{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:25:51Z","timestamp":1775064351306,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","award":["996548"],"award-info":[{"award-number":["996548"]}],"id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In non\u2010alcoholic fatty liver disease (NAFLD), characterised by progressive liver damage, inflammation, fibrosis and potential cirrhosis, treatment options are limited, with liver transplantation as the only definitive solution. To address this urgent need, in\u00a0vitro and tissue engineering studies have explored new drugs. This study investigated the anti\u2010inflammatory and anti\u2010fibrotic potential of Nicotinamide, utilising promising preliminary data for treating NAFLD. Multicellular liver microtissues comprising LX2 stellate cells, HepG2 hepatocytes and HUVECs were generated to establish a robust preclinical model for fibrosis. Cell viability and histological assessments confirmed successful co\u2010aggregation within the microtissues. To induce fibrosis, they were treated with a palmitic and oleic acid mixture, followed by exposure to Nicotinamide. Treatment effectiveness was evaluated by analysing inflammatory factors, including transforming growth factor \u03b21 (TGF\u2010\u03b21), tumour necrosis factor\u2010alpha (TNF\u2010\u03b1) and interleukin 1 beta and interleukin 6. Extracellular matrix deposition was assessed by measuring collagen type I (COL I) and \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA). Our data suggested that Nicotinamide application led to significant improvements across several measures. Specifically, it effectively reduced inflammatory response by reducing TGF\u2010\u03b21 levels and decreasing COL I and \u03b1\u2010SMA levels. Furthermore, Nicotinamide was crucial in reducing reactive oxygen species levels, indicating that activation of HSC, inflammatory signals and oxidative stress work together. These in\u00a0vitro findings suggest Nicotinamide may have therapeutic potential warranting further investigation in advanced preclinical models. Our findings demonstrated significant improvements across various parameters, including reduced expression of pro\u2010inflammatory cytokines and attenuated oxidative stress, underscoring the therapeutic potential of Nicotinamide in clinical studies.<\/jats:p>","DOI":"10.1111\/jcmm.70606","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:43:38Z","timestamp":1749015818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Innovative Approaches to\n                    <scp>NAFLD<\/scp>\n                    : Exploring the Role of Nicotinamide in Multicellular Microtissue Models of Liver Fibrosis"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-1382","authenticated-orcid":false,"given":"Farnaz","family":"Sani","sequence":"first","affiliation":[{"name":"Shiraz Institute for Stem Cell &amp; Regenerative Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shima","family":"Parsa","sequence":"additional","affiliation":[{"name":"Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine  Winston Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimia","family":"Falamarzi","sequence":"additional","affiliation":[{"name":"Shiraz Institute for Stem Cell &amp; Regenerative Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammadhossein","family":"Khorraminejad\u2010Shirazi","sequence":"additional","affiliation":[{"name":"Zoonoses Research Center Jahrom University of Medical Sciences  Jahrom Iran"},{"name":"Department of Pathology, School of Medicine Jahrom University of Medical Sciences  Jahrom Iran"},{"name":"Department of Pathology, School of Medicine Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Student Research Committee Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Negar","family":"Azarpira","sequence":"additional","affiliation":[{"name":"Shiraz Institute for Stem Cell &amp; Regenerative Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-6572","authenticated-orcid":false,"given":"Mahsa","family":"Sani","sequence":"additional","affiliation":[{"name":"Shiraz Institute for Stem Cell &amp; Regenerative Medicine Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0322-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.80"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1726952"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0082-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9"},{"issue":"1","key":"e_1_2_11_7_1","first-page":"14","article-title":"Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its Impact on Veterans","volume":"36","author":"Shetty A.","year":"2019","journal-title":"Federal Practitioner"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60121-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03364-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-023-03466-8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986711794940842"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2019.03.001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2131\/jts.46.31"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23639"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.03.064"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.110979"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100913RRR"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/8836452"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18529"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0079-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.666138"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg6276"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202007425"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep36750"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.201900104"},{"key":"e_1_2_11_26_1","first-page":"842","volume-title":"Steatohepatitis: A Tale of Two \u201cHits\u201d?","author":"Day C. 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