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1. Nanotechnology-Based Cisplatin Intracellular Delivery to Enhance Chemo-Sensitivity of Ovarian Cancer

Author

Bortot B, Mongiat M, Valencic E, Dal Monego S, Licastro D, Crosera M, Adami G, Rampazzo E, Ricci G, Romano F, Severini GM, and Biffi S

Subjects
cisplatin resistance, ovarian cancer, skov3, nanoparticle, epithelial-mesenchymal transition, ca125, apoptosis, Medicine (General), R5-920
Abstract

Barbara Bortot, 1 Maurizio Mongiat, 2 Erica Valencic, 3 Simeone Dal Monego, 4 Danilo Licastro, 4 Matteo Crosera, 5 Gianpiero Adami, 5 Enrico Rampazzo, 6 Giuseppe Ricci, 7, 8 Federico Romano, 7 Giovanni Maria Severini, 1 Stefania Biffi 7 1Department of Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Research and Diagnosis, Division of Molecular Oncology, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS, Aviano, Italy; 3Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 4ARGO Open Lab Platform for Genome Sequencing, AREA Science Park, Trieste, Italy; 5Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy; 6Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 7Department of Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 8Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, ItalyCorrespondence: Stefania Biffi Email stefania.biffi@burlo.trieste.itBackground: Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin’s pharmacokinetics and safety profile.Purpose: This work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells’ xenograft model in mice.Methods: Cell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells’ xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses.Results: We observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq actg 3nalysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug.Conclusion: Nanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.Keywords: cisplatin resistance, ovarian cancer, SKOV3, nanoparticle, epithelial-mesenchymal transition, Ca125, apoptosis

Published
2020

2. Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities

Author

Biffi S, Petrizza L, Garrovo C, Rampazzo E, Andolfi L, Giustetto P, Nikolov I, Kurdi G, Danailov MB, Zauli G, Secchiero P, and Prodi L

Subjects
Dye-doped nanoparticles, Optical imaging, NIR imaging, Photoacoustic Imaging, Photothermal Therapy, PEGylated nanoparticles., Medicine (General), R5-920
Abstract

Stefania Biffi,1 Luca Petrizza,2 Chiara Garrovo,1 Enrico Rampazzo,2 Laura Andolfi,3 Pierangela Giustetto,4 Ivaylo Nikolov,5 Gabor Kurdi,5 Miltcho Boyanov Danailov,5 Giorgio Zauli,1 Paola Secchiero,6 Luca Prodi2 1Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 2Department of Chemistry ‘‘G Ciamician’’, University of Bologna, Bologna, 3IOM-CNR TASC Laboratory, Basovizza, Trieste, 4Ephoran – Multi-Imaging Solutions, Bioindustry Park Silvano Fumero, Torino, 5Elettra-Sincrotrone Trieste, Trieste, 6Department of Morphology, Surgery and Experimental Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy Purpose: The aim of the present study was to develop nanoprobes with theranostic features, including – at the same time – photoacoustic, near-infrared (NIR) optical imaging, and photothermal properties, in a versatile and stable core–shell silica-polyethylene glycol (PEG) nanoparticle architecture. Materials and methods: We synthesized core–shell silica-PEG nanoparticles by a one-pot direct micelles approach. Fluorescence emission and photoacoustic and photothermal properties were obtained at the same time by appropriate doping with triethoxysilane-derivatized cyanine 5.5 (Cy5.5) and cyanine 7 (Cy7) dyes. The performances of these nanoprobes were measured in vitro, using nanoparticle suspensions in phosphate-buffered saline and blood, dedicated phantoms, and after incubation with MDA-MB-231 cells. Results: We obtained core–shell silica-PEG nanoparticles endowed with very high colloidal stability in water and in biological environment, with absorption and fluorescence emission in the NIR field. The presence of Cy5.5 and Cy7 dyes made it possible to reach a more reproducible and higher doping regime, producing fluorescence emission at a single excitation wavelength in two different channels, owing to the energy transfer processes within the nanoparticle. The nanoarchitecture and the presence of both Cy5.5 and Cy7 dyes provided a favorable agreement between fluorescence emission and quenching, to achieve optical imaging and photoacoustic and photothermal properties. Conclusion: We obtained rationally designed nanoparticles with outstanding stability in biological environment. At appropriate doping regimes, the presence of Cy5.5 and Cy7 dyes allowed us to tune fluorescence emission in the NIR for optical imaging and to exploit quenching processes for photoacoustic and photothermal capabilities. These nanostructures are promising in vivo theranostic tools for the near future. Keywords: dye-doped nanoparticles, optical imaging, NIR imaging, photoacoustic imaging, photothermal therapy, PEGylated nanoparticles

Published
2016

3. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

Author

Capolla S, Garrovo C, Zorzet S, Lorenzon A, Rampazzo E, Spretz R, Pozzato G, Núñez L, Tripodo C, Macor P, and Biffi S

Subjects
Medicine (General), R5-920
Abstract

Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl), Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of Chicago, Chicago, IL, USA; 8Department of Human Pathology, University of Palermo, Palermo, Italy; 9Callerio Foundation Onlus, Institutes of Biological Researches, Trieste, Italy Abstract: The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies. Keywords: active targeting, optical imaging, tumor accumulation

Published
2015

4. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

Author

Capone, S, Fusco, F, Milleri, S, Borre, S, Carbonara, S, Lo Caputo, S, Leone, S, Gori, G, Maggi, P, Cascio, A, Lichtner, M, Cauda, R, Dal Zoppo, S, Cossu, M, Gori, A, Roda, S, Confalonieri, P, Bonora, S, Missale, G, Codeluppi, M, Mezzaroma, I, Capici, S, Pontali, E, Libanore, M, Diani, A, Lanini, S, Battella, S, Contino, A, Piano Mortari, E, Genova, F, Parente, G, Dragonetti, R, Colloca, S, Visani, L, Iannacone, C, Carsetti, R, Folgori, A, Camerini, R, Ziviani, L, Malescio, F, Turrini, I, Lawlor, R, Romano, A, Nunziata, M, Armato, S, Mazzeo, N, Carleo, M, Dell'Isola, C, Pisapia, R, Pontarelli, A, Olivani, A, Grasselli, S, Laccabue, D, Leoni, M, Paolillo, F, Mancini, A, Ruaro, B, Confalonieri, M, Salton, F, Mancarella, G, Marocco, R, De Masi, M, Belvisi, V, Lamonica, S, Cingolani, A, Seguiti, C, Brambilla, P, Ferraresi, A, Lupi, M, Ludovisi, S, Renisi, G, Massafra, R, Pellicciotta, M, Armiento, L, Vimercati, S, Piacenza, M, Bonfanti, P, Columpsi, P, Cazzaniga, M, Rovelli, C, Ceresini, M, Previtali, L, Trentini, L, Alcantarini, C, Rugge, W, Biffi, S, Poletti, F, Rostagno, R, Moglia, R, De Negri, F, Fini, E, Cangialosi, A, Bruno, S, Rizzo, M, Niglio, M, Stritto, A, Matano, A, Petruzziello, A, Valsecchi, P, Pieri, T, Altamura, M, Calamo, A, Giannelli, A, Menolascina, S, Di Bari, S, Mauro, V, Aronica, R, Segala, D, Cultrera, R, Sighinolfi, L, Abbott, M, Gizzi, A, Marascia, F, Valenti, G, Feasi, M, Bobbio, N, Del Puente, F, Nicosia, A, Frasca, M, Mazzoleni, M, Garofalo, N, Ammendola, V, Grazioli, F, Napolitano, F, Vitelli, A, Marcellini, V, Capone S., Fusco F. M., Milleri S., Borre S., Carbonara S., Lo Caputo S., Leone S., Gori G., Maggi P., Cascio A., Lichtner M., Cauda R., Dal Zoppo S., Cossu M. V., Gori A., Roda S., Confalonieri P., Bonora S., Missale G., Codeluppi M., Mezzaroma I., Capici S., Pontali E., Libanore M., Diani A., Lanini S., Battella S., Contino A. M., Piano Mortari E., Genova F., Parente G., Dragonetti R., Colloca S., Visani L., Iannacone C., Carsetti R., Folgori A., Camerini R., Ziviani L., Malescio F., Turrini I., Lawlor R., Romano A., Nunziata M., Armato S., Mazzeo N., Carleo M. A., Dell'Isola C., Pisapia R., Pontarelli A., Olivani A., Grasselli S., Laccabue D., Leoni M. C., Paolillo F., Mancini A., Ruaro B., Confalonieri M., Salton F., Mancarella G., Marocco R., De Masi M., Belvisi V., Lamonica S., Cingolani A., Seguiti C., Brambilla P., Ferraresi A., Lupi M., Ludovisi S., Renisi G., Massafra R., Pellicciotta M., Armiento L., Vimercati S., Piacenza M., Bonfanti P., Columpsi P., Cazzaniga M. E., Rovelli C., Ceresini M., Previtali L., Trentini L., Alcantarini C., Rugge W., Biffi S., Poletti F., Rostagno R., Moglia R., De Negri F., Fini E., Cangialosi A., Bruno S. R., Rizzo M., Niglio M., Stritto A. D., Matano A., Petruzziello A., Valsecchi P., Pieri T., Altamura M., Calamo A., Giannelli A., Menolascina S., Di Bari S., Mauro V., Aronica R., Segala D., Cultrera R., Sighinolfi L., Abbott M., Gizzi A., Marascia F. G., Valenti G., Feasi M., Bobbio N., Del Puente F., Nicosia A., Frasca M., Mazzoleni M., Garofalo N., Ammendola V., Grazioli F., Napolitano F., Vitelli A., Marcellini V., Capone, S, Fusco, F, Milleri, S, Borre, S, Carbonara, S, Lo Caputo, S, Leone, S, Gori, G, Maggi, P, Cascio, A, Lichtner, M, Cauda, R, Dal Zoppo, S, Cossu, M, Gori, A, Roda, S, Confalonieri, P, Bonora, S, Missale, G, Codeluppi, M, Mezzaroma, I, Capici, S, Pontali, E, Libanore, M, Diani, A, Lanini, S, Battella, S, Contino, A, Piano Mortari, E, Genova, F, Parente, G, Dragonetti, R, Colloca, S, Visani, L, Iannacone, C, Carsetti, R, Folgori, A, Camerini, R, Ziviani, L, Malescio, F, Turrini, I, Lawlor, R, Romano, A, Nunziata, M, Armato, S, Mazzeo, N, Carleo, M, Dell'Isola, C, Pisapia, R, Pontarelli, A, Olivani, A, Grasselli, S, Laccabue, D, Leoni, M, Paolillo, F, Mancini, A, Ruaro, B, Confalonieri, M, Salton, F, Mancarella, G, Marocco, R, De Masi, M, Belvisi, V, Lamonica, S, Cingolani, A, Seguiti, C, Brambilla, P, Ferraresi, A, Lupi, M, Ludovisi, S, Renisi, G, Massafra, R, Pellicciotta, M, Armiento, L, Vimercati, S, Piacenza, M, Bonfanti, P, Columpsi, P, Cazzaniga, M, Rovelli, C, Ceresini, M, Previtali, L, Trentini, L, Alcantarini, C, Rugge, W, Biffi, S, Poletti, F, Rostagno, R, Moglia, R, De Negri, F, Fini, E, Cangialosi, A, Bruno, S, Rizzo, M, Niglio, M, Stritto, A, Matano, A, Petruzziello, A, Valsecchi, P, Pieri, T, Altamura, M, Calamo, A, Giannelli, A, Menolascina, S, Di Bari, S, Mauro, V, Aronica, R, Segala, D, Cultrera, R, Sighinolfi, L, Abbott, M, Gizzi, A, Marascia, F, Valenti, G, Feasi, M, Bobbio, N, Del Puente, F, Nicosia, A, Frasca, M, Mazzoleni, M, Garofalo, N, Ammendola, V, Grazioli, F, Napolitano, F, Vitelli, A, Marcellini, V, Capone S., Fusco F. M., Milleri S., Borre S., Carbonara S., Lo Caputo S., Leone S., Gori G., Maggi P., Cascio A., Lichtner M., Cauda R., Dal Zoppo S., Cossu M. V., Gori A., Roda S., Confalonieri P., Bonora S., Missale G., Codeluppi M., Mezzaroma I., Capici S., Pontali E., Libanore M., Diani A., Lanini S., Battella S., Contino A. M., Piano Mortari E., Genova F., Parente G., Dragonetti R., Colloca S., Visani L., Iannacone C., Carsetti R., Folgori A., Camerini R., Ziviani L., Malescio F., Turrini I., Lawlor R., Romano A., Nunziata M., Armato S., Mazzeo N., Carleo M. A., Dell'Isola C., Pisapia R., Pontarelli A., Olivani A., Grasselli S., Laccabue D., Leoni M. C., Paolillo F., Mancini A., Ruaro B., Confalonieri M., Salton F., Mancarella G., Marocco R., De Masi M., Belvisi V., Lamonica S., Cingolani A., Seguiti C., Brambilla P., Ferraresi A., Lupi M., Ludovisi S., Renisi G., Massafra R., Pellicciotta M., Armiento L., Vimercati S., Piacenza M., Bonfanti P., Columpsi P., Cazzaniga M. E., Rovelli C., Ceresini M., Previtali L., Trentini L., Alcantarini C., Rugge W., Biffi S., Poletti F., Rostagno R., Moglia R., De Negri F., Fini E., Cangialosi A., Bruno S. R., Rizzo M., Niglio M., Stritto A. D., Matano A., Petruzziello A., Valsecchi P., Pieri T., Altamura M., Calamo A., Giannelli A., Menolascina S., Di Bari S., Mauro V., Aronica R., Segala D., Cultrera R., Sighinolfi L., Abbott M., Gizzi A., Marascia F. G., Valenti G., Feasi M., Bobbio N., Del Puente F., Nicosia A., Frasca M., Mazzoleni M., Garofalo N., Ammendola V., Grazioli F., Napolitano F., Vitelli A., and Marcellini V.

Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Published
2023

5. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

Author

Capone S., Fusco F. M., Milleri S., Borre S., Carbonara S., Lo Caputo S., Leone S., Gori G., Maggi P., Cascio A., Lichtner M., Cauda R., Dal Zoppo S., Cossu M. V., Gori A., Roda S., Confalonieri P., Bonora S., Missale G., Codeluppi M., Mezzaroma I., Capici S., Pontali E., Libanore M., Diani A., Lanini S., Battella S., Contino A. M., Piano Mortari E., Genova F., Parente G., Dragonetti R., Colloca S., Visani L., Iannacone C., Carsetti R., Folgori A., Camerini R., Ziviani L., Malescio F., Turrini I., Lawlor R., Romano A., Nunziata M., Armato S., Mazzeo N., Carleo M. A., Dell'Isola C., Pisapia R., Pontarelli A., Olivani A., Grasselli S., Laccabue D., Leoni M. C., Paolillo F., Mancini A., Ruaro B., Confalonieri M., Salton F., Mancarella G., Marocco R., De Masi M., Belvisi V., Lamonica S., Cingolani A., Seguiti C., Brambilla P., Ferraresi A., Lupi M., Ludovisi S., Renisi G., Massafra R., Pellicciotta M., Armiento L., Vimercati S., Piacenza M., Bonfanti P., Columpsi P., Cazzaniga M. E., Rovelli C., Ceresini M., Previtali L., Trentini L., Alcantarini C., Rugge W., Biffi S., Poletti F., Rostagno R., Moglia R., De Negri F., Fini E., Cangialosi A., Bruno S. R., Rizzo M., Niglio M., Stritto A. D., Matano A., Petruzziello A., Valsecchi P., Pieri T., Altamura M., Calamo A., Giannelli A., Menolascina S., Di Bari S., Mauro V., Aronica R., Segala D., Cultrera R., Sighinolfi L., Abbott M., Gizzi A., Marascia F. G., Valenti G., Feasi M., Bobbio N., Del Puente F., Nicosia A., Frasca M., Mazzoleni M., Garofalo N., Ammendola V., Grazioli F., Napolitano F., Vitelli A., Marcellini V., Capone, Stefania, Fusco, Francesco M, Milleri, Stefano, Borrè, Silvio, Carbonara, Sergio, Lo Caputo, Sergio, Leone, Sebastiano, Gori, Giovanni, Maggi, Paolo, Cascio, Antonio, Lichtner, Miriam, Cauda, Roberto, Dal Zoppo, Sarah, Cossu, Maria V, Gori, Andrea, Roda, Silvia, Confalonieri, Paola, Bonora, Stefano, Missale, Gabriele, Codeluppi, Mauro, Mezzaroma, Ivano, Capici, Serena, Pontali, Emanuele, Libanore, Marco, Diani, Augusta, Lanini, Simone, Battella, Simone, Contino, Alessandra M, Piano Mortari, Eva, Genova, Francesco, Parente, Gessica, Dragonetti, Rosella, Colloca, Stefano, Visani, Luigi, Iannacone, Claudio, Carsetti, Rita, Folgori, Antonella, Camerini, Roberto, Capone, S, Fusco, F, Milleri, S, Borre, S, Carbonara, S, Lo Caputo, S, Leone, S, Gori, G, Maggi, P, Cascio, A, Lichtner, M, Cauda, R, Dal Zoppo, S, Cossu, M, Gori, A, Roda, S, Confalonieri, P, Bonora, S, Missale, G, Codeluppi, M, Mezzaroma, I, Capici, S, Pontali, E, Libanore, M, Diani, A, Lanini, S, Battella, S, Contino, A, Piano Mortari, E, Genova, F, Parente, G, Dragonetti, R, Colloca, S, Visani, L, Iannacone, C, Carsetti, R, Folgori, A, Camerini, R, Ziviani, L, Malescio, F, Turrini, I, Lawlor, R, Romano, A, Nunziata, M, Armato, S, Mazzeo, N, Carleo, M, Dell'Isola, C, Pisapia, R, Pontarelli, A, Olivani, A, Grasselli, S, Laccabue, D, Leoni, M, Paolillo, F, Mancini, A, Ruaro, B, Confalonieri, M, Salton, F, Mancarella, G, Marocco, R, De Masi, M, Belvisi, V, Lamonica, S, Cingolani, A, Seguiti, C, Brambilla, P, Ferraresi, A, Lupi, M, Ludovisi, S, Renisi, G, Massafra, R, Pellicciotta, M, Armiento, L, Vimercati, S, Piacenza, M, Bonfanti, P, Columpsi, P, Cazzaniga, M, Rovelli, C, Ceresini, M, Previtali, L, Trentini, L, Alcantarini, C, Rugge, W, Biffi, S, Poletti, F, Rostagno, R, Moglia, R, De Negri, F, Fini, E, Cangialosi, A, Bruno, S, Rizzo, M, Niglio, M, Stritto, A, Matano, A, Petruzziello, A, Valsecchi, P, Pieri, T, Altamura, M, Calamo, A, Giannelli, A, Menolascina, S, Di Bari, S, Mauro, V, Aronica, R, Segala, D, Cultrera, R, Sighinolfi, L, Abbott, M, Gizzi, A, Marascia, F, Valenti, G, Feasi, M, Bobbio, N, Del Puente, F, Nicosia, A, Frasca, M, Mazzoleni, M, Garofalo, N, Ammendola, V, Grazioli, F, Napolitano, F, Vitelli, A, and Marcellini, V

Subjects
immunological memory, phase 2 clinical trial, safety, Sars-CoV-2 vaccine, COVID-19, CD8, T cell response, simian adenoviral vector, General Biochemistry, Genetics and Molecular Biology, CD4, neutralizing antibodie
Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific Tcell response peaks after the first dose and is characterized by high frequencies of CD8s. Tcells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Published
2023

6. Adoption and potential of agri-environmental schemes in Europe: Cross-regional evidence from interviews with farmers

Author

Bartkowski, Bartosz, Beckmann, Michael, Bednář, M., Biffi, S., Domingo-Marimon, C., Mesaroš, M., Schüßler, Charlotte, Šarapatka, B., Tarčak, S., Václavík, T., Ziv, G., Wittstock, Felix, Bartkowski, Bartosz, Beckmann, Michael, Bednář, M., Biffi, S., Domingo-Marimon, C., Mesaroš, M., Schüßler, Charlotte, Šarapatka, B., Tarčak, S., Václavík, T., Ziv, G., and Wittstock, Felix

Abstract

In Europe and elsewhere, agri-environmental schemes (AES) are designed to reduce agriculture's impacts on the environment. Designing effective schemes requires an understanding of the reasons that drive farmers' decisions whether to adopt AES.Currently, most insights come from individual case studies or structured surveys based on predefined questions. There is a paucity of studies that do not rely on rigid preconceptions about relevant behavioural factors while also offering a geographically and socio-culturally broad perspective that can address the cultural and institutional context-specificity of behavioural studies. Also, most studies focus on the adoption decision, while implementation decisions and their consequences for the ecological effectiveness of AES remain understudied.In this article, we present the results from semi-structured farmer interviews conducted in five agricultural landscapes across Europe. The results are used to uncover reasons for AES adoption as well as the implications of AES implementation decisions for their ecological effectiveness.The main reason for AES adoption that was common across case study regions is the interplay of opportunity costs and payment levels, which has negative implications for the ecological effectiveness of AES as farmers prioritized marginal land or adopted non-additional AES. Among reasons that vary across regions, tenure relations and the role of ecological reasoning stand out.We find that AES are unlikely to trigger broader shifts towards sustainable management but there is some potential for improvement, mainly by increasing the flexibility, spatial targeting and ecological ambition of the schemes.

Published
2023

7. Soil carbon sequestration potential of planting hedgerows in agricultural landscapes

Author

Biffi, S, Chapman, PJ, Grayson, RP, and Ziv, G

Abstract

Realising the carbon (C) sequestration capacity of agricultural soils is needed to reach Paris Climate Agreement goals; thus, quantifying hedgerow planting potential to offset anthropogenic CO2 emissions is crucial for accurate climate mitigation modelling. Although being a widespread habitat in England and throughout Europe, the potential of hedgerows to contribute to net-zero targets is unclear. This is the first study to quantify the soil organic carbon (SOC) sequestration rate associated with planting hedgerows. We derived SOC stocks beneath hedgerows based on two estimation methods to assess differences from adjacent intensively managed grassland fields and how these may be affected by sampling depth and hedgerow age, as well as the SOC estimation method used. Twenty-six hedgerows on five dairy farms in Cumbria, England, were classified based on the time since their planting. We measured SOC stocks in 10 cm depth intervals in the top 50 cm of soil beneath hedgerows and in adjacent grassland fields. SOC beneath hedgerows was on average 31.3% higher than in the fields, 3.3% for 2–4 year old hedgerows, 14.4% for 10 year old, 45.2% for 37 year old, and 57.2% for older ones. We show that SOC sequestration rate beneath 37 year old hedgerows was 1.48 Mg C ha−1 yr−1 in the top 50 cm of soil. If England reaches its goal of a 40% increase in hedgerow length, 6.3 Tg CO2 will be stored in the soil over 40 years, annually offsetting 4.7%–6.4% of present-day agricultural CO2 emissions. However, the current rate of planting funded by agri-environment schemes, which today reaches only 0.02% of emissions, is too slow. Private-sector payments for ecosystem services initiatives (e.g., ‘Milk Plan’) show much higher rates of planting and are needed alongside agri-environment schemes to ensure hedgerow planting contributes to net-zero targets.

Published
2022

8. Deliverable D3.4 Summaries of data, obstacles and challenges from interview campaigns

Author

Wittstock, Felix, Hötten, David, Biffi, S., Domingo-Marimon, C., Šarapatka, B., Bednář, M., Mesaroš, M., Wittstock, Felix, Hötten, David, Biffi, S., Domingo-Marimon, C., Šarapatka, B., Bednář, M., and Mesaroš, M.

Abstract

This deliverable presents a Summaries of data, obstacles and challenges from interview campaigns of the H2020 BESTMAP project. It covers a detailed description of methodology, reporting on the concrete steps taken to collect and analyze interview data. It also discusses obstacles and challenges to BESTMAP interview campaigns. Finally, the deliverable presents the main qualitative and quantitative findings of the interview analysis, with a focus on qualitative content analysis of open interview questions.

Published
2022

10. Combination antifungal therapy for invasive mold infections among pediatric patients with hematological malignancies: Data from a real-life case-series

Author

Peri, A, Verna, M, Biffi, S, Alagna, L, Longhi, B, Migliorino, G, Foresti, S, Bandera, A, Rovelli, A, Rizzari, C, Gori, A, Colombini, A, Peri A. M., Verna M., Biffi S., Alagna L., Longhi B., Migliorino G. M., Foresti S., Bandera A., Rovelli A., Rizzari C., Gori A., Colombini A., Peri, A, Verna, M, Biffi, S, Alagna, L, Longhi, B, Migliorino, G, Foresti, S, Bandera, A, Rovelli, A, Rizzari, C, Gori, A, Colombini, A, Peri A. M., Verna M., Biffi S., Alagna L., Longhi B., Migliorino G. M., Foresti S., Bandera A., Rovelli A., Rizzari C., Gori A., and Colombini A.

Abstract

Background: Invasive mold infections in children with hematological malignancies are associated with high mortality rates. The use of combination antifungal therapy in cases with a severe clinical course is increasing, although information on the efficacy and safety of this approach is limited. Methods: We present a case series of 13 children affected by hemato-oncological disorders who received combination antifungal therapy for invasive mold infections at our center (Pediatric Hematology, San Gerardo Hospital, Monza, Italy) from 2011 to 2016, with the aim of describing their clinical characteristics, types of infections, treatment regimens, clinical outcomes, and treatment safety. Medical records were retrospectively reviewed in order to describe patients’ charac-teristics. Results: Combination antifungal therapy included liposomal amphotericin associated with caspofungin (5/13, 38.4%), voriconazole (5/13, 38.4%), or posaconazole (3/13, 23.1%). The 12-week treatment response rate was 69.2% (6/13 patients showed complete response, 3/13 partial re-sponse). The crude mortality was 30.7% (4/13): half was related to invasive mold infections (2/13, 15.38%) and half to disease progression (2/13, 15.38%). Overall, treatment was well tolerated, and we did not observe any permanent discontinuation of antifungals due to related side effects. Conclusions: In our experience, combination antifungal therapy seems to be a safe option in im-munocompromised children with invasive mold infections. Well-designed studies are needed to confirm the safety of this approach and to better understand its efficacy in the pediatric setting.

Published
2019

11. Aligning agri-environmental subsidies and environmental needs: A comparative analysis between the US and EU

Author

Biffi, S, Traldi, R, Crezee, B, Beckmann, M, Egli, L, Epp Schmidt, D, Motzer, N, Okumah, M, Seppelt, R, Slabbert, E, Tiedeman, K, Wang, H, and Ziv, G

Abstract

The global recognition of modern agricultural practices' impact on the environment has fuelled policy responses to ameliorate environmental degradation in agricultural landscapes. In the US and the EU, agri-environmental subsidies (AES) promote widespread adoption of sustainable practices by compensating farmers who voluntarily implement them on working farmland. Previous studies, however, have suggested limitations of their spatial targeting, with funds not allocated towards areas of the greatest environmental need. We analysed AES in the US and EU –specifically through the Environmental Quality Incentives Program (EQIP) and selected measures of the European Agricultural Fund for Rural Development (EAFRD)– to identify if AES are going where they are most needed to achieve environmental goals, using a set of environmental need indicators, socio-economic variables moderating allocation patterns, and contextual variables describing agricultural systems. Using linear mixed models and linear models we explored the associations among AES allocation and these predictors at different scales. We found that higher AES spending was associated with areas of low soil organic carbon and high greenhouse gas emissions both in the US and EU, and nitrogen surplus in the EU. More so than successes, however, clear mismatches of funding and environmental need emerged – AES allocation did not successfully target areas of highest water stress, biodiversity loss, soil erosion, and nutrient runoff. Socio-economic and agricultural context variables may explain some of these mismatches; we show that AES were allocated to areas with higher proportions of female producers in the EU but not in the US, where funds were directed towards areas with less tenant farmers. Moreover, we suggest that the potential for AES to remediate environmental issues may be curtailed by limited participation in intensive agricultural landscapes. These findings can help inform refinements to EQIP and EAFRD allocation mechanisms and identify opportunities for improving future targeting of AES spending.

Published
2021

12. Simple parameters from complete blood count predict in-hospital mortality in covid-19

Author

Bellan, M., Azzolina, D., Hayden, E., Gaidano, G., Pirisi, M., Acquaviva, A., Aimaretti, G., Valletti, P. A., Angilletta, R., Arioli, R., Avanzi, G. C., Avino, G., Balbo, P. E., Baldon, G., Baorda, F., Barbero, E., Baricich, A., Barini, M., Barone-Adesi, F., Battistini, S., Beltrame, M., Bertoli, M., Bertolin, S., Bertolotti, M., Betti, M., Bobbio, F., Boffano, P., Boglione, L., Borre, S., Brucoli, M., Calzaducca, E., Cammarata, E., Cantaluppi, V., Cantello, R., Capponi, A., Carriero, A., Casciaro, G. F., Castello, L. M., Ceruti, F., Chichino, G., Chirico, E., Cisari, C., Cittone, M. G., Colombo, C., Comi, C., Croce, E., Daffara, T., Danna, P., Corte, F. D., de Vecchi, S., Dianzani, U., Benedetto, D. D., Esposto, E., Faggiano, F., Falaschi, Z., Ferrante, D., Ferrero, A., Gagliardi, I., Galbiati, A., Gallo, S., Garavelli, P. L., Gardino, C. A., Garzaro, M., Gastaldello, M. L., Gavelli, F., Gennari, A., Giacomini, G. M., Giacone, I., Via, V. G., Giolitti, F., Gironi, L. C., Gramaglia, C., Grisafi, L., Inserra, I., Invernizzi, M., Krengli, M., Labella, E., Landi, I. C., Landi, R., Leone, I., Lio, V., Lorenzini, L., Maconi, A., Malerba, M., Manfredi, G. F., Martelli, M., Marzari, L., Marzullo, P., Mennuni, M., Montabone, C., Morosini, U., Mussa, M., Nerici, I., Nuzzo, A., Olivieri, C., Padelli, S. A., Panella, M., Parisini, A., Pasche, A., Patrucco, F., Patti, G., Pau, A., Pedrinelli, A. R., Percivale, I., Ragazzoni, L., Re, R., Rigamonti, C., Rizzi, E., Rognoni, A., Roveta, A., Salamina, L., Santagostino, M., Saraceno, M., Savoia, P., Sciarra, M., Schimmenti, A., Scotti, L., Spinoni, E., Smirne, C., Tarantino, V., Tillio, P. A., Tonello, S., Vaschetto, R., Vassia, V., Zagaria, D., Zavattaro, E., Zeppegno, P., Zottarelli, F., Sainaghi, P. P., Aiosa, G., Airoldi, A., Barco, A., Bargiacchi, O., Bazzano, S., Berni, P., Bianchi, B., Bianco, S., Biffi, S., Binda, V., Bolgeo, T., Bolla, C., Bonato, V., Bonizzoni, G., Bragantini, A., Brustia, D., Bullara, V., Burlone, M., Brustia, F., Caccia, S., Calareso, A., Cammarota, G., Cancelliere, L., Carbone, R., Cassinari, A., Ceriani, E., Cena, T., Clivati, E., Collimedaglia, L., Colombatto, A., Cornella, C., Costanzo, M., Croce, A., de Benedittis, C., Delorenzi, S., Dionisio, R., Donato, P., Esposito, M., Fangazio, S., Feggi, A., Ferrillo, S., Foci, V., Fra, G. P., Gaggino, C., Gambaro, E., Gattoni, E., Gattoni, L., Giacchero, F., Gianfreda, R., Giubertoni, A., Grecu, L., Grossi, F., Guglielmetti, G., Guido, S., Iannantuoni, G., Ingrao, S., Jona, A., Lazzarich, E., Lissandrin, R., Maduli, E., Magne, F., Mantia, E., Marangon, D., Massara, M., Matino, E., Mauri, M. G., Menegatti, M., Moglia, R., Molinari, R., Morelli, S., Morlino, P., Naldi, P., Nebbiolo, C., Omodeo, P., Palmieri, D., Panero, A., Parodi, M., Pedrazzoli, R., Pelazza, C., Penpa, S., Perucca, R., Pirovano, A., Pittau, S., Pochetti, P., Poletti, F., Polla, B., Prandi, P., Prodam, F., Prosperini, P., Puma, A., Quaglia, M., Raie, A., Rapetti, R., Ravera, S., Re, A., Reale, M., Rossati, A., Rossi, M., Rossi, P., Rostagno, R., Salomoni, G., Sama, M. T., Sarchi, E., Sarcoli, M., Sarda, C., Sguazzotti, I., Soddu, D., Sola, D., Stobbione, P., Todoerti, M., Vallese, G. C., Varrasi, C., Veia, A., Vignazia, G. L., Zanotti, I., Zecca, E., Zichittella, D., Zisa, G., and Zoppis, E.

Subjects
Adult, Male, medicine.medical_specialty, Medicine (General), Multivariate analysis, Article Subject, Clinical Decision Rules, COVID-19, Prognosis, Blood Cell Count, Hospital Mortality, Severity of Illness Index, Clinical Biochemistry, Asymptomatic, Severity of Illness Index, NO, R5-920, Internal medicine, Clinical Decision Rules, Severity of illness, Genetics, 80 and over, Medicine, Humans, Hospital Mortality, Molecular Biology, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Biochemistry (medical), Complete blood count, COVID-19, Retrospective cohort study, Red blood cell distribution width, General Medicine, Odds ratio, Middle Aged, Prognosis, Female, Italy, Multivariate Analysis, Blood Cell Count, Cohort, medicine.symptom, business, Research Article
Abstract

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Published
2021

13. Aligning agri-environmental subsidies and environmental needs: a comparative analysis between the US and EU

Author

Biffi, S., Traldi, R., Crezee, B., Beckmann, Michael, Egli, Lukas, Epp Schmidt, D., Motzer, N., Okumah, M., Seppelt, Ralf, Slabbert, Eleonore Louise, Tiedeman, Kate, Wang, H., Ziv, G., Biffi, S., Traldi, R., Crezee, B., Beckmann, Michael, Egli, Lukas, Epp Schmidt, D., Motzer, N., Okumah, M., Seppelt, Ralf, Slabbert, Eleonore Louise, Tiedeman, Kate, Wang, H., and Ziv, G.

Abstract

The global recognition of modern agricultural practices' impact on the environment has fuelled policy responses to ameliorate environmental degradation in agricultural landscapes. In the US and the EU, agri-environmental subsidies (AES) promote widespread adoption of sustainable practices by compensating farmers who voluntarily implement them on working farmland. Previous studies, however, have suggested limitations of their spatial targeting, with funds not allocated towards areas of the greatest environmental need. We analysed AES in the US and EU –specifically through the Environmental Quality Incentives Program (EQIP) and selected measures of the European Agricultural Fund for Rural Development (EAFRD)– to identify if AES are going where they are most needed to achieve environmental goals, using a set of environmental need indicators, socio-economic variables moderating allocation patterns, and contextual variables describing agricultural systems. Using linear mixed models and linear models we explored the associations among AES allocation and these predictors at different scales. We found that higher AES spending was associated with areas of low soil organic carbon and high greenhouse gas emissions both in the US and EU, and nitrogen surplus in the EU. More so than successes, however, clear mismatches of funding and environmental need emerged – AES allocation did not successfully target areas of highest water stress, biodiversity loss, soil erosion, and nutrient runoff. Socio-economic and agricultural context variables may explain some of these mismatches; we show that AES were allocated to areas with higher proportions of female producers in the EU but not in the US, where funds were directed towards areas with less tenant farmers. Moreover, we suggest that the potential for AES to remediate environmental issues may be curtailed by limited participation in intensive agricultural landscapes. These findings can help inform refinements to EQIP and EAFRD allocatio

Published
2021

15. Monarda citriodora hydrolate vs essential oil comparison in several anti-microbial applications

Author

Di Vito, Maura, Bellardi, M. G., Mondello, F., Modesto, M., Michelozzi, M., Bugli, Francesca, Sanguinetti, Maurizio, Sclocchi, M. C., Sebastiani, M. L., Biffi, S., Barbanti, L., Mattarelli, P., Di Vito M. (ORCID:0000-0002-2991-0855), Bugli F. (ORCID:0000-0001-9038-3233), Sanguinetti M. (ORCID:0000-0002-9780-7059), Di Vito, Maura, Bellardi, M. G., Mondello, F., Modesto, M., Michelozzi, M., Bugli, Francesca, Sanguinetti, Maurizio, Sclocchi, M. C., Sebastiani, M. L., Biffi, S., Barbanti, L., Mattarelli, P., Di Vito M. (ORCID:0000-0002-2991-0855), Bugli F. (ORCID:0000-0001-9038-3233), and Sanguinetti M. (ORCID:0000-0002-9780-7059)

Abstract

The hydrolate, or hydrosol, is the residue of essential oil (EO) distillation traditionally used in perfumery. Evidence that also this product exerts anti-microbial activity promoted a study on Monarda citriodora EO and hydrolate against thirty representative strains of bacteria and fungi. Additionally, the sole hydrolate was tested in four moulds responsible for the spoilage of paper artworks. The micro-broth dilution test served to assess EO (concentrations between 0.0078% and 4%) and hydrolate (concentrations between 12.5% and 50%) suppressiveness vs untreated control. EO and hydrolate were analysed (GC–MS), resulting in thymol being the major terpenic compound of both products (19.6% and 66.4% in the respective spectra). EO suppressed all micro-organisms, although resistant Pseudomonas aeruginosa strains required up to 4% EO as minimum inhibitory concentration (MIC). Hydrolate suppressed all micro-organisms, except three P. aeruginosa strains where even the highest concentration (50% hydrolate) failed to reach the MIC. In each strain, the concentration needed to obtain 50% inhibition (IC50) was calculated by means of an exponential decay function. Median IC50 was 0.06% (EO) and 7.35% (hydrolate), while six IC50 EO data were shown to be outliers. In non-outlier data, IC50 hydrolate and EO were significantly correlated (r = 0.73**), and IC50 hydrolate was approximately a hundred times higher than IC50 EO. Despite higher concentration needed for the same inhibitory effect, the amount of terpenes supplied with hydrolate was lower than with EO. This means a higher hydrolate effectiveness that was likely due to the hydrophilic environment promoting higher terpene availability. Lastly, hydrolate exhibited promising results in the control of fungal growth on paper artworks, suppressing the four tested strains at concentrations of 25–50%.

Published
2019

16. Dexamethasone Conjugation to Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective Liver Targeting and Improves Therapeutic Efficacy in an Autoimmune Hepatitis Murine Model

Author

Violatto, M, Casarin, E, Talamini, L, Russo, L, Baldan, S, Tondello, C, Messmer, M, Hintermann, E, Rossi, A, Passoni, A, Bagnati, R, Biffi, S, Toffanin, C, Gimondi, S, Fumagalli, S, De Simoni, M, Barisani, D, Salmona, M, Christen, U, Invernizzi, P, Bigini, P, Morpurgo, M, Violatto, MB, FUMAGALLI, STEFANO, De Simoni, MG, Violatto, M, Casarin, E, Talamini, L, Russo, L, Baldan, S, Tondello, C, Messmer, M, Hintermann, E, Rossi, A, Passoni, A, Bagnati, R, Biffi, S, Toffanin, C, Gimondi, S, Fumagalli, S, De Simoni, M, Barisani, D, Salmona, M, Christen, U, Invernizzi, P, Bigini, P, Morpurgo, M, Violatto, MB, FUMAGALLI, STEFANO, and De Simoni, MG

Abstract

Steroids are the standard therapy for autoimmune hepatitis (AIH) but the long-lasting administration is hampered by severe side effects. Methods to improve the tropism of the drug toward the liver are therefore required. Among them, conjugation to nanoparticles represents one possible strategy. In this study, we exploited the natural liver tropism of Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS) to carry dexamethasone selectively to the liver in an AIH animal model. An acid-labile biotin-hydrazone linker was developed for reversible dexamethasone loading onto ANANAS. The biodistribution, pharmacokinetics and efficacy of free and ANANAS-linked dexamethasone (ANANAS-Hz-Dex) in healthy and AIH mice were investigated upon intraperitoneal administration. In ANANAS-treated animals, the free drug was detected only in the liver. Super-resolution microscopy showed that nanoparticles segregate inside lysosomes of liver immunocompetent cells, mainly involved in AIH progression. In agreement with these observational results, chronic low-dose treatment with ANANAS-Hz-Dex reduced the expression of liver inflammation markers and, in contrast to the free drug, also the levels of circulating AIH-specific autoantibodies. These data suggest that the ANANAS carrier attenuates AIH-related liver damage without drug accumulation in off-site tissues. The safety and biodegradability of the ANANAS carrier make this formulation a promising tool for the treatment of autoimmune liver disorders.

Published
2019

18. The Tellus Project, A Study Of Seismic Precursors

Author

Nicolì, L., Biffi, S., Caccia, L., Cavallucci, M., Gullà, D., Lupo, G., Martini, M., Massimiani, G., and Massimo Zucchetti

Subjects
Tellus Project, radon, Tellus Project, Seismic Precursors, Tellus project, seismic precursors, Seismic Precursors
Published
2016

20. Endophytic and rhizospheric bacterial communities isolated from the medicinal plants Echinacea purpurea and Echinacea angustifolia

Author

Chiellini C., Maida I., Emiliani G., Mengoni A., Mocali S., Fabiani A., Biffi S., Maggini V., Gori L., Vannacci A., Gallo E., Firenzuoli F., and Fani R.

Subjects
Echinacea angustifolia, fungi, food and beverages, endophytes, rhizosphere, Echinacea purpurea, medicinal plants
Abstract

In this work we analyzed the composition and structure of cultivable bacterial communities isolated from the stem/leaf and root compartments of two medicinal plants, Echinacea Purpurea (L.) Moench and Echinacea angustifolia (DC.) Hell, grown in the same soil, as well as the bacterial community from their rhizospheric soils. Molecular PCR-based techniques were applied to cultivable bacteria isolated from the three compartments of the two plants. The results showed that the two plants and their respective compartments were characterized by different communities, indicating a low degree of strain sharing and a strong selective pressure within plants tissue. Pseudomanas was the most highly represented genus, together with Actino-bacteria and Bacullus spp.The presence of distinct bacterial communities in different plant species and among compartments of the same plant species could account for the differences in the medicinal properties of the two plants.

Published
2014

24. Influenza di Alfalfa Mosaic Virus sulla composizione dell’olio essenziale di Lavandula vera DC. E di cinque differenti cultivars di Lavandula hybrida Rev

Author

Bianchi A., Bruni R., Biffi S., BELLARDI, MARIA GRAZIA, SOCIETÀ BOTANICA ITALIANA, Bianchi A., Bruni R., Biffi S., and Bellardi M.G.

Subjects
ALFALFA MOSAIC VIRUS, LAVANDA, LAVANDINO, GC-MS, OLI ESSENZIALI
Abstract

Il virus del mosaico dell'erba medica è stato individuato in impianti di lavanda e lavandino dell'Emilia-Romagna. Le piante infette manifestavano mosaico giallo sulle foglie. Sono state selezionate piante sane ed AMV-infette. Da esse sono stati distillati gli oli essenziali da sottoporre ad analisi GC-MS. Sono state rilevate differenze significative nella composizione degli oli ottenuti da materiale sano ed infetto.

Published
2005

27. Correction: New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles

Author

Mezzaroba N, Zorzet S, Secco E, Biffi S, Claudio Tripodo, Calvaruso M, Mendoza-Maldonado R, Capolla S, Granzotto M, Spretz R, Larsen G, Noriega S, Lucafò M, Mansilla E, Garrovo C, Gh, Marín, Baj G, Gattei V, Pozzato G, Núñez L, and Macor P

Subjects
Multidisciplinary, Science, lcsh:R, lcsh:Medicine, Medicine, Correction, lcsh:Q, lcsh:Science
Published
2013

34. Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice

Author

Macor, P, primary, Secco, E, additional, Mezzaroba, N, additional, Zorzet, S, additional, Durigutto, P, additional, Gaiotto, T, additional, De Maso, L, additional, Biffi, S, additional, Garrovo, C, additional, Capolla, S, additional, Tripodo, C, additional, Gattei, V, additional, Marzari, R, additional, Tedesco, F, additional, and Sblattero, D, additional

Published
2014
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39. Response to paroxetine and polymorphism of the Catechol-O-ethyl transferase in panic disorder

Author

Favaron, E., Caldirola, D., Grassi, M., Biffi, S., Galimberti, E., and Bellodi, L.

Subjects
Panic attacks -- Research -- Care and treatment, Genetic polymorphisms -- Research -- Usage, Paroxetine -- Research -- Usage, Panic disorders -- Research -- Care and treatment, Pharmaceuticals and cosmetics industries, Psychology and mental health, Care and treatment, Usage, Research
Abstract

Background: Catechol-O-methyltransferase (COMT), one of the enzymes deputed to the inactivation of catecholamines, exists in two allelic variants modulated by a genetic polymorphism: COMT H allele with high activity and [...]

Published
2006

49. The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection

Author

Benincasa Monica, Pelillo Chiara, Zorzet Sonia, Garrovo Chiara, Biffi Stefania, Gennaro Renato, and Scocchi Marco

Subjects
Microbiology, QR1-502
Abstract

Abstract Background Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection. Results The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance. Conclusions Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule.

Published
2010
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50. Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix

Author

Enrico Rampazzo, Giovanni Di Lorenzo, F. Buonomo, Chiara Ripepi, Francesco Valle, Stefania Biffi, Blendi Ura, Riccardo Addobbati, Barbara Bortot, Federico Romano, Maura Apollonio, Andrea Ridolfi, Marco Brucale, Giuseppe Ricci, Bortot B., Apollonio M., Rampazzo E., Valle F., Brucale M., Ridolfi A., Ura B., Addobbati R., Di Lorenzo G., Romano F., Buonomo F., Ripepi C., Ricci G., Biffi S., Bortot, B., Apollonio, M., Rampazzo, E., Valle, F., Brucale, M., Ridolfi, A., Ura, B., Addobbati, R., Di Lorenzo, G., Romano, F., Buonomo, F., Ripepi, C., Ricci, G., and Biffi, S.

Subjects
Proteomics, Cancer Research, extracellular matrix, Carcinoma, Ovarian Epithelial, chemotherapy, Extracellular matrix, ascites, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, fibronectin, Cell Line, Tumor, Ascites, Genetics, medicine, Humans, RC254-282, Research Articles, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, biology, Chemistry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, General Medicine, medicine.disease, extracellular vesicles, ovarian cancer, Fibronectin, ascite, Oncology, Tumor progression, Cell culture, 030220 oncology & carcinogenesis, Plasminogen activator inhibitor-1, Cancer research, biology.protein, Molecular Medicine, extracellular vesicle, medicine.symptom, Ovarian cancer, Research Article
Abstract

The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre‐metastatic niche have not been fully discovered. In this study, we characterized ascites from high‐grade epithelial ovarian cancer patients. Small‐EVs (30–150 nm) were isolated from two sources—the bulk ascites and the ascitic fluid‐derived tumor cell cultures—and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small‐EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid‐derived small‐EVs were predominantly involved in the complement and coagulation cascade. Small‐EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor‐β‐I (TGFβI), plasminogen activator inhibitor 1 (PAI‐1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small‐EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment‐induced cancer adaption processes., The mechanisms by which extracellular vesicles (EVs) promote ovarian cancer progression in the pre‐metastatic niche have not been fully discovered. This study showed that sampling ascites before and after chemotherapy allows characterizing small‐EVs released by tumor cells, reflecting their biological status. Small‐EVs derived from ascitic fluid‐derived tumor cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators.

Published
2021

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