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1. Dissolution of variable-in-shape drug particles via the level-set method

Author

Cristiani, Emiliano, Grassi, Mario, Ignoto, Francesca L., and Pontrelli, Giuseppe

Subjects
Mathematics - Dynamical Systems, Physics - Fluid Dynamics
Abstract

In this work, we deal with a mathematical model describing the dissolution process of irregularly shaped particles. In particular, we consider a complete dissolution model accounting for both surface kinetics and convective diffusion, for three drugs with different solubility and wettability: theophylline, griseofulvin, and nimesulide. The possible subsequent recrystallization process in the bulk fluid is also considered. The governing differential equations are revisited in the context of the level-set method and Hamilton-Jacobi equations, then they are solved numerically. This choice allows us to deal with the simultaneous dissolution of hundreds of different polydisperse particles. We show the results of many computer simulations which investigate the impact of the particle size, shape, area/volume ratio, and the dependence of the interfacial mass transport coefficient on the surface curvature.

Published
2024

2. Diagnostic accuracy of research criteria for prodromal frontotemporal dementia

Author

Benussi, Alberto, Premi, Enrico, Grassi, Mario, Alberici, Antonella, Cantoni, Valentina, Gazzina, Stefano, Archetti, Silvana, Gasparotti, Roberto, Fumagalli, Giorgio G., Bouzigues, Arabella, Russell, Lucy L., Samra, Kiran, Cash, David M., Bocchetta, Martina, Todd, Emily G., Convery, Rhian S., Swift, Imogen, Sogorb-Esteve, Aitana, Heller, Carolin, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert Jr., Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, Mendonça, Alexandre, Tiraboschi, Pietro, Butler, Chris R., Santana, Isabel, Gerhard, Alexander, Le Ber, Isabelle, Pasquier, Florence, Ducharme, Simon, Levin, Johannes, Sorbi, Sandro, Otto, Markus, Padovani, Alessandro, Rohrer, Jonathan D., and Borroni, Barbara

Published
2024
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3. A Delicate Equilibrium: State Projects, Guild Dynamics, and Personal Interests in Silk Weaving in Ancient Regime (Turin, Eighteenth Century)

Author

Grassi, Mario, Okazaki, Tetsuji, Series Editor, Brandt, Loren, Editorial Board Member, Cha, Myung Soo, Editorial Board Member, Crafts, Nicholas, Editorial Board Member, Diebolt, Claude, Editorial Board Member, Eichengreen, Barry, Editorial Board Member, Fishback, Price V, Editorial Board Member, Greif, Avner, Editorial Board Member, Roy, Tirthanker, Editorial Board Member, Saito, Osamu, Editorial Board Member, Streb, Jochen, Editorial Board Member, Wolf, Nikolaus, Editorial Board Member, Vernus, Pierre, editor, Martini, Manuela, editor, and Hashino, Tomoko, editor

Published
2024
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4. Susceptibility to brain ischemia and the association between migraine and spontaneous cervical artery dissection

Author

Del Zotto, Elisabetta, Grassi, Mario, Zedde, Marialuisa, Zini, Andrea, Bersano, Anna, Gandolfo, Carlo, Silvestrelli, Giorgio, Baracchini, Claudio, Cerrato, Paolo, Lodigiani, Corrado, Marcheselli, Simona, Paciaroni, Maurizio, Spalloni, Alessandra, Cappellari, Manuel, Del Sette, Massimo, Cavallini, Anna, Lotti, Enrico Maria, DeLodovici, Maria Luisa, Gentile, Mauro, Magoni, Mauro, Padroni, Marina, Azzini, Cristiano, Calloni, Maria Vittoria, Giorli, Elisa, Braga, Massimiliano, La Spina, Paolo, Melis, Fabio, Tassi, Rossana, Terruso, Valeria, Calabrò, Rocco Salvatore, Piras, Valeria, Giossi, Alessia, Sanguigni, Sandro, Zanferrari, Carla, Mannino, Marina, Colombo, Irene, Dallocchio, Carlo, Nencini, Patrizia, Bignamini, Valeria, Adami, Alessandro, Bella, Rita, Pascarella, Rosario, and Pezzini, Alessandro

Published
2023
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7. SEMgraph: An R Package for Causal Network Analysis of High-Throughput Data with Structural Equation Models

Author

Palluzzi, Fernando and Grassi, Mario

Subjects
Quantitative Biology - Molecular Networks, Statistics - Applications
Abstract

With the advent of high-throughput sequencing (HTS) in molecular biology and medicine, the need for scalable statistical solutions for modeling complex biological systems has become of critical importance. The increasing number of platforms and possible experimental scenarios raised the problem of integrating large amounts of new heterogeneous data and current knowledge, to test novel hypotheses and improve our comprehension of physiological processes and diseases. Although network theory provided a framework to represent biological systems and study their hidden properties, different algorithms still offer low reproducibility and robustness, dependence on user-defined setup, and poor interpretability. Here we discuss the R package SEMgraph, combining network analysis and causal inference within the framework of structural equation modeling (SEM). It provides a fully automated toolkit, managing complex biological systems as multivariate networks, ensuring robustness and reproducibility through data-driven evaluation of model architecture and perturbation, that is readily interpretable in terms of causal effects among system components. In addition, SEMgraph offers several functions for perturbed path finding, model reduction, and parallelization options for the analysis of large interaction networks., Comment: 29 pages; 5 figures; original article; R package; CRAN stable version at: https://CRAN.R-project.org/package=SEMgraph; Development version available at https://github.com/fernandoPalluzzi/SEMgraph

Published
2021
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8. Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy

Author

Pezzini, Alessandro, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Tarantino, Barbara, de Gaetano, Giovanni, Zedde, Marialuisa, Marcheselli, Simona, Silvestrelli, Giorgio, Ciccone, Alfonso, DeLodovici, Maria Luisa, Princiotta Cariddi, Lucia, Paciaroni, Maurizio, Azzini, Cristiano, Padroni, Marina, Gamba, Massimo, Magoni, Mauro, Del Sette, Massimo, Tassi, Rossana, De Franco, Ivo Giuseppe, Cavallini, Anna, Calabrò, Rocco Salvatore, Cappellari, Manuel, Giorli, Elisa, Giacalone, Giacomo, Lodigiani, Corrado, Zenorini, Mara, Valletta, Francesco, Pascarella, Rosario, Grisendi, Ilaria, Assenza, Federica, Napoli, Manuela, Moratti, Claudio, Acampa, Maurizio, and Grassi, Mario

Published
2024
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17. Structural brain splitting is a hallmark of Granulin-related frontotemporal dementia

Author

Afonso, Sónia, Almeida, Maria Rosario, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bouzigues, Arabella, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Gazzina, Stefano, Grassi, Mario, Premi, Enrico, Alberici, Antonella, Benussi, Alberto, Archetti, Silvana, Gasparotti, Roberto, Bocchetta, Martina, Cash, David M., Todd, Emily G., Peakman, Georgia, Convery, Rhian S., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Jr, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Gerhard, Alexander, Ber, Isabelle Le, Pasquier, Florence, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Sorbi, Sandro, Otto, Markus, Rohrer, Jonathan D., and Borroni, Barbara

Published
2022
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19. Role of sonication pre-treatment and cation valence in nano-cellulose suspensions sol-gel transition

Author

Maestri, Cecilia Ada, Abrami, Michela, Hazan, Sharon, Chistè, Elena, Golan, Yuval, Rohrer, Julia, Bernkop-Schnürch, Andreas, Grassi, Mario, Scarpa, Marina, and Bettotti, Paolo

Subjects
Condensed Matter - Materials Science
Abstract

Sol-gel transition of carboxylated cellulose nanocrystals is investigated using rheology, SAXS, NMR and optical spectroscopies to unveil the distinctive roles of ultrasounds treatment and ions addition. Besides cellulose fibers fragmentation, sonication treatment induces fast gelling of the solution. Gelation is induced independently on the addition of cations, while the final rheological properties are highly influenced by the type, the concentration as well as on the sequence of the operations since salts must be added before sonication to produce stiff gels. Cations with various charge and dimension have been associated to ultrasounds to induce gelation and the gel elastic modulus increase proportionally with the charge over the ion size ratio. SAXS analysis of the Na+ hydrogel and Ca2+ hydrogel to which the ion was added after sonication shows the presence of structurally ordered domains where water is confined as indicated by 1H-NMR investigation of the dynamic of water exchange in the hydrogels. Conversely, separated phases containing essentially free water, characterize the hydrogels obtained by sonication after Ca2+ addition, confirming that this ion induces irreversible fiber aggregation. The rheological properties of the hydrogels depend on the duration of the ultrasound treatment and it enables the design of materials programmed with tailored energy dissipation response., Comment: 17 apges, 11 figures

Published
2017
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20. The Key Role of Wettability and Boundary Layer in Dissolution Rate Test.

Author

Biasin, Alice, Pribac, Federico, Franceschinis, Erica, Cortesi, Angelo, Grassi, Lucia, Voinovich, Dario, Colombo, Italo, Grassi, Gabriele, Milcovich, Gesmi, Grassi, Mario, and Abrami, Michela

Subjects
BOUNDARY layer (Aerodynamics), PARTICLE size distribution, DRUG bioavailability, CONTACT angle, PHENOMENOLOGICAL theory (Physics), DRUG solubility
Abstract

Background/Objectives: The present work proposes a mathematical model able to describe the dissolution of poly-disperse drug spherical particles in a solution (Dissolution Rate Test—DRT). DRT is a pivotal test performed in the pharmaceutical field to qualitatively assess drug bioavailability. Methods: The proposed mathematical model relies on the key hallmarks of DRT, such as particle size distribution, solubility, wettability, hydrodynamic conditions in the dissolving liquid of finite dimensions, and possible re-crystallization during the dissolution process. The spherical shape of the drug particles was the only cue simplification applied. Two model drugs were considered to check model robustness: theophylline (both soluble and wettable) and praziquantel (both poorly soluble and wettable). Results: The DRT data analysis within the proposed model allows us to understand that for theophylline, the main resistance to dissolution is due to the boundary layer surrounding drug particles, whereas wettability plays a negligible role. Conversely, the effect of low wettability cannot be neglected for praziquantel. These results are validated by the determination of drug wettability performed while measuring the solid–liquid contact angle on four liquids with decreasing polarities. Moreover, the percentage of drug polarity was determined. Conclusions: The proposed mathematical model confirms the importance of the different physical phenomena leading the dissolution of poly-disperse solid drug particles in a solution. Although a comprehensive mathematical model was proposed and applied, the DRT data of theophylline and praziquantel was successfully fitted by means of just two fitting parameters. [ABSTRACT FROM AUTHOR]

Published
2024
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21. SEMbap: Bow-free covariance search and data de-correlation.

Author

Grassi, Mario and Tarantino, Barbara

Subjects
*STRUCTURAL equation modeling, *DIRECTED acyclic graphs, *SEARCH algorithms, *PRINCIPAL components analysis, *GENE expression, *DIRECTED graphs
Abstract

Large-scale studies of gene expression are commonly influenced by biological and technical sources of expression variation, including batch effects, sample characteristics, and environmental impacts. Learning the causal relationships between observable variables may be challenging in the presence of unobserved confounders. Furthermore, many high-dimensional regression techniques may perform worse. In fact, controlling for unobserved confounding variables is essential, and many deconfounding methods have been suggested for application in a variety of situations. The main contribution of this article is the development of a two-stage deconfounding procedure based on Bow-free Acyclic Paths (BAP) search developed into the framework of Structural Equation Models (SEM), called SEMbap(). In the first stage, an exhaustive search of missing edges with significant covariance is performed via Shipley d-separation tests; then, in the second stage, a Constrained Gaussian Graphical Model (CGGM) is fitted or a low dimensional representation of bow-free edges structure is obtained via Graph Laplacian Principal Component Analysis (gLPCA). We compare four popular deconfounding methods to BAP search approach with applications on simulated and observed expression data. In the former, different structures of the hidden covariance matrix have been replicated. Compared to existing methods, BAP search algorithm is able to correctly identify hidden confounding whilst controlling false positive rate and achieving good fitting and perturbation metrics. Author summary: Directed acyclic graphs (DAGs) directed graph, with variables at the vertices and direct causal connections at the edges, can be used to illustrate the causal structure of the SEM, but this does not always mean that all significant factors are considered. We examine a class of models that may include some hidden variables. Specifically, we consider that the graph represents a bow-free acyclic path diagram (BAP), where the directed edges signify direct causal effects, while the bidirected edges suggest hidden confounders. In this paper, we provide a two-step deconfounding technique based on BAP search, which is included into the SEM framework via the SEMbap() function implemented in the R package SEMgraph. Secondly, we want to offer a significant evaluation of the most advanced deconfounding techniques using both synthetic and real data, as well as knowledge of a biological signaling pathway encoded in a DAG, in terms of (i) SEM fitting, (ii) system perturbation, and (iii) recovery performance metrics. The BAP search algorithm outperforms current techniques in accurately detecting hidden confounding, regulating false positive rate, and producing well-fitting and perturbation metrics. [ABSTRACT FROM AUTHOR]

Published
2024
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24. SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy

Author

Pezzini, Alessandro, Grassi, Mario, Silvestrelli, Giorgio, Locatelli, Martina, Rifino, Nicola, Beretta, Simone, Gamba, Massimo, Raimondi, Elisa, Giussani, Giuditta, Carimati, Federico, Sangalli, Davide, Corato, Manuel, Gerevini, Simonetta, Masciocchi, Stefano, Cortinovis, Matteo, La Gioia, Sara, Barbieri, Francesca, Mazzoleni, Valentina, Pezzini, Debora, Bonacina, Sonia, Pilotto, Andrea, Benussi, Alberto, Magoni, Mauro, Premi, Enrico, Prelle, Alessandro Cesare, Agostoni, Elio Clemente, Palluzzi, Fernando, De Giuli, Valeria, Magherini, Anna, Roccatagliata, Daria Valeria, Vinciguerra, Luisa, Puglisi, Valentina, Fusi, Laura, Diamanti, Susanna, Santangelo, Francesco, Xhani, Rubjona, Pozzi, Federico, Grampa, Giampiero, Versino, Maurizio, Salmaggi, Andrea, Marcheselli, Simona, Cavallini, Anna, Giossi, Alessia, Censori, Bruno, Ferrarese, Carlo, Ciccone, Alfonso, Sessa, Maria, and Padovani, Alessandro

Published
2022
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25. In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells

Author

Maddaloni, Marianna, primary, Farra, Rossella, additional, Dapas, Barbara, additional, Felluga, Fulvia, additional, Benedetti, Fabio, additional, Berti, Federico, additional, Drioli, Sara, additional, Vidali, Mattia, additional, Cemazar, Maja, additional, Kamensek, Urska, additional, Brancolini, Claudio, additional, Murano, Erminio, additional, Maremonti, Francesca, additional, Grassi, Mario, additional, Biasin, Alice, additional, Rizzolio, Flavio, additional, Cavarzerani, Enrico, additional, Scaggiante, Bruna, additional, Bulla, Roberta, additional, Balduit, Andrea, additional, Ricci, Giuseppe, additional, Zito, Gabriella, additional, Romano, Federico, additional, Bonin, Serena, additional, Azzalini, Eros, additional, Baj, Gabriele, additional, Tierno, Domenico, additional, and Grassi, Gabriele, additional

Published
2024
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26. Early seizures and risk of epilepsy and death after intracerebral haemorrhage: The MUCH Italy

Author

Pezzini, Alessandro, primary, Tarantino, Barbara, additional, Zedde, Marialuisa, additional, Marcheselli, Simona, additional, Silvestrelli, Giorgio, additional, Ciccone, Alfonso, additional, DeLodovici, Maria Luisa, additional, Princiotta Cariddi, Lucia, additional, Vidale, Simone, additional, Paciaroni, Maurizio, additional, Azzini, Cristiano, additional, Padroni, Marina, additional, Gamba, Massimo, additional, Magoni, Mauro, additional, Del Sette, Massimo, additional, Tassi, Rossana, additional, De Franco, Ivo Giuseppe, additional, Cavallini, Anna, additional, Calabrò, Rocco Salvatore, additional, Cappellari, Manuel, additional, Giorli, Elisa, additional, Giacalone, Giacomo, additional, Lodigiani, Corrado, additional, Zenorini, Mara, additional, Valletta, Francesco, additional, Cutillo, Gianni, additional, Bonelli, Guido, additional, Abrignani, Giorgia, additional, Castellini, Paola, additional, Genovese, Antonio, additional, Latte, Lilia, additional, Trapasso, Maria Claudia, additional, Ferraro, Chiara, additional, Piancatelli, Francesco, additional, Pascarella, Rosario, additional, Grisendi, Ilaria, additional, Assenza, Federica, additional, Napoli, Manuela, additional, Moratti, Claudio, additional, Acampa, Maurizio, additional, and Grassi, Mario, additional

Published
2024
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29. Contributors

Author

Abrami, Michela, primary, Aland, Sebastian, additional, Andreozzi, A., additional, Audi, Said H., additional, Becker, Sid, additional, Bianco, N., additional, Bomberna, Tim, additional, Chan, Christina, additional, Chiastra, Claudio, additional, Colombo, Monika, additional, Corti, Anna, additional, Cowley, Allen W., additional, Curatolo, Michele, additional, D’Alessandro, Giampaolo, additional, Dapas, Barbara, additional, Dash, Ranjan K., additional, De Bonis, Maria Valeria, additional, de Monte, Filippo, additional, De Nisco, Giuseppe, additional, Debbaut, Charlotte, additional, di Vittorio, Rosario, additional, Drexler, Dániel András, additional, Dvoriashyna, Mariia, additional, Farra, Rossella, additional, Formaggia, Luca, additional, Foss, Alexander J.E., additional, Fu, Bingmei M., additional, Gaffney, Eamonn A., additional, Grassi, Gabriele, additional, Grassi, Lucia, additional, Grassi, Mario, additional, Iasiello, M., additional, Khanafer, Khalil, additional, Kovács, Levente, additional, Kuznetsov, Andrey V., additional, Kuznetsov, Ivan A., additional, Ladd, Shay, additional, Lagonigro, Laura, additional, Marra, Francesco, additional, McGinty, Sean, additional, Migliavacca, Francesco, additional, Milcovich, Gesmi, additional, Nardinocchi, Paola, additional, Pontrelli, Giuseppe, additional, Reichel, Felix, additional, Repetto, Rodolfo, additional, Rodriguez Matas, Jose Felix, additional, Ruocco, Gianpaolo, additional, Sadri, Shima, additional, Si, Xiuhua April, additional, Teresi, Luciano, additional, Tomar, Namrata, additional, Tucci, C., additional, Vadasz, Alisa S., additional, Vadasz, Peter, additional, Vafai, Kambiz, additional, Wittwer, Lucas Daniel, additional, Wright, Neil T., additional, Xi, Jinxiang, additional, and Zunino, Paolo, additional

Published
2022
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30. Drug delivery and in vivo absorption

Author

Abrami, Michela, primary, Grassi, Lucia, additional, Farra, Rossella, additional, Dapas, Barbara, additional, di Vittorio, Rosario, additional, Grassi, Gabriele, additional, Milcovich, Gesmi, additional, and Grassi, Mario, additional

Published
2022
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37. In Vitro and In Vivo Evaluation of the Effects of Drug 2c and Derivatives on Ovarian Cancer Cells.

Author

Maddaloni, Marianna, Farra, Rossella, Dapas, Barbara, Felluga, Fulvia, Benedetti, Fabio, Berti, Federico, Drioli, Sara, Vidali, Mattia, Cemazar, Maja, Kamensek, Urska, Brancolini, Claudio, Murano, Erminio, Maremonti, Francesca, Grassi, Mario, Biasin, Alice, Rizzolio, Flavio, Cavarzerani, Enrico, Scaggiante, Bruna, Bulla, Roberta, and Balduit, Andrea

Subjects
DRUG derivatives, OVARIAN cancer, CANCER cells, PHARMACODYNAMICS, DEUBIQUITINATING enzymes, OVARIAN follicle, UBIQUITINATION
Abstract

Background: The identification of novel therapeutic strategies for ovarian cancer (OC), the most lethal gynecological neoplasm, is of utmost urgency. Here, we have tested the effectiveness of the compound 2c (4-hydroxy-2,6-bis(4-nitrobenzylidene)cyclohexanone 2). 2c interferes with the cysteine-dependent deubiquitinating enzyme (DUB) UCHL5, thus affecting the ubiquitin-proteasome-dependent degradation of proteins. Methods: 2c phenotypic/molecular effects were studied in two OC 2D/3D culture models and in a mouse xenograft model. Furthermore, we propose an in silico model of 2c interaction with DUB-UCHL5. Finally, we have tested the effect of 2c conjugated to several linkers to generate 2c/derivatives usable for improved drug delivery. Results: 2c effectively impairs the OC cell line and primary tumor cell viability in both 2D and 3D conditions. The effectiveness is confirmed in a xenograft mouse model of OC. We show that 2c impairs proteasome activity and triggers apoptosis, most likely by interacting with DUB-UCHL5. We also propose a mechanism for the interaction with DUB-UCHL5 via an in silico evaluation of the enzyme-inhibitor complex. 2c also reduces cell growth by down-regulating the level of the transcription factor E2F1. Eventually, 2c activity is often retained after the conjugation with linkers. Conclusion: Our data strongly support the potential therapeutic value of 2c/derivatives in OC. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Migraine improvement after spontaneous cervical artery dissection the Italian Project on Stroke in Young Adults (IPSYS)

Author

De Giuli, Valeria, Graziano, Francesca, Zini, Andrea, Zedde, Marialuisa, Patella, Rosalba, Lodigiani, Corrado, Marcheselli, Simona, DeLodovici, Maria Luisa, Paciaroni, Maurizio, Casetta, Ilaria, Giorli, Elisa, Adami, Alessandro, Braga, Massimiliano, Casella, Carmela, Giossi, Alessia, Silvestrelli, Giorgio, Tancredi, Lucia, Lotti, Enrico Maria, Poli, Loris, Caria, Filomena, Piras, Valeria, Cucurachi, Laura, Gamba, Massimo, Grassi, Mario, Padovani, Alessandro, Pezzini, Alessandro, and on behalf of the Italian Project on Stroke in Young Adults (IPSYS) Investigators

Published
2019
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48. Ionic Strength Impacts the Physical Properties of Agarose Hydrogels.

Author

Sacco, Pasquale, Piazza, Francesco, Marsich, Eleonora, Abrami, Michela, Grassi, Mario, and Donati, Ivan

Subjects
HYDROGELS, IONIC strength, POLYSACCHARIDES, TEMPERATURE effect, BIOPOLYMERS
Abstract

Agarose is a natural polysaccharide known for its ability to form thermoreversible hydrogels. While the effects of curing temperature and polysaccharide concentration on mechanical properties have been discussed in the literature, the role of ionic strength has been less studied. In the present manuscript, we investigate the effects of supporting salt concentration and the role of cation (i.e. Na+ or Li+, neighbors in the Hofmeister series), on the setting and performance of agarose hydrogels. Compressive and rheological measurements show that the supporting salts reduce the immediate elastic response of agarose hydrogels, with Li+ showing a stronger effect than Na+ at high ionic strength, while they significantly increase the extent of linear stress-strain response (i.e., linear elasticity). The presence of increasing amounts of added supporting salt also leads to a reduction in hysteresis during mechanical deformation due to loading and unloading cycles, which is more pronounced with Li+ than with Na+. The combination of rheological measurements and NMR relaxometry shows a mesh size in agarose hydrogels in the order of 6–17 nm, with a thickness of the water layer bound to the biopolymer of about 3 nm. Of note, the different structuring of the water within the hydrogel network due to the different alkali seems to play a role for the final performance of the hydrogels. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Sem Best Shortest Paths for the Characterization of Differentially Expressed Genes

Author

Pepe, Daniele, Palluzzi, Fernando, Grassi, Mario, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, DI Serio, Clelia, editor, Liò, Pietro, editor, Nonis, Alessandro, editor, and Tagliaferri, Roberto, editor

Published
2015
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