{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:00:31Z","timestamp":1771653631582,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174110"],"award-info":[{"award-number":["82174110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673711"],"award-info":[{"award-number":["81673711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573887"],"award-info":[{"award-number":["81573887"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CZZ23009"],"award-info":[{"award-number":["CZZ23009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Universities","award":["82174110"],"award-info":[{"award-number":["82174110"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["81673711"],"award-info":[{"award-number":["81673711"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["81573887"],"award-info":[{"award-number":["81573887"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["CZZ23009"],"award-info":[{"award-number":["CZZ23009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.<\/jats:p>","DOI":"10.3390\/ijms241814162","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:12:21Z","timestamp":1694931141000},"page":"14162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Promotion Effect of Coexposure to a High-Fat Diet and Nano-Diethylnitrosamine on the Progression of Fatty Liver Malignant Transformation into Liver Cancer"],"prefix":"10.3390","volume":"24","author":[{"given":"Xin","family":"Yin","sequence":"first","affiliation":[{"name":"Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Sang","family":"Li","sequence":"additional","affiliation":[{"name":"Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha-Zhou","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8630-5945","authenticated-orcid":false,"given":"Yang","family":"Xi","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-7882","authenticated-orcid":false,"given":"He-Bin","family":"Tang","sequence":"additional","affiliation":[{"name":"Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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