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Biophys"},{"issue":"6","key":"pone.0224632.ref081","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1089\/ars.2009.2607","article-title":"Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): causes and consequences for immune function, cell survival, and therapeutic intervention","volume":"12","author":"DC Phillips","year":"2010","journal-title":"Antioxid Redox Signal"},{"key":"pone.0224632.ref082","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1089\/ars.2015.6407","article-title":"The roles of mitochondrial damage-associated molecular patterns in diseases","volume":"23","author":"K Nakahira","year":"2015","journal-title":"Antioxid Redox Signal"},{"issue":"6","key":"pone.0224632.ref083","doi-asserted-by":"crossref","first-page":"e0199530","DOI":"10.1371\/journal.pone.0199530","article-title":"A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis","volume":"13","author":"V Panga","year":"2018","journal-title":"Plos One"},{"issue":"22","key":"pone.0224632.ref084","doi-asserted-by":"crossref","first-page":"e10997","DOI":"10.1097\/MD.0000000000010997","article-title":"Identification of key genes in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis","volume":"97","author":"N Zhu","year":"2018","journal-title":"Medicine"},{"key":"pone.0224632.ref085","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.4103\/0973-1482.189250","article-title":"Identification of significant ego networks and pathways in rheumatoid arthritis","volume":"14","author":"WZ Zhou","year":"2018","journal-title":"J Can Res Ther"},{"key":"pone.0224632.ref086","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s41065-019-0091-y","article-title":"Differentially expressed genes between systemic sclerosis and rheumatoid arthritis","volume":"156","author":"Z Sun","year":"2019","journal-title":"Hereditas"},{"key":"pone.0224632.ref087","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13020-019-0247-8","article-title":"Efficacy of leflunomide combined with ligustrazine in the treatment of rheumatoid arthritis: prediction with network pharmacology and validation in a clinical trial","volume":"14","author":"C Zhang","year":"2019","journal-title":"Chin Med"},{"key":"pone.0224632.ref088","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1186\/s13075-014-0489-x","article-title":"Shared signatures between rheumatoid arthritis, systemic lupus erythematosus and Sj\u00f6gren\u2019s syndrome uncovered through gene expression meta-analysis","volume":"16","author":"D Toro-Dom\u00ednguez","year":"2014","journal-title":"Arthritis Res Ther"},{"issue":"10","key":"pone.0224632.ref089","doi-asserted-by":"crossref","first-page":"6479","DOI":"10.4049\/jimmunol.179.10.6479","article-title":"Leflunomide inhibits PDK1\/Akt pathway and induces apoptosis of human mast cells","volume":"179","author":"N Sawamukai","year":"2007","journal-title":"J Immunol"},{"key":"pone.0224632.ref090","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cellimm.2016.10.007","article-title":"PDK1 promotes the inflammatory progress of fibroblast-like synoviocytes by phosphorylating RSK2","volume":"315","author":"C Sun","year":"2017","journal-title":"Cell Immunol"},{"issue":"12","key":"pone.0224632.ref091","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1002\/art.27750","article-title":"The transcriptional response of normal and rheumatoid arthritis synovial fibroblasts to hypoxia","volume":"62","author":"MJ Del Rey","year":"2010","journal-title":"Arthritis Rheum"},{"issue":"1","key":"pone.0224632.ref092","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1471-4159.2005.03554.x","article-title":"Molecular characterization of mitocalcin, a novel mitochondrial Ca2+-binding protein with EF-hand and coiled-coil domains","volume":"96","author":"M Tominaga","year":"2006","journal-title":"J Neurochem"},{"key":"pone.0224632.ref093","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1194\/jlr.M076489","article-title":"Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (\u2265C20)-acyl chains in macrophages","volume":"58","author":"VZ Wall","year":"2017","journal-title":"J Lipid Res"},{"issue":"16","key":"pone.0224632.ref094","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1093\/hmg\/ddi234","article-title":"Whole genome association study of rheumatoid arthritis using 27039 microsatellites","volume":"14","author":"G Tamiya","year":"2005","journal-title":"Hum Mol Genet"},{"issue":"2","key":"pone.0224632.ref095","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1124\/mi.5.2.7","article-title":"Role of mitochondria in toxic oxidative stress","volume":"5","author":"MW Fariss","year":"2005","journal-title":"Mol Interv"},{"key":"pone.0224632.ref096","first-page":"1935","article-title":"Increased degradation of tryptophan in blood of patients with rheumatoid arthritis","volume":"30","author":"K Schroecksnadel","year":"2003","journal-title":"J Rheumatol"},{"issue":"12","key":"pone.0224632.ref097","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/iub.1092","article-title":"An exploratory study of the interplay between decreased concentration of tryptophan, accumulation of kynurenines, and inflammatory arthritis","volume":"64","author":"L Kolodziej","year":"2012","journal-title":"IUBMB Life"},{"issue":"5","key":"pone.0224632.ref098","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s00296-001-0163-x","article-title":"Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis","volume":"21","author":"S Taysi","year":"2002","journal-title":"Rheumatol 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