprex maize (Reference diet), all resulted in high growth rates, ADC and feed utilization. Health, when evaluated by means of mortality (low), normal ranges of blood and plasma parameters, except somewhat elevated ASAT values and minor variations in organ sizes, were considered good in all diet groups. The changes in the glucose transport mechanism and intestinal maltase enzyme activity in the gastrointestinal tract warrant further studies. [ABSTRACT FROM AUTHOR]- Published
- 2007
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28. Pharmacokinetics of cephalexin in sea bream,Sparus aurata(L.), after a single intraperitoneal injection.
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Katharios, P., Iliopoulou-Georgudaki, J., Antimisiaris, S., Verri, T., Toma, P., Acierno, R., and Maffia, M.
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SPARUS aurata ,SPARUS ,SPARIDAE ,PHARMACOKINETICS ,CHEMICAL kinetics ,INTRAPERITONEAL injections - Abstract
The pharmacokinetic properties of cephalexin were studied in sea bream (mean weight 77 g), Sparus aurata (L.) after a single intraperitoneal injection (200 mg kg
-1 ). Pharmacokinetic analysis of the serum concentrations vs time points obtained was performed using non-compartmental analysis and a compartmental pharmacokinetic model approach. In the latter case, a two-compartment open model with a lag time gave the best fitting. The maximum peak serum concentration was 5.018 mg ml-1 kg-1 1 h post-treatment. The area under the curve (AUC) cephalexin was 17.394 mg·h kg-1 and the elimination half-life of 1.83 h. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
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29. Characterisation of intestinal peptide transporter of the Antartic haemoglobinless teleost Chionodraco hamatus.
- Author
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Maffia, M., Rizzelo, A., Acierno, R., Verri, T., Rollo, M., Danieli, A., Döring, F., Daniel, H., and Storelli, C.
- Subjects
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VASOACTIVE intestinal peptide , *ACIDIFICATION - Abstract
H[sup +]/peptide cotransport was studied in brush-border membrane vesicles (BBMV) from the intestine of the haemoglobinless Antarctic teleost Chionodraco hamatus by monitoring peptide-dependent intravesicular acidification with the pH-sensitive dye Acridine Orange. Diethylpyrocarbonate-inhibited intravesicular acidification was specifically achieved in the presence of extravesicular glycyl-L-proline (Gly-L-Pro) as well as of glycyl-L-alanine (Gly-L-Ala) and D-phenylalanyl-L-alanine (D-Phe-L-Ala). H[sup +]/Gly-L-Pro cotransport displayed saturable kinetics, involving a single carrier system with an apparent substrate affinity (K[sub m,app]) of 0.806±0.161 mmol l[sup -1]. Using degenerated primers from eel and human (PepT1) transporter sequence, a reverse transcription-polymerase chain reaction (RT-PCR) signal was detected in C. hamatus intestine. RT-PCR paralleled kinetic analysis, confirming the hypothesis of the existence of a PepT1-type transport system in the brush-border membranes of icefish intestine. Functional expression of H[sup +]/peptide cotransport was successfully performed in Xenopus laevis oocytes after injection of poly(A)[sup +] RNA (mRNA) isolated from icefish intestinal mucosa. Injection of mRNA stimulated DPhe-L-Ala uptake in a dose-dependent manner and an excess of glycyl-L-glutamine inhibited this transport. H[sup +]/peptide cotransport in the Antarctic teleost BBMV exhibited a marked difference in temperature optimum with respect to the temperate teleost Anguilla anguiila, the maximal activity rate occurring at approximately 0°C for the former and 25°C for the latter. Temperature dependence of icefish and eel intestinal mRNAstimulated uptake in the heterologous system (oocytes) was comparable. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
30. Carbonic anhydrase activity in tissues of the icefish Chionodraco hamatus and of the red-blooded....
- Author
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Maffia, M., Rizzello, A., Acierno, R., Rollo, M., Chiloiro, R., and Storelli, C.
- Subjects
- *
CARBONIC anhydrase , *TREMATOMUS bernacchii - Abstract
Examines carbonic anhydrase (CA) activity and distribution in blood gills, intestine and kidney of the hemoglobinless teleost Chionodraco hamatus with Trematomus bernacchii. Analysis of the highest CA activity; Molecular masses of CA isoforms; Presence of a different branchial systolic CA in the red-blooded teleosts.
- Published
- 2001
31. La competenza scritta in italiano L2 di apprendenti vulnerabili
- Author
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De Meo, Anna, Maffia, Marta, and Vitale, Giuseppina
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Adult refugees. Functional Adequacy Scale. L2 Italian. Standard Evaluation Scale. Written competence ,Language. Linguistic theory. Comparative grammar ,P101-410 - Abstract
The high number of low-literate vulnerable refugees and asylum seekers among L2 Italian learners requires a rethinking not only of approaches and teaching methods, but also of assessment strategies. The present study aims to investigate the effectiveness of two different rating scales in the assessment of writing skills for this peculiar target of learners, a Standard Evaluation Scale and a Functional Adequacy Scale. Application of the two assessment methods on a corpus of about 450 written texts produced by 50 refugees and asylum seekers from 16 different countries, with an Italian A2 level competence, demonstrated that a Functional Adequacy Scale can be a more reliable and efficient tool than a Standard Evaluation Scale for valorising also poor writing skills, instead of underlying the limits of low-literate productions.
- Published
- 2019
- Full Text
- View/download PDF
32. Na+-D-glucose cotransport by intestinal BBMVs of the Antarctic fish Trematomus bernacchii.
- Author
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Maffia, M. and Acierno, R.
- Subjects
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TREMATOMUS bernacchii , *SODIUM cotransport systems , *BRUSH border membrane - Abstract
Examines the Na+-D-glucose cotransport in the Antarctic fish Trematomus bernacchii by brush-border membrane vesicles (BBMV). Enzymatic characterization of BBMs isolated from T. bernacchii intestine; Temperature dependence in Anguial anguilla and T. bernacchii intestinal BBMV; Effect of electrical membrane potential on D-glucose uptake.
- Published
- 1996
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33. Immunolocalisation of angiotensin II receptors in icefish (Chionodraco hamatus) tissues.
- Author
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Marsigliante, S., Acierno, R., Maffia, M., Muscella, A., Vinson, G. P., and Storelli, C.
- Published
- 1997
34. Electrogenic, proton-coupled, intestinal dipeptide transport in herbivorous and carnivorous teleosts.
- Author
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THAMOTHARAN, M., GOMME, J., ZONNO, V., MAFFIA, M., STORELLI, C., and AHEARN, G. A.
- Published
- 1996
- Full Text
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35. Ascorbic acid transport by intestinal brush-border membrane vesicles of the teleost Anguilla anguilla.
- Author
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MAFFIA, M., AHEARN, G. A., VILELLA, S., ZONNO, V., and STORELLI, C.
- Published
- 1993
- Full Text
- View/download PDF
36. Brush border amino acid transport mechanisms in carnivourus eel intestine
- Author
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STORELLI C, ROMANO M. P, MAFFIA M. AND CASSANO G., VILELLA, Sebastiano, Storelli, C, Vilella, Sebastiano, ROMANO M., P, and Maffia, M. AND CASSANO G.
- Published
- 1989
37. 38 ANTIANGIOGENIC PROPERTIES OF IMMUNOMODULATORY DRUG LENALIDOMIDE IN ENDOTHELIAL CELLS OF PATIENTS WITH ACTIVE MULTIPLE MYELOMA.
- Author
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De Luisi, A., Ferrucci, A., Di Pietro, G., Berardi, S., Basile, A., Ria, R., Ribatti, D., Coluccia, A.M.L., Maffia, M., Ranieri, G., Paradiso, A., Guarini, A., and Vacca, A.
- Published
- 2010
- Full Text
- View/download PDF
38. Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects.
- Author
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De Riccardis, L., Buccolieri, A., Muci, M., Pitotti, E., De Robertis, F., Trianni, G., Manno, D., and Maffia, M.
- Subjects
- *
MULTIPLE sclerosis , *COPPER poisoning , *CEREBROSPINAL fluid , *CERULOPLASMIN , *COPPER in the body - Abstract
Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
39. The Biological Relevance of NHERF1 Protein in Gynecological Tumors
- Author
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Margherita Sonnessa, Sara Sergio, Concetta Saponaro, Michele Maffia, Daniele Vergara, Francesco Alfredo Zito, Andrea Tinelli, Sonnessa, M, Sergio, S, Saponaro, C, Maffia, M, Vergara, D, Zito, Fa, and Tinelli, A
- Subjects
Cancer Research ,ovarian cancer ,Oncology ,NHERF1 ,Wnt/beta-catenin pathway ,cervical cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,gynecological cancers ,RC254-282 - Abstract
Gynecological cancer management remains challenging and a better understanding of molecular mechanisms that lead to carcinogenesis and development of these diseases is needed to improve the therapeutic approaches. The Na+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein that contains modular protein-interaction domains able to interact with molecules with an impact on carcinogenesis and cancer progression. During recent years, its involvement in gynecological cancers has been explored, suggesting that NHERF1 could be a potential biomarker for the development of new targeted therapies suitable to the management of these tumors. This comprehensive review provides an update on the recent study on NHERF1 activity and its pathological role in cervical and ovarian cancer, as well as on its probable involvement in the therapeutic landscape of these cancer types.
- Published
- 2022
40. Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis
- Author
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Rosanna Martinelli, Marika Massaro, Tiziano Verri, Maria Annunziata Carluccio, Michele Maffia, Raffaele De Caterina, Egeria Scoditti, Valentina Gatta, Nadia Calabriso, Carluccio, M. A., Martinelli, R., Massaro, M., Calabriso, N., Scoditti, E., Maffia, M., Verri, T., Gatta, V., and De Caterina, R.
- Subjects
Olive oil polyphenol ,endothelial dysfunction ,Transcriptome ,chemistry.chemical_compound ,transcriptomics ,Nutrigenomics ,Endothelial cell ,Gene expression ,Hydroxytyrosol ,TX341-641 ,Endothelial dysfunction ,Nutrition and Dietetics ,Endothelial cells ,Microarray analysis ,Olive oil polyphenols ,Transcriptomics ,Microarray analysi ,NF-kappa B ,Interleukin ,Phenylethyl Alcohol ,endothelial cells ,Cell biology ,Up-Regulation ,hydroxytyrosol ,Nutrigenomic ,Human ,Signal Transduction ,Human Umbilical Vein Endothelial Cell ,Down-Regulation ,Reproducibility of Result ,Biology ,Article ,Proinflammatory cytokine ,nutrigenomics ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Microarray analysis techniques ,Nutrition. Foods and food supply ,Gene Expression Profiling ,Reproducibility of Results ,medicine.disease ,olive oil polyphenols ,Gene Ontology ,chemistry ,Transcriptomic ,Unfolded protein response ,Unfolded Protein Response ,gene expression ,microarray analysis ,Food Science - Abstract
Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are prominent targets for vasculo-protective effects of olive oil polyphenols, have been lacking. This study aims to comprehensively evaluate the genomic effects exerted by HT, at the transcriptional level, in endothelial cells under resting or proinflammatory conditions. Human umbilical vein endothelial cells (HUVECs) were treated with 10 µmol/L HT for 1 h and then stimulated with 5 ng/mL interleukin (IL)-1β for 3 h. Total RNA was extracted, and gene expression profile assessed with microarray analysis. Functional enrichment analysis and pathway analysis were performed by Ingenuity Pathways Analysis. Microarray data were validated by qRT-PCR. Fixing a significance threshold at 1.5-fold change, HT affected the expression of 708 and 599 genes, respectively, in HUVECs under resting and IL-1β-stimulated conditions, among these, 190 were common to both conditions. Unfolded protein response (UPR) and endoplasmic reticulum stress resulted from the two top canonical pathways common between HT and HT-IL-1β affected genes. IL-17F/A signaling was found in the top canonical pathways of HT modified genes under resting unstimulated conditions, whereas cardiac hypertrophy signaling was identified among the pathways affected by HT-IL-1β. The transcriptomic analysis allowed pinpointing immunological, inflammatory, proliferative, and metabolic-related pathways as the most affected by HT in endothelial cells. It also revealed previously unsuspected genes and related gene pathways affected by HT, thus broadening our knowledge of its biological properties. The unbiased identification of novel genes regulated by HT improves our understanding of mechanisms by which olive oil prevents or attenuates inflammatory diseases and identifies new genes to be enquired as potential contributors to the inter-individual variation in response to functional food consumption.
- Published
- 2021
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41. Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks
- Author
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Michel Salzet, Maxence Wisztorski, Michele Maffia, Marina Damato, Ilaria Cicalini, Tristan Cardon, Isabelle Fournier, Damiana Pieragostino, Daniele Vergara, Damato, M, Cardon, T, Wisztorski, M, Fournier, I, Pieragostino, D, Cicalini, I, Salzet, M, Vergara, D, Maffia, M, University of Salento [Lecce], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, and Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] [Ud'A]
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QH301-705.5 ,[SDV]Life Sciences [q-bio] ,oligodendrocytes ,Cell fate determination ,PKC ,differentiation ,ROCK ,cytoskeleton ,mass spectrometry ,signaling ,Catalysis ,Article ,Cell Line ,Inorganic Chemistry ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Protein kinase A ,Molecular Biology ,QD1-999 ,Spectroscopy ,Protein kinase C ,Protein Kinase C ,Cell Proliferation ,rho-Associated Kinases ,Chemistry ,Effector ,Organic Chemistry ,Oligodendrocyte differentiation ,Cell Differentiation ,General Medicine ,Computer Science Applications ,Cell biology ,Enzyme Activation ,Oligodendroglia ,Proteome ,Tetradecanoylphorbol Acetate ,Reprogramming ,Biological network ,Signal Transduction - Abstract
International audience; Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.
- Published
- 2021
42. Microbiota-Derived Metabolites in Tumor Progression and Metastasis
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Francesca Fanini, Daniele Vergara, Michele Maffia, Francesca Pirini, Sara Bravaccini, Tania Rossi, Rossi, T., Vergara, D., Fanini, F., Maffia, M., Bravaccini, S., and Pirini, F.
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Programmed cell death ,Inflammation ,tumor progression ,Review ,Metastasi ,Biology ,Catalysis ,Metastasis ,Inorganic Chemistry ,lcsh:Chemistry ,Immune system ,Neoplasms ,medicine ,Animals ,Humans ,metastasis ,tumor microenvironment ,Microbiome ,Physical and Theoretical Chemistry ,Neoplasm Metastasis ,Microbiota-derived metabolite ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Tumor microenvironment ,Microbiota ,Organic Chemistry ,General Medicine ,medicine.disease ,Tumor progression ,microbiota-derived metabolites ,Computer Science Applications ,Cell biology ,Crosstalk (biology) ,lcsh:Biology (General) ,lcsh:QD1-999 ,Disease Progression ,Metabolome ,medicine.symptom - Abstract
Microbial communities and human cells, through a dynamic crosstalk, maintain a mutualistic relationship that contributes to the maintenance of cellular metabolism and of the immune and neuronal systems. This dialogue normally occurs through the production and regulation of hormonal intermediates, metabolites, secondary metabolites, proteins, and toxins. When the balance between host and microbiota is compromised, the dynamics of this relationship change, creating favorable conditions for the development of diseases, including cancers. Microbiome metabolites can be important modulators of the tumor microenvironment contributing to regulate inflammation, proliferation, and cell death, in either a positive or negative way. Recent studies also highlight the involvement of microbiota metabolites in inducing epithelial–mesenchymal transition, thus favoring the setup of the metastatic niche. An investigation of microbe-derived metabolites in “liquid” human samples, such as plasma, serum, and urine, provide further information to clarify the relationship between host and microbiota.
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- 2020
43. Alternative proteins are functional regulators in cell reprogramming by pka activation
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Cardon, Tristan, Franck, Julien, Coyaud, Etienne, Laurent, Estelle M N, Damato, Marina, Maffia, Michele, Vergara, Daniele, Fournier, Isabelle, Salzet, Michel, INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM], University of Salento [Lecce], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardon, T., Franck, J., Coyaud, E., Laurent, E. M. N., Damato, M., Maffia, M., Vergara, D., Fournier, I., Salzet, M., and SALZET, Michel
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Proteomics ,AcademicSubjects/SCI00010 ,[SDV]Life Sciences [q-bio] ,Colforsin ,Nuclear Proteins ,RNA-Binding Proteins ,Receptor, EphA5 ,Genomics ,Tropomyosin ,Cellular Reprogramming ,Cyclic AMP-Dependent Protein Kinases ,Mass Spectrometry ,[SDV] Life Sciences [q-bio] ,Enzyme Activation ,Cell Line, Tumor ,Protein Interaction Mapping ,Humans ,Microtubule-Associated Proteins ,Signal Transduction - Abstract
International audience; It has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: NCH82 human glioma cells after 0, 16, 24 and 48 h Forskolin stimulation. Forskolin is a protein kinase A activator inducing cell differentiation and epithelial-mesenchymal transition. Our data show that AltMAP2, AltTRNAU1AP and AltEPHA5 interactions with tropomyosin 4 are downregulated under Forskolin treatment. In a wider perspective, Gene Ontology and pathway enrichment analysis (STRING) revealed that RefProts associated with AltProts are enriched in cellular mobility and transfer RNA regulation. This study strongly suggests novel roles of AltProts in multiple essential cellular functions and supports the importance of considering them in future biological studies.
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- 2020
44. Carbonic Anhydrase XII Expression Is Modulated during Epithelial Mesenchymal Transition and Regulated through Protein Kinase C Signaling
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Loredaria Adamo, Michele Maffia, Antonio Gaballo, Michel Salzet, Raffaela Barbano, Francesca Pirini, Sara Bravaccini, Isabelle Fournier, Julien Franck, Barbara Pasculli, Marina Damato, Eugenio Fonzi, Daniele Vergara, Sara Ravaioli, SALZET, Michel, University of Salento [Lecce], Liceo Classico Giovanni Paolo II [Lecce LE, Italie], IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (Meldola), CNR NANOTEC - Institute of Nanotechnology [Lecce, Italy], Laboratorio di Oncologia [San Giovanni Rotondo, Italy] (Fondazione IRCCS Casa Sollievo della Sofferenza ), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, Unit of Melanoma Medical Oncology [Fondazione IRCCS Istituto Nazionale Tumori, Milan], Vergara, D, Ravaioli, S, Fonzi, E, Adamo, L, Damato, M, Bravaccini, S, Pirini, F, Gaballo, A, Barbano, R, Pasculli, B, Franck, J, Fournier, I, Salzet, M, Maffia, M., and Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
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epithelial mesenchymal transition ,[SDV]Life Sciences [q-bio] ,carbonic anhydrase ,Cellular homeostasis ,Triple Negative Breast Neoplasms ,Protein kinase C signaling ,lcsh:Chemistry ,0302 clinical medicine ,Sodium Bicarbonate Cotransporter 3 ,PKC ,lcsh:QH301-705.5 ,Protein Kinase C ,Spectroscopy ,Carbonic Anhydrases ,0303 health sciences ,biology ,Chemistry ,General Medicine ,Middle Aged ,Computer Science Applications ,Cell biology ,Gene Expression Regulation, Neoplastic ,[SDV] Life Sciences [q-bio] ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Female ,Metabolon ,breast cancer ,proteomics ,transport metabolon ,metabolism ,Signal transduction ,Intracellular ,Signal Transduction ,Adult ,Epithelial-Mesenchymal Transition ,Down-Regulation ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Antigens, Neoplasm ,Cell Line, Tumor ,Carbonic anhydrase ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Protein kinase C ,Aged ,030304 developmental biology ,Sodium-Bicarbonate Symporters ,Organic Chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,biology.protein - Abstract
International audience; Members of the carbonic anhydrase family are functionally involved in the regulation of intracellular and extracellular pH in physiological and pathological conditions. Their expression is finely regulated to maintain a strict control on cellular homeostasis, and it is dependent on the activation of extracellular and intracellular signaling pathways. Combining RNA sequencing (RNA-seq), NanoString, and bioinformatics data, we demonstrated that the expression of carbonic anhydrase 12 (CAXII) is significantly different in luminal and triple negative breast cancer (BC) models and patients, and is associated with the activation of an epithelial mesenchymal transition (EMT) program. In BC models, the phorbol ester 12-myristate 13-acetate (PMA)-mediated activation of protein kinase C (PKC) induced a down-regulation of CAXII with a concomitant modulation of other members of the transport metabolon, including CAIX and the sodium bicarbonate cotransporter 3 (NBCn1). This is associated with a remodeling of tumor glycolytic metabolism induced after PKC activation. Overall, this analysis highlights the dynamic nature of transport metabolom and identifies signaling pathways finely regulating this plasticity.
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- 2020
45. The multiverse nature of epithelial to mesenchymal transition
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Michel Salzet, Isabelle Fournier, Marco Marchisio, Pasquale Simeone, Tristan Cardon, Daniele Vergara, Michele Maffia, Marco Trerotola, Julien Franck, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Center of Excellence on Aging and Translational Medicine (CeSI-MeT), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Salento [Lecce], Liceo Classico Giovanni Paolo II [Lecce LE, Italie], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Simeone, P, Trerotola, M, Franck, J, Cardon, T, Marchisio, M, Fournier, I, Salzet, M, Maffia, M, Vergara, D., and SALZET, Michel
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0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,Transcription, Genetic ,Plasticity ,Slug ,[SDV]Life Sciences [q-bio] ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Multiverse ,Transcriptional regulation ,Animals ,Humans ,Epithelial–mesenchymal transition ,Transcription factor ,Epithelial Cells ,biology.organism_classification ,Phenotype ,Cell biology ,[SDV] Life Sciences [q-bio] ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,RNA splicing ,embryonic structures ,Zeb1 ,Epithelial mesenchymal transition ,Single layer ,Transcription Factors - Abstract
International audience; The epithelial mesenchymal transition (EMT) program is defined as a cellular transition from an epithelial to a mesenchymal state. This process occurs to provide the cell with new phenotypic assets and new skills to perform complex processes. EMT is regulated at multilayer levels, including transcriptional control of gene expression, regulation of RNA splicing, and translational/post-translational control. Although transcriptional regulation by EMT-inducing transcription factors (EMT-TFs), including Zeb, Snail and Slug members, is generally considered the master step in this process, emerging data indicate that all these regulatory networks may have a role in the control of EMT. There is a sort of parallelism between the biological and still unrevealed EMT complexity and the cosmological hypothesis that sustains the universe may exist as a multiverse. The presence of different EMT transition states together with the occurrence of multiple layers of regulation support the idea that EMT is just one on many out there. Is the activation of a single layer of regulation sufficient to initiate the whole EMT program? Can we postulate the activation of different EMT "dimensions"? If we think about these layers as multiple separate "universes", various scenarios can be revealed.
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- 2019
46. Distinct Protein Expression Networks are Activated in Microglia Cells after Stimulation with IFN-γ and IL-4
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Michele Maffia, Angelo Quattrini, Tristan Cardon, Stefania De Domenico, Julien Franck, Roberto Furlan, Maxence Wistorski, Michel Salzet, Chiara Coricciati, Alessandro Romano, Marina Damato, Annamaria Nigro, Isabelle Fournier, Daniele Vergara, Vergara, D, Nigro, A, Romano, A, De Domenico, S, Damato, Marina, Franck, J, Coricciati, C, Wistorski, M, Cardon, T, Fournier, I, Quattrini, A, Salzet, M, Furlan, R, Maffia, M., INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, University of Salento [Lecce], IRCCS San Raffaele Scientific Institute [Milan, Italie], Institute of Sciences of Food Production [ISPA], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM], IRCCS Ospedale San Raffaele [Milan, Italy], SALZET, Michel, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)
- Subjects
Proteomics ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,Population ,microglia ,Stimulation ,Article ,microglia plasticity ,Cell Line ,03 medical and health sciences ,Interferon-gamma ,0302 clinical medicine ,Immune system ,medicine ,Humans ,education ,lcsh:QH301-705.5 ,IFN-γ ,Interleukin 4 ,030304 developmental biology ,mass spectrometry ,0303 health sciences ,education.field_of_study ,Proteomic Profile ,Microglia ,Chemistry ,IL-4 ,Proteins ,General Medicine ,Macrophage Activation ,proteomics ,IFN-gamma ,Cell biology ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Phenotype ,lcsh:Biology (General) ,nervous system ,Cell culture ,Interleukin-4 ,Signal transduction ,030217 neurology & neurosurgery ,Metabolic Networks and Pathways ,Signal Transduction - Abstract
Microglia cells are the primary immune population of the central nervous system with a role in the regulation of several physiological and pathological conditions. Upon appropriate stimulation, microglia cells can be polarized in a pro-inflammatory M1-like or anti-inflammatory M2-like status. Biological processes and pathways engaged in microglia polarization are starting to be elucidated. To help clarify this, we used a liquid chromatography-mass spectrometry (LC-MS/MS) label free approach to characterize the proteomic profile of human microglia cell line (CHME-5) stimulated with gamma-interferon (IFN-&gamma, ) and interleukin-4 (IL-4) to induce a M1 or M2 phenotype, respectively. Outside the classical M1/M2 polarization markers, the M1 status appears to center around the activation of a classical inflammatory response and through the activation of multiple signaling pathways. M2 polarization resulted in a different pattern of protein modulation related to RNA and cellular metabolic processes. Together, our findings provide information regarding the protein changes specific to M1 and M2 activation states, and potentially link the polarization of microglia cells to the acquisition of a specific proteomic profile.
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- 2019
47. A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program
- Author
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Francesco De Nuccio, Angelo Santino, Loredana Capobianco, Stefania De Domenico, Michele Maffia, Isabelle Fournier, Antonio Gaballo, Anna Maria Giudetti, Michel Salzet, Pasquale Simeone, Julien Franck, Giuseppe Nicolardi, Paola Lanuti, Paola Lunetti, Andrea Ragusa, Daniele Vergara, University of Salento [Lecce], Biotecgen [Lecce, Italy], Department of Biological and Environmental Sciences and Technologies [Lecce, Italy], CNR NANOTEC - Institute of Nanotechnology [Lecce, Italy], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Giudetti, A, De Domenico, S., Ragusa, A., Lunetti, P., Gaballo, A., Franck, J., Simeone, P., Nicolardi, G., De Nuccio, F., Santino, A., Capobianco, L., Lanuti, P., Fournier, I., Salzet, M., Maffia, M., Vergara, D., Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and SALZET, Michel
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Proteomics ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,β-Catenin ,[SDV]Life Sciences [q-bio] ,Breast Neoplasms ,Carbohydrate metabolism ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Lipid droplet ,Humans ,Epithelial–mesenchymal transition ,Molecular Biology ,Phospholipids ,Triglycerides ,beta Catenin ,Fatty acid synthesis ,chemistry.chemical_classification ,Mass spectrometry ,Chemistry ,Lipogenesis ,Fatty Acids ,Lipid metabolism ,Cell Biology ,Metabolism ,Lipid Metabolism ,Lipids ,[SDV] Life Sciences [q-bio] ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis ,Metabolome ,Cadherin ,epithelial-to-mesenchymal transition ,Transcriptome ,Epithelial mesenchymal transition ,Polyunsaturated fatty acid - Abstract
International audience; Several studies have identified a specific metabolic program that is associated with the process of epithelial-mesenchymal transition (EMT). Whereas much is known about the association between glucose metabolism and EMT, the contribution of lipid metabolism is not still completely understood. Here, we studied epithelial and mesenchymal breast cancer cells by proteomic and lipidomic approaches and identified significant differences that characterised these models concerning specific metabolic enzymes and metabolites including fatty acids and phospholipids. Higher levels of monounsaturated fatty acids together with increased expression of enzymes of de novo fatty acid synthesis is the distinct signature of epithelial with respect to mesenchymal cells that, on the contrary, show reduced lipogenesis, higher polyunsaturated fatty acids level and increased expression of genes involved in the triacylglycerol (TAG) synthesis and lipid droplets formation. In the mesenchymal model, the diacylglycerol acyltransferase (DGAT)-1 appears to be the major enzyme involved in TAG synthesis and inhibition of DGAT1, but not DGAT2, drastically reduces the incorporation of labeled palmitate into TAG. Moreover, knockdown of β-catenin demonstrated that this metabolic phenotype in under the control of a network of transcriptional factors and that β-catenin has a specific role in the regulation of lipid metabolism in mesenchymal cells.
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- 2019
48. The Cancer Microbiota: EMT and Inflammation as Shared Molecular Mechanisms Associated with Plasticity and Progression
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Daniele Vergara, Michele Maffia, Marco Trerotola, Paola Lanuti, Pasquale Simeone, Marina Damato, Vergara, D., Simeone, P., Damato, M., Maffia, M., Lanuti, P., Trerotola, M., Vergara, Daniele, Simeone, Pasquale, Damato, Marina, Maffia, Michele, Lanuti, Paola, and Trerotola, Marco
- Subjects
0301 basic medicine ,Biological therapies ,business.industry ,Reproductive tract ,Human microbiome ,Cancer ,Inflammation ,Review Article ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,medicine.symptom ,business ,Dysbiosis ,Human cancer ,Therapeutic strategy - Abstract
With the advent of novel molecular platforms for high-throughput/next-generation sequencing, the communities of commensal and pathogenic microorganisms that inhabit the human body have been defined in depth. In the last decade, the role of microbiota-host interactions in driving human cancer plasticity and malignant progression has been well documented. Germ-free preclinical models provided an invaluable tool to demonstrate that the human microbiota can confer susceptibility to various types of cancer and can also modulate the host response to therapeutic treatments. Of interest, besides the detrimental effects of dysbiosis on cancer etiopathogenesis, specific microorganisms have been shown to exert protective activities against cancer growth. This has strong clinical implications, as restoration of the physiologic microbiota is being rapidly implemented as a novel anticancer therapeutic strategy. Here, we reviewed past and recent literature depicting the role of microbiota-host interactions in modulating key molecular mechanisms that drive human cancer plasticity and lead to malignant progression. We analyzed microbiota-host interactions occurring in the gut as well as in other anatomic sites, such as oral and nasal cavities, lungs, breast, esophagus, stomach, reproductive tract, and skin. We revealed a common ground of biological alterations and pathways modulated by a dysbiotic microbiota and potentially involved in the control of cancer progression. The molecular mechanisms most frequently affected by the pathogenic microorganisms to induce malignant progression involve epithelial-mesenchymal transition- (EMT-) dependent barrier alterations and tumor-promoting inflammation. This evidence may pave the way to better stratify high-risk cancer patients based on unique microenvironmental/microbial signatures and to develop novel, personalized, biological therapies.
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- 2019
49. NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus
- Author
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Francesco Prattichizzo, Gianluca Storci, Francesco Paolo Fanizzi, Emanuela Mensà, Sara Bravaccini, Anna Rita Bonfigli, Andrea Ragusa, Massimiliano Bonafè, Andrea Casadei-Gardini, Daniele Vergara, Jacopo Sabbatinelli, Francesca Pirini, Serena De Matteis, Anna Maria Giudetti, Michele Maffia, Laura Del Coco, Fabiola Olivieri, Del Coco, Laura, Vergara, Daniele, De Matteis, Serena, Mensà, Emanuela, Sabbatinelli, Jacopo, Prattichizzo, Francesco, Bonfigli, Anna Rita, Storci, Gianluca, Bravaccini, Sara, Pirini, Francesca, Ragusa, Andrea, Casadei-Gardini, Andrea, Bonafè, Massimiliano, Maffia, Michele, Fanizzi, Francesco Paolo, Olivieri, Fabiola, Giudetti, Anna Maria, Del Coco, L, Vergara, D, De Matteis, S, Mensà, E, Sabbatinelli, J, Prattichizzo, F, Bonfigli, Ar, Storci, G, Bravaccini, S, Pirini, F, Ragusa, A, Casadei-Gardini, A, Bonafè, M, Maffia, M, Fanizzi, Fp, Olivieri, F, and Giudetti, Am
- Subjects
medicine.medical_specialty ,branched-chain amino acid ,endocrine system diseases ,type 2 diabetes mellitus ,medicine.medical_treatment ,Protein metabolism ,lcsh:Medicine ,Gastroenterology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,NMR spectroscopy ,Valine ,Internal medicine ,medicine ,Metabolome ,branched-chain amino acids ,030304 developmental biology ,0303 health sciences ,Methionine ,business.industry ,Insulin ,Metabolic disorder ,lcsh:R ,Type 2 Diabetes Mellitus ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,metabolomics ,Glutamine ,chemistry ,030220 oncology & carcinogenesis ,business ,metabolomic - Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naï, ve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.
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- 2019
50. Metabolic reprogramming in breast cancer results in distinct mitochondrial bioenergetics between luminal and basal subtypes
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Loredana Capobianco, Stefania De Domenico, Paola Lunetti, Vincenzo Zara, Daniele Vergara, Michele Maffia, Alessandra Ferramosca, Mariangela Di Giacomo, Lunetti, P, Di Giacomo, M, Vergara, D, De Domenico, S, Maffia, M, Zara, V, Capobianco, L, and Ferramosca, A
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Bioenergetics ,Breast Neoplasms ,Oxidative phosphorylation ,Biology ,Mitochondrion ,Biochemistry ,Oxidative Phosphorylation ,03 medical and health sciences ,Adenosine Triphosphate ,Oxygen Consumption ,0302 clinical medicine ,Tumor Cells, Cultured ,medicine ,Humans ,Glycolysis ,Molecular Biology ,Gene knockdown ,Cancer ,Cell Biology ,Cellular Reprogramming ,medicine.disease ,Phenotype ,Mitochondria ,Cell biology ,030104 developmental biology ,Carcinoma, Basal Cell ,030220 oncology & carcinogenesis ,Cancer cell ,Female ,Bioenergetic, mitochondria, oxidative stress, EMT, breast cancer ,Energy Metabolism ,Reactive Oxygen Species ,Oxidation-Reduction - Abstract
Mitochondrial dysfunction is a key feature of cancer and is frequently associated with increased aggressiveness and metastatic potential. Recent evidence has brought to light a metabolic rewiring that takes place during the epithelial-to-mesenchymal transition (EMT), a process that drives the invasive capability of malignant tumors, and highlights a mechanistic link between mitochondrial dysfunction and EMT that has been only partially investigated. In this study, we characterized mitochondrial function and bioenergetic status of cultured human breast cancer cell lines, including luminal-like and basal-like subtypes. Through a combination of biochemical and functional studies, we demonstrated that basal-like cell lines exhibit impaired, but not completely inactive, mitochondrial function, and rely on a consequent metabolic switch to glycolysis to support their ATP demand. These altered metabolic activities are linked to modifications of key electron transport chain proteins and a significant increase in levels of reactive oxygen species compared to luminal cells. Furthermore, we observed that the stable knockdown of EMT markers caused functional changes in mitochondria that result in acquisition of a hybrid glycolysis/OXPHOS phenotype in cancer cells as a means to sustain their metabolic demand.
- Published
- 2019
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