{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:50Z","timestamp":1760060270441,"version":"build-2065373602"},"reference-count":115,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"private Italian company in the agri-food sector","award":["FFR 2024\u20132025","CN00000033"],"award-info":[{"award-number":["FFR 2024\u20132025","CN00000033"]}]},{"name":"University of Palermo","award":["FFR 2024\u20132025","CN00000033"],"award-info":[{"award-number":["FFR 2024\u20132025","CN00000033"]}]},{"name":"National Biodiversity Future Center","award":["FFR 2024\u20132025","CN00000033"],"award-info":[{"award-number":["FFR 2024\u20132025","CN00000033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Nutrigenomics explores how dietary components influence genome function, especially via epigenetic mechanisms like DNA methylation. A key challenge is identifying healthy food-derived molecules capable of counteracting epigenetic damage from harmful dietary elements. Pistachio nuts (Pistacia vera L.), particularly the Bronte variety from Sicily, are rich in antioxidant polyphenols. In this study we used a methylomic approach to assess the nutrigenomic potential of a hydrophilic extract from Bronte pistachio (BPHE) in a model of human intestinal epithelium, as well as its capacity to modulate arsenic (As)-induced epigenotoxicity. Methods: BPHE was obtained via ethanol\/water Soxhlet extraction. CaCo-2 cells were treated with BPHE, alone and after exposure to sodium arsenite. The methylation pattern of the genomic DNA was assessed by methylation-sensitive arbitrarily primed PCR and the methylomic signature was defined by Next-generation bisulfite sequencing. Results: BPHE alone did not alter DNA methylation pattern but, at the highest dose, modulated the changes induced by As. The identification of differentially methylated gene promoters in cell treatment vs. untreated controls revealed that BPHE and As primarily induced hyper-methylation, with a synergistic effect when combined. In particular, all the treatments increased methylation levels of gene categories such as pseudogenes, key genes of specific pathways, genes for zinc-finger proteins, homeobox proteins, kinases, antisense RNA, and miRNA. Notably, in co-treatment with As, BPHE promoted hypo-methylation of genes involved in tumor suppression, detoxification, mitochondrial function, and cell division. Conclusions: These findings suggest that Bronte pistachio polyphenols may epigenetically steer gene expression toward a protective profile, reducing risks of genomic instability and disease. This supports their potential as nutraceuticals to counter harmful epigenetic effects of toxic food components like arsenic.<\/jats:p>","DOI":"10.3390\/nu17162678","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:59:01Z","timestamp":1755601141000},"page":"2678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methylomic Signature and Epigenetic Damage Modulation of Bronte Pistachio (Pistacia vera L.) Hydrophilic Extract in Differentiated CaCo-2 Cells"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-7270","authenticated-orcid":false,"given":"Ilenia","family":"Cruciata","sequence":"first","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8075-0642","authenticated-orcid":false,"given":"Flores","family":"Naselli","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9288-9859","authenticated-orcid":false,"given":"Sara","family":"Volpes","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8971-266X","authenticated-orcid":false,"given":"Paola Sofia","family":"Cardinale","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5949-784X","authenticated-orcid":false,"given":"Laura","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Earth and Marine Science (DiSTEM), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-767X","authenticated-orcid":false,"given":"Federico","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Florence, Via Madonna del Piano 6, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6862-9409","authenticated-orcid":false,"given":"Matteo","family":"Ramazzotti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, Viale G.B. Morgagni 50, 50134 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-6145","authenticated-orcid":false,"given":"Graziella","family":"Serio","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"},{"name":"Fondazione Umberto Veronesi ETS, 20121 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-3342","authenticated-orcid":false,"given":"Carla","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-7312","authenticated-orcid":false,"given":"Fabio","family":"Caradonna","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STeBiCeF), University of Palermo, Viale delle Scienze, Building 16, 90128 Palermo, Italy"},{"name":"NBFC, National Biodiversity Future Center, 90133 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.biochi.2019.03.006","article-title":"Primers on Nutrigenetics and Nutri(Epi)Genomics: Origins and Development of Precision Nutrition","volume":"160","author":"Bordoni","year":"2019","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Caradonna, F., Consiglio, O., Luparello, C., and Gentile, C. 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