{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:10:40Z","timestamp":1785413440068,"version":"3.56.0"},"reference-count":135,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Natural Science Foundation of China","award":["2024AFD226"],"award-info":[{"award-number":["2024AFD226"]}]},{"name":"Hubei University of Chinese Medicine","award":["2023ZDXM004"],"award-info":[{"award-number":["2023ZDXM004"]}]},{"award":["2023ZDXM004"],"award-info":[{"award-number":["2023ZDXM004"]}],"id":[{"id":"https:\/\/ror.org\/02my3bx32","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M771971"],"award-info":[{"award-number":["2025M771971"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025M771971"],"award-info":[{"award-number":["2025M771971"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Cancer is the second leading cause of death worldwide, and tumor heterogeneity remains a major obstacle to effective therapy. In vitro reconstruction of the tumor microenvironment (TME) is particularly challenging because of its complexity, dynamic nature, and spatial heterogeneity, which limits the predictive value of conventional models for anticancer drug evaluation. Traditional Chinese medicine (TCM) has attracted increasing attention in cancer therapy owing to its multi-component, multi-target, and multi-pathway therapeutic characteristics. However, the complexity of TCM formulations and the diversity of their bioactive constituents make their pharmacological mechanisms difficult to elucidate using conventional experimental models. Microfluidic tumor microenvironment-on-a-chip (TME-on-a-chip) platforms integrate engineered cell culture with dynamic perfusion systems to recapitulate key structural, biochemical, and cellular features of the TME, thus providing a more physiologically relevant platform for anticancer research. With advantages such as low sample consumption, precise spatiotemporal control, multicellular co-culture, and real-time monitoring, these platforms provide a promising strategy for evaluating the efficacy and microenvironment-dependent effects of TCM-derived compounds and formulations. In this review, we summarize recent advances in the construction of TME-on-a-chip models, including multicellular organization, extracellular matrix simulation, vascularization, and immune microenvironment reconstruction, and discuss how these systems can be applied to key questions in TCM-based anticancer research. We further analyze current technical and methodological challenges that limit their broader adoption in TCM research and highlight future directions for promoting mechanism-driven and precision-oriented development of TCM in cancer therapy.<\/jats:p>","DOI":"10.3390\/bios16080413","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:54Z","timestamp":1785411534000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Microenvironment-on-a-Chip: Construction and Application in Traditional Chinese Medicine Anti-Tumor Therapy"],"prefix":"10.3390","volume":"16","author":[{"given":"Yujie","family":"Sheng","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Cui","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiju","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"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":"1617","DOI":"10.1016\/j.cell.2024.02.041","article-title":"Cancer Biomarkers: Emerging Trends and Clinical Implications for Personalized Treatment","volume":"187","author":"Passaro","year":"2024","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108522","DOI":"10.1016\/j.pharmthera.2023.108522","article-title":"Cancer Metastasis: Molecular Mechanisms and Clinical Perspectives","volume":"250","author":"Khan","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107753","DOI":"10.1016\/j.pharmthera.2020.107753","article-title":"Tumor Microenvironment as a Therapeutic Target in Cancer","volume":"221","author":"Xiao","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107788","DOI":"10.1016\/j.phrs.2025.107788","article-title":"Targeting Tumor-Associated Macrophage Polarization with Traditional Chinese Medicine Active Ingredients: Dual Reversal of Chemoresistance and Immunosuppression in Tumor Microenvironment","volume":"216","author":"Qi","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.2147\/OTT.S444214","article-title":"Traditional Chinese Medicine in Regulating Tumor Microenvironment","volume":"17","author":"Wang","year":"2024","journal-title":"Onco Targets Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116172","DOI":"10.1016\/j.biopha.2024.116172","article-title":"Astragalus Polysaccharide Ameliorates CD8+ T Cell Dysfunction through STAT3\/Gal-3\/LAG3 Pathway in Inflammation-Induced Colorectal Cancer","volume":"171","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"603198","DOI":"10.1155\/2015\/603198","article-title":"Interferon-\u03b3-Mediated Natural Killer Cell Activation by an Aqueous Panax Ginseng Extract","volume":"2015","author":"Takeda","year":"2015","journal-title":"Evid.\u2014Based Complement. Altern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s13046-023-02888-7","article-title":"Ginseng-Derived Nanoparticles Reprogram Macrophages to Regulate Arginase-1 Release for Ameliorating T Cell Exhaustion in Tumor Microenvironment","volume":"42","author":"Lv","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.apsb.2015.07.008","article-title":"The Antitumor Effect of Tanshinone IIA on Anti-Proliferation and Decreasing VEGF\/VEGFR2 Expression on the Human Non-Small Cell Lung Cancer A549 Cell Line","volume":"5","author":"Xie","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116738","DOI":"10.1016\/j.biopha.2024.116738","article-title":"Matrine Induces Autophagic Cell Death by Triggering ROS\/AMPK\/MTOR Axis and Apoptosis in Multiple Myeloma","volume":"175","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","first-page":"8289","article-title":"Paclitaxel Suppresses Proliferation and Induces Apoptosis through Regulation of ROS and the AKT\/MAPK Signaling Pathway in Canine Mammary Gland Tumor Cells","volume":"17","author":"Ren","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115527","DOI":"10.1016\/j.bios.2023.115527","article-title":"Integration of Fluorescence and MALDI Imaging for Microfluidic Chip-Based Screening of Potential Thrombin Inhibitors from Natural Products","volume":"237","author":"Wang","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"ref_14","first-page":"335","article-title":"Organoids: The Future of Disease Modelling and Therapeutics","volume":"5","author":"Zhou","year":"2024","journal-title":"Biomater. Transl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101199","DOI":"10.1016\/j.jpha.2025.101199","article-title":"Tailoring a Traditional Chinese Medicine Prescription for Complex Diseases: A Novel Multi-Targets-Directed Gradient Weighting Strategy","volume":"15","author":"Yu","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s44222-024-00163-8","article-title":"Microfluidic High-Throughput 3D Cell Culture","volume":"2","author":"Ko","year":"2024","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s43556-023-00165-9","article-title":"Patient-Derived Organoids in Human Cancer: A Platform for Fundamental Research and Precision Medicine","volume":"5","author":"Qu","year":"2024","journal-title":"Mol. Biomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"114365","DOI":"10.1016\/j.addr.2022.114365","article-title":"Immunotherapy Discovery on Tumor Organoid-on-a-Chip Platforms That Recapitulate the Tumor Microenvironment","volume":"187","author":"Zhang","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107668","DOI":"10.1016\/j.pharmthera.2020.107668","article-title":"Tumor Organoid Models in Precision Medicine and Investigating Cancer-Stromal Interactions","volume":"218","author":"Xu","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6691","DOI":"10.1021\/acsnano.7b00824","article-title":"Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery","volume":"11","author":"Agarwal","year":"2017","journal-title":"ACS Nano"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.1039\/D0CS00705F","article-title":"Microfluidic Lumen-Based Systems for Advancing Tubular Organ Modeling","volume":"49","author":"Ayuso","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental Regulation of Tumor Progression and Metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/annonc\/mdw168","article-title":"Targeting the Tumor Microenvironment: Removing Obstruction to Anticancer Immune Responses and Immunotherapy","volume":"27","author":"Pitt","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s12964-023-01136-x","article-title":"Small Extracellular Vesicle-Mediated Metabolic Reprogramming: From Tumors to Pre-Metastatic Niche Formation","volume":"21","author":"Jiang","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s12276-023-01013-0","article-title":"Cancer-Associated Fibroblasts: From Basic Science to Anticancer Therapy","volume":"55","author":"Yang","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology Meets Immunology: The Cancer-Immunity Cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.aaa6204","article-title":"T Cell Exclusion, Immune Privilege, and the Tumor Microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cmet.2016.09.008","article-title":"Macrophage Metabolism Controls Tumor Blood Vessel Morphogenesis and Metastasis","volume":"24","author":"Wenes","year":"2016","journal-title":"Cell Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41568-020-00329-7","article-title":"The Matrix in Cancer","volume":"21","author":"Cox","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of Extracellular Matrix Remodelling in Tumour Progression and Metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/j.ijbiomac.2022.09.129","article-title":"A Concise Review of VEGF, PDGF, FGF, Notch, Angiopoietin, and HGF Signalling in Tumor Angiogenesis with a Focus on Alternative Approaches and Future Directions","volume":"221","author":"Vimalraj","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41577-022-00796-z","article-title":"TGF\u03b2 Control of Immune Responses in Cancer: A Holistic Immuno-Oncology Perspective","volume":"23","author":"Nixon","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2015.03.001","article-title":"Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy","volume":"27","author":"Topalian","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX Transcriptionally and Epigenetically Programs CD8+ T Cell Exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/S1470-2045(19)30388-2","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma (KEYNOTE-006): Post-Hoc 5-Year Results from an Open-Label, Multicentre, Randomised, Controlled, Phase 3 Study","volume":"20","author":"Robert","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/S0140-6736(17)33297-X","article-title":"Atezolizumab versus Chemotherapy in Patients with Platinum-Treated Locally Advanced or Metastatic Urothelial Carcinoma (IMvigor211): A Multicentre, Open-Label, Phase 3 Randomised Controlled Trial","volume":"391","author":"Powles","year":"2018","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved Survival with Ipilimumab in Patients with Metastatic Melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102945","DOI":"10.1016\/j.ctrv.2025.102945","article-title":"Optimal Bevacizumab Treatment Strategy in Advanced Ovarian Cancer: A Review","volume":"137","author":"Monk","year":"2025","journal-title":"Cancer Treat. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMoa1717002","article-title":"Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma","volume":"379","author":"Meyer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/S1470-2045(19)30274-8","article-title":"Epacadostat plus Pembrolizumab versus Placebo plus Pembrolizumab in Patients with Unresectable or Metastatic Melanoma (ECHO-301\/KEYNOTE-252): A Phase 3, Randomised, Double-Blind Study","volume":"20","author":"Long","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1158\/1078-0432.CCR-06-1586","article-title":"A Phase I Pharmacokinetic and Pharmacodynamic Study of S-3304, a Novel Matrix Metalloproteinase Inhibitor, in Patients with Advanced and Refractory Solid Tumors","volume":"13","author":"Chiappori","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1002\/jcsm.13638","article-title":"Tocilizumab for Advanced Non-Small-Cell Lung Cancer with Concomitant Cachexia: An Observational Study","volume":"15","author":"Du","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s40265-019-01210-0","article-title":"Pexidartinib: First Approval","volume":"79","author":"Lamb","year":"2019","journal-title":"Drugs"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1007\/s40265-025-02191-z","article-title":"Vimseltinib: First Approval","volume":"85","author":"Lee","year":"2025","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12943-024-02135-3","article-title":"Chinese Herbal Medicine for the Treatment of Intestinal Cancer: Preclinical Studies and Potential Clinical Applications","volume":"23","author":"Zhang","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-025-02245-6","article-title":"Traditional Chinese Medicine in Lung Cancer Treatment","volume":"24","author":"Xi","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4071","DOI":"10.62347\/NOAI4101","article-title":"Regulation of the Tumor Microenvironment by Traditional Chinese Medicine: Current Progress and Future Perspectives in Oncology","volume":"17","author":"Wang","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"154787","DOI":"10.1016\/j.phymed.2023.154787","article-title":"Panax Notoginseng Saponins Normalises Tumour Blood Vessels by Inhibiting EphA2 Gene Expression to Modulate the Tumour Microenvironment of Breast Cancer","volume":"114","author":"Xia","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s12272-024-01516-y","article-title":"Ginsenoside Rg3 Activates the Immune Function of CD8+ T Cells via CircFOXP1-MiR-4477a-PD-L1 Axis to Induce Ferroptosis in Gallbladder Cancer","volume":"47","author":"Ye","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118954","DOI":"10.1016\/j.jep.2024.118954","article-title":"Mechanism of Shashen-Maidong Herb Pair in Treating Hepatocellular Carcinoma Using Network Pharmacology and Experimental Validation","volume":"337","author":"Xie","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"157231","DOI":"10.1016\/j.cej.2024.157231","article-title":"Sensitizing Sorafenib to Hepatocellular Carcinoma with Dual-Targeted and PH-Responsive Nanodrugs via Overcoming the Hypoxia Tumor Microenvironment","volume":"500","author":"Li","year":"2024","journal-title":"Chem. Eng. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"107032","DOI":"10.1016\/j.phrs.2023.107032","article-title":"Baicalin and Baicalein in Modulating Tumor Microenvironment for Cancer Treatment: A Comprehensive Review with Future Perspectives","volume":"199","author":"Wang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13020-024-00995-x","article-title":"Application of Omics Technologies in Studies on Antitumor Effects of Traditional Chinese Medicine","volume":"19","author":"Tan","year":"2024","journal-title":"Chin. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"srep44822","DOI":"10.1038\/srep44822","article-title":"Astragalus Polysaccharides Exerts Immunomodulatory Effects via TLR4-Mediated MyD88-Dependent Signaling Pathway in Vitro and in Vivo","volume":"7","author":"Zhou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1136\/gutjnl-2020-321031","article-title":"Ginseng Polysaccharides Alter the Gut Microbiota and Kynurenine\/Tryptophan Ratio, Potentiating the Antitumour Effect of Antiprogrammed Cell Death 1\/Programmed Cell Death Ligand 1 (Anti-PD-1\/PD-L1) Immunotherapy","volume":"71","author":"Huang","year":"2022","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bamodu, O.A., Kuo, K.T., Wang, C.H., Huang, W.C., Wu, A.T.H., Tsai, J.T., Lee, K.Y., Yeh, C.T., and Wang, L.S. (2019). Astragalus Polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer. Nutrients, 11.","DOI":"10.20944\/preprints201908.0117.v1"},{"key":"ref_58","first-page":"56","article-title":"Polysaccharide from Astragalus Membranaceus Promotes the Activation of Human Peripheral Blood and Mouse Spleen Dendritic Cells","volume":"19","author":"Lim","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Li, H., Huang, N., Zhu, W., Wu, J., Yang, X., Teng, W., Tian, J., Fang, Z., Luo, Y., and Chen, M. (2018). Modulation the Crosstalk between Tumor-Associated Macrophages and Non-Small Cell Lung Cancer to Inhibit Tumor Migration and Invasion by Ginsenoside Rh2. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4299-4"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"120604","DOI":"10.1016\/j.biomaterials.2020.120604","article-title":"Celastrol Nanoemulsion Induces Immunogenicity and Downregulates PD-L1 to Boost Abscopal Effect in Melanoma Therapy","volume":"269","author":"Qiu","year":"2021","journal-title":"Biomaterials"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shanmugam, M.K., Ahn, K.S., Lee, J.H., Kannaiyan, R., Mustafa, N., Manu, K.A., Siveen, K.S., Sethi, G., Chng, W.J., and Kumar, A.P. (2018). Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00365"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e564","DOI":"10.1002\/ctm2.564","article-title":"Baicalein Is a Novel TLR4-targeting Therapeutics Agent That Inhibits TLR4\/HIF-1\u03b1\/VEGF Signaling Pathway in Colorectal Cancer","volume":"11","author":"Chen","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41392-021-00739-5","article-title":"Aiphanol, a Native Compound, Suppresses Angiogenesis via Dual-Targeting VEGFR2 and COX2","volume":"6","author":"Chen","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jconrel.2024.04.053","article-title":"Biomimetic \u201cNano-Spears\u201d for CAFs-Targeting: Splintered Three \u201cShields\u201d with Enhanced Cisplatin Anti-TNBC Efficiency","volume":"370","author":"Wu","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"105658","DOI":"10.1016\/j.phrs.2021.105658","article-title":"Bruceine A Induces Cell Growth Inhibition and Apoptosis through PFKFB4\/GSK3\u03b2 Signaling in Pancreatic Cancer","volume":"169","author":"Zhang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Huang, S.Y., Huang, G.J., Wu, H.C., Kao, M.C., and Huang, W.C. (2018). Ganoderma Tsugae Inhibits the SREBP-1\/AR Axis Leading to Suppression of Cell Growth and Activation of Apoptosis in Prostate Cancer Cells. Molecules, 23.","DOI":"10.3390\/molecules23102539"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Guo, W., Tan, H.Y., Chen, F., Wang, N., and Feng, Y. (2020). Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines. Cancers, 12.","DOI":"10.3390\/cancers12020404"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.7150\/ijbs.77720","article-title":"Active Ingredients from Chinese Medicine for Combination Cancer Therapy","volume":"19","author":"Wang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1159\/000453175","article-title":"Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3","volume":"40","author":"He","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e000317","DOI":"10.1136\/jitc-2019-000317","article-title":"Compound Kushen Injection Relieves Tumor-Associated Macrophage-Mediated Immunosuppression through TNFR1 and Sensitizes Hepatocellular Carcinoma to Sorafenib","volume":"8","author":"Yang","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"156039","DOI":"10.1016\/j.phymed.2024.156039","article-title":"XIAOPI Formula Inhibits Chemoresistance and Metastasis of Triple-Negative Breast Cancer by Suppressing Extracellular Vesicle\/CXCL1-Induced TAM\/PD-L1 Signaling","volume":"135","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6422","DOI":"10.1039\/C9FO01901D","article-title":"Curcumin-Enhanced Antitumor Effects of Sorafenib: Via Regulating the Metabolism and Tumor Microenvironment","volume":"11","author":"Man","year":"2020","journal-title":"Food Funct."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"155462","DOI":"10.1016\/j.phymed.2024.155462","article-title":"Andrographolide Sensitizes KRAS-Mutant Colorectal Cancer Cells to Cetuximab by Inhibiting the EGFR\/AKT and PDGFR\u03b2\/AKT Signaling Pathways","volume":"126","author":"Liu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"141371","DOI":"10.1016\/j.foodchem.2024.141371","article-title":"Bioavailability and Interactions of Schisandrin B with 5-Fluorouracil in a Xenograft Mouse Model of Colorectal Cancer","volume":"463","author":"Lee","year":"2025","journal-title":"Food Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.7150\/thno.44705","article-title":"Combinative Treatment of \u03b2-Elemene and Cetuximab Is Sensitive to KRAS Mutant Colorectal Cancer Cells by Inducing Ferroptosis and Inhibiting Epithelial-Mesenchymal Transformation","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"154701","DOI":"10.1016\/j.phymed.2023.154701","article-title":"Shikonin and Cisplatin Synergistically Overcome Cisplatin Resistance of Ovarian Cancer by Inducing Ferroptosis via Upregulation of HMOX1 to Promote Fe2+ Accumulation","volume":"112","author":"Ni","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2302686","DOI":"10.1002\/adhm.202302686","article-title":"Advances in Microfluidic Technologies in Organoid Research","volume":"13","author":"Liu","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nbt.2989","article-title":"Microfluidic Organs-on-Chips","volume":"32","author":"Bhatia","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1089\/omi.2015.0128","article-title":"Vasoregression: A Shared Vascular Pathology Underlying Macrovascular and Microvascular Pathologies?","volume":"19","author":"Gupta","year":"2015","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S1535-6108(03)00271-X","article-title":"Stage-Specific Vascular Markers Revealed by Phage Display in a Mouse Model of Pancreatic Islet Tumorigenesis","volume":"4","author":"Joyce","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41568-018-0104-6","article-title":"Modelling Cancer in Microfluidic Human Organs-on-Chips","volume":"19","author":"Hassell","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1038\/s41467-021-22676-1","article-title":"Lung Cancer Organoids Analyzed on Microwell Arrays Predict Drug Responses of Patients within a Week","volume":"12","author":"Hu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature05061","article-title":"Future Lab-on-a-Chip Technologies for Interrogating Individual Molecules","volume":"442","author":"Harold","year":"2006","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.aca.2009.04.051","article-title":"Microfluidic Chip: Next-Generation Platform for Systems Biology","volume":"650","author":"Feng","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e10627","DOI":"10.1002\/btm2.10627","article-title":"Advances in High Throughput Cell Culture Technologies for Therapeutic Screening and Biological Discovery Applications","volume":"9","author":"Ryoo","year":"2024","journal-title":"Bioeng. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Shah, S., and D\u2019Souza, G.G.M. (2025). Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis. Cells, 14.","DOI":"10.3390\/cells14100732"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Katt, M.E., Placone, A.L., Wong, A.D., Xu, Z.S., and Searson, P.C. (2016). In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform. Front. Bioeng. Biotechnol., 4.","DOI":"10.3389\/fbioe.2016.00012"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The Evolving Tumor Microenvironment: From Cancer Initiation to Metastatic Outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e2201784","DOI":"10.1002\/adhm.202201784","article-title":"New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay","volume":"12","author":"Wan","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"766","DOI":"10.7150\/thno.95334","article-title":"Vascularized Tumor on a Microfluidic Chip to Study Mechanisms Promoting Tumor Neovascularization and Vascular Targeted Therapies","volume":"15","author":"Skubal","year":"2025","journal-title":"Theranostics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1039\/D3LC00662J","article-title":"Enabling Continuous Immune Cell Recirculation on a Microfluidic Array to Study Immunotherapeutic Interactions in a Recapitulated Tumour Microenvironment","volume":"24","author":"Chi","year":"2024","journal-title":"Lab Chip"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"eabc2331","DOI":"10.1126\/sciadv.abc2331","article-title":"Microfluidic Tumor-on-a-Chip Model to Evaluate the Role of Tumor Environmental Stress on NK Cell Exhaustion","volume":"7","author":"Ayuso","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e2413457","DOI":"10.1002\/advs.202413457","article-title":"Tumor Microenvironment On-A-Chip and Single-Cell Analysis Reveal Synergistic Stromal\u2013Immune Crosstalk on Breast Cancer Progression","volume":"12","author":"Ravi","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00604-024-06362-9","article-title":"Establishment of a Novel Microfluidic Co-Culture System for Simultaneous Analysis of Multiple Indicators of Gefitinib Sensitivity in Colorectal Cancer Cells","volume":"191","author":"Li","year":"2024","journal-title":"Microchim. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"166746","DOI":"10.1016\/j.bbadis.2023.166746","article-title":"Targeting the Tumor Microenvironment: Potential Strategy for Cancer Therapeutics","volume":"1869","author":"Babar","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Liu, Z., Xie, Y., He, Y., Chen, K., Zhou, M., Ha, G., Duan, L., Zhao, Z., and Cai, D. (2026). Research Progress on Traditional Chinese Medicine-Assisted Immune Checkpoint Inhibitors Therapy for Solid Tumors. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1723860"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1021\/acssensors.0c01846","article-title":"An Oxygen-Concentration-Controllable Multiorgan Microfluidic Platform for Studying Hypoxia-Induced Lung Cancer-Liver Metastasis and Screening Drugs","volume":"6","author":"Zheng","year":"2021","journal-title":"ACS Sens."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1021\/acs.nanolett.9b01597","article-title":"Microchannel Stiffness and Confinement Jointly Induce the Mesenchymal-Amoeboid Transition of Cancer Cell Migration","volume":"19","author":"Wang","year":"2019","journal-title":"Nano Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"7696","DOI":"10.1038\/s41467-023-43586-4","article-title":"3D Bioprinted Multilayered Cerebrovascular Conduits to Study Cancer Extravasation Mechanism Related with Vascular Geometry","volume":"14","author":"Park","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ebiom.2018.10.046","article-title":"Organotypic Microfluidic Breast Cancer Model Reveals Starvation-Induced Spatial-Temporal Metabolic Adaptations","volume":"37","author":"Ayuso","year":"2018","journal-title":"eBioMedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e2412815","DOI":"10.1002\/adma.202412815","article-title":"Personalized Vascularized Tumor Organoid-on-a-Chip for Tumor Metastasis and Therapeutic Targeting Assessment","volume":"37","author":"Du","year":"2025","journal-title":"Adv. Mater."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling Development and Disease with Organoids","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.aaw7894","article-title":"Organoids-on-a-Chip","volume":"364","author":"Park","year":"2019","journal-title":"Science"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1053\/j.gastro.2015.11.047","article-title":"Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology","volume":"150","author":"In","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 Stem Cells Build Crypt-Villus Structures in Vitro without a Mesenchymal Niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1136\/gutjnl-2019-319256","article-title":"Liver Organoids: From Basic Research to Therapeutic Applications","volume":"68","author":"Prior","year":"2019","journal-title":"Gut"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Hoenig, M.P., and Hladik, G.A. (2018). Overview of Kidney Structure and Function. National Kidney Foundation\u2019s Primer on Kidney Diseases, Elsevier.","DOI":"10.1016\/B978-0-323-47794-9.00001-9"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1038\/s41596-023-00847-2","article-title":"Directed Differentiation of Ureteric Bud and Collecting Duct Organoids from Human Pluripotent Stem Cells","volume":"18","author":"Shi","year":"2023","journal-title":"Nat. Protoc."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1213\/00000539-197001000-00035","article-title":"Oxygen, Uptake, Transport, and Tissue Utilization","volume":"49","author":"Waltemath","year":"1970","journal-title":"Anesth. Analg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial TCA Cycle Metabolites Control Physiology and Disease","volume":"11","author":"Chandel","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2211685","DOI":"10.1080\/22221751.2023.2211685","article-title":"Reciprocal Enhancement of SARS-CoV-2 and Influenza Virus Replication in Human Pluripotent Stem Cell-Derived Lung Organoids","volume":"12","author":"Kim","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41378-022-00370-6","article-title":"Patient-Derived Pancreatic Cancer-on-a-Chip Recapitulates the Tumor Microenvironment","volume":"8","author":"Haque","year":"2022","journal-title":"Microsyst. Nanoeng."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"102358","DOI":"10.1016\/j.xcrp.2024.102358","article-title":"Hydrogel-Based Hollow Microfibers for Functional Esophageal Carcinoma Remodeling","volume":"6","author":"Shi","year":"2025","journal-title":"Cell Rep. Phys. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Koenig, L., Ramme, A.P., and Faust, D. (2022). A Human Stem Cell-Derived Brain-Liver Chip for Assessing Blood-Brain-Barrier Permeation of Pharmaceutical Drugs. Cells, 11.","DOI":"10.3390\/cells11203295"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2303943","DOI":"10.1002\/adhm.202303943","article-title":"An Organ-on-chip Platform for Simulating Drug Metabolism along the Gut\u2013Liver Axis","volume":"13","author":"Lucchetti","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1039\/D4LC00290C","article-title":"Microfluidic Synthesis of Hemin@ZIF-8 Nanozyme with Applications in Cellular Reactive Oxygen Species Detection and Anticancer Drug Screening","volume":"24","author":"Wang","year":"2024","journal-title":"Lab Chip"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13020-019-0228-y","article-title":"High Content Screening for Drug Discovery from Traditional Chinese Medicine","volume":"14","author":"Wang","year":"2019","journal-title":"Chin. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"123971","DOI":"10.1016\/j.talanta.2022.123971","article-title":"Construction of a Novel Blood Brain Barrier-Glioma Microfluidic Chip Model: Applications in the Evaluation of Permeability and Anti-Glioma Activity of Traditional Chinese Medicine Components","volume":"253","author":"Shi","year":"2023","journal-title":"Talanta"},{"key":"ref_119","first-page":"302","article-title":"Application of Microfluidic Chips in Anticancer Drug Screening","volume":"22","author":"Fan","year":"2022","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"10166","DOI":"10.1021\/acs.analchem.5b00826","article-title":"Microfluidic-Enabled Print-to-Screen Platform for High-Throughput Screening of Combinatorial Chemotherapy","volume":"87","author":"Ding","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2000111","DOI":"10.1002\/advs.202000111","article-title":"A Precise Microfluidic Assay in Single-Cell Profile for Screening of Transient Receptor Potential Channel Modulators","volume":"7","author":"Ai","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1039\/D1AN00754H","article-title":"Screening of High-Efficiency and Low-Toxicity Antitumor Active Components in: Macleaya Cordata Seeds Based on the Competitive Effect of Drugs on Double Targets by a New Laminar Flow Chip","volume":"146","author":"Gao","year":"2021","journal-title":"Analyst"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1039\/D2TB00225F","article-title":"Nano-Traditional Chinese Medicine: A Promising Strategy and Its Recent Advances","volume":"10","author":"Wei","year":"2022","journal-title":"J. Mater. Chem. B"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"115724","DOI":"10.1016\/j.jpba.2023.115724","article-title":"Development of Organic Three-Phase Laminar Flow Microfluidic Chip for Extraction of Ginsenosides from Panax Ginseng","volume":"236","author":"Chen","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"12285","DOI":"10.1038\/s41598-018-29848-y","article-title":"3D Microfluidic in Vitro Model and Bioinformatics Integration to Study the Effects of Spatholobi Caulis Tannin in Cervical Cancer","volume":"8","author":"Wang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Miyazaki, K., Xu, C., Shimada, M., and Goel, A. (2023). Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030383"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e2407900","DOI":"10.1002\/advs.202407900","article-title":"Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth","volume":"12","author":"Zhao","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"117669","DOI":"10.1016\/j.biopha.2024.117669","article-title":"Insights on Neuropharmacological Benefits and Risks: Aconitum carmichaelii Debx","volume":"181","author":"Liu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Hong, J., Chen, X.Z., Peng, Y.G., Zhang, W.K., Tang, H.B., and Li, Y.S. (2020). Nanoparticle-Encapsulated Liushenwan Could Treat Nanodiethylnitrosamine-Induced Liver Cancer in Mice by Interfering with Multiple Critical Factors for the Tumor Microenvironment. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01052"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"eaax5516","DOI":"10.1126\/scitranslmed.aax5516","article-title":"Reproducing Human and Cross-Species Drug Toxicities Using a Liver-Chip","volume":"11","author":"Jang","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1039\/b812987h","article-title":"Real-Time Detection of the Early Event of Cytotoxicity of Herbal Ingredients on Single Leukemia Cells Studied in a Microfluidic Biochip","volume":"1","author":"Li","year":"2009","journal-title":"Integr. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jpha.2022.11.007","article-title":"Neurotoxicity Mechanism of Aconitine in HT22 Cells Studied by Microfluidic Chip-Mass Spectrometry","volume":"13","author":"Zhang","year":"2023","journal-title":"J. Pharm. Anal."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"4898","DOI":"10.1039\/D4CC00396A","article-title":"Evaluation of Aconitine Cardiotoxicity with a Heart-on-a-Particle Prepared by a Microfluidic Device","volume":"60","author":"Xu","year":"2024","journal-title":"Chem. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Li, X., and Tian, T. (2018). Phytochemical Characterization of Mentha spicata L. Under Differential Dried-Conditions and Associated Nephrotoxicity Screening of Main Compound with Organ-on-a-Chip. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01067"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1021\/acsbiomaterials.7b00417","article-title":"Liver-Kidney-on-Chip to Study Toxicity of Drug Metabolites","volume":"4","author":"Theobald","year":"2018","journal-title":"ACS Biomater. Sci. Eng."}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/8\/413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:54:58Z","timestamp":1785412498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/8\/413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":135,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["bios16080413"],"URL":"https:\/\/doi.org\/10.3390\/bios16080413","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}