{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:00:51Z","timestamp":1781535651167,"version":"3.54.5"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.intimp.2025.115301","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T21:05:24Z","timestamp":1755119124000},"page":"115301","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Pedunculoside regulates tumor immune microenvironment and malignant characteristics of bladder cancer by TRAF6 mediated M2 macrophage polarization"],"prefix":"10.1016","volume":"164","author":[{"given":"Jinshan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxiong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhensheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0005","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-023-00468-9","volume":"9","author":"Dyrskj\u00f8t","year":"2023","journal-title":"Bladder cancer. Nature Reviews Disease Primers"},{"issue":"5","key":"10.1016\/j.intimp.2025.115301_bb0010","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41571-023-00744-3","article-title":"Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice","volume":"20","author":"van Hoogstraten","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.intimp.2025.115301_bb0015","first-page":"384","article-title":"Advances in diagnosis and treatment of bladder cancer","author":"Lopez-Beltran","year":"2024","journal-title":"bmj"},{"issue":"19","key":"10.1016\/j.intimp.2025.115301_bb0020","doi-asserted-by":"crossref","first-page":"7307","DOI":"10.3390\/ijms21197307","article-title":"The immune microenvironment in pancreatic cancer","volume":"21","author":"Huber","year":"2020","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"10.1016\/j.intimp.2025.115301_bb0025","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41568-024-00714-6","article-title":"Towards targeting the breast cancer immune microenvironment","volume":"24","author":"Harris","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.intimp.2025.115301_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellimm.2020.104119","article-title":"The roles of tumor-associated macrophages in tumor angiogenesis and metastasis","volume":"353","author":"Fu","year":"2020","journal-title":"Cell. Immunol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0035","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41698-024-00522-z","article-title":"Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance","volume":"8","author":"Wang","year":"2024","journal-title":"NPJ Precision Oncology"},{"issue":"6","key":"10.1016\/j.intimp.2025.115301_bb0040","doi-asserted-by":"crossref","first-page":"R246","DOI":"10.1016\/j.cub.2020.01.031","article-title":"Tumor-associated macrophages","volume":"30","author":"Cassetta","year":"2020","journal-title":"Curr. Biol."},{"issue":"5","key":"10.1016\/j.intimp.2025.115301_bb0045","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/pharmaceutics16050591","article-title":"In vitro stability and pharmacokinetic study of Pedunculoside and its Beta-CD polymer inclusion complex","volume":"16","author":"Wu","year":"2024","journal-title":"Pharmaceutics"},{"issue":"10","key":"10.1016\/j.intimp.2025.115301_bb0050","doi-asserted-by":"crossref","DOI":"10.1111\/cts.70043","article-title":"Preclinical metabolism and metabolic drug\u2013drug interaction profile of pedunculoside and rotundic acid","volume":"17","author":"Wu","year":"2024","journal-title":"Clin. Transl. Sci."},{"issue":"5","key":"10.1016\/j.intimp.2025.115301_bb0055","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1080\/03009742.2019.1600716","article-title":"Pedunculoside attenuates pathological phenotypes of fibroblast-like synoviocytes and protects against collagen-induced arthritis","volume":"48","author":"Ma","year":"2019","journal-title":"Scand. J. Rheumatol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13020-024-01033-6","article-title":"Pedunculoside alleviates cognitive deficits and neuronal cell apoptosis by activating the AMPK signaling cascade","volume":"19","author":"Li","year":"2024","journal-title":"Chin. Med."},{"key":"10.1016\/j.intimp.2025.115301_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.154884","article-title":"Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways","volume":"116","author":"Fan","year":"2023","journal-title":"Phytomedicine"},{"issue":"6","key":"10.1016\/j.intimp.2025.115301_bb0070","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1007\/s12015-023-10541-1","article-title":"Mesenchymal stem cell-derived exosomal miR-150-3p affects intracerebral hemorrhage by regulating TRAF6\/NF-\u03baB Axis, gut microbiota and metabolism","volume":"19","author":"Sun","year":"2023","journal-title":"Stem Cell Rev. Rep."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0075","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2023.13129","article-title":"MCPIP1 alleviates depressive-like behaviors in mice by inhibiting the TLR4\/TRAF6\/NF-\u03baB pathway to suppress neuroinflammation","volume":"29","author":"An","year":"2024","journal-title":"Mol. Med. Rep."},{"issue":"4","key":"10.1016\/j.intimp.2025.115301_bb0080","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/cas.15302","article-title":"TRAF6 regulates the signaling pathway influencing colorectal cancer function through ubiquitination mechanisms","volume":"113","author":"Guangwei","year":"2022","journal-title":"Cancer Sci."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0085","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.1038\/s41598-023-31557-0","article-title":"TRAF6 as a potential target in advanced breast cancer: a systematic review, meta-analysis, and bioinformatics validation","volume":"13","author":"Zeng","year":"2023","journal-title":"Sci. Rep."},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0090","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.stem.2021.12.007","article-title":"TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity","volume":"29","author":"Muto","year":"2022","journal-title":"Cell Stem Cell"},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0095","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.3892\/ol.2017.6427","article-title":"TRAF6 expression is associated with poorer prognosis and high recurrence in urothelial bladder cancer","volume":"14","author":"Wu","year":"2017","journal-title":"Oncol. Lett."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0100","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1080\/13880209.2022.2109688","article-title":"Asiaticoside reverses M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by TRAF6\/NF-\u03baB inhibition","volume":"60","author":"Li","year":"2022","journal-title":"Pharm. Biol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0105","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1080\/13880209.2022.2109688","article-title":"Asiaticoside reverses M2 phenotype macrophage polarization-evoked osteosarcoma cell malignant behaviour by TRAF6\/NF-\u03baB inhibition","volume":"60","author":"Li","year":"2022","journal-title":"Pharm. Biol."},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0110","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3390\/genes13020187","article-title":"Quantitative real-time analysis of differentially expressed genes in peripheral blood samples of hypertension patients","volume":"13","author":"Ali","year":"2022","journal-title":"Genes"},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0115","first-page":"15","volume":"8","author":"Saginala","year":"2020","journal-title":"Epidemiology of bladder cancer. Medical sciences"},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0120","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.eururo.2023.03.029","article-title":"Epidemiology of bladder cancer in 2023: a systematic review of risk factors","volume":"84","author":"Jubber","year":"2023","journal-title":"Eur. Urol."},{"key":"10.1016\/j.intimp.2025.115301_bb0125","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.583084","article-title":"Tumor-associated macrophages in tumor immunity","volume":"11","author":"Pan","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2025.115301_bb0130","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fonc.2020.00188","article-title":"Tumor-associated macrophages: recent insights and therapies","volume":"10","author":"Zhou","year":"2020","journal-title":"Front. Oncol."},{"key":"10.1016\/j.intimp.2025.115301_bb0135","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.976196","article-title":"Epigenetic therapy reprograms M2-type tumor-associated macrophages into an M1-like phenotype by upregulating miR-7083-5p","volume":"13","author":"Vadevoo","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2025.115301_bb0140","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2019.105880","article-title":"A review on the role of M2 macrophages in bladder cancer; pathophysiology and targeting","volume":"76","author":"Sharifi","year":"2019","journal-title":"Int. Immunopharmacol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0145","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3390\/cancers15010131","article-title":"Sulfatase 2 affects polarization of M2 macrophages through the IL-8\/JAK2\/STAT3 pathway in bladder cancer","volume":"15","author":"Zhang","year":"2022","journal-title":"Cancers"},{"key":"10.1016\/j.intimp.2025.115301_bb0150","doi-asserted-by":"crossref","DOI":"10.1177\/20503121211069012","article-title":"Tumor promoting roles of IL-10, TGF-\u03b2, IL-4, and IL-35: its implications in cancer immunotherapy","volume":"10","author":"Mirlekar","year":"2022","journal-title":"SAGE open medicine"},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.jdsct.2024.100021","article-title":"Pedunculoside promotes oral ulcer healing in mice by upregulating STAT3 and Smad3","volume":"1","author":"Xiao","year":"2024","journal-title":"Journal of Dermatologic Science and Cosmetic Technology"},{"issue":"09\/10","key":"10.1016\/j.intimp.2025.115301_bb0160","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1055\/a-0902-5300","article-title":"Effects of gut microbiota and ingredient-ingredient interaction on the pharmacokinetic properties of rotundic acid and pedunculoside","volume":"85","author":"Yang","year":"2019","journal-title":"Planta Med."},{"issue":"15","key":"10.1016\/j.intimp.2025.115301_bb0165","doi-asserted-by":"crossref","first-page":"19460","DOI":"10.18632\/aging.203357","article-title":"Pedunculoside protects against LPS-induced mastitis in mice by inhibiting inflammation and maintaining the integrity of blood-milk barrier","volume":"13","author":"Kan","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.intimp.2025.115301_bb0170","doi-asserted-by":"crossref","first-page":"1198878","DOI":"10.3389\/fimmu.2023.1198878","article-title":"Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients","volume":"14","author":"Chen","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2025.115301_bb0175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-021-00768-1","article-title":"Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression","volume":"19","author":"Jiang","year":"2021","journal-title":"Cell Communication and Signaling"},{"key":"10.1016\/j.intimp.2025.115301_bb0180","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.82998","article-title":"The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures","volume":"12","author":"Bal\u00e1\u017eov\u00e1","year":"2023","journal-title":"Elife"},{"issue":"10","key":"10.1016\/j.intimp.2025.115301_bb0185","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jtho.2022.06.011","article-title":"Tumor cells modulate macrophage phenotype in a novel in vitro co-culture model of the NSCLC tumor microenvironment","volume":"17","author":"Park","year":"2022","journal-title":"J. Thorac. Oncol."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0190","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13046-023-02756-4","article-title":"Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance","volume":"42","author":"Jiang","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0195","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3390\/genes15020197","article-title":"NF-\u03baB: governing macrophages in cancer","volume":"15","author":"Cornice","year":"2024","journal-title":"Genes"},{"issue":"9","key":"10.1016\/j.intimp.2025.115301_bb0200","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1089\/jir.2024.0008","article-title":"Roles of IL-4, IL-13, and their receptors in lung cancer","volume":"44","author":"Zhang","year":"2024","journal-title":"J. Interf. Cytokine Res."},{"issue":"2","key":"10.1016\/j.intimp.2025.115301_bb0205","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2316104121","article-title":"A TLR4\/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation","volume":"121","author":"Abe","year":"2024","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0210","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41419-022-05524-y","article-title":"TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1\/RIPK3\/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer","volume":"14","author":"Lin","year":"2023","journal-title":"Cell Death Dis."},{"issue":"1","key":"10.1016\/j.intimp.2025.115301_bb0215","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41417-022-00528-4","article-title":"MCPIP1 suppresses the NF-\u03baB signaling pathway through negative regulation of K63-linked Ubiquitylation of TRAF6 in colorectal Cancer","volume":"30","author":"Ye","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"10.1016\/j.intimp.2025.115301_bb0220","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.molimm.2020.09.001","article-title":"TRAF6 promotes IL-4-induced M2 macrophage activation by stabilizing STAT6","volume":"127","author":"Zhou","year":"2020","journal-title":"Mol. Immunol."},{"issue":"12","key":"10.1016\/j.intimp.2025.115301_bb0225","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41419-023-06332-8","article-title":"POU5F1 promotes the proliferation, migration, and invasion of gastric cancer cells by reducing the ubiquitination level of TRAF6","volume":"14","author":"Yang","year":"2023","journal-title":"Cell Death Dis."},{"issue":"5","key":"10.1016\/j.intimp.2025.115301_bb0230","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.ccell.2024.03.009","article-title":"The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia","volume":"42","author":"Liu","year":"2024","journal-title":"Cancer Cell"},{"key":"10.1016\/j.intimp.2025.115301_bb0235","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.652206","article-title":"LINC00467 promotes tumor progression via regulation of the NF-kb signal axis in bladder cancer","volume":"11","author":"Xiao","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.intimp.2025.115301_bb0240","series-title":"Polysaccharide of Atractylodes Macrocephala Koidz (PAMK) Enhance the Immunomodulatory Activity of RAW264. 7 Through TLR4\/MyD88\/NF-\u03baB Pathway","author":"Li","year":"2021"}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925012925?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925012925?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:45:37Z","timestamp":1758786337000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925012925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":48,"alternative-id":["S1567576925012925"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115301","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pedunculoside regulates tumor immune microenvironment and malignant characteristics of bladder cancer by TRAF6 mediated M2 macrophage polarization","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115301","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115301"}}