{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:02Z","timestamp":1787022182960,"version":"build-2736575974"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) and acute ischemic stroke (AIS) are both closely related to chronic inflammation and metabolic disorders, but the molecular mechanisms between them are not yet clear. This study aims to explore the common molecular characteristics between NAFLD and AIS using bioinformatics methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated transcriptomic data from GEO (GSE89632 for NAFLD and GSE16561 for AIS) to identify shared molecular signatures. Differentially expressed genes (DEGs) were screened using the limma package, and co-expression modules were identified via WGCNA. Functional enrichment and immune infiltration analyses were conducted using standard bioinformatics tools. Key genes were selected through LASSO and random forest algorithms, and candidate drugs were predicted using the CMap database. Experimental validation included qPCR, immunohistochemistry, and drug intervention in HepG2 and HMC3 cell models, as well as a high-fat diet-induced NAFLD mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through differential expression analysis, 65 common DEGs were identified in both NAFLD and AIS. Functional enrichment analysis showed that these genes mainly involve signal pathways related to immune regulation and inflammatory responses. Immune infiltration analysis showed a significant increase in monocytes, B cells, and plasma cells in NAFLD patients. Ultimately, four potential biomarkers were screened out using LASSO regression and random forest algorithms:\n                      <jats:italic>CEBPD<\/jats:italic>\n                      ,\n                      <jats:italic>SOCS2<\/jats:italic>\n                      ,\n                      <jats:italic>THBS1<\/jats:italic>\n                      , and\n                      <jats:italic>IFIT2<\/jats:italic>\n                      . Using cMAP, 10 candidate therapeutic drugs, including lamotrigine, were identified. Expression of\n                      <jats:italic>CEBPD<\/jats:italic>\n                      and\n                      <jats:italic>SOCS2<\/jats:italic>\n                      was consistently upregulated in NAFLD clinical datasets, FFA-treated HepG2 cells, and liver tissues of HFD-induced NAFLD mice, but not in AIS datasets or OGD-treated microglial cells. Furthermore, lamotrigine, cinnarizine, and lenvatinib significantly suppressed FFA-induced\n                      <jats:italic>CEBPD<\/jats:italic>\n                      and\n                      <jats:italic>SOCS2<\/jats:italic>\n                      expression in HepG2 cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), supporting their potential regulatory effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study identified common DEGs between NAFLD and AIS and experimentally validated\n                      <jats:italic>CEBPD<\/jats:italic>\n                      as a potential marker, revealing possible common molecular mechanisms between the two diseases, providing new directions for future diagnosis and treatment.\n                    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