{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:40:17Z","timestamp":1787020817623,"version":"build-2736575974"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["22KK0150"],"award-info":[{"award-number":["22KK0150"]}]},{"name":"Guangxi Natural Science Foundation","award":["2023GXNSFAA026201"],"award-info":[{"award-number":["2023GXNSFAA026201"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31900681"],"award-info":[{"award-number":["31900681"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"First-class discipline innovation-driven talent program of Guangxi Medical University","award":["2023-23"],"award-info":[{"award-number":["2023-23"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Clonorchiasis, a neglected tropical zoonosis, is caused by chronic infection with\n                      <jats:italic>Clonorchis sinensis<\/jats:italic>\n                      (\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      ). This infection can lead to cholangitis, bile duct epithelial hyperplasia, periductal fibrosis, and cholangiocarcinoma (CCA). However, the underlying carcinogenic mechanisms of CCA remain poorly understood, and there is not a well-developed model for\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      CCA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      -infected Sprague\u2013Dawley rat model, co-treated with\n                      <jats:italic>N<\/jats:italic>\n                      -nitrosodimethylamine, was established. The study comprised four groups: negative control (NC),\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection (CS),\n                      <jats:italic>N<\/jats:italic>\n                      -nitrosodimethylamine induction (NDMA), and combined\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection and\n                      <jats:italic>N<\/jats:italic>\n                      -nitrosodimethylamine induction (CSNDMA). Pathological damage to the hepatic ducts was evaluated at 10, 17, and 20\u00a0weeks after infection. The expression levels of the relevant genes and proteins were detected using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry, respectively. In addition, transcriptome sequencing was carried out on hepatic tissues infected for 20\u00a0weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Histopathological analysis using hematoxylin and eosin (H&amp;E) and Masson staining revealed bile duct dilation, inflammatory infiltration, and collagen deposition in the liver tissue of both CS and CSNDMA groups, with the most severe manifestations observed in the CSNDMA group. The CSNDMA group exhibited the earliest onset of CCA, occurring at 10\u00a0weeks post infection, with an overall incidence of 63%, peaking at 71% by 20\u00a0weeks. The CS group showed a 37% incidence of CCA, while only one case was noted in the NDMA group at 20\u00a0weeks. Quantitative PCR demonstrated that\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection induced upregulation of tumor-related markers in the liver, including\n                      <jats:italic>CK19<\/jats:italic>\n                      ,\n                      <jats:italic>PCNA<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>ITGB1<\/jats:italic>\n                      , and\n                      <jats:italic>MMP2<\/jats:italic>\n                      , particularly when co-exposed to\n                      <jats:italic>N<\/jats:italic>\n                      -nitrosodimethylamine. Immunohistochemistry detected the significant overexpression of CK19, CK7, and PCNA along bile ducts. Transcriptome sequencing further indicated that\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      significantly affected circadian rhythm and metabolic reprogramming in the liver, enriching pathways related to cancer, inflammation, and metabolism, including AMPK, PPAR, mTOR, and FoxO pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      can effectively promote the pathogenesis of CCA and significantly increase the expression of CCA-related genes (e.g.,\n                      <jats:italic>CK19<\/jats:italic>\n                      and\n                      <jats:italic>CK7<\/jats:italic>\n                      ). The inflammation, disrupting circadian rhythms and altering energy metabolism caused by\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection, may promote the progression of CCA. This study provides a foundational experimental basis for diagnosing and intervening in\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      -related CCA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-025-07183-2","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T07:13:52Z","timestamp":1765264432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploratory study on the role of Clonorchis sinensis infection in promoting cholangiocarcinoma progression"],"prefix":"10.1186","volume":"19","author":[{"given":"Shitao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kawanokuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganghuan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingzheng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeli","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"7183_CR1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/S0140-6736(15)60313-0","volume":"387","author":"MB Qian","year":"2016","unstructured":"Qian MB, Utzinger J, Keiser J, Zhou XN. Clonorchiasis. Lancet. 2016;387:800\u201310.","journal-title":"Lancet"},{"key":"7183_CR2","doi-asserted-by":"publisher","first-page":"e0000923","DOI":"10.1128\/cmr.00009-23","volume":"37","author":"MB Qian","year":"2024","unstructured":"Qian MB, Keiser J, Utzinger J, Zhou XN. Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control. Clin Microbiol Rev. 2024;37:e0000923.","journal-title":"Clin Microbiol Rev"},{"key":"7183_CR3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s40249-016-0166-1","volume":"5","author":"ZL Tang","year":"2016","unstructured":"Tang ZL, Huang Y, Yu XB. Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control. Infect Dis Poverty. 2016;5:71.","journal-title":"Infect Dis Poverty"},{"key":"7183_CR4","doi-asserted-by":"publisher","first-page":"e145","DOI":"10.3346\/jkms.2025.40.e145","volume":"40","author":"EM Kim","year":"2025","unstructured":"Kim EM, Hong ST. Clonorchis sinensis and cholangiocarcinoma. J Korean Med Sci. 2025;40:e145.","journal-title":"J Korean Med Sci"},{"key":"7183_CR5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S1470-2045(09)70096-8","volume":"10","author":"V Bouvard","year":"2009","unstructured":"Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et\u00a0al. A review of human carcinogens\u2014Part B: biological agents. Lancet Oncol. 2009;10:321\u20132.","journal-title":"Lancet Oncol"},{"key":"7183_CR6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/cancers13040791","volume":"13","author":"K Sawanyawisuth","year":"2021","unstructured":"Sawanyawisuth K, Sashida G, Sheng G. Epithelial-mesenchymal transition in liver fluke-induced cholangiocarcinoma. Cancers (Basel). 2021;13:4.","journal-title":"Cancers (Basel)"},{"key":"7183_CR7","doi-asserted-by":"publisher","first-page":"100737","DOI":"10.1016\/j.aohep.2022.100737","volume":"27","author":"A Elvevi","year":"2022","unstructured":"Elvevi A, Laffusa A, Scaravaglio M, Rossi RE, Longarini R, Stagno AM, et\u00a0al. Clinical treatment of cholangiocarcinoma: an updated comprehensive review. Ann Hepatol. 2022;27:100737.","journal-title":"Ann Hepatol"},{"key":"7183_CR8","doi-asserted-by":"publisher","first-page":"158","DOI":"10.32074\/1591-951X-252","volume":"113","author":"S Sarcognato","year":"2021","unstructured":"Sarcognato S, Sacchi D, Fassan M, Fabris L, Cadamuro M, Zanus G, et\u00a0al. Cholangiocarcinoma. Pathologica. 2021;113:158\u201369.","journal-title":"Pathologica"},{"key":"7183_CR9","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1017\/S0031182022000397","volume":"149","author":"MY Pakharukova","year":"2022","unstructured":"Pakharukova MY, Mordvinov VA. Similarities and differences among the Opisthorchiidae liver flukes: insights from Opisthorchis felineus. Parasitology. 2022;149:1306\u201318.","journal-title":"Parasitology"},{"key":"7183_CR10","doi-asserted-by":"publisher","first-page":"957","DOI":"10.4251\/wjgo.v12.i9.957","volume":"12","author":"B Rauff","year":"2020","unstructured":"Rauff B, Malik A, Bhatti YA, Chudhary SA, Qadri I, Rafiq S. Notch signalling pathway in development of cholangiocarcinoma. World J Gastrointest Oncol. 2020;12:957\u201374.","journal-title":"World J Gastrointest Oncol"},{"key":"7183_CR11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s13071-021-04717-2","volume":"14","author":"JW Kim","year":"2021","unstructured":"Kim JW, Yi J, Park J, Jeong JH, Kim J, Won J, et\u00a0al. Transcriptomic profiling of three-dimensional cholangiocyte spheroids long term exposed to repetitive Clonorchis sinensis excretory-secretory products. Parasit Vectors. 2021;14:213.","journal-title":"Parasit Vectors"},{"key":"7183_CR12","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.actatropica.2003.08.002","volume":"88","author":"B Sripa","year":"2003","unstructured":"Sripa B. Pathobiology of opisthorchiasis: an update. Acta Trop. 2003;88:209\u201320.","journal-title":"Acta Trop"},{"key":"7183_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00436-016-5276-y","volume":"116","author":"S Zheng","year":"2017","unstructured":"Zheng S, Zhu Y, Zhao Z, Wu Z, Okanurak K, Lv Z. Liver fluke infection and cholangiocarcinoma: a review. Parasitol Res. 2017;116:11\u20139.","journal-title":"Parasitol Res"},{"key":"7183_CR14","doi-asserted-by":"publisher","first-page":"236","DOI":"10.5009\/gnl17102","volume":"12","author":"P Prueksapanich","year":"2018","unstructured":"Prueksapanich P, Piyachaturawat P, Aumpansub P, Ridtitid W, Chaiteerakij R, Rerknimitr R. Liver fluke-associated biliary tract cancer. Gut Liver. 2018;12:236\u201345.","journal-title":"Gut Liver"},{"key":"7183_CR15","doi-asserted-by":"publisher","first-page":"590","DOI":"10.5483\/BMBRep.2016.49.11.109","volume":"49","author":"TS Kim","year":"2016","unstructured":"Kim TS, Pak JH, Kim JB, Bahk YY. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review. BMB Rep. 2016;49:590\u20137.","journal-title":"BMB Rep"},{"key":"7183_CR16","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s13071-023-05891-1","volume":"16","author":"Y Wu","year":"2023","unstructured":"Wu Y, Deng X, Wu Z, Liu D, Fu X, Tang L, et\u00a0al. Multilayer omics reveals the molecular mechanism of early infection of Clonorchis sinensis juvenile. Parasit Vectors. 2023;16:285.","journal-title":"Parasit Vectors"},{"key":"7183_CR17","doi-asserted-by":"publisher","first-page":"e0004008","DOI":"10.1371\/journal.pntd.0004008","volume":"9","author":"MH Uddin","year":"2015","unstructured":"Uddin MH, Choi MH, Kim WH, Jang JJ, Hong ST. Involvement of PSMD10, CDK4, and tumor suppressors in development of intrahepatic cholangiocarcinoma of Syrian golden hamsters induced by Clonorchis sinensis and N-nitrosodimethylamine. PLoS Negl Trop Dis. 2015;9:e0004008.","journal-title":"PLoS Negl Trop Dis"},{"key":"7183_CR18","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/0014-4894(54)90036-3","volume":"3","author":"JF Maldonado","year":"1954","unstructured":"Maldonado JF, Acosta-Matienzo J, Velez-Herrera F. Comparative value of fecal examination procedures in the diagnosis of helminth infections. Exp Parasitol. 1954;3:403\u201316.","journal-title":"Exp Parasitol"},{"key":"7183_CR19","doi-asserted-by":"publisher","first-page":"e0203811","DOI":"10.1371\/journal.pone.0203811","volume":"13","author":"M Calvopina","year":"2018","unstructured":"Calvopina M, Romero-Alvarez D, Diaz F, Cevallos W, Sugiyama H. A comparison of Kato-Katz technique to three other methods for diagnosis of Amphimerus spp. liver fluke infection and the prevalence of infection in Chachi Amerindians of Ecuador. PLoS ONE. 2018;13:e0203811.","journal-title":"PLoS ONE"},{"key":"7183_CR20","first-page":"e37872","volume":"15","author":"JK Chaurasia","year":"2023","unstructured":"Chaurasia JK, Ilyas AM, Walke V, Gupta V, Kapoor N. The role of cytomorphometric image analysis in the diagnosis of thyroid nodules. Cureus. 2023;15:e37872.","journal-title":"Cureus"},{"key":"7183_CR21","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1586\/17474124.2016.1104246","volume":"10","author":"Y Nakanuma","year":"2016","unstructured":"Nakanuma Y, Miyata T, Uchida T. Latest advances in the pathological understanding of cholangiocarcinomas. Expert Rev Gastroenterol Hepatol. 2016;10:113\u201327.","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"7183_CR22","first-page":"2522","volume":"506","author":"M El Homsi","year":"2025","unstructured":"El Homsi M, Alkhasawneh A, Arif-Tiwari H, Czeyda-Pommersheim F, Khasawneh H, Kierans AS, et\u00a0al. Classification of intrahepatic cholangiocarcinoma. Abdom Radiol (NY). 2025;506:2522\u201332.","journal-title":"Abdom Radiol (NY)"},{"key":"7183_CR23","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3390\/curroncol30010030","volume":"30","author":"N Guedj","year":"2022","unstructured":"Guedj N. Pathology of cholangiocarcinomas. Curr Oncol. 2022;30:370\u201380.","journal-title":"Curr Oncol"},{"key":"7183_CR24","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","volume":"7","author":"PJ Brindley","year":"2021","unstructured":"Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE, et\u00a0al. Cholangiocarcinoma. Nat Rev Dis Primers. 2021;7:65.","journal-title":"Nat Rev Dis Primers"},{"key":"7183_CR25","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, et\u00a0al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557\u201388.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7183_CR26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1136\/gutjnl-2023-330029","volume":"73","author":"SM Rushbrook","year":"2023","unstructured":"Rushbrook SM, Kendall TJ, Zen Y, Albazaz R, Manoharan P, Pereira SP, et\u00a0al. British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma. Gut. 2023;73:16\u201346.","journal-title":"Gut"},{"key":"7183_CR27","doi-asserted-by":"publisher","first-page":"396","DOI":"10.3350\/cmh.2021.0287","volume":"28","author":"M Komuta","year":"2022","unstructured":"Komuta M. Intrahepatic cholangiocarcinoma: tumour heterogeneity and its clinical relevance. Clin Mol Hepatol. 2022;28:396\u2013407.","journal-title":"Clin Mol Hepatol"},{"key":"7183_CR28","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3347\/kjp.1993.31.1.21","volume":"31","author":"JH Lee","year":"1993","unstructured":"Lee JH, Rim HJ, Bak UB. Effect of Clonorchis sinensis infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian golden hamsters. Korean J Parasitol. 1993;31:21\u201330.","journal-title":"Korean J Parasitol"},{"key":"7183_CR29","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3347\/kjp.2016.54.3.281","volume":"54","author":"MH Uddin","year":"2016","unstructured":"Uddin MH, Li S, Jin Y, Choi MH, Jang JJ, Hong ST. C3H\/He mice as an incompatible cholangiocarcinoma model by Clonorchis sinensis, dicyclanil and N-nitrosodimethylamine. Korean J Parasitol. 2016;54:281\u20139.","journal-title":"Korean J Parasitol"},{"key":"7183_CR30","doi-asserted-by":"publisher","first-page":"e0005614","DOI":"10.1371\/journal.pntd.0005614","volume":"11","author":"EM Kim","year":"2017","unstructured":"Kim EM, Kwak YS, Yi MH, Kim JY, Sohn WM, Yong TS. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo. PLoS Negl Trop Dis. 2017;11:e0005614.","journal-title":"PLoS Negl Trop Dis"},{"key":"7183_CR31","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3347\/kjp.2020.58.5.513","volume":"58","author":"WG Yoo","year":"2020","unstructured":"Yoo WG, Kang JM, L\u00ea HG, Pak JH, Hong SJ, Sohn WM, et\u00a0al. Bile ductal transcriptome identifies key pathways and hub genes in Clonorchis sinensis-infected Sprague-Dawley rats. Korean J Parasitol. 2020;58:513\u201325.","journal-title":"Korean J Parasitol"},{"key":"7183_CR32","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1007\/s00436-022-07699-x","volume":"121","author":"Y Qi","year":"2022","unstructured":"Qi Y, Hu J, Liang J, Hu X, Ma N, Xiang B. Clonorchis sinensis infection contributes to hepatocellular carcinoma progression in rat. Parasitol Res. 2022;121:3403\u201315.","journal-title":"Parasitol Res"},{"key":"7183_CR33","doi-asserted-by":"publisher","first-page":"1286977","DOI":"10.3389\/fcimb.2023.1286977","volume":"13","author":"T Zhan","year":"2023","unstructured":"Zhan T, Wu Y, Deng X, Li Q, Chen Y, Lv J, et\u00a0al. Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver. Front Cell Infect Microbiol. 2023;13:1286977.","journal-title":"Front Cell Infect Microbiol"},{"key":"7183_CR34","doi-asserted-by":"publisher","first-page":"1011378","DOI":"10.3389\/fcimb.2022.1011378","volume":"12","author":"JX Liu","year":"2022","unstructured":"Liu JX, Liu M, Yu GZ, Zhao QQ, Wang JL, Sun YH, et\u00a0al. Clonorchis sinensis infection induces hepatobiliary injury via disturbing sphingolipid metabolism and activating sphingosine 1-phosphate receptor 2. Front Cell Infect Microbiol. 2022;12:1011378.","journal-title":"Front Cell Infect Microbiol"},{"key":"7183_CR35","doi-asserted-by":"publisher","first-page":"526997","DOI":"10.3389\/fcimb.2020.526997","volume":"10","author":"C Yan","year":"2020","unstructured":"Yan C, Wu J, Xu N, Li J, Zhou QY, Yang HM, et\u00a0al. TLR4 deficiency exacerbates biliary injuries and peribiliary fibrosis caused by Clonorchis sinensis in a resistant mouse strain. Front Cell Infect Microbiol. 2020;10:526997.","journal-title":"Front Cell Infect Microbiol"},{"key":"7183_CR36","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060869","author":"JH Jeong","year":"2021","unstructured":"Jeong JH, Yi J, Hwang MK, Hong SJ, Sohn WM, Kim TS, et\u00a0al. The overactivation of NADPH oxidase during Clonorchis sinensis infection and the exposure to N-nitroso compounds promote periductal fibrosis. Antioxidants. 2021. https:\/\/doi.org\/10.3390\/antiox10060869.","journal-title":"Antioxidants"},{"key":"7183_CR37","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1590\/S1517-74912003000100016","volume":"171","author":"GB Martins","year":"2003","unstructured":"Martins GB, Reis SR, Silva TM. Collagen type I expression in squamous cell carcinoma of the oral cavity. Pesqui Odontol Bras. 2003;171:82\u20138.","journal-title":"Pesqui Odontol Bras"},{"key":"7183_CR38","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.ijpharm.2010.05.004","volume":"3941\u20132","author":"H Ichihara","year":"2010","unstructured":"Ichihara H, Funamoto K, Matsushita T, Matsumoto Y, Ueoka R. Histological bioanalysis for therapeutic effects of hybrid liposomes on the hepatic metastasis of colon carcinoma in vivo. Int J Pharm. 2010;3941\u20132:174\u20138.","journal-title":"Int J Pharm"},{"key":"7183_CR39","first-page":"1251","volume":"375","author":"K Okamoto","year":"2010","unstructured":"Okamoto K, Tajima H, Ohta T, Nakanuma S, Hayashi H, Nakagawara H, et\u00a0al. Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells. Int J Oncol. 2010;375:1251\u20139.","journal-title":"Int J Oncol"},{"key":"7183_CR40","doi-asserted-by":"publisher","first-page":"6622","DOI":"10.1158\/0008-5472.CAN-05-4609","volume":"66","author":"PA Farazi","year":"2006","unstructured":"Farazi PA, Zeisberg M, Glickman J, Zhang Y, Kalluri R, DePinho RA. Chronic bile duct injury associated with fibrotic matrix microenvironment provokes cholangiocarcinoma in p53-deficient mice. Cancer Res. 2006;66:6622\u20137.","journal-title":"Cancer Res"},{"key":"7183_CR41","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1055\/s-0040-1705109","volume":"40","author":"L Fabris","year":"2020","unstructured":"Fabris L, Cadamuro M, Cagnin S, Strazzabosco M, Gores GJ. Liver matrix in benign and malignant biliary tract disease. Semin Liver Dis. 2020;40:282\u201397.","journal-title":"Semin Liver Dis"},{"key":"7183_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115780","author":"Y Takahashi","year":"2021","unstructured":"Takahashi Y, Dungubat E, Kusano H, Ganbat D, Tomita Y, Odgerel S, et\u00a0al. Application of immunohistochemistry in the pathological diagnosis of liver tumors. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22115780.","journal-title":"Int J Mol Sci"},{"key":"7183_CR43","doi-asserted-by":"publisher","first-page":"21518","DOI":"10.18632\/aging.103936","volume":"12","author":"Q Liu","year":"2020","unstructured":"Liu Q, Lan T, Song Y, Cai J, Yu X, Chen W. Oncostatin M expression and TP53 mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma. Aging Albany NY. 2020;12:21518\u201343.","journal-title":"Aging Albany NY"},{"key":"7183_CR44","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1038\/s41419-021-04451-8","volume":"12","author":"Y Wang","year":"2021","unstructured":"Wang Y, Li K, Zhao W, Liu Z, Liu J, Shi A, et\u00a0al. Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression. Cell Death Dis. 2021;12:1158.","journal-title":"Cell Death Dis"},{"key":"7183_CR45","first-page":"3577","volume":"127","author":"S Pan","year":"2020","unstructured":"Pan S, Hu Y, Hu M, Jian H, Chen M, Gan L, et\u00a0al. Platelet-derived PDGF promotes the invasion and metastasis of cholangiocarcinoma by upregulating MMP2\/MMP9 expression and inducing EMT via the p38\/MAPK signalling pathway. Am J Transl Res. 2020;127:3577\u201395.","journal-title":"Am J Transl Res"},{"key":"7183_CR46","doi-asserted-by":"publisher","first-page":"101279","DOI":"10.1016\/j.aohep.2023.101279","volume":"29","author":"S Pan","year":"2024","unstructured":"Pan S, Hu Y, Gan L, Lai J, Zheng P, Zhang Y, et\u00a0al. Matrix metalloproteinase-2 inducing COL1A1 synthesis via integrin alpha \u2164 promotes invasion and metastasis of cholangiocarcinoma cells. Ann Hepatol. 2024;29:101279.","journal-title":"Ann Hepatol"},{"key":"7183_CR47","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030512","author":"K Voskarides","year":"2023","unstructured":"Voskarides K, Giannopoulou N. The role of TP53 in adaptation and evolution. Cells. 2023. https:\/\/doi.org\/10.3390\/cells12030512.","journal-title":"Cells"},{"key":"7183_CR48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13046-023-02929-1","volume":"43","author":"YJ Zhou","year":"2024","unstructured":"Zhou YJ, Yang ML, He X, Gu HY, Ren JH, Cheng ST, et\u00a0al. RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1\/FAK\/SRC signaling. J Exp Clin Cancer Res. 2024;43:45.","journal-title":"J Exp Clin Cancer Res"},{"key":"7183_CR49","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s12072-022-10428-2","volume":"17","author":"YS Chung","year":"2023","unstructured":"Chung YS, Jeon Y, Yoo JE, Chung T, Ryu HJ, Kim H, et\u00a0al. Albumin, filamin-A and cytokeratin 19 help distinguish intrahepatic cholangiocarcinoma from extrahepatic adenocarcinoma. Hepatol Int. 2023;17:77\u201385.","journal-title":"Hepatol Int"},{"key":"7183_CR50","doi-asserted-by":"publisher","first-page":"e12817","DOI":"10.1111\/hel.12817","volume":"26","author":"R Dangtakot","year":"2021","unstructured":"Dangtakot R, Intuyod K, Chamgramol Y, Pairojkul C, Pinlaor S, Jantawong C, et\u00a0al. CagA(+) Helicobacter pylori infection and N-nitrosodimethylamine administration induce cholangiocarcinoma development in hamsters. Helicobacter. 2021;26:e12817.","journal-title":"Helicobacter"},{"key":"7183_CR51","doi-asserted-by":"publisher","first-page":"8621","DOI":"10.1038\/s41598-025-93192-1","volume":"15","author":"R Jaidee","year":"2025","unstructured":"Jaidee R, Jusakul A, Pocasap P, Kukongviriyapan V, Senggunprai L, Prawan A, et\u00a0al. Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization. Sci Rep. 2025;15:8621.","journal-title":"Sci Rep"},{"key":"7183_CR52","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/jso.25027","volume":"117","author":"LZ Liu","year":"2018","unstructured":"Liu LZ, Yang LX, Zheng BH, Dong PP, Liu XY, Wang ZC, et\u00a0al. CK7\/CK19 index: a potential prognostic factor for postoperative intrahepatic cholangiocarcinoma patients. J Surg Oncol. 2018;117:1531\u20139.","journal-title":"J Surg Oncol"},{"key":"7183_CR53","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105679","author":"YL Wang","year":"2022","unstructured":"Wang YL, Wu WR, Lin PL, Shen YC, Lin YZ, Li HW, et\u00a0al. The functions of PCNA in tumor stemness and invasion. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms23105679.","journal-title":"Int J Mol Sci"},{"key":"7183_CR54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.semcancer.2024.08.002","volume":"106\u2013107","author":"V Penugurti","year":"2024","unstructured":"Penugurti V, Manne RK, Bai L, Kant R, Lin HK. AMPK: The energy sensor at the crossroads of aging and cancer. Semin Cancer Biol. 2024;106\u2013107:15\u201327.","journal-title":"Semin Cancer Biol"},{"key":"7183_CR55","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.semcancer.2021.04.006","volume":"85","author":"CC Hsu","year":"2022","unstructured":"Hsu CC, Peng D, Cai Z, Lin HK. AMPK signaling and its targeting in cancer progression and treatment. Semin Cancer Biol. 2022;85:52\u201368.","journal-title":"Semin Cancer Biol"},{"key":"7183_CR56","doi-asserted-by":"publisher","first-page":"108391","DOI":"10.1016\/j.pharmthera.2023.108391","volume":"245","author":"H Chen","year":"2023","unstructured":"Chen H, Tan H, Wan J, Zeng Y, Wang J, Wang H, et\u00a0al. PPAR-\u03b3 signaling in nonalcoholic fatty liver disease: pathogenesis and therapeutic targets. Pharmacol Ther. 2023;245:108391.","journal-title":"Pharmacol Ther"},{"key":"7183_CR57","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062061","author":"Y Wang","year":"2020","unstructured":"Wang Y, Nakajima T, Gonzalez FJ, Tanaka N. PPARs as metabolic regulators in the liver: lessons from liver-specific PPAR-null mice. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21062061.","journal-title":"Int J Mol Sci"},{"key":"7183_CR58","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.ctrv.2018.11.001","volume":"72","author":"F Corti","year":"2019","unstructured":"Corti F, Nichetti F, Raimondi A, Niger M, Prinzi N, Torchio M, et\u00a0al. Targeting the PI3K\/AKT\/mTOR pathway in biliary tract cancers: a review of current evidences and future perspectives. Cancer Treat Rev. 2019;72:45\u201355.","journal-title":"Cancer Treat Rev"},{"key":"7183_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041266","author":"G Ferr\u00edn","year":"2020","unstructured":"Ferr\u00edn G, Guerrero M, Amado V, Rodr\u00edguez-Per\u00e1lvarez M, la De Mata M. Activation of mTOR signaling pathway in hepatocellular carcinoma. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21041266.","journal-title":"Int J Mol Sci"},{"key":"7183_CR60","doi-asserted-by":"publisher","first-page":"e0086224","DOI":"10.1128\/mbio.00862-24","volume":"156","author":"CJ Genito","year":"2024","unstructured":"Genito CJ, Darwitz BP, Reber CP, Moorman NJ, Graves CL, Monteith AJ, et\u00a0al. mTOR signaling is required for phagocyte free radical production, GLUT1 expression, and control of Staphylococcus aureus infection. mBio. 2024;156:e0086224.","journal-title":"mBio"},{"key":"7183_CR61","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1080\/15548627.2019.1628536","volume":"16","author":"YF Wu","year":"2020","unstructured":"Wu YF, Li ZY, Dong LL, Li WJ, Wu YP, Wang J, et\u00a0al. Inactivation of MTOR promotes autophagy-mediated epithelial injury in particulate matter-induced airway inflammation. Autophagy. 2020;16:435\u201350.","journal-title":"Autophagy"},{"key":"7183_CR62","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1172\/JCI133264","volume":"130","author":"Y Xie","year":"2020","unstructured":"Xie Y, Zhao Y, Shi L, Li W, Chen K, Li M, et\u00a0al. Gut epithelial TSC1\/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer. J Clin Invest. 2020;130:2111\u201328.","journal-title":"J Clin Invest"},{"key":"7183_CR63","doi-asserted-by":"publisher","first-page":"R67","DOI":"10.1530\/JOE-17-0002","volume":"2332","author":"S Lee","year":"2017","unstructured":"Lee S, Dong HH. FoxO integration of insulin signaling with glucose and lipid metabolism. J Endocrinol. 2017;2332:R67-r79.","journal-title":"J Endocrinol"},{"key":"7183_CR64","doi-asserted-by":"publisher","first-page":"1489077","DOI":"10.3389\/fimmu.2024.1489077","volume":"15","author":"Z Tang","year":"2024","unstructured":"Tang Z, Wei C, Deng X, Lin Q, Hu Q, Li S, et\u00a0al. Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with Clonorchis sinensis. Front Immunol. 2024;15:1489077.","journal-title":"Front Immunol"},{"key":"7183_CR65","doi-asserted-by":"publisher","first-page":"e0155024","DOI":"10.1128\/spectrum.01550-24","volume":"132","author":"X Deng","year":"2025","unstructured":"Deng X, Li S, Wu Y, Yao J, Hou W, Zheng J, et\u00a0al. Correlation analysis of the impact of Clonorchis sinensis juvenile on gut microbiota and transcriptome in mice. Microbiol Spectr. 2025;132:e0155024.","journal-title":"Microbiol Spectr"},{"key":"7183_CR66","doi-asserted-by":"publisher","first-page":"C306","DOI":"10.1152\/ajpcell.00166.2022","volume":"3232","author":"Z Taleb","year":"2022","unstructured":"Taleb Z, Karpowicz P. Circadian regulation of digestive and metabolic tissues. Am J Physiol Cell Physiol. 2022;3232:C306\u201321.","journal-title":"Am J Physiol Cell Physiol"},{"key":"7183_CR67","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nrgastro.2016.8","volume":"134","author":"Y Tahara","year":"2016","unstructured":"Tahara Y, Shibata S. Circadian rhythms of liver physiology and disease: experimental and clinical evidence. Nat Rev Gastroenterol Hepatol. 2016;134:217\u201326.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"7183_CR68","doi-asserted-by":"publisher","first-page":"e12639","DOI":"10.1111\/jpi.12639","volume":"683","author":"K Sato","year":"2020","unstructured":"Sato K, Meng F, Francis H, Wu N, Chen L, Kennedy L, et\u00a0al. Melatonin and circadian rhythms in liver diseases: functional roles and potential therapies. J Pineal Res. 2020;683:e12639.","journal-title":"J Pineal Res"},{"key":"7183_CR69","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.jhep.2022.04.038","volume":"773","author":"C Raggi","year":"2022","unstructured":"Raggi C, Taddei ML, Rae C, Braconi C, Marra F. Metabolic reprogramming in cholangiocarcinoma. J Hepatol. 2022;773:849\u201364.","journal-title":"J Hepatol"},{"key":"7183_CR70","doi-asserted-by":"publisher","first-page":"217714","DOI":"10.1016\/j.canlet.2025.217714","volume":"622","author":"Q Wang","year":"2025","unstructured":"Wang Q, Long T, Tang P, Xu C, Wang L, Liu J. Metabolic reprogramming in cholangiocarcinoma cancer stem cells: emerging therapeutic paradigms. Cancer Lett. 2025;622:217714.","journal-title":"Cancer Lett"},{"key":"7183_CR71","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201606","author":"X Bian","year":"2021","unstructured":"Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Lipid metabolism and cancer. J Exp Med. 2021. https:\/\/doi.org\/10.1084\/jem.20201606.","journal-title":"J Exp Med"},{"key":"7183_CR72","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-023-01498-2","volume":"161","author":"HR Jin","year":"2023","unstructured":"Jin HR, Wang J, Wang ZJ, Xi MJ, Xia BH, Deng K, et\u00a0al. Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics. J Hematol Oncol. 2023;161:103.","journal-title":"J Hematol Oncol"}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-07183-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13071-025-07183-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-07183-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T04:54:45Z","timestamp":1768366485000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13071-025-07183-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["7183"],"URL":"https:\/\/doi.org\/10.1186\/s13071-025-07183-2","relation":{},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"3 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal protocol was reviewed and approved by the Animal Ethics Committee of Guangxi Medical University (approval no. 202310023). All the experiments were conducted according to the guidelines of the National Standard GB\/T35892-2018 of the People\u2019s Republic of China. The number of animals used was minimized in accordance with the guidelines of the Institutional Animal Ethics Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}