{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T05:13:14Z","timestamp":1780722794627,"version":"3.54.1"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017569","name":"Salzburg State Government","doi-asserted-by":"publisher","award":["WISS 2025 F 2000237-FIP"],"award-info":[{"award-number":["WISS 2025 F 2000237-FIP"]}],"id":[{"id":"10.13039\/501100017569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001543","name":"Children&apos;s Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011852","name":"Paracelsus Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Peptides"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.peptides.2025.171405","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:30:30Z","timestamp":1744039830000},"page":"171405","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Spexin expression in the human bile duct and perihilar cholangiocarcinoma"],"prefix":"10.1016","volume":"188","author":[{"given":"Sara","family":"Huber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresia","family":"Fitzner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Gaisbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hochmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Sotlar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-4776","authenticated-orcid":false,"given":"Barbara","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Varga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.peptides.2025.171405_bib1","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1053\/gast.1999.0029900420","article-title":"Vasoactive intestinal polypeptide is a potent regulator of bile secretion from rat cholangiocytes","volume":"117","author":"Cho","year":"1999","journal-title":"Gastroenterology"},{"key":"10.1016\/j.peptides.2025.171405_bib2","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.12688\/f1000research.18039.1","article-title":"Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system","volume":"8","author":"Iwasaki","year":"2019","journal-title":"F1000Res"},{"issue":"2","key":"10.1016\/j.peptides.2025.171405_bib3","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/hep.29138","article-title":"Substance P increases liver fibrosis by differential changes in senescence of cholangiocytes and hepatic stellate cells","volume":"66","author":"Wan","year":"2017","journal-title":"Hepatology"},{"issue":"5","key":"10.1016\/j.peptides.2025.171405_bib4","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0016-5085(97)70050-7","article-title":"Neuropeptide Y in the dorsal vagal complex stimulates bicarbonate-dependent bile secretion in rats","volume":"112","author":"Yoneda","year":"1997","journal-title":"Gastroenterology"},{"issue":"13","key":"10.1016\/j.peptides.2025.171405_bib5","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.3390\/cells12131678","article-title":"Galanin System in the Human Bile Duct and Perihilar Cholangiocarcinoma","volume":"12","author":"Huber","year":"2023","journal-title":"Cells"},{"issue":"1","key":"10.1016\/j.peptides.2025.171405_bib6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1476-5381.1985.tb09455.x","article-title":"Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations","volume":"86","author":"Ekblad","year":"1985","journal-title":"Br. J. Pharm."},{"issue":"4","key":"10.1016\/j.peptides.2025.171405_bib7","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/BF01316802","article-title":"Neuropeptides in pig sphincter of Oddi, bile duct, gallbladder, and duodenum","volume":"38","author":"Sand","year":"1993","journal-title":"Dig. Dis. Sci."},{"issue":"4","key":"10.1016\/j.peptides.2025.171405_bib8","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.ajpath.2016.12.015","article-title":"The neuropeptide galanin is up-regulated during cholestasis and contributes to cholangiocyte proliferation","volume":"187","author":"McMillin","year":"2017","journal-title":"Am. J. Pathol."},{"issue":"3","key":"10.1016\/j.peptides.2025.171405_bib9","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.ajpath.2019.10.023","article-title":"Coordinated targeting of galanin receptors on cholangiocytes and hepatic stellate cells ameliorates liver fibrosis in multidrug resistance protein 2 knockout mice","volume":"190","author":"Petrescu","year":"2020","journal-title":"Am. J. Pathol."},{"issue":"3","key":"10.1016\/j.peptides.2025.171405_bib10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1101\/gr.5755407","article-title":"Identification of novel peptide hormones in the human proteome by hidden Markov model screening","volume":"17","author":"Mirabeau","year":"2007","journal-title":"Genome Res"},{"issue":"1","key":"10.1016\/j.peptides.2025.171405_bib11","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000258","article-title":"Evolutionary sequence modeling for discovery of peptide hormones","volume":"5","author":"Sonmez","year":"2009","journal-title":"PLoS Comput. Biol."},{"issue":"7","key":"10.1016\/j.peptides.2025.171405_bib12","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1177\/15353702211072443","article-title":"Impact of spexin on metabolic diseases and inflammation: An updated minireview","volume":"247","author":"Turkel","year":"2022","journal-title":"Exp. Biol. Med."},{"issue":"5","key":"10.1016\/j.peptides.2025.171405_bib13","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1210\/en.2013-2106","article-title":"Coevolution of the spexin\/galanin\/kisspeptin family: spexin activates galanin receptor type II and III","volume":"155","author":"Kim","year":"2014","journal-title":"Endocrinology"},{"key":"10.1016\/j.peptides.2025.171405_bib14","doi-asserted-by":"crossref","DOI":"10.1017\/S1462399409000994","article-title":"Cholangiocyte proliferation and liver fibrosis","volume":"11","author":"Glaser","year":"2009","journal-title":"Expert Rev. Mol. Med"},{"key":"10.1016\/j.peptides.2025.171405_bib15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3389\/fendo.2019.00379","article-title":"Evolution of structural and functional diversity of spexin in mammalian and non-mammalian vertebrate species","volume":"10","author":"Lim","year":"2019","journal-title":"Front Endocrinol. (Lausanne)"},{"issue":"2","key":"10.1016\/j.peptides.2025.171405_bib16","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41574-020-00438-1","article-title":"Functions of galanin, spexin and kisspeptin in metabolism, mood and behaviour","volume":"17","author":"Mills","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.peptides.2025.171405_bib17","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3389\/fphar.2019.00457","article-title":"Emerging roles of NPQ\/spexin in physiology and pathology","volume":"10","author":"Lv","year":"2019","journal-title":"Front Pharm."},{"key":"10.1016\/j.peptides.2025.171405_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.peptides.2023.171096","article-title":"An update on galanin and spexin and their potential for the treatment of type 2 diabetes and related metabolic disorders","volume":"171","author":"Gallagher","year":"2024","journal-title":"Peptides"},{"key":"10.1016\/j.peptides.2025.171405_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2021.108033","article-title":"Spexin: Its role, regulation, and therapeutic potential in the hypothalamus","volume":"233","author":"Tran","year":"2022","journal-title":"Pharm. Ther."},{"key":"10.1016\/j.peptides.2025.171405_bib20","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3389\/fphys.2018.00378","article-title":"Spexin acts as novel regulator for bile acid synthesis","volume":"9","author":"Lin","year":"2018","journal-title":"Front Physiol."},{"issue":"5","key":"10.1016\/j.peptides.2025.171405_bib21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert consensus document: cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"9","key":"10.1016\/j.peptides.2025.171405_bib22","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"2","key":"10.1016\/j.peptides.2025.171405_bib23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.suc.2018.12.004","article-title":"Cholangiocarcinoma","volume":"99","author":"Khan","year":"2019","journal-title":"Surg. Clin. North Am."},{"issue":"5","key":"10.1016\/j.peptides.2025.171405_bib24","doi-asserted-by":"crossref","first-page":"v28","DOI":"10.1093\/annonc\/mdw324","article-title":"E.G. Committee, Biliary cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Valle","year":"2016","journal-title":"Ann. Oncol."},{"issue":"15","key":"10.1016\/j.peptides.2025.171405_bib25","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14153755","article-title":"The galaninergic system: a target for cancer treatment","volume":"14","author":"Sanchez","year":"2022","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.peptides.2025.171405_bib26","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1124\/pr.112.006536","article-title":"Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity","volume":"67","author":"Lang","year":"2015","journal-title":"Pharm. Rev."},{"key":"10.1016\/j.peptides.2025.171405_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2024.102601","article-title":"Isthmin-1 and spexin as promising novel biomarker candidates for invasive ductal breast carcinoma","volume":"91","author":"Turk","year":"2024","journal-title":"Tissue Cell"},{"issue":"11","key":"10.1016\/j.peptides.2025.171405_bib28","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1158\/1055-9965.EPI-06-0740","article-title":"Galanin is up-regulated in colon adenocarcinoma","volume":"16","author":"Kim","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"issue":"19","key":"10.1016\/j.peptides.2025.171405_bib29","doi-asserted-by":"crossref","first-page":"5412","DOI":"10.1158\/1078-0432.CCR-12-1780","article-title":"Identification of galanin and its receptor GalR1 as novel determinants of resistance to chemotherapy and potential biomarkers in colorectal cancer","volume":"18","author":"Stevenson","year":"2012","journal-title":"Clin. Cancer Res"},{"issue":"10","key":"10.1016\/j.peptides.2025.171405_bib30","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1007\/s00403-024-03431-0","article-title":"Role of spexin and DARS2 as potential biomarkers in basal cell carcinoma and cutaneous malignant melanoma diagnosis, and as therapeutic targets","volume":"316","author":"Erdogan","year":"2024","journal-title":"Arch. Dermatol. Res"},{"key":"10.1016\/j.peptides.2025.171405_bib31","article-title":"TNM Classification, StatPearls","author":"Rosen","year":"2024","journal-title":"Treasure Isl. (FL)"},{"issue":"11","key":"10.1016\/j.peptides.2025.171405_bib32","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.3390\/antiox11112235","article-title":"Hydrogen sulfide metabolizing enzymes in the intestinal mucosa in pediatric and adult inflammatory bowel disease","volume":"11","author":"Stummer","year":"2022","journal-title":"Antioxidants"},{"key":"10.1016\/j.peptides.2025.171405_bib33","unstructured":"T.H.P. Atlas.org, Tissue expression of SPX - Summary - The Human Protein Atlas, n.d. \u3008https:\/\/www.proteinatlas.org\/ENSG00000134548-SPX\/tissue\u3009. (Accessed 17.12.2024 2024)."},{"issue":"6220","key":"10.1016\/j.peptides.2025.171405_bib34","doi-asserted-by":"crossref","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"issue":"7","key":"10.1016\/j.peptides.2025.171405_bib35","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1210\/jc.2018-01008","article-title":"New avenues in the regulation of gallbladder motility-implications for the use of glucagon-like peptide-derived drugs","volume":"104","author":"Gether","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.peptides.2025.171405_bib36","article-title":"Spexin enhances bowel movement through activating l-type voltage-dependent calcium channel via galanin receptor 2 in mice","volume":"5","author":"Lin","year":"2015","journal-title":"Sci. Rep."},{"issue":"10","key":"10.1016\/j.peptides.2025.171405_bib37","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.bbalip.2018.08.001","article-title":"Spexin: a novel regulator of adipogenesis and fat tissue metabolism","volume":"1863","author":"Kolodziejski","year":"2018","journal-title":"Biochim Biophys. Acta Mol. Cell Biol. Lipids"},{"issue":"1","key":"10.1016\/j.peptides.2025.171405_bib38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3390\/genes13010081","article-title":"Spexin Promotes the proliferation and differentiation of C2C12 cells in vitro-the effect of exercise on spx and spx receptor expression in skeletal muscle in vivo","volume":"13","author":"Leciejewska","year":"2021","journal-title":"Genes"},{"issue":"7","key":"10.1016\/j.peptides.2025.171405_bib39","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1073\/pnas.0712300105","article-title":"Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2)","volume":"105","author":"Tofighi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"10","key":"10.1016\/j.peptides.2025.171405_bib40","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1515\/hsz-2016-0320","article-title":"Galanin suppresses proliferation of human U251 and T98G glioma cells via its subtype 1 receptor","volume":"398","author":"Mei","year":"2017","journal-title":"Biol. Chem."},{"issue":"2","key":"10.1016\/j.peptides.2025.171405_bib41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s13402-021-00631-y","article-title":"Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma","volume":"45","author":"de Medeiros","year":"2022","journal-title":"Cell Oncol. (Dordr. )"},{"issue":"16","key":"10.1016\/j.peptides.2025.171405_bib42","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The tumor microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr. Biol."},{"key":"10.1016\/j.peptides.2025.171405_bib43","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.686792","article-title":"The inflammatory profile of the tumor microenvironment, orchestrated by cyclooxygenase-2, promotes epithelial-mesenchymal transition","volume":"11","author":"Gomez-Valenzuela","year":"2021","journal-title":"Front Oncol."},{"issue":"5","key":"10.1016\/j.peptides.2025.171405_bib44","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1007\/s00018-020-03696-4","article-title":"Role of inflammatory microenvironment: potential implications for improved breast cancer nano-targeted therapy","volume":"78","author":"Lan","year":"2021","journal-title":"Cell Mol. Life Sci."},{"issue":"19","key":"10.1016\/j.peptides.2025.171405_bib45","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.3390\/cells13191666","article-title":"Beyond cancer cells: how the tumor microenvironment drives cancer progression","volume":"13","author":"Sabit","year":"2024","journal-title":"Cells"}],"container-title":["Peptides"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S019697812500066X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S019697812500066X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:41:24Z","timestamp":1777527684000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S019697812500066X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":45,"alternative-id":["S019697812500066X"],"URL":"https:\/\/doi.org\/10.1016\/j.peptides.2025.171405","relation":{},"ISSN":["0196-9781"],"issn-type":[{"value":"0196-9781","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Spexin expression in the human bile duct and perihilar cholangiocarcinoma","name":"articletitle","label":"Article Title"},{"value":"Peptides","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.peptides.2025.171405","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"171405"}}