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157 results on '"Ruvoletto, Mariagrazia"'

1. The protease activated receptor 2 - CCAAT/enhancer-binding protein beta - SerpinB3 axis inhibition as a novel strategy for the treatment of non-alcoholic steatohepatitis

Author

Villano, Gianmarco, Novo, Erica, Turato, Cristian, Quarta, Santina, Ruvoletto, Mariagrazia, Biasiolo, Alessandra, Protopapa, Francesca, Chinellato, Monica, Martini, Andrea, Trevellin, Elisabetta, Granzotto, Marnie, Cannito, Stefania, Cendron, Laura, De Siervi, Silvia, Guido, Maria, Parola, Maurizio, Vettor, Roberto, and Pontisso, Patrizia

Published
2024
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2. 1-Piperidine Propionic Acid Protects from Septic Shock Through Protease Receptor 2 Inhibition.

Author

Luisetto, Roberto, Scarpa, Marco, Villano, Gianmarco, Martini, Andrea, Quarta, Santina, Ruvoletto, Mariagrazia, Guerra, Pietro, Scarpa, Melania, Chinellato, Monica, Biasiolo, Alessandra, Campigotto, Edoardo, Basso, Daniela, Fassan, Matteo, and Pontisso, Patrizia

Subjects
SEPTIC shock, PROTEASE-activated receptors, PROPIONIC acid, SMALL molecules, ENDOTOXEMIA
Abstract

Sepsis is a complex disorder caused by a dysregulated host response to infection, with high levels of morbidity and mortality. Treatment aimed to modulate immune response and maintain vascular function is still one of the major clinical challenges. This study was designed to test the effect of the small molecule 1-Piperidine Propionic Acid (1-PPA) as molecular targeted agent to block protease-activated receptor 2 (PAR2), one of the major modulators of inflammatory response in LPS-induced experimental endotoxemia. In the THP-1 cell line, LPS-induced cytokine expression was inhibited by 1-PPA in a dose-dependent manner. In LPS-injected mice, treatment with 1-PPA was effective in reducing mortality and sepsis-related symptoms and improved cardiac function parameters. After 6 h from LPS injection, a significant decrease in IL-6, IL-1β, and IL-10 was observed in the lung tissue of 1-PPA-treated mice, compared to controls. In these mice, a significant decrease in vasoactive molecules, especially kininogen-1, was also observed, mainly in the liver. Histopathological analysis confirmed typical features of sepsis in different organs and these findings were markedly reduced in mice treated with 1-PPA. These data demonstrate the effectiveness of 1-PPA in protecting the whole organism from sepsis-induced damage. [ABSTRACT FROM AUTHOR]

Published
2024
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3. SAT-219 Discovering 1-piperidine propionic acid inhibiting effect on protease activated receptor 2 and serpinb3 as a new therapeutic strategy for metabolic dysfunction-associated steatohepatitis

Author

Chinellato, Monica, primary, Villano, Gianmarco, additional, Novo, Erica, additional, Turato, Cristian, additional, Quarta, Santina, additional, Ruvoletto, Mariagrazia, additional, Biasiolo, Alessandra, additional, Martini, Andrea, additional, Cannito, Stefania, additional, Mazzucco, Camilla, additional, Gasparotto, Matteo, additional, Filippini, Francesco, additional, Spiezia, Luca, additional, Cendron, Laura, additional, Guido, Maria, additional, Vettor, Roberto, additional, Parola, Maurizio, additional, and Pontisso, Patrizia, additional

Published
2024
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4. Inhibition of Protease-Activated Receptor-2 Activation in Parkinson's Disease Using 1-Piperidin Propionic Acid.

Author

Quarta, Santina, Sandre, Michele, Ruvoletto, Mariagrazia, Campagnolo, Marta, Emmi, Aron, Biasiolo, Alessandra, Pontisso, Patrizia, and Antonini, Angelo

Subjects
PARKINSON'S disease, PROPIONIC acid, NEUROGLIA, FIBROBLASTS, MICROGLIA
Abstract

In Parkinson's disease, neuroinflammation is a double-edged sword; when inflammation occurs it can have harmful effects, despite its important role in battling infections and healing tissue. Once triggered by microglia, astrocytes acquire a reactive state and shift from supporting the survival of neurons to causing their destruction. Activated microglia and Proteinase-activated receptor-2 (PAR2) are key points in the regulation of neuroinflammation. 1-Piperidin Propionic Acid (1-PPA) has been recently described as a novel inhibitor of PAR2. The aim of our study was to evaluate the effect of 1-PPA in neuroinflammation and microglial activation in Parkinson's disease. Protein aggregates and PAR2 expression were analyzed using Thioflavin S assay and immunofluorescence in cultured human fibroblasts from Parkinson's patients, treated or untreated with 1-PPA. A significant decrease in amyloid aggregates was observed after 1-PPA treatment in all patients. A parallel decrease in PAR2 expression, which was higher in sporadic Parkinson's patients, was also observed both at the transcriptional and protein level. In addition, in mouse LPS-activated microglia, the inflammatory profile was significantly downregulated after 1-PPA treatment, with a remarkable decrease in IL-1β, IL-6, and TNF-α, together with a decreased expression of PAR2. In conclusion, 1-PPA determines the reduction in neuroglia inflammation and amyloid aggregates formation, suggesting that the pharmacological inhibition of PAR2 could be proposed as a novel strategy to control neuroinflammation. [ABSTRACT FROM AUTHOR]

Published
2024
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5. The polymorphic variant of SerpinB3 (SerpinB3‐PD) is associated with faster cirrhosis decompensation

Author

Martini, Andrea, primary, Turato, Cristian, additional, Cannito, Stefania, additional, Quarta, Santina, additional, Biasiolo, Alessandra, additional, Ruvoletto, Mariagrazia, additional, Novo, Erica, additional, Marafatto, Filippo, additional, Guerra, Pietro, additional, Tonon, Marta, additional, Clemente, Nausicaa, additional, Bocca, Claudia, additional, Piano, Salvatore Silvio, additional, Guido, Maria, additional, Gregori, Dario, additional, Parola, Maurizio, additional, Angeli, Paolo, additional, and Pontisso, Patrizia, additional

Published
2023
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8. The polymorphic variant of SerpinB3 (SerpinB3‐PD) is associated with faster cirrhosis decompensation.

Author

Martini, Andrea, Turato, Cristian, Cannito, Stefania, Quarta, Santina, Biasiolo, Alessandra, Ruvoletto, Mariagrazia, Novo, Erica, Marafatto, Filippo, Guerra, Pietro, Tonon, Marta, Clemente, Nausicaa, Bocca, Claudia, Piano, Salvatore Silvio, Guido, Maria, Gregori, Dario, Parola, Maurizio, Angeli, Paolo, and Pontisso, Patrizia

Subjects
HEPATIC fibrosis, CYSTEINE proteinase inhibitors, CIRRHOSIS of the liver, PORTAL hypertension, LIVER diseases
Abstract

Summary: Background: SerpinB3 is a cysteine protease inhibitor involved in liver disease progression due to its proinflammatory and profibrogenic properties. The polymorphic variant SerpinB3‐PD (SB3‐PD), presents a substitution in its reactive centre loop, determining the gain of function. Aims: To disclose the clinical characteristics of a cohort of patients with cirrhosis in relation to the presence of SB3‐PD and to assess the effect of this genetic variant on fibrogenic and inflammatory cytokines in vitro. Methods: We assessed SB3 polymorphism in 90 patients with cirrhosis, prospectively followed up in our referral centre. We used HepG2 and HuH‐7 cells transfected to overexpress either wild‐type SB3 (SB3‐WT) or SB3‐PD to assess their endogenous effect, while LX2 and THP‐1 cells were treated with exogenous SB3‐WT or SB3‐PD proteins. Results: Patients carrying SB3‐PD had more severe portal hypertension and higher MELD scores, than patients carrying SB3‐WT. In multivariate analysis, SB3‐PD was an independent predictor of cirrhosis complications. Patients with SB3‐PD polymorphism presented with more severe liver fibrosis and inflammatory features. Hepatoma cells overexpressing SB3‐PD showed higher TGF‐β1 expression than controls. The addition of recombinant SB3‐PD induced an up‐regulation of TGF‐β1 in LX2 cells and a more prominent inflammatory profile in THP‐1 cells, compared to the effect of SB3‐WT protein. Conclusions: The polymorphic variant SB3‐PD is highly effective in determining activation of TGF‐β1 and inflammation in vitro. Patients with cirrhosis who carry SB3‐PD polymorphism may be more prone to develop severe liver disease progression. However, further validation studies are warranted to support the in vivo relevance of this polymorphism. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Inhibition of CCAT/enhancer-binding protein beta-serpinB3 axis by 1-piperidin propionic acid: a new targeted therapy for non-alcoholic steatohepatitis

Author

Protopapa, Francesca, primary, Villano, Gianmarco, additional, Novo, Erica, additional, Turato, Cristian, additional, Quarta, Santina, additional, Ruvoletto, Mariagrazia, additional, Biasiolo, Alessandra, additional, Chinellato, Monica, additional, Martini, Andrea, additional, Trevellin, Elisabetta, additional, Granzotto, Marnie, additional, Cannito, Stefania, additional, Cendron, Laura, additional, Guido, Maria, additional, Parola, Maurizio, additional, Vettor, Roberto, additional, and Pontisso, Patrizia, additional

Published
2023
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10. SerpinB3 Upregulates Low-Density Lipoprotein Receptor-Related Protein (LRP) Family Members, Leading to Wnt Signaling Activation and Increased Cell Survival and Invasiveness

Author

Quarta, Santina, primary, Cappon, Andrea, additional, Turato, Cristian, additional, Ruvoletto, Mariagrazia, additional, Cannito, Stefania, additional, Villano, Gianmarco, additional, Biasiolo, Alessandra, additional, Maggi, Maristella, additional, Protopapa, Francesca, additional, Bertazza, Loris, additional, Fasolato, Silvano, additional, Parola, Maurizio, additional, and Pontisso, Patrizia, additional

Published
2023
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14. The CCAAT/Enhancer-Binding Protein Beta - SerpinB3 Axis Inhibition as a Novel Strategy for Non-Alcoholic Steatohepatitis Treatment

Author

Villano, Gianmarco, primary, Novo, Erica, additional, Turato, Cristian, additional, Quarta, Santina, additional, Ruvoletto, Mariagrazia, additional, Biasiolo, Alessandra, additional, Protopapa, Francesca, additional, Chinellato, Monica, additional, Martini, Andrea, additional, Trevellin, Elisabetta, additional, Granzotto, Marnie, additional, Cannito, Stefania, additional, Cendron, Laura, additional, De Siervi, Silvia, additional, Guido, Maria, additional, Parola, Maurizio, additional, Vettor, Robertoi, additional, and Pontisso, Patrizia, additional

Published
2023
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16. Semisolid Wet Sol–Gel Silica/Hydroxypropyl Methyl Cellulose Formulation for Slow Release of Serpin B3 Promotes Wound Healing In Vivo

Author

Albiero, Mattia, primary, Fullin, Alice, additional, Villano, Gianmarco, additional, Biasiolo, Alessandra, additional, Quarta, Santina, additional, Bernardotto, Simone, additional, Turato, Cristian, additional, Ruvoletto, Mariagrazia, additional, Fadini, Gian Paolo, additional, Pontisso, Patrizia, additional, and Morpurgo, Margherita, additional

Published
2022
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18. SerpinB3 as a Pro-Inflammatory Mediator in the Progression of Experimental Non-Alcoholic Fatty Liver Disease

Author

Novo, Erica, primary, Cappon, Andrea, additional, Villano, Gianmarco, additional, Quarta, Santina, additional, Cannito, Stefania, additional, Bocca, Claudia, additional, Turato, Cristian, additional, Guido, Maria, additional, Maggiora, Marina, additional, Protopapa, Francesca, additional, Sutti, Salvatore, additional, Provera, Alessia, additional, Ruvoletto, Mariagrazia, additional, Biasiolo, Alessandra, additional, Foglia, Beatrice, additional, Albano, Emanuele, additional, Pontisso, Patrizia, additional, and Parola, Maurizio, additional

Published
2022
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20. Engineered EVs for Oxidative Stress Protection

Author

Tolomeo, Anna Maria, primary, Quarta, Santina, additional, Biasiolo, Alessandra, additional, Ruvoletto, Mariagrazia, additional, Pozzobon, Michela, additional, De Lazzari, Giada, additional, Malvicini, Ricardo, additional, Turato, Cristian, additional, Arrigoni, Giorgio, additional, Pontisso, Patrizia, additional, and Muraca, Maurizio, additional

Published
2021
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21. Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma

Author

Fasolato, Silvano, primary, Ruvoletto, Mariagrazia, additional, Nardo, Giorgia, additional, Rasola, Andrea, additional, Sciacovelli, Marco, additional, Zanus, Giacomo, additional, Turato, Cristian, additional, Quarta, Santina, additional, Terrin, Liliana, additional, Fadini, Gian Paolo, additional, Ceolotto, Giulio, additional, Guido, Maria, additional, Cillo, Umberto, additional, Indraccolo, Stefano, additional, Bernardi, Paolo, additional, and Pontisso, Patrizia, additional

Published
2021
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22. WED-449 - Inhibition of CCAT/enhancer-binding protein beta-serpinB3 axis by 1-piperidin propionic acid: a new targeted therapy for non-alcoholic steatohepatitis

Author

Protopapa, Francesca, Villano, Gianmarco, Novo, Erica, Turato, Cristian, Quarta, Santina, Ruvoletto, Mariagrazia, Biasiolo, Alessandra, Chinellato, Monica, Martini, Andrea, Trevellin, Elisabetta, Granzotto, Marnie, Cannito, Stefania, Cendron, Laura, Guido, Maria, Parola, Maurizio, Vettor, Roberto, and Pontisso, Patrizia

Published
2023
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23. SERPINB3 inhibition as a novel target therapy for non-alcoholic steatohepatitis

Author

Martini, Andrea, primary, Villano, Gianmarco, additional, Quarta, Santina, additional, Turato, Cristian, additional, Ruvoletto, Mariagrazia, additional, Biasiolo, Alessandra, additional, Cappon, Andrea, additional, Novo, Erica, additional, Cannito, Stefania, additional, Guido, Maria, additional, Parola, Maurizio, additional, and Pontisso, Patrizia, additional

Published
2020
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29. SerpinB3 Differently Up-Regulates Hypoxia Inducible Factors -1α and -2α in Hepatocellular Carcinoma: Mechanisms Revealing Novel Potential Therapeutic Targets

Author

Cannito, Stefania, primary, Foglia, Beatrice, additional, Villano, Gianmarco, additional, Turato, Cristian, additional, Delgado, Teresa C, additional, Morello, Elisabetta, additional, Pin, Fabrizio, additional, Novo, Erica, additional, Napione, Lucia, additional, Quarta, Santina, additional, Ruvoletto, Mariagrazia, additional, Fasolato, Silvano, additional, Zanus, Giacomo, additional, Colombatto, Sebastiano, additional, Lopitz-Otsoa, Fernando, additional, Fernández-Ramos, David, additional, Bussolino, Federico, additional, Sutti, Salvatore, additional, Albano, Emanuele, additional, Martínez-Chantar, Maria Luz, additional, Pontisso, Patrizia, additional, and Parola, Maurizio, additional

Published
2019
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30. FRI-117-The gain of function mutation of SerpinB3 (SCCA-PD) is associated with the severity of portal hypertension and complications onset in patients with advanced liver disease

Author

Martini, Andrea, primary, Marafatto, Filippo, additional, Turato, Cristian, additional, Novo, Erica, additional, Parola, Maurizio, additional, Biasiolo, Alessandra, additional, Quarta, Santina, additional, Ruvoletto, Mariagrazia, additional, Angeli, Paolo, additional, and Pontisso, Patrizia, additional

Published
2019
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32. SerpinB3 upregulates the Cyclooxygenase-2 / β-Catenin positive loop in colorectal cancer

Author

Terrin, Liliana, Agostini, Marco, Ruvoletto, Mariagrazia, Martini, Andrea, Pucciarelli, Salvatore, Bedin, Chiara, Nitti, Donato, and Pontisso, Patrizia

Subjects
Male, 0301 basic medicine, Oncology, Pathology, Colorectal cancer, Perineural invasion, Kaplan-Meier Estimate, Tumor stage, beta Catenin, Aged, 80 and over, COX-2, SerpinB3, colorectal cancer, tumor stage, β-Catenin, biology, Reverse Transcriptase Polymerase Chain Reaction, Hep G2 Cells, Middle Aged, Prognosis, Immunohistochemistry, Up-Regulation, Gene Expression Regulation, Neoplastic, Female, Colorectal Neoplasms, HT29 Cells, Research Paper, Signal Transduction, Adult, medicine.medical_specialty, Poor prognosis, Immunoblotting, 03 medical and health sciences, Downregulation and upregulation, Antigens, Neoplasm, Cell Line, Tumor, Internal medicine, medicine, Humans, Serpins, Aged, business.industry, medicine.disease, Cellular phenotype, 030104 developmental biology, Microscopy, Fluorescence, Cyclooxygenase 2, Catenin, biology.protein, Cyclooxygenase, business
Abstract

// Liliana Terrin 1 , Marco Agostini 2, 3, 4 , Mariagrazia Ruvoletto 1 , Andrea Martini 1 , Salvatore Pucciarelli 2 , Chiara Bedin 3 , Donato Nitti 2 , Patrizia Pontisso 1 1 Department of Medicine, University of Padua, Italy 2 Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padua, Italy 3 Nano-Inspired Biomedicine Lab, Istituto di Ricerca Pediatrica - Citta della Speranza, Padua, Italy 4 Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA Correspondence to: Patrizia Pontisso, email: patrizia@unipd.it Liliana Terrin, email: liliana.terrin@gmail.com Keywords: colorectal cancer, SerpinB3, COX-2, β-Catenin, tumor stage Received: June 29, 2016 Accepted: January 03, 2017 Published: February 02, 2017 ABSTRACT Colorectal cancer is characterized by aberrant Cyclooxigenase-2 (COX-2) and β-Catenin pathways. Recently, the protease inhibitor SerpinB3 has been described overexpressed in more advanced stages of this tumor. Aim of the study was to explore the possible relationship between these molecules in this setting. We evaluated colorectal cancer specimens from 105 patients and a positive correlation between SerpinB3, COX-2 and β-Catenin expression was observed, with higher levels in tumor than in adjacent tissue. The highest levels were associated with pathologic parameters of poor prognosis, including vascular invasion, lymph node metastasis and perineural invasion. The molecular and protein profiles of COX-2 and β-Catenin were analyzed in cell lines with different expression of SerpinB3. In those with high expression of SerpinB3, COX-2 and β-Catenin were higher than in controls. Cells with high levels of SerpinB3 showed higher proliferation and invasion compared to controls. In conclusion, in colorectal cancer SerpinB3, COX-2 and β-Catenin are positively correlated and associated with more advanced tumor stage. The in vitro experimental results support a driving role of SerpinB3 in the upregulation of COX-2/ β-Catenin positive loop, associated with a more aggressive cellular phenotype.

Published
2017

34. SerpinB3 and Yap Interplay Increases Myc Oncogenic Activity

Author

Turato, Cristian, Cannito, Stefania, Simonato, Davide, Villano, Gianmarco, Morello, Elisabetta, Terrin, Liliana, Quarta, SANTINA MARIA, Biasiolo, Alessandra, Ruvoletto, Mariagrazia, Martini, Andrea, Fasolato, Silvano, Zanus, Giacomo, Cillo, Umberto, Gatta, Angelo, Parola, Maurizio, and Pontisso, Patrizia

Subjects
0301 basic medicine, Genetically modified mouse, Carcinoma, Hepatocellular, Transcription, Genetic, Carcinogenesis, Regulator, Mice, Transgenic, Serpin, medicine.disease_cause, Article, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Mice, 0302 clinical medicine, Antigens, Neoplasm, medicine, Animals, Humans, Serpins, Adaptor Proteins, Signal Transducing, Hippo signaling pathway, Multidisciplinary, biology, Effector, Calpain, Liver Neoplasms, YAP-Signaling Proteins, Hep G2 Cells, Phosphoproteins, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Transcription Factors
Abstract

SerpinB3 has been recently described as an early marker of liver carcinogenesis, but the potential mechanistic role of this serpin in tumor development is still poorly understood. Overexpression of Myc often correlates with more aggressive tumour forms, supporting its involvement in carcinogenesis. Yes-associated protein (Yap), the main effector of the Hippo pathway, is a central regulator of proliferation and it has been found up-regulated in hepatocellular carcinomas. The study has been designed to investigate and characterize the interplay and functional modulation of Myc by SerpinB3 in liver cancer. Results from this study indicate that Myc was up-regulated by SerpinB3 through calpain and Hippo-dependent molecular mechanisms in transgenic mice and hepatoma cells overexpressing human SerpinB3 and also in human hepatocellular carcinomas. Human recombinant SerpinB3 was capable to inhibit the activity of Calpain in vitro, likely reducing its ability to cleave Myc in its non oncogenic Myc-nick cytoplasmic form. SerpinB3 indirectly increased the transcription of Myc through the induction of Yap pathway. These findings provide for the first time evidence that SerpinB3 can improve the production of Myc through direct and indirect mechanisms that include the inhibition of generation of its cytoplasmic form and the activation of Yap pathway.

Published
2015

35. CORRIGENDUM: SERPINB3 is associated with longer survival in transgenic mice

Author

Villano, Gianmarco, Ruvoletto, Mariagrazia, Ceolotto, Giulio, Quarta, Santina, Calabrese, Fiorella, Turato, Cristian, Tono, Natascia, Crescenzi, Marika, Biasiolo, Alessandra, Cattelan, Arianna, Merkel, Carlo, Avogaro, Angelo, Gatta, Angelo, and Pontisso, Patrizia

Subjects
Corrigenda
Published
2014

36. Binding and Uptake into Human Hepatocellular Carcinoma Cells of Peptide-Functionalized Gold Nanoparticles

Author

Jha, Satadru, primary, Ramadori, Federico, additional, Quarta, Santina, additional, Biasiolo, Alessandra, additional, Fabris, Enrica, additional, Baldan, Paola, additional, Guarino, Gaetano, additional, Ruvoletto, Mariagrazia, additional, Villano, Gianmarco, additional, Turato, Cristian, additional, Gatta, Angelo, additional, Mancin, Fabrizio, additional, Pontisso, Patrizia, additional, and Scrimin, Paolo, additional

Published
2016
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37. RUOLO DI SERPINB3 ELLA PROGRESSIONE DELLA MALATTIA EPATICA

Author

Quarta, SANTINA MARIA, Ruvoletto, Mariagrazia, Biasiolo, Alessandra, Turato, Cristian, Villano, Gianmarco, Tono, N, Ciscato, Francesco, Crescenzi, Marika, Martini, A, Gatta, Angelo, and Pontisso, Patrizia

Published
2011

43. SERPINB3 AND TGF-BETA IN CHRONIC LIVER DISEASE

Author

Turato, Cristian, Calabrese, Fiorella, Biasiolo, Alessandra, Quarta, SANTINA MARIA, Ruvoletto, Mariagrazia, Tono, N, Franzosi, L, Paccagnella, D, Fassina, G, Gatta, Angelo, and Pontisso, Patrizia

Published
2009

47. SERPINB3 PROMUOVE L’INVASIVITA’ CELLULARE

Author

Quarta, SANTINA MARIA, Vidalino, Laura, Turato, Cristian, Ruvoletto, Mariagrazia, Calabrese, Fiorella, Valente, Marialuisa, Fassina, G, Gatta, Angelo, and Pontisso, Patrizia

Published
2008

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