{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:19:47Z","timestamp":1790835587422,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010839","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000}}],"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Program, Research and Graduate Studies, Khon Kaen University"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA164719"],"award-info":[{"award-number":["CA164719"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1085309"],"award-info":[{"award-number":["APP1085309"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1117504"],"award-info":[{"award-number":["APP1117504"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107475\/Z\/15\/Z"],"award-info":[{"award-number":["107475\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infection with the food-borne liver fluke\n                    <jats:italic>Opisthorchis viverrini<\/jats:italic>\n                    is the principal risk factor for cholangiocarcinoma (CCA) in the Mekong Basin countries of Thailand, Lao PDR, Vietnam, Myanmar and Cambodia. Using a novel model of CCA, involving infection with gene-edited liver flukes in the hamster during concurrent exposure to dietary nitrosamine, we explored the role of the fluke granulin-like growth factor\n                    <jats:italic>Ov<\/jats:italic>\n                    -GRN-1 in malignancy. We derived RNA-guided gene knockout flukes (\n                    <jats:italic>\u0394Ov-grn-1)<\/jats:italic>\n                    using CRISPR\/Cas9\/gRNA materials delivered by electroporation. Genome sequencing confirmed programmed Cas9-catalyzed mutations of the targeted genes, which was accompanied by rapid depletion of transcripts and the proteins they encode. Gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes. However, less hepatobiliary tract disease manifested during chronic infection with\n                    <jats:italic>\u0394Ov-grn-1<\/jats:italic>\n                    worms in comparison to hamsters infected with control gene-edited and mock-edited parasites. Specifically, immuno- and colorimetric-histochemical analysis of livers revealed markedly less periductal fibrosis surrounding the flukes and less fibrosis globally within the hepatobiliary tract during infection with\n                    <jats:italic>\u0394Ov-grn-1<\/jats:italic>\n                    genotype worms, minimal biliary epithelial cell proliferation, and significantly fewer mutations of\n                    <jats:italic>TP53<\/jats:italic>\n                    in biliary epithelial cells. Moreover, fewer hamsters developed high-grade CCA compared to controls. The clinically relevant, pathophysiological phenotype of the hepatobiliary tract confirmed a role for this secreted growth factor in malignancy and morbidity during opisthorchiasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010839","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T14:28:18Z","timestamp":1663856898000},"page":"e1010839","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini"],"prefix":"10.1371","volume":"18","author":[{"given":"Sujittra","family":"Chaiyadet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirikachorn","family":"Tangkawattana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Smout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wannaporn","family":"Ittiprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria H.","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raksawan","family":"Deenonpoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patpicha","family":"Arunsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0002","authenticated-orcid":true,"given":"Paul J.","family":"Brindley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thewarach","family":"Laha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"issue":"1","key":"ppat.1010839.ref001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"PJ Brindley","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"ppat.1010839.ref002","article-title":"Opisthorchis felineus infection is a risk factor for cholangiocarcinoma in Western Siberia: a hospital-based case-control study","author":"OS Fedorova","year":"2022","journal-title":"Clin Infect Dis"},{"issue":"Pt B","key":"ppat.1010839.ref003","first-page":"1","article-title":"Biological agents. 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