{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:37:05Z","timestamp":1792532225098,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine Research Fund, Chiang Mai University","award":["068-2565"],"award-info":[{"award-number":["068-2565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer that is often diagnosed at an advanced metastatic stage. The processes of cancer cell migration and invasion involve epithelial-to-mesenchymal transition (EMT), which is crucial for metastasis. Targeting cancer aggressiveness with effective plant compounds has gained attention as a potential adjuvant therapy. Eurycomanone (ECN), a bioactive quassinoid found in the root of Eurycoma longifolia Jack, has demonstrated anti-cancer activity against various carcinoma cell lines, including human NSCLC cells. This study aimed to investigate the in vitro effects of ECN on the migration and invasion of human NSCLC cells and to elucidate the mechanisms by which ECN modulates the EMT in these cells. Non-toxic doses (\u2264IC20) of ECN were determined using the MTT assay on two human NSCLC cell lines: A549 and Calu-1. The results from wound healing and transwell migration assays indicated that ECN significantly suppressed the migration of both TGF-\u03b21-induced A549 and Calu-1 cells. ECN exhibited a strong anti-invasive effect, as its non-toxic doses significantly suppressed the TGF-\u03b21-induced invasion of NSCLC cells through Matrigel and decreased the secretion of MMP-2 from these cancer cells. Furthermore, ECN could affect the TGF-\u03b21-induced EMT process in various ways in NSCLC cells. In TGF-\u03b21-induced A549 cells, ECN significantly restored the expression of E-cadherin by inhibiting the Akt signaling pathway. Conversely, in Calu-1, ECN reduced the aggressive phenotype by decreasing the expression of the mesenchymal protein N-cadherin and inhibiting the TGF-\u03b21\/Smad pathway. In conclusion, this study demonstrated the anti-invasive activity of eurycomanone from E. longifolia Jack in human NSCLC cells and provided insights into its mechanism of action by suppressing the effects of TGF-\u03b21 signaling on the EMT program. These findings offer scientific evidence to support the potential of ECN as an alternative therapy for metastatic NSCLC.<\/jats:p>","DOI":"10.3390\/ijms26157120","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T16:04:51Z","timestamp":1753286691000},"page":"7120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Eurycomanone Blocks TGF-\u03b21-Induced Epithelial-to-Mesenchymal Transition, Migration, and Invasion Pathways in Human Non-Small Cell Lung Cancer Cells by Targeting Smad and Non-Smad Signaling"],"prefix":"10.3390","volume":"26","author":[{"given":"Pratchayanon","family":"Soddaen","sequence":"first","affiliation":[{"name":"Graduate\/M.Sc. Program in Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kongthawat","family":"Chairatvit","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-386X","authenticated-orcid":false,"given":"Pornsiri","family":"Pitchakarn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanongsak","family":"Laowanitwattana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2787-2461","authenticated-orcid":false,"given":"Arisa","family":"Imsumran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-0447","authenticated-orcid":false,"given":"Ariyaphong","family":"Wongnoppavich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1203543","article-title":"A perspective on cancer cell metastasis","volume":"331","author":"Chaffer","year":"2011","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.mayocp.2019.01.013","article-title":"Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment","volume":"94","author":"Duma","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guo, H., Li, H., Zhu, L., Feng, J., Huang, X., and Baak, J.P.A. (2021). \u201cHow long have I got?\u201d in stage IV NSCLC patients with at least 3 months up to 10 years survival, accuracy of long-, intermediate-, and short-term survival prediction is not good enough to answer this question. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.761042"},{"key":"ref_4","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","article-title":"Matrix metalloproteinase inhibitors in cancer therapy: Turning past failures into future successes","volume":"17","author":"Winer","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41568-019-0213-x","article-title":"Controversies around epithelial-mesenchymal plasticity in cancer metastasis","volume":"19","author":"Williams","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hao, Y., Baker, D., and Ten Dijke, P. (2019). TGF-\u03b2-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112767"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41392-025-02148-4","article-title":"Invasion and metastasis in cancer: Molecular insights and therapeutic targets","volume":"10","author":"Li","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhang, L., Chen, W.X., Li, L.L., Cao, Y.Z., Geng, Y.D., Feng, X.J., Wang, A.Y., Chen, Z.L., Lu, Y., and Shen, A.Z. (2020). Paeonol suppresses proliferation and motility of non-small-cell lung cancer cells by disrupting STAT3\/NF-\u03baB signaling. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.572616"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Guo, K., Feng, Y., Zheng, X., Sun, L., Wasan, H.S., Ruan, S., and Shen, M. (2021). Resveratrol and its analogs: Potent agents to reverse epithelial-to-mesenchymal transition in tumors. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.644134"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rehman, S.U., Choe, K., and Yoo, H.H. (2016). Review on a traditional herbal medicine, Eurycoma longifolia Jack (Tongkat Ali): Its traditional uses, chemistry, evidence-based pharmacology and toxicology. Molecules, 21.","DOI":"10.3390\/molecules21030331"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.fitote.2010.04.006","article-title":"Tongkat Ali (Eurycoma longifolia Jack): A review on its ethnobotany and pharmacological importance","volume":"81","author":"Bhat","year":"2010","journal-title":"Fitoterapia"},{"key":"ref_13","first-page":"1009","article-title":"Cytotoxic activity of quassinoids from Eurycoma longifolia","volume":"5","author":"Miyake","year":"2010","journal-title":"Nat. Prod. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ahmad, N., Samiulla, D.S., Teh, B.P., Zainol, M., Zolkifli, N.A., Muhammad, A., Matom, E., Zulkapli, A., Abdullah, N.R., and Ismail, Z. (2018). Bioavailability of Eurycomanone in Its Pure Form and in a Standardised Eurycoma longifolia Water Extract. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030090"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109676","DOI":"10.1016\/j.microc.2023.109676","article-title":"Efficient extraction of quassinoids and alkaloids from Eurycoma longifolia Jack roots using natural deep eutectic solvents and microwave-assisted extraction","volume":"196","author":"Sitthisak","year":"2024","journal-title":"Microchem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.bmc.2003.11.017","article-title":"Cytotoxic and antimalarial constituents from the roots of Eurycoma longifolia","volume":"12","author":"Kuo","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_17","first-page":"16","article-title":"Eurycomanone induce apoptosis in HepG2 cells via up regulation of p53","volume":"9","author":"Zakaria","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_18","first-page":"1441","article-title":"Inactivation of AKT\/NF-\u03baB signaling by eurycomalactone decreases human NSCLC cell viability and improves the chemosensitivity to cisplatin","volume":"44","author":"Dukaew","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14649","DOI":"10.3390\/molecules190914649","article-title":"Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death and inflammation","volume":"19","author":"Hajjouli","year":"2014","journal-title":"Molecules"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3727\/096504019X15736439848765","article-title":"Enhancement of radiosensitivity by eurycomalactone in human NSCLC cells through G2\/M cell cycle arrest and delayed DNA double-strand break repair","volume":"28","author":"Dukaew","year":"2020","journal-title":"Oncol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1021\/np400701k","article-title":"NF-\u03baB inhibitors from Eurycoma longifolia","volume":"77","author":"Tran","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/jphp.13289","article-title":"14,15\u03b2-Dihydroxyklaineanone inhibits HepG2 cell proliferation and migration through p38MAPK pathway","volume":"72","author":"Pei","year":"2020","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3892\/ijmm.2021.5076","article-title":"Ailanthone suppresses the activity of human colorectal cancer cells through the STAT3 signaling pathway","volume":"49","author":"Ding","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"500","DOI":"10.4103\/wjtcm.wjtcm_42_20","article-title":"A study on the mechanism of bruceine D in the treatment of non-small cell lung cancer H1299 cells","volume":"6","author":"Shen","year":"2020","journal-title":"World J. Tradit. Chin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.biopha.2018.06.065","article-title":"Comprehensive anti tumor effect of Brusatol through inhibition of cell viability and promotion of apoptosis caused by autophagy via the PI3K\/Akt\/mTOR pathway in hepatocellular carcinoma","volume":"105","author":"Ye","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e40118","DOI":"10.1016\/j.heliyon.2024.e40118","article-title":"Endothelial-to-mesenchymal transition in the tumor microenvironment: Roles of transforming growth factor-\u03b2 and matrix metalloproteins","volume":"10","author":"Du","year":"2024","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6014","DOI":"10.7150\/jca.35017","article-title":"Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-\u03b2\/SMAD2 signaling pathway","volume":"10","author":"Chen","year":"2019","journal-title":"J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.omto.2021.01.006","article-title":"Inhibition of tumor invasion and metastasis by targeting TGF-\u03b2-Smad-MMP2 pathway with Asiatic acid and Naringenin","volume":"20","author":"Lian","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tcb.2018.12.001","article-title":"EMT transition states during tumor progression and metastasis","volume":"29","author":"Pastushenko","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10555-020-09936-0","article-title":"Targeting the cytoskeleton against metastatic dissemination","volume":"40","author":"Ruggiero","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Niland, S., Riscanevo, A.X., and Eble, J.A. (2021). Matrix metalloproteinases shape the tumor microenvironment in cancer progression. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010146"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"285","DOI":"10.4103\/jomfp.JOMFP_166_20","article-title":"Evaluation of E-Cadherin and vimentin expression for different grades of oral epithelial dysplasia and oral squamous cell carcinoma\u2014An immunohistochemical study","volume":"26","author":"Puneeta","year":"2022","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85502","DOI":"10.18632\/oncotarget.13453","article-title":"Expression Analysis and Clinical Significance of EIF4E, VEGF-C, E-Cadherin and MMP-2 in Colorectal Adenocarcinoma","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","first-page":"346","article-title":"HDAC inhibitors, trichostatin A and valproic acid, increase E-cadherin and vimentin expression but inhibit migration and invasion of cholangiocarcinoma cells","volume":"40","author":"Wang","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_36","first-page":"2547","article-title":"Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells","volume":"11","author":"Miyaki","year":"1995","journal-title":"Oncogene"},{"key":"ref_37","first-page":"3552","article-title":"Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection","volume":"59","author":"Luo","year":"1999","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0002-9440(10)63692-9","article-title":"E-Cadherin mediates MMP down-regulation in highly invasive bronchial tumor cells","volume":"163","author":"Gilles","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Loh, C.Y., Chai, J.Y., Tang, T.F., Wong, W.F., Sethi, G., Shanmugam, M.K., Chong, P.P., and Looi, C.Y. (2019). The E-Cadherin and N-Cadherin switch in epithelial-to-mesenchymal transition: Signaling, therapeutic implications, and challenges. Cells, 8.","DOI":"10.3390\/cells8101118"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2005420","DOI":"10.1080\/21688370.2021.2005420","article-title":"Dual Role of E-Cadherin in Cancer Cells","volume":"10","author":"Rubtsova","year":"2021","journal-title":"Tissue Barrier"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rudisch, A., Dewhurst, M.R., Horga, L.G., Kramer, N., Harrer, N., Dong, M., van der Kuip, H., Wernitznig, A., Bernthaler, A., and Dolznig, H. (2015). High EMT signature score of invasive non-small cell lung cancer (NSCLC) cells correlates with NF\u03baB driven colony-stimulating factor 2 (CSF2\/GM-CSF) secretion by neighboring stromal fibroblasts. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124283"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41467-017-00268-2","article-title":"Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures","volume":"8","author":"Khan","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_43","first-page":"679","article-title":"Correlation of N-cadherin and MMP-9 expression with regional nodal metastasis in laryngeal squamous cell carcinoma","volume":"16","author":"Kusumastuti","year":"2024","journal-title":"Pharmacogn. J."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hsu, C.C., Huang, S.F., Wang, J.S., Chu, W.K., Nien, J.E., Chen, W.S., and Chow, S.E. (2016). Interplay of N-Cadherin and matrix metalloproteinase 9 enhances human nasopharyngeal carcinoma cell invasion. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2846-4"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1083\/jcb.201902046","article-title":"Vimentin protects cells against nuclear rupture and DNA damage during migration","volume":"218","author":"Patteson","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e41964","DOI":"10.1016\/j.heliyon.2025.e41964","article-title":"Targeting epithelial-mesenchymal transition signaling pathways with dietary phytocompounds and repurposed drug combinations for overcoming drug resistance in various cancers","volume":"11","author":"Sravani","year":"2025","journal-title":"Heliyon"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12032-018-1104-9","article-title":"The inhibition of invasion of human melanoma cells through N-cadherin knock-down","volume":"35","author":"Laidler","year":"2018","journal-title":"Med. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/cam4.463","article-title":"PI3K\/AKT pathway regulates E-cadherin and Desmoglein 2 in aggressive prostate cancer","volume":"4","author":"Barber","year":"2015","journal-title":"Cancer Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/bjd.12967","article-title":"Epithelial-Mesenchymal Transition during invasion of cutaneous squamous cell carcinoma is paralleled by akt activation","volume":"171","author":"Barrette","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3892\/or.2014.3220","article-title":"Blocking PI3K\/Akt signaling attenuates metastasis of nasopharyngeal carcinoma cells through induction of mesenchymal-epithelial reverting transition","volume":"32","author":"Jiang","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bbrc.2018.10.193","article-title":"Bovine lactoferrin reverses programming of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition in oral squamous cell carcinoma","volume":"507","author":"Chea","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Song, Q., Wu, H., Jin, Y., Hou, J., Liu, J., Zhang, X., Hu, W., Sun, G., and Zhang, Z. (2025). Fruquintinib inhibits the migration and invasion of colorectal cancer cells by modulating epithelial-mesenchymal transition via TGF-\u03b2\/Smad signaling pathway. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1503133"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11010-019-03557-0","article-title":"Transforming growth factor \u03b21 promotes fibroblast-like synoviocytes migration and invasion via TGF-\u03b21\/Smad signaling in rheumatoid arthritis","volume":"459","author":"Zhu","year":"2019","journal-title":"Mol. Cell Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1158\/2159-8290.CD-11-0085","article-title":"mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling","volume":"1","author":"Chandarlapaty","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_55","first-page":"132","article-title":"Eurycomanone stimulates bone mineralization in zebrafish larvae and promotes osteogenic differentiation of mesenchymal stem cells by upregulating AKT\/GSK-3\u03b2\/\u03b2-catenin signaling","volume":"40","author":"Zhong","year":"2023","journal-title":"J. Orthop. Transl."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:56Z","timestamp":1760033696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":55,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157120"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157120","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}