{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:51:30Z","timestamp":1784235090009,"version":"3.55.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T00:00:00Z","timestamp":1412899200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0109123","type":"journal-article","created":{"date-parts":[[2014,10,10]],"date-time":"2014-10-10T18:09:16Z","timestamp":1412964556000},"page":"e109123","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Circulating AIM as an Indicator of Liver Damage and Hepatocellular Carcinoma in Humans"],"prefix":"10.1371","volume":"9","author":[{"given":"Tomoko","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Tateishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihoko","family":"Ban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Nishijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeharu","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohiro","family":"Izumino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Aoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Takebayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Gunji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Ohnishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Hiasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Koike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Yamamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichiro","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3322\/caac.20107","article-title":"Global cancer statistics","volume":"61","author":"A Jemal","year":"2011","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cld.2004.12.009","article-title":"Epidemiology of hepatocellular carcinoma","volume":"9","author":"FX Bosch","year":"2005","journal-title":"Clin Liver Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma: epidemiology and molecular carcinogenesis","volume":"132","author":"HB El-Serag","year":"2007","journal-title":"Gastroenterology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1016\/j.jhep.2011.10.027","article-title":"Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace","volume":"56","author":"G Baffy","year":"2012","journal-title":"J Hepatol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic fatty liver disease","volume":"346","author":"P Angulo","year":"2002","journal-title":"N Engl J Med"},{"key":"ref6","volume":"36","unstructured":"Hytiroglou P, Park YN, Krinsky G, Theise ND (2007) Hepatic precancerous lesions and small hepatocellular carcinoma. Gastroenterol Clin North Am <volume>36<\/volume>: : 867\u2013887, vii."},{"key":"ref7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/cr.2010.183","article-title":"NF-\u03baB and STAT3 - key players in liver inflammation and cancer","volume":"21","author":"G He","year":"2011","journal-title":"Cell Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2009.12.052","article-title":"Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression","volume":"140","author":"EJ Park","year":"2010","journal-title":"Cell"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/hep.1840110114","article-title":"The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years","volume":"11","author":"EE Powell","year":"1990","journal-title":"Hepatology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"S377","DOI":"10.1046\/j.1440-1746.17.s3.31.x","article-title":"Non-alcoholic steatohepatitis: definitions and pathogenesis","volume":"17","author":"CP Day","year":"2002","journal-title":"J Gastroenterol Hepatol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1111\/j.1572-0241.2003.07659.x","article-title":"The natural history of nonalcoholic fatty liver disease: a clinical histopathological study","volume":"98","author":"SA Harrison","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1055\/s-0032-1306424","article-title":"Nonalcoholic steatohepatitis and noncirrhotic hepatocellular carcinoma: fertile soil","volume":"32","author":"DM Torres","year":"2012","journal-title":"Semin Liver Dis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1002\/hep.23594","article-title":"Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection","volume":"51","author":"BQ Starley","year":"2010","journal-title":"Hepatology"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1007\/s00535-009-0112-0","article-title":"Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis","volume":"44","author":"N Kawada","year":"2009","journal-title":"J Gastroenterol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1590\/S0100-879X2009005000019","article-title":"Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?","volume":"42","author":"AL Chagas","year":"2009","journal-title":"Braz J Med Biol Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1002\/ijc.25797","article-title":"Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis","volume":"128","author":"J Ertle","year":"2011","journal-title":"Int J Cancer"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/hep.22734","article-title":"Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis","volume":"49","author":"V Paradis","year":"2009","journal-title":"Hepatology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.3748\/wjg.v16.i12.1436","article-title":"Nonalcoholic steatohepatitis-associated hepatocellular carcinoma: our case series and literature review","volume":"16","author":"Y Takuma","year":"2010","journal-title":"World J Gastroenterol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1084\/jem.189.2.413","article-title":"Increased susceptibility of thymocytes to apoptosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily","volume":"189","author":"T Miyazaki","year":"1999","journal-title":"J Exp Med"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cmet.2005.02.002","article-title":"A role of the apoptosis inhibitory factor AIM\/Sp\u03b1\/Api6 in atherosclerosis development","volume":"1","author":"S Arai","year":"2005","journal-title":"Cell Metab"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cell.2004.09.032","article-title":"LXR-dependent gene expression is important for macrophage survival and the innate immune response","volume":"119","author":"SB Joseph","year":"2004","journal-title":"Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"17813","DOI":"10.1073\/pnas.0407749101","article-title":"Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis","volume":"101","author":"AF Valledor","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.celrep.2013.03.006","article-title":"Obesity-associated autoantibody production requires AIM to retain IgM immune complex on follicular dendritic cells","volume":"3","author":"S Arai","year":"2013","journal-title":"Cell Rep"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1002\/1522-2683(200204)23:7\/8<1203::AID-ELPS1203>3.0.CO;2-1","article-title":"IgM are associated to Sp alpha (CD5 antigen-like)","volume":"23","author":"JD Tissot","year":"2002","journal-title":"Electrophoresis"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1373\/clinchem.2007.089144","article-title":"Novel serum biomarker candidates for liver fibrosis in hepatitis C patients","volume":"53","author":"B Gangadharan","year":"2007","journal-title":"Clin Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/1471-2407-9-271","article-title":"A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease","volume":"9","author":"J Gray","year":"2009","journal-title":"BMC Cancer"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3858\/emm.2008.40.6.677","article-title":"Glycoproteomic analysis of plasma from patients with atopic dermatitis: CD5L and ApoE as potential biomarkers","volume":"40","author":"WK Kim","year":"2008","journal-title":"Exp Mol Med"},{"key":"ref28","first-page":"14","article-title":"Serum levels of apoptosis inhibitor of macrophage are associated with hepatic fibrosis in patients with chronic hepatitis C","volume":"13","author":"K Mera","year":"2014","journal-title":"BMC Gastroenterol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cmet.2010.04.013","article-title":"AIM is endocytosed into adipocytes and decreases lipid droplets via inhibition of fatty acid synthase activity","volume":"11","author":"J Kurokawa","year":"2010","journal-title":"Cell Metab"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.bbrc.2012.05.018","article-title":"Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes","volume":"422","author":"Y Iwamura","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00281-013-0405-5","article-title":"Impacts of the apoptosis inhibitor of macrophage (AIM) on obesity-associated inflammatory diseases","volume":"36","author":"S Arai","year":"2014","journal-title":"Semin Immunopathol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0928-4346(96)00325-8","article-title":"New Inuyama classification; new criteria for histological assessment of chronic hepatitis","volume":"6","author":"F Ichida","year":"1996","journal-title":"Int hepatol commun"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"E904","DOI":"10.1152\/ajpendo.90248.2008","article-title":"Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice","volume":"295","author":"G Bryzgalova","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1210\/me.2006-0012","article-title":"Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob\/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3","volume":"20","author":"H Gao","year":"2006","journal-title":"Mol Endocrinol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/hep.26951","article-title":"Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen receptor\/Liver X receptor pathway in mice","volume":"59","author":"SI Han","year":"2014","journal-title":"Hepatology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1677\/jme.0.0320879","article-title":"Gene expression profiling identifies liver X receptor alpha as an estrogen-regulated gene in mouse adipose tissue","volume":"32","author":"L Lundholm","year":"2004","journal-title":"J Mol Endocrinol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1210\/en.2011-1980","article-title":"Molecular mechanisms of estrogen receptors&apos; suppression of lipogenesis in pancreatic \u03b2-cells","volume":"153","author":"JP Tiano","year":"2012","journal-title":"Endocrinology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/HCO.0b013e32836205e7","article-title":"Ovarian hormones and vascular disease","volume":"28","author":"FG Hage","year":"2013","journal-title":"Curr Opin Cardiol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"933","DOI":"10.7326\/0003-4819-133-12-200012190-00008","article-title":"A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease","volume":"133","author":"F Grodstein","year":"2000","journal-title":"Ann Intern Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1001\/jama.288.1.49","article-title":"Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen\/progestin Replacement Study follow-up (HERS II)","volume":"288","author":"D Grady","year":"2002","journal-title":"JAMA"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3892\/ijmm.2014.1619","article-title":"17\u03b2-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor \u03b1-dependent pathway","volume":"33","author":"H Wang","year":"2014","journal-title":"Int J Mol Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1038\/ncomms4147","article-title":"MafB promotes atherosclerosis by inhibiting foam-cell apoptosis","volume":"5","author":"M Hamada","year":"2014","journal-title":"Nat Commun"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1253\/circj.CJ-11-0891","article-title":"AIMing at Metabolic Syndrome: Towards the development of novel therapies for metabolic diseases via apoptosis inhibitor of macrophage (AIM)","volume":"75","author":"T Miyazaki","year":"2011","journal-title":"Cir J"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cellimm.2012.07.007","article-title":"17\u03b2-Estradiol enhances response of mice spleen B cells elicited by TLR9 agonist","volume":"278","author":"Y Xu","year":"2012","journal-title":"Cell Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e8412","DOI":"10.1371\/journal.pone.0008412","article-title":"17beta-estradiol enhances the response of plasmacytoid dendritic cell to CpG","volume":"4","author":"X Li","year":"2009","journal-title":"PLoS One"},{"key":"ref46","first-page":"345","article-title":"The metabolism of different immunoglobulin classes in irradiated mice","volume":"17","author":"H Bazin","year":"1969","journal-title":"Immunology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/eji.1830180221","article-title":"The half-lives of serum immunoglobulins in adult mice","volume":"18","author":"P Vieira","year":"1988","journal-title":"Eur J Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"e97037","DOI":"10.1371\/journal.pone.0097037","article-title":"Stabilization and augmentation of circulating AIM in mice by synthesized IgM-Fc","volume":"9","author":"T Kai","year":"2014","journal-title":"PLoS One"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0109123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T20:16:07Z","timestamp":1650399367000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0109123"}},"subtitle":[],"editor":[{"given":"Kalpana","family":"Ghoshal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,10,10]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0109123","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,10]]}}}