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8. OC.15.2 SMALL BOWEL CARCINOMAS MAY COMPLICATE COELIAC DISEASE DESPITE STRICT ADHERENCE TO GLUTEN-FREE DIET: A CASE SERIES FROM THE SMALL BOWEL CANCER ITALIAN CONSORTIUM

Author

Bianchi, P.I., primary, Vanoli, A., additional, Lenti, M., additional, Guerini, C., additional, Arpa, G., additional, Quaquarini, E., additional, Aronico, N., additional, Grillo, F., additional, Nesi, G., additional, Furlan, D., additional, Latella, G., additional, Sessa, F., additional, Mescoli, C., additional, Rugge, M., additional, Ferrero, S., additional, Macciomei, M., additional, Santini, D., additional, Volta, U., additional, De Giorgio, R., additional, Caio, G., additional, Calabro, A., additional, Ciacci, C., additional, D'Armiento, M., additional, Villanacci, V., additional, Cannizzaro, R., additional, Canzonieri, V., additional, Florena, A., additional, Ciardi, A., additional, Elli, L., additional, Vecchi, M., additional, Zingone, F., additional, Reggiani Bonetti, L., additional, Astegiano, M., additional, Sandri, G., additional, Silano, M., additional, Usai, P., additional, Perfetti, V., additional, Giannone, A., additional, Barresi, V., additional, Ciccocioppo, R., additional, Biletta, E., additional, Corazza, G., additional, and Di Sabatino, A., additional

Published
2023
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10. PC.01.9 HYPOMETHYLATION OF LINE-1 IN SMALL BOWEL CARCINOMAS AND COELIAC DISEASE

Author

Guerini, C., primary, Bianchi, P.I., additional, Libera, L., additional, Vanoli, A., additional, Arpa, G., additional, Aronico, N., additional, Furlan, D., additional, Grillo, F., additional, Nesi, G., additional, Sampietro, G., additional, Ardizzone, S., additional, Fociani, P., additional, Fiocca, R., additional, Latella, G., additional, Sessa, F., additional, D'Errico, A., additional, Malvi, D., additional, Mescoli, C., additional, Rugge, M., additional, Ferrero, S., additional, Poggioli, G., additional, Rizzello, F., additional, Macciomei, M., additional, Santini, D., additional, Volta, U., additional, De Giorgio, R., additional, Caio, G., additional, Calabro, A., additional, Ciacci, C., additional, D'Armiento, M., additional, Rizzo, A., additional, Solina, G., additional, Tonelli, F., additional, Villanacci, V., additional, Cannizzaro, R., additional, Canzonieri, V., additional, Florena, A., additional, Biancone, L., additional, Monteleone, G., additional, Caronna, R., additional, Ciardi, A., additional, Elli, L., additional, Caprioli, F., additional, Vecchi, M., additional, D'Inca, R., additional, Zingone, F., additional, D'Odorico, A., additional, Oreggia, B., additional, Reggiani Bonetti, L., additional, Astegiano, M., additional, Cantoro, L., additional, Papi, C., additional, Sandri, G., additional, Silano, M., additional, Usai, P., additional, Perfetti, V., additional, Quaquarini, E., additional, Giannone, A., additional, Orlandi, A., additional, Barresi, V., additional, Ciccocioppo, R., additional, Amodeo, G., additional, Biletta, E., additional, and Di Sabatino, A., additional

Published
2023
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11. Administration of Linoleoylethanolamide Reduced Weight Gain, Dyslipidemia, and Inflammation Associated with High-Fat-Diet-Induced Obesity

Author

Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Ministerio de Cultura y Deporte (España), Tovar, R., de Ceglia, M, Ubaldi, M., Rodríguez-Pozo, M., Soverchia, L., Cifani, C., Rojo, G., Gavito, A., Hernández-Folgado, Laura, Jagerovic, Nadine, Ciccocioppo, R., Baixeras, E., Rodríguez de Fonseca, F., Decara, J., Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Ministerio de Cultura y Deporte (España), Tovar, R., de Ceglia, M, Ubaldi, M., Rodríguez-Pozo, M., Soverchia, L., Cifani, C., Rojo, G., Gavito, A., Hernández-Folgado, Laura, Jagerovic, Nadine, Ciccocioppo, R., Baixeras, E., Rodríguez de Fonseca, F., and Decara, J.

Abstract

Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, the pharmacology of those derived from either arachidonic acid (Anandamide), oleic acid (OEA), and palmitic acid (PEA) have been extensively characterized in diet-induced obesity. For the present work, we extended those studies to linoleoylethanolamide (LEA), one of the most abundant NAEs found not only in plasma and body tissues but also in foods such as cereals. In our initial study, circulating concentrations of LEA were found to be elevated in overweight humans (body mass index (BMI, Kg/m) > 25) recruited from a representative population from the south of Spain, together with AEA and the endocannabinoid 2-Arachidonoyl glycerol (2-AG). In this population, LEA concentrations correlated with the circulating levels of cholesterol and triglycerides. In order to gain insight into the pharmacology of LEA, we administered it for 14 days (10 mg/kg i.p. daily) to obese male Sprague Dawley rats receiving a cafeteria diet or a standard chow diet for 12 consecutive weeks. LEA treatment resulted in weight loss and a reduction in circulating triglycerides, cholesterol, and inflammatory markers such as Il-6 and Tnf-alpha. In addition, LEA reduced plasma transaminases and enhanced acetyl-CoA-oxidase (Acox) and Uncoupling protein-2 (Ucp2) expression in the liver of the HFD-fed animals. Although the liver steatosis induced by the HFD was not reversed by LEA, the overall data suggest that LEA contributes to the homeostatic signals set in place in response to diet-induced obesity, potentially contributing with OEA to improve lipid metabolism after high fat intake. The anti-inflammatory response associated with its administration suggests its potential for use as a nutrient supplement in non-alcoholic steatohepatitis.

Published
2023

16. Brain Network Allostasis after Chronic Alcohol Drinking Is Characterized by Functional Dedifferentiation and Narrowing

Author

Perez-Ramirez U, Lopez-Madrona V, Perez-Segura A, Pallares V, Moreno A, Ciccocioppo R, Hyytia P, Sommer W, Moratal D, and Canals S

Subjects
AUD, alcohol, fMRI, network, MEMRI, allostasis
Abstract

Alcohol use disorder (AUD) causes complex alterations in the brain that are poorly understood. The heterogeneity of drinking patterns and the high incidence of comorbid factors compromise mechanistic investigations in AUD patients. Here we used male Marchigian Sardinian alcohol-preferring (msP) rats, a well established animal model of chronic alcohol drinking, and a combination of longitudinal resting-state fMRI and manganese-enhanced MRI to provide objective measurements of brain connectivity and activity, respectively. We found that 1 month of chronic alcohol drinking changed the correlation between resting-state networks. The change was not homogeneous, resulting in the reorganization of pairwise interactions and a shift in the equilibrium of functional connections. We identified two fundamentally different forms of network reorganization. First is functional dedifferentiation, which is defined as a regional increase in neuronal activity and overall correlation, with a concomitant decrease in preferential connectivity between specific networks. Through this mechanism, occipital cortical areas lost their specific interaction with sensory-insular cortex, striatal, and sensorimotor networks. Second is functional narrowing, which is defined as an increase in neuronal activity and preferential connectivity between specific brain networks. Functional narrowing strengthened the interaction between striatal and prefrontocortical networks, involving the anterior insular, cingulate, orbitofrontal, prelimbic, and infralimbic cortices. Importantly, these two types of alterations persisted after alcohol discontinuation, suggesting that dedifferentiation and functional narrowing rendered persistent network states. Our results support the idea that chronic alcohol drinking, albeit at moderate intoxicating levels, induces an allostatic change in the brain functional connectivity that propagates into early abstinence.

Published
2022

18. Moderate ethanol drinking is sufficient to alter Ventral Tegmental Area dopamine neurons activity via functional and structural remodeling of GABAergic transmission

Author

Ilari, A., primary, Curti, L., additional, Petrella, M., additional, Cannella, N., additional, La Rocca, A., additional, Ranieri, G., additional, Gerace, E., additional, Iezzi, D., additional, Silvestri, L., additional, Mannaioni, G., additional, Ciccocioppo, R., additional, and Masi, A., additional

Published
2022
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21. Developing cell therapies as drug products

Author

Ciccocioppo, R., Comoli, P., Astori, G., del Bufalo, F., Prapa, M., Dominici, M., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Ciccocioppo, R., Comoli, P., Astori, G., del Bufalo, F., Prapa, M., Dominici, M., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

In the last 20 years, the global regulatory frameworks for drug assessment have been managing the challenges posed by using cellular products as new therapeutic tools. Currently, they are defined as “Advanced Therapy Medicinal Products”, comprising a large group of cellular types that either alone or in combination with gene and tissue engineering technology. They have the potential to change the natural course of still lethal or highly debilitating diseases, including cancers, opportunistic infections and chronic inflammatory conditions. Globally, more than 50 cell-based products have obtained market authorization. This overview describes the advantages and unsolved challenges on developing cells as innovative therapeutic vehicles. The main cell therapy players and the legal framework are discussed, starting from chimeric antigen receptor T-cells for leukaemia and solid tumours, dealing then with lymphocytes as potent anti-microbiological tools and then focusing on mesenchymal stem/stromal cells whose role covers regenerative medicine, immunology and anti-tumour therapy.

Published
2021

26. Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability (Modern Pathology, (2020), 33, 7, (1398-1409), 10.1038/s41379-020-0497-0)

Author

Giuffrida, P., Arpa, G., Grillo, F., Klersy, C., Sampietro, G., Ardizzone, S., Fociani, P., Fiocca, R., Latella, G., Sessa, F., D'Errico, A., Malvi, D., Mescoli, C., Rugge, M., Nesi, G., Ferrero, S., Furlan, D., Poggioli, G., Rizzello, F., Macciomei, M. C., Santini, D., Volta, U., De Giorgio, R., Caio, G., Calabro, A., Ciacci, C., D'Armiento, M., Rizzo, A., Solina, G., Martino, M., Tonelli, F., Villanacci, V., Cannizzaro, R., Canzonieri, V., Florena, A. M., Biancone, L., Monteleone, G., Caronna, R., Ciardi, A., Elli, L., Caprioli, F., Vecchi, M., D'Inca, R., Zingone, F., D'Odorico, A., Lenti, M. V., Oreggia, B., Bonetti, L. R., Astegiano, M., Biletta, E., Cantoro, L., Giannone, A. G., Orlandi, A., Papi, C., Perfetti, V., Quaquarini, E., Sandri, G., Silano, M., Usai, P., Barresi, V., Ciccocioppo, R., Luinetti, O., Pedrazzoli, P., Pietrabissa, A., Viglio, A., Paulli, M., Corazza, G. R., Solcia, E., Vanoli, A., and Di Sabatino, A.

Published
2020

28. Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease

Author

Di Sabatino, A., Ciccocioppo, R., Cinque, B., Millimaggi, D., Morera, R., Ricevuti, L., Cifone, M.G., and Corazza, G.R.

Subjects
Health
Abstract

Gut 2004;53:70-77 Background and aims: To verify whether targeting defective mucosal T cell death underlies the sustained therapeutic benefit of infliximab in Crohn's disease, we explored its in vivo proapoptotic [...]

Published
2004

31. T03.01.10 RELIABILITY OF THE DIAGNOSTIC WORK-UP IN A PROSPECTIVE SERIES OF OPERATED CYSTIC PANCREATIC NEOPLASMS: A REAL-LIFE SCENARIO

Author

Amodio, A., primary, De Marchi, G., additional, Gabrieletto, E.M., additional, Campagnola, P., additional, Paiella, S., additional, Capelli, P., additional, Bernardoni, L., additional, Crinò, S.F., additional, Gabbrielli, A., additional, Salvia, R., additional, Ciccocioppo, R., additional, Bassi, C., additional, and Frulloni, L., additional

Published
2020
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49. Pharmacological and behavioral effects of the synthetic cannabinoid akb48 in rats

Author

Bilel, S., Tirri, M., Arfe, R., Stopponi, S., Soverchia, L., Ciccocioppo, R., Frisoni, P., Strano Rossi, Sabina, Miliano, C., De Giorgio, Fabio, Serpelloni, G., Fantinati, A., De Luca, M. A., Neri, M., Marti, M., Strano Rossi S. (ORCID:0000-0001-7530-2968), De Giorgio F. (ORCID:0000-0002-9447-9707), Bilel, S., Tirri, M., Arfe, R., Stopponi, S., Soverchia, L., Ciccocioppo, R., Frisoni, P., Strano Rossi, Sabina, Miliano, C., De Giorgio, Fabio, Serpelloni, G., Fantinati, A., De Luca, M. A., Neri, M., Marti, M., Strano Rossi S. (ORCID:0000-0001-7530-2968), and De Giorgio F. (ORCID:0000-0002-9447-9707)

Abstract

AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the in vivo pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid.

Published
2019

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