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Sciences"]}" data-trace="false" data-dom-id="Pill-react-component-f120235e-0ebd-4753-8d98-16846d5e0149"></div> <div id="Pill-react-component-f120235e-0ebd-4753-8d98-16846d5e0149"></div> </a></div></div></div></div><div class="right-panel-container"><div class="user-content-wrapper"><div class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by George Yeoh</h3></div><div class="js-work-strip profile--work_container" data-work-id="124015416"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/124015416/CCDC_1408487_Experimental_Crystal_Structure_Determination"><img alt="Research paper thumbnail of CCDC 1408487: Experimental Crystal Structure Determination" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/124015416/CCDC_1408487_Experimental_Crystal_Structure_Determination">CCDC 1408487: Experimental Crystal Structure Determination</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">An entry from the Cambridge Structural Database, the world&#39;s repository for small molecule cr...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">An entry from the Cambridge Structural Database, the world&#39;s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="124015416"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="124015416"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 124015416; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=124015410]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":124015410,"title":"Additional file 14 of Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma","internal_url":"https://www.academia.edu/124015410/Additional_file_14_of_Epigenetic_reactivation_of_tumor_suppressor_genes_with_CRISPRa_technologies_as_precision_therapy_for_hepatocellular_carcinoma","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235868"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235868/FRL_19_an_embryonic_liver_stem_cell_line_particularly_sensitive_to_lentivirus_vector_mediated_gene_transfer"><img alt="Research paper thumbnail of FRL 19, an embryonic liver stem cell line particularly sensitive to lentivirus vector-mediated gene transfer" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235868/FRL_19_an_embryonic_liver_stem_cell_line_particularly_sensitive_to_lentivirus_vector_mediated_gene_transfer">FRL 19, an embryonic liver stem cell line particularly sensitive to lentivirus vector-mediated gene transfer</a></div><div class="wp-workCard_item"><span>Journal of Gene Medicine</span><span>, 2003</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235868"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235868"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235868; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235868]").text(description); $(".js-view-count[data-work-id=118235868]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235868; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235868']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235866"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235866/Kupffer_cell_cytokines_interleukin_1%CE%B2_and_interleukin_10_may_mediate_sepsis_induced_hypoglycaemia"><img alt="Research paper thumbnail of Kupffer cell cytokines, interleukin-1尾 and interleukin-10 may mediate sepsis-induced hypoglycaemia" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235866/Kupffer_cell_cytokines_interleukin_1%CE%B2_and_interleukin_10_may_mediate_sepsis_induced_hypoglycaemia">Kupffer cell cytokines, interleukin-1尾 and interleukin-10 may mediate sepsis-induced hypoglycaemia</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235866"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235866"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235866; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235866]").text(description); $(".js-view-count[data-work-id=118235866]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235866; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235866']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=118235866]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":118235866,"title":"Kupffer cell cytokines, interleukin-1尾 and interleukin-10 may mediate sepsis-induced hypoglycaemia","internal_url":"https://www.academia.edu/118235866/Kupffer_cell_cytokines_interleukin_1%CE%B2_and_interleukin_10_may_mediate_sepsis_induced_hypoglycaemia","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235865"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235865/Presence_of_Oval_Cells_in_the_Liver_of_P53_Null_Mice"><img alt="Research paper thumbnail of Presence of Oval Cells in the Liver of P53 Null Mice" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235865/Presence_of_Oval_Cells_in_the_Liver_of_P53_Null_Mice">Presence of Oval Cells in the Liver of P53 Null Mice</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235865"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235865"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235865; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235865]").text(description); $(".js-view-count[data-work-id=118235865]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235865; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235865']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=118235865]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":118235865,"title":"Presence of Oval Cells in the Liver of P53 Null Mice","internal_url":"https://www.academia.edu/118235865/Presence_of_Oval_Cells_in_the_Liver_of_P53_Null_Mice","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235864"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235864/5_Regulatory_Elements_Direct_Developmental_Expression_of_Tyrosine_Aminotransferase_in_Primary_Cultures_of_Fetal_Rat_Hepatocytes"><img alt="Research paper thumbnail of 5' Regulatory Elements Direct Developmental Expression of Tyrosine Aminotransferase in Primary Cultures of Fetal Rat Hepatocytes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235864/5_Regulatory_Elements_Direct_Developmental_Expression_of_Tyrosine_Aminotransferase_in_Primary_Cultures_of_Fetal_Rat_Hepatocytes">5' Regulatory Elements Direct Developmental Expression of Tyrosine Aminotransferase in Primary Cultures of Fetal Rat Hepatocytes</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235864"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235864"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235864; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235864]").text(description); $(".js-view-count[data-work-id=118235864]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235864; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235864']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=118235864]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":118235864,"title":"5' Regulatory Elements Direct Developmental Expression of Tyrosine Aminotransferase in Primary Cultures of Fetal Rat Hepatocytes","internal_url":"https://www.academia.edu/118235864/5_Regulatory_Elements_Direct_Developmental_Expression_of_Tyrosine_Aminotransferase_in_Primary_Cultures_of_Fetal_Rat_Hepatocytes","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235863"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235863/Transdifferentiation_of_pancreatic_progenitor_cells_to_hepatocyte_like_cells_is_not_serum_dependent_when_facilitated_by_extracellular_matrix_proteins"><img alt="Research paper thumbnail of Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/113909953/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235863/Transdifferentiation_of_pancreatic_progenitor_cells_to_hepatocyte_like_cells_is_not_serum_dependent_when_facilitated_by_extracellular_matrix_proteins">Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins</a></div><div class="wp-workCard_item"><span>Scientific Reports</span><span>, Mar 12, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for l...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin-or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="12cb6834155197ea3ac3b6deb5990617" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909953,"asset_id":118235863,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909953/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235863"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235863"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235863; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235862"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235862/Interleukin_6_secreted_by_bipotential_murine_oval_liver_stem_cells_induces_apoptosis_of_activated_hepatic_stellate_cells_by_activating_NF_%CE%BAB_inducible_nitric_oxide_synthase_signaling"><img alt="Research paper thumbnail of Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-魏B-inducible nitric oxide synthase signaling" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235862/Interleukin_6_secreted_by_bipotential_murine_oval_liver_stem_cells_induces_apoptosis_of_activated_hepatic_stellate_cells_by_activating_NF_%CE%BAB_inducible_nitric_oxide_synthase_signaling">Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-魏B-inducible nitric oxide synthase signaling</a></div><div class="wp-workCard_item"><span>Biochemistry and Cell Biology</span><span>, Apr 1, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liver fibrosis is now well recognized as the causative factor for increased mortality from compli...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liver fibrosis is now well recognized as the causative factor for increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and (or) treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated HSCs to prevent progression of liver fibrosis. We used a conditioned medium-based approach to study the effect of BMOL cells on activated HSC survival and function. Our data showed that BMOL cells block the contraction of activated HSCs by inducing apoptosis of these cells. We demonstrated that BMOL cells secrete soluble factors, such as interleukin-6 (IL-6), which induced apoptosis of activated HSCs. Using both pharmacological and molecular inhibitor approaches, we further identified that IL-6-mediated activation of NF-魏B鈥搃NOS鈥揘O鈥揜OS signaling in activated HSCs plays a critical role in BMOL-cell-mediated apoptosis of activated HSCs. Thus, the present study provides an alternative cell-based therapeutic approach to treat liver fibrosis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235862"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235862"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235862; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235862]").text(description); 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235860"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235860/CX3CR1_reduces_choline_deficient_ethionine_supplemented_diet_induced_liver_injury_and_liver_progenitor_cell_proliferation"><img alt="Research paper thumbnail of CX3CR1 reduces choline-deficient, ethionine-supplemented diet-induced liver injury and liver progenitor cell proliferation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235860/CX3CR1_reduces_choline_deficient_ethionine_supplemented_diet_induced_liver_injury_and_liver_progenitor_cell_proliferation">CX3CR1 reduces choline-deficient, ethionine-supplemented diet-induced liver injury and liver progenitor cell proliferation</a></div><div class="wp-workCard_item"><span>European Journal of Immunology</span><span>, 2016</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235860"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235860"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235860; 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235858"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235858/Cells_of_the_ductular_reaction_produce_the_chemokine_monocyte_chemotaxis_protein_1_which_initiates_fibrosis_in_pediatric_cholestatic_liver_disease"><img alt="Research paper thumbnail of Cells of the ductular reaction produce the chemokine monocyte chemotaxis protein-1, which initiates fibrosis in pediatric cholestatic liver disease" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235858/Cells_of_the_ductular_reaction_produce_the_chemokine_monocyte_chemotaxis_protein_1_which_initiates_fibrosis_in_pediatric_cholestatic_liver_disease">Cells of the ductular reaction produce the chemokine monocyte chemotaxis protein-1, which initiates fibrosis in pediatric cholestatic liver disease</a></div><div class="wp-workCard_item"><span>Journal of Gastroenterology and Hepatology</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235858"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235858"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235858; 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} }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235856"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235856/Tumor_necrosis_factor_like_weak_inducer_of_apoptosis_is_a_mitogen_for_liver_progenitor_cells"><img alt="Research paper thumbnail of Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells" class="work-thumbnail" src="https://attachments.academia-assets.com/113909951/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235856/Tumor_necrosis_factor_like_weak_inducer_of_apoptosis_is_a_mitogen_for_liver_progenitor_cells">Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells</a></div><div class="wp-workCard_item"><span>Hepatology</span><span>, Mar 15, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration du...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDEtreated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin-positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFjB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFjB subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14dependent and NFjB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (HEPATOLOGY 2010;52:291-302) See Editorial on Page 13. H epatocyte-driven liver regeneration following acute injury is a highly orchestrated process in which remaining, healthy hepatocytes proliferate under the control of well-understood genetic, cellular, and metabolic networks. 1 During chronic liver injury, however, when the functional liver mass is reduced and coincidentally hepatocyte proliferation is wholly or partly impaired, liver regeneration is</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d6cd7297ba37fd3036b8f2081e6455da" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909951,"asset_id":118235856,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909951/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235856"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235856"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235856; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235856]").text(description); $(".js-view-count[data-work-id=118235856]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235856; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235856']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "d6cd7297ba37fd3036b8f2081e6455da" } } $('.js-work-strip[data-work-id=118235856]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":118235856,"title":"Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells","internal_url":"https://www.academia.edu/118235856/Tumor_necrosis_factor_like_weak_inducer_of_apoptosis_is_a_mitogen_for_liver_progenitor_cells","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[{"id":113909951,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/113909951/thumbnails/1.jpg","file_name":"tumor_necrosis_factor.pdf","download_url":"https://www.academia.edu/attachments/113909951/download_file","bulk_download_file_name":"Tumor_necrosis_factor_like_weak_inducer.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/113909951/tumor_necrosis_factor-libre.pdf?1714358525=\u0026response-content-disposition=attachment%3B+filename%3DTumor_necrosis_factor_like_weak_inducer.pdf\u0026Expires=1740536326\u0026Signature=dwuZF7yc4UhJWM1~AJ4LgKEZulwq-~V96MfI8yn5cy9Q5EKcOZSHJ0FX7zLfsF-4NtIqzneUZevuAiBAdkbXAkF8i~c57dUQ1gHjGolepHVigeHVNJ8M2cfWzJOK1mUKHQD2gvysesGfD9KKQ0RNKGhZZBJmxQeXVsURzWGIfoy9Ig7uq1CFu9IsAFp2xi0gEsvBPvVOLbD6K2atRHiUatWrvh0R8eZwTx4J4o0gNtJdMKDfwi-qiI-OndIVI~ay8b0A0TSBds83WoXsnToZAt43n1DsznGZSN4pjGsYEsnKnTX2Jm7GtdGj2XqC~TerSPT6fVrayGJqw13E8D0xHA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235854"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235854/Antiproliferative_effects_of_interferon_alpha_on_hepatic_progenitor_cells_i_in_vitro_i_and_i_in_vivo_i_"><img alt="Research paper thumbnail of Antiproliferative effects of interferon alpha on hepatic progenitor cells<i>in vitro</i>and<i>in vivo</i>" class="work-thumbnail" src="https://attachments.academia-assets.com/113909961/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235854/Antiproliferative_effects_of_interferon_alpha_on_hepatic_progenitor_cells_i_in_vitro_i_and_i_in_vivo_i_">Antiproliferative effects of interferon alpha on hepatic progenitor cells<i>in vitro</i>and<i>in vivo</i></a></div><div class="wp-workCard_item"><span>Hepatology</span><span>, May 1, 2006</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatic progenitor cells (called oval cells in rodents) proliferate during chronic liver injury. ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatic progenitor cells (called oval cells in rodents) proliferate during chronic liver injury. They have been suggested as targets of malignant transformation in chronic liver diseases, including chronic hepatitis C. Interferon alpha therapy reduces the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C regardless of viral clearance. The aim of this study was to determine whether interferon alpha could reduce the risk of HCC by modifying preneoplastic events in the hepatic progenitor cell population. Pre-and post-treatment liver biopsies were evaluated for changes in the hepatic progenitor cell population in 16 patients with non-responding chronic hepatitis C. Interferon alpha-based treatment significantly reduced the numbers of c-kit-positive hepatic progenitor cells by 50%. To determine the mechanism of cell number reduction, the effects of interferon alpha on murine hepatic progenitor cells were studied in vitro. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay and proliferating cell nuclear antigen staining showed that interferon alpha had a dose-dependent, anti-proliferative effect. Interferon alpha stimulated hepatocytic and biliary differentiation of the oval cell lines reflected by increased expression of albumin and cytoker-atin19 accompanied by decreased expression of alphafetoprotein and Thy-1. To validate these results in vivo, mice were placed on the choline-deficient, ethionine-supplemented diet to induce liver injury and oval cell proliferation and treated with pegylated interferon alpha 2b for 2 weeks. This resulted in a significant four-fold reduction in the number of oval cells (P < .05). In conclusion, interferon alpha-based treatment reduced the number of hepatic progenitor cells in chronic liver injury by modulating apoptosis, proliferation, and differentiation. Supplementary material for this article can be found on the HEPATOLOGY website (<a href="http://interscience.wiley.com/jpages/0270-9139/suppmat/" rel="nofollow">http://interscience.wiley.com/jpages/0270-9139/suppmat/</a> index.html). (HEPATOLOGY 2006;43:1074-1083.) U p to 3% of the world's populations may be infected with hepatitis C virus. Ten percent of chronically infected individuals progress to cirrhosis, with 2% to 9% of subjects with cirrhosis developing hepatocellular carcinoma (HCC) each year. 1-4 Evidence suggests that HCC may arise due to the transformation of adult hepatic progenitor cells, called "intermediate hepatobiliary" cells in humans 5 and "oval" cells in mice. 6 In humans, hepatic progenitor cells proliferate after chronic liver injury due to chronic viral hepatitis, alcoholic liver disease, or metabolic liver conditions, and their numbers increase in direct proportion with the disease severity. 7-9 In rodents, oval cells proliferate in response to a variety of stimuli, primarily associated with exposure to hepatocarcinogens. 10 We have shown in a mouse model that an attenuated oval cell response correlates with reduced incidence of HCC after prolonged liver injury. 11 Oval cells are easily transformed in culture, giving rise to cells capable of forming solid tumors in immune-deficient mice. 12,13 Thus, despite early skepticism, the concept of progenitor cells as targets of malignant transformation is now widely accepted, and hence differentiation therapy, in addition to therapeutic control of proliferation and</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9bde6b2f01c9f8b3bf74e9788a158596" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909961,"asset_id":118235854,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909961/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235854"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235854"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235854; 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</script> </div><div class="profile--tab_content_container js-tab-pane tab-pane" data-section-id="3215606" id="papers"><div class="js-work-strip profile--work_container" data-work-id="124015416"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/124015416/CCDC_1408487_Experimental_Crystal_Structure_Determination"><img alt="Research paper thumbnail of CCDC 1408487: Experimental Crystal Structure Determination" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/124015416/CCDC_1408487_Experimental_Crystal_Structure_Determination">CCDC 1408487: Experimental Crystal Structure Determination</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">An entry from the Cambridge Structural Database, the world&#39;s repository for small molecule cr...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">An entry from the Cambridge Structural Database, the world&#39;s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="124015416"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="124015416"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 124015416; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); 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} }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235868"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235868/FRL_19_an_embryonic_liver_stem_cell_line_particularly_sensitive_to_lentivirus_vector_mediated_gene_transfer"><img alt="Research paper thumbnail of FRL 19, an embryonic liver stem cell line particularly sensitive to lentivirus vector-mediated gene transfer" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235868/FRL_19_an_embryonic_liver_stem_cell_line_particularly_sensitive_to_lentivirus_vector_mediated_gene_transfer">FRL 19, an embryonic liver stem cell line particularly sensitive to lentivirus vector-mediated gene transfer</a></div><div class="wp-workCard_item"><span>Journal of Gene Medicine</span><span>, 2003</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235868"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235868"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235868; 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235866"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235866/Kupffer_cell_cytokines_interleukin_1%CE%B2_and_interleukin_10_may_mediate_sepsis_induced_hypoglycaemia"><img alt="Research paper thumbnail of Kupffer cell cytokines, interleukin-1尾 and interleukin-10 may mediate sepsis-induced hypoglycaemia" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235866/Kupffer_cell_cytokines_interleukin_1%CE%B2_and_interleukin_10_may_mediate_sepsis_induced_hypoglycaemia">Kupffer cell cytokines, interleukin-1尾 and interleukin-10 may mediate sepsis-induced hypoglycaemia</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235866"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235866"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235866; 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window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235865]").text(description); $(".js-view-count[data-work-id=118235865]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235865; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235865']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235863"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235863/Transdifferentiation_of_pancreatic_progenitor_cells_to_hepatocyte_like_cells_is_not_serum_dependent_when_facilitated_by_extracellular_matrix_proteins"><img alt="Research paper thumbnail of Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins" class="work-thumbnail" src="https://attachments.academia-assets.com/113909953/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235863/Transdifferentiation_of_pancreatic_progenitor_cells_to_hepatocyte_like_cells_is_not_serum_dependent_when_facilitated_by_extracellular_matrix_proteins">Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins</a></div><div class="wp-workCard_item"><span>Scientific Reports</span><span>, Mar 12, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for l...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin-or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="12cb6834155197ea3ac3b6deb5990617" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909953,"asset_id":118235863,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909953/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235863"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235863"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235863; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235863]").text(description); $(".js-view-count[data-work-id=118235863]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 118235863; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='118235863']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-a9bf3a2bc8c89fa2a77156577594264ee8a0f214d74241bc0fcd3f69f8d107ac.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "12cb6834155197ea3ac3b6deb5990617" } } $('.js-work-strip[data-work-id=118235863]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":118235863,"title":"Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins","internal_url":"https://www.academia.edu/118235863/Transdifferentiation_of_pancreatic_progenitor_cells_to_hepatocyte_like_cells_is_not_serum_dependent_when_facilitated_by_extracellular_matrix_proteins","owner_id":33049687,"coauthors_can_edit":true,"owner":{"id":33049687,"first_name":"George","middle_initials":null,"last_name":"Yeoh","page_name":"GYeoh","domain_name":"independent","created_at":"2015-07-13T23:13:06.933-07:00","display_name":"George Yeoh","url":"https://independent.academia.edu/GYeoh"},"attachments":[{"id":113909953,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/113909953/thumbnails/1.jpg","file_name":"s41598-018-22596-z.pdf","download_url":"https://www.academia.edu/attachments/113909953/download_file","bulk_download_file_name":"Transdifferentiation_of_pancreatic_proge.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/113909953/s41598-018-22596-z-libre.pdf?1714358534=\u0026response-content-disposition=attachment%3B+filename%3DTransdifferentiation_of_pancreatic_proge.pdf\u0026Expires=1740536326\u0026Signature=Csap8d4l9r6mzJ-5EGxObb2dOAS1iJWCiEQfsit4q23O~KqqCwO~8UipbDV2csDPVNWtWlw~lNgnEozkOq-PTmlDZLD-F4Z6X~rOHvXMhvU1DQrnvLAnz3vwpth41--CJKyEY-VhSr4nZ74vekfqX5o9h6KbvMqUfbZIrfmet088PagBQAbQdi9E4eSNiZA-3xo7vQPo4-HO00YUC09oS3dwrnC2CjCsvfQmbos7cqWF0q8pqc1m5FdOgF7ApG5bqckzS4xI7pNjkG0NF~8k1rxc~7VYRIL2xJ03acSioZYysusEu0PbT22FZxKH2vjY1kXH87raGZAkERPGmqGRAw__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235862"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235862/Interleukin_6_secreted_by_bipotential_murine_oval_liver_stem_cells_induces_apoptosis_of_activated_hepatic_stellate_cells_by_activating_NF_%CE%BAB_inducible_nitric_oxide_synthase_signaling"><img alt="Research paper thumbnail of Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-魏B-inducible nitric oxide synthase signaling" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235862/Interleukin_6_secreted_by_bipotential_murine_oval_liver_stem_cells_induces_apoptosis_of_activated_hepatic_stellate_cells_by_activating_NF_%CE%BAB_inducible_nitric_oxide_synthase_signaling">Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-魏B-inducible nitric oxide synthase signaling</a></div><div class="wp-workCard_item"><span>Biochemistry and Cell Biology</span><span>, Apr 1, 2017</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liver fibrosis is now well recognized as the causative factor for increased mortality from compli...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liver fibrosis is now well recognized as the causative factor for increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and (or) treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated HSCs to prevent progression of liver fibrosis. We used a conditioned medium-based approach to study the effect of BMOL cells on activated HSC survival and function. Our data showed that BMOL cells block the contraction of activated HSCs by inducing apoptosis of these cells. We demonstrated that BMOL cells secrete soluble factors, such as interleukin-6 (IL-6), which induced apoptosis of activated HSCs. Using both pharmacological and molecular inhibitor approaches, we further identified that IL-6-mediated activation of NF-魏B鈥搃NOS鈥揘O鈥揜OS signaling in activated HSCs plays a critical role in BMOL-cell-mediated apoptosis of activated HSCs. Thus, the present study provides an alternative cell-based therapeutic approach to treat liver fibrosis.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235862"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235862"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235862; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=118235862]").text(description); 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235860"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235860/CX3CR1_reduces_choline_deficient_ethionine_supplemented_diet_induced_liver_injury_and_liver_progenitor_cell_proliferation"><img alt="Research paper thumbnail of CX3CR1 reduces choline-deficient, ethionine-supplemented diet-induced liver injury and liver progenitor cell proliferation" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235860/CX3CR1_reduces_choline_deficient_ethionine_supplemented_diet_induced_liver_injury_and_liver_progenitor_cell_proliferation">CX3CR1 reduces choline-deficient, ethionine-supplemented diet-induced liver injury and liver progenitor cell proliferation</a></div><div class="wp-workCard_item"><span>European Journal of Immunology</span><span>, 2016</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235860"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235860"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235860; 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</script> <div class="js-work-strip profile--work_container" data-work-id="118235858"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/118235858/Cells_of_the_ductular_reaction_produce_the_chemokine_monocyte_chemotaxis_protein_1_which_initiates_fibrosis_in_pediatric_cholestatic_liver_disease"><img alt="Research paper thumbnail of Cells of the ductular reaction produce the chemokine monocyte chemotaxis protein-1, which initiates fibrosis in pediatric cholestatic liver disease" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/118235858/Cells_of_the_ductular_reaction_produce_the_chemokine_monocyte_chemotaxis_protein_1_which_initiates_fibrosis_in_pediatric_cholestatic_liver_disease">Cells of the ductular reaction produce the chemokine monocyte chemotaxis protein-1, which initiates fibrosis in pediatric cholestatic liver disease</a></div><div class="wp-workCard_item"><span>Journal of Gastroenterology and Hepatology</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235858"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235858"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235858; 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} }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235856"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235856/Tumor_necrosis_factor_like_weak_inducer_of_apoptosis_is_a_mitogen_for_liver_progenitor_cells"><img alt="Research paper thumbnail of Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells" class="work-thumbnail" src="https://attachments.academia-assets.com/113909951/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235856/Tumor_necrosis_factor_like_weak_inducer_of_apoptosis_is_a_mitogen_for_liver_progenitor_cells">Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells</a></div><div class="wp-workCard_item"><span>Hepatology</span><span>, Mar 15, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration du...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDEtreated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin-positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFjB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFjB subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14dependent and NFjB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (HEPATOLOGY 2010;52:291-302) See Editorial on Page 13. H epatocyte-driven liver regeneration following acute injury is a highly orchestrated process in which remaining, healthy hepatocytes proliferate under the control of well-understood genetic, cellular, and metabolic networks. 1 During chronic liver injury, however, when the functional liver mass is reduced and coincidentally hepatocyte proliferation is wholly or partly impaired, liver regeneration is</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d6cd7297ba37fd3036b8f2081e6455da" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909951,"asset_id":118235856,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909951/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235856"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235856"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235856; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="118235854"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/118235854/Antiproliferative_effects_of_interferon_alpha_on_hepatic_progenitor_cells_i_in_vitro_i_and_i_in_vivo_i_"><img alt="Research paper thumbnail of Antiproliferative effects of interferon alpha on hepatic progenitor cells<i>in vitro</i>and<i>in vivo</i>" class="work-thumbnail" src="https://attachments.academia-assets.com/113909961/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/118235854/Antiproliferative_effects_of_interferon_alpha_on_hepatic_progenitor_cells_i_in_vitro_i_and_i_in_vivo_i_">Antiproliferative effects of interferon alpha on hepatic progenitor cells<i>in vitro</i>and<i>in vivo</i></a></div><div class="wp-workCard_item"><span>Hepatology</span><span>, May 1, 2006</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hepatic progenitor cells (called oval cells in rodents) proliferate during chronic liver injury. ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hepatic progenitor cells (called oval cells in rodents) proliferate during chronic liver injury. They have been suggested as targets of malignant transformation in chronic liver diseases, including chronic hepatitis C. Interferon alpha therapy reduces the risk of hepatocellular carcinoma (HCC) in chronic hepatitis C regardless of viral clearance. The aim of this study was to determine whether interferon alpha could reduce the risk of HCC by modifying preneoplastic events in the hepatic progenitor cell population. Pre-and post-treatment liver biopsies were evaluated for changes in the hepatic progenitor cell population in 16 patients with non-responding chronic hepatitis C. Interferon alpha-based treatment significantly reduced the numbers of c-kit-positive hepatic progenitor cells by 50%. To determine the mechanism of cell number reduction, the effects of interferon alpha on murine hepatic progenitor cells were studied in vitro. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay and proliferating cell nuclear antigen staining showed that interferon alpha had a dose-dependent, anti-proliferative effect. Interferon alpha stimulated hepatocytic and biliary differentiation of the oval cell lines reflected by increased expression of albumin and cytoker-atin19 accompanied by decreased expression of alphafetoprotein and Thy-1. To validate these results in vivo, mice were placed on the choline-deficient, ethionine-supplemented diet to induce liver injury and oval cell proliferation and treated with pegylated interferon alpha 2b for 2 weeks. This resulted in a significant four-fold reduction in the number of oval cells (P < .05). In conclusion, interferon alpha-based treatment reduced the number of hepatic progenitor cells in chronic liver injury by modulating apoptosis, proliferation, and differentiation. Supplementary material for this article can be found on the HEPATOLOGY website (<a href="http://interscience.wiley.com/jpages/0270-9139/suppmat/" rel="nofollow">http://interscience.wiley.com/jpages/0270-9139/suppmat/</a> index.html). (HEPATOLOGY 2006;43:1074-1083.) U p to 3% of the world's populations may be infected with hepatitis C virus. Ten percent of chronically infected individuals progress to cirrhosis, with 2% to 9% of subjects with cirrhosis developing hepatocellular carcinoma (HCC) each year. 1-4 Evidence suggests that HCC may arise due to the transformation of adult hepatic progenitor cells, called "intermediate hepatobiliary" cells in humans 5 and "oval" cells in mice. 6 In humans, hepatic progenitor cells proliferate after chronic liver injury due to chronic viral hepatitis, alcoholic liver disease, or metabolic liver conditions, and their numbers increase in direct proportion with the disease severity. 7-9 In rodents, oval cells proliferate in response to a variety of stimuli, primarily associated with exposure to hepatocarcinogens. 10 We have shown in a mouse model that an attenuated oval cell response correlates with reduced incidence of HCC after prolonged liver injury. 11 Oval cells are easily transformed in culture, giving rise to cells capable of forming solid tumors in immune-deficient mice. 12,13 Thus, despite early skepticism, the concept of progenitor cells as targets of malignant transformation is now widely accepted, and hence differentiation therapy, in addition to therapeutic control of proliferation and</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9bde6b2f01c9f8b3bf74e9788a158596" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":113909961,"asset_id":118235854,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/113909961/download_file?s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="118235854"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="118235854"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 118235854; 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