{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:05:50Z","timestamp":1790201150779,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA025964"],"award-info":[{"award-number":["AA025964"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA029925"],"award-info":[{"award-number":["AA029925"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA030221"],"award-info":[{"award-number":["AA030221"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Thymic atrophy is characterized by loss of thymocytes, destruction of thymic architecture, and a subsequent decrease in na\u00efve T cells with compromised immunity. Thymic atrophy occurs during aging. Environmental factors including alcohol misuse also induce thymic atrophy. Despite the link between alcohol misuse and thymic atrophy, the underlying mechanism is understudied. We aimed to identify molecules and signaling pathways that underly alcohol\u2010induced thymic atrophy during aging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>F344 rats were given 3\u2010day binge\u2010ethanol (4.8\u2009g\/kg\/day; 52% w\/v; i.g.) and the thymus was collected and weighed. Molecular mechanisms underlying ethanol\u2010induced thymic atrophy were investigated by network meta\u2010analysis using the QIAGEN Ingenuity Pathway Analysis (IPA). The molecules associated with ethanol were identified from the QIAGEN Knowledge Base (QKB) and those associated with thymic atrophy were identified from QKB and Mouse Genome Informatics (MGI). Aging\u2010mediated Differential Expression Genes (DEGs) from mouse thymocytes were obtained from the Gene Expression Omnibus (GEO) database (GSE132136). The relationship between the molecules and associated signaling pathways were studied using IPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Binge\u2010ethanol decreased thymic weight in F344 rats. Our meta\u2010analysis using IPA identified molecules commonly shared by ethanol and thymic atrophy through which simulation with ethanol increased thymic atrophy. We then obtained aging\u2010mediated DEGs from the atrophied thymocytes. We found that ethanol contributed to thymic atrophy through modulation of the aging\u2010mediated DEGs. Our network meta\u2010analysis suggests that ethanol may augment thymic atrophy through increased expression of cytokines (e.g., IL\u20106, IL\u201017A and IL\u201033) along with their regulators (e.g., STAT1 and STAT3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Exposure to alcohol may augment thymic atrophy by altering the activity of key inflammatory mediators, such as STAT family members and inflammatory cytokines. These findings provide insights into the signaling pathways and upstream regulators that underly alcohol\u2010induced thymic atrophy\u00a0during aging, suggesting that alcohol consumption could prepone thymic atrophy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15292","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T02:07:41Z","timestamp":1711764461000},"page":"795-809","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Network meta\u2010analysis of the molecular mechanisms and signaling pathways underlying alcohol\u2010induced thymic atrophy"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-9948","authenticated-orcid":false,"given":"Tatiana","family":"Rengifo","sequence":"first","affiliation":[{"name":"Institute of NeuroImmune Pharmacology Seton Hall University  South Orange New Jersey USA"},{"name":"Department of Biological Sciences Seton 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