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This study evaluated the effects of dietary supplementation with date palm seed nanoparticles (DPS-NPs) at 0 (control), 40, 80, and 120\u00a0mg\/kg diet on serum biochemical parameters, gene expression, and histomorphology in Nile tilapia over a 30-day period. The results revealed a clear positive response across biochemical, molecular, and histological markers. Serum analysis revealed significant increases in total protein and globulin at doses of 80\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) and 120\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), while albumin levels were elevated only at 120\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Marked reductions in the oxidative stress marker MDA were observed at both 80 and 120\u00a0mg\/kg. In addition, hepatic enzymes (ALT and AST) and renal function markers (creatinine and uric acid) were significantly decreased at 120\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 for ALT and AST;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001 for creatinine;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 for uric acid), indicating improved liver and kidney function. Gene expression analysis showed consistent upregulation of\n                    <jats:italic>il1\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>tnf\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>tgf\u03b2<\/jats:italic>\n                    in the intestine, liver, and spleen, with peak expression in the intestine at 120\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Furthermore, innate immune genes (\n                    <jats:italic>\u03b2-defensin 1<\/jats:italic>\n                    ,\n                    <jats:italic>nkl<\/jats:italic>\n                    ) and antioxidant genes (\n                    <jats:italic>sod2<\/jats:italic>\n                    ,\n                    <jats:italic>cat<\/jats:italic>\n                    ) were significantly upregulated, reaching their highest expression levels at 120\u00a0mg\/kg (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Histological observations further confirmed enhanced intestinal villus architecture, increased goblet cell activity, proliferative melano-macrophage centers in the spleen, and restored hepatic structure with active Kupffer cells and telocytes. Collectively, these findings demonstrate that dietary supplementation with DPS-NPs, particularly at 120\u00a0mg\/kg, strengthens immunity, enhances antioxidant defenses, and improves tissue integrity in Nile tilapia, highlighting its potential as a sustainable functional feed additive in aquaculture.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-43559-9","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:03:31Z","timestamp":1775757811000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dietary date palm seed nanoparticles modulate biochemical parameters, immune-antioxidant gene expression, and histomorphology in Nile tilapia"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6609-2476","authenticated-orcid":false,"given":"Karima A.","family":"Bakry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4157-5372","authenticated-orcid":false,"given":"Haitham G.","family":"Abo-Al-Ela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-9081","authenticated-orcid":false,"given":"Abdullah A. 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