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1. Extracellular vesicles from the microalga Tetraselmis chuii are biocompatible and exhibit unique bone tropism along with antioxidant and anti-inflammatory properties

Author

Adamo, Giorgia, Santonicola, Pamela, Picciotto, Sabrina, Gargano, Paola, Nicosia, Aldo, Longo, Valeria, Aloi, Noemi, Romancino, Daniele P., Paterna, Angela, Rao, Estella, Raccosta, Samuele, Noto, Rosina, Salamone, Monica, Deidda, Irene, Costa, Salvatore, Di Sano, Caterina, Zampi, Giuseppina, Morsbach, Svenja, Landfester, Katharina, Colombo, Paolo, Wei, Mingxing, Bergese, Paolo, Touzet, Nicolas, Manno, Mauro, Di Schiavi, Elia, and Bongiovanni, Antonella

Published
2024
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5. MiRNAs in Extracellular Vesicles as Biomarkers in Plasma of Papillary Thyroid Cancer Patients: A Proof-of-Concept Study.

Author

D'Amico, Giuseppa, Santonocito, Radha, Grech, Godfrey, Graceffa, Giuseppa, Cipolla, Calogero, Scalia, Federica, Raccosta, Samuele, Manno, Mauro, Conway de Macario, Everly, Macario, Alberto J. L., Cappello, Francesco, Rappa, Francesca, Caruso Bavisotto, Celeste, and Campanella, Claudia

Subjects
NON-coding RNA, EXTRACELLULAR vesicles, TUMOR markers, THYROID cancer, SMALL molecules
Abstract

Simple Summary: Cancer diagnoses, including papillary thyroid carcinoma (PTC), are increasing, and early detection is critical for successful treatment. To help address this, our study focuses on identifying reliable biomarkers—specific molecules indicating the presence of disease—that can be detected through non-invasive methods like liquid biopsies. We examined small RNA molecules, known as microRNAs (miRNAs), found in microparticles called extracellular vesicles (EVs) in blood samples from PTC patients, which are linked to the development of PTC. Our results showed these miRNAs were present at higher levels in PTC patients and returned to normal after surgery, suggesting their potential as reliable indicators of PTC. The use of these biomarkers in EVs could allow easier, less invasive, and more frequent testing compared to current methods, improving early detection and monitoring of thyroid cancer, thus benefiting patients and healthcare systems. Background: The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC. Conclusions: Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Nanovesicular Mediation of the Gut–Brain Axis by Probiotics: Insights into Irritable Bowel Syndrome

Author

Santonocito, Radha, primary, Paladino, Letizia, additional, Vitale, Alessandra Maria, additional, D'Amico, Giuseppa, additional, Zummo, Francesco Paolo, additional, Pirrotta, Paolo, additional, Raccosta, Samuele, additional, Manno, Mauro, additional, Accomando, Salvatore, additional, D’Arpa, Francesco, additional, Carini, Francesco, additional, Barone, Rosario, additional, Rappa, Francesca, additional, Marino Gammazza, Antonella, additional, Bucchieri, Fabio, additional, Cappello, Francesco, additional, and Caruso Bavisotto, Celeste, additional

Published
2024
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8. Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors

Author

D’Amico, Ferdinando, Amato, Arnaldo, Iannone, Andrea, Trovato, Cristina, Romana, Chiara, Angeletti, Stefano, Maselli, Roberta, Radaelli, Franco, Fiori, Giancarla, Viale, Edi, Di Giulio, Emilio, Soriani, Paola, Manno, Mauro, Rondonotti, Emanuele, Galtieri, Piera Alessia, Anderloni, Andrea, Fugazza, Alessandro, Ferrara, Elisa Chiara, Carrara, Silvia, Di Leo, Milena, Pellegatta, Gaia, Spadaccini, Marco, Lamonaca, Laura, Craviotto, Vincenzo, Belletrutti, Paul J., Hassan, Cesare, and Repici, Alessandro

Published
2021
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9. Factors That Affect Adequacy of Colon Cleansing for Colonoscopy in Hospitalized Patients

Author

Laterza, Liboria, Alemanni, Luigina Vanessa, Buttitta, Francesco, Cirota, Giovanna, Cominardi, Anna, Impellizzeri, Giovanna, La Marca, Marina, Marasco, Giovanni, Metelli, Flavio, Pierantoni, Chiara, Sansone, Vito, Tamanini, Giacomo, Cesaro, Paola, Piccirelli, Stefania, Feletti, Valentina, Triossi, Omero, Arena, Rosario, Binda, Cecilia, Nicolini, Gianni, Sbrancia, Monica, Trebbi, Margherita, Cuffari, Biagio, Soriani, Paola, Comparato, Giuseppe, Prati, Gian Maria, Reati, Raffaella, Corte, Cristina della, Liggi, Mauro, Mura, Donatella, Fuccio, Lorenzo, Frazzoni, Leonardo, Spada, Cristiano, Mussetto, Alessandro, Fabbri, Carlo, Manno, Mauro, Aragona, Giovanni, Zagari, Rocco Maurizio, Rondonotti, Emanuele, Manes, Gianpiero, Occhipinti, Pietro, Cadoni, Sergio, Bazzoli, Franco, Hassan, Cesare, and Radaelli, Franco

Published
2021
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10. EUS-Guided Gallbladder Drainage Using a Lumen-Apposing Metal Stent for Acute Cholecystitis: Results of a Nationwide Study with Long-Term Follow-Up

Author

Binda, Cecilia, primary, Anderloni, Andrea, additional, Forti, Edoardo, additional, Fusaroli, Pietro, additional, Macchiarelli, Raffaele, additional, Manno, Mauro, additional, Fugazza, Alessandro, additional, Redaelli, Alessandro, additional, Aragona, Giovanni, additional, Lovera, Mauro, additional, Togliani, Thomas, additional, Armellini, Elia, additional, Amato, Arnaldo, additional, Brancaccio, Mario Luciano, additional, Badas, Roberta, additional, Leone, Nicola, additional, de Nucci, Germana, additional, Mangiavillano, Benedetto, additional, Sbrancia, Monica, additional, Pollino, Valeria, additional, Lisotti, Andrea, additional, Maida, Marcello, additional, Sinagra, Emanuele, additional, Ventimiglia, Marco, additional, Repici, Alessandro, additional, Fabbri, Carlo, additional, and Tarantino, Ilaria, additional

Published
2024
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12. Application of a novel swallowable telemetric device for real time luminal blood detection to guide timing of enteroscopy in a patient with occult gastrointestinal bleeding. A case report.

Author

Rainer, Joachim, primary, Biancheri, Paolo, additional, Bonura, Giuliano Francesco, additional, Deiana, Simona, additional, Gabbani, Tommaso, additional, Gualandi, Noemi, additional, Pileggi, Roberta, additional, Soriani, Paola, additional, and Manno, Mauro, additional

Published
2023
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14. Proof-of-Concept Study on the Use of Tangerine-Derived Nanovesicles as siRNA Delivery Vehicles toward Colorectal Cancer Cell Line SW480.

Author

Rabienezhad Ganji, Nima, Urzì, Ornella, Tinnirello, Vincenza, Costanzo, Elisa, Polito, Giulia, Palumbo Piccionello, Antonio, Manno, Mauro, Raccosta, Samuele, Gallo, Alessia, Lo Pinto, Margot, Calligaris, Matteo, Scilabra, Simone Dario, Di Bella, Maria Antonietta, Conigliaro, Alice, Fontana, Simona, Raimondo, Stefania, and Alessandro, Riccardo

Subjects
NANOMEDICINE, COLORECTAL cancer, RNA interference, CANCER cells, SMALL interfering RNA, CELL lines
Abstract

In the last years, the field of nanomedicine and drug delivery has grown exponentially, providing new platforms to carry therapeutic agents into the target sites. Extracellular vesicles (EVs) are ready-to-use, biocompatible, and non-toxic nanoparticles that are revolutionizing the field of drug delivery. EVs are involved in cell–cell communication and mediate many physiological and pathological processes by transferring their bioactive cargo to target cells. Recently, nanovesicles from plants (PDNVs) are raising the interest of the scientific community due to their high yield and biocompatibility. This study aims to evaluate whether PDNVs may be used as drug delivery systems. We isolated and characterized nanovesicles from tangerine juice (TNVs) that were comparable to mammalian EVs in size and morphology. TNVs carry the traditional EV marker HSP70 and, as demonstrated by metabolomic analysis, contain flavonoids, organic acids, and limonoids. TNVs were loaded with DDHD1-siRNA through electroporation, obtaining a loading efficiency of 13%. We found that the DDHD1-siRNA complex TNVs were able to deliver DDHD1-siRNA to human colorectal cancer cells, inhibiting the target expression by about 60%. This study represents a proof of concept for the use of PDNVs as vehicles of RNA interference (RNAi) toward mammalian cells. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Linear EUS Accuracy in Preoperative Staging of Gastric Cancer: A Retrospective Multicenter Study

Author

de Nucci, Germana, primary, Gabbani, Tommaso, additional, Impellizzeri, Giovanna, additional, Deiana, Simona, additional, Biancheri, Paolo, additional, Ottaviani, Laura, additional, Frazzoni, Leonardo, additional, Mandelli, Enzo Domenico, additional, Soriani, Paola, additional, Vecchi, Maurizio, additional, Manes, Gianpiero, additional, and Manno, Mauro, additional

Published
2023
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16. Feasibility and Accuracy of Transduodenal Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Solid Lesions Using a 19-Gauge Flexible Needle: A Multicenter Study

Author

de Nucci, Germana, Petrone, Maria Chiara, Imperatore, Nicola, Forti, Edoardo, Grassia, Roberto, Giovanelli, Silvia, Ottaviani, Laura, Mirante, Vincenzo, Sabatino, Giuseppe, Fabbri, Carlo, Manno, Mauro, Arcidiacono, Paolo Giorgio, Manes, Gianpiero, de Nucci, G., Petrone, M. C., Imperatore, N., Forti, E., Grassia, R., Giovanelli, S., Ottaviani, L., Mirante, V., Sabatino, G., Fabbri, C., Manno, M., Arcidiacono, P. G., Manes, G., de Nucci, Germana, Petrone, Maria Chiara, Imperatore, Nicola, Forti, Edoardo, Grassia, Roberto, Giovanelli, Silvia, Ottaviani, Laura, Mirante, Vincenzo, Sabatino, Giuseppe, Fabbri, Carlo, Manno, Mauro, Arcidiacono, Paolo Giorgio, and Manes, Gianpiero

Subjects
Endoscopic ultrasound, medicine.medical_specialty, Medicine (miscellaneous), RC799-869, Endosonography, Feasibility studies, 03 medical and health sciences, 0302 clinical medicine, Endoscopic ultrasound-guided fine-needle aspiration, medicine, Radiology, Nuclear Medicine and imaging, endoscopic ultrasound-guided fine-needle aspiration, Transduodenal approach, Internal medicine, medicine.diagnostic_test, business.industry, feasibility studies, endosonography, Gastroenterology, Diseases of the digestive system. Gastroenterology, Predictive value, RC31-1245, Confidence interval, Endoscopy, Fine-needle aspiration, Multicenter study, 030220 oncology & carcinogenesis, Original Article, 030211 gastroenterology & hepatology, Radiology, business, Fine-needle aspirate
Abstract

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the go-to method for obtaining samples from gastrointestinal tract and pancreatic lesions. When the transduodenal approach is utilized, the use of a more flexible needle, such as a nitinol 19-gauge (G) needle, has been recommended. The aim of this study was to evaluate the feasibility and accuracy of 19-G flexible aspiration needles in obtaining samples from solid lesions through a transduodenal approach. Methods: This was a retrospective analysis of prospectively collected data from eight Italian endoscopy centers. Consecutive patients with solid lesions who underwent transduodenal EUS-FNA with a 19-G flexible needle were included. Results: A total of 201 patients were enrolled. According to histology, EUS, radiology and 12 months of follow-up, 151 patients had malignant lesions and 50 patients had benign lesions. EUS-FNA was feasible in all cases. An adequate histologic sample was obtained in all except eight cases (96.1%). The sensitivity of EUS-FNA was 92.1% (95% confidence interval [CI], 86.8%-95.7%), and the specificity was 100% (95% CI, 90.5%-100%). The positive predictive value was 100% (95% CI, 93.4%-100%), and the negative predictive value was 74% (95% CI, 62.8%-82.7%). The diagnostic accuracy was 93.5% (95% CI, 89.2%-96.5%). Conclusions: The transduodenal approach for obtaining samples from solid lesions using a 19-G flexible needle seems feasible and accurate. Clin Endosc 2021;54:229-235

Published
2021

17. Ultrastructure and stability of cellular nanoparticles isolated from Phaeodactylum tricornutum and Dunaliella tertiolecta conditioned media

Author

Božič, Darja, primary, Hočevar, Matej, additional, Jeran, Marko, additional, Kisovec, Matic, additional, Bedina Zavec, Apolonija, additional, Romolo, Anna, additional, Škufca, David, additional, Podobnik, Marjetka, additional, Kogej, Ksenija, additional, Iglič, Aleš, additional, Touzet, Nicolas, additional, Manno, Mauro, additional, Pocsfalvi, Gabriella, additional, Bongiovanni, Antonella, additional, and Kralj Iglič, Veronika, additional

Published
2022
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18. Digital single-operator cholangioscopy in diagnostic and therapeutic bilio-pancreatic diseases: A prospective, multicenter study

Author

Fugazza, Alessandro, Gabbiadini, Roberto, Tringali, Andrea, De Angelis, Claudio Giovanni, Mosca, Piergiorgio, Maurano, Attilio, Di Mitri, Roberto, Manno, Mauro, Mariani, Alberto, Cereatti, Fabrizio, Bertani, Helga, Sferrazza, Sandro, Donato, Giulio, Tarantino, Ilaria, Cugia, Luigi, Aragona, Giovanni, Cantù, Paolo, Mazzocchi, Alessandro, Canfora, Maria Laura, Venezia, Ludovica, Bendia, Emanuele, Maroni, Luca, Zulli, Claudio, Conte, Elisabetta, Soriani, Paola, Ligresti, Dario, Vilardo, Emmanuelle, Penagini, Roberto, Benedetti, Antonio, Arcidiacono, Paolo Giorgio, Khalaf, Kareem, Troncone, Edoardo, Costamagna, Guido, Repici, Alessandro, Anderloni, Andrea, Tringali, Andrea (ORCID:0000-0002-9614-3449), Costamagna, Guido (ORCID:0000-0002-8100-2731), Fugazza, Alessandro, Gabbiadini, Roberto, Tringali, Andrea, De Angelis, Claudio Giovanni, Mosca, Piergiorgio, Maurano, Attilio, Di Mitri, Roberto, Manno, Mauro, Mariani, Alberto, Cereatti, Fabrizio, Bertani, Helga, Sferrazza, Sandro, Donato, Giulio, Tarantino, Ilaria, Cugia, Luigi, Aragona, Giovanni, Cantù, Paolo, Mazzocchi, Alessandro, Canfora, Maria Laura, Venezia, Ludovica, Bendia, Emanuele, Maroni, Luca, Zulli, Claudio, Conte, Elisabetta, Soriani, Paola, Ligresti, Dario, Vilardo, Emmanuelle, Penagini, Roberto, Benedetti, Antonio, Arcidiacono, Paolo Giorgio, Khalaf, Kareem, Troncone, Edoardo, Costamagna, Guido, Repici, Alessandro, Anderloni, Andrea, Tringali, Andrea (ORCID:0000-0002-9614-3449), and Costamagna, Guido (ORCID:0000-0002-8100-2731)

Abstract

Background and aim: Digital single-operator cholangioscopy (D-SOC) is an endoscopic procedure that is increasingly used for the management of bilio-pancreatic diseases. We aimed to investigate the efficacy and safety of D-SOC for diagnostic and therapeutic indications. Methods: This is a multicenter, prospective study(January 2016-June 2019) across eighteen tertiary centers. The primary outcome was procedural success of D-SOC. Secondary outcomes were: D-SOC visual assessment and diagnostic yield of SpyBite biopsy in cases of biliary strictures, stone clearance rate in cases of difficult biliary stones, rate of adverse events(AEs) for all indications. Results: D-SOC was performed in 369 patients (201(54,5%) diagnostic and 168(45,5%)therapeutic). Overall, procedural success rate was achieved in 360(97,6%) patients. The sensitivity, specificity, PPV, NPV and accuracy in biliary strictures were: 88,5%, 77,3%, 83,3%, 84,1% and 83,6% for D-SOC visual impression; 80,2%, 92,6%, 95,1%, 72,5% and 84,7% for the SpyBite biopsy, respectively. For difficult biliary stones, complete duct clearance was obtained in 92,1% patients (82,1% in a single session). Overall, AEs occurred in 37(10%) cases.The grade of AEs was mild or moderate for all cases, except one which was fatal. Conclusion: D-SOC is effective for diagnostic and therapeutic indications.Most of the AEs were minor and managed conservatively, even though a fatal event has happened that is not negligible and should be considered before using D-SOC.

Published
2022

19. Extracellular Vesicles From Microalgae: Uptake Studies in Human Cells and Caenorhabditis elegans

Author

Picciotto, Sabrina, primary, Santonicola, Pamela, additional, Paterna, Angela, additional, Rao, Estella, additional, Raccosta, Samuele, additional, Romancino, Daniele Paolo, additional, Noto, Rosina, additional, Touzet, Nicolas, additional, Manno, Mauro, additional, Di Schiavi, Elia, additional, Bongiovanni, Antonella, additional, and Adamo, Giorgia, additional

Published
2022
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24. BOW project-Deliverable 1.3 (D1.3): Quality check guidance for a robust BOW-EV characterization

Author

Manno, Mauro, Antonella Bongiovanni, Paolo Bergese, Svenja Morshbach, Francesco Valle, Olivia Candini, Andrea Zendrini, Giorgia Adamo, and Samuele Raccosta

Abstract

The BOW deliverable 1.3 (D1.3) report ameasurement set for the quality check of MSC- and microalgal-derived extracellular vesicles (EVs); it includes a selection of optimized biochemical-biophysical techniques to evaluate specific EV features (e.g., size distribution, density,morphology, concentration, stability in biological fluids and purity). Here, the D1.3 and the fundamental cited literature are uploaded. Further, datasets uploaded are related to the performed analysesshowedas example in figure 1-3 and 5 (DLS, NTA, Conan assay, and AFM).

Published
2021
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27. Scaling Concepts in Serpin Polymer Physics

Author

Raccosta, Samuele, primary, Librizzi, Fabio, additional, Jagger, Alistair M., additional, Noto, Rosina, additional, Martorana, Vincenzo, additional, Lomas, David A., additional, Irving, James A., additional, and Manno, Mauro, additional

Published
2021
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28. Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Author

Raimondo, Stefania, primary, Nikolic, Dragana, additional, Conigliaro, Alice, additional, Giavaresi, Gianluca, additional, Lo Sasso, Bruna, additional, Giglio, Rosaria Vincenza, additional, Chianetta, Roberta, additional, Manno, Mauro, additional, Raccosta, Samuele, additional, Corleone, Valeria, additional, Ferrante, Giovanni, additional, Citarrella, Roberto, additional, Rizzo, Manfredi, additional, De Leo, Giacomo, additional, Ciaccio, Marcello, additional, Montalto, Giuseppe, additional, and Alessandro, Riccardo, additional

Published
2021
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29. Nanoalgosomes: Introducing extracellular vesicles produced by microalgae

Author

Adamo, Giorgia, primary, Fierli, David, additional, Romancino, Daniele P., additional, Picciotto, Sabrina, additional, Barone, Maria E., additional, Aranyos, Anita, additional, Božič, Darja, additional, Morsbach, Svenja, additional, Raccosta, Samuele, additional, Stanly, Christopher, additional, Paganini, Carolina, additional, Gai, Meiyu, additional, Cusimano, Antonella, additional, Martorana, Vincenzo, additional, Noto, Rosina, additional, Carrotta, Rita, additional, Librizzi, Fabio, additional, Randazzo, Loredana, additional, Parkes, Rachel, additional, Capasso Palmiero, Umberto, additional, Rao, Estella, additional, Paterna, Angela, additional, Santonicola, Pamela, additional, Iglič, Ales, additional, Corcuera, Laura, additional, Kisslinger, Annamaria, additional, Schiavi, Elia Di, additional, Liguori, Giovanna L., additional, Landfester, Katharina, additional, Kralj‐Iglič, Veronika, additional, Arosio, Paolo, additional, Pocsfalvi, Gabriella, additional, Touzet, Nicolas, additional, Manno, Mauro, additional, and Bongiovanni, Antonella, additional

Published
2021
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30. Factors That Affect Adequacy of Colon Cleansing for Colonoscopy in Hospitalized Patients

Author

Fuccio, Lorenzo, primary, Frazzoni, Leonardo, additional, Spada, Cristiano, additional, Mussetto, Alessandro, additional, Fabbri, Carlo, additional, Manno, Mauro, additional, Aragona, Giovanni, additional, Zagari, Rocco Maurizio, additional, Rondonotti, Emanuele, additional, Manes, Gianpiero, additional, Occhipinti, Pietro, additional, Cadoni, Sergio, additional, Bazzoli, Franco, additional, Hassan, Cesare, additional, Radaelli, Franco, additional, Laterza, Liboria, additional, Alemanni, Luigina Vanessa, additional, Buttitta, Francesco, additional, Cirota, Giovanna, additional, Cominardi, Anna, additional, Impellizzeri, Giovanna, additional, La Marca, Marina, additional, Marasco, Giovanni, additional, Metelli, Flavio, additional, Pierantoni, Chiara, additional, Sansone, Vito, additional, Tamanini, Giacomo, additional, Cesaro, Paola, additional, Piccirelli, Stefania, additional, Feletti, Valentina, additional, Triossi, Omero, additional, Arena, Rosario, additional, Binda, Cecilia, additional, Nicolini, Gianni, additional, Sbrancia, Monica, additional, Trebbi, Margherita, additional, Cuffari, Biagio, additional, Soriani, Paola, additional, Comparato, Giuseppe, additional, Prati, Gian Maria, additional, Reati, Raffaella, additional, Corte, Cristina della, additional, Liggi, Mauro, additional, and Mura, Donatella, additional

Published
2021
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31. N-Glycosylation as a Tool to Study Antithrombin Secretion, Conformation, and Function

Author

Águila, Sonia, primary, Noto, Rosina, additional, Luengo-Gil, Ginés, additional, Espín, Salvador, additional, Bohdan, Nataliya, additional, de la Morena-Barrio, María Eugenia, additional, Peñas, Julia, additional, Rodenas, Maria Carmen, additional, Vicente, Vicente, additional, Corral, Javier, additional, Manno, Mauro, additional, and Martínez-Martínez, Irene, additional

Published
2021
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32. Biomanufacturing of Tomato-Derived Nanovesicles

Author

Bokka, Ramesh, primary, Ramos, Anna Paulina, additional, Fiume, Immacolata, additional, Manno, Mauro, additional, Raccosta, Samuele, additional, Turiák, Lilla, additional, Sugár, Simon, additional, Adamo, Giorgia, additional, Csizmadia, Tamás, additional, and Pocsfalvi, Gabriella, additional

Published
2020
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35. Neuroserpin: structure, function, physiology and pathology.

Author

D'Acunto, Emanuela, Fra, Annamaria, Visentin, Cristina, Manno, Mauro, Ricagno, Stefano, Galliciotti, Giovanna, and Miranda, Elena

Subjects
PHYSIOLOGY, TISSUE plasminogen activator, PATHOLOGY, NERVOUS system, MOLECULAR structure
Abstract

Neuroserpin is a serine protease inhibitor identified in a search for proteins implicated in neuronal axon growth and synapse formation. Since its discovery over 30 years ago, it has been the focus of active research. Many efforts have concentrated in elucidating its neuroprotective role in brain ischemic lesions, the structural bases of neuroserpin conformational change and the effects of neuroserpin polymers that underlie the neurodegenerative disease FENIB (familial encephalopathy with neuroserpin inclusion bodies), but the investigation of the physiological roles of neuroserpin has increased over the last years. In this review, we present an updated and critical revision of the current literature dealing with neuroserpin, covering all aspects of research including the expression and physiological roles of neuroserpin, both inside and outside the nervous system; its inhibitory and non-inhibitory mechanisms of action; the molecular structure of the monomeric and polymeric conformations of neuroserpin, including a detailed description of the polymerisation mechanism; and the involvement of neuroserpin in human disease, with particular emphasis on FENIB. Finally, we briefly discuss the identification by genome-wide screening of novel neuroserpin variants and their possible pathogenicity. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors.

Author

D'Amico, Ferdinando, Amato, Arnaldo, Iannone, Andrea, Trovato, Cristina, Romana, Chiara, Angeletti, Stefano, Maselli, Roberta, Radaelli, Franco, Fiori, Giancarla, Viale, Edi, Di Giulio, Emilio, Soriani, Paola, Manno, Mauro, Rondonotti, Emanuele, Galtieri, Piera Alessia, Anderloni, Andrea, Fugazza, Alessandro, Ferrara, Elisa Chiara, Carrara, Silvia, and Di Leo, Milena

Abstract

Granular mixed laterally spreading tumors (GM-LSTs) have an intermediate level of risk for submucosal invasive cancer (SMICs) without clear signs of invasion (covert); the optimal resection method is uncertain. We aimed to determine the risk of covert SMIC in GM-LSTs based on clinical and endoscopic factors. We collected data from 693 patients (50.6% male; median age, 69 years) with colorectal GM-LSTs, without signs of invasion, who underwent endoscopic resection (74.2%) or endoscopic submucosal dissection (25.2%) at 7 centers in Italy from 2016 through 2019. We performed multivariate and univariate analyses to identify demographic and endoscopic factors associated with risk of SMIC. We developed a multivariate model to calculate the number needed to treat (NNT) to detect 1 SMIC. Based on pathology analysis, 66 patients (9.5%) had covert SMIC. In multivariate analyses, increased risk of covert SMIC were independently associated with increasing lesion size (odds ratio per mm increase, 1.02, 95% CI, 1.01–1.03; P =.003) and rectal location (odds ratio, 3.08; 95% CI, 1.62-5.83; P =.004). A logistic regression model based on lesion size (with a cutoff of 40 mm) and rectal location identified patients with covert SMIC with 47.0% sensitivity, 82.6% specificity, and an area under the curve of 0.69. The NNT to identify 1 patient with a nonrectal SMIC smaller than 4 cm was 20; the NNT to identify 1 patient with a rectal SMIC of 4 cm or more was 5. In an analysis of data from 693 patients, we found the risk of covert SMIC in patients with GM-LSTs to be approximately 10%. GM-LSTs of 4 cm or more and a rectal location are high risk and should be treated by en-bloc resection. ClinicalTrials.gov , Number: NCT03836131. [ABSTRACT FROM AUTHOR]

Published
2021
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37. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs

Author

Raimondi, Lavinia, primary, De Luca, Angela, primary, Gallo, Alessia, primary, Costa, Viviana, primary, Russelli, Giovanna, primary, Cuscino, Nicola, primary, Manno, Mauro, primary, Raccosta, Samuele, primary, Carina, Valeria, primary, Bellavia, Daniele, primary, Conigliaro, Alice, primary, Alessandro, Riccardo, primary, Fini, Milena, primary, Conaldi, Pier Giulio, primary, and Giavaresi, Gianluca, primary

Published
2019
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38. Feasibility and Accuracy of Transduodenal Endoscopic Ultrasound- Guided Fine-Needle Aspiration of Solid Lesions Using a 19-Gauge Flexible Needle: A Multicenter Study.

Author

Nucci, Germana de, Petrone, Maria Chiara, Imperatore, Nicola, Forti, Edoardo, Grassia, Roberto, Giovanelli, Silvia, Ottaviani, Laura, Mirante, Vincenzo, Sabatino, Giuseppe, Fabbri, Carlo, Manno, Mauro, Arcidiacono, Paolo Giorgio, and Manes, Gianpiero

Subjects
NEEDLE biopsy, PANCREATIC tumors, NEEDLES & pins, GASTROINTESTINAL system, NICKEL-titanium alloys
Abstract

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the go-to method for obtaining samples from gastrointestinal tract and pancreatic lesions. When the transduodenal approach is utilized, the use of a more flexible needle, such as a nitinol 19-gauge (G) needle, has been recommended. The aim of this study was to evaluate the feasibility and accuracy of 19-G flexible aspiration needles in obtaining samples from solid lesions through a transduodenal approach. Methods: This was a retrospective analysis of prospectively collected data from eight Italian endoscopy centers. Consecutive patients with solid lesions who underwent transduodenal EUS-FNA with a 19-G flexible needle were included. Results: A total of 201 patients were enrolled. According to histology, EUS, radiology and 12 months of follow-up, 151 patients had malignant lesions and 50 patients had benign lesions. EUS-FNA was feasible in all cases. An adequate histologic sample was obtained in all except eight cases (96.1%). The sensitivity of EUS-FNA was 92.1% (95% confidence interval [CI], 86.8%–95.7%), and the specificity was 100% (95% CI, 90.5%–100%). The positive predictive value was 100% (95% CI, 93.4%–100%), and the negative predictive value was 74% (95% CI, 62.8%–82.7%). The diagnostic accuracy was 93.5% (95% CI, 89.2%–96.5%). Conclusions: The transduodenal approach for obtaining samples from solid lesions using a 19-G flexible needle seems feasible and accurate. [ABSTRACT FROM AUTHOR]

Published
2021
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39. The role of glycosylation in the functional activity and pathological consequences of serpin proteins

Author

Manno, Mauro, Daniellou, Richard, Studium, Le, Le Studium Loire Valley Institute for Advanced Studies, 45000 Orléans, France, CNR - National Research Council of Italy, Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and This project has been supported by LE STUDIUM Loire Valley Institute for Advanced Studies, Orléans & Tours, France with funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665790

Subjects
Serpin, [SDV] Life Sciences [q-bio], Glycosylation, [SDV]Life Sciences [q-bio], Neuroserpin, C1-inhibitor, Conformational diseases
Abstract

International audience; This project focus on the molecular basis of a peculiar class of conformational diseases, called Serpinopathies, with a special emphasis to glycosylation, an important post-translational modification which rules the functional and pathological behaviour of the proteins responsible for the diseases. The authors exploited their expertise on protein biophysics and glyco-biochemistry to set up a long-term program for the studies on the role of glycosylation in the functional activity and pathological consequences of serpin proteins. An experimental work was accomplished to start the expression and production of two serpins, neuroserpin and C1-inhibitor, in a novel eukaryotic expression model. Further, the program was given a wider scope by consolidating a European network of researchers working on closely related issues.

Published
2017

40. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs.

Author

Raimondi, Lavinia, Luca, Angela De, Gallo, Alessia, Costa, Viviana, Russelli, Giovanna, Cuscino, Nicola, Manno, Mauro, Raccosta, Samuele, Carina, Valeria, Bellavia, Daniele, Conigliaro, Alice, Alessandro, Riccardo, Fini, Milena, Conaldi, Pier Giulio, and Giavaresi, Gianluca

Subjects
TUMOR microenvironment, EXOSOMES, MICRORNA, NON-coding RNA, OSTEOSARCOMA
Abstract

Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Embelin binds to human neuroserpin and impairs its polymerisation

Author

Saga, Giorgia, Sessa, Fabio, Barbiroli, Alberto, Santambrogio, Carlo, Russo, Rosaria, Sala, Michela, Raccosta, Samuele, Martorana, Vincenzo, Caccia, Sonia, Noto, Rosina, Moriconi, Claudia, Miranda, Elena, Grandori, Rita, Manno, Mauro, Bolognesi, Martino, Ricagno, Stefano, Saga, G, Sessa, F, Barbiroli, A, Santambrogio, C, Russo, R, Sala, M, Raccosta, S, Martorana, V, Caccia, S, Noto, R, Moriconi, C, Miranda, E, Grandori, R, Manno, M, Bolognesi, M, and Ricagno, S

Subjects
toxic protein misfolding, 0301 basic medicine, Circular dichroism, Protein Conformation, Mutant, Multidisciplinary, plasminogen-activator inhibitor-1, inclusion-bodies, forms polymers, familial encephalopathy, proteinase-inhibitor, molecular-basis, dementia fenib, serpin, alpha(1)-antitrypsin, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), Plasma protein binding, Serpin, Ligands, Bioinformatics, Tissue plasminogen activator, Article, Mass Spectrometry, 03 medical and health sciences, Protein structure, protein polymerisation, CHIM/01 - CHIMICA ANALITICA, Neuroserpin, Benzoquinones, medicine, Humans, Familial encephalopathy with neuroserpin inclusion bodies, Serpins, conformational stability, 030102 biochemistry & molecular biology, Protein Stability, Chemistry, anti-aggregation molecule, Circular Dichroism, Neuropeptides, medicine.disease, BIO/10 - BIOCHIMICA, Kinetics, 030104 developmental biology, Tissue Plasminogen Activator, Biophysics, embelin, Protein Multimerization, Protein Binding, medicine.drug
Abstract

Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain.

Published
2016
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44. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth

Author

Bellavia, Daniele, primary, Raimondo, Stefania, additional, Calabrese, Giovanna, additional, Forte, Stefano, additional, Cristaldi, Marta, additional, Patinella, Agostina, additional, Memeo, Lorenzo, additional, Manno, Mauro, additional, Raccosta, Samuele, additional, Diana, Patrizia, additional, Cirrincione, Girolamo, additional, Giavaresi, Gianluca, additional, Monteleone, Francesca, additional, Fontana, Simona, additional, De Leo, Giacomo, additional, and Alessandro, Riccardo, additional

Published
2017
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45. Additional file 1: of CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA

Author

Conigliaro, Alice, Costa, Viviana, Dico, Alessia Lo, Saieva, Laura, Buccheri, Simona, Dieli, Francesco, Manno, Mauro, Raccosta, Samuele, Mancone, Carmine, Tripodi, Marco, Leo, Giacomo De, and Alessandro, Riccardo

Subjects
embryonic structures
Abstract

(a) Characterization of isolated exosomes. Left panel: DSL for exosomes released by SKHep Middle panel: Western blot forTsg101 and HSC70 in SkHep cells and their relative exosomes. Right panel: Confocal microscopy analysis on HUVECs treated for 1, 3 and 6 hours with 5 mg/ml of SKHep-derived exosomes. HUVECs were stained with phalloidin Alexa Fluor (green), nuclear counterstaining was performed using DAPI (blue), exosomes were labelled with PKH26 (red). (b) Target analysis. Real time-PCR analysis on HUVECs treated for 18 h with 5 mg/ml of SkHep-derived exosomes. Normalized for b-actin the DDct were indicated as fold of induction respect to control (untreated cells). *p

Published
2015
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46. Advances in Endoscopic Visualization of Barrett’s Esophagus: The Role of Confocal Laser Endomicroscopy

Author

Bertani, Helga, Pigò, Flavia, Dabizzi, Emanuele, Frazzoni, Marzio, Mirante, Vincenzo Giorgio, Manno, Mauro, Manta, Raffaele, and Conigliaro, Rita

Subjects
Article Subject
Abstract

Many endoscopic imaging modalities have been developed and introduced into clinical practice to enhance the diagnostic capabilities of upper endoscopy. In the past, detection of dysplasia and carcinoma of esophagus had been dependent on biopsies taken during standard white-light endoscopy (WLE). Recently high-resolution (HR) endoscopy enables us to visualize esophageal mucosa but resolution for glandular structures and cells is still low. Probe-based confocal laser endomicroscopy (pCLE) is a new promising diagnostic technique by which details of glandular and vascular structures of mucosal layer can be observed. However, the clinical utility of this new diagnostic tool has not yet been fully explored in a clinical setting. In this paper we will highlight this new technique for detection of esophageal dysplasia and carcinoma from a clinical practice perspective.

Published
2012
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48. CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA

Author

Conigliaro, Alice, primary, Costa, Viviana, additional, Lo Dico, Alessia, additional, Saieva, Laura, additional, Buccheri, Simona, additional, Dieli, Francesco, additional, Manno, Mauro, additional, Raccosta, Samuele, additional, Mancone, Carmine, additional, Tripodi, Marco, additional, De Leo, Giacomo, additional, and Alessandro, Riccardo, additional

Published
2015
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50. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death

Author

Raimondo, Stefania, primary, Naselli, Flores, additional, Fontana, Simona, additional, Monteleone, Francesca, additional, Lo Dico, Alessia, additional, Saieva, Laura, additional, Zito, Giovanni, additional, Flugy, Anna, additional, Manno, Mauro, additional, Di Bella, Maria Antonietta, additional, De Leo, Giacomo, additional, and Alessandro, Riccardo, additional

Published
2015
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