{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:14:42Z","timestamp":1774977282500,"version":"3.50.1"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":89,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["532223-18"],"award-info":[{"award-number":["532223-18"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008572","name":"University of Ottawa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008572","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Breast Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Exposure to immune stress or lipopolysaccharide (LPS) during critical developmental stages like puberty may lead to gut microbiome dysbiosis and epigenetic dysregulation in mammary glands, affecting gene expression and potentially elevating breast cancer susceptibility in adulthood. Although LPS\u2019s adverse impacts on intestinal and brain functions are well\u2010documented, its effects on mammary glands remain underexplored. Using an immunocompetent BALB\/c mouse model, we administered an acute LPS dose (1.5\u2009mg\/kg body weight) during puberty. The study evaluated the long\u2010term consequences of LPS exposure alone and combined with AHCC (\n                    <jats:italic>Lentinula edodes<\/jats:italic>\n                    cultured extract, 2\u2009g\/kg body weight\/day) on DNA methylation patterns, cytokine profiles, and microRNA expression in mammary glands at 9\u2009weeks of age. Analyses included DNA methylation sequencing, multiplex immunoassays, quantitative PCR, and image processing. Pubertal LPS exposure produced persistent molecular dysregulation in mammary glands, including differential DNA methylation (&gt; 5% change vs. control; FDR\u2010adjusted\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05), elevated inflammatory mediators, and altered microRNA expression. Differentially methylated regions were enriched in regulatory features, with decreased methylation at transcription start sites, promoters, and 5\u2032 UTRs of genes implicated in mammary development and oncogenic signaling (including\n                    <jats:italic>Vav3, Pdgfa, Pdgfc, Jag2, Hras, Ksr1, Il2rb, Il17b,<\/jats:italic>\n                    and\n                    <jats:italic>Il17rb<\/jats:italic>\n                    ) in the LPS group, whereas the AHCC\u2009+\u2009LPS group exhibited a shift toward hypermethylation at these loci (approximately 5%\u201310% decrease). Inflammatory profiling showed increased IL\u201017A\/F (\u223c2\u2010fold vs. control;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05), while microRNA analyses indicated reduced let\u20107a\/c (\u223c30% vs. control;\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Notably, miR\u2010130a and miR\u201034a increased \u223c1.5\u2010fold across all treatment groups relative to control. Pubertal LPS exposure induces enduring epigenetic and inflammatory changes in mammary glands that may heighten breast cancer risk. AHCC\u2019s mitigating role indicates potential for dietary interventions to counteract these effects.\n                  <\/jats:p>","DOI":"10.1155\/tbj\/2122220","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:22:17Z","timestamp":1774974137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Lentinula edodes<\/i>\n                    Cultured Extract Intake at Puberty Mitigates Inflammatory Signals at the Mammary Glands by the Involvement of Epigenetic Mechanisms in BALB\/c 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