{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T05:28:03Z","timestamp":1732771683013,"version":"3.29.0"},"reference-count":49,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine","award":["GXZYB20220329"],"award-info":[{"award-number":["GXZYB20220329"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Plasma from patients with active thyroid-associated orbitopathy (TAO-A) could cause inflammation to fibroblasts, and such a mechanism was explored in the context of melanoma.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Plasma samples collected from TAO-A patients and healthy control (HC) were primarily co-cultured with the melanoma-associated fibroblasts (MAFs) derived from melanoma patients. The survival and inflammation of the co-cultured MAFs were measured after confirming the levels of pro-inflammatory cytokines. Ki67 and Vimentin (VIM) markers were analyzed by immunofluorescence, and cell survival and migration were assessed using cell counting kit-8 (CCK-8) and Transwell. The THP-1 cells were induced to differentiate into macrophages, which were subsequently co-cultured to assess M1\/M2 polarization status. Meanwhile, the levels of inflammatory factor were detected by enzyme-linked immunosorbent assay (ELISA). The gene expression was measured by reverse transcription quantitative PCR (RT-qPCR), and the activation of PI3K\/AKT, STAT1, p65, and ERK signaling pathways was detected by Western Blot.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Plasmas derived from TAO-A patients were characterized by elevated levels of pro-inflammatory cytokines, which enhanced the inflammation status and survival of MAFs, promoted the levels of PI3K and AKT, and downregulated expression of Bax. The co-culture of the plasma with MAFs evidently promoted M1 polarization and the phosphorylation of STAT1, P65 and ERK1\/2.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These findings proved the effects of the plasmas of TAO-A patients on the survival and inflammation of MAFs, providing evidence for future studies to delve into the relevant mechanisms.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18612","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:36:36Z","timestamp":1732710996000},"page":"e18612","source":"Crossref","is-referenced-by-count":0,"title":["The effects of plasma from patients with active thyroid-associated orbitopathy on the survival and inflammation of melanoma-associated fibroblasts"],"prefix":"10.7717","volume":"12","author":[{"given":"Huifang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine, Guangxi University of Science and Technology, Liuzhou, China"},{"name":"Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangxi University of Science and Technology, Liuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"issue":"4","key":"10.7717\/peerj.18612\/ref-1","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1615\/CritRevEukaryotGeneExpr.2020028454","article-title":"Malignant melanoma: skin cancer-diagnosis, prevention, and treatment","volume":"30","author":"Ahmed","year":"2020","journal-title":"Critical Reviews in Eukaryotic Gene Expression"},{"issue":"8","key":"10.7717\/peerj.18612\/ref-2","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2174\/1573412918666220509032754","article-title":"A review on PCR and POC-PCR\u2014a boon in the diagnosis of COVID-19","volume":"18","author":"Amuthalakshmi","year":"2022","journal-title":"Current Pharmaceutical Analysis"},{"issue":"1","key":"10.7717\/peerj.18612\/ref-3","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/medicina56010015","article-title":"Tumor microenvironment","volume":"56","author":"Arneth","year":"2019","journal-title":"Medicina (Kaunas, Lithuania)"},{"issue":"8","key":"10.7717\/peerj.18612\/ref-4","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy","volume":"362","author":"Bahn","year":"2010","journal-title":"The New England Journal of Medicine"},{"issue":"11","key":"10.7717\/peerj.18612\/ref-5","doi-asserted-by":"publisher","first-page":"3400","DOI":"10.3390\/cancers12113400","article-title":"A framework of major tumor-promoting signal transduction pathways implicated in melanoma-fibroblast dialogue","volume":"12","author":"Bellei","year":"2020","journal-title":"Cancers"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-6","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1210\/en.2015-1829","article-title":"Comparative assessment of female mouse model of graves\u2019 orbitopathy under different environments, accompanied by proinflammatory cytokine and T-cell responses to thyrotropin hormone receptor antigen","volume":"157","author":"Berchner-Pfannschmidt","year":"2016","journal-title":"Endocrinology"},{"issue":"5","key":"10.7717\/peerj.18612\/ref-7","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1097\/PAT.0b013e328363b3bd","article-title":"Melanoma\u2019s connections to the tumour microenvironment","volume":"45","author":"Brandner","year":"2013","journal-title":"Pathology"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-8","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/j.1365-2133.2005.06780.x","article-title":"Differential expression of melanoma-associated growth factors in keratinocytes and fibroblasts by ultraviolet A and ultraviolet B radiation","volume":"153","author":"Brenner","year":"2005","journal-title":"The British Journal of Dermatology"},{"issue":"24","key":"10.7717\/peerj.18612\/ref-9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/cancers13246173","article-title":"Mesenchymal-stromal cell-like melanoma-associated fibroblasts increase IL-10 production by macrophages in a cyclooxygenase\/indoleamine 2,3-dioxygenase-dependent manner","volume":"13","author":"\u00c7ak\u0131r","year":"2021","journal-title":"Cancers"},{"issue":"2","key":"10.7717\/peerj.18612\/ref-10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1097\/PPO.0b013e31824d448c","article-title":"The role of the PI3K-AKT pathway in melanoma","volume":"18","author":"Davies","year":"2012","journal-title":"Cancer Journal (Sudbury, Massachusetts)"},{"issue":"11","key":"10.7717\/peerj.18612\/ref-11","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1080\/15384047.2019.1640032","article-title":"Current state of melanoma diagnosis and treatment","volume":"20","author":"Davis","year":"2019","journal-title":"Cancer Biology & Therapy"},{"issue":"3","key":"10.7717\/peerj.18612\/ref-12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s10585-019-09966-1","article-title":"The extracellular matrix in tumor progression and metastasis","volume":"36","author":"Eble","year":"2019","journal-title":"Clinical & Experimental Metastasis"},{"issue":"3","key":"10.7717\/peerj.18612\/ref-13","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.ccell.2023.01.010","article-title":"Spatial profiling technologies illuminate the tumor microenvironment","volume":"41","author":"Elhanani","year":"2023","journal-title":"Cancer Cell"},{"issue":"2","key":"10.7717\/peerj.18612\/ref-14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s00018-020-03517-8","article-title":"Melanoma-associated fibroblasts impair CD8+ T cell function and modify expression of immune checkpoint regulators via increased arginase activity","volume":"78","author":"\u00c9rsek","year":"2021","journal-title":"Cellular and Molecular Life Sciences: CMLS"},{"key":"10.7717\/peerj.18612\/ref-15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-3-030-36214-0","article-title":"Tumour microenvironment in skin carcinogenesis","volume":"1226","author":"Georgescu","year":"2020","journal-title":"Advances in Experimental Medicine and Biology"},{"issue":"5","key":"10.7717\/peerj.18612\/ref-16","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1515\/oncologie-2023-0177","article-title":"Ethosomes as delivery system for treatment of melanoma: a mini-review","volume":"25","author":"Grossi","year":"2023","journal-title":"Oncologie"},{"issue":"8","key":"10.7717\/peerj.18612\/ref-17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/1744666X.2024.2326626","article-title":"Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma","volume":"20","author":"Habib","year":"2024","journal-title":"Expert Review of Clinical Immunology"},{"issue":"16","key":"10.7717\/peerj.18612\/ref-18","doi-asserted-by":"publisher","first-page":"12893","DOI":"10.3390\/ijms241612893","article-title":"Targeting melanoma-associated fibroblasts (MAFs) with activated \u03b3\u03b4 (V\u03b42) T cells: an in vitro cytotoxicity model","volume":"24","author":"Hajdara","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.18612\/ref-19","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1080\/2576117X.2021.1991182","article-title":"Thyroid-associated orbitopathy: management and treatment","volume":"72","author":"Hennein","year":"2022","journal-title":"Journal of Binocular Vision and Ocular Motility"},{"key":"10.7717\/peerj.18612\/ref-20","doi-asserted-by":"publisher","first-page":"106432","DOI":"10.1016\/j.intimp.2020.106432","article-title":"RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis","volume":"83","author":"Huangfu","year":"2020","journal-title":"International Immunopharmacology"},{"issue":"7467","key":"10.7717\/peerj.18612\/ref-21","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nature12626","article-title":"Influence of tumour micro-environment heterogeneity on therapeutic response","volume":"501","author":"Junttila","year":"2013","journal-title":"Nature"},{"issue":"11","key":"10.7717\/peerj.18612\/ref-22","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1016\/j.jid.2022.04.024","article-title":"M1 macrophages induce protumor inflammation in melanoma cells through TNFR-NF-\u03baB signaling","volume":"142","author":"Kainulainen","year":"2022","journal-title":"The Journal of Investigative Dermatology"},{"issue":"7\u20138","key":"10.7717\/peerj.18612\/ref-23","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1080\/09273948.2021.1942498","article-title":"The role of TPOAb in thyroid-associated orbitopathy: a systematic review","volume":"30","author":"Kyriakos","year":"2022","journal-title":"Ocular Immunology and Inflammation"},{"issue":"3","key":"10.7717\/peerj.18612\/ref-24","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.3892\/mmr.2014.2914","article-title":"Ki67 is a promising molecular target in the diagnosis of cancer (review)","volume":"11","author":"Li","year":"2015","journal-title":"Molecular Medicine Reports"},{"issue":"42","key":"10.7717\/peerj.18612\/ref-25","doi-asserted-by":"publisher","first-page":"7015","DOI":"10.2174\/0109298673282799231211113347","article-title":"Single-cell RNA sequencing analysis reveals the role of cancer-associated fibroblasts in skin melanoma","volume":"31","author":"Lian","year":"2024","journal-title":"Current Medicinal Chemistry"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-26","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods (San Diego, California)"},{"issue":"Pt B","key":"10.7717\/peerj.18612\/ref-27","doi-asserted-by":"publisher","first-page":"111175","DOI":"10.1016\/j.intimp.2023.111175","article-title":"Herbal compound cepharanthine attenuates inflammatory arthritis by blocking macrophage M1 polarization","volume":"125","author":"Lu","year":"2023","journal-title":"International Immunopharmacology"},{"key":"10.7717\/peerj.18612\/ref-28","doi-asserted-by":"publisher","first-page":"109659","DOI":"10.1016\/j.cbi.2021.109659","article-title":"Fluoride regulates chondrocyte proliferation and autophagy via PI3K\/AKT\/mTOR signaling pathway","volume":"349","author":"Ma","year":"2021","journal-title":"Chemico-Biological Interactions"},{"issue":"2","key":"10.7717\/peerj.18612\/ref-29","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.semcancer.2019.08.002","article-title":"Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment","volume":"59","author":"Marzagalli","year":"2019","journal-title":"Seminars in Cancer Biology"},{"key":"10.7717\/peerj.18612\/ref-30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1515\/oncologie-2023-0459","article-title":"The tumor microenvironment: a key player in multidrug resistance in cancer","volume":"26","author":"Meng","year":"2024","journal-title":"Oncologie"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-31","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1111\/wrr.12920","article-title":"Vimentin regulates the assembly and function of matrix adhesions","volume":"29","author":"Ostrowska-Podhorodecka","year":"2021","journal-title":"Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society"},{"issue":"14","key":"10.7717\/peerj.18612\/ref-32","doi-asserted-by":"publisher","first-page":"7255","DOI":"10.3390\/ijms22147255","article-title":"Profiling cancer-associated fibroblasts in melanoma","volume":"22","author":"Papaccio","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.18612\/ref-33","doi-asserted-by":"publisher","first-page":"13132","DOI":"10.1038\/s41598-023-40362-8","article-title":"Downregulation of DNA methylation enhances differentiation of THP-1 cells and induces M1 polarization of differentiated macrophages","volume":"13","author":"Park","year":"2023","journal-title":"Scientific Reports"},{"issue":"8","key":"10.7717\/peerj.18612\/ref-34","doi-asserted-by":"publisher","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":"Annals of Oncology: Official Journal of the European Society for Medical Oncology"},{"issue":"10","key":"10.7717\/peerj.18612\/ref-35","doi-asserted-by":"publisher","first-page":"5283","DOI":"10.3390\/ijms22105283","article-title":"Influence of tumor microenvironment and fibroblast population plasticity on melanoma growth, therapy resistance and immunoescape","volume":"22","author":"Romano","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"11","key":"10.7717\/peerj.18612\/ref-36","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1078\/0171-9335-00280","article-title":"The human melanoma associated protein melanotransferrin promotes endothelial cell migration and angiogenesis in vivo","volume":"81","author":"Sala","year":"2002","journal-title":"European Journal of Cell Biology"},{"issue":"10151","key":"10.7717\/peerj.18612\/ref-37","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet (London, England)"},{"key":"10.7717\/peerj.18612\/ref-38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-22539-5","article-title":"Heterogeneity in melanoma","volume":"167","author":"Shannan","year":"2016","journal-title":"Cancer Treatment and Research"},{"issue":"1","key":"10.7717\/peerj.18612\/ref-39","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s12865-023-00587-8","article-title":"Dissecting cellular states of infiltrating microenvironment cells in melanoma by integrating single-cell and bulk transcriptome analysis","volume":"24","author":"Shi","year":"2023","journal-title":"BMC Immunology"},{"issue":"3","key":"10.7717\/peerj.18612\/ref-40","doi-asserted-by":"publisher","first-page":"1903827","DOI":"10.1080\/21645515.2021.1903827","article-title":"Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review","volume":"18","author":"Tagliaferri","year":"2022","journal-title":"Human Vaccines & Immunotherapeutics"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-41","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1111\/cas.15271","article-title":"HSP90\/IKK-rich small extracellular vesicles activate pro-angiogenic melanoma-associated fibroblasts via the NF-\u03baB\/CXCL1 axis","volume":"113","author":"Tang","year":"2022","journal-title":"Cancer Science"},{"issue":"8","key":"10.7717\/peerj.18612\/ref-42","doi-asserted-by":"publisher","first-page":"e16569","DOI":"10.7717\/peerj.16569","article-title":"Differentially expressed genes in orbital adipose\/connective tissue of thyroid-associated orbitopathy","volume":"11","author":"Wang","year":"2023","journal-title":"PeerJ"},{"issue":"1","key":"10.7717\/peerj.18612\/ref-43","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s40123-020-00318-x","article-title":"Physician-perceived impact of thyroid eye disease on patient quality of life in the United States","volume":"10","author":"Wang","year":"2021","journal-title":"Ophthalmology and Therapy"},{"issue":"7","key":"10.7717\/peerj.18612\/ref-44","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1080\/21645515.2017.1312043","article-title":"Pro-tumor activities of macrophages in the progression of melanoma","volume":"13","author":"Wang","year":"2017","journal-title":"Human Vaccines & Immunotherapeutics"},{"issue":"1","key":"10.7717\/peerj.18612\/ref-45","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1186\/s12967-024-05263-y","article-title":"Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts","volume":"22","author":"Wei","year":"2024","journal-title":"Journal of Translational Medicine"},{"key":"10.7717\/peerj.18612\/ref-46","doi-asserted-by":"publisher","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":"Pharmacology & Therapeutics"},{"issue":"4","key":"10.7717\/peerj.18612\/ref-47","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1515\/oncologie-2024-0071","article-title":"Single-cell RNA-binding protein pattern-mediated molecular subtypes depict the hallmarks of the tumor microenvironment in bladder urothelial carcinoma","volume":"26","author":"Zhang","year":"2024","journal-title":"Oncologie"},{"issue":"13","key":"10.7717\/peerj.18612\/ref-48","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1093\/hmg\/ddae056","article-title":"Melanoma-associated fibroblasts in tumor-promotion flammation and antitumor immunity: novel mechanisms and potential immunotherapeutic strategies","volume":"33","author":"Zhou","year":"2024","journal-title":"Human Molecular Genetics"},{"issue":"12","key":"10.7717\/peerj.18612\/ref-49","doi-asserted-by":"publisher","first-page":"19780","DOI":"10.18632\/oncotarget.15540","article-title":"Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through matrix-metalloproteinases secretion","volume":"8","author":"Ziani","year":"2017","journal-title":"Oncotarget"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/18612.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18612.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18612.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:36:42Z","timestamp":1732711002000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/18612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":49,"alternative-id":["10.7717\/peerj.18612"],"URL":"https:\/\/doi.org\/10.7717\/peerj.18612","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]},"article-number":"e18612"}}