{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:02:28Z","timestamp":1782903748703,"version":"3.54.5"},"reference-count":38,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82400917"],"award-info":[{"award-number":["82400917"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170800"],"award-info":[{"award-number":["82170800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200960"],"award-info":[{"award-number":["82200960"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271072"],"award-info":[{"award-number":["82271072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2024A1515012893"],"award-info":[{"award-number":["2024A1515012893"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>High-throughput proteomics (HTP) helps identify characteristic signaling networks specific to certain diseases, thus offering a range of potential applications in basic research and precision medicine. Immunohistochemistry can uncover local orbital immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate key proteins linked to the progression of Graves' orbitopathy (GO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty-one orbital connective tissue samples from patients with GO (11 with clinically severe and 12 with mild GO), and from 8 control subjects were examined using HTP. We focused on the intersection of differentially expressed proteins (DEPs) that differ between severe GO and both mild GO and control. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DEPs. Immunohistochemical verification was performed using 11 severe and 7 mild GO orbital tissues. Immunostaining was quantitatively analyzed using reliable and automated software that ensures objective, operator-independent evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 4579 proteins were identified: 847, 790, and 208 DEPs were registered when comparing mild GO vs control, severe GO vs control, and severe vs mild GO, respectively (all P &amp;lt; .05). Using a cutoff threshold of fold change \u22652.0 during screening, 5 significantly upregulated DEPs (Latent-transforming growth factor \u03b2-binding protein 2, Lysyl oxidase homolog, Ras-interacting protein 1, Integrin beta 3, Coagulation factor XII) overlapped between severe GO and both mild GO and control, while 163 upregulated DEPs were involved in various biological processes (angiogenesis, inflammation, tissue remodeling, and fibrosis). Subsequent immunohistochemical tissue validation confirmed the HTP findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For the first time, combined proteomics and immunohistochemistry detected upregulated orbital tissue proteins potentially implicated in GO progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf299","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:56:22Z","timestamp":1747817782000},"page":"199-208","source":"Crossref","is-referenced-by-count":4,"title":["High-Throughput Proteomics and Immunohistochemistry of Orbital Connective Tissue in Graves' Orbitopathy"],"prefix":"10.1210","volume":"111","author":[{"given":"Yuanping","family":"Hai","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]},{"name":"Molecular Thyroid Research Lab, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center , Mainz 55101 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qintao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1423-4820","authenticated-orcid":false,"given":"Sijie","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranak","family":"Bahramimehr","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Johannes Gutenberg University , Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genfeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Johannes Gutenberg University , Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Johannes Gutenberg University , Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University , Haikou, Hainan Province 570311 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Peking University Third Hospital , Beijing 100083 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-861X","authenticated-orcid":false,"given":"Huifang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200023 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Johannes Gutenberg University , Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-430X","authenticated-orcid":false,"given":"George J","family":"Kahaly","sequence":"additional","affiliation":[{"name":"Molecular Thyroid Research Lab, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center , Mainz 55101 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-9541","authenticated-orcid":false,"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (the First People's Hospital of Shunde, Foshan) , Foshan, Guangdong 528308 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"issue":"11","key":"2025121807430907900_dgaf299-B1","first-page":"1170","article-title":"High-throughput proteomics: a methodological mini-review","volume":"102","author":"Cui","year":"2022","journal-title":"Lab Invest"},{"issue":"6","key":"2025121807430907900_dgaf299-B2","first-page":"465","article-title":"Proteomics in autoimmune thyroid eye disease","volume":"41","author":"Okrojek","year":"2009","journal-title":"Horm Metab 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orbitopathy","volume":"251","author":"Cheng","year":"2013","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"4","key":"2025121807430907900_dgaf299-B14","first-page":"G43","article-title":"The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy","volume":"185","author":"Bartalena","year":"2021","journal-title":"Eur J Endocrinol"},{"issue":"5","key":"2025121807430907900_dgaf299-B15","first-page":"359","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat Methods"},{"key":"2025121807430907900_dgaf299-B16","unstructured":"Hai Y, Ma Q, Fang S, et al \u00a02025. 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fibrosis","volume":"132","author":"Enomoto","year":"2018","journal-title":"Clin Sci (Lond)"},{"key":"2025121807430907900_dgaf299-B21","first-page":"788714","article-title":"Latent transforming growth factor-beta binding protein-2 regulates lung fibroblast-to-myofibroblast differentiation in pulmonary fibrosis via NF-kappaB signaling","volume":"12","author":"Zou","year":"2021","journal-title":"Front Pharmacol"},{"key":"2025121807430907900_dgaf299-B22","first-page":"44","article-title":"Latent TGF-beta-binding proteins","volume":"47","author":"Robertson","year":"2015","journal-title":"Matrix Biol"},{"issue":"11","key":"2025121807430907900_dgaf299-B23","first-page":"907","article-title":"Serum lysyl oxidase is a potential diagnostic biomarker for kidney fibrosis","volume":"51","author":"Zhang","year":"2020","journal-title":"Am J Nephrol"},{"issue":"11","key":"2025121807430907900_dgaf299-B24","first-page":"1729","article-title":"Induction of LOX by TGF-beta1\/smad\/AP-1 signaling 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