126 results on '"Maffia, M"'
Search Results
2. 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
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- 2021
3. Spatio-temporal analysis of rat peripheral nerve regeneration
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Maffia, M., primary, Vergara, D., additional, Romano, A., additional, Corricciati, C., additional, Damato, M., additional, Frank, J., additional, Fournier, I., additional, Salzet, M., additional, and Quattrini, A., additional
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- 2019
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4. Physiological role of prion protein in copper homeostasis and angiogenic mechanisms of endothelial cells
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Rizzo, F., primary, De Riccardis, L., additional, Garzarelli, V., additional, Intini, C., additional, Greco, M., additional, Maffia, M., additional, and Urso, E., additional
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- 2019
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5. 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.
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- 2005
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6. 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.
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- 2005
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7. Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects
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De Riccardis, L., primary, Buccolieri, A., additional, Muci, M., additional, Pitotti, E., additional, De Robertis, F., additional, Trianni, G., additional, Manno, D., additional, and Maffia, M., additional
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- 2018
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8. Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients
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Frassanito, M A, primary, De Veirman, K, additional, Desantis, V, additional, Marzo, L Di, additional, Vergara, D, additional, Ruggieri, S, additional, Annese, T, additional, Nico, B, additional, Menu, E, additional, Catacchio, I, additional, Ria, R, additional, Racanelli, V, additional, Maffia, M, additional, Angelucci, E, additional, Derudas, D, additional, Fumarulo, R, additional, Dammacco, F, additional, Ribatti, D, additional, Vanderkerken, K, additional, and Vacca, A, additional
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- 2015
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9. 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
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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.
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- 2010
10. Lipid and Fatty Acid Compositions of Mytilus galloprovincialis Cultured in the Mar Grande of Taranto (Southern Italy): Feeding Strategies and Trophic Relationships
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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.
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- 2010
11. NA+/H+ exchange in the kidneys of eels adapted to sea-water or to fresh water environments: Studies with brush border membrane vesicles
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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.
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- 1991
12. 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.
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- 1990
13. Exploring Local Flexibility/Rigidity in Psychrophilic and Mesophilic Carbonic Anhydrases
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Chiuri, R., primary, Maiorano, G., additional, Rizzello, A., additional, del Mercato, L.L., additional, Cingolani, R., additional, Rinaldi, R., additional, Maffia, M., additional, and Pompa, P.P., additional
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- 2009
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14. Characterisation of intestinal peptide transporter of the Antarctic haemoglobinless teleostChionodraco hamatus
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Maffia, M., primary, Rizzello, A., additional, Acierno, R., additional, Verri, T., additional, Rollo, M., additional, Danieli, A., additional, Döring, F., additional, Daniel, H., additional, and Storelli, C., additional
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- 2003
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15. Carbonic anhydrase activity in tissues of the icefish Chionodraco hamatus and of the red-blooded teleosts Trematomus bernacchii and Anguilla anguilla
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Maffia, M., primary, Rizzello, A., additional, Acierno, R., additional, Rollo, M., additional, Chiloiro, R., additional, and Storelli, C., additional
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- 2001
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16. Characterisation of the H(+)/peptide cotransporter of eel intestinal brush-border membranes
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Verri, T., primary, Maffia, M., additional, Danieli, A., additional, Herget, M., additional, Wenzel, U., additional, Daniel, H., additional, and Storelli, C., additional
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- 2000
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17. Rabbit small intestinal trehalase. Purification, cDNA cloning, expression, and verification of glycosylphosphatidylinositol anchoring.
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Ruf, J., primary, Wacker, H., additional, James, P., additional, Maffia, M., additional, Seiler, P., additional, Galand, G., additional, von Kieckebusch, A., additional, Semenza, G., additional, and Matei, N., additional
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- 1990
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18. Characterisation of intestinal peptide transporter of the Antartic haemoglobinless teleost Chionodraco hamatus.
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Maffia, M., Rizzelo, A., Acierno, R., Verri, T., Rollo, M., Danieli, A., Döring, F., Daniel, H., and Storelli, C.
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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]
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- 2003
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19. La competenza scritta in italiano L2 di apprendenti vulnerabili
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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.
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- 2019
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20. Brush border amino acid transport mechanisms in carnivourus eel intestine
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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.
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- 1989
21. Optical characterization of glutamate dehydrogenase monolayers chemisorbed on SiO2
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Pompa, P. P., Blasi, L., Longo, L., Cingolani, R., Ciccarella, G., Vasapollo, G., ROSARIA RINALDI, Rizzello, A., Storelli, C., Maffia, M., P. P., Pompa, L., Blasi, L., Longo, Cingolani, Roberto, Ciccarella, Giuseppe, Vasapollo, Giuseppe, Rinaldi, Rosaria, A., Rizzello, Storelli, Carlo, and Maffia, Michele
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This paper describes the formation of glutamate dehydrogenase monolayers on silicon dioxide, and their characterization by phys. techniques, i.e., fluorescence spectroscopy and Fourier-transform IR spectroscopy. Detailed investigations of the intrinsic stability of native proteins in soln. were carried out to elucidate the occurrence of conformational changes induced by the immobilization procedure. The enzyme monolayers were deposited on SiO2 after pre-exposing silicon surfaces to 3-aminopropyltriethoxysilane and reacting the silylated surfaces with glutaric dialdehyde. The optical characterization demonstrates that the immobilization does not interfere with the fold pattern of the native enzyme. In addn., fluorescence spectroscopy, thermal denaturation, and quenching studies performed on the enzyme in soln. well describe the folding and unfolding properties of glutamate dehydrogenase. The photophys. studies reported here are relevant for nanobioelectronics applications requiring protein immobilization on a chip.
22. A Hidden Human Proteome Signature Characterizes the Epithelial Mesenchymal Transition Program
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Michele Maffia, Marco Trerotola, Marina Damato, Isabelle Fournier, Julien Franck, Daniele Vergara, Tiziano Verri, Pasquale Simeone, Michel Salzet, University of Salento [Lecce], Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), 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), SALZET, Michel, Vergara, D., Verri, T., Damato, M., Trerotola, M., Simeone, P., Franck, J., Fournier, I., Salzet, M., and Maffia, M.
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Gene isoform ,Epithelial-Mesenchymal Transition ,Proteome ,alternative proteins ,proteome ,[SDV]Life Sciences [q-bio] ,Predicted isoform ,Breast Neoplasms ,Inflammation ,Computational biology ,Biology ,03 medical and health sciences ,Breast cancer ,breast cancer ,0302 clinical medicine ,Cell Line, Tumor ,Drug Discovery ,medicine ,Human proteome project ,Humans ,Epithelial–mesenchymal transition ,OpenProt database ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Cancer ,predicted isoforms ,medicine.disease ,[SDV] Life Sciences [q-bio] ,Open reading frame ,030220 oncology & carcinogenesis ,MCF-7 Cells ,medicine.symptom ,Alternative protein ,Epithelial mesenchymal transition - Abstract
Background: Molecular changes associated with the initiation of the epithelial to mesenchymal transition (EMT) program involve alterations of large proteome-based networks. The role of protein products mapping to non-coding genomic regions is still unexplored. Objective: The goal of this study was the identification of an alternative protein signature in breast cancer cellular models with a distinct expression of EMT markers. Methods: We profiled MCF-7 and MDA-MB-231 cells using liquid-chromatography mass/spectrometry (LCMS/ MS) and interrogated the OpenProt database to identify novel predicted isoforms and novel predicted proteins from alternative open reading frames (AltProts). Results: Our analysis revealed an AltProt and isoform protein signature capable of classifying the two breast cancer cell lines. Among the most highly expressed alternative proteins, we observed proteins potentially associated with inflammation, metabolism and EMT. Conclusion: Here, we present an AltProts signature associated with EMT. Further studies will be needed to define their role in cancer progression.
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- 2020
23. 3D-microenvironments initiate TCF4 expression rescuing nuclear β-catenin activity in MCF-7 breast cancer cells
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Sara Sergio, Addolorata Coluccia, Ferruccio Pisanello, Enrico Domenico Lemma, Barbara Spagnolo, Massimo De Vittorio, Daniele Vergara, Michele Maffia, Sergio, S., Coluccia, A., Lemma, E. D., Spagnolo, B., Vergara, D., Maffia, M., De Vittorio, M., and Pisanello, F.
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T cell ,0206 medical engineering ,Biomedical Engineering ,Breast Neoplasms ,Cell Communication ,02 engineering and technology ,Biology ,medicine.disease_cause ,Biochemistry ,Biomaterials ,Tumor Microenvironment ,medicine ,Humans ,Vimentin ,Neoplasm Invasiveness ,Mechanotransduction ,Molecular Biology ,Transcription factor ,beta Catenin ,Cell Proliferation ,Cell Nucleus ,Cell Membrane ,General Medicine ,Cadherins ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Cell biology ,medicine.anatomical_structure ,MCF-7 ,Catenin ,Cancer cell ,MCF-7 Cells ,Female ,Signal transduction ,0210 nano-technology ,Carcinogenesis ,Transcription Factor 7-Like 2 Protein ,Biotechnology - Abstract
Mechanical cues sensed by tumor cells in their microenvironment can influence important mechanisms including adhesion, invasion and proliferation. However, a common mechanosensitive protein and/or pathway can be regulated in different ways among diverse types of tumors. Of particular interest are human breast epithelial cancers, which markedly exhibit a heterogeneous pattern of nuclear β-catenin localization, a protein known to be involved in both mechanotransduction and tumorigenesis. β-catenin can be aberrantly accumulated in the nucleus wherein it binds to and activates lymphoid enhancer factor/T cell factor (LEF/TCF) transcription factors. At present, little is known about how mechanical cues are integrated into breast cancer cells harboring impaired mechanisms of β-catenin's nuclear uptake and/or retention. This prompted us to investigate the influence of mechanical cues on MCF-7 human breast cancer cells which are known to fail in relocating β-catenin into the nucleus due to very low baseline levels of LEF/TCFs. Exploiting three-dimensional (3D) microscaffolds realized by two-photon lithography, we show that surrounding MCF-7 cells have not only a nuclear pool of β-catenin, but also rescue from their defective expression of TCF4 and boost invasiveness. Together with heightened amounts of vimentin, a β-catenin/TCF-target gene regulator of proliferation and invasiveness, such 3D-elicited changes indicate an epithelial-to-mesenchymal phenotypic switch of MCF-7 cells. This is also consistent with an increased in situ MCF-7 cell proliferation that can be abrogated by blocking β-catenin/TCF-transcription activity. Collectively, these data suggest that 3D microenvironments are per se sufficient to prime a TCF4-dependent rescuing of β-catenin nuclear activity in MCF-7 cells. The employed methodology could, therefore, provide a mechanism-based rationale to dissect further aspects of mechanotranscription in breast cancerogenesis, somewhat independent of β-catenin's nuclear accumulation. More importantly, by considering the heterogeneity of β-catenin signaling pathway in breast cancer patients, these data may open alternative avenues for personalized disease management and prevention. Statement of significance: Mechanical cues play a critical role in cancer pathogenesis. Little is known about their influence in breast cancer cells harboring impaired mechanisms of β-catenin's nuclear uptake and/or retention, involved in both mechanotransduction and tumorigenesis. We engineered 3D scaffold, by two-photon lithography, to study the influence of mechanical cues on MCF-7 cells which are known to fail in relocating β-catenin into the nucleus. We found that 3D microenvironments are per se sufficient to prime a TCF4-dependent rescuing of β-catenin nuclear activity that boost cell proliferation and invasiveness. Thus, let us suggest that our system could provide a mechanism-based rationale to further dissect key aspects of mechanotranscription in breast cancerogenesis and progression, somewhat independent of β-catenin's nuclear accumulation. © 2019
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- 2020
24. The Biological Relevance of NHERF1 Protein in Gynecological Tumors
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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
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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.
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- 2022
25. Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis
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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.
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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.
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- 2021
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26. Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes
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Pietrina Romano, Emanuela Civino, Nicola Di Renzo, Elena Pitotti, Michele Maffia, Marcello Salvatore Lenucci, Giammarco Surico, Cosimo Neglia, Daniele Vergara, Alessandro Distante, Prisco Piscitelli, Giampiero Romano, Andrea Ragusa, Ragusa, A., Romano, P., Lenucci, M. S., Civino, E., Vergara, D., Pitotti, E., Neglia, C., Distante, A., Romano, G. D., Di Renzo, N., Surico, G., Piscitelli, P., and Maffia, M.
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glycoprotein ,Saliva ,Glycosylation ,glycosylation ,Endocrinology, Diabetes and Metabolism ,Mannose ,Bioinformatics ,Microbiology ,Biochemistry ,Article ,glycomics ,Abnormal glycosylation ,chemistry.chemical_compound ,Breast cancer ,breast cancer ,HPEAC-PAD ,fucose ,medicine ,Lung cancer ,Molecular Biology ,Fucose ,chemistry.chemical_classification ,Glucosamine ,saliva ,business.industry ,mannose ,Early diagnosi ,medicine.disease ,QR1-502 ,lung cancer ,chemistry ,Glycomic ,glucosamine ,Cancer biomarkers ,Glycoprotein ,business ,early diagnosis - Abstract
Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.
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- 2021
27. Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks
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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.
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- 2021
28. Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
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Claudia Pagano, Michele Maffia, Debora Musarò, Simona Di Giulio, Daniela Manno, Marco Greco, Chiara Carmela Spinelli, Alessandro Buccolieri, Lidia De Riccardis, Greco, M., Spinelli, C. C., De Riccardis, L., Buccolieri, A., Di Giulio, S., Musaro, D., Pagano, C., Manno, D., and Maffia, M.
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0301 basic medicine ,Cellular differentiation ,medicine.disease_cause ,lcsh:Chemistry ,Neuroblastoma ,0302 clinical medicine ,Copper Transport Proteins ,oxidative stress ,Phosphorylation ,lcsh:QH301-705.5 ,Spectroscopy ,chemistry.chemical_classification ,α‐synuclein ,Chemistry ,Kinase ,ROS ,Cell Differentiation ,General Medicine ,Parkinson’s disease (PD) ,Computer Science Applications ,Cell biology ,Transport protein ,alpha-Synuclein ,Cell Survival ,Oxidative phosphorylation ,Protein Serine-Threonine Kinases ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,α-synuclein ,Cell Line, Tumor ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Reactive oxygen species ,Organic Chemistry ,Protein phosphatase 2 ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,nervous system ,Copper-Transporting ATPases ,Oxidative stre ,030217 neurology & neurosurgery ,Oxidative stress ,Copper ,Molecular Chaperones - Abstract
Copper (Cu) dyshomeostasis plays a pivotal role in several neuropathologies, such as Parkinson’s disease (PD). Metal accumulation in the central nervous system (CNS) could result in loss-of-function of proteins involved in Cu metabolism and redox cycling, generating reactive oxygen species (ROS). Moreover, neurodegenerative disorders imply the presence of an excess of misfolded proteins known to lead to neuronal damage. In PD, Cu accumulates in the brain, binds α-synuclein, and initiates its aggregation. We assessed the correlation between neuronal differentiation, Cu homeostasis regulation, and α-synuclein phosphorylation. At this purpose, we used differentiated SHSY5Y neuroblastoma cells to reproduce some of the characteristics of the dopaminergic neurons. Here, we reported that differentiated cells expressed a significantly higher amount of a copper transporter protein 1 (CTR1), increasing the copper uptake. Cells also showed a significantly more phosphorylated form of α-synuclein, further increased by copper treatment, without modifications in α-synuclein levels. This effect depended on the upregulation of the polo-like kinase 2 (PLK2), whereas the levels of the relative protein phosphatase 2A (PP2A) remained unvaried. No changes in the oxidative state of the cells were identified. The Cu dependent alteration of α-synuclein phosphorylation pattern might potentially offer new opportunities for clinical intervention.
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- 2021
29. 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
30. 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
31. 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
32. 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
33. 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)
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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
34. A specific lipid metabolic profile is associated with the epithelial mesenchymal transition program
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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
35. 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
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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
36. NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus
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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
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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
37. 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
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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.
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- 2019
38. Comparative proteomic profiling of Hodgkin lymphoma cell lines
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Claudio Agostinelli, S. De Matteis, Marco Marchisio, Michele Maffia, Pasquale Simeone, Sebastiano Miscia, Silvia Carloni, Paola Lanuti, Daniele Vergara, Roberta Napolitano, Antonio Rizzello, Vergara, D., Simeone, P., De Matteis, S., Carloni, S., Lanuti, P., Marchisio, M., Miscia, S., Rizzello, A., Napolitano, R., Agostinelli, C., Maffia, M., Vergara, Daniele, Simeone, P, De Matteis, S, Carloni, S, Lanuti, P, Marchisio, M, Miscia, S, Rizzello, Antonia, Napolitano, R, Agostinelli, C, and Maffia, Michele
- Subjects
Proteomics ,0301 basic medicine ,Proteome ,macromolecular substances ,Biology ,Models, Biological ,Flow cytometry ,Pathogenesis ,03 medical and health sciences ,Cell Line, Tumor ,Protein Interaction Mapping ,medicine ,Humans ,Protein Interaction Maps ,Molecular Biology ,medicine.diagnostic_test ,Proteomic Profiling ,Proteomic ,Cell migration ,Flow Cytometry ,Hodgkin Disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Blot ,030104 developmental biology ,Cell culture ,Protein Interaction Map ,Human ,Biotechnology - Abstract
Classical Hodgkin lymphoma (cHL) is a malignancy with complex pathogenesis. The hallmark of the disease is the presence of large mononucleated Hodgkin and bi- or multinucleated Reed/Sternberg (H/RS) cells. The origin of HRS cells in cHL is controversial as these cells show the coexpression of markers of several lineages. Using a proteomic approach, we compared the protein expression profile of cHL models of T- and B-cell derivation to find proteins differentially expressed in these cell lines. A total of 67 proteins were found differentially expressed between the two cell lines including metabolic proteins and proteins involved in the regulation of the cytoskeleton and/or cell migration, which were further validated by western blotting. Additionally, the expression of selected B- and T-cell antigens was also assessed by flow cytometry to reveal significant differences in the expression of different surface markers. Bioinformatics analysis was then applied to our dataset to find enriched pathways and networks, and to identify possible key regulators. In the present study, a proteomic approach was used to compare the protein expression profiles of two cHL cell lines. The identified proteins and/or networks, many of which not previously related to cHL, may be important to better define the pathogenesis of the disease, to identify novel diagnostic markers, and to design new therapeutic strategies.
- Published
- 2016
39. Proteomic expression profile of injured rat peripheral nerves revealed biological networks and processes associated with nerve regeneration
- Author
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Alessandro Sannino, Stefania De Domenico, Michel Salzet, Isabelle Fournier, Anna Maria Giudetti, Velia La Pesa, Alessandro Romano, Ilaria Cicalini, Eleonora Stanca, Daniele Vergara, Angelo Quattrini, Damiana Pieragostino, Federica Cerri, Elisa Storelli, Laura Aloisi, Michele Maffia, Julien Franck, University of Salento [Lecce], Liceo Classico Giovanni Paolo II [Lecce LE, Italie], IRCCS Ospedale San Raffaele [Milan, Italy], Institute of Food Production Sciences [Lecce, Italy], 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 'G. d'Annunzio' of Chieti-Pescara [Chieti], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SALZET, Michel, Vergara, D, Romano, A, Stanca, E, La Pesa, V, Aloisi, Al, De Domenico, S, Franck, J, Cicalini, I, Giudetti, Am, Storelli, E, Pieragostino, D, Fournier, I, Sannino, A, Salzet, M, Cerri, F, Quattrini, A, and Maffia, M
- Subjects
0301 basic medicine ,Physiology ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,Proteomics ,DGAT ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,proteomics ,Tandem Mass Spectrometry ,lipid metabolism ,medicine ,Animals ,peripheral nerve injury ,Diacylglycerol O-Acyltransferase ,LC-MS/MS ,Cytoskeleton ,Chemistry ,Regeneration (biology) ,Computational Biology ,Lipid metabolism ,Cell Biology ,Metabolism ,Nerve injury ,Sciatic Nerve ,Cell biology ,Nerve Regeneration ,Rats ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Peripheral nerve injury ,Female ,Sciatic nerve ,Schwann Cells ,medicine.symptom ,Nervous System Diseases ,030217 neurology & neurosurgery ,Chromatography, Liquid ,Signal Transduction - Abstract
International audience; Peripheral nerve regeneration is regulated through the coordinated spatio-temporal activation of multiple cellular pathways. In this work, an integrated proteomics and bioinformatics approach was employed to identify differentially expressed proteins at the injury-site of rat sciatic nerve at 20 days after damage. By a label-free liquid chromatography mass-spectrometry (LC-MS/MS) approach, we identified 201 differentially proteins that were assigned to specific canonical and disease and function pathways. These include proteins involved in cytoskeleton signaling and remodeling, acute phase response, and cellular metabolism. Metabolic proteins were significantly modulated after nerve injury to support a specific metabolic demand. In particular, we identified a group of proteins involved in lipid uptake and lipid storage metabolism. Immunofluorescent staining for acyl-CoA diacylglycerol acyltransferase 1 (DGAT1) and DAGT2 expression provided evidence for the expression and localization of these two isoforms in Schwann cells at the injury site in the sciatic nerve. This further supports a specific local regulation of lipid metabolism in peripheral nerve after damage.
- Published
- 2018
40. An SPR based immunoassay for the sensitive detection of the soluble epithelial marker E-cadherin
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Ludovico Valli, Loredana Capobianco, Alessandra Zizzari, Monica Bianco, Elena Pitotti, Livia Giotta, Valentina Arima, Sonia Carallo, Flora Guerra, Daniele Vergara, Paola Lunetti, Rosanna Pagano, Michele Maffia, Antonio Gaballo, Paola Priore, Simona Bettini, Cecilia Bucci, Vergara, D, Bianco, M, Pagano, R, Priore, P, Lunetti, P, Guerra, F, Bettini, S, Carallo, S, Zizzari, A, Pitotti, E, Giotta, L, Capobianco, L, Bucci, C, Valli, L, Maffia, M, Arima, V, and Gaballo, A.
- Subjects
0301 basic medicine ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Context (language use) ,Breast Neoplasms ,Biosensing Techniques ,Diagnostic tools ,03 medical and health sciences ,Antigens, CD ,Limit of Detection ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Humans ,General Materials Science ,Surface plasmon resonance ,Detection limit ,Immunoassay ,medicine.diagnostic_test ,Cadherin ,Chemistry ,Cancer ,Surface Plasmon Resonance ,medicine.disease ,Cadherins ,030104 developmental biology ,Biochemistry ,Molecular Medicine ,Biomarker (medicine) ,Female - Abstract
Protein biomarkers are important diagnostic tools for cancer and several other diseases. To be validated in a clinical context, a biomarker should satisfy some requirements including the ability to provide reliable information on a pathological state by measuring its expression levels. In parallel, the development of an approach capable of detecting biomarkers with high sensitivity and specificity would be ideally suited for clinical applications. Here, we performed an immune-based label free assay using Surface Plasmon Resonance (SPR)-based detection of the soluble form of E-cadherin, a cell-cell contact protein that is involved in the maintaining of tissue integrity. With this approach, we obtained a specific and quantitative detection of E-cadherin from a few hundred microliters of serum of breast cancer patients by obtaining a 10-fold enhancement in the detection limit over a traditional colorimetric ELISA.
- Published
- 2018
41. Copper and ceruloplasmin dyshomeostasis in serum and cerebrospinal fluid of multiple sclerosis subjects
- Author
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Michele Maffia, M. Muci, L. De Riccardis, Giorgio Trianni, Elena Pitotti, Alessandro Buccolieri, Daniela Manno, F. De Robertis, De Riccardis, L., Buccolieri, A., Muci, M., Pitotti, E., De Robertis, F., Trianni, G., Manno, D., and Maffia, M.
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0301 basic medicine ,Serum ,Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,chemistry.chemical_element ,Oxidative phosphorylation ,medicine.disease_cause ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Internal medicine ,Multiple Sclerosi ,medicine ,Humans ,Molecular Biology ,biology ,business.industry ,Multiple sclerosis ,Ceruloplasmin ,Metabolism ,Middle Aged ,medicine.disease ,Copper ,030104 developmental biology ,Endocrinology ,chemistry ,biology.protein ,Oxidative stre ,Molecular Medicine ,Female ,business ,030217 neurology & neurosurgery ,Oxidative stress ,Human - 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.
- Published
- 2018
42. β-catenin knockdown promotes nherf1-mediated survival of colorectal cancer cells: implications for a double-targeted therapy
- Author
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Michel Salzet, Valeria Famiglini, Concetta Saponaro, Luca Mologni, Giuseppe La Regina, Sara Sergio, Michele Maffia, Romano Silvestri, Candice Gautier, Valentina Naccarato, Addolorata Coluccia, Stefano Gianni, Antonio Coluccia, Carlo Gambacorti Passerini, Daniele Vergara, Maria De Luca, Cecilia Bucci, Isabelle Fournier, Daniela Bonetti, Istituto Tumori 'Giovanni Paolo II' [Bari], Liceo Classico Giovanni Paolo II [Lecce LE, Italie], University of Salento [Lecce], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Laboratorio Pasteur [Istituto Pasteur-Fondazione Cenci Bolognetti, Rome], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), 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), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SALZET, Michel, Saponaro, C, Sergio, S, Coluccia, A, De Luca, M, La Regina, G, Mologni, L, Famiglini, V, Naccarato, V, Bonetti, D, Gautier, C, Gianni, S, Vergara, D, Salzet, M, Fournier, I, Bucci, C, Silvestri, R, Passerini, C, Maffia, M, Passerini, Cg, and Coluccia, Aml
- Subjects
0301 basic medicine ,Cancer Research ,Sodium-Hydrogen Exchangers ,Cell Survival ,[SDV]Life Sciences [q-bio] ,beta-catenin ,nherf1 ,colorectal cancer cells ,Apoptosis ,Biology ,medicine.disease_cause ,Small hairpin RNA ,03 medical and health sciences ,Transcription Factor 4 ,Genetic ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,Gene Knockdown Techniques ,medicine ,Humans ,Molecular Biology ,beta Catenin ,Gene knockdown ,Sulfonamides ,Wnt signaling pathway ,Phosphoproteins ,3. Good health ,Gene Expression Regulation, Neoplastic ,[SDV] Life Sciences [q-bio] ,Protein Transport ,030104 developmental biology ,Catenin ,Mutation ,Cancer research ,KRAS ,Carcinogenesis ,Colorectal Neoplasms ,Chromatin immunoprecipitation - Abstract
International audience; Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+/H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity. Chromatin immunoprecipitation (ChIP) assays demonstrated that β-catenin represses NHERF1 via TCF4 directly, while the association between TCF1 and the Nherf1 promoter increased upon β-catenin knockdown. To note, the occurrence of a cytostatic survival response in settings of single β-catenin-depleted CRC cells was abrogated by combining NHERF1 inhibition via small hairpin RNA (shRNA) or RS5517, a novel PDZ1-domain ligand of NHERF1 that prevented its ectopic nuclear entry. Mechanistically, dual NHERF1/β-catenin targeting promoted an autophagy-to-apoptosis switch consistent with the activation of Caspase-3, the cleavage of PARP and reduced levels of phospho-ERK1/2, Beclin-1, and Rab7 autophagic proteins compared with β-catenin knockdown alone. Collectively, our data unveil novel β-catenin/TCF-dependent mechanisms of CRC carcinogenesis, also offering preclinical proof of concept for combining β-catenin and NHERF1 pharmacological inhibitors as a mechanism-based strategy to augment apoptotic death of CRC cells refractory to current Wnt/β-catenin-targeted therapeutics.
- Published
- 2018
43. Imatinib-loaded polyelectrolyte microcapsules for sustained targeting of BCR-ABL+ leukemia stem cells
- Author
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Ilaria Elena Palamà, Ross Rinaldi, Roberto Cingolani, Nicola Di Renzo, Carlo Gambacorti-Passerini, Stefano Leporatti, Giuseppe Gigli, Addolorata Coluccia, Michele Maffia, Emanuela de Luca, Palamà, I, Leporatti, S, De Luca, E, Di Renzo, N, Maffia, M, Gambacorti-Passerini, C, Rinaldi, R, Gigli, G, Cingolani, R, Coluccia, A, Palamà, I. E., S., Leporatti, E., de Luca, N., Di Renzo, Maffia, Michele, C., Gambacorti Passerini, Rinaldi, Rosaria, G., Gigli, R., Cingolani, A. M., Coluccia, I. E., Palamà, E., DE LUCA, N., DI RENZO, C., GAMBACORTI PASSERINI, Gigli, Giuseppe, Cingolani, Roberto, and Coluccia, Addolorata
- Subjects
Materials science ,layer-by-layer ,Drug delivery system ,microcapsule ,Fusion Proteins, bcr-abl ,Biomedical Engineering ,CD34 ,Medicine (miscellaneous) ,Antineoplastic Agents ,Apoptosis ,Bone Marrow Cells ,Capsules ,Bioengineering ,Development ,Pharmacology ,Piperazines ,Microcapsule ,chronic myeloid leukemia ,imatinib mesylate ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,drug delivery system ,Humans ,General Materials Science ,Progenitor cell ,polyelectrolyte ,Cell Proliferation ,drug resistance ,Stem cell ,Chronic myeloid leukemia ,Myeloid leukemia ,Imatinib ,Polyelectrolyte ,Layer-by-layer ,medicine.disease ,stem cell ,Imatinib mesylate ,Leukemia ,Pyrimidines ,Delayed-Action Preparations ,Drug resistance ,Benzamides ,imatinib mesylate layer-by-layer microcapsules ,polyelectrolytes ,Ex vivo ,medicine.drug - Abstract
Aim: The lack of sensitivity of chronic myeloid leukemia (CML) stem cells to imatinib mesylate (IM) commonly leads to drug dose escalation or early disease relapses when therapy is stopped. Here, we report that packaging of IM into a biodegradable carrier based on polyelectrolyte microcapsules increases drug retention and antitumor activity in CML stem cells, also improving the ex vivo purging of malignant progenitors from patient autografts. Materials & methods: Microparticles/capsules were obtained by layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolyte multilayers on removable calcium carbonate (CaCO3) templates and loaded with or without IM. A leukemic cell line (KU812) and CD34+ cells freshly isolated from healthy donors or CML patients were tested. Results & discussion: Polyelectrolyte microcapsules (PMCs) with an average diameter of 3 µm, fluorescently labelled multilayers sensitive to the action of intracellular proteases and 95–99% encapsulation efficiency of IM, were prepared. Cell uptake efficiency of such biodegradable carriers was quantified in KU812, leukemic and normal CD34+ stem cells (range: 70–85%), and empty PMCs did not impact cell viability. IM-loaded PMCs selectively targeted CML cells, by promoting apoptosis at doses that exert only cytostatic effects by IM alone. More importantly, residual CML cells from patient leukapheresis products were reduced or eliminated more efficiently by using IM-loaded PMCs compared with freely soluble IM, with a purging efficiency of several logs. No adverse effects on normal CD34+ stem-cell survival and their clonogenic potential was noticed in long-term cultures of hematopoietic progenitors in vitro. Conclusion: This pilot study provides the proof-of-principle for the clinical application of biodegradable IM-loaded PMC as feasible, safe and effective ex vivo purging agents to target CML stem cells, in order to improve transplant outcome of resistant/relapsed patients or reduce IM dose escalation.
- Published
- 2010
44. Targeting of GSK3β promotes imatinib-mediated apoptosis in quiescent CD34+ chronic myeloid leukemia progenitors, preserving normal stem cells
- Author
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Luciana Dini, Emanuela de Luca, Carlo Gambacorti Passerini, Addolorata Coluccia, Simone De Leo, Giovanni Reddiconto, Serena De Matteis, Ilaria Elena Palamà, Michele Maffia, Claudia Toto, Nicola Di Renzo, Reddiconto, G, Toto, C, Palamà, I, De Leo, S, de Luca, E, De Matteis, S, Dini, L, GAMBACORTI PASSERINI, C, Di Renzo, N, Maffia, M, Coluccia, A, Dini, Luciana, Passerini, Cg, Maffia, Michele, Coluccia, Am, G., Reddiconto, C., Toto, I., Palamà, S., DE LEO, E., DE LUCA, S., DE MATTEIS, C. G., Passerini, N., DI RENZO, and Coluccia, Addolorata
- Subjects
Indoles ,Dasatinib ,Fusion Proteins, bcr-abl ,Antigens, CD34 ,Apoptosis ,Biochemistry ,Piperazines ,Maleimides ,Glycogen Synthase Kinase 3 ,GSK3-beta, CD34+, chronic myeloid leukemia ,hemic and lymphatic diseases ,Cyclin D1 ,Phosphorylation ,Cells, Cultured ,beta Catenin ,Microscopy, Confocal ,ABL ,Myeloid leukemia ,Drug Synergism ,Hematology ,Protein Transport ,Benzamides ,Imatinib Mesylate ,Neoplastic Stem Cells ,Cytokines ,Mitogen-Activated Protein Kinases ,Stem cell ,Signal Transduction ,medicine.drug ,Blotting, Western ,Proto-Oncogene Proteins pp60(c-src) ,Immunology ,macromolecular substances ,Biology ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Progenitor cell ,Protein Kinase Inhibitors ,neoplasms ,PI3K/AKT/mTOR pathway ,Cell Nucleus ,Glycogen Synthase Kinase 3 beta ,Imatinib ,Cell Biology ,Hematopoietic Stem Cells ,Thiazoles ,Pyrimidines ,Imatinib mesylate ,Cancer research - Abstract
The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)-initiating cells. Activation of beta-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL-dependent Y phosphorylation and impaired binding to GSK3 beta (glycogen synthase kinase 3 beta). Herein, we show that GSK3 beta is constitutively Y-216 phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3 beta activity and its altered subcellular localization were correlated with BCR-ABL-dependent and -independent activation of MAPK and p60-SRC/GSK3 beta complex formation. Specifically, GSK3 beta activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL- and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl-negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the beta-catenin, cyclinD1, C-EBP alpha, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib. (Blood. 2012;119(10):2335-2345)
- Published
- 2012
45. Cuprizone neurotoxicity, copper deficiency and neurodegeneration
- Author
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Stefano Mammi, Benedetto Salvato, Andrea Zitolo, Stefano Ceola, Paola D'Angelo, Donatella Carbonera, Benedetta Salmini, Enzo Spisni, Emanuela Urso, Michele Maffia, Marcello Ventura, Federico Benetti, Benetti F., Ventura M., Salmini B., Ceola S., Carbonera D., Mammi S., Zitolo A., D'Angelo P., Urso E., Maffia M., Salvato B., Spisni E., F., Benetti, M., Ventura, B., Salmini, S., Ceola, D., Carbonera, S., Mammi, A., Zitolo, P., D'Angelo, Urso, Emanuela, Maffia, Michele, B., Salvato, and E., Spisni
- Subjects
medicine.medical_specialty ,Cell Membrane Permeability ,Monoamine Oxidase Inhibitors ,Chemical Phenomena ,Solution chemistry ,Toxicology ,Mass Spectrometry ,Mice ,Neuroblastoma ,Cuprizone ,Internal medicine ,Cell Line, Tumor ,ceruloplasmin activity ,copper deficiency ,cuprizone ,neurodegeneration ,medicine ,Animals ,Humans ,Neurodegeneration ,biology ,Dose-Response Relationship, Drug ,Chemistry ,General Neuroscience ,Spectrophotometry, Atomic ,Cell Cycle ,Neurotoxicity ,Brain ,Ceruloplasmin ,Biological activity ,Status spongiosus ,medicine.disease ,Copper deficiency ,Ceruloplasmin activity ,Disease Models, Animal ,Cuprizone, Copper deficiency, Ceruloplasmin activity, Neurodegeneration ,Endocrinology ,Liver ,Immunology ,Toxicity ,CUPRIZON ,Nerve Degeneration ,biology.protein ,Neurotoxicity Syndromes ,Oxidoreductases ,Copper - Abstract
Cuprizone is used to obtain demyelination in mice. Cuprizone-treated mice show symptoms similar to several neurodegenerative disorders such as severe status spongiosus. Although it has a simple chemical formula, its neurotoxic mechanism is still unknown. In this work, we examined both physico-chemical properties and biological effects of cuprizone. Our results indicate that cuprizone has very complicated and misunderstood solution chemistry. Moreover, we show here the inability of cuprizone to cross neither the intestinal epithelial barrier nor the neuronal cell membrane, as well its high tolerability by cultured neurons. If added to mice diet, cuprizone does not accumulate in liver or in brain. Therefore, its neurotoxic effect is explainable only in terms of its capability to chelate copper, leading to chronic copper deficiency.
- Published
- 2010
46. Molecular and biochemical alterations in epithelial to mesenchymal transition
- Author
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Michele Maffia, Dominga Latorre, Anna Maria Giudetti, Dario Domenico Lofrumento, Loredana Capobianco, Francesco Denuccio, Paola Lunetti, Pasquale Simeone, Daniele Vergara, Giuseppe Nicolardi, Vergara, D, Giudetti, A, Latorre, D, Lunetti, P, Simeone, P, Lofrumento, D, De Nuccio, F, Nicolardi, G, Capobianco, L, and Maffia, M
- Subjects
Chemistry ,Bioengineering ,General Medicine ,Epithelial–mesenchymal transition ,Applied Microbiology and Biotechnology ,Biotechnology ,Cell biology - Published
- 2014
47. Characterisation of the H+/peptide cotransporter of eel intestinal brush-border membranes
- Author
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Michele Maffia, Hannelore Daniel, Antonio Danieli, Tiziano Verri, Carlo Storelli, Martina Herget, Uwe Wenzel, Verri, T, Maffia, M, Danieli, A, Herget, M, Wenzel, U, Daniel, H, and Storelli, C
- Subjects
Brush border ,Physiology ,Biological Transport, Active ,Peptide ,Aquatic Science ,Peptide Transporter 1 ,Animals ,Humans ,Intestinal Mucosa ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,DNA Primers ,chemistry.chemical_classification ,Membrane potential ,Base Sequence ,Microvilli ,Symporters ,biology ,Membrane transport protein ,Peptide transporter 1 ,Membrane Transport Proteins ,Dipeptides ,Anguilla ,Cadherins ,Kinetics ,Membrane ,chemistry ,Biochemistry ,Insect Science ,Symporter ,biology.protein ,Animal Science and Zoology ,Protons ,Carrier Proteins ,Peptides ,Cotransporter - Abstract
H+/peptide cotransport in brush-border membrane vesicles (BBMVs) from eel (Anguilla anguilla) intestine was studied by measuring D-[3H]-phenylalanyl-L-alanine uptake and by monitoring peptide-dependent intravesicular acidification using the pH-sensitive dye Acridine Orange. D-[3H]-phenylalanyl-L-alanine influx was greatly stimulated by an inside-negative membrane potential and enhanced by an inwardly directed H+ gradient. In parallel, vesicular H+ influx was significantly increased in the presence of extravesicular D-phenylalanyl-L-alanine or a series of glycyl and L-prolyl peptides. H+/peptide cotransport displayed saturable kinetics involving a single carrier system with apparent substrate affinities of 0.9–2.6 mmol l−1 depending on the particular peptide. All substrates tested competed with this system. Pre-incubation of BBMVs with dipeptides prevented diethylpyrocarbonate inhibition of transport activity, suggesting that the substrates mask histidine residues involved in the catalytic function of the transporter. Using human PepT1-specific primers, a reverse transcription–polymerase chain reaction (RT-PCR) signal was detected in eel intestine. Our results suggest that, in eel intestine, a brush-border membrane ‘low-affinity’-type H+/peptide cotransport system is present that shares kinetic features with the mammalian intestinal PepT1-type transporters.
- Published
- 2000
48. Copper Dyshomeostasis In Neurodegenerative Diseases
- Author
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MICHELE MAFFIA, Greco, M., Rizzo, F., Garzarelli, V., Intini, V., Maffia, Mc, Danieli, A., daniele vergara, Riccardis, L., Maffia, M, Greco, M, Rizzo, F, Garzarelli, V, Intini, V, Maffia, Mc, Danieli, A, Vergara, D, and De Riccardis, L
49. Large-scale analysis of protein networks involved in oligodendrocytes differentiation reveals novel key regulators of the differentiation program
- Author
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daniele vergara, Damato, M., Musaro, D., Fournier, I., Salzet, M., MICHELE MAFFIA, Vergara, D, Damato, M, Musaro, D, Fournier, I, Salzet, M, and Maffia, M
50. The impact and future of artificial intelligence in medical genetics and molecular medicine: an ongoing revolution.
- Author
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Ozcelik F, Dundar MS, Yildirim AB, Henehan G, Vicente O, Sánchez-Alcázar JA, Gokce N, Yildirim DT, Bingol NN, Karanfilska DP, Bertelli M, Pojskic L, Ercan M, Kellermayer M, Sahin IO, Greiner-Tollersrud OK, Tan B, Martin D, Marks R, Prakash S, Yakubi M, Beccari T, Lal R, Temel SG, Fournier I, Ergoren MC, Mechler A, Salzet M, Maffia M, Danalev D, Sun Q, Nei L, Matulis D, Tapaloaga D, Janecke A, Bown J, Cruz KS, Radecka I, Ozturk C, Nalbantoglu OU, Sag SO, Ko K, Arngrimsson R, Belo I, Akalin H, and Dundar M
- Subjects
- Humans, Genetics, Medical trends, Genetics, Medical methods, Precision Medicine methods, Genomics methods, Artificial Intelligence, Molecular Medicine methods
- Abstract
Artificial intelligence (AI) platforms have emerged as pivotal tools in genetics and molecular medicine, as in many other fields. The growth in patient data, identification of new diseases and phenotypes, discovery of new intracellular pathways, availability of greater sets of omics data, and the need to continuously analyse them have led to the development of new AI platforms. AI continues to weave its way into the fabric of genetics with the potential to unlock new discoveries and enhance patient care. This technology is setting the stage for breakthroughs across various domains, including dysmorphology, rare hereditary diseases, cancers, clinical microbiomics, the investigation of zoonotic diseases, omics studies in all medical disciplines. AI's role in facilitating a deeper understanding of these areas heralds a new era of personalised medicine, where treatments and diagnoses are tailored to the individual's molecular features, offering a more precise approach to combating genetic or acquired disorders. The significance of these AI platforms is growing as they assist healthcare professionals in the diagnostic and treatment processes, marking a pivotal shift towards more informed, efficient, and effective medical practice. In this review, we will explore the range of AI tools available and show how they have become vital in various sectors of genomic research supporting clinical decisions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2024
- Full Text
- View/download PDF
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