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107 results on '"Stronati, L"'

1. NOD2 and inflammation: current insights

Author: Negroni A, Pierdomenico M, Cucchiara S, and Stronati L
Subjects: innate immunity, intestinal homeostasis, ER stress, autophagy, Inflammatory Bowel Disease, extra-intestinal disease, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract: Anna Negroni,1 Maria Pierdomenico,2 Salvatore Cucchiara,2 Laura Stronati3 1Division of Health Protection Technologies, Territorial and Production Systems Sustainability Department, ENEA, Rome, Italy; 2Department of Pediatrics and Infantile Neuropsychiatry, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy; 3Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Abstract: The nucleotide-binding oligomerization domain (NOD) protein, NOD2, belonging to the intracellular NOD-like receptor family, detects conserved motifs in bacterial peptidoglycan and promotes their clearance through activation of a proinflammatory transcriptional program and other innate immune pathways, including autophagy and endoplasmic reticulum stress. An inactive form due to mutations or a constitutive high expression of NOD2 is associated with several inflammatory diseases, suggesting that balanced NOD2 signaling is critical for the maintenance of immune homeostasis. In this review, we discuss recent developments about the pathway and mechanisms of regulation of NOD2 and illustrate the principal functions of the gene, with particular emphasis on its central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. Furthermore, we survey recent studies illustrating the role of NOD2 in several inflammatory diseases, in particular, inflammatory bowel disease, of which it is the main susceptibility gene. Keywords: innate immunity, intestinal homeostasis, ER stress, autophagy, inflammatory bowel disease, extraintestinal disease
Published: 2018

2. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Author: Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., S. M. E., Ng, Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., S. M., Ng, Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Romagnoni, A., Jegou, S., Van Steen, K., Wainrib, G., Hugot, J. -P., Peyrin-Biroulet, L., Chamaillard, M., Colombel, J. -F., Cottone, M., D'Amato, M., D'Inca, R., Halfvarson, J., Henderson, P., Karban, A., Kennedy, N. A., Khan, M. A., Lemann, M., Levine, A., Massey, D., Milla, M., Ng, S. M. E., Oikonomou, I., Peeters, H., Proctor, D. D., Rahier, J. -F., Rutgeerts, P., Seibold, F., Stronati, L., Taylor, K. M., Torkvist, L., Ublick, K., Van Limbergen, J., Van Gossum, A., Vatn, M. H., Zhang, H., Zhang, W., Andrews, J. M., Bampton, P. A., Barclay, M., Florin, T. H., Gearry, R., Krishnaprasad, K., Lawrance, I. C., Mahy, G., Montgomery, G. W., Radford-Smith, G., Roberts, R. L., Simms, L. A., Hanigan, K., Croft, A., Amininijad, L., Cleynen, I., Dewit, O., Franchimont, D., Georges, M., Laukens, D., Theatre, E., Vermeire, S., Aumais, G., Baidoo, L., Barrie, A. M., Beck, K., Bernard, E. -J., Binion, D. G., Bitton, A., Brant, S. R., Cho, J. H., Cohen, A., Croitoru, K., Daly, M. J., Datta, L. W., Deslandres, C., Duerr, R. H., Dutridge, D., Ferguson, J., Fultz, J., Goyette, P., Greenberg, G. R., Haritunians, T., Jobin, G., Katz, S., Lahaie, R. G., Mcgovern, D. P., Nelson, L., Ng, S. M., Ning, K., Pare, P., Regueiro, M. D., Rioux, J. D., Ruggiero, E., Schumm, L. P., Schwartz, M., Scott, R., Sharma, Y., Silverberg, M. S., Spears, D., Steinhart, A. H., Stempak, J. M., Swoger, J. M., Tsagarelis, C., Zhang, C., Zhao, H., Aerts, J., Ahmad, T., Arbury, H., Attwood, A., Auton, A., Ball, S. G., Balmforth, A. J., Barnes, C., Barrett, J. C., Barroso, I., Barton, A., Bennett, A. J., Bhaskar, S., Blaszczyk, K., Bowes, J., Brand, O. J., Braund, P. S., Bredin, F., Breen, G., Brown, M. J., Bruce, I. N., Bull, J., Burren, O. S., Burton, J., Byrnes, J., Caesar, S., Cardin, N., Clee, C. M., Coffey, A. J., MC Connell, J., Conrad, D. F., Cooper, J. D., Dominiczak, A. F., Downes, K., Drummond, H. E., Dudakia, D., Dunham, A., Ebbs, B., Eccles, D., Edkins, S., Edwards, C., Elliot, A., Emery, P., Evans, D. M., Evans, G., Eyre, S., Farmer, A., Ferrier, I. N., Flynn, E., Forbes, A., Forty, L., Franklyn, J. A., Frayling, T. M., Freathy, R. M., Giannoulatou, E., Gibbs, P., Gilbert, P., Gordon-Smith, K., Gray, E., Green, E., Groves, C. J., Grozeva, D., Gwilliam, R., Hall, A., Hammond, N., Hardy, M., Harrison, P., Hassanali, N., Hebaishi, H., Hines, S., Hinks, A., Hitman, G. A., Hocking, L., Holmes, C., Howard, E., Howard, P., Howson, J. M. M., Hughes, D., Hunt, S., Isaacs, J. D., Jain, M., Jewell, D. P., Johnson, T., Jolley, J. D., Jones, I. R., Jones, L. A., Kirov, G., Langford, C. F., Lango-Allen, H., Lathrop, G. M., Lee, J., Lee, K. L., Lees, C., Lewis, K., Lindgren, C. M., Maisuria-Armer, M., Maller, J., Mansfield, J., Marchini, J. L., Martin, P., Massey, D. C., Mcardle, W. L., Mcguffin, P., Mclay, K. E., Mcvean, G., Mentzer, A., Mimmack, M. L., Morgan, A. E., Morris, A. P., Mowat, C., Munroe, P. B., Myers, S., Newman, W., Nimmo, E. R., O'Donovan, M. C., Onipinla, A., Ovington, N. R., Owen, M. J., Palin, K., Palotie, A., Parnell, K., Pearson, R., Pernet, D., Perry, J. R., Phillips, A., Plagnol, V., Prescott, N. J., Prokopenko, I., Quail, M. A., Rafelt, S., Rayner, N. W., Reid, D. M., Renwick, A., Ring, S. M., Robertson, N., Robson, S., Russell, E., Clair, D. S., Sambrook, J. G., Sanderson, J. D., Sawcer, S. J., Schuilenburg, H., Scott, C. E., Seal, S., Shaw-Hawkins, S., Shields, B. M., Simmonds, M. J., Smyth, D. J., Somaskantharajah, E., Spanova, K., Steer, S., Stephens, J., Stevens, H. E., Stirrups, K., Stone, M. A., Strachan, D. P., Su, Z., Symmons, D. P. M., Thompson, J. R., Thomson, W., Tobin, M. D., Travers, M. E., Turnbull, C., Vukcevic, D., Wain, L. V., Walker, M., Walker, N. M., Wallace, C., Warren-Perry, M., Watkins, N. A., Webster, J., Weedon, M. N., Wilson, A. G., Woodburn, M., Wordsworth, B. P., Yau, C., Young, A. H., Zeggini, E., Brown, M. A., Burton, P. R., Caulfield, M. J., Compston, A., Farrall, M., Gough, S. C. L., Hall, A. S., Hattersley, A. T., Hill, A. V. S., Mathew, C. G., Pembrey, M., Satsangi, J., Stratton, M. R., Worthington, J., Hurles, M. E., Duncanson, A., Ouwehand, W. H., Parkes, M., Rahman, N., Todd, J. A., Samani, N. J., Kwiatkowski, D. P., Mccarthy, M. I., Craddock, N., Deloukas, P., Donnelly, P., Blackwell, J. M., Bramon, E., Casas, J. P., Corvin, A., Jankowski, J., Markus, H. S., Palmer, C. N., Plomin, R., Rautanen, A., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Pirinen, M., Strange, A., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Jayakumar, A., Mccann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Daly, Mark J. [0000-0002-0949-8752], Apollo - University of Cambridge Repository, Hugot, Jean-Pierre [0000-0002-8446-6056], UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Romagnoni, A, Jegou, S, VAN STEEN, Kristel, Wainrib, G, Hugot, JP, Peyrin-Biroulet, L, Chamaillard, M, Colombel, JF, Cottone, M, D'Amato, M, D'Inca, R, Halfvarson, J, Henderson, P, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Ng, SME, Oikonomou, I, Peeters, H, Proctor, DD, Rahier, JF, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Andrews, JM, Bampton, PA, Barclay, M, Florin, TH, Gearry, R, Krishnaprasad, K, Lawrance, IC, Mahy, G, Montgomery, GW, Radford-Smith, G, Roberts, RL, Simms, LA, Hanigan, K, Croft, A, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie, AM, Beck, K, Bernard, EJ, Binion, DG, Bitton, A, Brant, SR, Cho, JH, Cohen, A, Croitoru, K, Daly, MJ, Datta, LW, Deslandres, C, Duerr, RH, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, GR, Haritunians, T, Jobin, G, Katz, S, Lahaie, RG, McGovern, DP, Nelson, L, Ng, SM, Ning, K, Pare, P, Regueiro, MD, Rioux, JD, Ruggiero, E, Schumm, LP, Schwartz, M, Scott, R, Sharma, Y, Silverberg, MS, Spears, D, Steinhart, AH, Stempak, JM, Swoger, JM, Tsagarelis, C, Zhang, C, Zhao, HY, AERTS, Jan, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, SG, Balmforth, AJ, Barnes, C, Barrett, JC, Barroso, I, Barton, A, Bennett, AJ, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, OJ, Braund, PS, Bredin, F, Breen, G, Brown, MJ, Bruce, IN, Bull, J, Burren, OS, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, CM, Coffey, AJ, Mc Connell, J, Conrad, DF, Cooper, JD, Dominiczak, AF, Downes, K, Drummond, HE, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, DM, Evans, G, Eyre, S, Farmer, A, Ferrier, IN, Flynn, E, Forbes, A, Forty, L, Franklyn, JA, Frayling, TM, Freathy, RM, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon-Smith, K, Gray, E, Green, E, Groves, CJ, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, GA, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, JMM, Hughes, D, Hunt, S, Isaacs, JD, Jain, M, Jewell, DP, Johnson, T, Jolley, JD, Jones, IR, Jones, LA, Kirov, G, Langford, CF, Lango-Allen, H, Lathrop, GM, Lee, J, Lee, KL, Lees, C, Lewis, K, Lindgren, CM, Maisuria-Armer, M, Maller, J, Mansfield, J, Marchini, JL, Martin, P, Massey, DCO, McArdle, WL, McGuffin, P, McLay, KE, McVean, G, Mentzer, A, Mimmack, ML, Morgan, AE, Morris, AP, Mowat, C, Munroe, PB, Myers, S, Newman, W, Nimmo, ER, O'Donovan, MC, Onipinla, A, Ovington, NR, Owen, MJ, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, JRB, Phillips, A, Plagnol, V, Prescott, NJ, Prokopenko, I, Quail, MA, Rafelt, S, Rayner, NW, Reid, DM, Renwick, A, Ring, SM, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, JG, Sanderson, JD, Sawcer, SJ, Schuilenburg, H, Scott, CE, Seal, S, Shaw-Hawkins, S, Shields, BM, Simmonds, MJ, Smyth, DJ, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, HE, Stirrups, K, Stone, MA, Strachan, DP, Su, Z, Symmons, DPM, Thompson, JR, Thomson, W, Tobin, MD, Travers, ME, Turnbull, C, Vukcevic, D, Wain, LV, Walker, M, Walker, NM, Wallace, C, Warren-Perry, M, Watkins, NA, Webster, J, Weedon, MN, Wilson, AG, Woodburn, M, Wordsworth, BP, Yau, C, Young, AH, Zeggini, E, Brown, MA, Burton, PR, Caulfield, MJ, Compston, A, Farrall, M, Gough, SCL, Hall, AS, Hattersley, AT, Hill, AVS, Mathew, CG, Pembrey, M, Satsangi, J, Stratton, MR, Worthington, J, Hurles, ME, Duncanson, A, Ouwehand, WH, Parkes, M, Rahman, N, Todd, JA, Samani, NJ, Kwiatkowski, DP, McCarthy, MI, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, JM, Bramon, E, Casas, JP, Corvin, A, Jankowski, J, Markus, HS, Palmer, CNA, Plomin, R, Rautanen, A, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, and Kwiatkowski, D
Subjects: Male, 692/4020/1503/257/1402, Genotype, Genotyping Techniques, LOCI, 45/43, lcsh:Medicine, Polymorphism, Single Nucleotide, Crohn's disease, genetics, genome wide association, Article, Deep Learning, Crohn Disease, INDEL Mutation, Genetics research, Humans, genetics, Genetic Predisposition to Disease, 129, lcsh:Science, Alleles, Science & Technology, genome wide association, RISK PREDICTION, 45, Models, Genetic, lcsh:R, Decision Trees, 692/308/2056, ASSOCIATION, Multidisciplinary Sciences, Crohn's disease, Logistic Models, Nonlinear Dynamics, ROC Curve, Area Under Curve, Science & Technology - Other Topics, lcsh:Q, Female, Neural Networks, Computer, INFLAMMATORY-BOWEL-DISEASE, Genome-Wide Association Study
Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise.
Published: 2019

3. Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat

Author: Corte, C. Della, Mosca, A., Majo, F., Lucidi, V., Panera, N., Giglioni, E., Monti, L., Stronati, L., Alisi, A., and Nobili, V.
Published: 2015
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4. Lactobacillus Reuteri grows in the Microalga Isochrysis Galbana Generating a Fermented Compound that reduces the AIEC Bacteria Harmfulness

Author: Colantoni, E., primary, Palone, F., additional, Cesi, V., additional, Leter, B., additional, Sugoni, G., additional, Laudadio, I., additional, Negroni, A., additional, Vitali, R., additional, and Stronati, L., additional
Published: 2021
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5. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Author: Patsopoulos, NA, Baranzini, SE, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, AH, James, T, Replogle, J, Vlachos, IS, McCabe, C, Pers, TH, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, IP, Robbins, A, Andlauer, TFM, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, HB, Sellebjerg, F, Sorensen, PS, Ullum, H, Thorner, LW, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, CM, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, MD, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, MA, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, SD, Celius, EG, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, IL, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, SJ, Calabresi, P, Cree, BAC, Cross, A, Davis, M, de Bakker, PWI, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, IY, Gourraud, PA, Haines, JL, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, MH, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, CP, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, MA, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, RJ, Lechner-Scott, J, Leal, R, Moscato, P, Booth, DR, Stewart, GJ, Vucic, S, Pame, G, BamettO, M, Mason, D, GriffithS, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, BV, Charlesworth, J, Kilpatrick, TJ, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, WM, Kermode, AG, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, JF, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, JP, Karban, A, Kennedy, NA, Khan, MA, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, GW, Ng, SME, Oikonomnou, J, Peeters, H, Proctor, DD, Rahier, JF, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, KM, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, MH, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, DA, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, HF, Hauser, SL, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, LF, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, McCauley, JL, Oksenberg, JR, Oturai, A, Sawcer, S, Ivinson, AJ, Olsson, T, De Jager, PL, Patsopoulos, Na, Baranzini, Se, Santaniello, A, Shoostari, P, Cotsapas, C, Wong, G, Beecham, Ah, James, T, Replogle, J, Vlachos, I, Mccabe, C, Pers, Th, Brandes, A, White, C, Keenan, B, Cimpean, M, Winn, P, Panteliadis, Ip, Robbins, A, Andlauer, Tfm, Zarzycki, O, Dubois, B, Goris, A, Sondergaard, Hb, Sellebjerg, F, Sorensen, P, Ullum, H, Thorner, Lw, Saarela, J, Cournu-Rebeix, I, Damotte, V, Fontaine, B, Guillot-Noel, L, Lathrop, M, Vukusic, S, Berthele, A, Pongratz, V, Gasperi, C, Graetz, C, Grummel, V, Hemmer, B, Hoshi, M, Knier, B, Korn, T, Lill, Cm, Luessi, F, Muhlau, M, Zipp, F, Dardiotis, E, Agliardi, C, Amoroso, A, Barizzone, N, Benedetti, Md, Bernardinelli, L, Cavalla, P, Clarelli, F, Comi, G, Cusi, D, Esposito, F, Ferre, L, Galimberti, D, Guaschino, C, Leone, Ma, Martinelli, V, Moiola, L, Salvetti, M, Sorosina, M, Vecchio, D, Zauli, A, Santoro, S, Mancini, N, Zuccala, M, Mescheriakova, J, van Duijn, C, Bos, Sd, Celius, Eg, Spurkland, A, Comabella, M, Montalban, X, Alfredsson, L, Bomfim, Il, Gomez-Cabrero, D, Hillert, J, Jagodic, M, Linden, M, Piehl, F, Jelcic, I, Martin, R, Sospedra, M, Baker, A, Ban, M, Hawkins, C, Hysi, P, Kalra, S, Karpe, F, Khadake, J, Lachance, G, Molyneux, P, Neville, M, Thorpe, J, Bradshaw, E, Caillier, Sj, Calabresi, P, Cree, Bac, Cross, A, Davis, M, de Bakker, Pwi, Delgado, S, Dembele, M, Edwards, K, Fitzgerald, K, Frohlich, Iy, Gourraud, Pa, Haines, Jl, Hakonarson, H, Kimbrough, D, Isobe, N, Konidari, I, Lathi, E, Lee, Mh, Li, T, An, D, Zimmer, A, Madireddy, L, Manrique, Cp, Mitrovic, M, Olah, M, Patrick, E, Pericak-Vance, Ma, Piccio, L, Schaefer, C, Weiner, H, Lage, K, Scott, Rj, Lechner-Scott, J, Leal, R, Moscato, P, Booth, Dr, Stewart, Gj, Vucic, S, Pame, G, Bametto, M, Mason, D, Griffiths, L, Broadley, S, Tajouri, L, Baxter, A, Slee, M, Taylor, Bv, Charlesworth, J, Kilpatrick, Tj, Rubio, J, Jokubaitis, V, Wiley, J, Butzkueven, H, Leslie, S, Motyer, A, Stankovich, J, Carroll, Wm, Kermode, Ag, Edrin, M, Barclay, M, Peyrin-Biroulet, L, Chamaillard, M, Colombe, Jf, Cottone, M, Croft, A, D'Inca, R, Halfvarson, J, Hanigan, K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lemann, M, Levine, A, Massey, D, Milla, M, Motoey, Gw, Ng, Sme, Oikonomnou, J, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, L, Taylor, Km, Torkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Donnelly, P, Barroso, I, Blackwe, Jm, Bramon, E, Brown, Ma, Casas, Jp, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, H, Mathew, Cg, Palmer, Cna, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cca, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Sul, Z, Vukcevic, Da, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Compston, A, Hafler, D, Harbo, Hf, Hauser, Sl, Stewart, G, D'Alfonso, S, Hadjigeorgiou, G, Taylor, B, Barcellos, Lf, Booth, D, Hintzen, R, Kockum, I, Martinelli-Boneschi, F, Mccauley, Jl, Oksenberg, Jr, Oturai, A, Sawcer, S, Ivinson, Aj, Olsson, T, De Jager, Pl, Neurology, and Immunology
Subjects: 0301 basic medicine, Multiple Sclerosis, Quantitative Trait Loci, Inheritance Patterns, Cell Cycle Proteins, Genome-wide association study, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Major Histocompatibility Complex, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Immune system, Gene Frequency, Autoimmune Process, medicine, Humans, RNA-Seq, X chromosome, Genetics, Chromosomes, Human, X, Multidisciplinary, Microglia, Multiple sclerosis, GTPase-Activating Proteins, Chromosome Mapping, Genomics, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Genetic Loci, Case-Control Studies, biology.protein, Genome-Wide Association Study, 030217 neurology & neurosurgery
Abstract: Genetic roots of multiple sclerosis The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis. Science , this issue p. eaav7188 ; see also p. 1383
Published: 2019

6. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author: Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, AS, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, MJ, de Jong, AE, van der Woude, C.J., Visschedijk, MC, Lathrop, M, Hugot, JP, Weersma, RK, Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, JP, Ahmad, T, Ananthakrishnan, AN, Andersen, V, Anderson, CA, Andrews, JM, Annese, V, Aumais, G, Baidoo, L, Baldassano, RN, Bampton, PA, Barclay, M, Barrett, JC, Bayless, TM, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, SR, Buning, C, Chew, A, Cho, JH, Cleynen, I, Cohain, A, Croft, A, Daly, MJ, D'Amato, M, Danese, S, Jong, D, Denapiene, G, Denson, LA, Devaney, KL, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, RH, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, LR, Festen, EA, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, AM, Guthery, SL, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, de Hart, A, Hawkey, C, Hayward, NK, Hedl, M, Henderson, P, Hu, XH, Huang, HL, Hui, KY, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, TH, Kennedy, NA, Khan, MA, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, IC, Lee, JC, Lees, CW, Leja, M, van Limbergen, J, Lionetti, P, Liu, JZ, Mahy, G, Mansfield, J, Massey, D, Mathew, CG, McGovern, DPB, Milgrom, R, Mitrovic, M, Montgomery, GW, Mowat, C, Newman, W, Ng, A, Ng, SC, Ng, SME, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, Radford-Smith, G, Rahier, JF, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, JD, Ripke, S, Roberts, R, Russell, RK, Sanderson, JD, Sans, M, Satsangi, J, Schadt, EE, Schreiber, S, Schulte, D, Schumm, LP, Scott, R, Seielstad, M, Sharma, Y, Silverberg, MS, Simms, LA, Skieceviciene, J, Spain, SL, Steinhart, AH, Stempak, JM, Stronati, L, Sventoraityte, J, Targan, SR, Taylor, KM, Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, HW, Walters, T, Wang, K, Wang, MH, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, DC, Winkelmann, J, Xavier, RJ, Zhang, B, Zhang, CK, Zhang, H, Zhang, W, Zhao, HY, Zhao, ZZ, Momozawa, Y, Dmitrieva, J, Theatre, E, Deffontaine, V, Rahmouni, S, Charloteaux, B, Crins, F, Docampo, E, Elansary, M, Gori, A, Lecut, C, Mariman, R, Mni, M, Oury, C, Altukhov, I, Alexeev, D, Aulchenko, Y, Amininejad, L, Bouma, G, Hoentjen, F, Lowenberg, M, Oldenburg, B, Pierik, Mj, vander Meulen-de Jong, Ae, van der Woude, Cj, Visschedijk, Mc, Lathrop, M, Hugot, Jp, Weersma, Rk, De Vos, M, Franchimont, D, Vermeire, S, Kubo, M, Louis, E, Georges, M, Abraham, C, Achkar, Jp, Ahmad, T, Ananthakrishnan, An, Andersen, V, Anderson, Ca, Andrews, Jm, Annese, V, Aumais, G, Baidoo, L, Baldassano, Rn, Bampton, Pa, Barclay, M, Barrett, Jc, Bayless, Tm, Bethge, J, Bitton, A, Boucher, G, Brand, S, Brandt, B, Brant, Sr, Buning, C, Chew, A, Cho, Jh, Cleynen, I, Cohain, A, Croft, A, Daly, Mj, D'Amato, M, Danese, S, De Jong, D, Denapiene, G, Denson, La, Devaney, Kl, Dewit, O, D'Inca, R, Dubinsky, M, Duerr, Rh, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, Lr, Festen, Ea, Fleshner, P, Florin, T, Franke, A, Fransen, K, Gearry, R, Gieger, C, Glas, J, Goyette, P, Green, T, Griffiths, Am, Guthery, Sl, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, Nk, Hedl, M, Henderson, P, Hu, Xh, Huang, Hl, Hui, Ky, Imielinski, M, Ippoliti, A, Jonaitis, L, Jostins, L, Karlsen, Th, Kennedy, Na, Khan, Ma, Kiudelis, G, Krishnaprasad, K, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, Ic, Lee, Jc, Lees, Cw, Leja, M, Van Limbergen, J, Lionetti, P, Liu, Jz, Mahy, G, Mansfield, J, Massey, D, Mathew, Cg, Mcgovern, Dpb, Milgrom, R, Mitrovic, M, Montgomery, Gw, Mowat, C, Newman, W, Ng, A, Ng, Sc, Ng, Sme, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, Cy, Potocnik, U, Prescott, Nj, Proctor, Dd, Radford-Smith, G, Rahier, Jf, Raychaudhuri, S, Regueiro, M, Rieder, F, Rioux, Jd, Ripke, S, Roberts, R, Russell, Rk, Sanderson, Jd, Sans, M, Satsangi, J, Schadt, Ee, Schreiber, S, Schulte, D, Schumm, Lp, Scott, R, Seielstad, M, Sharma, Y, Silverberg, M, Simms, La, Skieceviciene, J, Spain, Sl, Steinhart, Ah, Stempak, Jm, Stronati, L, Sventoraityte, J, Targan, Sr, Taylor, Km, ter Velde, A, Torkvist, L, Tremelling, M, van Sommeren, S, Vasiliauskas, E, Verspaget, Hw, Walters, T, Wang, K, Wang, Mh, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, Dc, Winkelmann, J, Xavier, Rj, Zhang, B, Zhang, Ck, Zhang, H, Zhang, W, Zhao, Hy, Zhao, Zz, Gastroenterology & Hepatology, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (MGD) Service de gastro-entérologie
Subjects: Adult, Male, Multifactorial Inheritance, QUANTITATIVE TRAIT LOCUS, Genotype, SEQUENCING DATA, Quantitative Trait Loci, SUSCEPTIBILITY, Polymorphism, Single Nucleotide, Article, Cohort Studies, CODING VARIANTS, Crohn Disease, 80 and over, Journal Article, Medicine and Health Sciences, LOCUS, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, Genetic Association Studies, Aged, Aged, 80 and over, Science & Technology, Female, Gene Expression Profiling, Inflammatory Bowel Diseases, Middle Aged, Sequence Analysis, DNA, COMPLEX TRAITS, Biology and Life Sciences, Single Nucleotide, DNA, CROHNS-DISEASE, Multidisciplinary Sciences, QUANTITATIVE TRAIT, RARE VARIANTS, Science & Technology - Other Topics, LOW-FREQUENCY, Sequence Analysis, INFLAMMATORY-BOWEL-DISEASE
Abstract: GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach., Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.
Published: 2018

7. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author: Stronati, L. and Stronati, L.
Abstract: GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach. © 2018 The Author(s).
Published: 2018

8. Low Dose of Dipotassium Glycyrrhizate Counteracts Atherosclerosis Progression in Apoe-/- Female Mice

Author: Palone, F., Pasquali, E., Giardullo, P., Stronati, L., Vitali, R., and Mancuso, M.
Subjects: Animal, Mice, Knockout, ApoE, Thoracic, Knockout, Aortic Diseases, Aorta, Thoracic, Atherosclerosis, Glycyrrhizic Acid, Lipids, Plaque, Atherosclerotic, Animals, Disease Models, Animal, Disease Progression, Female, HMGB1 Protein, Inflammation Mediators, Sex Factors, Mice, Disease Models, Aorta, ApoE, Plaque, Atherosclerotic
Published: 2019

9. PARP1 promotes the release of HMGB1 increasing intestinal inflammation

Author: Mancuso, Ab, Vitali, R, Palone, F, Fiaschini, N, Colantoni, E, Cucchiara, S, Rossi, P, Falconieri, P, and and Stronati, L
Subjects: Inflammation, HMGB1, PARP1, Inflammation, PARP1, HMGB1
Published: 2019

10. What is that 2?: Advertisements of follow-up formula and their perception by pregnant women and mothers in Italy

Author: Cattaneo, A, Pani, P, Carletti, C, Guidetti, M, Mutti, V, Guidetti, C, Knowles, A, Barbiero, C, Montico, M, Locatelli, M, Conti, S, Pellegrini, E, Papa, O, Nespoli, A, Bettinelli, M, De Gioia, C, Lelli, M, Mascheroni, R, Cetin, I, Pileri, P, Gatti, R, Pompilio, G, Ortenzi, V, Stronati, L, Giusti, A, Spadea, A, Rinaldi, I, Galluzzo, L, Vadacca, P, Sarta, S, Nibali, S, Crisafulli, R, Nibali, R, Corrado, F, Garraffa, M, Di Pasquale, M, Gallo, M, Cattaneo A., Pani P., Carletti C., Guidetti M., Mutti V., Guidetti C., Knowles A., Barbiero C., Montico M., Locatelli M., Conti S., Pellegrini E., Papa O., Nespoli A., Bettinelli M. E., De Gioia C., Lelli M., Mascheroni R., Cetin I., Pileri P., Gatti R., Pompilio G., Ortenzi V., Stronati L., Giusti A., Spadea A., Rinaldi I., Galluzzo L., Vadacca P., Sarta S., Nibali S. C., Crisafulli R., Nibali R. C., Corrado F., Garraffa M., Di Pasquale M., Gallo M. C., Cattaneo, A, Pani, P, Carletti, C, Guidetti, M, Mutti, V, Guidetti, C, Knowles, A, Barbiero, C, Montico, M, Locatelli, M, Conti, S, Pellegrini, E, Papa, O, Nespoli, A, Bettinelli, M, De Gioia, C, Lelli, M, Mascheroni, R, Cetin, I, Pileri, P, Gatti, R, Pompilio, G, Ortenzi, V, Stronati, L, Giusti, A, Spadea, A, Rinaldi, I, Galluzzo, L, Vadacca, P, Sarta, S, Nibali, S, Crisafulli, R, Nibali, R, Corrado, F, Garraffa, M, Di Pasquale, M, Gallo, M, Cattaneo A., Pani P., Carletti C., Guidetti M., Mutti V., Guidetti C., Knowles A., Barbiero C., Montico M., Locatelli M., Conti S., Pellegrini E., Papa O., Nespoli A., Bettinelli M. E., De Gioia C., Lelli M., Mascheroni R., Cetin I., Pileri P., Gatti R., Pompilio G., Ortenzi V., Stronati L., Giusti A., Spadea A., Rinaldi I., Galluzzo L., Vadacca P., Sarta S., Nibali S. C., Crisafulli R., Nibali R. C., Corrado F., Garraffa M., Di Pasquale M., and Gallo M. C.
Abstract: Background: In most European countries advertisements of infant formula are forbidden, while those of follow-on formula are allowed. Recent researches carried out in Australia and Great Britain have suggested that advertisement of toddler formula is used by the producing industry as a line extension to promote infant and follow-on formulas. Objectives: The objective of the study is to assess how advertisements of follow-on formulas are perceived by pregnant women and mothers in Italy. Materials and Methods: The study was carried out in 8 cities of the North, Centre and South of Italy and had two components: 1) a quantitative analysis of 562 self-administered questionnaires for mothers of children under 3 years of age, to explore their exposure to and perception of formula advertisements; 2) a qualitative analysis of 80 in-depth semi-structured interviews to 80 pregnant women, in their 32-36 weeks of gestation with no other children, on their understanding and perception of two advertisements for follow-on formulas. Results: Asked in the self-administered questionnaires whether they had ever come across advertisements of infant formulas, 81% of mothers reported that they had, despite the fact that such advertisements are prohibited by law. The qualitative interviews to pregnant women showed their inability to identify the advertised products at first glance due to the ambiguity of the numeral 2 and the presumed age of the portrayed babies; this confusion did not disappear after careful observation of the advertisements and reading of the text. Conclusions: Advertisements of follow-on formulas are perceived by many pregnant women and mothers as promoting infant formulas.
Published: 2016

11. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author: Momozawa, Y., Dmitrieva, J., Theatre, E., Deffontaine, V., Rahmouni, S., Charloteaux, B., Crins, F., Docampo, E., Elansary, M., Gori, A.S., Lecut, C., Mariman, R., Mni, M., Oury, C., Altukhov, I., Alexeev, D., Aulchenko, Y., Amininejad, L., Bouma, G., Hoentjen, F., Lowenberg, M., Oldenburg, B., Pierik, M.J., vander Meulen-de Jong, A.E., Woude, C.J. van der, Visschedijk, M.C., Lathrop, M., Hugot, J.P., Weersma, R.K., Vos, M. de, Franchimont, D., Vermeire, S., Kubo, M., Louis, E., Georges, M., Abraham, C., Achkar, J.P., Ahmad, T., Ananthakrishnan, A.N., Andersen, V., Anderson, C.A., Andrews, J.M., Annese, V., Aumais, G., Baidoo, L., Baldassano, R.N., Bampton, P.A., Barclay, M., Barrett, J.C., Bayless, T.M., Bethge, J., Bitton, A., Boucher, G., Brand, S., Brandt, B., Brant, S.R., Buning, C., Chew, A., Cho, J.H., Cleynen, I., Cohain, A., Croft, A., Daly, M.J., D'Amato, M., Danese, S., Jong, D. de, Denapiene, G., Denson, L.A., Devaney, K.L., Dewit, O., D'Inca, R., Dubinsky, M., Duerr, R.H., Edwards, C., Ellinghaus, D., Essers, J., Ferguson, L.R., Festen, E.A., Fleshner, P., Florin, T., Franke, A., Fransen, K., Gearry, R., Gieger, C., Glas, J., Goyette, P., Green, T., Griffiths, A.M., Guthery, S.L., Hakonarson, H., Halfvarson, J., Hanigan, K., Haritunians, T., Hart, A., Hawkey, C., Hayward, N.K., Hedl, M., Henderson, P., Hu, X.H., Huang, H.L., Hui, K.Y., Imielinski, M., Ippoliti, A., Jonaitis, L., Jostins, L., Karlsen, T.H., Kennedy, N.A., Khan, M.A., Kiudelis, G., Krishnaprasad, K., Kugathasan, S., Kupcinskas, L., Latiano, A., Laukens, D., Lawrance, I.C., Lee, J.C., Lees, C.W., Leja, M., Limbergen, J. van, Lionetti, P., Liu, J.Z., Mahy, G., Mansfield, J., Massey, D., Mathew, C.G., McGovern, D.P.B., Milgrom, R., Mitrovic, M., Montgomery, G.W., Mowat, C., Newman, W., Ng, A., Ng, S.C., Ng, S.M.E., Nikolaus, S., Ning, K., Nothen, M., Oikonomou, I., Palmieri, O., Parkes, M., Phillips, A., Ponsioen, C.Y., Potocnik, U., Prescott, N.J., Proctor, D.D., Radford-Smith, G., Rahier, J.F., Raychaudhuri, S., Regueiro, M., Rieder, F., Rioux, J.D., Ripke, S., Roberts, R., Russell, R.K., Sanderson, J.D., Sans, M., Satsangi, J., Schadt, E.E., Schreiber, S., Schulte, D., Schumm, L.P., Scott, R., Seielstad, M., Sharma, Y., Silverberg, M.S., Simms, L.A., Skieceviciene, J., Spain, S.L., Steinhart, A.H., Stempak, J.M., Stronati, L., Sventoraityte, J., Targan, S.R., Taylor, K.M., Velde, A. ter, Torkvist, L., Tremelling, M., Sommeren, S. van, Vasiliauskas, E., Verspaget, H.W., Walters, T., Wang, K., Wang, M.H., Wei, Z., Whiteman, D., Wijmenga, C., Wilson, D.C., Winkelmann, J., Xavier, R.J., Zhang, B., Zhang, C.K., Zhang, H., Zhang, W., Zhao, H.Y., Zhao, Z.Z., and Int IBD Genetics Consortium
Published: 2018

12. What is that 2?: Advertisements of follow-up formula and their perception by pregnant women and mothers in Italy

Author: Cattaneo A., Pani P., Carletti C., Guidetti M., Mutti V., Guidetti C., Knowles A., Barbiero C., Montico M., Locatelli M., Conti S., Pellegrini E., Papa O., Nespoli A., Bettinelli M. E., De Gioia C., Lelli M., Mascheroni R., Cetin I., Pileri P., Gatti R., Pompilio G., Ortenzi V., Stronati L., Giusti A., Spadea A., Rinaldi I., Galluzzo L., Vadacca P., Sarta S., Nibali S. C., Crisafulli R., Nibali R. C., Corrado F., Garraffa M., Di Pasquale M., Gallo M. C., Cattaneo, A, Pani, P, Carletti, C, Guidetti, M, Mutti, V, Guidetti, C, Knowles, A, Barbiero, C, Montico, M, Locatelli, M, Conti, S, Pellegrini, E, Papa, O, Nespoli, A, Bettinelli, M, De Gioia, C, Lelli, M, Mascheroni, R, Cetin, I, Pileri, P, Gatti, R, Pompilio, G, Ortenzi, V, Stronati, L, Giusti, A, Spadea, A, Rinaldi, I, Galluzzo, L, Vadacca, P, Sarta, S, Nibali, S, Crisafulli, R, Nibali, R, Corrado, F, Garraffa, M, Di Pasquale, M, and Gallo, M
Subjects: Marketing, Breast milk substitutes, Infant feeding, Follow-on formula, International code, Breast milk substitute
Abstract: Background: In most European countries advertisements of infant formula are forbidden, while those of follow-on formula are allowed. Recent researches carried out in Australia and Great Britain have suggested that advertisement of toddler formula is used by the producing industry as a line extension to promote infant and follow-on formulas. Objectives: The objective of the study is to assess how advertisements of follow-on formulas are perceived by pregnant women and mothers in Italy. Materials and Methods: The study was carried out in 8 cities of the North, Centre and South of Italy and had two components: 1) a quantitative analysis of 562 self-administered questionnaires for mothers of children under 3 years of age, to explore their exposure to and perception of formula advertisements; 2) a qualitative analysis of 80 in-depth semi-structured interviews to 80 pregnant women, in their 32-36 weeks of gestation with no other children, on their understanding and perception of two advertisements for follow-on formulas. Results: Asked in the self-administered questionnaires whether they had ever come across advertisements of infant formulas, 81% of mothers reported that they had, despite the fact that such advertisements are prohibited by law. The qualitative interviews to pregnant women showed their inability to identify the advertised products at first glance due to the ambiguity of the numeral 2 and the presumed age of the portrayed babies; this confusion did not disappear after careful observation of the advertisements and reading of the text. Conclusions: Advertisements of follow-on formulas are perceived by many pregnant women and mothers as promoting infant formulas.
Published: 2016

13. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author: Momozawa, Y. (Yukihide), Dmitrieva, J. (Julia), Théâtre, E. (Emilie), Deffontaine, V. (Valérie), Rahmouni, S. (Souad), Charloteaux, B. (Benoît), Crins, F. (François), Docampo, E. (Elisa), Elansary, M. (Mahmoud), Gori, A.-S. (Ann-Stephan), Lecut, C. (Christelle), Mariman, R. (Rob), Mni, M. (Myriam), Oury, C. (Cécile), Altukhov, I. (Ilya), Alexeev, D. (Dmitry), Aulchenko, Y.S. (Yurii), Amininejad, L. (Leila), Bouma, G. (Gerd), Hoentjen, F., Löwenberg, M., Oldenburg, B. (Bas), Pierik, M. (Marieke), Vander Meulen-De Jong, A.E. (Andrea E.), Woude, C.J. (Janneke) van der, Visschedijk, M. (Marijn), Lathrop, M. (Mark), Hugot, J.P. (J.), Weersma, R.K. (Rinse), De Vos, M. (Martine), Franchimont, D. (Denis), Vermeire, S. (Séverine), Kubo, M. (Michiaki), Louis, E. (Edouard), Georges, M. (Michel), Abraham, C. (Clara), Achkar, J.-P. (Jean-Paul), Ahmad, T. (Tariq), Ananthakrishnan, A.N. (Ashwin N.), Andersen, V. (Vibeke), Anderson, C.A. (Carl A.), Andrews, J.M. (Jane M.), Annese, V. (Vito), Aumais, G. (Guy), Baidoo, L. (Leonard), Baldassano, R.N. (Robert), Bampton, P.A. (Peter A.), Barclay, M. (Murray), Barrett, J.C. (Jeffrey), Bayless, T.M. (Theodore M.), Bethge, J. (Johannes), Bitton, A., Boucher, G. (Gabrielle), Brand, S. (Stephan), Brandt, B. (Berenice), Brant, S.R. (Steven R.), Büning, C. (Carsten), Chew, A. (Angela), Cho, J.H. (Judy H.), Cleynen, I. (Isabelle), Cohain, A. (Ariella), Croft, A. (Anthony), Daly, M.J. (Mark J.), D'Amato, M. (Mauro), Danese, S. (Silvio), De Jong, D.J. (Dirk J.), Denapiene, G. (Goda), Denson, L.A. (Lee A.), Devaney, K.L. (Kathy L.), Dewit, O. (Olivier), D'Inca, R. (Renata), Dubinsky, M. (Marla), Duerr, R.H. (Richard), Edwards, C. (Cathryn), Ellinghaus, D. (David), Essers, J.B. (Jonah), Ferguson, L.R. (Lynnette R.), Festen, E.A.M. (Eleonora), Fleshner, P. (Philip), Florin, T. (Tim), Franke, A. (Andre), Fransen, K. (Karin), Gearry, R. (Richard), Gieger, C. (Christian), Glas, J. (Jürgen), Goyette, P. (Philippe), Green, T. (Todd), Griffiths, A.M. (Anne), Guthery, S.L. (Stephen L.), Hakonarson, H. (Hakon), Halfvarson, J. (Jonas), Hanigan, K. (Katherine), Haritunians, T. (Talin), Hart, A. (Ailsa), Hawkey, S., Hayward, N.K. (Nicholas K.), Hedl, M. (Matija), Henderson, P. (Paul), Hu, X. (Xinli), Huang, H. (Hailiang), Hui, K.Y. (Ken Y.), Imielinski, M. (Marcin), Ippoliti, A. (Andrew), Jonaitis, L. (Laimas), Jostins, L. (Luke), Karlsen, T.H. (Tom), Kennedy, N.A. (Nicholas A.), Khan, M.A. (Mohammed Azam), Kiudelis, G. (Gediminas), Krishnaprasad, K. (Krupa), Kugathasan, S. (Subra), Kupcinskas, L. (Limas), Latiano, A. (Anna), Laukens, D. (Debby), Lawrance, I.C. (Ian C.), Lee, J.C. (James C.), Lees, C.W. (Charlie), Leja, M. (Marcis), Van Limbergen, J. (Johan), Lionetti, P. (Paolo), Liu, J.Z. (Jimmy Z.), Mahy, G. (Gillian), Mansfield, J. (John), Massey, D. (Dunecan), Mathew, J. (Joseph), McGovern, D.P.B. (Dermot P.B.), Milgrom, R. (Raquel), Mitrovic, M. (Mitja), Montgomery, G.W. (Grant W.), Mowat, C. (Craig), Newman, W.G. (William G.), Ng, A. (Aylwin), Ng, S.C. (Siew C.), Ng, S.M.E. (Sok Meng Evelyn), Nikolaus, S. (Susanna), Ning, K. (Kaida), Nöthen, M.M. (Markus), Oikonomou, I. (Ioannis), Palmieri, O. (Orazio), Parkes, M. (Miles), Phillips, A. (Anne), Ponsioen, C.Y. (Cyril), Potocnik, U. (Uros), Prescott, N.J. (Natalie J.), Proctor, D.D. (Deborah D.), Radford-Smith, G. (Graham), Rahier, J.F. (J.), Raychaudhuri, S. (Soumya), Regueiro, M. (Miguel), Rieder, F. (Florian), Rioux, J.D. (John), Ripke, S. (Stephan), Roberts, R. (Rebecca), Russell, R.K. (Richard), Sanderson, J.D. (Jeremy), Sans, S. (Susana), Satsangi, J. (Jack), Schadt, E.E. (Eric), Schreiber, S. (Stefan), Schulte, D. (Dominik), Schumm, L.P. (L. Philip), Scott, R. (Regan), Seielstad, M. (Mark), Sharma, Y. (Yashoda), Silverberg, M. (Mark), Simms, L.A. (Lisa A.), Skieceviciene, J. (Jurgita), Spain, S.L. (Sarah L.), Steinhart, A.H. (A. Hillary), Stempak, J.M. (Joanne M.), Stronati, L. (Laura), Sventoraityte, J. (Jurgita), Targan, S.R. (Stephan R.), Taylor, K.M. (Kirstin M.), Ter Velde, A. (Anje), Torkvist, L. (Leif), Tremelling, M. (Mark), Van Sommeren, S. (Suzanne), Vasiliauskas, E. (Eric), Verspaget, H.W., Walters, T. (Thomas), Wang, K. (Kai), Wang, M.-H. (Ming-Hsi), Wei, Z. (Zhi), Whiteman, D.C. (David C.), Wijmenga, C. (Cisca), Wilson, D.C. (David C.), Winkelmann, B., Xavier, R.J. (Ramnik J.), Zhang, B. (Bin), Zhang, C.K. (Clarence K.), Zhang, H. (Hu), Zhang, W. (Wei), Zhao, H. (Hongyu), Zhao, Z.Z. (Zhen Z.), Momozawa, Y. (Yukihide), Dmitrieva, J. (Julia), Théâtre, E. (Emilie), Deffontaine, V. (Valérie), Rahmouni, S. (Souad), Charloteaux, B. (Benoît), Crins, F. (François), Docampo, E. (Elisa), Elansary, M. (Mahmoud), Gori, A.-S. (Ann-Stephan), Lecut, C. (Christelle), Mariman, R. (Rob), Mni, M. (Myriam), Oury, C. (Cécile), Altukhov, I. (Ilya), Alexeev, D. (Dmitry), Aulchenko, Y.S. (Yurii), Amininejad, L. (Leila), Bouma, G. (Gerd), Hoentjen, F., Löwenberg, M., Oldenburg, B. (Bas), Pierik, M. (Marieke), Vander Meulen-De Jong, A.E. (Andrea E.), Woude, C.J. (Janneke) van der, Visschedijk, M. (Marijn), Lathrop, M. (Mark), Hugot, J.P. (J.), Weersma, R.K. (Rinse), De Vos, M. (Martine), Franchimont, D. (Denis), Vermeire, S. (Séverine), Kubo, M. (Michiaki), Louis, E. (Edouard), Georges, M. (Michel), Abraham, C. (Clara), Achkar, J.-P. (Jean-Paul), Ahmad, T. (Tariq), Ananthakrishnan, A.N. (Ashwin N.), Andersen, V. (Vibeke), Anderson, C.A. (Carl A.), Andrews, J.M. (Jane M.), Annese, V. (Vito), Aumais, G. (Guy), Baidoo, L. (Leonard), Baldassano, R.N. (Robert), Bampton, P.A. (Peter A.), Barclay, M. (Murray), Barrett, J.C. (Jeffrey), Bayless, T.M. (Theodore M.), Bethge, J. (Johannes), Bitton, A., Boucher, G. (Gabrielle), Brand, S. (Stephan), Brandt, B. (Berenice), Brant, S.R. (Steven R.), Büning, C. (Carsten), Chew, A. (Angela), Cho, J.H. (Judy H.), Cleynen, I. (Isabelle), Cohain, A. (Ariella), Croft, A. (Anthony), Daly, M.J. (Mark J.), D'Amato, M. (Mauro), Danese, S. (Silvio), De Jong, D.J. (Dirk J.), Denapiene, G. (Goda), Denson, L.A. (Lee A.), Devaney, K.L. (Kathy L.), Dewit, O. (Olivier), D'Inca, R. (Renata), Dubinsky, M. (Marla), Duerr, R.H. (Richard), Edwards, C. (Cathryn), Ellinghaus, D. (David), Essers, J.B. (Jonah), Ferguson, L.R. (Lynnette R.), Festen, E.A.M. (Eleonora), Fleshner, P. (Philip), Florin, T. (Tim), Franke, A. (Andre), Fransen, K. (Karin), Gearry, R. (Richard), Gieger, C. (Christian), Glas, J. (Jürgen), Goyette, P. (Philippe), Green, T. (Todd), Griffiths, A.M. (Anne), Guthery, S.L. (Stephen L.), Hakonarson, H. (Hakon), Halfvarson, J. (Jonas), Hanigan, K. (Katherine), Haritunians, T. (Talin), Hart, A. (Ailsa), Hawkey, S., Hayward, N.K. (Nicholas K.), Hedl, M. (Matija), Henderson, P. (Paul), Hu, X. (Xinli), Huang, H. (Hailiang), Hui, K.Y. (Ken Y.), Imielinski, M. (Marcin), Ippoliti, A. (Andrew), Jonaitis, L. (Laimas), Jostins, L. (Luke), Karlsen, T.H. (Tom), Kennedy, N.A. (Nicholas A.), Khan, M.A. (Mohammed Azam), Kiudelis, G. (Gediminas), Krishnaprasad, K. (Krupa), Kugathasan, S. (Subra), Kupcinskas, L. (Limas), Latiano, A. (Anna), Laukens, D. (Debby), Lawrance, I.C. (Ian C.), Lee, J.C. (James C.), Lees, C.W. (Charlie), Leja, M. (Marcis), Van Limbergen, J. (Johan), Lionetti, P. (Paolo), Liu, J.Z. (Jimmy Z.), Mahy, G. (Gillian), Mansfield, J. (John), Massey, D. (Dunecan), Mathew, J. (Joseph), McGovern, D.P.B. (Dermot P.B.), Milgrom, R. (Raquel), Mitrovic, M. (Mitja), Montgomery, G.W. (Grant W.), Mowat, C. (Craig), Newman, W.G. (William G.), Ng, A. (Aylwin), Ng, S.C. (Siew C.), Ng, S.M.E. (Sok Meng Evelyn), Nikolaus, S. (Susanna), Ning, K. (Kaida), Nöthen, M.M. (Markus), Oikonomou, I. (Ioannis), Palmieri, O. (Orazio), Parkes, M. (Miles), Phillips, A. (Anne), Ponsioen, C.Y. (Cyril), Potocnik, U. (Uros), Prescott, N.J. (Natalie J.), Proctor, D.D. (Deborah D.), Radford-Smith, G. (Graham), Rahier, J.F. (J.), Raychaudhuri, S. (Soumya), Regueiro, M. (Miguel), Rieder, F. (Florian), Rioux, J.D. (John), Ripke, S. (Stephan), Roberts, R. (Rebecca), Russell, R.K. (Richard), Sanderson, J.D. (Jeremy), Sans, S. (Susana), Satsangi, J. (Jack), Schadt, E.E. (Eric), Schreiber, S. (Stefan), Schulte, D. (Dominik), Schumm, L.P. (L. Philip), Scott, R. (Regan), Seielstad, M. (Mark), Sharma, Y. (Yashoda), Silverberg, M. (Mark), Simms, L.A. (Lisa A.), Skieceviciene, J. (Jurgita), Spain, S.L. (Sarah L.), Steinhart, A.H. (A. Hillary), Stempak, J.M. (Joanne M.), Stronati, L. (Laura), Sventoraityte, J. (Jurgita), Targan, S.R. (Stephan R.), Taylor, K.M. (Kirstin M.), Ter Velde, A. (Anje), Torkvist, L. (Leif), Tremelling, M. (Mark), Van Sommeren, S. (Suzanne), Vasiliauskas, E. (Eric), Verspaget, H.W., Walters, T. (Thomas), Wang, K. (Kai), Wang, M.-H. (Ming-Hsi), Wei, Z. (Zhi), Whiteman, D.C. (David C.), Wijmenga, C. (Cisca), Wilson, D.C. (David C.), Winkelmann, B., Xavier, R.J. (Ramnik J.), Zhang, B. (Bin), Zhang, C.K. (Clarence K.), Zhang, H. (Hu), Zhang, W. (Wei), Zhao, H. (Hongyu), and Zhao, Z.Z. (Zhen Z.)
Abstract: GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
Published: 2018
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14. The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

Author: Ashley Beecham, David A. Hafler, Colombe J, Ublick K, Stephen Sawcer, Marcus C. S. Lee, Adam Santaniello, An Goris, Frank Seibold, Xavier Montalban, G. Comi, Christiane Gasperi, Sandra D'Alfonso, Federica Esposito, Laurent Peyrin-Biroulet, Frauke Zipp, Ioanna Konidari, Elisabeth Gulowsen Celius, Achim Berthele, Amoroso A, Rogier Q. Hintzen, Johan Van Limbergen, Marieme Dembele, Fredrik Karpe, Zhang W, Robbins A, Moiola L, Annette Bang Oturai, Cristin McCabe, Filippo Martinelli-Boneschi, M Lindén, Keith R Edwards, Hanne F. Harbo, Zuccalà M, Marc Lémann, Felix Luessi, Noriko Isobe, Nadia Barizzone, Renata D'Incà, Croft A, Ioannis S. Vlachos, Frohlich I, Martinelli, Daniela Galimberti, Efthimios Dardiotis, Lisa F. Barcellos, Brendan T. Keenan, Maja Jagodic, Ferdinando Clarelli, Bénédicte Dubois, Nicholas A. Kennedy, Lohith Madireddy, Grant W. Montgomery, Tommy Olsson, Phil De Jager, Lo A, Peter A. Calabresi, Brandes A, Chris Cotsapas, Bakker Pd, Steffan D. Bos, Christina M. Lill, Karban A, Thoerner Lw, Tojo James, Wong G, Harald Peeters, M.-M. Hoshi, Roberts R, Fredrik Piehl, Lars Alfredsson, Giorgos M. Hadjigeorgiou, Bertrand Fontaine, Melissa Sorosina, Benedetti M, Maria Ban, Jorge R. Oksenberg, Howard L. Weiner, Ingrid Kockum, Mireia Sospedra, Taylor Km, Henrik Ullum, Izaura Lima Bomfim, Stronati L, Molyneux P, Replogle J, Stacy J. Caillier, Zhang H, Till F. M. Andlauer, Margaret A. Pericak-Vance, Jan Hillert, Luisa Bernardinelli, Taibo Li, Helle Bach Søndergaard, Ilijas Jelcic, Nikolaos A. Patsopoulos, Silvia Delgado, Cathy Schaefer, Thomas Korn, Laura Piccio, Mark Mühlau, Deborah D. Proctor, B. Hemmer, Elizabeth M. Bradshaw, Hysi P, Megan C Neville, Mary F. Davis, Dorlan J. Kimbrough, Jyoti Khadake, Jean-Pierre Hugot, David Gomez-Cabrero, Murray L. Barclay, Anne H. Cross, Kasper Lage, Stephen L. Hauser, A Compston, Zimmer A, Ivinson A, Anne Spurkland, Jonas Halfvarson, Charles C. White, Biberacher, Zarzycki O, Kathryn C. Fitzgerald, Finn Sellebjerg, Ellis Patrick, Andrea Zauli, Bruce V. Taylor, Maurizio Leone, Genevieve Lachance, Marta Olah, B. Cree, Manuel Comabella, Arie Levine, Domizia Vecchio, Mathias Chamaillard, Mark Lathrop, Clara Guaschino, Roland Martin, Hanigan K, Pierre-Antoine F. D. Gourraud, Maria Cimpean, Jonathan L. Haines, Dorothea Buck, Marco Salvetti, Per Soelberg Sørensen, Noel Lg, Mitja Mitrovic, Graeme J. Stewart, Benjamin Knier, Ellen Lathi, Cottone M, Laura Ferrè, Winn P, Duijn Cv, Monica Milla, Tune H. Pers, I. Oikonomou, An D, David R. Booth, Rebeix Ic, Clara P. Manrique, Massey D, Evelyn Ng Sm, Törkvist L, Daniele Cusi, Shoostari P, Vatn Mh, Paola Cavalla, Silvia Santoro, Gossum Av, Seema Kalra, Paul Rutgeerts, Clive Hawkins, Sandra Vukusik, Khan Ma, Hakon Hakonarson, Paul Henderson, Christiane Graetz, Julia Y Mescheriakova, Jean-François Rahier, Panteliadis I, Cristina Agliardi, Grummel, Jacob L. McCauley, Amie Baker, Janna Saarela, Sergio E. Baranzini, J W Thorpe, and Damotte
Subjects: 0303 health sciences, Microglia, Multiple sclerosis, Central nervous system, Biology, medicine.disease, Major histocompatibility complex, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine.anatomical_structure, Autoimmune Process, Immunology, medicine, biology.protein, Gene, 030217 neurology & neurosurgery, X chromosome, 030304 developmental biology
Abstract: We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.One Sentence Summary:We report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.
Published: 2017

15. P069 Zinc finger transcription factor ZNF281: a novel promoter of intestinal fibrosis?

Author: Pierdomenico, M., primary, Palone, F., additional, Mancuso, A.B., additional, Oliva, S., additional, Isoldi, S., additional, Cucchiara, S., additional, and Stronati, L., additional
Published: 2018
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16. P075 Lactobacillus reuteri cultured in green unicellular microalga Isochrysis rich in omega-3 provides a novel tool to limit AIEC growth and reduce gut inflammation

Author: Stronati, L., primary, Costanzo, M., additional, Cesi, V., additional, Palone, F., additional, Negroni, A., additional, Mancuso, A.B., additional, Isoldi, S., additional, Oliva, S., additional, and Cucchiara, S., additional
Published: 2018
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17. Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

Author: Costanzo, M., primary, Cesi, V., additional, Palone, F., additional, Pierdomenico, M., additional, Colantoni, E., additional, Leter, B., additional, Vitali, R., additional, Negroni, A., additional, Cucchiara, S., additional, and Stronati, L., additional
Published: 2018
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18. Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition

Author: Putignani, L, Del Chierico, F, Vernocchi, P, Cicala, M, Cucchiara, S, Dallapiccola, B, Dysbiotrack Study Group Collaborators: Alisi, A, Altomare, A, Aloi, M, Belzer, C, Cavalieri, D, Carapito, C, Comera, C, De Angelis, P, Delaere, F, De Filippo, C, de Vos, W, Dorè, J, Donati, C, Furlanello, C, Gasbarrini, A, Gil, C, Guarino, M, Hugot, Jp, Juste, C, Knol, J, Koletzko, B, Monnet, V, Nobili, V, Oozeer, R, Scaldaferri, F, Stensvold, Cr, Stronati, L, Tack, J, Theodoridis, G, Torre, G, and Urbani, A.
Subjects: digestive system, Gut Microbiota, Dysbiosis, Inflammatory Bowel Disease, Irritable Bowel Syndrome, Childhood
Published: 2016

19. RIP3, a regulator of necroptosis, promotes inflammation by increasing cytokine and inflammasome molecule levels as well as altering membrane permeability in intestinal epithelial cells

Author: Colantoni, E., primary, Negroni, A., additional, Stronati, L., additional, Cesi, V., additional, Costanzo, M., additional, Palone, F., additional, Pierdomenico, M., additional, Mallardo, S., additional, and Cucchiara, S., additional
Published: 2017
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20. NOD2 induces autophagy to control AIEC bacteria infectiveness in intestinal epithelial cells

Author: Negroni, A., primary, Colantoni, E., additional, Pierdomenico, M., additional, Costanzo, M., additional, Aloi, M., additional, Cucchiara, S., additional, Civitelli, F., additional, and Stronati, L., additional
Published: 2016
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21. Gut and liver in obese children: Beware of that pair

Author: Mennini, M., primary, Ferrari, F., additional, Morcaldi, L., additional, Principessa, L., additional, Stronati, L., additional, and Cucchiara, S., additional
Published: 2016
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22. Fecal HMGB1 reveals microscopic inflammation in adult and pediatric patients with inflammatory bowel disease who are in clinical and endoscopic remission

Author: Palone, F., primary, Vitali, R., additional, Mennini, M., additional, Armuzzi, A., additional, D’Incà, R., additional, Aloi, M., additional, Oliva, S., additional, Dilillo, A., additional, Cucchiara, S., additional, and Stronati, L., additional
Published: 2016
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23. Omega 3, Lactobacillus reuteri and vitamin D collaborate in diminishing gut inflammation

Author: Stronati, L., primary, Cesi, V., additional, Costanzo, M., additional, Palone, F., additional, Pierdomenico, M., additional, Colantoni, E., additional, Aloi, M., additional, Viola, F., additional, and Cucchiara, S., additional
Published: 2016
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24. OC.02.5 EXPERIMENTAL COMPARISON BETWEEN TWO MARKERS OF INTESTINAL INFLAMMATION, HMGB1 AND FECAL CALPROTECTIN, IN INFLAMMATORY BOWEL DISEASES

Author: Barberio, B., primary, D'Inca, R., additional, Stronati, L., additional, Vitali, R., additional, Palone, F., additional, Cucchiara, S., additional, and Sturniolo, G.C., additional
Published: 2016
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25. Whole Exome Sequencing of very early onset ulcerative colitis patients identifies new variants in candidate genes

Author: Palmieri, O., primary, Aloi, M., additional, Prudente, S., additional, Mazza, T., additional, Stronati, L., additional, Corritore, G., additional, Latiano, T., additional, Bossa, F., additional, Andriulli, A., additional, Cucchiara, S., additional, and Latiano, A., additional
Published: 2015
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26. Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat

Author: Della Corte, C., primary, Mosca, A., additional, Majo, F., additional, Lucidi, V., additional, Panera, N., additional, Giglioni, E., additional, Monti, L., additional, Stronati, L., additional, Alisi, A., additional, and Nobili, V., additional
Published: 2015
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27. Krill oil, vitamin D and Lactobacillus reutericooperate to reduce gut inflammation

Author: Costanzo, M., Cesi, V., Palone, F., Pierdomenico, M., Colantoni, E., Leter, B., Vitali, R., Negroni, A., Cucchiara, S., and Stronati, L.
Published: 2018
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28. Intestinal inflammation alters the expression of hepatic bile acid receptors causing liver impairment

Author: Roberta Vitali, Marina Aloi, Ilaria Laudadio, Francesca Palone, Anna Negroni, Eleonora Colantoni, Salvatore Cucchiara, Salvatore Oliva, Noemi Fiaschini, Laura Stronati, Negroni, A., Fiaschini, N., Palone, F., Vitali, R., Colantoni, E., Laudadio, I., Oliva, S., Aloi, M., Cucchiara, S., and Stronati, L.
Subjects: medicine.medical_specialty, medicine.drug_class, Receptor expression, Inflammation, liver, digestive system, Inflammatory bowel disease, Bile Acids and Salts, Mice, 03 medical and health sciences, 0302 clinical medicine, inflammatory bowel disease, 030225 pediatrics, Internal medicine, medicine, Animals, Humans, Colitis, Child, Receptor, bile acid receptors, gut, inflammation, Bile acid, business.industry, Liver Diseases, Gastroenterology, medicine.disease, G protein-coupled bile acid receptor, digestive system diseases, Mice, Inbred C57BL, Endocrinology, Pediatrics, Perinatology and Child Health, Hepatic stellate cell, 030211 gastroenterology & hepatology, Caco-2 Cells, medicine.symptom, business
Abstract: Objectives The gut-liver axis has been recently investigated in depth in relation to intestinal and hepatic diseases. Key actors are bile acid (BA) receptors, as farnesoid-X-receptor (FXR), pregnane-X-receptor (PXR), and G-protein-coupled-receptor (GPCR; TGR5), that control a broad range of metabolic processes as well as inflammation and fibrosis. The present study aims to investigate the impact of intestinal inflammation on liver health with a focus on FXR, PXR, and TGR5 expression. The strategy to improve liver health by reducing gut inflammation is also considered. Modulation of BA receptors in the inflamed colonic tissues of inflammatory bowel disease (IBD) pediatric patients is analyzed. Methods A dextran sodium sulphate (DSS) colitis animal model was built. Co-cultures with Caco2 and HepG2 cell lines were set up. Modulation of BA receptors in biopsies of IBD pediatric patients was assessed by real-time PCR and immunohistochemistry. Results Histology showed inflammatory cell infiltration in the liver of DSS mice, where FXR and PXR were significantly decreased and oxidative stress was increased. Exposure of Caco2 to inflammatory stimuli resulted in the reduction of BA receptor expression in HepG2. Caco2 treatment with dipotassium glycyrrhizate (DPG) reduced these effects on liver cells. Inflamed colon of patients showed altered FXR, PXR, and TGR5 expression. Conclusions This study strongly suggests that gut inflammation affects hepatic cells by altering BA receptor levels as well as increasing the production of pro-inflammatory cytokines and oxidative stress. Hence, reducing gut inflammation is needed not only to improve the intestinal disease but also to protect the liver.
Published: 2020

29. Dipotassium Glycyrrhizate Improves Intestinal Mucosal Healing by Modulating Extracellular Matrix Remodeling Genes and Restoring Epithelial Barrier Functions

Author: Salvatore Cucchiara, Laura Stronati, Anna Barbara Mancuso, Roberta Vitali, Eleonora Colantoni, Francesca Palone, Vincenzo Cesi, Sara Isoldi, Anna Negroni, Stronati, L., Palone, F., Negroni, A., Colantoni, E., Mancuso, A. B., Cucchiara, S., Cesi, V., Isoldi, S., and Vitali, R.
Subjects: 0301 basic medicine, MMP9, Extracellular matrix, Mice, 0302 clinical medicine, Immunology and Allergy, HMGB1 Protein, Intestinal Mucosa, CCL12, DSS-induced colitis, Original Research, dipotassium glycyrrhizate, biology, Chemistry, Colitis, Extracellular Matrix, Cell biology, CXCL1, Cytokines, Female, medicine.symptom, HT29 Cells, DSS-induced coliti, lcsh:Immunologic diseases. Allergy, VTN, Immunology, Inflammation, HMGB1, Cell Line, mucosal healing, 03 medical and health sciences, plaur, Cell Line, Tumor, medicine, Animals, Humans, Wound Healing, Epithelial Cells, Glycyrrhizic Acid, medicine.disease, Dipotassium glycyrrhizate, Mucosal healing, Plaur, Mice, Inbred C57BL, 030104 developmental biology, biology.protein, Caco-2 Cells, lcsh:RC581-607, Wound healing, 030215 immunology
Abstract: Gut mucosal healing (MH) is considered a key therapeutic target and prognostic parameter in the management of inflammatory bowel disease (IBD). The dipotassium glycyrrhizate (DPG), a salt of the glycoconjugated triterpene glycyrrhizin, has been shown to inhibit the High Mobility Group Box 1 (HMGB1) protein, an allarmin strongly implicated in the pathogenesis of most inflammatory and auto-immune disorders. Here we discuss new insights on how DPG acts on MH comparing the acute phase and the recovery phase from experimental colitis in mice. We found that DPG strongly accelerates MH by differently regulating pro-inflammatory (CXCL1, CXCL3, CXCL5, PTGS2, IL-1β, IL-6, CCL12, CCL7) and wound healing (COL3A1, MMP9, VTN, PLAUR, SERPINE, CSF3, FGF2, FGF7, PLAT, TIMP1) genes as observed only during the recovery phase of colitis. Relevant issue is the identification of extracellular matrix (ECM) remodeling genes, VTN, and PLAUR, as crucial genes to achieve MH during DPG treatment. Furthermore, a noticeable recovery of intestinal epithelial barrier structural organization, wound repair ability, and functionality is observed in two human colorectal adenocarcinoma cell lines exposed to DPG during inflammation. Thus, our study identifies DPG as a potent tool for controlling intestinal inflammation and improving MH.
Published: 2019

30. Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders

Author: Chiara Alfonsi, Vincenzo Cesi, Valerio Fulci, Sara Isoldi, Salvatore Cucchiara, Claudia Carissimi, Laura Stronati, Francesca Palone, Francesco Cardona, Ilaria Laudadio, Carissimi, C., Laudadio, I., Palone, F., Fulci, V., Cesi, V., Cardona, F., Alfonsi, C., Cucchiara, S., Isoldi, S., and Stronati, L.
Subjects: Male, Lipopolysaccharide, Gastrointestinal Diseases, autism spectrum disorders, Inflammation, gut microbiota, metagenomics, inflammation, hmgb1, Comorbidity, Gut flora, behavioral disciplines and activities, Feces, 03 medical and health sciences, chemistry.chemical_compound, Child Development, 0302 clinical medicine, Immune system, Autism spectrum disorders, Gut microbiota, HMGB1, Metagenomics, mental disorders, Escherichia coli, medicine, Humans, Autism spectrum disorder, Child, Phenylpropionates, Hepatology, biology, Catabolism, business.industry, Gastroenterology, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, chemistry, Case-Control Studies, Child, Preschool, 030220 oncology & carcinogenesis, Immunology, Cytokines, Biomarker (medicine), Autism, Female, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, medicine.symptom, business
Abstract: Background and Aims Recent evidence implicates gut microbiota (GM) and immune alterations in autism spectrum disorders (ASD). We assess GM profile and peripheral levels of immunological, neuronal and bacterial molecules in ASD children and controls. Alarmin HMGB1 was explored as a non-invasive biomarker to monitor gastrointestinal (GI) symptoms. Methods Thirty ASD children and 14 controls entered into the study. GM metagenomic analysis was performed for 16 ASD patients and 7 controls. GM functional profile was assessed by GO term analysis. Blood levels of IL-1β, TNFα, TGFβ, IL-10, INFγ, IL-8, lipopolysaccharide, Neurotensin, Sortilin1 and GSSG/GSH ratio were analyzed in all subjects by ELISA. Fecal HMGB1 was analyzed by Western blot. Results We observed a significant decrease in bacterial diversity. Furthermore, 82 GO terms underrepresented in ASD. Four of them pointed at 3,3 phenylpropionate catabolism and were imputable to Escherichia coli (E. coli) group. Serum levels of TNFα, TGFβ, NT, and SORT-1 increased in ASD patients. Fecal levels of HMGB1 correlated with GI sign severity in ASD children. Conclusions We suggest that a decrease of E. coli might affect the propionate catabolism in ASD. We report occurrence of peripheral inflammation in ASD children. We propose fecal HMGB1 as a non-invasive biomarker to detect GI symptoms.
Published: 2019

31. Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines

Author: Annalisa Crudele, Claudia Della Corte, Valerio Nobili, Laura Stronati, Anna Alisi, Nadia Panera, and Stronati, L.
Subjects: 0301 basic medicine, FGF21, leptin, IL-6, resistin, hepatokines, adiponectin, fetuin-A, Adipocytokines, TNF-α, NAFLD, Adipose tissue, Adipokine, Disease, Adipocytokine, Chronic liver disease, 03 medical and health sciences, 0302 clinical medicine, Adipokines, Non-alcoholic Fatty Liver Disease, Risk Factors, hepatokine, medicine, Animals, Humans, Obesity, Hepatology, Adiponectin, business.industry, Fatty liver, Gastroenterology, Protective Factors, medicine.disease, 030104 developmental biology, Adipose Tissue, Liver, Immunology, Disease Progression, 030211 gastroenterology & hepatology, Inflammation Mediators, Steatohepatitis, business, Signal Transduction
Abstract: Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions. © 2015 Taylor & Francis.
Published: 2015

32. Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

Author: Anna Negroni, Laura Stronati, Salvatore Cucchiara, Eleonora Colantoni, Negroni, A., Colantoni, E., Cucchiara, S., and Stronati, L.
Subjects: 0301 basic medicine, Programmed cell death, Necroptosis, lcsh:QR1-502, gastroenterology, Inflammation, Review, Biology, Medical Oncology, Biochemistry, lcsh:Microbiology, 03 medical and health sciences, RIPK1, 0302 clinical medicine, inhibitors, Intestinal Neoplasms, medicine, cancer, Animals, Humans, Molecular Targeted Therapy, inflammation, intestinal diseases, programmed cell death, Molecular Biology, Tissue homeostasis, Innate immune system, Intestinal epithelium, Gastroenteritis, Intestines, 030104 developmental biology, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, medicine.symptom
Abstract: Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.
Published: 2020

33. LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease

Author: Chiara Rychlicki, Stefania Petrini, Gianluca Svegliati-Baroni, Cristiano De Stefanis, Sara Ceccarelli, Marco Mina, Nadia Panera, Daniela Gnani, Salvatore Cucchiara, Giovanni Musso, Valerio Nobili, Anna Alisi, Laura Agostinelli, Cesare Furlanello, Laura Stronati, Annalisa Crudele, Giovannella Bruscalupi, and Stronati, L.
Subjects: Lipopolysaccharides, Liver Cirrhosis, Male, Time Factors, Transcription, Genetic, Fibrosi, medicine.medical_treatment, Interleukin-1beta, LITAF, p38 Mitogen-Activated Protein Kinases, Mice, Non-alcoholic Fatty Liver Disease, Fibrosis, LPS, NAFLD, Pathology Section, fibrosis, inflammation, Promoter Regions, Genetic, Mice, Inbred BALB C, Fatty liver, Nuclear Proteins, Up-Regulation, Pathology section, DNA-Binding Proteins, Phenotype, Cytokine, Liver, Oncology, Cytokines, Female, RNA Interference, Tumor necrosis factor alpha, Inflammation Mediators, medicine.symptom, Inflammation, Signal Transduction, Transfection, Cell Line, Hepatic Stellate Cells, medicine, Animals, Humans, Gene silencing, Protein Kinase Inhibitors, Binding Sites, business.industry, medicine.disease, Research Paper: Pathology, Immunology, Hepatic stellate cell, Steatohepatitis, business, Transcription Factors
Abstract: Lipopolysaccharide (LPS) is currently considered one of the major players in non-alcoholic fatty liver disease (NAFLD) pathogenesis and progression. Here, we aim to investigate the possible role of LPS-induced TNF-α factor (LITAF) in inducing a pro-inflammatory and pro-fibrogenic phenotype of non-alcoholic steatohepatitis (NASH). We found that children with NAFLD displayed, in different liver-resident cells, an increased expression of LITAF which correlated with histological traits of hepatic inflammation and fibrosis. Total and nuclear LITAF expression increased in mouse and human hepatic stellate cells (HSCs). Moreover, LPS induced LITAF-dependent transcription of IL-1β, IL-6 and TNF-α in the clonal myofibroblastic HSC LX-2 cell line, and this effect was hampered by LITAF silencing. We showed, for the first time in HSCs, that LITAF recruitment to these cytokine promoters is LPS dependent. However, preventing LITAF nuclear translocation by p38MAPK inhibitor, the expression of IL-6 and TNF-α was significantly reduced with the aid of p65NF-ĸB, while IL-1β transcription exclusively required LITAF expression/activity. Finally, IL-1β levels in plasma mirrored those in the liver and correlated with LPS levels and LITAF-positive HSCs in children with NASH. In conclusion, a more severe histological profile in paediatric NAFLD is associated with LITAF over-expression in HSCs, which in turn correlates with hepatic and circulating IL-1β levels outlining a panel of potential biomarkers of NASH-related liver damage. The in vitro study highlights the role of LITAF as a key regulator of the LPS-induced pro-inflammatory pattern in HSCs and suggests p38MAPK inhibitors as a possible therapeutic approach against hepatic inflammation in NASH.
Published: 2015

34. Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway

Author: Valerio Nobili, Gianfranco Alpini, Guido Carpino, Anna Alisi, Paolo Onori, Laura Stronati, Anastasia Renzi, Cristiano De Stefanis, Rita De Vito, Eugenio Gaudio, Antonio Franchitto, and Stronati, L.
Subjects: 0301 basic medicine, Male, Pathology, Steatosis, Biopsy, Anti-Inflammatory Agents, lcsh:Medicine, Pathology and Laboratory Medicine, Pediatrics, Cytopathology, White Blood Cells, 0302 clinical medicine, Animal Cells, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, hepatic progenitor cell, Medicine and Health Sciences, Macrophage, Phosphorylation, lcsh:Science, Child, Immune Response, beta Catenin, Liver injury, Multidisciplinary, Liver Diseases, Stem Cells, Fatty liver, 3. Good health, medicine.anatomical_structure, Liver, Docosahexaenoic acid, Hepatocyte, Disease Progression, 030211 gastroenterology & hepatology, Female, Cellular Types, Anatomy, Research Article, Signal Transduction, medicine.medical_specialty, liver, non-alcoholic fatty liver disease, Adolescent, Docosahexaenoic Acids, Kupffer Cells, Immune Cells, Immunology, Macrophage polarization, Surgical and Invasive Medical Procedures, Gastroenterology and Hepatology, Biology, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Wnt3A Protein, medicine, Humans, Progenitor cell, Inflammation, Blood Cells, Macrophages, lcsh:R, Biology and Life Sciences, Cell Biology, Macrophage Activation, medicine.disease, Fibrosis, Fatty Liver, 030104 developmental biology, Gene Expression Regulation, Anatomical Pathology, Hepatocytes, lcsh:Q, Developmental Biology
Abstract: Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric nonalcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included. 20 out of 32 patients were treated with docosahexaenoic acid for 18 months and biopsies at the baseline and after 18 months were included. Hepatic progenitor cell activation, macrophage subsets and Wnt/β-catenin pathway were evaluated by immunohistochemistry and immunofluorescence. Our results indicated that in pediatric non-alcoholic fatty liver disease, pro-inflammatory macrophages were the predominant subset. Macrophage polarization was correlated with Non-alcoholic fatty liver disease Activity Score, ductular reaction, and portal fibrosis; docosahexaenoic acid treatment determined a macrophage polarization towards an anti-inflammatory phenotype in correlation with the reduction of serum inflammatory cytokines, with increased macrophage apoptosis, and with the upregulation of macrophage Wnt3a expression; macrophage Wnt3a expression was correlated with β-catenin phosphorylation in hepatic progenitor cells and signs of commitment towards hepatocyte fate. In conclusion, macrophage polarization seems to have a key role in the progression of pediatric non-alcoholic fatty liver disease; the modulation of macrophage polarization could drive hepatic progenitor cell response by Wnt3a production. © 2016 Carpino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Published: 2016

35. NOD2 Is Regulated by MIR-320 in Physiological Conditions but this Control Is Altered in Inflamed Tissues of Patients with Inflammatory Bowel Disease

Author: Maria Pierdomenico, Manuela Costanzo, Enrica Prete, Salvatore Cucchiara, Roberta Vitali, Laura Stronati, Vincenzo Cesi, Salvatore Oliva, Marina Aloi, Stronati, L., Costanzo, M., Prete, E., Vitali, R., and Cesi, V.
Subjects: 0301 basic medicine, Male, Nod2 Signaling Adaptor Protein, Fluorescent Antibody Technique, pediatric IBD, Inflammatory bowel disease, Immunoenzyme Techniques, Crohn Disease, NOD2, miRNAs, inflammation, innate immunity, Immunology and Allergy, Child, Cells, Cultured, Regulation of gene expression, Reverse Transcriptase Polymerase Chain Reaction, Gastroenterology, Transfection, Prognosis, Child, Preschool, Cytokines, Female, medicine.symptom, HT29 Cells, Adolescent, Blotting, Western, Inflammation, Biology, Real-Time Polymerase Chain Reaction, Proinflammatory cytokine, 03 medical and health sciences, microRNA, medicine, Humans, RNA, Messenger, miRNA, medicine.disease, digestive system diseases, Immunity, Innate, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Immunology, Cancer research, Colitis, Ulcerative, Ex vivo, Follow-Up Studies
Abstract: Background: Large evidence supports the role of microRNAs as new important inflammatory mediators by regulating both the adaptive and innate immunity. In the present study, we speculated that miR-320 controls NOD2 (nucleotide-binding oligomerization domain) expression, because it contains multiple binding sites in the 3′-untranslated region of the gene. NOD2, the first gene associated to increased susceptibility to Crohn's disease, is a cytosolic receptor that senses wall peptides of bacteria and promotes their clearance through initiation of a proinflammatory transcriptional program. This study aims at demonstrating that NOD2 is a target of miR-320 as well as investigating the role of inflammation in modulating the miR-320 control on NOD2 expression and analyzing miR-320 expression in intestinal biopsies of children with inflammatory bowel disease. Methods: The colonic adenocarcinoma cell line HT29 was used to assess the miR-320-mediated regulation of NOD2 expression. MiR-320 and NOD2 expression were analyzed in mucosal samples of 40 children with inflammatory bowel disease. Results: During inflammation, NOD2 expression is inversely correlated with miR-320 expression in vitro and ex vivo. Exogenous miR-320 transfection in HT29 cells leads to a significant decrease of NOD2 expression, whereas the miR-320 inhibitor transfection leads to increase of NOD2 expression, nuclear translocation of nuclear factor B, and activation of downstream cytokines. Conclusions: We show for the first time that NOD2 expression is under the control of miR-320. We also show in vitro and ex vivo that inflammation induces a decrease of miR-320 and the latter correlates negatively with NOD2 expression. © 2016 Crohn's & Colitis Foundation of America, Inc.
Published: 2016

36. Krill oil reduces intestinal inflammation by improving epithelial integrity and impairing adherent-invasive Escherichia coli pathogenicity

Author: Beatrice Leter, Francesca Palone, Vincenzo Cesi, Laura Stronati, Anna Negroni, Salvatore Oliva, Manuela Costanzo, Enrica Prete, Salvatore Cucchiara, Stronati, L., Palone, F., Negroni, A., Prete, E., Cesi, V., and Costanzo, M.
Subjects: 0301 basic medicine, Cell Survival, Inflammation, Biology, Antarctic krill, Intestinal epithelium, Luminal bacteria, Krill oil, Bacterial Adhesion, Microbiology, 03 medical and health sciences, HT29 Cells, Interferon-gamma, Mice, Gentamicin protection assay, Fatty Acids, Omega-3, medicine, Cell Adhesion, Escherichia coli, Animals, Humans, RNA, Messenger, Escherichia coli Infections, Wound Healing, Microbial Viability, Hepatology, Cell Death, Tumor Necrosis Factor-alpha, Interleukin-8, Gastroenterology, Cadherins, Actins, 030104 developmental biology, RAW 264.7 Cells, Caco-2, Zonula Occludens-1 Protein, Tumor necrosis factor alpha, medicine.symptom, Caco-2 Cells, Wound healing, Euphausiacea
Abstract: Background: Krill oil is a marine derived oil rich in phospholipids, astaxanthin and omega-3 fatty acids. Several studies have found benefits of krill oil against oxidative and inflammatory damage. Aims: We aimed at assessing the ability of krill oil to reduce intestinal inflammation by improving epithelial barrier integrity, increasing cell survival and reducing pathogenicity of adherent-invasive Escherichia coli. Methods: CACO2 and HT29 cells were exposed to cytomix (TNFα and IFNγ) to induce inflammation and co-exposed to cytomix and krill oil. E-cadherin, ZO-1 and F-actin levels were analyzed by immunofluorescence to assess barrier integrity. Scratch test was performed to measure wound healing. Cell survival was analyzed by flow cytometry. Adherent-invasive Escherichia coli LF82 was used for adhesion/invasion assay. Results: In inflamed cells E-cadherin and ZO-1 decreased, with loss of cell-cell adhesion, and F-actin polymerization increased stress fibres; krill oil restored initial conditions and improved wound healing, reduced bacterial adhesion/invasion in epithelial cells and survival within macrophages; krill oil reduced LF82-induced mRNA expression of pro-inflammatory cytokines. Conclusions: Krill oil improves intestinal barrier integrity and epithelial restitution during inflammation and controls bacterial adhesion and invasion to epithelial cells. Thus, krill oil may represent an innovative tool to reduce intestinal inflammation. © 2015 Editrice Gastroenterologica Italiana S.r.l.
Published: 2015

37. Apoptosis, necrosis, and necroptosis in the gut and intestinal homeostasis

Author: Laura Stronati, Salvatore Cucchiara, Anna Negroni, Stronati, L., and Negroni, A.
Subjects: Programmed cell death, Necrosis, Necroptosis, Immunology, Apoptosis, Review Article, Biology, Immune system, Cell Biology, Intestinal mucosa, medicine, lcsh:Pathology, Animals, Homeostasis, Humans, Intestinal Mucosa, Tissue homeostasis, Intestinal epithelium, Immunity, Innate, Epithelium, Cell biology, Intestines, medicine.anatomical_structure, medicine.symptom, lcsh:RB1-214
Abstract: Intestinal epithelial cells (IECs) form a physiochemical barrier that separates the intestinal lumen from the host's internal milieu and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota. Moreover, IECs are strongly involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This review is focused on previous reports on different forms of cell death in intestinal epithelium. © 2015 Anna Negroni et al.
Published: 2015

38. Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation

Author: Francesca Palone, Anna Negroni, Maria Pierdomenico, Salvatore Oliva, Marina Aloi, Laura Stronati, Roberta Vitali, Salvatore Cucchiara, Stronati, L., Negroni, A., Pierdomenico, M., Palone, F., and Vitali, R.
Subjects: Lipopolysaccharides, Nitric Oxide Synthase Type II, Inflammation, Oxidative phosphorylation, AMP-Activated Protein Kinases, Pharmacology, medicine.disease_cause, HMGB1, Biochemistry, Cell Line, Intestinal mucosa, AMP-activated protein kinase, medicine, Animals, HMGB1 Protein, Intestinal Mucosa, biology, Chemistry, Macrophages, AMPK, Colitis, Glycyrrhizic Acid, Mice, Inbred C57BL, Disease Models, Animal, Oxidative Stress, Mechanism of action, Cyclooxygenase 2, biology.protein, Chemical compound studied in this article Dipotassium glycyrrhizate (PubChem CID: 656852), Female, medicine.symptom, Oxidative stress, Signal Transduction
Abstract: Aims Oxidative stress and inflammation are always associated. Appropriate management of oxidative mediators may represent a therapeutic strategy to reduce inflammation, and use of antioxidant can be protective against inflammatory diseases. Glycyrrhizin (GL) plays an anti-inflammatory and antioxidant effect by inhibiting high mobility group box 1 (HMGB1) or 11-β-hydroxysteroid dehydrogenase type II (11βHSD2) enzyme. In this study, the potential role of dipotassium glycyrrhizate (DPG), a salt of GL, to reduce oxidative stress in intestinal inflammatory condition was investigated in vivo and the mechanism of action of DPG was studied in vitro. Results In a colitis mouse model DPG affected oxidative stress reducing iNOS and COX-2 expression, as well as NO and PGE2 levels. By means of LPS-stimulated macrophages we found that DPG inhibited the expression of pro-inflammatory cytokines and reduced iNOS and COX-2 expression in a time dependent manner, through two different ways of signal. DPG reduced, at a later time, both iNOS and COX-2, through a mechanism HMGB1-dependent, and at an earlier time only COX-2, through a mechanism AMP-activated kinase (AMPK)-phosphorylation-mediated. Conclusion DPG has a protective effect on colitis and inflammation through the inhibition of oxidative stress. This study clarifies the two-ways mechanism by which DPG inhibits iNOS and COX-2 during inflammation and demonstrates for the first time that AMPK is a target of DPG. Uncovering this mechanism is significant to clarify the relationship between energy homeostasis and anti-oxidative responses and suggests that DPG could play a relevant role in the development of new therapy against inflammatory diseases associated to oxidative stress. © 2015 Elsevier Inc. All rights reserved.
Published: 2015

39. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach

Author: Milena Villarini, Silvano Monarca, Cristina Fatigoni, Laura Stronati, Laura Sabatini, Elisabetta Ceretti, Mariella Carrieri, Giuseppe Mastrangelo, Maria Giuseppa Grollino, Massimo Appolloni, Anna Barbieri, Sofia Pavanello, Giovanni Battista Bartolucci, Roberta Bonfiglioli, Francesca Mussi, Massimo Moretti, Luca Dominici, Stronati, L., Appolloni, M., Grollino, M. G., Moretti, Massimo, Grollino, Maria Giuseppa, Pavanello, Sofia, Bonfiglioli, Roberta, Villarini, Milena, Appolloni, Massimo, Carrieri, Mariella, Sabatini, Laura, Dominici, Luca, Stronati, Laura, Mastrangelo, Giuseppe, Barbieri, Anna, Fatigoni, Cristina, Bartolucci, Giovanni Battista, Ceretti, Elisabetta, Mussi, Francesca, and Monarca, Silvano
Subjects: Adult, medicine.medical_specialty, Cyclophosphamide, Antineoplastic drugs, Occupational exposure, Genotoxic hazard, Micronuclei, Chromosome aberrations, GSTM1 and GSTT1 polymorphisms, Antineoplastic Agents, Urine, Nursing Staff, Hospital, Pharmacology, Dermal exposure, Hospital, Internal medicine, Humans, Medicine, Antineoplastic drug, Lymphocytes, GSTM1 and GSTT1 polymorphism, Biomarkers, Chromosome Aberrations, DNA Damage, Environmental Monitoring, Female, Italy, Micronuclei, Chromosome-Defective, Occupational Exposure, Oncology Nursing, business.industry, Environmental and Occupational Health, Public Health, Environmental and Occupational Health, Metabolic detoxification, Micronucleus test, Antineoplastic Drugs, Biomarker (medicine), Nursing Staff, Public Health, Chromosome aberration, business, Chromosome-Defective, medicine.drug
Abstract: Objectives: Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. Methods: Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses’ clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. Results: We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p
Published: 2015

40. Inhibition of intestinal inflammation and fibrosis by Scutellaria Baicalensis georgi and Boswellia serrata in human epithelial cells and fibroblasts.

Author: Laudadio I, Leter B, Palone F, Cucchiara S, Carissimi C, Scafa N, Secci D, Vitali R, and Stronati L
Subjects: Humans, Anti-Inflammatory Agents pharmacology, Cytokines metabolism, Intestinal Mucosa drug effects, Intestinal Mucosa pathology, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases metabolism, HT29 Cells, Cell Line, Inflammation pathology, Inflammation drug therapy, Actins metabolism, Snail Family Transcription Factors metabolism, Plant Extracts pharmacology, Epithelial Cells drug effects, Epithelial Cells pathology, Epithelial Cells metabolism, Scutellaria baicalensis chemistry, Fibroblasts drug effects, Fibroblasts metabolism, Fibroblasts pathology, Boswellia chemistry, Fibrosis
Abstract: Objective and Rationale: Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach. Previous results suggest that Scutellaria baicalensis Georgi (SBG) and Boswellia serrata (BS) display anti-inflammatory properties. The aim of this study was to investigate in intestinal epithelial cells and fibroblasts the anti-inflammatory and anti-fibrotic potential of SBG and BS, alone or in combination., Methods: Human colorectal adenocarcinoma cells (HT29), human intestinal epithelial cells (HIEC6) and human colon fibroblasts (CCD-18Co) were used. Cells were pretreated with SBG and BS and then exposed to pro-inflammatory and pro-fibrotic cytokines., Results: SBG and BS extracts significantly decreased pro-inflammatory cytokine expression and improved epithelial restitution in HT29 and HIEC6 cells. Besides, fibrotic marker expression, including SNAIL, ACTA2, ZNF281, was strongly reduced. Colon myofibroblasts treated with SBG and BS showed a significant decrease of fibrotic markers as well., Conclusions: SBG and BS extracts significantly reduce inflammation and impair fibrosis in intestinal epithelial cells and colon myofibroblasts. No cooperative effect is observed., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)
Published: 2024
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41. A Novel Microbial Dysbiosis Index and Intestinal Microbiota-Associated Markers as Tools of Precision Medicine in Inflammatory Bowel Disease Paediatric Patients.

Author: Toto F, Marangelo C, Scanu M, De Angelis P, Isoldi S, Abreu MT, Cucchiara S, Stronati L, Del Chierico F, and Putignani L
Subjects: Humans, Child, Female, Male, Adolescent, RNA, Ribosomal, 16S genetics, Feces microbiology, Child, Preschool, Intestinal Mucosa microbiology, Intestinal Mucosa pathology, Intestinal Mucosa metabolism, Ileum microbiology, Ileum pathology, Colitis, Ulcerative microbiology, Dysbiosis microbiology, Gastrointestinal Microbiome, Inflammatory Bowel Diseases microbiology, Biomarkers, Precision Medicine methods
Abstract: Recent evidence indicates that the gut microbiota (GM) has a significant impact on the inflammatory bowel disease (IBD) progression. Our aim was to investigate the GM profiles, the Microbial Dysbiosis Index (MDI) and the intestinal microbiota-associated markers in relation to IBD clinical characteristics and disease state. We performed 16S rRNA metataxonomy on both stools and ileal biopsies, metabolic dysbiosis tests on urine and intestinal permeability and mucosal immunity activation tests on the stools of 35 IBD paediatric patients. On the GM profile, we assigned the MDI to each patient. In the statistical analyses, the MDI was correlated with clinical parameters and intestinal microbial-associated markers. In IBD patients with high MDI, Gemellaceae and Enterobacteriaceae were increased in stools, and Fusobacterium , Haemophilus and Veillonella were increased in ileal biopsies. Ruminococcaceae and WAL_1855D were enriched in active disease condition; the last one was also positively correlated to MDI. Furthermore, the MDI results correlated with PUCAI and Matts scores in ulcerative colitis patients (UC). Finally, in our patients, we detected metabolic dysbiosis, intestinal permeability and mucosal immunity activation. In conclusion, the MDI showed a strong association with both severity and activity of IBD and a positive correlation with clinical scores, especially in UC. Thus, this evidence could be a useful tool for the diagnosis and prognosis of IBD.
Published: 2024
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42. PARP1 inactivation increases regulatory T / Th17 cell proportion in intestinal inflammation. Role of HMGB1.

Author: Vitali R, Novelli F, Palone F, Cucchiara S, Stronati L, and Pioli C
Abstract: Inflammatory bowel diseases (IBD) are chronic relapsing disorders with increasing prevalence. Knowledge gaps still limit the possibility to develop more specific and effective therapies. Using a dextran sodium sulfate colitis mouse model, we found that inflammation increased the total number and altered the frequencies of leukocytes within colon mesenteric lymph nodes (cMLNs). Although the inflammation reduced the frequency of regulatory T (Treg) cells, their absolute numbers were increased. Increased frequency of colitogenic Th17 cells was also observed. Noteworthy, untreated mice lacking Poly(ADP-ribose)-Polimerase-1 functional gene (PARP-1KO) displayed higher frequency of Treg cells and lower percentage of Th17 cells in cMLNs. In colitic PARP-1KO mice the inflammation driven expansion of the Foxp3 Treg population was more pronounced than in WT mice. Conversely, colitis increased Th17 cells to a lower extent in PARP-1KO mice compared with WT mice, resulting in a more protective Treg/Th17 cell ratio. Consequently PARP-1KO mice developed less severe colitis with reduced expression of inflammatory cytokines. In ex vivo experiments PARP-1KO and WT CD11c dendritic cells (DCs) promoted naïve CD4 T cell differentiation differently, the former sustaining more efficiently the generation of Treg cells, the latter that of Th17 cells. Addition of HMGB1 B box or of dipotassium glycyrrhizate, which sequesters extracellular HMGB1, revealed a role for this alarmin in the regulation exerted by PARP-1 on the stimulating vs. tolerogenic function of DCs during colitis. Moreover, a higher percentage of CD11c DC from PARP-1KO mice expressed CD103, a marker associated with the ability of DC to induce Treg cells, compared with WT DC. Conversely, PARP-1KO DC were including a reduced percentage of CX3CR1+ DC, described to induce Th17 cells. These findings were observed in both splenic and colon lamina propria DC., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2024
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43. Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease.

Author: Laudadio I, Carissimi C, Scafa N, Bastianelli A, Fulci V, Renzini A, Russo G, Oliva S, Vitali R, Palone F, Cucchiara S, and Stronati L
Subjects: Humans, Inflammatory Bowel Diseases pathology, Child, Female, Male, Intestinal Mucosa pathology, Adolescent, Crohn Disease pathology, Crohn Disease metabolism, Colitis, Ulcerative pathology, Intestines pathology, Organoids pathology, Fibrosis, Transforming Growth Factor beta1 metabolism, Tumor Necrosis Factor-alpha metabolism
Abstract: Background and Aims: Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), but the precise mechanism by which it occurs is incompletely understood hampering the development of effective therapeutic strategies. Here, we aimed at inducing and characterizing an inflammation-mediated fibrosis in patient-derived organoids (PDOs) issued from crypts isolated from colonic mucosal biopsies of IBD pediatric patients and age matched-control subjects (CTRLs)., Methods: Inflammatory-driven fibrosis was induced by exposing CTRL-, CD- and UC-PDOs to the pro-inflammatory cytokine TNF-α for one day, followed by a co-treatment with TNF-α and TGF-β1 for three days. Fibrotic response was proven by analyzing inflammatory and fibrotic markers by RT-qPCR and immunofluorescence. Transcriptomic changes were assessed by RNA-sequencing., Results: Co-treatment with TNF-α and TGF-β1 caused in CTRL- and IBD-PDOs morphological changes towards a mesenchymal-like phenotype and up-regulation of inflammatory, mesenchymal, and fibrotic markers. Transcriptomic profiling highlighted that in all intestinal PDOs, regardless of the disease, the co-exposure to TNF-α and TGF-β1 regulated EMT genes and specifically increased genes involved in positive regulation of cell migration. Finally, we demonstrated that CD-PDOs display a specific response to fibrosis compared to both CTRL- and UC-PDOs, mainly characterized by upregulation of nuclear factors controlling transcription., Conclusions: This study demonstrates that intestinal PDOs may develop an inflammatory-derived fibrosis thus representing a promising tool to study fibrogenesis in IBD. Fibrotic PDOs show increased expression of EMT genes. In particular, fibrotic CD-PDOs display a specific gene expression signature compared to UC and CTRL-PDOs., (© 2024. The Author(s).)
Published: 2024
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44. PARP1 Activation Induces HMGB1 Secretion Promoting Intestinal Inflammation in Mice and Human Intestinal Organoids.

Author: Vitali R, Mancuso AB, Palone F, Pioli C, Cesi V, Negroni A, Cucchiara S, Oliva S, Carissimi C, Laudadio I, and Stronati L
Subjects: Animals, Humans, Mice, Cytokines, Inflammation, Organoids, Colitis chemically induced, HMGB1 Protein genetics, HMGB1 Protein metabolism, Inflammatory Bowel Diseases, Poly (ADP-Ribose) Polymerase-1 genetics
Abstract: Extracellular High-mobility group box 1 (HMGB1) contributes to the pathogenesis of inflammatory disorders, including inflammatory bowel diseases (IBD). Poly (ADP-ribose) polymerase 1 (PARP1) has been recently reported to promote HMGB1 acetylation and its secretion outside cells. In this study, the relationship between HMGB1 and PARP1 in controlling intestinal inflammation was explored. C57BL6/J wild type (WT) and PARP1 -/- mice were treated with DSS to induce acute colitis, or with the DSS and PARP1 inhibitor, PJ34. Human intestinal organoids, which are originated from ulcerative colitis (UC) patients, were exposed to pro-inflammatory cytokines (INFγ + TNFα) to induce intestinal inflammation, or coexposed to cytokines and PJ34. Results show that PARP1 -/- mice develop less severe colitis than WT mice, evidenced by a significant decrease in fecal and serum HMGB1, and, similarly, treating WT mice with PJ34 reduces the secreted HMGB1. The exposure of intestinal organoids to pro-inflammatory cytokines results in PARP1 activation and HMGB1 secretion; nevertheless, the co-exposure to PJ34, significantly reduces the release of HMGB1, improving inflammation and oxidative stress. Finally, HMGB1 release during inflammation is associated with its PARP1-induced PARylation in RAW264.7 cells. These findings offer novel evidence that PARP1 favors HMGB1 secretion in intestinal inflammation and suggest that impairing PARP1 might be a novel approach to manage IBD.
Published: 2023
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45. Proteomic Analysis Identifies Three Reliable Biomarkers of Intestinal Inflammation in the Stools of Patients With Inflammatory Bowel Disease.

Author: Vitali R, Palone F, Armuzzi A, Fulci V, Negroni A, Carissimi C, Cucchiara S, and Stronati L
Subjects: Humans, Chymotrypsin metabolism, Gelsolin metabolism, Proteomics, rho Guanine Nucleotide Dissociation Inhibitor beta metabolism, Intestinal Mucosa metabolism, Biomarkers analysis, Inflammation metabolism, Leukocyte L1 Antigen Complex analysis, Feces chemistry, Severity of Illness Index, Inflammatory Bowel Diseases complications, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases metabolism, Colitis, Ulcerative diagnosis, Colitis, Ulcerative metabolism, Crohn Disease diagnosis, Crohn Disease metabolism
Abstract: Background: Faecal biomarkers have emerged as important tools in managing of inflammatory bowel disease [IBD], which includes Crohn's disease [CD] and ulcerative colitis [UC]., Aim: To identify new biomarkers of gut inflammation in the stools of IBD patients using a proteomic approach., Methods: Proteomic analysis of stools was performed in patients with both active CD and CD in remission and in controls by 2-DIGE and MALDI-TOF/TOF MS. An ELISA was used to confirm results in a second cohort of IBD patients and controls., Results: 2-DIGE analysis detected 70 spots in the stools of patients with active CD or patients in remission CD and in controls. MALDI-TOF/TOF MS analysis identified 21 proteins with Chymotrypsin C, Gelsolin and Rho GDP-dissociation inhibitor 2 [RhoGDI2] best correlating with the levels of intestinal inflammation. Results were confirmed in a second cohort of IBD patients and controls [57 CD, 60 UC, 31 controls]. The identified faecal markers significantly correlated with the severity of intestinal inflammation in IBD patients [SES-CD in CD, Mayo endoscopic subscore in UC] [CD; Chymotrypsin-C: r = 0.64, p < 0.001; Gelsolin: r = 0.82, p < 0.001; RhoGDI2: r = 0.64, p < 0.001; UC; Chymotrypsin-C: r = 0.76, p < 0.001; Gelsolin: r = 0.75, p < 0.001; RhoGDI2: r = 0.63, p < 0.001]. Moreover, ROC analysis showed that Gelsolin [p < 0.0002] and RhoGDI2 [p < 0.0001] in CD, and RhoGDI2 [p = 0.0004] in UC, have higher sensitivity and specificity than faecal calprotectin in discriminating between patients and controls., Conclusions: We show for the first time that 2-DIGE is a reliable method to detect proteins in human stools. Three novel faecal biomarkers of gut inflammation have been identified that display good specificity and sensitivity for identifying IBD and significantly correlate with IBD severity., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Published: 2023
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46. Liver Steatosis and Steatohepatitis Alter Bile Acid Receptors in Brain and Induce Neuroinflammation: A Contribution of Circulating Bile Acids and Blood-Brain Barrier.

Author: Fiaschini N, Mancuso M, Tanori M, Colantoni E, Vitali R, Diretto G, Lorenzo Rebenaque L, Stronati L, and Negroni A
Subjects: Animals, Mice, Blood-Brain Barrier metabolism, Occludin metabolism, Endothelial Cells metabolism, Neuroinflammatory Diseases, Brain metabolism, Bile Acids and Salts, Non-alcoholic Fatty Liver Disease metabolism
Abstract: A tight relationship between gut-liver diseases and brain functions has recently emerged. Bile acid (BA) receptors, bacterial-derived molecules and the blood-brain barrier (BBB) play key roles in this association. This study was aimed to evaluate how non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) impact the BA receptors Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) expression in the brain and to correlate these effects with circulating BAs composition, BBB integrity and neuroinflammation. A mouse model of NAFLD was set up by a high-fat and sugar diet, and NASH was induced with the supplementation of dextran-sulfate-sodium (DSS) in drinking water. FXR, TGR5 and ionized calcium-binding adaptor molecule 1 (Iba-1) expression in the brain was detected by immunohistochemistry, while Zonula occludens (ZO)-1, Occludin and Plasmalemmal Vesicle Associated Protein-1 (PV-1) were analyzed by immunofluorescence. Biochemical analyses investigated serum BA composition, lipopolysaccharide-binding protein (LBP) and S100β protein (S100β) levels. Results showed a down-regulation of FXR in NASH and an up-regulation of TGR5 and Iba-1 in the cortex and hippocampus in both treated groups as compared to the control group. The BA composition was altered in the serum of both treated groups, and LBP and S100β were significantly augmented in NASH. ZO-1 and Occludin were attenuated in the brain capillary endothelial cells of both treated groups versus the control group. We demonstrated that NAFLD and NASH provoke different grades of brain dysfunction, which are characterized by the altered expression of BA receptors, FXR and TGR5, and activation of microglia. These effects are somewhat promoted by a modification of circulating BAs composition and by an increase in LBP that concur to damage BBB, thus favoring neuroinflammation., Competing Interests: The authors declare no conflict of interest.
Published: 2022
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47. ZNF281 Promotes Colon Fibroblast Activation in TGFβ1-Induced Gut Fibrosis.

Author: Laudadio I, Bastianelli A, Fulci V, Carissimi C, Colantoni E, Palone F, Vitali R, Lorefice E, Cucchiara S, Negroni A, and Stronati L
Subjects: Animals, Colon pathology, Dextran Sulfate, Fibroblasts metabolism, Fibrosis, Humans, Mice, Mice, Inbred C57BL, RNA, Small Interfering metabolism, Transcription Factors metabolism, Transforming Growth Factor beta metabolism, Zinc metabolism, Colitis chemically induced, Colitis genetics, Colitis metabolism, Crohn Disease metabolism, Repressor Proteins metabolism
Abstract: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract. Chronic inflammation is the main factor leading to intestinal fibrosis, resulting in recurrent stenosis, especially in CD patients. Currently, the underlying molecular mechanisms of fibrosis are still unclear. ZNF281 is a zinc-finger transcriptional regulator that has been characterized as an epithelial-to-mesenchymal transition (EMT)-inducing transcription factor, suggesting its involvement in the regulation of pluripotency, stemness, and cancer. The aim of this study is to investigate in vivo and in vitro the role of ZNF281 in intestinal fibrogenesis. Intestinal fibrosis was studied in vivo in C57BL/6J mice with chronic colitis induced by two or three cycles of administration of dextran sulfate sodium (DSS). The contribution of ZNF281 to gut fibrosis was studied in vitro in the human colon fibroblast cell line CCD-18Co, activated by the pro-fibrotic cytokine TGFβ1. ZNF281 was downregulated by siRNA transfection, and RNA-sequencing was performed to identify genes regulated by TGFβ1 in activated colon fibroblasts via ZNF281. Results showed a marked increase of ZNF281 in in vivo murine fibrotic colon as well as in in vitro human colon fibroblasts activated by TGFβ1. Moreover, abrogation of ZNF281 in TGFβ1-treated fibroblasts affected the expression of genes belonging to specific pathways linked to fibroblast activation and differentiation into myofibroblasts. We demonstrated that ZNF281 is a key regulator of colon fibroblast activation and myofibroblast differentiation upon fibrotic stimuli by transcriptionally controlling extracellular matrix (ECM) composition, remodeling, and cell contraction, highlighting a new role in the onset and progression of gut fibrosis.
Published: 2022
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48. Colonic inflammation accelerates the progression of liver disease: A protective role of dipotassium glycyrrhizate.

Author: Fiaschini N, Negroni A, Palone F, Vitali R, Colantoni E, Laudadio I, Mancuso M, Cucchiara S, and Stronati L
Subjects: Animals, Diet, High-Fat, Disease Models, Animal, Inflammation complications, Liver pathology, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease pathology
Abstract: Background: The incidence of non-alcoholic fatty liver disease (NAFLD) and its more severe and progressive form, non-alcoholic steatohepatitis (NASH) is increasing worldwide. Gut inflammation seems to concur to the pathogenesis of NASH. No drugs are currently approved for NASH treatment., Aims: To investigate if inflamed gut directly contributes to the progression of NASH through gut epithelial and vascular barrier impairment and to evaluate the efficacy of dipotassium glycyrrhizate (DPG) to improve the liver disease., Methods: A NASH model was set up by feeding mice, for 8 and 13 weeks, with high fat diet with high fructose and glucose (HFD-FG) supplemented periodically with dextran sulfate sodium (DSS) in drinking water. A group was also treated with DPG by gavage. Histological, immunohistochemical and molecular analysis were performed., Results: DSS-induced colitis increased steatosis, inflammatory (IL-6, TNFα, NLRP3, MCP-1) as well as fibrotic (TGF-β, α-SMA) mediator expression in HFD-FG mice. Beneficial effect of DPG was associated with restoration of intestinal epithelial and vascular barriers, evaluated respectively by ZO-1 and PV-1 expression, that are known to limit bacterial translocation., Conclusion: Colonic inflammation strongly contributes to the progression of NASH, likely by favouring bacterial translocation. DPG treatment could represent a novel strategy to reduce liver injury., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021. Published by Elsevier Ltd.)
Published: 2022
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49. Innovative method to grow the probiotic Lactobacillus reuteri in the omega3-rich microalga Isochrysis galbana.

Author: Colantoni E, Palone F, Cesi V, Leter B, Sugoni G, Laudadio I, Negroni A, Vitali R, and Stronati L
Subjects: Culture Media chemistry, Docosahexaenoic Acids chemistry, Eicosapentaenoic Acid chemistry, Fatty Acids, Omega-3, Fatty Acids, Unsaturated chemistry, Fermentation, Haptophyta metabolism, Microalgae chemistry, Probiotics metabolism, Batch Cell Culture Techniques methods, Haptophyta microbiology, Limosilactobacillus reuteri growth & development
Abstract: Microalgae are natural sources of valuable bioactive compounds, such as polyunsaturated fatty acids (PUFAs), that show antioxidant, anti-inflammatory, anticancer and antimicrobial activities. The marine microalga Isochrysis galbana (I. galbana) is extremely rich in ω3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Probiotics are currently suggested as adjuvant therapy in the management of diseases associated with gut dysbiosis. The Lactobacillus reuteri (L. reuteri), one of the most widely used probiotics, has been shown to produce multiple beneficial effects on host health. The present study aimed to present an innovative method for growing the probiotic L. reuteri in the raw seaweed extracts from I. galbana as an alternative to the conventional medium, under conditions of oxygen deprivation (anaerobiosis). As a result, the microalga I. galbana was shown for the first time to be an excellent culture medium for growing L. reuteri. Furthermore, the gas-chromatography mass-spectrometry analysis showed that the microalga-derived ω3 PUFAs were still available after the fermentation by L. reuteri. Accordingly, the fermented compound (FC), obtained from the growth of L. reuteri in I. galbana in anaerobiosis, was able to significantly reduce the adhesiveness and invasiveness of the harmful adherent-invasive Escherichia coli to intestinal epithelial cells, due to a cooperative effect between L. reuteri and microalgae-released ω3 PUFAs. These findings open new perspectives in the use of unicellular microalgae as growth medium for probiotics and in the production of biofunctional compounds., (© 2022. The Author(s).)
Published: 2022
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50. Fecal and mucosal microbiota profiling in pediatric inflammatory bowel diseases.

Author: Putignani L, Oliva S, Isoldi S, Del Chierico F, Carissimi C, Laudadio I, Cucchiara S, and Stronati L
Subjects: Adult, Child, Feces, Humans, Intestinal Mucosa, RNA, Ribosomal, 16S genetics, Colitis, Ulcerative diagnosis, Inflammatory Bowel Diseases, Microbiota
Abstract: Background: An altered gut microbiota profile has been widely documented in inflammatory bowel diseases (IBD). The intestinal microbial community has been more frequently investigated in the stools than at the level of the mucosa, while most of the studies have been performed in adults. We aimed to define the gut microbiota profile either by assessing fecal and colonic mucosa samples (inflamed or not) from pediatric IBD patients., Patients and Methods: Fecal and colonic samples from pediatric IBD (Crohn's disease or ulcerative colitis) and controls were analyzed. The relative abundance of bacteria at phylum and genus/species levels and bacterial diversity were determined through 16S rRNA sequence-based of fecal and mucosal microbiota analysis., Results: A total of 59 children with IBD (26 Crohn's disease, 33 ulcerative colitis) and 39 controls were analyzed. A clear separation between IBD and controls in the overall composition of fecal and mucosal microbiota was found, as well as a reduced bacterial richness in the fecal microbiota of IBD. At the phylum level, abundance of Proteobacteria and Actinobacteria occurred in fecal microbiota of IBD, while species with anti-inflammatory properties (i.e., Ruminococcus) were reduced. Fusobacterium prevailed in inflamed IBD areas in comparison to noninflamed and controls samples., Conclusion: Significant alterations in gut microbiota profile were shown in our IBD pediatric patients, in whom an abundance of species with a proinflammatory mucosal activity was clearly detected. An analysis of gut microbiota could be incorporated in designing personalized IBD treatment scenarios in future., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2021
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