{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:23Z","timestamp":1785422723247,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004154","name":"Mae Fah Luang University","doi-asserted-by":"publisher","award":["681A05004"],"award-info":[{"award-number":["681A05004"]}],"id":[{"id":"10.13039\/501100004154","id-type":"DOI","asserted-by":"publisher"}]},{"award":["681A05004"],"award-info":[{"award-number":["681A05004"]}],"id":[{"id":"https:\/\/ror.org\/00mwhaw71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide, highlighting the need for safer and more effective therapeutic agents. This study investigated the potential anticancer compounds and mechanisms of Paris polyphylla against CRC using an integrated approach combining network pharmacology, molecular docking, and in vitro validation. Bioactive compounds were screened from multiple databases, and their putative targets were intersected with CRC-related genes. Protein\u2013protein interaction and enrichment analyses were performed to identify key targets and pathways, followed by the docking of selected compounds with major hub proteins. The cytotoxic and molecular effects of P. polyphylla rhizome extract (PPRE) were then evaluated in SW480 and HCT116 cells. A total of 74 compounds were identified, of which 12 were retained for target prediction, yielding 180 overlapping genes between P. polyphylla targets and CRC-associated genes. Network analysis highlighted STAT3, EGFR, SRC, IL-6, and AKT1 as key hub targets, with enrichment in cancer-related, EGFR resistance, and PI3K\u2013Akt pathways. Docking showed favorable binding affinities, particularly between prosapogenin A and AKT1. Experimentally, PPRE reduced CRC cell viability and downregulated STAT3, EGFR, SRC, IL-6, and AKT1 expression. These findings suggest that P. polyphylla exerts anticancer effects through the coordinated modulation of multiple oncogenic pathways in CRC.<\/jats:p>","DOI":"10.3390\/ijms27093874","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:33:37Z","timestamp":1777376017000},"page":"3874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology and Molecular Docking-Based Approach Revealing the Potential Anticancer Compounds and Molecular Mechanisms of Paris polyphylla Against Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Chakkrit","family":"Khanaree","sequence":"first","affiliation":[{"name":"School of Traditional and Alternative Medicine, Chiang Rai Rajabhat University, Chiang Rai 57100, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7775-3762","authenticated-orcid":false,"given":"Ratchanon","family":"Inpan","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-2230","authenticated-orcid":false,"given":"Weerakit","family":"Taychaworaditsakul","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\/0000-0002-8198-6128","authenticated-orcid":false,"given":"Nahathai","family":"Dukeaw","sequence":"additional","affiliation":[{"name":"School of Health Science, Mae Fah Luang University, Chiang Rai 57100, Thailand"},{"name":"Biomedical Technology Research Group for Vulnerable Populations, Mae Fah Luang University, Chiang Rai 57100, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN","volume":"72","author":"Morgan","year":"2023","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1200\/JCO.22.01690","article-title":"Treatment of Metastatic Colorectal Cancer: ASCO Guideline","volume":"41","author":"Morris","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Cervantes","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_5","first-page":"233","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13148-023-01481-1","article-title":"Epigenetic effects of herbal medicine","volume":"15","author":"Wu","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bu, F., Tu, Y., Wan, Z., and Tu, S. (2023). Herbal medicine and its impact on the gut microbiota in colorectal cancer. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1096008"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"154723","DOI":"10.1016\/j.phymed.2023.154723","article-title":"Shenlingcao oral liquid for patients with non-small cell lung cancer receiving adjuvant chemotherapy after radical resection: A multicenter randomized controlled trial","volume":"113","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153575","DOI":"10.1016\/j.phymed.2021.153575","article-title":"Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT\/CyclinD1\/p21\/p27 pathway","volume":"87","author":"Yang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S2468-1253(19)30409-1","article-title":"Berberine versus placebo for the prevention of recurrence of colorectal adenoma: A multicentre, double-blinded, randomised controlled study","volume":"5","author":"Chen","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rawat, J.M., Pandey, S., Rawat, B., Purohit, S., Anand, J., Negi, A.S., Thakur, A., Mahmoud, M.H., El-Gazzar, A.M., and El-Saber Batiha, G. (2023). In vitro production of steroidal saponin, total phenols and antioxidant activity in callus suspension culture of Paris polyphylla Smith: An important Himalayan medicinal plant. Front. Plant Sci., 14.","DOI":"10.3389\/fpls.2023.1225612"},{"key":"ref_12","first-page":"6343","article-title":"Traditional use of Paris polyphylla and its active components","volume":"46","author":"Yan","year":"2021","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114293","DOI":"10.1016\/j.jep.2021.114293","article-title":"The traditional uses, phytochemistry, and pharmacological properties of Paris L. (Liliaceae): A review","volume":"278","author":"Ding","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s12672-024-00882-9","article-title":"Research progress of Paris polyphylla in the treatment of digestive tract cancers","volume":"15","author":"Wang","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lin, L.T., Uen, W.C., Choong, C.Y., Shi, Y.C., Lee, B.H., Tai, C.J., and Tai, C.J. (2019). Paris polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin. Molecules, 24.","DOI":"10.3390\/molecules24112102"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kshetrimayum, V., Heisnam, R., Keithellakpam, O.S., Radhakrishnanand, P., Akula, S.J., Mukherjee, P.K., and Sharma, N. (2023). Paris polyphylla Sm. Induces Reactive Oxygen Species and Caspase 3-Mediated Apoptosis in Colorectal Cancer Cells In Vitro and Potentiates the Therapeutic Significance of Fluorouracil and Cisplatin. Plants, 12.","DOI":"10.3390\/plants12071446"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1080\/14786419.2017.1353512","article-title":"Anticancer effect of Polyphyllin \u0399 in colorectal cancer cells through ROS-dependent autophagy and G2\/M arrest mechanisms","volume":"32","author":"Yu","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Luo, Q., Jia, L., Huang, C., Qi, Q., Jahangir, A., Xia, Y., Liu, W., Shi, R., Tang, L., and Chen, Z. (2022). Polyphyllin I Promotes Autophagic Cell Death and Apoptosis of Colon Cancer Cells via the ROS-Inhibited AKT\/mTOR Pathway. Int. J. Mol. Sci., 23, Erratum in Int. J. Mol. Sci. 2025, 26, 11528. https:\/\/doi.org\/10.3390\/ijms23169368.","DOI":"10.3390\/ijms262311528"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.phrs.2018.11.029","article-title":"Paris saponin II inhibits colorectal carcinogenesis by regulating mitochondrial fission and NF-\u03baB pathway","volume":"139","author":"Chen","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lin, L.T., Shi, Y.C., Choong, C.Y., and Tai, C.J. (2021). The Fruits of Paris polyphylla Inhibit Colorectal Cancer Cell Migration Induced by Fusobacterium nucleatum-Derived Extracellular vesicles. Molecules, 26.","DOI":"10.3390\/molecules26134081"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bcp.2014.01.018","article-title":"Paris saponin VII inhibits growth of colorectal cancer cells through Ras signaling pathway","volume":"88","author":"Li","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/ptr.6029","article-title":"Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt\/MAPK pathway and inhibition of P-glycoprotein in K562\/ADR cells","volume":"32","author":"Yan","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_23","first-page":"25","article-title":"Polyphyllin VII suppresses cell proliferation, the cell cycle and cell migration in colorectal cancer","volume":"21","author":"Song","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109246","DOI":"10.1016\/j.cbi.2020.109246","article-title":"PP9, a steroidal saponin, induces G2\/M arrest and apoptosis in human colorectal cancer cells by inhibiting the PI3K\/Akt\/GSK3\u03b2 pathway","volume":"331","author":"Yao","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_25","first-page":"1","article-title":"TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches","volume":"19","author":"Wang","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: A powerful approach for structure-based drug discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1442906","DOI":"10.1155\/2021\/1442906","article-title":"Chemical Constituents and Pharmacological Activities of Steroid Saponins Isolated from Rhizoma Paridis","volume":"2021","author":"Liu","year":"2021","journal-title":"J. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7947224","DOI":"10.1155\/2023\/7947224","article-title":"Traditional Uses, Active Ingredients, and Biological Activities of Paris polyphylla Smith: A Comprehensive Review of an Important Himalayan Medicinal Plant","volume":"2023","author":"Rawat","year":"2023","journal-title":"J. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bouabdallah, S., Al-Maktoum, A., and Amin, A. (2023). Steroidal Saponins: Naturally Occurring Compounds as Inhibitors of the Hallmarks of Cancer. Cancers, 15.","DOI":"10.3390\/cancers15153900"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.7314\/APJCP.2015.16.3.1169","article-title":"Steroidal saponins from Paris polyphylla induce apoptotic cell death and autophagy in A549 human lung cancer cells","volume":"16","author":"He","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31914","DOI":"10.1021\/acsomega.3c03649","article-title":"Apoptotic Potential and Antitumor Efficacy of Trilliumoside A: A New Steroidal Saponin Isolated from Rhizomes of Trillium govanianum","volume":"8","author":"Tabassum","year":"2023","journal-title":"ACS Omega"},{"key":"ref_32","unstructured":"Bizzarri, M. (2020). Synergistic Effects of Chinese Herbal Medicine and Biological Networks. Approaching Complex Diseases: Network-Based Pharmacology and Systems Approach in Bio-Medicine, Springer International Publishing."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.2174\/138945011793591626","article-title":"Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy","volume":"12","author":"Efferth","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s12032-023-02180-w","article-title":"Diosmetin induces apoptosis and protective autophagy in human gastric cancer HGC-27 cells via the PI3K\/Akt\/FoxO1 and MAPK\/JNK pathways","volume":"40","author":"Pan","year":"2023","journal-title":"Med. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.12659\/MSM.914058","article-title":"Anti-Proliferation and Pro-Apoptotic Effects of Diosmetin via Modulating Cell Cycle Arrest and Mitochondria-Mediated Intrinsic Apoptotic Pathway in MDA-MB-231 Cells","volume":"25","author":"Wang","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1007\/s11655-023-3693-1","article-title":"Anticancer Activity of Diosgenin and its Molecular Mechanism","volume":"29","author":"Ren","year":"2023","journal-title":"Chin. J. Integr. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"800","DOI":"10.5530\/ijper.20250474","article-title":"Pennogenin Induces Apoptosis in Colon Cancer HCT 116 Cells via Increasing Apoptotic Markers and Downregulating PI3K AKT mTOR Pathway","volume":"59","author":"Zheng","year":"2025","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gargalionis, A.N., Papavassiliou, K.A., and Papavassiliou, A.G. (2021). Targeting STAT3 Signaling Pathway in Colorectal Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081016"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/S2468-1253(23)00479-X","article-title":"Targeting the EGFR signalling pathway in metastatic colorectal cancer","volume":"9","author":"Napolitano","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s40265-019-01113-0","article-title":"Targeting EGFR and RAS\/RAF Signaling in the Treatment of Metastatic Colorectal Cancer: From Current Treatment Strategies to Future Perspectives","volume":"79","author":"Mizukami","year":"2019","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"801","DOI":"10.2741\/e287","article-title":"Src-family tyrosine kinases as therapeutic targets in advanced cancer","volume":"3","author":"Gelman","year":"2011","journal-title":"Front. Biosci. (Elite Ed.)"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13023","DOI":"10.2147\/OTT.S278013","article-title":"Progress in Understanding the IL-6\/STAT3 Pathway in Colorectal Cancer","volume":"13","author":"Lin","year":"2020","journal-title":"Oncol. Targets Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Leiphrakpam, P.D., and Are, C. (2024). PI3K\/Akt\/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063178"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s43556-026-00433-4","article-title":"Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances","volume":"7","author":"Chen","year":"2026","journal-title":"Mol. Biomed."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"BSR20200265","DOI":"10.1042\/BSR20200265","article-title":"Colorectal cancer (CRC) as a multifactorial disease and its causal correlations with multiple signaling pathways","volume":"40","author":"Wan","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1200\/JCO.2009.24.6116","article-title":"Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer","volume":"28","author":"Bardelli","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e202500447","DOI":"10.1002\/cmdc.202500447","article-title":"Recent Insights in Multi-Target Drugs in Pharmacology and Medicinal Chemistry","volume":"20","author":"Cemali","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s43440-025-00715-8","article-title":"Polypharmacology: New drugs in 2023\u20132024","volume":"77","author":"Ryszkiewicz","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zoi, V., Kyritsis, A.P., Galani, V., Lazari, D., Sioka, C., Voulgaris, S., and Alexiou, G.A. (2024). The role of curcumin in cancer: A focus on the PI3K\/Akt pathway. Cancers, 16.","DOI":"10.3390\/cancers16081554"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1007\/s12672-025-03190-y","article-title":"Therapeutic potential of natural compounds in targeting cancer stem cells: A promising approach for cancer treatment","volume":"16","author":"Debnath","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Shalayel, M.H.F., Al-Mazaideh, G.M., Alanezi, A.A., Almuqati, A.F., and Alotaibi, M. (2023). Diosgenin and Monohydroxy Spirostanol from Prunus amygdalus var. amara Seeds as Potential Suppressors of EGFR and HER2 Tyrosine Kinases: A Computational Approach. Pharmaceuticals, 16.","DOI":"10.3390\/ph16050704"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1002\/pep2.70009","article-title":"Exploring the Pharmacodynamic and Molecular Interactions of Diosgenin as a multitarget Therapeutic Agent in Breast and Ovarian Cancer Pathways","volume":"117","author":"Ullah","year":"2025","journal-title":"Pept. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"114252","DOI":"10.1016\/j.phytochem.2024.114252","article-title":"A systematic review of spirostanol saponins and anticancer natural products isolated from Tacca plantaginea (Hance) Drenth","volume":"228","author":"Bailly","year":"2024","journal-title":"Phytochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1038\/nm.3967","article-title":"The consensus molecular subtypes of colorectal cancer","volume":"21","author":"Guinney","year":"2015","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41392-024-01953-7","article-title":"Signaling pathways involved in colorectal cancer: Pathogenesis and targeted therapy","volume":"9","author":"Li","year":"2024","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:48:43Z","timestamp":1777376923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/3874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27093874"],"URL":"https:\/\/doi.org\/10.3390\/ijms27093874","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]}}}