{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:12:49Z","timestamp":1782817969372,"version":"3.54.5"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["82104520"],"award-info":[{"award-number":["82104520"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["82104520"],"award-info":[{"award-number":["82104520"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["82104520"],"award-info":[{"award-number":["82104520"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}]},{"name":"Science and Technology Plan Project of Fujian Provincial Health Commission","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["82104520"],"award-info":[{"award-number":["82104520"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}]},{"name":"Fujian Provincial Science and Technology Innovation Joint Fund Project","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104520"],"award-info":[{"award-number":["82104520"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["82104520"],"award-info":[{"award-number":["82104520"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}]},{"name":"Fujian Medical University High-level Talent Research Startup Funding Project","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["2021J01409"],"award-info":[{"award-number":["2021J01409"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["2021J05045"],"award-info":[{"award-number":["2021J05045"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["2021CXA033"],"award-info":[{"award-number":["2021CXA033"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["2020Y9155"],"award-info":[{"award-number":["2020Y9155"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["82104520"],"award-info":[{"award-number":["82104520"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["XRCZX2020014"],"award-info":[{"award-number":["XRCZX2020014"]}]},{"name":"Open Research Fund of Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University","award":["FMUTM-202301"],"award-info":[{"award-number":["FMUTM-202301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8\/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, \u03b2-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt\/\u03b2-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8\/SVneo cells.<\/jats:p>","DOI":"10.3390\/toxics12050339","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T06:53:27Z","timestamp":1715064807000},"page":"339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt\/\u03b2-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity"],"prefix":"10.3390","volume":"12","author":[{"given":"Qibin","family":"Wu","sequence":"first","affiliation":[{"name":"Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350108, China"},{"name":"Fujian Key Laboratory of Women and Children\u2019s Critical Diseases Research, Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Women and Children\u2019s Hospital), Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caijin","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350108, China"},{"name":"Fujian Key Laboratory of Women and Children\u2019s Critical Diseases Research, Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Women and Children\u2019s Hospital), Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"},{"name":"School of Public Health, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5850-2578","authenticated-orcid":false,"given":"Mengting","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Bao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5072-6091","authenticated-orcid":false,"given":"Pengming","family":"Sun","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350108, China"},{"name":"Fujian Key Laboratory of Women and Children\u2019s Critical Diseases Research, Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Women and Children\u2019s Hospital), Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9821-2946","authenticated-orcid":false,"given":"An","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350108, China"},{"name":"Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350108, China"},{"name":"School of Public Health, Fujian Medical University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.sjbs.2017.01.042","article-title":"Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells","volume":"24","author":"Zhang","year":"2017","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejmech.2016.06.015","article-title":"Discovery and development of natural product oridonin-inspired anticancer agents","volume":"122","author":"Ding","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"645824","DOI":"10.3389\/fphar.2021.645824","article-title":"Oridonin: A review of its pharmacology, pharmacokinetics and toxicity","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, S., Dai, M., Nai, J., Zhu, L., and Sheng, H. (2020). Solubility and bioavailability enhancement of oridonin: A review. Molecules, 25.","DOI":"10.3390\/molecules25020332"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1111\/jcmm.15106","article-title":"Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer cells by suppressing FAK-ERK1\/2 signalling pathway","volume":"24","author":"Xu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Park, H., Jeong, Y.J., Han, N.K., Kim, J.S., and Lee, H.J. (2018). Oridonin enhances radiation-induced cell death by promoting DNA damage in non-small cell lung cancer cells. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201807.0066.v1"},{"key":"ref_7","unstructured":"Ying, Y. (2017). Effects of Oridonin on Estrogen and Antioxidative Function of Ovarian Granulosa Cells. [Master\u2019s Thesis, Beijing University of Agriculture]."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153412","DOI":"10.1016\/j.tox.2022.153412","article-title":"Prediction of drug-induced mitochondrial dysfunction using succinate-cytochrome c reductase activity, QSAR and molecular docking","volume":"485","author":"Moore","year":"2023","journal-title":"Toxicology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2010.01.032","article-title":"Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways","volume":"294","author":"Kang","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27255","DOI":"10.1074\/jbc.M112.374629","article-title":"Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions","volume":"287","author":"Quinlan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/bj2940719","article-title":"Oxidative damage to mitochondria is mediated by the Ca2+-dependent inner-membrane permeability transition","volume":"294","author":"Takeyama","year":"1993","journal-title":"Biochem. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1586\/14737159.7.2.161","article-title":"Strategies to reduce late-stage drug attrition due to mitochondrial toxicity","volume":"7","author":"Dykens","year":"2007","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-catenin signaling, disease, and emerging therapeutic modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s12943-020-01276-5","article-title":"Wnt signaling in breast cancer: Biological mechanisms, challenges and opportunities","volume":"19","author":"Xu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.3389\/fimmu.2019.02551","article-title":"Wnt signaling: Pathogen incursion and immune defense","volume":"10","author":"Jati","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2741\/3957","article-title":"The Wnt signaling pathways and cell adhesion","volume":"17","author":"Amin","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12022-014-9341-8","article-title":"The Wnt signalling cascade and the adherens junction complex in craniopharyngioma tumorigenesis","volume":"26","author":"Preda","year":"2015","journal-title":"Endocr. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/2046-2530-1-7","article-title":"Cilia, Wnt signaling, and the cytoskeleton","volume":"1","author":"Kelley","year":"2012","journal-title":"Cilia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/1476-4598-13-167","article-title":"Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis","volume":"13","author":"Pope","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_20","first-page":"3","article-title":"\u201cOmics\u201d in pharmaceutical research: Overview, applications, challenges, and future perspectives","volume":"13","author":"Yan","year":"2015","journal-title":"Chin. J. Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D106","DOI":"10.1093\/nar\/gkac1061","article-title":"DirectRMDB: A database of post-transcriptional RNA modifications unveiled from direct RNA sequencing technology","volume":"51","author":"Zhang","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wu, Y., Chen, X., Bao, W., Hong, X., Li, C., Lu, J., Zhang, D., and Zhu, A. (2022). Effect of humantenine on mRNA m6A modification and expression in human colon cancer cell line HCT116. Genes, 13.","DOI":"10.3390\/genes13050781"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D196","DOI":"10.1093\/nar\/gkab1075","article-title":"m5C-Atlas: A comprehensive database for decoding and annotating the 5-methylcytosine (m5C) epitranscriptome","volume":"50","author":"Ma","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/j.cell.2012.05.003","article-title":"Comprehensive analysis of mRNA methylation reveals enrichment in 3\u2019 UTRs and near stop codons","volume":"149","author":"Meyer","year":"2012","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Shen, X., Chen, M., Zhang, J., Lin, Y., Gao, X., Tu, J., Chen, K., Zhu, A., and Xu, S. (2024). Unveiling the impact of ApoF deficiency on liver and lipid metabolism: Insights from transcriptome-wide m6A methylome analysis in mice. Genes, 15.","DOI":"10.3390\/genes15030347"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.molcel.2019.04.025","article-title":"Where, When, and How: Context-dependent functions of RNA methylation writers, readers, and erasers","volume":"74","author":"Shi","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nmeth.4111","article-title":"Reversible RNA modifications in meiosis and pluripotency","volume":"14","author":"Klungland","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nature21671","article-title":"RNA m6A methylation regulates the ultraviolet-induced DNA damage response","volume":"543","author":"Xiang","year":"2017","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wu, Y., Bao, W., Ren, J., Li, C., Chen, M., Zhang, D., and Zhu, A. (2022). Integrated profiles of transcriptome and mRNA m6A modification reveal the intestinal cytotoxicity of Aflatoxin B1 on HCT116 cells. Genes, 14.","DOI":"10.3390\/genes14010079"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1164\/rccm.201712-2410OC","article-title":"Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis","volume":"199","author":"Reyfman","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3389\/fphar.2019.00517","article-title":"METTL3\/m6A\/miRNA-873-5p attenuated oxidative stress and apoptosis in colistin-induced kidney injury by modulating Keap1\/Nrf2 pathway","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41573-020-0063-y","article-title":"Monitoring protein communities and their responses to therapeutics","volume":"19","author":"Budayeva","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/pmic.200800155","article-title":"Proteomic identification of molecular targets of gambogic acid: Role of stathmin in hepatocellular carcinoma","volume":"9","author":"Wang","year":"2009","journal-title":"Proteomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1021\/np050255w","article-title":"Metabolomics reviewed: A new \u201comics\u201d platform technology for systems biology and implications for natural products research","volume":"68","author":"Rochfort","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1021\/pr050404w","article-title":"Metabonomic study of aristolochic acid-induced nephrotoxicity in rats","volume":"5","author":"Chen","year":"2006","journal-title":"J. Proteome Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"174372","DOI":"10.1016\/j.ejphar.2021.174372","article-title":"Computational and experimental characterization of isomers of escin-induced renal cytotoxicity by inhibiting heat shock proteins","volume":"908","author":"Sun","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"152929","DOI":"10.1016\/j.phymed.2019.152929","article-title":"Effect of euphorbia factor L1 on oxidative stress, apoptosis, and autophagy in human gastric epithelial cells","volume":"64","author":"Zhu","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/cjoc.202100456","article-title":"SPONGE: A GPU-accelerated molecular dynamics package with enhanced sampling and AI-driven algorithms","volume":"40","author":"Huang","year":"2022","journal-title":"Chin. J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"124511","DOI":"10.1063\/1.2841127","article-title":"A computational investigation of thermodynamics, structure, dynamics and solvation behavior in modified water models","volume":"128","author":"Chatterjee","year":"2008","journal-title":"J. Chem. Phys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1038\/s41467-018-04947-6","article-title":"Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity","volume":"9","author":"He","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13046-023-02702-4","article-title":"Oridonin promotes endoplasmic reticulum stress via TP53-repressed TCF4 transactivation in colorectal cancer","volume":"42","author":"Zhou","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Cao, Y., Wei, W., Zhang, N., Yu, Q., Xu, W.B., Yu, W.J., Chen, G.Q., Wu, Y.L., and Yan, H. (2015). Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-\u03baB signaling. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1219-8"},{"key":"ref_45","first-page":"38","article-title":"DNA damage induced by oridonin involves cell cycle arrest at G2\/M phase in human MCF-7 cells","volume":"17","author":"Zhang","year":"2013","journal-title":"Contemp. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1365-2184.2012.00849.x","article-title":"Oridonin: Targeting programmed cell death pathways as an anti-tumour agent","volume":"45","author":"Liu","year":"2012","journal-title":"Cell Prolif."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22623","DOI":"10.18632\/oncotarget.8033","article-title":"Oridonin, a novel lysine acetyltransferases inhibitor, inhibits proliferation and induces apoptosis in gastric cancer cells through p53- and caspase-3-mediated mechanisms","volume":"7","author":"Shi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.3892\/ijo.2015.3186","article-title":"Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells","volume":"47","author":"Kang","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.3892\/ol.2017.5751","article-title":"Oridonin induces G2\/M cell cycle arrest and apoptosis via the PI3K\/Akt signaling pathway in hormone-independent prostate cancer cells","volume":"13","author":"Lu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"116055","DOI":"10.1016\/j.jep.2022.116055","article-title":"Integration of metabolomics and transcriptomics to reveal ferroptosis is involved in Tripterygium wilfordii polyglycoside tablet-induced testicular injury","volume":"304","author":"Qin","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rehnitz, J., Messmer, B., Bender, U., Nguyen, X.P., Germeyer, A., Hinderhofer, K., Strowitzki, T., and Capp, E. (2022). Activation of AKT\/mammalian target of rapamycin signaling in the peripheral blood of women with premature ovarian insufficiency and its correlation with FMR1 expression. Reprod. Biol. Endocrinol., 20.","DOI":"10.1186\/s12958-022-00919-0"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7403","DOI":"10.1038\/s41467-023-43261-8","article-title":"Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12964-019-0366-y","article-title":"Oridonin protects LPS-induced acute lung injury by modulating Nrf2-mediated oxidative stress and Nrf2-independent NLRP3 and NF-\u03baB pathways","volume":"17","author":"Yang","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/ddr.22024","article-title":"Oridonin ameliorates acetaminophen-induced acute liver injury through ATF4\/PGC-1\u03b1 pathway","volume":"84","author":"Yu","year":"2023","journal-title":"Drug Dev. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pi, J., Cai, H., Jin, H., Yang, F., Jiang, J., Wu, A., Zhu, H., Liu, J., Su, X., and Yang, P. (2015). Qualitative and quantitative analysis of ROS-mediated oridonin-induced oesophageal cancer KYSE-150 cell apoptosis by atomic force microscopy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140935"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ding, Y., Wang, H., Niu, J., Luo, M., Gou, Y., Miao, L., Zou, Z., and Cheng, Y. (2016). Induction of ROS overload by alantolactone prompts oxidative DNA damage and apoptosis in colorectal cancer cells. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040558"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/iub.1130","article-title":"What is the nature of the mitochondrial permeability transition pore and what is it not?","volume":"65","author":"Siemen","year":"2013","journal-title":"IUBMB Life"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sidrat, T., Rehman, Z.U., Joo, M.D., Lee, K.L., and Kong, I.K. (2021). Wnt\/\u03b2-catenin pathway-mediated PPAR\u03b4 expression during embryonic development differentiation and disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041854"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/onc.2016.304","article-title":"Wnt signaling in cancer","volume":"36","author":"Zhan","year":"2017","journal-title":"Oncogene"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1159\/000493412","article-title":"Berberine exerts a protective effect on gut-vascular barrier via the modulation of the Wnt\/Beta-catenin signaling pathway during depsis","volume":"49","author":"He","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1242\/jcs.111.12.1741","article-title":"Identification of connexin43 as a functional target for Wnt signalling","volume":"111","author":"Rook","year":"1998","journal-title":"J. Cell Sci."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/5\/339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:43Z","timestamp":1760107243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/5\/339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":61,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["toxics12050339"],"URL":"https:\/\/doi.org\/10.3390\/toxics12050339","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,7]]}}}