{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:36:19Z","timestamp":1793730979983,"version":"4.6.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ulcerative colitis and Crohn\u2019s disease are forms of inflammatory bowel disease whose incidence and prevalence are increasing worldwide. These diseases lead to chronic inflammation of the gastrointestinal tract as a result of an abnormal response of the immune system. Recent studies positioned Cortistatin, which shows low stability in plasma, as a candidate for IBD treatment. Here, using NMR structural information, we design five Cortistatin analogues adopting selected native Cortistatin conformations in solution. One of them, A5, preserves the anti-inflammatory and immunomodulatory activities of Cortistatin in vitro and in mouse models of the disease. Additionally, A5 displays an increased half-life in serum and a unique receptor binding profile, thereby overcoming the limitations of the native Cortistatin as a therapeutic agent. This study provides an efficient approach to the rational design of Cortistatin analogues and opens up new possibilities for the treatment of patients that fail to respond to other therapies.<\/jats:p>","DOI":"10.1038\/s41467-021-22076-5","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T07:06:58Z","timestamp":1616656018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease"],"prefix":"10.1038","volume":"12","author":[{"given":"\u00c1lvaro","family":"Rol","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-2830","authenticated-orcid":false,"given":"Toni","family":"Todorovski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5867-5535","authenticated-orcid":false,"given":"Pau","family":"Martin-Malpartida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Escol\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gonzalez-Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Arag\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Verdaguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3712-1634","authenticated-orcid":false,"given":"Mariona","family":"Vall\u00e8s-Miret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Farrera-Sinfreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3506-2829","authenticated-orcid":false,"given":"Eduard","family":"Puig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Fern\u00e1ndez-Carneado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Ponsati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-5982","authenticated-orcid":false,"given":"Mario","family":"Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-7675","authenticated-orcid":false,"given":"Antoni","family":"Riera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6915-963X","authenticated-orcid":false,"given":"Maria J.","family":"Macias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"22076_CR1","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/ncpgasthep0528","volume":"3","author":"RB Sartor","year":"2006","unstructured":"Sartor, R. B. Mechanisms of disease: pathogenesis of Crohn\u2019s disease and ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 390\u2013407 (2006).","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"22076_CR2","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1056\/NEJM199710093371502","volume":"337","author":"SR Targan","year":"1997","unstructured":"Targan, S. R. et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn\u2019s disease. Crohn\u2019s Disease cA2 Study Group. N. Engl. J. Med. 337, 1029\u20131035 (1997).","journal-title":"N. Engl. J. Med."},{"key":"22076_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms19082244","volume":"19","author":"SO Adegbola","year":"2018","unstructured":"Adegbola, S. O., Sahnan, K., Warusavitarne, J., Hart, A. & Tozer, P. Anti-TNF therapy in Crohn\u2019s disease. Int. J. Mol. Sci. 19, 1\u201321 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"22076_CR4","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1056\/NEJMra020831","volume":"347","author":"DK Podolsky","year":"2002","unstructured":"Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417\u2013429 (2002).","journal-title":"N. Engl. J. Med."},{"key":"22076_CR5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/ajg.2014.357","volume":"110","author":"CN Bernstein","year":"2015","unstructured":"Bernstein, C. N. Treatment of IBD: where we are and where we are going. Am. J. Gastroenterol. 110, 114\u2013126 (2015).","journal-title":"Am. J. Gastroenterol."},{"key":"22076_CR6","unstructured":"Crohn\u2019s and Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases (Crohn\u2019s & Colitis Foundation, New York,\u00a02014)."},{"key":"22076_CR7","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/381242a0","volume":"381","author":"L de Lecea","year":"1996","unstructured":"de Lecea, L. et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381, 242\u2013245 (1996).","journal-title":"Nature"},{"key":"22076_CR8","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1006\/geno.1997.4763","volume":"42","author":"L de Lecea","year":"1997","unstructured":"de Lecea, L. et al. Cloning, mRNA expression, and chromosomal mapping of mouse and human preprocortistatin. Genomics 42, 499\u2013506 (1997).","journal-title":"Genomics"},{"key":"22076_CR9","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1084\/jem.20052017","volume":"203","author":"E Gonzalez-Rey","year":"2006","unstructured":"Gonzalez-Rey, E., Chorny, A., Robledo, G. & Delgado, M. Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia. J. Exp. Med. 203, 563\u2013571 (2006).","journal-title":"J. Exp. Med."},{"key":"22076_CR10","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1073\/pnas.0508997103","volume":"103","author":"E Gonzalez-Rey","year":"2006","unstructured":"Gonzalez-Rey, E. et al. Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease. Proc. Natl Acad. Sci. USA 103, 4228\u20134233 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22076_CR11","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.2174\/138161210790963814","volume":"16","author":"SA Snoek","year":"2010","unstructured":"Snoek, S. A., Borensztajn, K. S., van den Wijngaard, R. M. & de Jonge, W. J. Neuropeptide receptors in intestinal disease: physiology and therapeutic potential. Curr. Pharm. Des. 16, 1091\u20131105 (2010).","journal-title":"Curr. Pharm. Des."},{"key":"22076_CR12","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.mce.2007.12.002","volume":"286","author":"M Volante","year":"2008","unstructured":"Volante, M. et al. Somatostatin, cortistatin and their receptors in tumours. Mol. Cell Endocrinol. 286, 219\u2013229 (2008).","journal-title":"Mol. Cell Endocrinol."},{"key":"22076_CR13","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.yfrne.2013.07.005","volume":"34","author":"M Theodoropoulou","year":"2013","unstructured":"Theodoropoulou, M. & Stalla, G. K. Somatostatin receptors: from signaling to clinical practice. Front. Neuroendocrinol. 34, 228\u2013252 (2013).","journal-title":"Front. Neuroendocrinol."},{"key":"22076_CR14","doi-asserted-by":"publisher","first-page":"4800","DOI":"10.1210\/en.2011-1542","volume":"152","author":"J Cordoba-Chacon","year":"2011","unstructured":"Cordoba-Chacon, J. et al. Cortistatin is not a somatostatin analogue but stimulates prolactin release and inhibits GH and ACTH in a gender-dependent fashion: potential role of ghrelin. Endocrinology 152, 4800\u20134812 (2011).","journal-title":"Endocrinology"},{"key":"22076_CR15","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.coph.2010.05.007","volume":"10","author":"A Mizoguchi","year":"2010","unstructured":"Mizoguchi, A. & Mizoguchi, E. Animal models of IBD: linkage to human disease. Curr. Opin. Pharmacol. 10, 578\u2013587 (2010).","journal-title":"Curr. Opin. Pharmacol."},{"key":"22076_CR16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0006-3495(83)84442-7","volume":"41","author":"LA Buffington","year":"1983","unstructured":"Buffington, L. A., Garsky, V., Rivier, J. & Gibbons, W. A. Conformation of somatostatin using scalar coupling constants from 270 and 600 MHz simulated proton magnetic resonance spectra. Biophys. J. 41, 299\u2013304 (1983).","journal-title":"Biophys. J."},{"key":"22076_CR17","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1073\/pnas.73.4.1199","volume":"73","author":"LA Holladay","year":"1976","unstructured":"Holladay, L. A. & Puett, D. Somatostatin conformation: evidence for a stable intramolecular structure from circular dichroism, diffusion, and sedimentation equilibrium. Proc. Natl Acad. Sci. USA 73, 1199\u20131202 (1976).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"22076_CR18","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/0167-4838(82)90103-0","volume":"700","author":"M Knappenberg","year":"1982","unstructured":"Knappenberg, M. et al. The conformational properties of somatostatin. IV. The conformers contributing to the conformation equilibrium of somatostatin in aqueous solution as found by semi-empirical energy calculations and high-resolution NMR experiments. Biochim Biophys. Acta 700, 229\u2013246 (1982).","journal-title":"Biochim Biophys. Acta"},{"key":"22076_CR19","doi-asserted-by":"publisher","first-page":"14564","DOI":"10.3390\/molecules181214564","volume":"18","author":"P Martin-Gago","year":"2013","unstructured":"Martin-Gago, P. et al. Insights into structure-activity relationships of somatostatin analogs containing mesitylalanine. Molecules 18, 14564\u201314584 (2013).","journal-title":"Molecules"},{"key":"22076_CR20","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1002\/anie.201106406","volume":"51","author":"P Martin-Gago","year":"2012","unstructured":"Martin-Gago, P. et al. Fine-tuning the \u03c0-\u03c0 aromatic interactions in peptides: somatostatin analogues containing mesityl alanine. Angew. Chem. Int. Ed. Engl. 51, 1820\u20131825 (2012).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"22076_CR21","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.bmcl.2013.11.065","volume":"24","author":"P Martin-Gago","year":"2014","unstructured":"Martin-Gago, P. et al. A tetradecapeptide somatostatin dicarba-analog: Synthesis, structural impact and biological activity. Bioorg. Med. Chem. Lett. 24, 103\u2013107 (2014).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"22076_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/srep27285","volume":"6","author":"P Martin-Gago","year":"2016","unstructured":"Martin-Gago, P. et al. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3\u2019,5\u2019difluorophenyl)-alanine. Sci. Rep. 6, 27285 (2016).","journal-title":"Sci. Rep."},{"key":"22076_CR23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1399-3011.1990.tb00939.x","volume":"35","author":"GB Fields","year":"1990","unstructured":"Fields, G. B. & Noble, R. L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int. J. Pept. Protein Res. 35, 161\u2013214 (1990).","journal-title":"Int. J. Pept. Protein Res."},{"key":"22076_CR24","doi-asserted-by":"publisher","DOI":"10.1051\/epn\/19861701011","volume-title":"NMR of Proteins And Nucleic Acids.","author":"K W\u00fcthrich","year":"1986","unstructured":"W\u00fcthrich, K. NMR of Proteins And Nucleic Acids. (Wiley, New York, 1986)."},{"key":"22076_CR25","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1107\/S0907444998003254","volume":"54","author":"AT Brunger","year":"1998","unstructured":"Brunger, A. T. et al. Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D. Biol. Crystallogr. 54, 905\u2013921 (1998).","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"22076_CR26","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1111\/j.1747-0285.2007.00493.x","volume":"69","author":"GV Nikiforovich","year":"2007","unstructured":"Nikiforovich, G. V., Marshall, G. R. & Achilefu, S. Molecular modeling suggests conformational scaffolds specifically targeting five subtypes of somatostatin receptors. Chem. Biol. Drug Des. 69, 163\u2013169 (2007).","journal-title":"Chem. Biol. Drug Des."},{"key":"22076_CR27","doi-asserted-by":"publisher","first-page":"625","DOI":"10.2174\/1568026618666180518090705","volume":"18","author":"RW Mull","year":"2018","unstructured":"Mull, R. W., Harrington, A., Sanchez, L. A. & Tal-Gan, Y. Cyclic peptides that govern signal transduction pathways: from prokaryotes to multi-cellular organisms. Curr. Top. Med. Chem. 18, 625\u2013644 (2018).","journal-title":"Curr. Top. Med. Chem."},{"key":"22076_CR28","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.1210\/endo.141.11.7757","volume":"141","author":"Y Date","year":"2000","unstructured":"Date, Y. et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141, 4255\u20134261 (2000).","journal-title":"Endocrinology"},{"key":"22076_CR29","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1002\/adsc.201300662","volume":"356","author":"E Crist\u00f3bal-Lecina","year":"2014","unstructured":"Crist\u00f3bal-Lecina, E. et al. MaxPHOS ligand: PH\/NH tautomerism and rhodium- catalyzed asymmetric hydrogenations. Adv. Synth. Catal. 356, 795\u2013804 (2014).","journal-title":"Adv. Synth. Catal."},{"key":"22076_CR30","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1002\/(SICI)1097-4547(19990615)56:6<611::AID-JNR7>3.0.CO;2-G","volume":"56","author":"JR Criado","year":"1999","unstructured":"Criado, J. R. et al. Structural and compositional determinants of cortistatin activity. J. Neurosci. Res. 56, 611\u2013619 (1999).","journal-title":"J. Neurosci. Res."},{"key":"22076_CR31","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/S0165-0173(00)00031-X","volume":"33","author":"AD Spier","year":"2000","unstructured":"Spier, A. D. & de Lecea, L. Cortistatin: a member of the somatostatin neuropeptide family with distinct physiological functions. Brain Res. Brain Res. Rev. 33, 228\u2013241 (2000).","journal-title":"Brain Res. Brain Res. Rev."},{"key":"22076_CR32","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1053\/j.gastro.2006.10.023","volume":"131","author":"E Gonzalez-Rey","year":"2006","unstructured":"Gonzalez-Rey, E. & Delgado, M. Therapeutic treatment of experimental colitis with regulatory dendritic cells generated with vasoactive intestinal peptide. Gastroenterology 131, 1799\u20131811 (2006).","journal-title":"Gastroenterology"},{"key":"22076_CR33","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1358\/dnp.2006.19.7.1021490","volume":"19","author":"E Gonzalez-Rey","year":"2006","unstructured":"Gonzalez-Rey, E. & Delgado, M. Cortistatin as a potential multistep therapeutic agent for inflammatory disorders. Drug News Perspect. 19, 393\u2013399 (2006).","journal-title":"Drug News Perspect."},{"key":"22076_CR34","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","volume":"28","author":"A Kaser","year":"2010","unstructured":"Kaser, A., Zeissig, S. & Blumberg, R. S. Inflammatory bowel disease. Annu. Rev. Immunol. 28, 573\u2013621 (2010).","journal-title":"Annu. Rev. Immunol."},{"key":"22076_CR35","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/39614","volume":"389","author":"H Groux","year":"1997","unstructured":"Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737\u2013742 (1997).","journal-title":"Nature"},{"key":"22076_CR36","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/psc.743","volume":"12","author":"M Gairi","year":"2006","unstructured":"Gairi, M. et al. Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution. J. Pept. Sci. 12, 82\u201391 (2006).","journal-title":"J. Pept. Sci."},{"key":"22076_CR37","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1021\/jm049518u","volume":"48","author":"CR Grace","year":"2005","unstructured":"Grace, C. R. et al. Somatostatin receptor 1 selective analogues: 4. Three-dimensional consensus structure by NMR. J. Med. Chem. 48, 523\u2013533 (2005).","journal-title":"J. Med. Chem."},{"key":"22076_CR38","doi-asserted-by":"publisher","first-page":"5606","DOI":"10.1021\/jm030246p","volume":"46","author":"CR Grace","year":"2003","unstructured":"Grace, C. R. et al. Novel sst(4)-selective somatostatin (SRIF) agonists. 4. Three-dimensional consensus structure by NMR. J. Med. Chem. 46, 5606\u20135618 (2003).","journal-title":"J. Med. Chem."},{"key":"22076_CR39","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.drudis.2016.11.003","volume":"22","author":"N Qvit","year":"2017","unstructured":"Qvit, N., Rubin, S. J. S., Urban, T. J., Mochly-Rosen, D. & Gross, E. R. Peptidomimetic therapeutics: scientific approaches and opportunities. Drug Discov. Today 22, 454\u2013462 (2017).","journal-title":"Drug Discov. Today"},{"key":"22076_CR40","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.tem.2007.06.004","volume":"18","author":"F Broglio","year":"2007","unstructured":"Broglio, F., Papotti, M., Muccioli, G. & Ghigo, E. Brain-gut communication: cortistatin, somatostatin and ghrelin. Trends Endocrinol. Metab. 18, 246\u2013251 (2007).","journal-title":"Trends Endocrinol. Metab."},{"key":"22076_CR41","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1210\/jc.2005-2148","volume":"91","author":"H Rubinfeld","year":"2006","unstructured":"Rubinfeld, H. et al. Cortistatin inhibits growth hormone release from human fetal and adenoma pituitary cells and prolactin secretion from cultured prolactinomas. J. Clin. Endocrinol. Metab. 91, 2257\u20132263 (2006).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"22076_CR42","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1136\/ard.2006.062703","volume":"66","author":"E Gonzalez-Rey","year":"2007","unstructured":"Gonzalez-Rey, E., Chorny, A., Del Moral, R. G., Varela, N. & Delgado, M. Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses. Ann. Rheum. Dis. 66, 582\u2013588 (2007).","journal-title":"Ann. Rheum. Dis."},{"key":"22076_CR43","unstructured":"Keller R. The Computer Aided Resonance Assignment Tutorial (Cantina Verlag, 2004)."},{"key":"22076_CR44","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.str.2007.03.005","volume":"15","author":"B Morales","year":"2007","unstructured":"Morales, B. et al. NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands. Structure 15, 473\u2013483 (2007).","journal-title":"Structure"},{"key":"22076_CR45","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1053\/j.gastro.2008.11.041","volume":"136","author":"MA Gonzalez","year":"2009","unstructured":"Gonzalez, M. A., Gonzalez-Rey, E., Rico, L., Buscher, D. & Delgado, M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 136, 978\u2013989 (2009).","journal-title":"Gastroenterology"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22076-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22076-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22076-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T06:38:54Z","timestamp":1669963134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-021-22076-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["22076"],"URL":"https:\/\/doi.org\/10.1038\/s41467-021-22076-5","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]},"assertion":[{"value":"21 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Analogue 5 is patented, EP 3046933 B1 (BCN PEPTIDES, S.A.) 2019-02-27, \u201cCortistatin analogues for the treatment of inflammatory and\/or immune diseases\u201d. All authors declare no other competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1869"}}