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1. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author: Di Maio, V. C., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M. C., Antonucci, F. P., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L. A., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C. F., Babudieri, S., Mura, M. S., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C. F., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Vecchiet, J., Bruzzone, B., De Maria, A., Di Biagio, A., Marenco, S., Nicolini, L. A., Picciotto, A., Viscoli, C., Casinelli, K., Monache, M. Delle, Lichtner, M., Mastroianni, C., Aghemo, A., Bruno, S., Cerrone, M., Colombo, M., Monforte, A. DʼArminio, Danieli, E., Donato, F., Gubertini, G., Landonio, S., Magni, C. F., Mancon, A., Micheli, V., Monico, S., Niero, F., Puoti, M., Rizzardini, G., Russo, M. L., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Romagnoli, D., Brancaccio, G., Caporaso, N., Gaeta, G. B., Lembo, V., Morisco, F., Calvaruso, V., Craxì, A., Di Marco, V., Mazzola, A., Petta, S., DʼAmico, E., Cacciatore, P., Consorte, A., Palitti, V. Pace, Parruti, G., Pieri, A., Polilli, E., Tontodonati, M., Andreoni, M., Angelico, M., Antenucci, F., Antonucci, F. P., Aragri, M., Armenia, D., Baiocchi, L., Bellocchi, M., Bertoli, A., Biliotti, E., Biolato, M., Carioti, L., Ceccherini-Silberstein, F., Cento, V., Cerasari, G., Cerva, C., Ciotti, M., DʼAmbrosio, C., DʼEttorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Francioso, S., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Gianserra, L., Grieco, A., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Milana, M., Nosotti, L., Palazzo, D., Pasquazzi, C., Pellicelli, A., Perno, C. F., Romano, M., Santopaolo, F., Santoro, M. M., Sarmati, L., Sarrecchia, C., Sforza, D., Siciliano, M., Sorbo, M. C., Spaziante, M., Svicher, V., Taliani, G., Teti, E., Tisone, G., Vespasiani-Gentilucci, U., Vullo, V., Mangia, A., Babudieri, S., Maida, I., Melis, M., Mura, M. S., Falconi, L., Di Giammartino, D., and Tarquini, P.
Published: 2016
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2. Evaluating the Performance of Climate Models Based on Wasserstein Distance

Author: Vissio G.[1, Lembo V.[1, Lucarini V.[1, 4, Ghil M.[6, Meteorological Institute [Hamburg], University of Hamburg, CNR Institute of Atmospheric Sciences and Climate (ISAC), Consiglio Nazionale delle Ricerche (CNR), University of Reading (UOR), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), and University of California
Subjects: Mathematical optimization, 010504 meteorology & atmospheric sciences, Computer science, Rank (computer programming), Climatic variables, Climate change, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, 010502 geochemistry & geophysics, 01 natural sciences, Measure (mathematics), Geophysics, Ranking, 13. Climate action, climate models, Wasserstein distance, General Earth and Planetary Sciences, Probability distribution, Climate model, Specific model, 0105 earth and related environmental sciences
Abstract: International audience; We propose a methodology for intercomparing climate models and evaluating their performance against benchmarks based on the use of the Wasserstein distance (WD). This distance provides a rigorous way to measure quantitatively the difference between two probability distributions. The proposed approach is flexible and can be applied in any number of dimensions; it allows one to rank climate models taking into account all the moments of the distributions. By selecting the combination of climatic variables and the regions of interest, it is possible to highlight specific model deficiencies. The WD enables a comprehensive evaluation of the skill of a climate model. We apply this approach to a selected number of physical fields, ranking the models in terms of their performance in simulating them and pinpointing their weaknesses in the simulation of some of the selected physical fields in specific areas of the Earth.
Published: 2020
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3. Singular case of fingers onychomycosis due to Aspergillus terreus implicated in patientʼs bronchitis: P410

Author: Harak, H., Wuhrer, E., and Lembo, V.
Published: 2012

4. Spectral Decomposition and Extremes of Atmospheric Meridional Energy Transport in the Northern Hemisphere Midlatitudes

Author: Lembo, V., Messori, Gabriele, Graversen, R., Lucarini, V., Lembo, V., Messori, Gabriele, Graversen, R., and Lucarini, V.
Abstract: The atmospheric meridional energy transport in the Northern Hemisphere midlatitudes is mainly accomplished by planetary and synoptic waves. A decomposition into wave components highlights the strong seasonal dependence of the transport, with both the total transport and the contributions from planetary and synoptic waves peaking in winter. In both winter and summer months, poleward transport extremes primarily result from a constructive interference between planetary and synoptic motions. The contribution of the mean meridional circulation is close to climatology. Equatorward transport extremes feature a mean meridional equatorward transport in winter, while the planetary and synoptic modes mostly transport energy poleward. In summer, a systematic destructive interference occurs, with planetary modes mostly transporting energy equatorward and synoptic modes again poleward. This underscores that baroclinic conversion dominates regardless of season in the synoptic wave modes, whereas the planetary waves can be either free or forced, depending on the season. Plain Language Summary The atmospheric heat transport from low to high latitudes is the main mechanism through which the climate reequilibrates the latitudinally uneven absorption of solar radiation. The atmospheric transport is fueled by instabilities driven by the presence of temperature differences between low and high latitudes and acts in such a way to reduce such gradient. This is one of the main stabilizing mechanisms of the climate system. In this work, we investigate how motions of different spatial scales contribute to atmospheric heat transports in the Northern Hemisphere. We discover that the relative importance of synoptic and planetary scale atmospheric motions is different in summer and winter. Our analysis delves into the analysis of events associated with extreme heat transport toward high latitudes, where we see a compensating mechanism between synoptic and planetary atmospheric motions. We furthe
Published: 2019
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5. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author: Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, Collaborators (129) Mariani R, HCV Italian Resistance Network Study Group., Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio VC, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, Ms, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V C, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M C, Antonucci, F P, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L A, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C F, Babudieri, S, Mura, M S, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C F, Ceccherini-Silberstein, F, HCV Italian Resistance Network Study Group., Collaborators (129) Mariani R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Nicolini, La, Viscoli, C, Casinelli, K, Monache, Md, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, Monforte, Ad, Danieli, E, Donato, F, Gubertini, G, Magni, Cf, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, Ml, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, Gb, Lembo, V, Calvaruso, V, Craxì, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Palitti, Vp, Pieri, A, Polilli, E, Antenucci, F, Antonucci, Fp, Armenia, D, Baiocchi, L, Bellocchi, M, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Di Maio, Vc, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Perno, Cf, Santopaolo, F, Santoro, Mm, Sforza, D, Sorbo, Mc, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Mura, M, Falconi, L, Di Giammartino, D, Tarquini, P., Di Maio, V. C, Bellocchi, M. C, Antonucci, F. P, Nicolini, L. A, Magni, C. F, Mura, M. S, Vespasiani Gentilucci, U, Morisco, Filomena, Perno, C. F, Ceccherini Silberstein, F., Caporaso, Nicola, Di Maio, V., Cento, V., Di Paolo, D., Aragri, M., De Leonardis, F., Tontodonati, M., Micheli, V., Bellocchi, M., Antonucci, F., Bertoli, A., Lenci, I., Milana, M., Gianserra, L., Melis, M., Di Biagio, A., Sarrecchia, C., Sarmati, L., Landonio, S., Francioso, S., Lambiase, L., Nicolini, L., Marenco, S., Nosotti, L., Giannelli, V., Siciliano, M., Romagnoli, D., Pellicelli, A., Vecchiet, J., Magni, C., Babudieri, S., Mura, M., Taliani, G., Mastroianni, C., Vespasiani-Gentilucci, U., Romano, M., Morisco, F., Gasbarrini, A., Vullo, V., Bruno, S., Baiguera, C., Pasquazzi, C., Tisone, G., Picciotto, A., Andreoni, M., Parruti, G., Rizzardini, G., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Paoloni, M., Iapadre, N., Grimaldi, A., Menzaghi, B., Quirino, T., Bruzzone, B., De Maria, A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Mancon, A., Monico, S., Niero, F., Puoti, M., Russo, M., Alfieri, R., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Caporaso, N., Gaeta, G., Lembo, V., Calvaruso, V., Craxã, A., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pace Palitti, V., Pieri, A., Polilli, E., Antenucci, F., Armenia, D., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Sanctis, A., Furlan, C., Gallo, P., Grieco, A., Grieco, S., Lattanzi, B., Malagnino, V., Manuelli, M., Merli, M., Miglioresi, L., Palazzo, D., Santopaolo, F., Santoro, M., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Teti, E., Mangia, A., Maida, I., Falconi, L., and Di Giammartino, D.
Subjects: 0301 basic medicine, ns3, Genotyping Techniques, viruses, Drug Resistance, Hepacivirus, Viral Nonstructural Proteins, medicine.disease_cause, Gastroenterology, Telaprevir, chemistry.chemical_compound, genotype, genotyping techniques, hepacivirus, hepatitis C, humans, RNA viral, retrospective studies, sequence analysis, DNA, viral nonstructural proteins, drug resistance, viral, mutation, pharmacology, infectious diseases, 0302 clinical medicine, Retrospective Studie, Genotype, Pharmacology (medical), Viral, Hepatitis C, Humans, RNA, Viral, Retrospective Studies, Sequence Analysis, DNA, Drug Resistance, Viral, Mutation, Proteolytic enzymes, virus diseases, Settore MED/07 - Microbiologia e Microbiologia Clinica, hcv-rna levels, Infectious Diseases, HCV-RNA, 030211 gastroenterology & hepatology, Sequence Analysis, medicine.drug, Human, Microbiology (medical), medicine.medical_specialty, Hepatitis C virus, Concordance, Settore MED/12 - GASTROENTEROLOGIA, Pharmacology, Biology, 03 medical and health sciences, Boceprevir, Internal medicine, medicine, hcv, Genotyping, Hepaciviru, Viral Nonstructural Protein, Settore MED/09 - MEDICINA INTERNA, Virology, digestive system diseases, 030104 developmental biology, chemistry, Sequence Analysi, RNA, Genotyping Technique
Abstract: OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.
Published: 2016
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6. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Author: Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio Maria, Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxì, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini Silberstein, Francesca, Mariani, R., Iapadre, N., Grimaldi, A., Cozzolongo, R., Andreone, P., Verucchi, G., Menzaghi, B., Quirino, T., Pisani, V., Torti, MARIA CHIARA, Vecchiet, J., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L. A., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, Miriam, Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Magni, C. F., Mancon, A., Monico, S., Niero, F., Russo, M. L., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Brancaccio, G., Gaeta, G. B., Lembo, V., Sangiovanni, V., Di Marco, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Aragri, M., Baiocchi, L., Barbaliscia, S., Biliotti, Elisa, Biolato, M., Carioti, L., Ceccherini Silberstein, F., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Maio, V. C., Di Paolo, D., Furlan, Caterina, Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lenci, I., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, Donatella, Pellicelli, A., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M. C., Spaziante, M., Svicher, V., Tisone, G., Vespasiani Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M. S., Falconi, L., Di Giammartino, D., Di Maio, V., Cento, V., Lenci, I., Aragri, M., Rossi, P., Barbaliscia, S., Melis, M., Verucchi, G., Magni, C., Teti, E., Bertoli, A., Antonucci, F., Bellocchi, M., Micheli, V., Masetti, C., Landonio, S., Francioso, S., Santopaolo, F., Pellicelli, A., Calvaruso, V., Gianserra, L., Siciliano, M., Romagnoli, D., Cozzolongo, R., Grieco, A., Vecchiet, J., Morisco, F., Merli, M., Brancaccio, G., Di Biagio, A., Loggi, E., Mastroianni, C., Pace Palitti, V., Tarquini, P., Puoti, M., Taliani, G., Sarmati, L., Picciotto, A., Vullo, V., Caporaso, N., Paoloni, M., Pasquazzi, C., Rizzardini, G., Parruti, G., Craxã¬, A., Babudieri, S., Andreoni, M., Angelico, M., Perno, C., Ceccherini-Silberstein, F., Mariani, R., Iapadre, N., Grimaldi, A., Andreone, P., Menzaghi, B., Quirino, T., Pisani, V., Torti, C., Bruzzone, B., De Maria, A., Marenco, S., Nicolini, L., Viscoli, C., Casinelli, K., Delle Monache, M., Lichtner, M., Aghemo, A., Boccaccio, V., Bruno, S., Cerrone, M., Colombo, M., D'Arminio Monforte, A., Danieli, E., Donato, F., Gubertini, G., Lleo, A., Mancon, A., Monico, S., Niero, F., Russo, M., Gnocchi, M., Orro, A., Milanesi, L., Baldelli, E., Bertolotti, M., Borghi, V., Mussini, C., Gaeta, G., Lembo, V., Sangiovanni, V., DI MARCO, V., Mazzola, A., Petta, S., D'Amico, E., Cacciatore, P., Consorte, A., Pieri, A., Polilli, E., Sozio, F., Antenucci, F., Baiocchi, L., Biliotti, E., Biolato, M., Carioti, L., Cerasari, G., Cerva, C., Ciotti, M., D'Ambrosio, C., D'Ettorre, G., De Leonardis, F., De Sanctis, A., Di Paolo, D., Furlan, C., Gallo, P., Gasbarrini, A., Giannelli, V., Grieco, S., Lambiase, L., Lattanzi, B., Lula, R., Malagnino, V., Manuelli, M., Miglioresi, L., Milana, M., Moretti, A., Nosotti, L., Palazzo, D., Romano, M., Sarrecchia, C., Sforza, D., Sorbo, M., Spaziante, M., Svicher, V., Tisone, G., Vespasiani-Gentilucci, U., D'Adamo, G., Mangia, A., Maida, I., Mura, M., Falconi, L., Di Giammartino, D., Di Maio, V, Cento, V, Lenci, I, Aragri, M, Rossi, P, Barbaliscia, S, Melis, M, Verucchi, G, Magni, C, Teti, E, Bertoli, A, Antonucci, F, Bellocchi, M, Micheli, V, Masetti, C, Landonio, S, Francioso, S, Santopaolo, F, Pellicelli, A, Calvaruso, V, Gianserra, L, Siciliano, M, Romagnoli, D, Cozzolongo, R, Grieco, A, Morisco, F, Merli, M, Brancaccio, G, Di Biagio, A, Loggi, E, Mastroianni, C, Pace Palitti, V, Tarquini, P, Puoti, M, Taliani, G, Sarmati, L, Picciotto, A, Vullo, V, Caporaso, N, Paoloni, M, Pasquazzi, C, Rizzardini, G, Parruti, G, Craxì, A, Babudieri, S, Andreoni, M, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Velia C. Di Maio, Valeria Cento, Ilaria Lenci, Marianna Aragri, Piera Rossi, Silvia Barbaliscia, Michela Meli, Gabriella Verucchi, Carlo F. Magni, Elisabetta Teti, Ada Bertoli, Francesco Paolo Antonucci, Maria C. Bellocchi, Valeria Micheli, Chiara Masetti, Simona Landonio, Simona Francioso, Francesco Santopaolo, Adriano M. Pellicelli, Vincenza Calvaruso, Laura Gianserra, Massimo Siciliano, Dante Romagnoli, Raffaele Cozzolongo, Antonio Grieco, Jacopo Vecchiet, Filomena Morisco, Manuela Merli, Giuseppina Brancaccio, Antonio Di Biagio, Elisabetta Loggi, Claudio M. Mastroianni, Valeria Pace Palitti, Pierluigi Tarquini, Massimo Puoti, Gloria Taliani, Loredana Sarmati, Antonino Picciotto, Vincenzo Vullo, Nicola Caporaso, Maurizio Paoloni, Caterina Pasquazzi, Giuliano Rizzardini, Giustino Parruti, Antonio Craxì, Sergio Babudieri, Massimo Andreoni, Mario Angelico, Carlo F. Perno, Francesca Ceccherini-Silberstein, for the HCV Italian Resistance Network Study Group: [.., P. Andreone, E. Loggi, G. Verucchi, ], Di Maio, Velia C., Cento, Valeria, Lenci, Ilaria, Aragri, Marianna, Rossi, Piera, Barbaliscia, Silvia, Melis, Michela, Verucchi, Gabriella, Magni, Carlo F., Teti, Elisabetta, Bertoli, Ada, Antonucci, Francescopaolo, Bellocchi, Maria C., Micheli, Valeria, Masetti, Chiara, Landonio, Simona, Francioso, Simona, Santopaolo, Francesco, Pellicelli, Adriano M., Calvaruso, Vincenza, Gianserra, Laura, Siciliano, Massimo, Romagnoli, Dante, Cozzolongo, Raffaele, Grieco, Antonio, Vecchiet, Jacopo, Morisco, Filomena, Merli, Manuela, Brancaccio, Giuseppina, Di Biagio, Antonio, Loggi, Elisabetta, Mastroianni, Claudio M., Pace Palitti, Valeria, Tarquini, Pierluigi, Puoti, Massimo, Taliani, Gloria, Sarmati, Loredana, Picciotto, Antonino, Vullo, Vincenzo, Caporaso, Nicola, Paoloni, Maurizio, Pasquazzi, Caterina, Rizzardini, Giuliano, Parruti, Giustino, Craxã¬, Antonio, Babudieri, Sergio, Andreoni, Massimo, Angelico, Mario, Perno, Carlo F., Ceccherini-Silberstein, Francesca, Nicolini, L. A., Magni, C. F., Russo, M. L., Gaeta, G. B., Di Marco, V., Di Maio, V. C., Sorbo, M. C., Mura, M. S., Di Maio, Velia C, Magni, Carlo F, Bellocchi, Maria C, Pellicelli, Adriano M, Mastroianni, Claudio M, Craxì, Antonio, Perno, Carlo F, and Ceccherini Silberstein, Francesca
Subjects: Male, 0301 basic medicine, hepatitis C virus, Sustained Virologic Response, Sofosbuvir, Hepacivirus, Drug Resistance, resistance-associated substitutions, Viral Nonstructural Proteins, VARIANTS, NS5A, medicine.disease_cause, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, INFECTION, antiviral therapy, Medicine, hepatitis C viru, Viral, Treatment Failure, Chronic, direct-acting antivirals, resistance test, hepatology, biology, GENOTYPE 1, virus diseases, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Hepatitis C, Italy, Combination, Interferon, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Author Keywords:antiviral therapy, RIBAVIRIN, Sequence Analysis, Human, medicine.drug, medicine.medical_specialty, Daclatasvir, Genotype, Hepatitis C virus, Antiviral Agents, LONG-TERM PERSISTENCE, DACLATASVIR, 03 medical and health sciences, Drug Therapy, Aged, Drug Resistance, Viral, Hepatitis C, Chronic, Humans, Interferons, Mutation, Ribavirin, Sequence Analysis, DNA, Hepatology, TREATMENT-NAIVE, Internal medicine, Antiviral Agent, resistance-associated substitution, direct-acting antiviral, Hepaciviru, resistance test KeyWords Plus:HEPATITIS-C VIRUS, business.industry, Viral Nonstructural Protein, DNA, biology.organism_classification, Clinical trial, 030104 developmental biology, SOFOSBUVIR, chemistry, Sequence Analysi, Immunology, business
Abstract: Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring.
Published: 2017
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7. Decaffeinated coffee consumption induces expression of tight junction proteins in high fat diet fed rats

Author: Mazzone G, Lembo V, D’Argenio G, Vitaglione P, Rossi A, Guarino M, Caporaso N, and Morisco F
Subjects: lcsh:R5-920, Occludin, rat model, coffee, HFD, TLR-4, lcsh:TX341-641, Zonulin-1, lcsh:Medicine (General), lcsh:Nutrition. Foods and food supply
Abstract: Background: Recent evidence indicates that gut microbiota plays a key role in the development of NAFLD through the gut-liver axis. An altered gut permeability induced by alterations of tight junction (TJ) proteins allows the passage of bacteria and substances leading to liver inflammation, hepatocyte damage and fibrosis. This study aims to evaluate the influence of decaffeinated coffee on gut permeability in a rat model of fat liver damage induced by a high fat diet (HFD). Methods: Twelve male Wistar rats were assigned to 3 groups. The first group received HFD for 5 months and drank water. The second group received HFD for 5 months and drank water added with 1.2mL decaffeinated coffee/day starting from the 4th month. The third group received standard diet (SD) and drank water. Protein and mRNA expression levels of Toll-Like Receptor- 4 (TLR-4), Occludin and Zonula occludens-1 (ZO-1) were assessed in rat intestines. Results: A significant reduction of Occludin and ZO-1 was observed in HFD fed rats (0.97±0.05 vs 0.15±0.08 p˂0.01, and 0.97±0.05 vs 0.57±0.14 p˂0.001 respectively. This reduction was reverted in HFD+COFFEE rats (0.15±0.08 vs 0.83±0.27 p˂0.01 and 0.57±0.14 vs 0.85±0.12 p˂0.01 respectively). The TLR-4 expression up-regulated by HFD was partially reduced by coffee administration. Conclusions: HFD impairs the intestinal TJ barrier integrity. Coffee increases the expression of TJ proteins, reverting the altered gut permeability and reducing TLR-4 expression.
Published: 2016

8. HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels

Author: Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., Tarquini P., Di Maio, V, Cento, V, Di Paolo, D, Aragri, M, De Leonardis, F, Tontodonati, M, Micheli, V, Bellocchi, M, Antonucci, F, Bertoli, A, Lenci, I, Milana, M, Gianserra, L, Melis, M, Di Biagio, A, Sarrecchia, C, Sarmati, L, Landonio, S, Francioso, S, Lambiase, L, Nicolini, L, Marenco, S, Nosotti, L, Giannelli, V, Siciliano, M, Romagnoli, D, Pellicelli, A, Vecchiet, J, Magni, C, Babudieri, S, Mura, M, Taliani, G, Mastroianni, C, Vespasiani-Gentilucci, U, Romano, M, Morisco, F, Gasbarrini, A, Vullo, V, Bruno, S, Baiguera, C, Pasquazzi, C, Tisone, G, Picciotto, A, Andreoni, M, Parruti, G, Rizzardini, G, Angelico, M, Perno, C, Ceccherini-Silberstein, F, Mariani, R, Paoloni, M, Iapadre, N, Grimaldi, A, Menzaghi, B, Quirino, T, Bruzzone, B, De Maria, A, Viscoli, C, Casinelli, K, Delle Monache, M, Lichtner, M, Aghemo, A, Cerrone, M, Colombo, M, D'Arminio Monforte, A, Danieli, E, Donato, F, Gubertini, G, Mancon, A, Monico, S, Niero, F, Puoti, M, Russo, M, Alfieri, R, Gnocchi, M, Orro, A, Milanesi, L, Baldelli, E, Bertolotti, M, Borghi, V, Mussini, C, Brancaccio, G, Caporaso, N, Gaeta, G, Lembo, V, Calvaruso, V, Craxi, A, Di Marco, V, Mazzola, A, Petta, S, D'Amico, E, Cacciatore, P, Consorte, A, Pace Palitti, V, Pieri, A, Polilli, E, Antenucci, F, Armenia, D, Baiocchi, L, Biliotti, E, Biolato, M, Carioti, L, Cerasari, G, Cerva, C, Ciotti, M, D'Ambrosio, C, D'Ettorre, G, De Sanctis, A, Furlan, C, Gallo, P, Grieco, A, Grieco, S, Lattanzi, B, Malagnino, V, Manuelli, M, Merli, M, Miglioresi, L, Palazzo, D, Santopaolo, F, Santoro, M, Sforza, D, Sorbo, M, Spaziante, M, Svicher, V, Teti, E, Mangia, A, Maida, I, Falconi, L, Di Giammartino, D, Tarquini, P, Di Maio V. C., Cento V., Di Paolo D., Aragri M., De Leonardis F., Tontodonati M., Micheli V., Bellocchi M. C., Antonucci F. P., Bertoli A., Lenci I., Milana M., Gianserra L., Melis M., Di Biagio A., Sarrecchia C., Sarmati L., Landonio S., Francioso S., Lambiase L., Nicolini L. A., Marenco S., Nosotti L., Giannelli V., Siciliano M., Romagnoli D., Pellicelli A., Vecchiet J., Magni C. F., Babudieri S., Mura M. S., Taliani G., Mastroianni C., Vespasiani-Gentilucci U., Romano M., Morisco F., Gasbarrini A., Vullo V., Bruno S., Baiguera C., Pasquazzi C., Tisone G., Picciotto A., Andreoni M., Parruti G., Rizzardini G., Angelico M., Perno C. F., Ceccherini-Silberstein F., Mariani R., Paoloni M., Iapadre N., Grimaldi A., Menzaghi B., Quirino T., Bruzzone B., De Maria A., Viscoli C., Casinelli K., Delle Monache M., Lichtner M., Aghemo A., Cerrone M., Colombo M., D'Arminio Monforte A., Danieli E., Donato F., Gubertini G., Mancon A., Monico S., Niero F., Puoti M., Russo M. L., Alfieri R., Gnocchi M., Orro A., Milanesi L., Baldelli E., Bertolotti M., Borghi V., Mussini C., Brancaccio G., Caporaso N., Gaeta G. B., Lembo V., Calvaruso V., Craxi A., Di Marco V., Mazzola A., Petta S., D'Amico E., Cacciatore P., Consorte A., Pace Palitti V., Pieri A., Polilli E., Antenucci F., Armenia D., Baiocchi L., Biliotti E., Biolato M., Carioti L., Cerasari G., Cerva C., Ciotti M., D'Ambrosio C., D'Ettorre G., De Sanctis A., Furlan C., Gallo P., Grieco A., Grieco S., Lattanzi B., Malagnino V., Manuelli M., Merli M., Miglioresi L., Palazzo D., Santopaolo F., Santoro M. M., Sforza D., Sorbo M. C., Spaziante M., Svicher V., Teti E., Mangia A., Maida I., Falconi L., Di Giammartino D., and Tarquini P.
Abstract: Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable
Published: 2016

9. Spectral Decomposition and Extremes of Atmospheric Meridional Energy Transport in the Northern Hemisphere Midlatitudes

Author: Lembo, V., primary, Messori, G., additional, Graversen, R., additional, and Lucarini, V., additional
Published: 2019
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10. Does the gut play a pivotal role in the protective effect of coffee on liver damage?

Author: Mazzone, G., primary, Rossi, A., additional, Vitaglione, P., additional, Lembo, V., additional, D’argenio, G., additional, Maria, G., additional, Savoia, M., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2018
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11. P.09.21 BENEFICIAL EFFECTS OF BERBERIS ARISTATA, ELAEIS GUINEENSIS AND COFFEA CANEPHORA EXTRACTS ON INSULIN RESISTANCE AND HEPATIC STEATOSIS INDUCED BY HIGH-FAT DIET IN MICE

Author: Lembo, V., primary, Nigro, C., additional, Mazzone, G., additional, Rossi, A., additional, D'Argenio, G., additional, Cossiga, V., additional, Miele, C., additional, Beguinot, F., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2018
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12. P.09.13 BERBERIS ARISTATA, ELAEIS GUINEENSIS AND COFFEA CANEPHORA EXTRACTS IMPROVES HEPATIC STEATOSIS THROUGH THE MODULATION OF MICRORNA-122 IN AN ANIMAL MODEL OF NAFLD

Author: Lembo, V., primary, Mirra, P., additional, Mazzone, G., additional, Rossi, A., additional, D'Argenio, G., additional, Cossiga, V., additional, Nigro, C., additional, Miele, C., additional, Beguinot, F., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2018
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13. P.09.20 IS THE GUT THE FIRST PLAYER IN THE PROTECTIVE EFFECT OF COFFEE ON LIVER DAMAGE

Author: Mazzone, G., primary, Vitaglione, P., additional, Lembo, V., additional, D'Argenio, G., additional, Rossi, A., additional, Guido, M., additional, Savoia, M., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2018
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14. Berberis aristata , Elaeis guineensis and Coffea canephora extracts modulates the microRNA-122 expression and improves hepatic steatosis in mice fed high fat diet

Author: Lembo, V., primary, Mirra, P., additional, Mazzone, G., additional, Rossi, A., additional, D’Argenio, G., additional, Cossiga, V., additional, Nigro, C., additional, Miele, C., additional, Beguinot, F., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2018
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15. Analysis of breath by proton transfer reaction time of flight mass spectrometry in rats with steatohepatitis induced by high-fat diet

Author: Aprea, E., Morisco, F., Biasioli, F., Vitaglione, P., Cappellin, L., Soukoulis, C., Lembo, V., Gasperi, F., D'Argenio, G., Fogliano, V., Caporaso, N., Aprea, E., Morisco, Filomena, Biasioli, F., Vitaglione, Paola, Cappellin, L., Soukoulis, C., Lembo, V., Gasperi, F., D'Argenio, G., Fogliano, Vincenzo, and Caporaso, Nicola
Subjects: Settore CHIM/01 - CHIMICA ANALITICA, volatile organic compounds, NAFLD, Direct injection mass spectrometry, Breath analysis, Diet, Volatile organic compounds, direct injection mass spectrometry, breath analysis, diet
Abstract: Breath testing has been largely used as a diagnostic tool, but the difficulties in data interpretation and sample collection have limited its application. We developed a fast (< 20 s), on-line, non-invasive method for the collection and analysis of exhaled breath in awake rats based on proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS) and applied it to investigate possible relationships between pathologies induced by dietary regime and breath composition. As a case study, we investigated rats with dietary induced non-alcoholic steatohepatitis (NASH) and modifications induced by coffee addition to the diet. We considered two different diets (standard and high fat) complemented with two different drinking possibilities (water or decaffeinated coffee) for a total of four groups with four rats each. Several spectrometric peaks were reliable markers for both dietary fat content and coffee supplementation. The high resolution and accuracy of PTR-ToF-MS allowed the identification of related compounds such as methanol, dimethyl sulphide, dimethyl sulphone and ammonia. In conclusion, the rapid and minimally invasive breath analysis of awake rats permitted the identification of markers related to diet and specific pathologic conditions and provided a useful tool for broader metabolic investigations.
Published: 2012

16. RAT LIVER FIBROSIS IS IMPROVED BY GARLIC EXTRACT VIA TGF-BETA AND TISSUE TRANSGLUTAMINASE INACTIVATION

Author: Mazzone, G., Ribecco, M. T., Morisco, F., Vitaglione, P., Lembo, V., Mapolitano, M., vincenzo fogliano, Caporaso, N., D Argenio, G., Angelico M, Mazzone, G, Ribecco, Mt, Morisco, Filomena, Vitaglione, Paola, Lembo, V, Napolitano, M, Fogliano, Vincenzo, Caporaso, Nicola, and D'Argenio, G.
Published: 2011

17. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota

Author: Piazzi, G., D'Argenio, G., Prossomariti, A., Lembo, V., Mazzone, G., Candela, M., Biagi, E., Brigidi, P., Vitaglione, P., Fogliano, V., and D'Angelo and others, L.
Subjects: intestinal microbiota, mice, inflammatory-bowel-disease, mouse model, differentiation, docosahexaenoic acid, Food Quality and Design, cells, chemoprevention, lipids (amino acids, peptides, and proteins), sodium, health care economics and organizations, VLAG, dietary fish-oil
Abstract: Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ¿-3 polyunsaturated fatty acids (¿-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM-DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear ß-catenin expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to increased membrane switch from ¿-6 to ¿-3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we found that EPA-FFA treatment restored the loss of Notch signaling found in the AOM-DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent candidate for CRC chemoprevention in CAC.
Published: 2014

18. Coffee and Intestinal Permeability in a Mice Model of Non-Alcoholic Fatty Liver Disease

Author: Mazzone, G., primary, Lembo, V., additional, D’Argenio, G., additional, Vitaglione, P., additional, Rossi, A., additional, Piscosquito, I., additional, Savoia, M., additional, Guido, M., additional, Morisco, F., additional, and Caporaso, N., additional
Published: 2016
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19. SAT-007 - Does the gut play a pivotal role in the protective effect of coffee on liver damage?

Author: Mazzone, G., Rossi, A., Vitaglione, P., Lembo, V., D’argenio, G., Maria, G., Savoia, M., Caporaso, N., and Morisco, F.
Published: 2018
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20. Rapid 'breath-print' of liver cirrhosis by Proton Transfer Reaction Time of Flight Mass Spectrometry

Author: Lembo, V., Aprea, Eugenio, Fogliano, V., Vitaglione, P., Mazzone, G., Cappellin, Luca, Gasperi, Flavia, Biasioli, Franco, Morisco, F., and Caporaso, N.
Subjects: Breath-print, Liver cirrhosis, Proton Transfer Reaction Time of Flight Mass Spectrometry
Published: 2013

21. ONLINE ANALYSIS OF BREATH BY PROTON TRANSFER REACTION TIME OF FLIGHT MASS SPECTROMETRY IN CIRRHOTIC PATIENTS

Author: Lembo, V., Aprea, E., Fogliano, V., Vitaglione, P., Mazzone, G., Loperto, I., Luca Cappellin, Gasperi, F., Biasioli, F., Morisco, F., Caporaso, N., European Assoc Study Liver (EASL), Lembo, Vincenzo, Aprea, E, Fogliano, Vincenzo, Vitaglione, Paola, Mazzone, G, Loperto, I, Cappellin, L, Gasperi, F, Biasioli, F, Morisco, Filomena, and Caporaso, Nicola
Subjects: Settore CHIM/01 - CHIMICA ANALITICA, Liver cirrhosis, Breath analysis, Proton Transfer Reaction Time of Flight Mass Spectrometry
Published: 2013

22. Proton Transfer Reaction Time of Flight Mass Spectrometry (PTR-ToF-MS) for in vivo breath analysis of rats under different diet conditions

Author: Eugenio Aprea, Franco Biasioli, Luca Cappellin, Soukoulis, C., Flavia Gasperi, Morisco, F., D Argenio, G., Lembo, V., Fogliano, V., Caporaso, N., E., Aprea, F., Biasioli, L., Cappellin, C., Soukouli, F., Gasperi, Morisco, Filomena, G., D'Argenio, V., Lembo, V., Fogliano, and Caporaso, Nicola
Subjects: Proton transfer reaction-mass spectrometry, Breath analysis, Analisi del respiro, Dieta, Diet
Published: 2011

23. Daily supplementation of cholecalciferol prevents liver steatosis and diabetes by improving insulin sensitivity in an animal model of NAFLD

Author: Mazzone, G., primary, Lembo, V., additional, D’Armiento, M., additional, D’Argenio, G., additional, Morisco, F., additional, and Caporaso, N., additional
Published: 2015
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24. OC.10.1 EICOSAPENTAENOIC ACID-FREE FATTY ACID PREVENTS AND SUPPRESSES COLONIC TUMOURS IN COLITIS-ASSOCIATED COLORECTAL CANCER

Author: Piazzi, G., primary, D'Argenio, G., additional, Prossomariti, A., additional, Lembo, V., additional, Mazzone, G., additional, Candela, M., additional, Biagi, E., additional, Brigidi, P., additional, Vitaglione, P., additional, Fogliano, V., additional, D'Angelo, L., additional, Fazio, C., additional, Munarini, A., additional, Belluzzi, A., additional, Ceccarelli, C., additional, Chieco, P., additional, Balbi, T., additional, Loadman, P.M., additional, Hull, M.A., additional, Romano, M., additional, Bazzoli, F., additional, and Ricciardiello, L., additional
Published: 2014
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25. P.02.12 HIGH FAT DIET AND GUT PERMEABILITY: THE ROLE OF DECAFFEINATED COFFEE

Author: Mazzone, G., primary, Lembo, V., additional, D'Argenio, G., additional, Vitaglione, P., additional, Cossiga, V., additional, Guarino, M., additional, Clery, E., additional, Vitiello, A., additional, Loperto, I., additional, Ferraiuoli, C., additional, Fogliano, V., additional, Caporaso, N., additional, and Morisco, F., additional
Published: 2014
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26. SAT-342 - Coffee and Intestinal Permeability in a Mice Model of Non-Alcoholic Fatty Liver Disease

Author: Mazzone, G., Lembo, V., D’Argenio, G., Vitaglione, P., Rossi, A., Piscosquito, I., Savoia, M., Guido, M., Morisco, F., and Caporaso, N.
Published: 2016
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27. 209 ONLINE ANALYSIS OF BREATH BY PROTON TRANSFER REACTION TIME OF FLIGHT MASS SPECTROMETRY IN CIRRHOTIC PATIENTS

Author: Lembo, V., primary, Aprea, E., additional, Fogliano, V., additional, Vitaglione, P., additional, Mazzone, G., additional, Loperto, I., additional, Cappellin, L., additional, Gasperi, F., additional, Biasioli, F., additional, Morisco, F., additional, and Caporaso, N., additional
Published: 2013
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28. P.11.11 RAPID “BREATH-PRINT” OF LIVER CIRRHOSIS BY PROTON TRANSFER REACTION TIME OF FLIGHT MASS SPECTROMETRY

Author: Lembo, V., primary, Aprea, E., additional, Fogliano, V., additional, Vitaglione, P., additional, Mazzone, G., additional, Cappellin, L., additional, Gasperi, F., additional, Biasioli, F., additional, Morisco, F., additional, and Caporaso, N., additional
Published: 2013
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29. P.1.127: RAT LIVER FIBROSIS IS IMPROVED BY GARLIC EXTRACT VIA TGF-BETA AND TISSUE TRANSGLUTAMINASE INACTIVATION

Author: Mazzone, G., primary, Ribecco, M.T., additional, Morisco, F., additional, Vitaglione, P., additional, Lembo, V., additional, Mapolitano, M., additional, Fogliano, V., additional, Caporaso, N., additional, and D'Argenio, G., additional
Published: 2011
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30. F-25 Garlic extract reduces rat liver fibrosis and collagen content via TGFβ and tissue transglutaminase inactivation

Author: Morisco, F., primary, D'Argenio, G., additional, Mazzone, G., additional, Ribecco, M.T., additional, Vitaglione, P., additional, Lembo, V., additional, Napolitano, M., additional, Fogliano, V., additional, and Caporaso, N., additional
Published: 2011
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31. Breath analysis on animal models and humans as a non invasive tool for studying liver diseases and their interaction with diet

Author: Eugenio Aprea, Morisco, F., Vitaglione, P., Luca Cappellin, Lembo, V., Flavia Gasperi, D’argenio, G., Fogliano, V., Caporaso, N., and Franco Biasioli
Subjects: Settore CHIM/01 - CHIMICA ANALITICA, Liver disease, PTR-ToF-MS, Breath analysis, Animal models, Non-alcoholic steatohepatitis

32. PTR‐ToF‐MS for breath analysis on animal and humans as a noninvasive tool to monitor diseases and diet interactions

Author: Eugenio Aprea, Morisco, F., Vitaglione, P., Luca Cappellin, Lembo, V., Flavia Gasperi, D’argenio, G., Fogliano, V., Caporaso, N., and Franco Biasioli
Subjects: Settore CHIM/01 - CHIMICA ANALITICA

33. Garlic extract reduces rat liver fibrosis and collagen content via TGF beta and tissue transglutaminase inactivation

Author: Morisco, F., D Argenio, G., Mazzone, G., Ribecco, M. T., Paola Vitaglione, Lembo, V., Napolitano, M., Fogliano, V., and Caporaso, N.

34. Breath analysis by Proton Transfer Reaction - Time of Flight - Mass Spectrometry for liver disease diagnostic

Author: Eugenio Aprea, Morisco, F., Vitaglione, P., Luca Cappellin, Lembo, V., Flavia Gasperi, D Argenio, G., Fogliano, V., Caporaso, N., and Franco Biasioli

35. Detection of Deletion and Insertion of Tones in Bandlimited Noise

Author: Bourbon, W. T., primary and Lembo, V. L., additional
Published: 1973
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36. Earth System Model Evaluation Tool (ESMValTool) v2.0 - An extended set of large-scale diagnostics for quasi-operational and comprehensive evaluation of Earth system models in CMIP

Author: Eyring, Veronika, Bock, Lisa, Lauer, Axel, Righi, Mattia, Schlund, Manuel, Andela, Bouwe, Arnone, Enrico, Bellprat, Omar, Carvalhais, Nuno, Cionni, Irene, Cortesi, Nicola, Crezee, Bas, L. Davin, Edouard, Davini, Paolo, Debeire, Kevin, De Mora, Lee, Deser, Clara, Docquier, David, Earnshaw, Paul, Ehbrecht, Carsten, K. Gier, Bettina, Gonzalez-Reviriego, Nube, Goodman, Paul, Hagemann, Stefan, Hardiman, Steven, Hassler, Birgit, Hunter, Alasdair, Kadow, Christopher, Kindermann, Stephan, Koirala, Sujan, Koldunov, Nikolay, Lejeune, Quentin, Lembo, Valerio, Lovato, Tomas, Lucarini, Valerio, Müller, Benjamin, Pandde, Amarjiit, Phillips, Adam, Predoi, Valeriu, Russell, Joellen, Sellar, Alistair, Serva, Federico, Stacke, Tobias, Swaminathan, Ranjini, Vegas-Regidor, Javier, Von Hardenberg, Jost, Weigel, Katja, Zimmermann, Klaus, DCEA - Departamento de Ciências e Engenharia do Ambiente, Eyring, V., Bock, L., Lauer, A., Righi, M., Schlund, M., Andela, B., Arnone, E., Bellprat, O., Carvalhais, N., Cionni, I., Cortesi, N., Crezee, B., L. Davin, E., Davini, P., Debeire, K., De Mora, L., Deser, C., Docquier, D., Earnshaw, P., Ehbrecht, C., K. Gier, B., Gonzalez-Reviriego, N., Goodman, P., Hagemann, S., Hardiman, S., Hassler, B., Hunter, A., Kadow, C., Kindermann, S., Koirala, S., Koldunov, N., Lejeune, Q., Lembo, V., Lovato, T., Lucarini, V., Muller, B., Pandde, A., Phillips, A., Predoi, V., Russell, J., Sellar, A., Serva, F., Stacke, T., Swaminathan, R., Vegas-Regidor, J., Von Hardenberg, J., Weigel, K., and Zimmermann, K.
Subjects: COUPLED MODEL, LAND-COVER CHANGES, INTERNAL VARIABILITY, Earth and Planetary Sciences(all), VERSION 2, NORTH-ATLANTIC, PART I, Modelling and Simulation, GLOBAL CLIMATE MODEL, VEGETATION COVER, SDG 13 - Climate Action, MIDLATITUDE ATMOSPHERIC VARIABILITY, WEATHER REGIMES, SDG 15 - Life on Land
Abstract: 824084 grant no. 274762653 grant no. CMIP6-DICAD The Earth System Model Evaluation Tool (ESMValTool) is a community diagnostics and performance metrics tool designed to improve comprehensive and routine evaluation of Earth system models (ESMs) participating in the Coupled Model Intercomparison Project (CMIP). It has undergone rapid development since the first release in 2016 and is now a well-tested tool that provides end-to-end provenance tracking to ensure reproducibility. It consists of (1) an easy-to-install, well-documented Python package providing the core functionalities (ESMValCore) that performs common preprocessing operations and (2) a diagnostic part that includes tailored diagnostics and performance metrics for specific scientific applications. Here we describe large-scale diagnostics of the second major release of the tool that supports the evaluation of ESMs participating in CMIP Phase 6 (CMIP6). ESMValTool v2.0 includes a large collection of diagnostics and performance metrics for atmospheric, oceanic, and terrestrial variables for the mean state, trends, and variability. ESMValTool v2.0 also successfully reproduces figures from the evaluation and projections chapters of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and incorporates updates from targeted analysis packages, such as the NCAR Climate Variability Diagnostics Package for the evaluation of modes of variability, the Thermodynamic Diagnostic Tool (TheDiaTo) to evaluate the energetics of the climate system, as well as parts of AutoAssess that contains a mix of top-down performance metrics. The tool has been fully integrated into the Earth System Grid Federation (ESGF) infrastructure at the Deutsches Klimarechenzentrum (DKRZ) to provide evaluation results from CMIP6 model simulations shortly after the output is published to the CMIP archive. A result browser has been implemented that enables advanced monitoring of the evaluation results by a broad user community at much faster timescales than what was possible in CMIP5. publishersversion published
Published: 2020
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37. The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Author: G. Mazzone, Claudia Miele, Iolanda Veneruso, Nicola Caporaso, Paola Mirra, Valentina Cossiga, Filomena Morisco, Vincenzo Lembo, Valeria D'Argenio, Alessia Leone, Francesco Beguinot, Cecilia Nigro, Maria Guido, Cossiga, V., Lembo, V., Nigro, C., Mirra, P., Miele, C., D'Argenio, V., Leone, A., Mazzone, G., Veneruso, I., Guido, M., Beguinot, F., Caporaso, N., and Morisco, F.
Subjects: Male, 0301 basic medicine, Berberis, Berberine, gut microbiome, Coffea, Arecaceae, Gut flora, Mice, Liver disease, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, MiR-122, Nutrition and Dietetics, biology, Tocotrienols, digestive, oral, and skin physiology, food and beverages, miR-122, Liver, 030220 oncology & carcinogenesis, lipids (amino acids, peptides, and proteins), miR-34a, medicine.medical_specialty, Berberis aristata, Diet, High-Fat, Article, metabolic syndrome, 03 medical and health sciences, Insulin resistance, NAFLD, Internal medicine, medicine, MiR‐122, Animals, Humans, Plant Extracts, Gut microbiome, Metabolic syndrome, MiR‐34a, nutritional and metabolic diseases, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Disease Models, Animal, MicroRNAs, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Dysbiosis, Insulin Resistance, Steatosis, Food Science
Abstract: Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p &lt, 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p &lt, 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.
Published: 2021
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38. Antifibrotic Effect of Marine Ovothiol in an In Vivo Model of Liver Fibrosis

Author: Immacolata Castellano, Anna Palumbo, Vincenzo Lembo, Mariarita Brancaccio, Giuseppe D’Argenio, Brancaccio, M., D'Argenio, G., Lembo, V., Palumbo, A., and Castellano, I.
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Aging, Article Subject, Liver Cirrhosi, CCL4, Matrix metalloproteinase, Pharmacology, Biochemistry, Extracellular matrix, 03 medical and health sciences, Ovothiol A, chemistry.chemical_compound, Mice, 0302 clinical medicine, In vivo, Animals, Humans, lcsh:QH573-671, lcsh:Cytology, Animal, Cell Biology, General Medicine, Methylhistidines, 3. Good health, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Carbon tetrachloride, Methylhistidine, Homeostasis, Transforming growth factor, Human, Research Article
Abstract: Liver fibrosis is a complex process caused by chronic hepatic injury, which leads to an excessive increase in extracellular matrix protein accumulation and fibrogenesis. Several natural products, including sulfur-containing compounds, have been investigated for their antifibrotic effects; however, the molecular mechanisms underpinning their action are partially still obscure. In this study, we have investigated for the first time the effect of ovothiol A, π-methyl-5-thiohistidine, isolated from sea urchin eggs on an in vivo murine model of liver fibrosis. Mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce liver fibrosis and treated with ovothiol A at the dose of 50 mg/kg 3 times a week for 2 months. Treatment with ovothiol A caused a significant reduction of collagen fibers as observed by histopathological changes and serum parameters compared to mice treated with control solution. This antifibrotic effect was associated to the decrease of fibrogenic markers involved in liver fibrosis progression, such as the transforming growth factor (TGF-β), the α-smooth muscle actin (α-SMA), and the tissue metalloproteinases inhibitor (TIMP-1). Finally, we provided evidence that the attenuation of liver fibrosis by ovothiol A treatment can be regulated by the expression and activity of the membrane-bound γ-glutamyl-transpeptidase (GGT), which is a key player in maintaining intracellular redox homoeostasis. Overall, these findings indicate that ovothiol A has significant antifibrotic properties and can be considered as a new marine drug or dietary supplement in potential therapeutic strategies for the treatment of liver fibrosis.
Published: 2018

39. Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut-liver axis

Author: G. Mazzone, Antonella Rossi, Nicola Caporaso, Giuseppe D'Argenio, Danilo Ercolini, Paola Vitaglione, Vincenzo Lembo, Marcella Savoia, Ilario Mennella, Federico Salomone, Filomena Morisco, Francesca De Filippis, Maria Guido, Vitaglione, P., Mazzone, G., Lembo, V., D'Argenio, G., Rossi, A., Guido, M., Savoia, M., Salomone, F., Mennella, I., De Filippis, F., Ercolini, D., Caporaso, N., and Morisco, F.
Subjects: Male, ALT, Endocrinology, Diabetes and Metabolism, ABCA1, Feces, Mice, 0302 clinical medicine, ATP-binding cassette subfamily G1, LXR-α, liver X receptor-α, Non-alcoholic steatohepatitis, chemistry.chemical_classification, digestive, oral, and skin physiology, HFD plus decaffeinated coffee, FFAR, free fatty acid receptor, high-fat diet, Cholesterol, standard diet, Free fatty acid receptor, free fatty acid receptor, 030211 gastroenterology & hepatology, zonulin-1, ACOX1, medicine.medical_specialty, ABCA1, ATP-binding cassette subfamily A1, Gut microbiota, Diet, High-Fat, 03 medical and health sciences, NAFLD, ATP-binding cassette subfamily A1, PPAR alpha, RNA, Messenger, Protein Precursors, Gut permeability, SD, ZO-1, zonulin-1, Fatty acid, nutritional and metabolic diseases, Polyphenols, ABCG1, ATP-binding cassette subfamily G1, ACOX1, acyl-CoA oxidase 1, ALT, alanine aminotransferase, HFD+COFFEE, HFD plus decaffeinated coffee, HFD, high-fat diet, Metabolic syndrome, NAFLD, non-alcoholic fatty liver disease, PYY, peptide YY, SD, standard diet, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Peptide YY, Claudins, HFD, Acyl-CoA Oxidase, Non-alcoholic steatohepatiti, 0301 basic medicine, Blood Glucose, LXR-α, Gut flora, Coffee, chemistry.chemical_compound, Non-alcoholic Fatty Liver Disease, peptide YY, ZO-1, ATP Binding Cassette Transporter, Subfamily G, Member 1, Metabolic Syndrome, Nutrition and Dietetics, biology, Fatty liver, Alanine Transaminase, Intestines, Liver, lipids (amino acids, peptides, and proteins), ATP Binding Cassette Transporter 1, Research Article, ABCG1, alanine aminotransferase, FFAR, liver X receptor-α, Internal medicine, medicine, Animals, acyl-CoA oxidase 1, HFD+COFFEE, PYY, Haptoglobins, business.industry, biology.organism_classification, Gastrointestinal Microbiome, Dietary Supplements, business, Food Science, Alcaligenaceae
Abstract: Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P P P PPAR- α(P P ABCA1) and subfamily G1 (ABCG1) (P P P P Alcaligenaceaein the faeces (P
Published: 2018

40. Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial

Author: Nicola Caporaso, Giuseppina Pontillo, Federica Morando, Maria Guarino, Vincenzo Lembo, Filomena Morisco, Concetta Tuccillo, Andrea Fiorentino, Valentina Cossiga, Cossiga, V., Lembo, V., Guarino, M., Tuccillo, C., Morando, F., Pontillo, G., Fiorentino, A., Caporaso, N., and Morisco, F.
Subjects: Adult, Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Controlled attenuation parameter (CAP), Berberis aristata, Coffea, Hepatic steatosi, Palm Oil, Article, Plant Extract, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Elasticity Imaging Technique, Antigens, CD, Non-alcoholic Fatty Liver Disease, NAFLD, Internal medicine, Diabetes mellitus, medicine, Insulin, Pilot Project, Nutrition and Dietetics, biology, business.industry, hepatic steatosis, Fatty liver, Middle Aged, medicine.disease, biology.organism_classification, Receptor, Insulin, 030104 developmental biology, Endocrinology, Homeostatic model assessment, Female, 030211 gastroenterology & hepatology, Insulin Resistance, Berberi, Steatosis, Transient elastography, business, Insulin receptor, Human, Food Science
Abstract: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p &lt, 0.001), insulin levels (p &lt, 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p &lt, 0.001), and CAP value (p &lt, 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p &lt, 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients.
Published: 2019
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41. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota

Author: PIAZZI, GIULIA, PROSSOMARITI, ANNA, CANDELA, MARCO, BIAGI, ELENA, BRIGIDI, PATRIZIA, D'ANGELO, LEONARDA, FAZIO, CHIARA, BELLUZZI, ANDREA, CECCARELLI, CLAUDIO, CHIECO, PASQUALE, BALBI, TIZIANA, BAZZOLI, FRANCO, RICCIARDIELLO, LUIGI, Giuseppe D'Argenio, Vincenzo Lembo, Giovanna Mazzone, Paola Vitaglione, Vincenzo Fogliano, Alessandra Munarini, Paul M. Loadman, Mark A. Hull, Marco Romano, Piazzi, G, D'Argenio, G, Prossomariti, A, Lembo, V, Mazzone, G, Candela, M, Biagi, E, Brigidi, P, Vitaglione, Paola, Fogliano, Vincenzo, D'Angelo, L, Fazio, C, Munarini, A, Belluzzi, A, Ceccarelli, C, Chieco, P, Balbi, T, Loadman, Pm, Hull, Ma, Romano, M, Bazzoli, F, Ricciardiello, L., Giulia Piazzi, Giuseppe D'Argenio, Anna Prossomariti, Vincenzo Lembo, Giovanna Mazzone, Marco Candela, Elena Biagi, Patrizia Brigidi, Paola Vitaglione, Vincenzo Fogliano, Leonarda D'Angelo, Chiara Fazio, Alessandra Munarini, Andrea Belluzzi, Claudio Ceccarelli, Pasquale Chieco, Tiziana Balbi, Paul M Loadman, Mark A Hull, Marco Romano, Franco Bazzoli, and Luigi Ricciardiello
Subjects: Inflammation, Male, Receptors, Notch, Colon, Reverse Transcriptase Polymerase Chain Reaction, Microbiota, Apoptosis, COLON CANCER, Fatty Acids, Nonesterified, Colitis, Real-Time Polymerase Chain Reaction, Gastrointestinal Tract, Immunoenzyme Techniques, Mice, Inbred C57BL, NOTCH, Mice, Eicosapentaenoic Acid, Animals, lipids (amino acids, peptides, and proteins), OMEGA 3, RNA, Messenger, Colorectal Neoplasms, Cell Proliferation
Abstract: Inflammatory bowel diseases are associated with increased risk of developing colitis-associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM-DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA-FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β-catenin expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to increased membrane switch from ω-6 to ω-3 PUFAs and a concomitant reduction in PGE2 production. We observed no significant changes in intestinal inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we found that EPA-FFA treatment restored the loss of Notch signaling found in the AOM-DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent candidate for CRC chemoprevention in CAC.
Published: 2013

42. Rapid ‘‘Breath-Print’’ of liver cirrhosis by Proton Transfer Reaction Time-of-Flight Mass Spectrometry: a pilot study

Author: Paola Vitaglione, Franco Biasioli, Nicola Caporaso, Giovanni Domenico De Palma, Vincenzo Lembo, Stefania Masone, Vincenzo Fogliano, Eugenio Aprea, Flavia Gasperi, Filomena Morisco, Luca Cappellin, Riccardo Marmo, G. Mazzone, Morisco, Filomena, Aprea, E., Lembo, V., Fogliano, Vincenzo, Vitaglione, Paola, Mazzone, Giovanna, Cappellin, L., Gasperi, F., Masone, S., DE PALMA, G. D., Marmo, R., Caporaso, Nicola, and Biasioli, F.
Subjects: Liver Cirrhosis, Male, Pathology, Settore CHIM/01 - CHIMICA ANALITICA, Cirrhosis, Alcoholic Liver Disease, Nonalcoholic Steatohepatitis, Pilot Projects, Toxicology, Gastroenterology, Mass Spectrometry, Analytical Chemistry, chemistry.chemical_compound, Aged, 80 and over, Multidisciplinary, Liver Diseases, Healthy subjects, Ketones, Middle Aged, Chemistry, Breath Tests, Exhalation, Medicine, Female, Research Article, Biotechnology, Adult, medicine.medical_specialty, Bilirubin, Science, Predictive Toxicology, Gastroenterology and Hepatology, Chemical Analysis, Internal medicine, medicine, Humans, Life Science, Biology, Aged, Receiver operating characteristic, business.industry, Case-control study, Quantitative Analysis, medicine.disease, Alkadienes, chemistry, Breath gas analysis, ROC Curve, Small Molecules, Case-Control Studies, Monoterpenes, Time-of-flight mass spectrometry, Qualitative Analysis, business, Biomarkers
Abstract: UnlabelledThe aim of the present work was to test the potential of Proton Transfer Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) in the diagnosis of liver cirrhosis and the assessment of disease severity by direct analysis of exhaled breath. Twenty-six volunteers have been enrolled in this study: 12 patients (M/F 8/4, mean age 70.5 years, min-max 42-80 years) with liver cirrhosis of different etiologies and at different severity of disease and 14 healthy subjects (M/F 5/9, mean age 52.3 years, min-max 35-77 years). Real time breath analysis was performed on fasting subjects using a buffered end-tidal on-line sampler directly coupled to a PTR-ToF-MS. Twelve volatile organic compounds (VOCs) resulted significantly differently in cirrhotic patients (CP) compared to healthy controls (CTRL): four ketones (2-butanone, 2- or 3- pentanone, C8-ketone, C9-ketone), two terpenes (monoterpene, monoterpene related), four sulphur or nitrogen compounds (sulfoxide-compound, S-compound, NS-compound, N-compound) and two alcohols (heptadienol, methanol). Seven VOCs (2-butanone, C8-ketone, a monoterpene, 2,4-heptadienol and three compounds containing N, S or NS) resulted significantly differently in compensate cirrhotic patients (Child-Pugh A; CP-A) and decompensated cirrhotic subjects (Child-Pugh B+C; CP-B+C). ROC (Receiver Operating Characteristic) analysis was performed considering three contrast groups: CP vs CTRL, CP-A vs CTRL and CP-A vs CP-B+C. In these comparisons monoterpene and N-compound showed the best diagnostic performance.ConclusionsBreath analysis by PTR-ToF-MS was able to distinguish cirrhotic patients from healthy subjects and to discriminate those with well compensated liver disease from those at more advanced severity stage. A breath-print of liver cirrhosis was assessed for the first time.
Published: 2013

43. Garlic extract attenuating rat liver fibrosis by inhibiting TGF-β1

Author: Paola Vitaglione, Nicola Caporaso, Maria Guarino, Vincenzo Lembo, Manuela Napolitano, Giuseppe D'Argenio, G. Mazzone, Maria T. Ribecco, Vincenzo Fogliano, Filomena Morisco, D'Argenio, G, Mazzone, G, Ribecco, Mt, Lembo, V, Vitaglione, Paola, Guarino, M, Morisco, Filomena, Napolitano, M, Fogliano, V, and Caporaso, Nicola
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Pathology, Tissue transglutaminase, Metalloproteinase Inhibitor 1, Semaphorins, Critical Care and Intensive Care Medicine, Transforming Growth Factor beta1, Extracellular matrix, Antigens, CD, Fibrosis, Internal medicine, TGF-β1, medicine, Animals, Rats, Wistar, Garlic, Carbon Tetrachloride, TIMP1, Tissue Inhibitor of Metalloproteinase-1, Transglutaminases, Nutrition and Dietetics, biology, Plant Extracts, business.industry, Alanine Transaminase, Histology, medicine.disease, Transglutaminase, Actins, Rats, Endocrinology, Liver, biology.protein, Liver function, business, Myofibroblast
Abstract: Background & aims: We previously demonstrated the efficacy of garlic extract (GE) in the prevention of rat liver fibrosis by inhibiting tissue transglutaminase (tTG) activity. In the present study we aimed to evaluate the potential of GE in the regression of liver fibrosis and the underlining mechanism. Methods: Male Wistar rats were i.p. injected, twice a week, for 7 weeks, with CCl4 to develop liver fibrosis. Successively, a group was immediately sacrificed, while the remaining two groups received the GE or the vehicle, respectively, over the following 2 wks. A group of normal rats was also included in the study. Liver function, histology, and collagen deposition in parallel with gene and protein expression of α-SMA, tTG, TGF-β1, SEMA-7A, and metalloproteinase inhibitor 1 (TIMP1) as well as measure of active by total TGF-β1 were assessed. Results: CCl4 administration increased alanine-aminotransferase (ALT) activity, hepatic collagen deposition and gene and protein expression of all monitored markers. GE, but not the sole vehicle, restored liver histology and function by decreasing fibrogenesis markers (α-SMA, tTG, TGF-β1, SEMA-7A and TIMP1). Active by total TGF-β1 was significantly reduced (p < 0.05) in GE treated rats compared to the CCl4 at 7 weeks, and vehicle rats. Conclusions: These findings concurrently suggested that GE elicited therapeutic effect against liver fibrosis. Regression of liver fibrosis occurred by reducing myofibroblasts (through modulation of HSCs activation mechanisms), remodelling extracellular matrix (through increase of its degradation) and regenerating liver tissue and functions: three processes regulated by fine mechanisms where active TGF-β1 and tTG play a central role.
Published: 2013

44. Statistical physics and dynamical systems perspectives on geophysical extreme events.

Author: Faranda D, Messori G, Alberti T, Alvarez-Castro C, Caby T, Cavicchia L, Coppola E, Donner RV, Dubrulle B, Galfi VM, Holmberg E, Lembo V, Noyelle R, Yiou P, Spagnolo B, Valenti D, Vaienti S, and Wormell C
Abstract: Statistical physics and dynamical systems theory are key tools to study high-impact geophysical events such as temperature extremes, cyclones, thunderstorms, geomagnetic storms, and many others. Despite the intrinsic differences between these events, they all originate as temporary deviations from the typical trajectories of a geophysical system, resulting in well-organized, coherent structures at characteristic spatial and temporal scales. While statistical extreme value analysis techniques are capable of providing return times and probabilities of occurrence of certain geophysical events, they are not apt to account for their underlying physics. Their focus is to compute the probability of occurrence of events that are large or small with respect to some specific observable (e.g., temperature, precipitation, solar wind), rather than to relate rare or extreme phenomena to the underlying anomalous geophysical regimes. This paper outlines this knowledge gap, presenting some related challenges, new formalisms and briefly commenting on how stochastic approaches tailored to the study of extreme geophysical events can help to advance their understanding.
Published: 2024
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45. Systematic Investigation of Dual-Target-Directed Ligands.

Author: Lembo V and Bottegoni G
Subjects: Ligands, Humans, Polypharmacology, Proteins chemistry, Proteins metabolism, Drug Design
Abstract: Multitarget-directed ligands (MTDLs) are compounds rationally designed to affect multiple targets, aiming for a better therapeutic profile. For over 20 years, MTDLs have garnered increasing attention, the idea being that their full potential would have been achieved, thanks to unprecedented target combinations and advanced medicinal chemistry strategies. This study presents a literature mining effort resulting in a data set of dual-target-directed ligands (DTDLs), the fundamental example of MTDLs. We used this data set to evaluate the rationale behind target selection and the chemical novelty of DTDLs targeting specific protein combinations. Our analysis focused on DTDL targets in terms of biological function, disease association, structure, and chemogenomic traits. We also compared DTDLs with single-target compounds. We found that well-known target pathology associations often guide DTDL design, leveraging existing chemical scaffolds and binding pocket similarities. These findings highlight the current state of the field and suggest substantial untapped potential for rational polypharmacology.
Published: 2024
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46. Hepatitis C Epidemiology: Insights from a Comprehensive Cohort Study in ASST Melegnano and Martesana, Lombardia Region, Northern Italy.

Author: Nardone M, Di Stasio D, Lucchese A, Gentili D, Cattabianchi G, Signorelli C, Sarchi P, Pulcrano G, Lembo V, Pirola PM, Lauritano D, and Carinci F
Abstract: Hepatitis C virus (HCV) infection is a significant public health problem affecting 58 million people worldwide, including 3.9 million in Europe. Many of these infections go undiagnosed because chronic infection is often asymptomatic. This observational cohort study presents a detailed examination of hepatitis C virus epidemiology in Lombardia (Italy) and was conducted within the ASST "Melegnano e della Martesana". The study involved comprehensive HCV screening of 3290 patients accessing the collection points and/or hospitalized in the facilities of the ASST from 20 May 2022 to 13 April 2023. Screening was conducted using serological assays. The prevalence of anti-HCV-positive patients (HCV-Ab) and then HCV-positive patients (RNA) was calculated. Chi-square tests examined the associations between continuous and categorical variables. Logistic regression was used to evaluate the influence of demographic and geographic variables as predictors of HCV positivity. The study revealed an overall HCV-Ab prevalence of 0.912% (CI (0.59-1.24%)) in the examined cohort, of whom 15.15% (two females and three males) were positive for HCV RNA. The prevalence of HCV RNA positivity was 0.152% (CI (0.05-0.35%)). Sex disparity was evident, with male patients exhibiting a higher prevalence compared to females, confirmed by logistic regression (0.0147 vs. 0.0061-OR = 2.44; CI (0.0059-0.0124)). Age stratification indicated an ascending trend in prevalence with age, peaking at 1.35% in individuals aged over 50. These findings underscore the critical need for targeted HCV screening, contributing valuable insights to the global epidemiology of HCV in the era of DAAs.
Published: 2024
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47. Galantamine-memantine hybrids for Alzheimer's disease: The influence of linker rigidity in biological activity and pharmacokinetic properties.

Author: Basagni F, Ortega JA, Bertozzi SM, Armirotti A, Summa M, Bertorelli R, Bartolini M, Mellor IR, Bedeschi M, Bottegoni G, Lembo V, Minarini A, Cavalli A, and Rosini M
Subjects: Humans, Mice, Animals, Memantine pharmacology, Acetylcholinesterase, Cholinesterase Inhibitors pharmacology, Cholinesterase Inhibitors therapeutic use, Receptors, N-Methyl-D-Aspartate, Galantamine pharmacokinetics, Alzheimer Disease drug therapy
Abstract: Neurodegenerative processes characterizing Alzheimer's disease (AD) are strictly related to the impairment of cholinergic and glutamatergic neurotransmitter systems which provoke synaptic loss. These experimental evidences still represent the foundation of the actual standard-of-care treatment for AD, albeit palliative, consisting on the coadministration of an acetylcholinesterase inhibitor and the NMDAR antagonist memantine. In looking for more effective treatments, we previously developed a series of galantamine-memantine hybrids where compound 1 (ARN14140) emerged with the best-balanced action toward the targets of interest paired to neuroprotective efficacy in a murine AD model. Unfortunately, it showed a suboptimal pharmacokinetic profile, which required intracerebroventricular administration for in vivo studies. In this work we designed and synthesized new hybrids with fewer rotatable bonds, which is related to higher brain exposure. Particularly, compound 2, bearing a double bond in the tether, ameliorated the biological profile of compound 1 in invitro studies, increasing cholinesterases inhibitory potencies and selective antagonism toward excitotoxic-related GluN1/2B NMDAR over beneficial GluN1/2A NMDAR. Furthermore, it showed increased plasma stability and comparable microsomal stability in vitro, paired with lower half-life and faster clearance in vivo. Remarkably, pharmacokinetic evaluations of compound 2 showed a promising increase in brain uptake in comparison to compound 1, representing the starting point for further chemical optimizations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Published: 2023
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48. Coffee Restores Expression of lncRNAs Involved in Steatosis and Fibrosis in a Mouse Model of NAFLD.

Author: Di Mauro S, Salomone F, Scamporrino A, Filippello A, Morisco F, Guido M, Lembo V, Cossiga V, Pipitone RM, Grimaudo S, Malaguarnera R, Purrello F, and Piro S
Subjects: Animals, Disease Models, Animal, Liver drug effects, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Coffee metabolism, Fatty Liver metabolism, Gene Expression drug effects, Liver Cirrhosis metabolism, Non-alcoholic Fatty Liver Disease metabolism, RNA, Long Noncoding drug effects
Abstract: Background and Aim: Coffee intake exerts protective effects against non-alcoholic fatty liver disease (NAFLD), although without fully cleared mechanisms. In this study we aimed to assess whether coffee consumption may influence the expression of long non-coding RNAs (lncRNAs) in the liver., Methods: C57BL/6J mice were fed a 12-week standard diet (SD), high-fat diet (HFD) or HFD plus decaffeinated coffee solution (HFD + coffee). Expression of specific lncRNAs involved in NAFLD was analyzed by real-time PCR. For the most differentially expressed lncRNAs, the analysis was also extended to their mRNA targets., Results: Decaffeinated coffee intake reduced body weight gain, prevented NAFLD, lowered hyperglycemia and hypercholesterolemia. NAFLD was associated with lower hepatic expression of Gm16551, a lncRNA inhibiting de novo lipogenesis, and higher expression of H19, a lncRNA promoting fibrogenesis. Coffee intake restored Gm16551 to levels observed in lean mice and downregulated gene expression of its targets acetyl coenzyme A carboxylase 1 and stearoyl coenzyme A desaturase 1. Furthermore, coffee consumption markedly decreased hepatic expression of H19 and of its target gene collagen alpha-1(I) chain; consistently, in mice fed HFD + coffee liver expression of αSMA protein returned to levels of mice fed SD. Expression of lncRNA involved in circadian clock such as fatty liver-related lncRNA 1 (FLRL1) and fatty liver-related lncRNA 2 (FLRL2) were upregulated by HFD and were also modulated by coffee intake., Conclusion: Hepatoprotective effects of coffee may be depending on the modulation of lncRNAs involved in key pathways of NAFLD onset and progression.
Published: 2021
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49. The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice.

Author: Cossiga V, Lembo V, Nigro C, Mirra P, Miele C, D'Argenio V, Leone A, Mazzone G, Veneruso I, Guido M, Beguinot F, Caporaso N, and Morisco F
Subjects: Animals, Arecaceae chemistry, Berberine administration & dosage, Berberis chemistry, Coffea chemistry, Diet, High-Fat adverse effects, Disease Models, Animal, Dysbiosis immunology, Dysbiosis microbiology, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome immunology, Gene Expression Regulation drug effects, Gene Expression Regulation immunology, Humans, Insulin Resistance immunology, Liver pathology, Male, Mice, MicroRNAs metabolism, Non-alcoholic Fatty Liver Disease immunology, Non-alcoholic Fatty Liver Disease pathology, Plant Extracts chemistry, Tocotrienols administration & dosage, Dysbiosis drug therapy, Liver drug effects, Non-alcoholic Fatty Liver Disease drug therapy, Plant Extracts administration & dosage
Abstract: Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora , on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight ( p < 0.01), amelioration of insulin-sensitivity ( p = 0.021), total cholesterol ( p = 0.014), low-density-lipoprotein-cholesterol ( p < 0.001), alanine-aminotransferase ( p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.
Published: 2021
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50. Interrupting vaccination policies can greatly spread SARS-CoV-2 and enhance mortality from COVID-19 disease: The AstraZeneca case for France and Italy.

Author: Faranda D, Alberti T, Arutkin M, Lembo V, and Lucarini V
Subjects: France, Humans, Italy, Policy, Vaccination, COVID-19, SARS-CoV-2
Abstract: Several European countries have suspended the inoculation of the AstraZeneca vaccine out of suspicion that it causes deep vein thrombosis. In this letter, we report some Fermi estimates performed using a stochastic model aimed at making a risk-benefit analysis of the interruption of the delivery of the AstraZeneca vaccine in France and Italy. Our results clearly show that excess deaths due to the interruption of the vaccination campaign injections largely overrun those due to thrombosis even in worst case scenarios of frequency and gravity of the vaccine side effects.
Published: 2021
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