107 results on '"Maffioli E"'
Search Results
2. Acute environmental temperature variation affects brain protein expression, anxiety and explorative behaviour in adult zebrafish
- Author
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Nonnis, S., Angiulli, E., Maffioli, E., Frabetti, F., Negri, A., Cioni, C., Alleva, E., Romeo, V., Tedeschi, G., and Toni, M.
- Published
- 2021
- Full Text
- View/download PDF
3. Environmental temperature variation affects brain protein expression and cognitive abilities in adult zebrafish (Danio rerio): A proteomic and behavioural study
- Author
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Toni, M., Angiulli, E., Miccoli, G., Cioni, C., Alleva, E., Frabetti, F., Pizzetti, F., Grassi Scalvini, F., Nonnis, S., Negri, A., Tedeschi, G., and Maffioli, E.
- Published
- 2019
- Full Text
- View/download PDF
4. Serine metabolism during differentiation of human iPSC-derived astrocytes
- Author
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Tripodi, F, Motta, Z, Murtas, G, Rabattoni, V, Nonnis, S, Grassi Scalvini, F, Rinaldi, A, Rizzi, R, Bearzi, C, Badone, B, Sacchi, S, Tedeschi, G, Maffioli, E, Coccetti, P, Pollegioni, L, Tripodi, Farida, Motta, Zoraide, Murtas, Giulia, Rabattoni, Valentina, Nonnis, Simona, Grassi Scalvini, Francesca, Rinaldi, Anna Maria, Rizzi, Roberto, Bearzi, Claudia, Badone, Beatrice, Sacchi, Silvia, Tedeschi, Gabriella, Maffioli, Elisa, Coccetti, Paola, Pollegioni, Loredano, Tripodi, F, Motta, Z, Murtas, G, Rabattoni, V, Nonnis, S, Grassi Scalvini, F, Rinaldi, A, Rizzi, R, Bearzi, C, Badone, B, Sacchi, S, Tedeschi, G, Maffioli, E, Coccetti, P, Pollegioni, L, Tripodi, Farida, Motta, Zoraide, Murtas, Giulia, Rabattoni, Valentina, Nonnis, Simona, Grassi Scalvini, Francesca, Rinaldi, Anna Maria, Rizzi, Roberto, Bearzi, Claudia, Badone, Beatrice, Sacchi, Silvia, Tedeschi, Gabriella, Maffioli, Elisa, Coccetti, Paola, and Pollegioni, Loredano
- Abstract
Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations.
- Published
- 2023
5. Mass spectrometry-based proteomic strategy for ecchymotic skin examination in forensic pathology
- Author
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Toma, L., Vignali, G., Maffioli, E., Tambuzzi, S., Giaccari, R., Mattarozzi, M., Nonnis, S., Milioli, M., Franceschetti, L., Paredi, G., Negri, A., Riccardi, B., Cattaneo, C., Careri, M., Tedeschi, G., and Bruno, S.
- Subjects
Settore BIO/10 - Biochimica - Published
- 2023
6. Suggestive evidence on the involvement of polypyrimidine-tract binding protein in regulating alternative splicing of MAP/microtubule affinity-regulating kinase 4 in glioma
- Author
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Fontana, L., Rovina, D., Novielli, C., Maffioli, E., Tedeschi, G., Magnani, I., and Larizza, L.
- Published
- 2015
- Full Text
- View/download PDF
7. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus
- Author
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Maffioli, E, Murtas, G, Rabattoni, V, Badone, B, Tripodi, F, Iannuzzi, F, Licastro, D, Nonnis, S, Rinaldi, A, Motta, Z, Sacchi, S, Canu, N, Tedeschi, G, Coccetti, P, Pollegioni, L, Maffioli, Elisa, Murtas, Giulia, Rabattoni, Valentina, Badone, Beatrice, Tripodi, Farida, Iannuzzi, Filomena, Licastro, Danilo, Nonnis, Simona, Rinaldi, Anna Maria, Motta, Zoraide, Sacchi, Silvia, Canu, Nadia, Tedeschi, Gabriella, Coccetti, Paola, Pollegioni, Loredano, Maffioli, E, Murtas, G, Rabattoni, V, Badone, B, Tripodi, F, Iannuzzi, F, Licastro, D, Nonnis, S, Rinaldi, A, Motta, Z, Sacchi, S, Canu, N, Tedeschi, G, Coccetti, P, Pollegioni, L, Maffioli, Elisa, Murtas, Giulia, Rabattoni, Valentina, Badone, Beatrice, Tripodi, Farida, Iannuzzi, Filomena, Licastro, Danilo, Nonnis, Simona, Rinaldi, Anna Maria, Motta, Zoraide, Sacchi, Silvia, Canu, Nadia, Tedeschi, Gabriella, Coccetti, Paola, and Pollegioni, Loredano
- Abstract
Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women.
- Published
- 2022
8. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1
- Author
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Zanotti, L, Angioni, R, Calì, B, Soldani, C, Ploia, C, Moalli, F, Gargesha, M, DʼAmico, G, Elliman, S, Tedeschi, G, Maffioli, E, Negri, A, Zacchigna, S, Sarukhan, A, Stein, J V, and Viola, A
- Published
- 2016
- Full Text
- View/download PDF
9. Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells
- Author
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Tripodi, F, Badone, B, Vescovi, M, Milanesi, R, Nonnis, S, Maffioli, E, Bonanomi, M, Gaglio, D, Tedeschi, G, Coccetti, P, Tripodi, Farida, Badone, Beatrice, Vescovi, Marta, Milanesi, Riccardo, Nonnis, Simona, Maffioli, Elisa, Bonanomi, Marcella, Gaglio, Daniela, Tedeschi, Gabriella, Coccetti, Paola, Tripodi, F, Badone, B, Vescovi, M, Milanesi, R, Nonnis, S, Maffioli, E, Bonanomi, M, Gaglio, D, Tedeschi, G, Coccetti, P, Tripodi, Farida, Badone, Beatrice, Vescovi, Marta, Milanesi, Riccardo, Nonnis, Simona, Maffioli, Elisa, Bonanomi, Marcella, Gaglio, Daniela, Tedeschi, Gabriella, and Coccetti, Paola
- Abstract
Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti‐cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP‐activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.
- Published
- 2020
10. Towards the standardization of mitochondrial proteomics: the Italian mt-HPP initiative
- Author
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Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., FONTANA, Simona, Garavaglia, B., Giusti, L., Greco, V., Lucacchini, A., Maffioli, E., Magni, F., Monteleone, Francesca, Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, R., Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, A., Fasano, M., Alberio, T, Pieroni, L, Ronci, M, Banfi, C, Bongarzone, I, Bottoni, P, Brioschi, M, Caterino, M, Chinello, C, Cormio, A, Cozzolino, F, Cunsolo, V, Fontana, S, Garavaglia, B, Giusti, L, Greco, V, Lucacchini, A, Maffioli, E, Magni, F, Monteleone, F, Monti, M, Monti, V, Musicco, C, Petrosillo, G, Porcelli, V, Saletti, R, Scatena, R, Soggiu, A, Tedeschi, G, Zilocchi, M, Roncada, P, Urbani, A, Fasano, M, Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., Fontana, S., Garavaglia, B., Giusti, L., Greco, V., Lucacchini, A., Maffioli, E., Magni, F., Monteleone, F., Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, R., Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, A., and Fasano, M.
- Subjects
itlian mt-HPP iniziative ,Mitochondria, standardization, enrichment protocol, Mitochondrial Human Proteome Project ,mitochondrial proteomic ,BIO/10 - BIOCHIMICA ,proteomic - Abstract
The mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed datasets were analysed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and sub-mitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted nodes of this network but with a different ability in co-isolating mitochondria-associated structures for each enrichment protocol/cell line pair.
- Published
- 2017
11. Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans
- Author
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Galli, A., Maffioli, E., Sogne, E., Moretti, S., Di Cairano, E., Negri, A., Nonnis, S., Norata, Giuseppe, Bonacina, F., Borghi, F., Podestà, A., Bertuzzi, F., Milani, P., Lenardi, C., Tedeschi, G., Perego, C., Galli, A., Maffioli, E., Sogne, E., Moretti, S., Di Cairano, E., Negri, A., Nonnis, S., Norata, Giuseppe, Bonacina, F., Borghi, F., Podestà, A., Bertuzzi, F., Milani, P., Lenardi, C., Tedeschi, G., and Perego, C.
- Abstract
Ex vivo expansion and differentiation of human pancreatic ß-cell are enabling steps of paramount importance for accelerating the development of therapies for diabetes. The success of regenerative strategies depends on their ability to reproduce the chemical and biophysical properties of the microenvironment in which ß-cells develop, proliferate and function. In this paper we focus on the biophysical properties of the extracellular environment and exploit the cluster-assembled zirconia substrates with tailored roughness to mimic the nanotopography of the extracellular matrix. We demonstrate that ß-cells can perceive nanoscale features of the substrate and can convert these stimuli into mechanotransductive processes which promote long-term in vitro human islet culture, thus preserving ß-cell differentiation and function. Proteomic and quantitative immunofluorescence analyses demonstrate that the process is driven by nanoscale topography, via remodelling of the actin cytoskeleton and nuclear architecture. These modifications activate a transcriptional program which stimulates an adaptive metabolic glucose response. Engineered cluster-assembled substrates coupled with proteomic approaches may provide a useful strategy for identifying novel molecular targets for treating diabetes mellitus and for enhancing tissue engineering in order to improve the efficacy of islet cell transplantation therapies.
- Published
- 2018
12. Peptidomic characterization of hemorrhagic shock plasma samples: Effects of tranexamic acid
- Author
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Maffioli, E., primary, Aletti, F., additional, Grassi Scalvini, F., additional, Nonnis, S., additional, Santagata, F., additional, Morelli, S., additional, Kistler, E.B., additional, Schmid-Schoenbein, G.W., additional, Negri, A., additional, and Tedeschi, G., additional
- Published
- 2017
- Full Text
- View/download PDF
13. A porcine model of severe hemorrhagic shock with fluid and blood resuscitation to evaluate plasma peptidomic modifications
- Author
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Babini, G., primary, Maffioli, E., additional, Grassi Scalvini, F., additional, Luciani, A., additional, De Giorgio, D., additional, Staszewsky, L., additional, Baselli, G., additional, Tedeschi, G., additional, and Ristagno, G., additional
- Published
- 2017
- Full Text
- View/download PDF
14. Towards the standardization of mitochondrial proteomics: the Italian mt-HPP initiative
- Author
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Alberio, T, Pieroni, L, Ronci, M, Banfi, C, Bongarzone, I, Bottoni, P, Brioschi, M, Caterino, M, Chinello, C, Cormio, A, Cozzolino, F, Cunsolo, V, Fontana, S, Garavaglia, B, Giusti, L, Greco, V, Lucacchini, A, Maffioli, E, Magni, F, Monteleone, F, Monti, M, Monti, V, Musicco, C, Petrosillo, G, Porcelli, V, Saletti, R, Scatena, R, Soggiu, A, Tedeschi, G, Zilocchi, M, Roncada, P, Urbani, A, Fasano, M, CHINELLO, CLIZIA, MAGNI, FULVIO, MONTI, MARIA GIOVANNA, Fasano, M., Alberio, T, Pieroni, L, Ronci, M, Banfi, C, Bongarzone, I, Bottoni, P, Brioschi, M, Caterino, M, Chinello, C, Cormio, A, Cozzolino, F, Cunsolo, V, Fontana, S, Garavaglia, B, Giusti, L, Greco, V, Lucacchini, A, Maffioli, E, Magni, F, Monteleone, F, Monti, M, Monti, V, Musicco, C, Petrosillo, G, Porcelli, V, Saletti, R, Scatena, R, Soggiu, A, Tedeschi, G, Zilocchi, M, Roncada, P, Urbani, A, Fasano, M, CHINELLO, CLIZIA, MAGNI, FULVIO, MONTI, MARIA GIOVANNA, and Fasano, M.
- Abstract
The mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed datasets were analysed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and sub-mitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted nodes of this network but with a different ability in co-isolating mitochondria-associated structures for each enrichment protocol/cell line pair.
- Published
- 2017
15. Toward the Standardization of Mitochondrial Proteomics: The Italian Mitochondrial Human Proteome Project Initiative
- Author
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Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., Fontana, S., Garavaglia, B., Giusti, L., Greco, Viviana, Lucacchini, A., Maffioli, E., Magni, F., Monteleone, F., Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, Roberto, Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, Andrea, Fasano, M., Greco V. (ORCID:0000-0003-4521-0020), Scatena R. (ORCID:0000-0002-9425-8293), Urbani A. (ORCID:0000-0001-9168-3174), Alberio, T., Pieroni, L., Ronci, M., Banfi, C., Bongarzone, I., Bottoni, P., Brioschi, M., Caterino, M., Chinello, C., Cormio, A., Cozzolino, F., Cunsolo, V., Fontana, S., Garavaglia, B., Giusti, L., Greco, Viviana, Lucacchini, A., Maffioli, E., Magni, F., Monteleone, F., Monti, M., Monti, V., Musicco, C., Petrosillo, G., Porcelli, V., Saletti, R., Scatena, Roberto, Soggiu, A., Tedeschi, G., Zilocchi, M., Roncada, P., Urbani, Andrea, Fasano, M., Greco V. (ORCID:0000-0003-4521-0020), Scatena R. (ORCID:0000-0002-9425-8293), and Urbani A. (ORCID:0000-0001-9168-3174)
- Abstract
The Mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed data sets were analyzed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and submitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted in nodes of this network but with a different ability in coisolating mitochondria-associated structures for each enrichment protocol/cell line pair.
- Published
- 2017
16. Randomized algorithms: An annotated bibliography: In alphabetical order
- Author
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Maffioli, E., Speranza, M. G., and Vercellis, C.
- Published
- 1984
- Full Text
- View/download PDF
17. A new bioadhesive material from fish parasite Neobenedenia girellae
- Author
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Maffioli, E, Nonnis, S, Polo, N, Negri, A, Forcella, M, Fusi, P, Galli, P, Tedeschi, G, Maffioli, Elisa, Nonnis, Simona, Polo, Nerea Cuevas, Negri, Armando, Forcella, Matilde, Fusi, Paola, Galli, Paolo, Tedeschi, Gabriella, Maffioli, E, Nonnis, S, Polo, N, Negri, A, Forcella, M, Fusi, P, Galli, P, Tedeschi, G, Maffioli, Elisa, Nonnis, Simona, Polo, Nerea Cuevas, Negri, Armando, Forcella, Matilde, Fusi, Paola, Galli, Paolo, and Tedeschi, Gabriella
- Abstract
The purpose of the work was to identify the proteins present in the adhesive material of the capsalid Neobenedenia girellae by a proteomic approach based on de novo sequencing and data base search to overcome the lack of information concerning the genome of these parasites. Glandular secretions were obtained by a new method, set up in our laboratory, which allowed collecting a small amount of secretion without any contamination from other tissues either from the parasites as well as from the skin of the host. The proteomic analysis reveals that the adhesive is mainly composed of cytoskeletal proteins (actin, keratin and tubulin) but contains also ATP-synthase, 78. kDa glucose regulated protein and albumin. Biological significance: This paper reports for the first time the characterization of a novel bioadhesive material used by capsalid parasites to adhere to fish. Such information broadens our knowledge of the molecular mechanisms involved in adhesiveness of parasites to hosts. Moreover, it offers new clues in understanding the mechanism of stickiness and adhesion of cytoskeleton components, often involved in both physiological and pathological processes, including neurodegenerative diseases. © 2014 Elsevier B.V.
- Published
- 2014
18. Phosphomimetic mutant of LSD1-8a splicing variant in complex with CoREST
- Author
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Toffolo, E., primary, Paganini, L., additional, Rusconi, F., additional, Tortorici, M., additional, Pilotto, S., additional, Verpelli, C., additional, Tedeschi, G., additional, Maffioli, E., additional, Sala, C., additional, Mattevi, A., additional, and Battaglioli, E., additional
- Published
- 2013
- Full Text
- View/download PDF
19. Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction
- Author
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Galli Alessandra, Marku Algerta, Marciani Paola, Schulte Carsten, Lenardi Cristina, Milani Paolo, Maffioli Elisa, Tedeschi Gabriella, and Perego Carla
- Subjects
β-cells ,mechanotransduction ,diabetes ,stem cells ,nanotopography ,islet of langerhans ,integrin ,yap/taz ,actin ,Cytology ,QH573-671 - Abstract
Embryonic and pluripotent stem cells hold great promise in generating β-cells for both replacing medicine and novel therapeutic discoveries in diabetes mellitus. However, their differentiation in vitro is still inefficient, and functional studies reveal that most of these β-like cells still fail to fully mirror the adult β-cell physiology. For their proper growth and functioning, β-cells require a very specific environment, the islet niche, which provides a myriad of chemical and physical signals. While the nature and effects of chemical stimuli have been widely characterized, less is known about the mechanical signals. We here review the current status of knowledge of biophysical cues provided by the niche where β-cells normally live and differentiate, and we underline the possible machinery designated for mechanotransduction in β-cells. Although the regulatory mechanisms remain poorly understood, the analysis reveals that β-cells are equipped with all mechanosensors and signaling proteins actively involved in mechanotransduction in other cell types, and they respond to mechanical cues by changing their behavior. By engineering microenvironments mirroring the biophysical niche properties it is possible to elucidate the β-cell mechanotransductive-regulatory mechanisms and to harness them for the promotion of β-cell differentiation capacity in vitro.
- Published
- 2020
- Full Text
- View/download PDF
20. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1
- Author
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Elliman, S, Moalli, Federica, Soldani, C, Viola, A, Zanotti, L, D'Amico, G, Zacchigna, S, Ploia, C, Tedeschi, G, Calì, B, Sarukhan, A, Negri, A, Angioni, R, Gargesha, M, Maffioli, E, and Stein, Jens Volker
- Subjects
610 Medicine & health ,3. Good health - Abstract
Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases.
21. Serine metabolism during differentiation of human <scp>iPSC</scp> ‐derived astrocytes
- Author
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Farida Tripodi, Zoraide Motta, Giulia Murtas, Valentina Rabattoni, Simona Nonnis, Francesca Grassi Scalvini, Anna Maria Rinaldi, Roberto Rizzi, Claudia Bearzi, Beatrice Badone, Silvia Sacchi, Gabriella Tedeschi, Elisa Maffioli, Paola Coccetti, Loredano Pollegioni, Tripodi, F, Motta, Z, Murtas, G, Rabattoni, V, Nonnis, S, Grassi Scalvini, F, Rinaldi, A, Rizzi, R, Bearzi, C, Badone, B, Sacchi, S, Tedeschi, G, Maffioli, E, Coccetti, P, and Pollegioni, L
- Subjects
d-serine ,amino acid metabolism ,neurotransmission ,Cell Biology ,BIO/10 - BIOCHIMICA ,Molecular Biology ,Biochemistry ,proteomic ,metabolomic - Abstract
Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations.
- Published
- 2023
22. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus
- Author
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Elisa Maffioli, Giulia Murtas, Valentina Rabattoni, Beatrice Badone, Farida Tripodi, Filomena Iannuzzi, Danilo Licastro, Simona Nonnis, Anna Maria Rinaldi, Zoraide Motta, Silvia Sacchi, Nadia Canu, Gabriella Tedeschi, Paola Coccetti, Loredano Pollegioni, Maffioli, E, Murtas, G, Rabattoni, V, Badone, B, Tripodi, F, Iannuzzi, F, Licastro, D, Nonnis, S, Rinaldi, A, Motta, Z, Sacchi, S, Canu, N, Tedeschi, G, Coccetti, P, and Pollegioni, L
- Subjects
Proteomics ,Male ,sex differences ,insulin ,sex difference ,D-serine ,amino acid metabolism ,Receptors, N-Methyl-D-Aspartate ,Hippocampus ,General Biochemistry, Genetics and Molecular Biology ,transcriptomics ,Alzheimer Disease ,Settore BIO/10 - Biochimica ,Receptors ,Serine ,Humans ,phosphorylated pathway ,proteomic ,aging ,transcriptomic ,NMDA receptor ,BIO/10 - BIOCHIMICA ,CP: Metabolism ,CP: Neuroscience ,metabolomics ,proteomics ,Female ,Insulin ,Quality of Life ,metabolomic ,N-Methyl-D-Aspartate - Abstract
Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women.
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- 2022
23. Brain proteome and behavioural analysis in wild type, BDNF+/− and BDNF−/− adult zebrafish (danio rerio) exposed to two different temperatures
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Elisa Maffioli, Elisa Angiulli, Simona Nonnis, Francesca Grassi Scalvini, Armando Negri, Gabriella Tedeschi, Ivan Arisi, Flavia Frabetti, Salvatore D’Aniello, Enrico Alleva, Carla Cioni, Mattia Toni, Maffioli E., Angiulli E., Nonnis S., Grassi Scalvini F., Negri A., Tedeschi G., Arisi I., Frabetti F., D'aniello S., Alleva E., Cioni C., and Toni M.
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Proteome ,Animal ,Brain-Derived Neurotrophic Factor ,Organic Chemistry ,Brain ,temperature ,General Medicine ,zebrafish ,Mammal ,Catalysis ,Computer Science Applications ,behaviour ,Inorganic Chemistry ,BDNF ,Behavior Rating Scale ,proteomic ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy - Abstract
Experimental evidence suggests that environmental stress conditions can alter the expression of BDNF and that the expression of this neurotrophin influences behavioural responses in mammalian models. It has been recently demonstrated that exposure to 34 °C for 21 days alters the brain proteome and behaviour in zebrafish. The aim of this work was to investigate the role of BDNF in the nervous system of adult zebrafish under control and heat treatment conditions. For this purpose, zebrafish from three different genotypes (wild type, heterozygous BDNF+/− and knock out BDNF−/−) were kept for 21 days at 26 °C or 34 °C and then euthanized for brain molecular analyses or subjected to behavioural tests (Y-maze test, novel tank test, light and dark test, social preference test, mirror biting test) for assessing behavioural aspects such as boldness, anxiety, social preference, aggressive behaviour, interest for the novel environment and exploration. qRT-PCR analysis showed the reduction of gene expression of BDNF and its receptors after heat treatment in wild type zebrafish. Moreover, proteomic analysis and behavioural tests showed genotype- and temperature-dependent effects on brain proteome and behavioural responding. Overall, the absent expression of BDNF in KO alters (1) the brain proteome by reducing the expression of proteins involved in synapse functioning and neurotransmitter-mediated transduction; (2) the behaviour, which can be interpreted as bolder and less anxious and (3) the cellular and behavioural response to thermal treatment.
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- 2022
24. Living in future ocean acidification, physiological adaptive responses of the immune system of sea urchins resident at a CO2 vent system
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Valeria Matranga, Abigail M. Smith, Anna Palumbo, Gabriella Tedeschi, Maria Cristina Gambi, Elisa Maffioli, Oriana Migliaccio, Maria Byrne, Annalisa Pinsino, Claudio Agnisola, Simona Nonnis, Migliaccio, O., Pinsino, A., Maffioli, E., Smith, A. M., Agnisola, C., Matranga, V., Nonnis, S., Tedeschi, G., Byrne, M., Gambi, M. C., and Palumbo, A.
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Sea urchin ,Environmental Engineering ,010504 meteorology & atmospheric sciences ,Population ,Zoology ,010501 environmental sciences ,Cell morphology ,01 natural sciences ,Paracentrotus lividus ,Mesocosm ,Immune system ,biology.animal ,Eco-physiology ,Environmental Chemistry ,Seawater ,14. Life underwater ,Adaptation ,education ,Waste Management and Disposal ,Immune cells ,Ocean acidification ,Proteomics ,Sea urchins ,0105 earth and related environmental sciences ,Immune cell ,Phenotypic plasticity ,education.field_of_study ,biology ,Animal ,Proteomic ,Carbon Dioxide ,Hydrogen-Ion Concentration ,biology.organism_classification ,Adaptation, Physiological ,Pollution ,13. Climate action ,Immune System ,Paracentrotu ,Hydrothermal Vent ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
The effects of ocean acidification, a major anthropogenic impact on marine life, have been mainly investigated in laboratory/mesocosm experiments. We used the CO2 vents at Ischia as a natural laboratory to study the long-term effects of ocean acidification on the sea urchin Paracentrotus lividus population resident in low-pH (7.8 ± 0.2) compared to that at two control sites (pH 8.02 ± 0.00; 8.02 ± 0.01). The novelty of the present study is the analysis of the sea urchin immune cells, the sentinels of environmental stress responses, by a wide-ranging approach, including cell morphology, biochemistry and proteomics. Immune cell proteomics showed that 311 proteins were differentially expressed in urchins across sites with a general shift towards antioxidant processes in the vent urchins. The vent urchin immune cells showed higher levels of total antioxidant capacity, up-regulation of phagosome and microsomal proteins, enzymes of ammonium metabolism, amino-acid degradation, and modulation of carbon metabolism proteins. Lipid-hydroperoxides and nitric oxide levels were not different in urchins from the different sites. No differences in the coelomic fluid pH, immune cell composition, animal respiration, nitrogen excretion and skeletal mineralogy were observed. Our results reveal the phenotypic plasticity of the immune system of sea urchins adapted to life at vent site, under conditions commensurate with near-future ocean acidification projections.
- Published
- 2019
25. Antimicrobial D-amino acid oxidase-derived peptides specify gut microbiota
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Murtas, Giulia, Sacchi, Silvia, Tedeschi, Gabriella, Maffioli, Elisa, Notomista, Eugenio, Cafaro, Valeria, Abbondi, Monica, Mothet, Jean-Pierre, Pollegioni, Loredano, University of Insubria, Varese, University of Milan, University of Naples Federico II, Laboratoire Lumière, Matière et Interfaces (LuMIn), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Murtas, G., Sacchi, S., Tedeschi, G., Maffioli, E., Notomista, E., Cafaro, V., Abbondi, M., Mothet, J. -P., and Pollegioni, L.
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Male ,D-Amino acids ,Protein Conformation ,d-Amino acid ,D-amino acid oxidase ,Sequence Homology ,Gut flora ,Flavoprotein ,Microbiota selection ,Novel function ,Mice ,0302 clinical medicine ,Intestine, Small ,Amino Acids ,chemistry.chemical_classification ,0303 health sciences ,Oxidase test ,biology ,Anti-Bacterial Agents ,Amino acid ,Amino Acid ,Pore Forming Cytotoxic Protein ,Biochemistry ,Molecular Medicine ,Original Article ,Female ,Human ,Pore Forming Cytotoxic Proteins ,D-Amino-Acid Oxidase ,Proteases ,Antimicrobial peptides ,Gram-Positive Bacteria ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Anti-Bacterial Agent ,Gram-Negative Bacteria ,Animals ,Humans ,Secretion ,Amino Acid Sequence ,Rats, Wistar ,Molecular Biology ,030304 developmental biology ,Pharmacology ,Animal ,Cell Biology ,biology.organism_classification ,Rats ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,chemistry ,Rat ,030217 neurology & neurosurgery ,Bacteria - Abstract
The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.
- Published
- 2021
26. Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells
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Farida Tripodi 1, Beatrice Badone 1, Marta Vescovi 1, Riccardo Milanesi 1, Simona Nonnis 2, 3, Elisa Maffioli 2, Marcella Bonanomi 1, 4, Daniela Gaglio 4, 5, Gabriella Tedeschi 2, Paola Coccetti 1, Tripodi, F, Badone, B, Vescovi, M, Milanesi, R, Nonnis, S, Maffioli, E, Bonanomi, M, Gaglio, D, Tedeschi, G, and Coccetti, P
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AMPK ,growth ,TCA cycle ,migration ,proteomics ,metabolomics ,HCC ,AMP-Activated Protein Kinases ,Article ,chemistry.chemical_compound ,Adenosine Triphosphate ,Methionine ,medicine ,Humans ,lcsh:QH301-705.5 ,proteomic ,PI3K/AKT/mTOR pathway ,Essential amino acid ,Cell Proliferation ,chemistry.chemical_classification ,Chemistry ,Cell growth ,TOR Serine-Threonine Kinases ,Liver Neoplasms ,Cancer ,General Medicine ,Hep G2 Cells ,medicine.disease ,BIO/10 - BIOCHIMICA ,Mitochondria ,Citric acid cycle ,lcsh:Biology (General) ,Cancer research ,Liver cancer ,metabolomic ,Signal Transduction - Abstract
Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.
- Published
- 2020
27. Environmental temperature variation affects brain protein expression and cognitive abilities in adult zebrafish (Danio rerio): A proteomic and behavioural study
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F. Grassi Scalvini, G. Miccoli, Gabriella Tedeschi, Armando Negri, Fabrizio Pizzetti, F. Frabetti, Carla Cioni, Elisa Angiulli, Simona Nonnis, Mattia Toni, Elisa Maffioli, Enrico Alleva, and Toni M, Angiulli E, Miccoli G, Cioni C, Alleva E, Frabetti F, Pizzetti F, Grassi Scalvini F, Nonnis S, Negri A, Tedeschi G, Maffioli E.
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Proteomics ,0301 basic medicine ,Nervous system ,Hot Temperature ,Central nervous system ,Biophysics ,Danio ,Neurotransmission ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Cognition ,medicine ,Animals ,Environmental temperature ,Behaviour ,Danio rerio ,Shotgun proteomic ,Y-maze ,Maze Learning ,Neurotransmitter ,Zebrafish ,Behavior, Animal ,030102 biochemistry & molecular biology ,biology ,Brain ,Zebrafish Proteins ,biology.organism_classification ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,Ectotherm ,Proteome ,Neuroscience - Abstract
Water temperature is an important environmental parameter influencing the distribution and the health of fishes and it plays a central role in ectothermic animals. The aim of this study is to determine the effects of environmental temperature on the brain proteome and the behavioural responses in zebrafish, a widely used animal model for environmental “omics” studies. Adult specimens of wild-type zebrafish were kept at 18 °C, 34 °C and 26 °C (control) for 21 days. Proteomic data revealed that several proteins involved in cytoskeletal organization, mitochondrial regulation and energy metabolism are differently regulated at the extreme temperatures. In particular, the expression of proteins associated to synapses and neurotransmitter release is down-regulated at 18 °C and 34 °C. In both thermal conditions, fish exhibited a reduced interest for the novel environment and an impairment of cognitive abilities during Y-Maze behavioural tests. The observed pathways of protein expression are possibly associated to functional alterations of the synaptic transmission that may result in cognitive functions impairment at central nervous system level as those revealed by behavioural tests. This study indicates that temperature variations can elicit biochemical changes that may affect fish health and behaviour. This combined approach provides insights into mechanisms supporting thermal acclimation and plasticity in fishes. Significance Environmental temperature variation may impact on all levels of biological life. Understanding the impact of thermal variation on the nervous system and animal behaviour is of primary importance since the results obtained can be applied from the ecological to the biomedical fields.
- Published
- 2019
28. A new bioadhesive material from fish parasite Neobenedenia girellae
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Gabriella Tedeschi, Matilde Forcella, Simona Nonnis, Nerea Cuevas Polo, Armando Negri, Elisa Maffioli, Paolo Galli, Paola Fusi, Maffioli, E, Nonnis, S, Polo, N, Negri, A, Forcella, M, Fusi, P, Galli, P, and Tedeschi, G
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Molecular Sequence Data ,Adhesive ,Biophysics ,Biochemistry ,Genome ,Sequence Analysis, Protein ,Adhesives ,Heat shock protein ,Materials Testing ,Keratin ,Animals ,De novo MS/MS sequencing ,Parasite hosting ,Secretion ,Amino Acid Sequence ,Natural glue ,Cytoskeleton ,Endoplasmic Reticulum Chaperone BiP ,Neobenedenia girellae ,Heat-Shock Proteins ,Actin ,chemistry.chemical_classification ,Biological Products ,biology ,Fishes ,Capsalid ,Molecular biology ,Cell biology ,ATP Synthetase Complexes ,Cytoskeletal Proteins ,Tubulin ,chemistry ,Platyhelminths ,biology.protein - Abstract
The purpose of the work was to identify the proteins present in the adhesive material of the capsalid Neobenedenia girellae by a proteomic approach based on de novo sequencing and data base search to overcome the lack of information concerning the genome of these parasites. Glandular secretions were obtained by a new method, set up in our laboratory, which allowed collecting a small amount of secretion without any contamination from other tissues either from the parasites as well as from the skin of the host. The proteomic analysis reveals that the adhesive is mainly composed of cytoskeletal proteins (actin, keratin and tubulin) but contains also ATP-synthase, 78. kDa glucose regulated protein and albumin. Biological significance: This paper reports for the first time the characterization of a novel bioadhesive material used by capsalid parasites to adhere to fish. Such information broadens our knowledge of the molecular mechanisms involved in adhesiveness of parasites to hosts. Moreover, it offers new clues in understanding the mechanism of stickiness and adhesion of cytoskeleton components, often involved in both physiological and pathological processes, including neurodegenerative diseases. © 2014 Elsevier B.V.
- Published
- 2014
29. Protein Kinase CK2 Holoenzyme Promotes Start-Specific Transcription in Saccharomyces cerevisiae
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Lilia Alberghina, Gabriella Tedeschi, Raffaele Nicastro, Claudia Cirulli, Elisa Maffioli, Sara Busnelli, Paola Coccetti, Farida Tripodi, Tripodi, F, Nicastro, R, Busnelli, S, Cirulli, C, Maffioli, E, Tedeschi, G, Alberghina, L, and Coccetti, P
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animal structures ,Saccharomyces cerevisiae Proteins ,Transcription, Genetic ,Specificity factor ,RNA polymerase II ,Saccharomyces cerevisiae ,CK2 beta subunits, phosphorylation, transcription, RNA polymerase II, cell cycle, SBF/MBF complexes, Swi6 ,Microbiology ,S Phase ,Transcription (biology) ,Sigma factor ,Gene Expression Regulation, Fungal ,Casein Kinase II ,Promoter Regions, Genetic ,Molecular Biology ,RNA polymerase II holoenzyme ,Regulation of gene expression ,biology ,fungi ,G1 Phase ,Promoter ,Articles ,General Medicine ,BIO/10 - BIOCHIMICA ,Molecular biology ,Cell biology ,DNA-Binding Proteins ,embryonic structures ,biology.protein ,RNA Polymerase II ,Transcription Initiation Site ,Transcription factor II D ,Holoenzymes ,Gene Deletion ,Protein Binding ,Transcription Factors - Abstract
In Saccharomyces cerevisiae , the entrance into S phase requires the activation of a specific burst of transcription, which depends on SBF (SCB binding factor, Swi4/Swi6) and MBF (MCB binding factor, Mbp1/Swi6) complexes. CK2 is a pleiotropic kinase involved in several cellular processes, including the regulation of the cell cycle. CK2 is composed of two catalytic subunits (α and α′) and two regulatory subunits (β and β′), both of which are required to form the active holoenzyme. Here we investigate the function of the CK2 holoenzyme in Start-specific transcription. The ckb1 Δ ckb2 Δ mutant strain, bearing deletions of both genes encoding CK2 regulatory subunits, shows a delay of S-phase entrance due to a severe reduction of the expression of SBF- and MBF-dependent genes. This transcriptional defect is caused by an impaired recruitment of Swi6 and Swi4 to G 1 gene promoters. Moreover, CK2 α and β′ subunits interact with RNA polymerase II, whose binding to G 1 promoters is positively regulated by the CK2 holoenzyme. Collectively, these findings suggest a novel role for the CK2 holoenzyme in the activation of G 1 transcription.
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- 2013
30. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1
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Gabriella Tedeschi, Madhu Gargesha, Giovanna D'Amico, Jens V. Stein, Federica Moalli, Bianca Calì, Cristiana Soldani, Roberta Angioni, Adelaida Sarukhan, C. Ploia, Lucia Zanotti, Antonella Viola, Elisa Maffioli, Stephen J. Elliman, Armando Negri, Serena Zacchigna, Zanotti, L., Angioni, R., Calì, B., Soldani, C., Ploia, C., Moalli, F., Gargesha, M., D'Amico, G., Elliman, S., Tedeschi, G., Maffioli, E., Negri, A., Zacchigna, Serena, Sarukhan, A., Stein, J. V., and Viola, A.
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0301 basic medicine ,signaling pathway ,Cancer Research ,Genetic Vectors ,High endothelial venules ,regenerative medicine ,Angiogenesis Inhibitors ,610 Medicine & health ,growth-factor ,Mesenchymal Stem Cell Transplantation ,in-vivo ,Mice ,03 medical and health sciences ,synovial-fluid ,Hematology ,Anesthesiology and Pain Medicine ,Animals ,Medicine ,Lymphocytes ,dendritic cells ,Lymphocyte homing receptor ,t-cells ,Inflammation ,Tissue Inhibitor of Metalloproteinase-1 ,business.industry ,Mesenchymal stem cell ,Gene Transfer Techniques ,Endothelial Cells ,Mesenchymal Stem Cells ,3. Good health ,Transplantation ,Endothelial stem cell ,Haematopoiesis ,030104 developmental biology ,Oncology ,Immunology ,Cancer research ,rheumatoid-arthritis ,Original Article ,Lymph Nodes ,tissue inhibitor ,adhesion molecule-1 ,Stem cell ,business ,Homing (hematopoietic) - Abstract
Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases.
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- 2016
31. Protein nitration as footprint of oxidative stress-related nitric oxide signaling pathways in developing Ciona intestinalis
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Elena Ercolesi, Anna Palumbo, Gabriella Tedeschi, Elisa Maffioli, Gabriella Fiore, Armando Negri, Marco d'Ischia, Ercolesi, E., Tedeschi, G., Fiore, G., Negri, A., Maffioli, E., D'Ischia, M., Palumbo, A., and D'Ischia, Marco
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MAPK/ERK pathway ,Male ,Proteomics ,Cancer Research ,animal structures ,Physiology ,Biochemical Phenomena ,ascidian ,Clinical Biochemistry ,medicine.disease_cause ,Nitric Oxide ,Biochemistry ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,nitric oxide ,medicine ,Animals ,Ciona intestinalis ,Tyrosine ,030304 developmental biology ,0303 health sciences ,reactive oxygen specie ,marine organisms ,nitrotyrosine ,biology ,fungi ,Metamorphosis, Biological ,Proteins ,biology.organism_classification ,Immunohistochemistry ,Ciona ,Oxidative Stress ,chemistry ,embryonic structures ,Female ,Signal transduction ,Mitogen-Activated Protein Kinases ,030217 neurology & neurosurgery ,Peroxynitrite ,Oxidative stress ,Biomarkers ,Signal Transduction - Abstract
Developmental processes in the ascidian Ciona intestinalis depend on a complex interplay of events including, during metamorphosis, a caspase-dependent apoptosis which is regulated by the nitric oxide (NO)–cGMP signaling pathway. Herein we disclose an alternate NO-mediated signaling pathway during Ciona development which appears to be critically dependent on local redox control. Evidence in support of this conclusion includes: (a) inhibitors of NO synthase (NOS) and scavengers of NO-derived nitrating agents markedly decrease the rate of Ciona metamorphosis; (b) an NO donor or peroxynitrite caused an opposite effect; (c) increased protein nitration is observed at larva stage. Integrated proteomic and immunochemical methodologies identified nitrated tyrosine residues in ERK and snail. Overall, these results point to protein nitration as a hitherto overlooked NO-dependent regulatory mechanism in Ciona which is specifically triggered by elevated ROS production during developmental processes.
- Published
- 2011
32. Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish ( Danio rerio ).
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Maffioli E, Nonnis S, Negri A, Fontana M, Frabetti F, Rossi AR, Tedeschi G, and Toni M
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- Animals, Phospholipids metabolism, Lipids analysis, Sphingolipids metabolism, Sphingolipids analysis, Zebrafish metabolism, Brain metabolism, Temperature, Lipid Metabolism, Lipidomics methods
- Abstract
This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish ( Danio rerio ) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming.
- Published
- 2024
- Full Text
- View/download PDF
33. SAA1-dependent reprogramming of adipocytes by tumor cells is associated with triple negative breast cancer aggressiveness.
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Rybinska I, Mangano N, Romero-Cordoba SL, Regondi V, Ciravolo V, De Cecco L, Maffioli E, Paolini B, Bianchi F, Sfondrini L, Tedeschi G, Agresti R, Tagliabue E, and Triulzi T
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- Humans, Signal Transduction, Stromal Cells pathology, Adipocytes metabolism, Inflammation pathology, Tumor Microenvironment, Serum Amyloid A Protein metabolism, Triple Negative Breast Neoplasms pathology
- Abstract
Triple negative breast cancers (TNBC) are characterized by a poor prognosis and a lack of targeted treatments. Their progression depends on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Although adipocytes, the primary stromal cells of the breast, have been determined to be plastic in physiology and cancer, the tumor-derived molecular mediators of tumor-adipocyte crosstalk have not been identified yet. In this study, we report that the crosstalk between TNBC cells and adipocytes in vitro beyond adipocyte dedifferentiation, induces a unique transcriptional profile that is characterized by inflammation and pathways that are related to interaction with the tumor microenvironment. Accordingly, increased cancer stem-like features and recruitment of pro-tumorigenic immune cells are induced by this crosstalk through CXCL5 and IL-8 production. We identified serum amyloid A1 (SAA1) as a regulator of the adipocyte reprogramming through CD36 and P2XR7 signaling. In human TNBC, SAA1 expression was associated with cancer-associated adipocyte infiltration, inflammation, stimulated lipolysis, stem-like properties, and a distinct tumor immune microenvironment. Our findings constitute evidence that the interaction between tumor cells and adipocytes through the release of SAA1 is relevant to the aggressiveness of TNBC., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
- Full Text
- View/download PDF
34. The Neurotoxic Effect of Environmental Temperature Variation in Adult Zebrafish ( Danio rerio ).
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Maffioli E, Nonnis S, Grassi Scalvini F, Negri A, Tedeschi G, and Toni M
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- Animals, Temperature, Proteome metabolism, Proteomics, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, Zebrafish metabolism, Neurotoxicity Syndromes
- Abstract
Neurotoxicity consists of the altered functionality of the nervous system caused by exposure to chemical agents or altered chemical-physical parameters. The neurotoxic effect can be evaluated from the molecular to the behavioural level. The zebrafish Danio rerio is a model organism used in many research fields, including ecotoxicology and neurotoxicology. Recent studies by our research group have demonstrated that the exposure of adult zebrafish to low (18 °C) or high (34 °C) temperatures alters their brain proteome and fish behaviour compared to control (26 °C). These results showed that thermal variation alters the functionality of the nervous system, suggesting a temperature-induced neurotoxic effect. To demonstrate that temperature variation can be counted among the factors that generate neurotoxicity, eight different protein datasets, previously published by our research group, were subjected to new analyses using an integrated proteomic approach by means of the Ingenuity Pathway Analysis (IPA) software (Release December 2022). The datasets consist of brain proteome analyses of wild type adult zebrafish kept at three different temperatures (18 °C, 26 °C, and 34 °C) for 4 days (acute) or 21 days (chronic treatment), and of BDNF
+/- and BDNF-/- zebrafish kept at 26 °C or 34 °C for 21 days. The results (a) demonstrate that thermal alterations generate an effect that can be defined as neurotoxic ( p value ≤ 0.05, activation Z score ≤ -2 or ≥2), (b) identify 16 proteins that can be used as hallmarks of the neurotoxic processes common to all the treatments applied and (c) provide three protein panels ( p value ≤ 0.05) related to 18 °C, 34 °C, and BDNF depletion that can be linked to anxiety-like or boldness behaviour upon these treatments.- Published
- 2023
- Full Text
- View/download PDF
35. Serine metabolism during differentiation of human iPSC-derived astrocytes.
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Tripodi F, Motta Z, Murtas G, Rabattoni V, Nonnis S, Grassi Scalvini F, Rinaldi AM, Rizzi R, Bearzi C, Badone B, Sacchi S, Tedeschi G, Maffioli E, Coccetti P, and Pollegioni L
- Subjects
- Humans, Serine metabolism, Proteomics, Cell Differentiation, Receptors, N-Methyl-D-Aspartate genetics, Glycine pharmacology, Glycine metabolism, Astrocytes metabolism, Induced Pluripotent Stem Cells metabolism
- Abstract
Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2023
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36. Mass spectrometry-based proteomic strategy for ecchymotic skin examination in forensic pathology.
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Toma L, Vignali G, Maffioli E, Tambuzzi S, Giaccari R, Mattarozzi M, Nonnis S, Milioli M, Franceschetti L, Paredi G, Negri A, Riccardi B, Cattaneo C, Careri M, Tedeschi G, and Bruno S
- Subjects
- Humans, Proteomics methods, Forensic Pathology, Proteins metabolism, Biomarkers, Glycophorins, Tandem Mass Spectrometry methods
- Abstract
Mass spectrometry (MS)-based proteomics has recently attracted the attention from forensic pathologists. This work is the first report of the development of a shotgun bottom-up proteomic approach based on rapid protein extraction and nano-liquid chromatography/high-resolution mass spectrometry applied to full-thickness human skin for the differential analysis of normal and ecchymotic tissues to identify new biomarkers for bruise characterization and dating. We identified around 2000 proteins from each pooled extract. The method showed excellent precision on independent replicates, with Pearson correlation coefficients always higher than 95%. Glycophorin A, a known biomarker of vital wounds from immunochemical studies, was identified only in ecchymotic tissues, as confirmed by Western blotting analysis. This finding suggests that this protein can be used as a MS-detectable biomarker of wound vitality. By focusing on skin samples from individuals with known wound dating, besides Glycophorin A, other proteins differentially expressed in ecchymotic samples and dependant on wound age were identified, although further analysis on larger datasets are needed to validate these findings. This study paves the way for an in-depth investigation of the potential of MS-based techniques for wound examination in forensic pathology, overcoming the limitations of immunochemical assays., (© 2023. The Author(s).)
- Published
- 2023
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37. Response to microplastic exposure: An exploration into the sea urchin immune cell proteome.
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Murano C, Nonnis S, Scalvini FG, Maffioli E, Corsi I, Tedeschi G, and Palumbo A
- Subjects
- Animals, Proteome, Proteomics, Sea Urchins, Polystyrenes toxicity, Microplastics analysis, Plastics
- Abstract
It is now known that the Mediterranean Sea currently is one of the major hotspot for microplastics (MPs; < 5 mm) pollution and that the risks will be even more pronounced in the coming years. Thus, the in-depth study of the mechanisms underlying the MPs toxicity in key Mediterranean organisms, subjected to high anthropic pressures, has become a categorical imperative to pursue. Here, we explore for the first time the sea urchins immune cells profile combined to their proteome upon in vivo exposure (72 h) to different concentrations of polystyrene-microbeads (micro-PS) starting from relevant environmental concentrations (10, 50, 10
3 , 104 MP/L). Every 24 h, immunological parameters were monitored. After 72 h, the abundance of MPs was examined in various organs and coelomocytes were collected for proteomic analysis based on a shotgun label free proteomic approach. While sea urchins treated with the lowest concentration tested (10 and 50 micro-PS/L) did not show the presence of micro-PS in any tissue, in the specimens exposed to the highest concentration (103 and 104 micro-PS) there was an internalisation of 9.75 ± 2.75 and 113.75 ± 34.5 MP/g, respectively. Proteomic analyses revealed that MPs exposure altered coelomocytes protein profile not only compared to the control group but also among the different micro-PS concentrations and these variations are micro-PS concentration dependent. The proteins exclusively expressed in the coelomocytes of specimens exposed to MPs are mainly metabolite interconversion enzymes, involved in cellular processes, indicating a severe alteration of the cellular metabolic pathways. Overall, these findings provide new insights on the mode of action of MPs in the sea urchin immune cells both at the molecular and cellular level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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38. Phosphoproteomic mapping of CCR5 and ACKR2 signaling properties.
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Vacchini A, Maffioli E, Di Silvestre D, Cancellieri C, Milanesi S, Nonnis S, Badanai S, Mauri P, Negri A, Locati M, Tedeschi G, and Borroni EM
- Abstract
ACKR2 is an atypical chemokine receptor which is structurally uncoupled from G proteins and is unable to activate signaling pathways used by conventional chemokine receptors to promote cell migration. Nonetheless, ACKR2 regulates inflammatory and immune responses by shaping chemokine gradients in tissues via scavenging inflammatory chemokines. To investigate the signaling pathways downstream to ACKR2, a quantitative SILAC-based phosphoproteomic analysis coupled with a systems biology approach with network analysis, was carried out on a HEK293 cell model expressing either ACKR2 or its conventional counterpart CCR5. The model was stimulated with the common agonist CCL3L1 for short (3 min) and long (30 min) durations. As expected, many of the identified proteins are known to participate in conventional signal transduction pathways and in the regulation of cytoskeleton dynamics. However, our analyses revealed unique phosphorylation and network signatures, suggesting roles for ACKR2 other than its scavenger activity. In conclusion, the mapping of phosphorylation events at a holistic level indicated that conventional and atypical chemokine receptors differ in signaling properties. This provides an unprecedented level of detail in chemokine receptor signaling and identifying potential targets for the regulation of ACKR2 and CCR5 function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vacchini, Maffioli, Di Silvestre, Cancellieri, Milanesi, Nonnis, Badanai, Mauri, Negri, Locati, Tedeschi and Borroni.)
- Published
- 2022
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39. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus.
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Maffioli E, Murtas G, Rabattoni V, Badone B, Tripodi F, Iannuzzi F, Licastro D, Nonnis S, Rinaldi AM, Motta Z, Sacchi S, Canu N, Tedeschi G, Coccetti P, and Pollegioni L
- Subjects
- Female, Hippocampus metabolism, Humans, Insulin metabolism, Male, Proteomics, Quality of Life, Receptors, N-Methyl-D-Aspartate metabolism, Serine metabolism, Alzheimer Disease metabolism
- Abstract
Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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40. Molecular response of Sargassum vulgare to acidification at volcanic CO 2 vents: Insights from proteomic and metabolite analyses.
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Kumar A, Nonnis S, Castellano I, AbdElgawad H, Beemster GTS, Buia MC, Maffioli E, Tedeschi G, and Palumbo A
- Subjects
- Carbon Dioxide chemistry, Hydrogen-Ion Concentration, Proteomics, Seawater chemistry, Sargassum
- Abstract
Ocean acidification is impacting marine life all over the world. Understanding how species can cope with the changes in seawater carbonate chemistry represents a challenging issue. We addressed this topic using underwater CO
2 vents that naturally acidify some marine areas off the island of Ischia. In the most acidified area of the vents, having a mean pH value of 6.7, comparable to far-future predicted acidification scenarios (by 2300), the biomass is dominated by the brown alga Sargassum vulgare. The novelty of the present study is the characterization of the S. vulgare proteome together with metabolite analyses to identify the key proteins, metabolites, and pathways affected by ocean acidification. A total of 367 and 387 proteins were identified in populations grown at pH that approximates the current global average (8.1) and acidified sites, respectively. Analysis of their relative abundance revealed that 304 proteins are present in samples from both sites: 111 proteins are either higher or exclusively present under acidified conditions, whereas 120 proteins are either lower or present only under control conditions. Functionally, under acidification, a decrease in proteins related to translation and post-translational processes and an increase of proteins involved in photosynthesis, glycolysis, oxidation-reduction processes, and protein folding were observed. In addition, small-molecule metabolism was affected, leading to a decrease of some fatty acids and antioxidant compounds under acidification. Overall, the results obtained by proteins and metabolites analyses, integrated with previous transcriptomic, physiological, and biochemical studies, allowed us to delineate the molecular strategies adopted by S. vulgare to grow in future acidified environments, including an increase of proteins involved in energetic metabolism, oxidation-reduction processes, and protein folding at the expense of proteins involved in translation and post-translational processes., (© 2022 John Wiley & Sons Ltd.)- Published
- 2022
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- View/download PDF
41. Continuous enteral protease inhibition as a novel treatment for experimental trauma/hemorrhagic shock.
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Aletti F, DeLano FA, Maffioli E, Mu H, Schmid-Schönbein GW, Tedeschi G, and Kistler EB
- Subjects
- Animals, Disease Models, Animal, Humans, Intestine, Small, Ischemia, Protease Inhibitors pharmacology, Protease Inhibitors therapeutic use, Rats, Rats, Wistar, Shock, Hemorrhagic drug therapy, Tranexamic Acid therapeutic use
- Abstract
Purpose: Trauma and hemorrhagic shock (T/HS) is a major cause of morbidity and mortality. Existing treatment options are largely limited to source control and fluid and blood repletion. Previously, we have shown that enteral protease inhibition improves outcomes in experimental models of T/HS by protecting the gut from malperfusion and ischemia. However, enteral protease inhibition was achieved invasively, by laparotomy and direct injection of tranexamic acid (TXA) into the small intestine. In this study, we tested a minimally invasive method of enteral protease inhibitor infusion in experimental T/HS that can be readily adapted for clinical use., Methods: Wistar rats were exsanguinated to a mean arterial blood pressure (MABP) of 40 mmHg, with laparotomy to induce trauma. Hypovolemia was maintained for 120 min and was followed by reperfusion of shed blood. Animals were monitored for an additional 120 min. A modified orogastric multi-lumen tube was developed to enable rapid enteral infusion of a protease inhibitor solution while simultaneously mitigating risk of reflux aspiration into the airways. The catheter was used to deliver TXA (T/HS + TXA) or vehicle (T/HS) continuously into the proximal small intestine, starting 20 min into the ischemic period., Results: Rats treated with enteral protease inhibition (T/HS + TXA) displayed improved outcomes compared to control animals (T/HS), including significantly improved MABP (p = 0.022) and lactate (p = 0.044). Mass spectrometry-based analysis of the plasma peptidome after T/HS indicated mitigation of systemic proteolysis in T/HS + TXA., Conclusion: Minimally invasive, continuous enteral protease inhibitor delivery improves outcomes in T/HS and is readily translatable to the clinical arena., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)
- Published
- 2022
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42. Brain Proteome and Behavioural Analysis in Wild Type, BDNF +/- and BDNF -/- Adult Zebrafish ( Danio rerio ) Exposed to Two Different Temperatures.
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Maffioli E, Angiulli E, Nonnis S, Grassi Scalvini F, Negri A, Tedeschi G, Arisi I, Frabetti F, D'Aniello S, Alleva E, Cioni C, and Toni M
- Subjects
- Animals, Behavior Rating Scale, Brain metabolism, Brain-Derived Neurotrophic Factor metabolism, Mammals metabolism, Proteomics, Temperature, Proteome genetics, Proteome metabolism, Zebrafish metabolism
- Abstract
Experimental evidence suggests that environmental stress conditions can alter the expression of BDNF and that the expression of this neurotrophin influences behavioural responses in mammalian models. It has been recently demonstrated that exposure to 34 °C for 21 days alters the brain proteome and behaviour in zebrafish. The aim of this work was to investigate the role of BDNF in the nervous system of adult zebrafish under control and heat treatment conditions. For this purpose, zebrafish from three different genotypes (wild type, heterozygous BDNF
+/- and knock out BDNF-/- ) were kept for 21 days at 26 °C or 34 °C and then euthanized for brain molecular analyses or subjected to behavioural tests (Y-maze test, novel tank test, light and dark test, social preference test, mirror biting test) for assessing behavioural aspects such as boldness, anxiety, social preference, aggressive behaviour, interest for the novel environment and exploration. qRT-PCR analysis showed the reduction of gene expression of BDNF and its receptors after heat treatment in wild type zebrafish. Moreover, proteomic analysis and behavioural tests showed genotype- and temperature-dependent effects on brain proteome and behavioural responding. Overall, the absent expression of BDNF in KO alters (1) the brain proteome by reducing the expression of proteins involved in synapse functioning and neurotransmitter-mediated transduction; (2) the behaviour, which can be interpreted as bolder and less anxious and (3) the cellular and behavioural response to thermal treatment.- Published
- 2022
- Full Text
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43. A Wide-Proteome Analysis to Identify Molecular Pathways Involved in Kidney Response to High-Fat Diet in Mice.
- Author
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Dozio E, Maffioli E, Vianello E, Nonnis S, Grassi Scalvini F, Spatola L, Roccabianca P, Tedeschi G, and Corsi Romanelli MM
- Subjects
- Animals, Biomarkers metabolism, Fibrosis, Kidney metabolism, Lipids, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Obesity metabolism, Proteome metabolism, Proteomics, Diet, High-Fat adverse effects, Renal Insufficiency, Chronic metabolism
- Abstract
The etiopathogenesis of obesity-related chronic kidney disease (CKD) is still scarcely understood. To this aim, we assessed the effect of high-fat diet (HF) on molecular pathways leading to organ damage, steatosis, and fibrosis. Six-week-old male C57BL/6N mice were fed HF diet or normal chow for 20 weeks. Kidneys were collected for genomic, proteomic, histological studies, and lipid quantification. The main findings were as follows: (1) HF diet activated specific pathways leading to fibrosis and increased fatty acid metabolism; (2) HF diet promoted a metabolic shift of lipid metabolism from peroxisomes to mitochondria; (3) no signs of lipid accumulation and/or fibrosis were observed, histologically; (4) the early signs of kidney damage seemed to be related to changes in membrane protein expression; (5) the proto-oncogene MYC was one of the upstream transcriptional regulators of changes occurring in protein expression. These results demonstrated the potential usefulness of specific selected molecules as early markers of renal injury in HF, while histomorphological changes become visible later in obesity-related CDK. The integration of these information with data from biological fluids could help the identification of biomarkers useful for the early detection and prevention of tissue damage in clinical practice.
- Published
- 2022
- Full Text
- View/download PDF
44. Cellular studies of the two main isoforms of human d-aspartate oxidase.
- Author
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Rabattoni V, Pollegioni L, Tedeschi G, Maffioli E, and Sacchi S
- Subjects
- D-Aspartate Oxidase analysis, D-Aspartate Oxidase genetics, D-Aspartic Acid metabolism, Escherichia coli cytology, Humans, Isoenzymes analysis, Isoenzymes genetics, Isoenzymes metabolism, Tumor Cells, Cultured, D-Aspartate Oxidase metabolism, Escherichia coli metabolism
- Abstract
Human d-aspartate oxidase (hDASPO) is a FAD-dependent enzyme responsible for the degradation of d-aspartate (d-Asp). In the mammalian central nervous system, d-Asp behaves as a classical neurotransmitter, it is thought to be involved in neural development, brain morphology and behavior, and appears to be involved in several pathological states, such as schizophrenia and Alzheimer's disease. Apparently, the human DDO gene produces alternative transcripts encoding for three putative hDASPO isoforms, constituted by 341 (the 'canonical' form), 369, and 282 amino acids. Despite the increasing interest in hDASPO and its physiological role, little is known about these different isoforms. Here, the additional N-terminal peptide present in the hDASPO_369 isoform only has been identified in hippocampus of Alzheimer's disease female patients, while peptides corresponding to the remaining part of the protein were present in samples from male and female healthy controls and Alzheimer's disease patients. The hDASPO_369 isoform was largely expressed in E. coli as insoluble protein, hampering with its biochemical characterization. Furthermore, we generated U87 human glioblastoma cell clones stably expressing hDASPO_341 and, for the first time, hDASPO_369 isoforms; the latter protein showed a lower expression compared with the canonical isoform. Both protein isoforms are active (showing similar kinetic properties), localize to the peroxisomes, are very stable (a half-life of approximately 100 h has been estimated), and are primarily degraded through the ubiquitin-proteasome system. These studies shed light on the properties of hDASPO isoforms with the final aim to clarify the mechanisms controlling brain levels of the neuromodulator d-Asp., (© 2021 Federation of European Biochemical Societies.)
- Published
- 2021
- Full Text
- View/download PDF
45. Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits.
- Author
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Genova F, Nonnis S, Maffioli E, Tedeschi G, Strillacci MG, Carisetti M, Sironi G, Cupaioli FA, Di Nanni N, Mezzelani A, Mosca E, Helps CR, Leegwater PAJ, Dorso L, and Longeri M
- Subjects
- Amyloidosis, Familial metabolism, Animals, Genetic Variation genetics, Kidney Diseases metabolism, MicroRNAs, Proteomics, Whole Genome Sequencing, Amyloidogenic Proteins metabolism, Amyloidosis, Familial genetics, Amyloidosis, Familial veterinary, Cat Diseases genetics, Cat Diseases metabolism, Cats genetics, Cats metabolism, Kidney metabolism, Kidney Diseases genetics, Kidney Diseases veterinary
- Abstract
The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Whole-genome sequences of two affected Abyssinians and 195 controls of other breeds (part of the 99 Lives initiative) were screened to prioritize potential disease-associated variants. Proteome and miRNAome from formalin-fixed paraffin-embedded kidney specimens of fully necropsied Abyssinian cats, three affected and three non-amyloidosis-affected were characterized. While the trigger of the disorder remains unclear, overall, (i) 35,960 genomic variants were detected; (ii) 215 and 56 proteins were identified as exclusive or overexpressed in the affected and control kidneys, respectively; (iii) 60 miRNAs were differentially expressed, 20 of which are newly described. With omics data integration, the general conclusions are: (i) the familial amyloid renal form in Abyssinians is not a simple monogenic trait; (ii) amyloid deposition is not triggered by mutated amyloidogenic proteins but is a mix of proteins codified by wild-type genes; (iii) the form is biochemically classifiable as AA amyloidosis.
- Published
- 2021
- Full Text
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46. Antimicrobial D-amino acid oxidase-derived peptides specify gut microbiota.
- Author
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Murtas G, Sacchi S, Tedeschi G, Maffioli E, Notomista E, Cafaro V, Abbondi M, Mothet JP, and Pollegioni L
- Subjects
- Amino Acid Sequence, Amino Acids chemistry, Amino Acids metabolism, Animals, D-Amino-Acid Oxidase chemistry, D-Amino-Acid Oxidase genetics, Female, Humans, Intestine, Small metabolism, Intestine, Small microbiology, Male, Mice, Mice, Inbred C57BL, Protein Conformation, Rats, Rats, Wistar, Sequence Homology, Anti-Bacterial Agents pharmacology, D-Amino-Acid Oxidase metabolism, Gastrointestinal Microbiome drug effects, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Intestine, Small drug effects, Pore Forming Cytotoxic Proteins pharmacology
- Abstract
The flavoenzyme D-amino acid oxidase (DAAO) is deputed to the degradation of D-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal D-amino acids to generate hydrogen peroxide (H
2 O2 ), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1-16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.- Published
- 2021
- Full Text
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47. Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells.
- Author
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Tripodi F, Badone B, Vescovi M, Milanesi R, Nonnis S, Maffioli E, Bonanomi M, Gaglio D, Tedeschi G, and Coccetti P
- Subjects
- Adenosine Triphosphate metabolism, Cell Proliferation drug effects, Hep G2 Cells, Humans, Liver Neoplasms drug therapy, Methionine metabolism, Mitochondria drug effects, Mitochondria metabolism, Signal Transduction drug effects, TOR Serine-Threonine Kinases drug effects, TOR Serine-Threonine Kinases metabolism, AMP-Activated Protein Kinases metabolism, Liver Neoplasms metabolism, Liver Neoplasms pathology, Methionine pharmacology
- Abstract
Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
- Full Text
- View/download PDF
48. High-Resolution Mass Spectrometry-Based Approaches for the Detection and Quantification of Peptidase Activity in Plasma.
- Author
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Maffioli E, Jiang Z, Nonnis S, Negri A, Romeo V, Lietz CB, Hook V, Ristagno G, Baselli G, Kistler EB, Aletti F, O'Donoghue AJ, and Tedeschi G
- Subjects
- Amino Acid Sequence, Animals, Peptide Hydrolases chemistry, Proteomics, Substrate Specificity, Swine, Peptide Hydrolases blood, Tandem Mass Spectrometry methods
- Abstract
Proteomic technologies have identified 234 peptidases in plasma but little quantitative information about the proteolytic activity has been uncovered. In this study, the substrate profile of plasma proteases was evaluated using two nano-LC-ESI-MS/MS methods. Multiplex substrate profiling by mass spectrometry (MSP-MS) quantifies plasma protease activity in vitro using a global and unbiased library of synthetic peptide reporter substrates, and shotgun peptidomics quantifies protein degradation products that have been generated in vivo by proteases. The two approaches gave complementary results since they both highlight key peptidase activities in plasma including amino- and carboxypeptidases with different substrate specificity profiles. These assays provide a significant advantage over traditional approaches, such as fluorogenic peptide reporter substrates, because they can detect active plasma proteases in a global and unbiased manner, in comparison to detecting select proteases using specific reporter substrates. We discovered that plasma proteins are cleaved by endoproteases and these peptide products are subsequently degraded by amino- and carboxypeptidases. The exopeptidases are more active and stable in plasma and therefore were found to be the most active proteases in the in vitro assay. The protocols presented here set the groundwork for studies to evaluate changes in plasma proteolytic activity in shock.
- Published
- 2020
- Full Text
- View/download PDF
49. Rational Design of a User-Friendly Aptamer/Peptide-Based Device for the Detection of Staphylococcus aureus .
- Author
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Ronda L, Tonelli A, Sogne E, Autiero I, Spyrakis F, Pellegrino S, Abbiati G, Maffioli E, Schulte C, Piano R, Cozzini P, Mozzarelli A, Bettati S, Clerici F, Milani P, Lenardi C, Tedeschi G, and Gelmi ML
- Subjects
- Peptides, Aptamers, Nucleotide, Biosensing Techniques, Staphylococcus aureus isolation & purification
- Abstract
The urgent need to develop a detection system for Staphylococcus aureus , one of the most common causes of infection, is prompting research towards novel approaches and devices, with a particular focus on point-of-care analysis. Biosensors are promising systems to achieve this aim. We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. We show that the displacement of fluorescent peptides upon the competitive binding of S. aureus to immobilized aptamers can be detected and quantified through fluorescence loss. This approach could be also applied to the detection of other bacterial species once aptamers interacting with specific antigens will be identified, allowing the development of a platform for easy detection of a pathogen without requiring access to a healthcare environment.
- Published
- 2020
- Full Text
- View/download PDF
50. Proteomic Analysis Reveals a Mitochondrial Remodeling of βTC3 Cells in Response to Nanotopography.
- Author
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Maffioli E, Galli A, Nonnis S, Marku A, Negri A, Piazzoni C, Milani P, Lenardi C, Perego C, and Tedeschi G
- Abstract
Recently, using cluster-assembled zirconia substrates with tailored roughness produced by supersonic cluster beam deposition, we demonstrated that β cells can sense nanoscale features of the substrate and can translate these stimuli into a mechanotransductive pathway capable of preserveing β-cell differentiation and function in vitro in long-term cultures of human islets. Using the same proteomic approach, we now focused on the mitochondrial fraction of βTC3 cells grown on the same zirconia substrates and characterized the morphological and proteomic modifications induced by the nanostructure. The results suggest that, in βTC3 cells, mitochondria are perturbed by the nanotopography and activate a program involving metabolism modification and modulation of their interplay with other organelles. Data were confirmed in INS1E, a different β-cell model. The change induced by the nanostructure can be pro-survival and prime mitochondria for a metabolic switch to match the new cell needs., (Copyright © 2020 Maffioli, Galli, Nonnis, Marku, Negri, Piazzoni, Milani, Lenardi, Perego and Tedeschi.)
- Published
- 2020
- Full Text
- View/download PDF
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