{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:37:42Z","timestamp":1784547462193,"version":"3.55.0"},"reference-count":66,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Saudi Arabia","award":["14-MED-543-02"],"award-info":[{"award-number":["14-MED-543-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteomes"],"abstract":"<jats:p>Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that predominantly affects synovial joints, leading to inflammation, pain, and progressive joint damage. Despite therapeutic advancements, the molecular basis of established RA remains poorly defined. Methods: In this study, we conducted an untargeted plasma proteomic analysis using two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in samples from RA patients and healthy controls in the discovery phase. Results: Significantly (ANOVA, p \u2264 0.05, fold change &gt; 1.5) differentially abundant proteins (DAPs) were identified. Notably, upregulated proteins included mitochondrial dicarboxylate carrier, hemopexin, and 28S ribosomal protein S18c, while CCDC124, osteocalcin, apolipoproteins A-I and A-IV, and haptoglobin were downregulated. Receiver operating characteristic (ROC) analysis identified CCDC124, osteocalcin, and metallothionein-2 with high diagnostic potential (AUC = 0.98). Proteins with the highest selected frequency were quantitatively verified by multiple reaction monitoring (MRM) analysis in the validation cohort. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) revealed the underlying molecular pathways and key interaction networks involved STAT1, TNF, and CD40. These central nodes were associated with immune regulation, cell-to-cell signaling, and hematological system development. Conclusions: Our combined proteomic and bioinformatic approaches underscore the involvement of dysregulated immune pathways in RA pathogenesis and highlight potential diagnostic biomarkers. The utility of these markers needs to be evaluated in further studies and in a larger cohort of patients.<\/jats:p>","DOI":"10.3390\/proteomes13030032","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T03:47:26Z","timestamp":1751600846000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Proteomic Profiling Reveals Novel Molecular Insights into Dysregulated Proteins in Established Cases of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8082-9326","authenticated-orcid":false,"given":"Afshan","family":"Masood","sequence":"first","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Department of Chemistry and Biochemistry, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montreal, QC H2L 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-2959","authenticated-orcid":false,"given":"Hicham","family":"Benabdelkamel","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-5188","authenticated-orcid":false,"given":"Assim A.","family":"Alfadda","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"},{"name":"Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8680-439X","authenticated-orcid":false,"given":"Abdurhman S.","family":"Alarfaj","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-607X","authenticated-orcid":false,"given":"Amina","family":"Fallata","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-638X","authenticated-orcid":false,"given":"Salini Scaria","family":"Joy","sequence":"additional","affiliation":[{"name":"Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6842","authenticated-orcid":false,"given":"Maha","family":"Al Mogren","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Precision Medicine Laboratory Department, Genome Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-9424","authenticated-orcid":false,"given":"Anas M. Abdel","family":"Rahman","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Precision Medicine Laboratory Department, Genome Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0499-4260","authenticated-orcid":false,"given":"Mohamed","family":"Siaj","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM), Montreal, QC H2L 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00296-020-04731-0","article-title":"The global prevalence of rheumatoid arthritis: A meta-analysis based on a systematic review","volume":"41","author":"Almutairi","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Huang, Q., Xu, W.-D., Su, L.-C., Liu, X.-Y., and Huang, A.-F. (2021). Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.642929"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"475","DOI":"10.55563\/clinexprheumatol\/l9lyen","article-title":"Pathogenesis of rheumatoid arthritis: One year in review 2022","volume":"40","author":"Petrelli","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nrrheum.2012.153","article-title":"Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis and treatment","volume":"8","author":"Schett","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s12016-021-08890-1","article-title":"Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings","volume":"63","author":"Sokolova","year":"2022","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102392","DOI":"10.1016\/j.jaut.2019.102392","article-title":"An overview of autoantibodies in rheumatoid arthritis","volume":"110","author":"Huizinga","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mun, S., Lee, J., Park, A., Kim, H.-J., Lee, Y.-J., Son, H., Shin, M., Lim, M.-K., and Kang, H.-G. (2019). Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184368"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4110\/in.2015.15.4.177","article-title":"Proteomics in Rheumatoid Arthritis Research","volume":"15","author":"Park","year":"2015","journal-title":"Immune Netw."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12014-020-09292-9","article-title":"Proteomic analysis of synovial fluid from rheumatic arthritis and spondyloarthritis patients","volume":"17","author":"Birkelund","year":"2020","journal-title":"Clin. Proteom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1021\/acs.jproteome.1c00399","article-title":"Quantitative Proteomic Analysis of Synovial Tissue Reveals That Upregulated OLFM4 Aggravates Inflammation in Rheumatoid Arthritis","volume":"20","author":"Ren","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"O\u2019Neil, L.J., Hu, P., Liu, Q., Islam, M., Spicer, V., Rech, J., Hueber, A., Anaparti, V., Smolik, I., and El-Gabalawy, H.S. (2021). Proteomic Approaches to Defining Remission and the Risk of Relapse in Rheumatoid Arthritis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.729681"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hu, C., Dai, Z., Xu, J., Zhao, L., Xu, Y., Li, M., Yu, J., Zhang, L., Deng, H., and Liu, L. (2022). Proteome Profiling Identifies Serum Biomarkers in Rheumatoid Arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.865425"},{"key":"ref_13","first-page":"538","article-title":"Serum proteome altered in pre-RA","volume":"16","author":"Onuora","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Jung, N., Park, S., Kong, T., Park, H., Seo, W.M., Lee, S., Kang, K.-S., and Haque, N. (2022). LC-MS\/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0277218"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s10753-014-9871-8","article-title":"Identification of potential serum biomarkers for rheumatoid arthritis by high-resolution quantitative proteomic analysis","volume":"37","author":"Cheng","year":"2014","journal-title":"Inflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1002\/art.20720","article-title":"Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis","volume":"50","author":"Liao","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117501","DOI":"10.1016\/j.cca.2023.117501","article-title":"Quantitative analysis of soluble costimulatory molecules as potential diagnostic biomarkers for rheumatoid arthritis using LC-MS\/MS in MRM mode","volume":"548","author":"Malkawi","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Benabdelkamel, H., Alamri, H., Okla, M., Masood, A., Jabar, M.A., Alanazi, I.O., Alfadda, A.A., Nizami, I., Dasouki, M., and Rahman, A.M.A. (2020). Serum-Based Proteomics Profiling in Adult Patients with Cystic Fibrosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197415"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Clayton, S.A., MacDonald, L., Kurowska-Stolarska, M., and Clark, A.R. (2021). Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.673916"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.mam.2012.05.005","article-title":"The mitochondrial transporter family SLC25: Identification, properties and physiopathology","volume":"34","author":"Palmieri","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jhep.2021.03.006","article-title":"The mitochondrial dicarboxylate carrier prevents hepatic lipotoxicity by inhibiting white adipocyte lipolysis","volume":"75","author":"An","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9271","DOI":"10.18632\/oncotarget.3375","article-title":"The mitochondrial carrier SLC25A10 regulates cancer cell growth","volume":"6","author":"Zhou","year":"2015","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1189\/jlb.1208742","article-title":"Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages","volume":"86","author":"Liang","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1189\/jlb.0309137","article-title":"Editorial: Hemopexin: Newest member of the anti-inflammatory mediator club","volume":"86","author":"Fink","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.4049\/jimmunol.1203076","article-title":"Acute-phase protein hemopexin is a negative regulator of Th17 response and experimental autoimmune encephalomyelitis development","volume":"191","author":"Rolla","year":"2013","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"W\u00e5hl\u00e9n, K., Ernberg, M., Kosek, E., Mannerkorpi, K., Gerdle, B., and Ghafouri, B. (2020). Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-69422-z"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13658","DOI":"10.1074\/jbc.M117.783951","article-title":"Identification of oxidative modifications of hemopexin and their predicted physiological relevance","volume":"292","author":"Hahl","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1093\/rheumatology\/keab838","article-title":"Human carbamylome description identifies carbamylated alpha2-macroglobulin and hemopexin as two novel autoantigens in early rheumatoid arthritis","volume":"61","author":"Sidiras","year":"2022","journal-title":"Rheumatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1002\/eji.200939291","article-title":"Haptoglobin deficiency facilitates the development of autoimmune inflammation","volume":"39","author":"Galicia","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.jbspin.2012.08.004","article-title":"Common bone turnover markers in rheumatoid arthritis and ankylosing spondylitis: A literature review","volume":"80","author":"Coiffier","year":"2013","journal-title":"Jt. Bone Spine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"484280","DOI":"10.1155\/2014\/484280","article-title":"Bone remodelling markers in rheumatoid arthritis","volume":"2014","author":"Fardellone","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bone.2015.05.046","article-title":"New insights into the biology of osteocalcin","volume":"82","author":"Zoch","year":"2016","journal-title":"Bone"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"ITC1","DOI":"10.7326\/AITC201901010","article-title":"Rheumatoid Arthritis","volume":"170","author":"Sparks","year":"2019","journal-title":"Ann. Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sakthiswary, R., Veshaaliini, R.U., Chin, K.-Y., Das, S., and Sirasanagandla, S.R. (2022). Pathomechanisms of bone loss in rheumatoid arthritis. Front. Med., 9.","DOI":"10.3389\/fmed.2022.962969"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1749-6632.2002.tb04254.x","article-title":"Serum osteocalcin levels in premenopausal rheumatoid arthritis patients","volume":"966","author":"Seriolo","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/ard.48.8.654","article-title":"Serum osteocalcin concentrations in patients with rheumatoid arthritis","volume":"48","author":"Pietschmann","year":"1989","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/rheumatology\/25.3.260","article-title":"Increased levels of osteocalcin (serum bone Gla-protein) in rheumatoid arthritis","volume":"25","author":"Gevers","year":"1986","journal-title":"Br. J. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41401-019-0311-z","article-title":"Uncarboxylated osteocalcin ameliorates hepatic glucose and lipid metabolism in KKAy mice via activating insulin signaling pathway","volume":"41","author":"Zhang","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"197519","DOI":"10.1155\/2013\/197519","article-title":"Association between Osteocalcin, Metabolic Syndrome, and Cardiovascular Risk Factors: Role of Total and Undercarboxylated Osteocalcin in Patients with Type 2 Diabetes","volume":"2013","author":"Alfadda","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Xu, C., Khin, L.W., Tam, H.Z., Goh, L.L., Koh, E.T., Dalan, R., and Leong, K.P. (2024). Haptoglobin 2-2 genotype is associated with increased risk of cardiovascular disease in patients with rheumatoid arthritis: A matched case-control study. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1442858"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1016\/j.jchromb.2011.04.024","article-title":"Altered glycosylation and expression of plasma alpha-1-acid glycoprotein and haptoglobin in rheumatoid arthritis","volume":"879","author":"Saroha","year":"2011","journal-title":"J. Chromatogr. B"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3233\/CBM-200802","article-title":"Coiled-coil domain-containing protein-124 (Ccdc124) is a novel RNA binding factor up-regulated in endometrial, ovarian, and urinary bladder cancers","volume":"31","author":"Arslan","year":"2021","journal-title":"Cancer Biomark."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/elps.1150190234","article-title":"Analysis of changes in acute-phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis","volume":"19","author":"Doherty","year":"1998","journal-title":"Electrophoresis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"36158","DOI":"10.1074\/jbc.M110.134130","article-title":"Apolipoprotein A-I modulates regulatory T cells in autoimmune LDLr-\/-, ApoA-I-\/- mice","volume":"285","author":"Wilhelm","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/art.41613","article-title":"Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation","volume":"73","author":"Weber","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1182\/blood.V97.8.2381","article-title":"Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes","volume":"97","author":"Hyka","year":"2001","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00393-005-0735-3","article-title":"[T cell-dependent monocyte activation, TNFalpha and apolipoprotein A-I in autoimmunity and inflammation]","volume":"64","author":"Rossol","year":"2005","journal-title":"Z. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3109\/03009742.2012.654815","article-title":"Apolipoprotein-defined lipoprotein abnormalities in rheumatoid arthritis patients and their potential impact on cardiovascular disease","volume":"41","author":"Knowlton","year":"2012","journal-title":"Scand. J. Rheumatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"R563-6","DOI":"10.1186\/ar1443","article-title":"Apolipoprotein A-I infiltration in rheumatoid arthritis synovial tissue: A control mechanism of cytokine production?","volume":"6","author":"Bresnihan","year":"2004","journal-title":"Arthritis Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1161\/01.ATV.0000119353.03690.22","article-title":"Human apolipoprotein A-IV reduces secretion of proinflammatory cytokines and atherosclerotic effects of a chronic infection mimicked by lipopolysaccharide","volume":"24","author":"Recalde","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Li, W.-H., Zhang, L., Li, Y.-Y., Wang, X.-Y., Li, J.-L., Zhao, S.-N., Ni, M.-Q., Li, Q., and Sun, H. (2022). Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010670"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3892\/ijmm.2015.2272","article-title":"Overexpression of heparan sulfate 6-O-sulfotransferase-2 enhances fibroblast growth factor-mediated chondrocyte growth and differentiation","volume":"36","author":"Wang","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.matbio.2014.08.016","article-title":"Heparan sulfate differences in rheumatoid arthritis versus healthy sera","volume":"40","author":"Sabol","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ajpath.2018.11.011","article-title":"Heparan Sulfate Proteoglycan Synthesis Is Dysregulated in Human Osteoarthritic Cartilage","volume":"189","author":"Chanalaris","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jang, S., Kwon, E.J., and Lee, J.J. (2022). Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020905"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e914","DOI":"10.1002\/iid3.914","article-title":"Altered expression of apoptosis-related genes in rheumatoid arthritis peripheral blood mononuclear cell and related miRNA regulation","volume":"11","author":"Ebrahimian","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.gene.2007.02.032","article-title":"RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8alpha and ARMC8beta are components of the CTLH complex","volume":"396","author":"Kobayashi","year":"2007","journal-title":"Gene"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Maitland, M.E.R., Lajoie, G.A., Shaw, G.S., and Schild-Poulter, C. (2022). Structural and Functional Insights into GID\/CTLH E3 Ligase Complexes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115863"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Balendran, T., Lim, K., Hamilton, J.A., and Achuthan, A.A. (2023). Targeting transcription factors for therapeutic benefit in rheumatoid arthritis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1196931"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/(SICI)1099-0496(199911)28:5<321::AID-PPUL3>3.0.CO;2-V","article-title":"Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis","volume":"28","author":"Rosenfeld","year":"1999","journal-title":"Pediatr. Pulmonol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.exger.2013.07.008","article-title":"Proteomic analysis of mature adipo cytes from obese patients in relation to aging","volume":"48","author":"Alfadda","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.mce.2014.11.021","article-title":"Mature adipocyte proteome reveals differentially altered protein abundances between lean, overweight and morbidly obese human subjects","volume":"401","author":"Benabdelkamel","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Alfadda, A.A., Benabdelkamel, H., Masood, A., Jammah, A.A., and Ekhzaimy, A.A. (2018). Differences in the Plasma Proteome of Patients with Hypothyroidism before and after Thyroid Hormone Replacement: A Proteomic Analysis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010088"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Masood, A., Benabdelkamel, H., Ekhzaimy, A.A., and Alfadda, A.A. (2020). Plasma-based proteomics profiling of patients with hyperthyroidism after antithyroid treatment. Molecules, 25.","DOI":"10.3390\/molecules25122831"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"339009","DOI":"10.1016\/j.aca.2021.339009","article-title":"Absolute quantification of senescence mediators in cells using multiple reaction monitoring liquid chromatography-Tandem mass spectrometry","volume":"1184","author":"Galal","year":"2021","journal-title":"Anal. Chim. Acta"}],"container-title":["Proteomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-7382\/13\/3\/32\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:17Z","timestamp":1760033057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-7382\/13\/3\/32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":66,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["proteomes13030032"],"URL":"https:\/\/doi.org\/10.3390\/proteomes13030032","relation":{},"ISSN":["2227-7382"],"issn-type":[{"value":"2227-7382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}