{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:51Z","timestamp":1753890951024,"version":"3.41.2"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Omega-3 polyunsaturated fatty acids (n3-PUFA) are known for their anti-inflammatory benefits, particularly in chronic conditions like rheumatoid arthritis (RA). To resolve an acute inflammation, conversion of n3-PUFA into specialized pro-resolving mediators (SPM) is crucial. Recently, it was shown that the probiotic Bacillus megaterium DSM32963 supports this conversion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study evaluates a synbiotic formulation combining Bacillus megaterium DSM32963 and a unique n3-PUFA-lysine salt as adjunct nutritional supplement to tofacitinib in adjuvant-induced arthritis (AIA) in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings reveal that a combination of low-dose tofacitinib and the synbiotic (ldTofa+Syn) significantly improved all measured arthritis severity parameters, outperforming either single treatment as well as supplementation with a conventional omega-3 ethyl ester that showed no effects on disease severity. The ldTofa+Syn combination also led to a notable reduction in C-reactive protein (CRP) and markers of NETosis in joint tissue, with a significant decrease in neutrophil chemokine CXCL1 observed only in synbiotic-containing groups. Additionally, there was a marked trend towards lower levels of the key inflammatory cytokines TNF\u03b1, IL-1\u03b2, and IL-6 in the ldTofa+Syn group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, the specific synbiotic formulation shows promise as a complementary nutritional therapy for RA, improving disease outcomes and modulating immune responses.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1540878","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:10:45Z","timestamp":1748232645000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing tofacitinib\u2019s therapeutic efficacy in murine arthritis with a synbiotic formulation comprising Bacillus megaterium DSM 32963 and an Omega-3 fatty acid lysine salt"],"prefix":"10.3389","volume":"16","author":[{"given":"Annette","family":"Zehrer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Werz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Tom Dieck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Berngruber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00316","article-title":"Inflammation-nature\u2019s way to efficiently respond to all types of challenges: implications for understanding and managing \u201cthe epidemic\u201d of chronic diseases","volume":"5","author":"Bennett","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/ard-2022-223356","article-title":"Eular recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update","volume":"82","author":"Smolen","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109104","article-title":"Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: an umbrella meta-analysis","volume":"111","author":"Kavyani","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.31138\/mjr.31.2.190","article-title":"The effect of omega-3 fatty acids on rheumatoid arthritis","volume":"31","author":"Kostoglou-Athanassiou","year":"2020","journal-title":"Mediterr J Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114515002718","article-title":"Plasma N-3 fatty acids and clinical outcomes in recent-onset rheumatoid arthritis","volume":"114","author":"Proudman","year":"2015","journal-title":"Br J Nutr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1136\/annrheumdis-2013-204145","article-title":"Fish oil in recent onset rheumatoid arthritis: A randomised, double-blind controlled trial within algorithm-based drug use","volume":"74","author":"Proudman","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ni1276","article-title":"Resolution of inflammation: the beginning programs the end","volume":"6","author":"Serhan","year":"2005","journal-title":"Nat Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nri.2015.4","article-title":"Specialized pro-resolving mediators: endogenous regulators of infection and inflammation","volume":"16","author":"Basil","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M060392","article-title":"Bioactive products formed in humans from fish oils","volume":"56","author":"Skarke","year":"2015","journal-title":"J Lipid Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7172","DOI":"10.1038\/s41467-023-41766-w","article-title":"Failure to apply standard limit-of-detection or limit-of-quantitation criteria to specialized pro-resolving mediator analysis incorrectly characterizes their presence in biological samples","volume":"14","author":"O\u2019Donnell","year":"2023","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.838782","article-title":"Formation, signaling and occurrence of specialized pro-resolving lipid mediators\u2014What is the evidence so far","volume":"13","author":"Schebb","year":"2022","journal-title":"Front Pharmacol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2407130121","article-title":"Spms exert anti-inflammatory and pro-resolving effects through positive allosteric modulation of the prostaglandin Ep4 receptor","volume":"121","author":"Alnouri","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0828","article-title":"Impaired local production of proresolving lipid mediators in obesity and 17-hdha as a potential treatment for obesity-associated inflammation","volume":"62","author":"Neuhofer","year":"2013","journal-title":"Diabetes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01331","article-title":"Actors and factors in the resolution of intestinal inflammation: lipid mediators as a new approach to therapy in inflammatory bowel diseases","volume":"8","author":"Ungaro","year":"2017","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.09.038","article-title":"Defects in 15-hete production and control of epithelial permeability by human enteric glial cells from patients with Crohn\u2019s disease","volume":"150","author":"Pochard","year":"2016","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.729134","article-title":"Harnessing inflammation resolution in arthritis: current understanding of specialized pro-resolving lipid mediators\u2019 Contribution to arthritis physiopathology and future perspectives","volume":"12","author":"Zaninelli","year":"2021","journal-title":"Front Physiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502268","article-title":"Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation","volume":"197","author":"Arnardottir","year":"2016","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.imlet.2020.08.006","article-title":"Low levels of pro-resolving lipid mediators lipoxin-A4, resolvin-D1 and resolvin-E1 in patients with rheumatoid arthritis","volume":"227","author":"\u00d6zg\u00fcl \u00d6zdemir","year":"2020","journal-title":"Immunol Lett"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5420","DOI":"10.1038\/s41467-020-19176-z","article-title":"Blood pro-resolving mediators are linked with synovial pathology and are predictive of Dmard responsiveness in rheumatoid arthritis","volume":"11","author":"Gomez","year":"2020","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13075-020-2133-2","article-title":"Resolvin D1 suppresses pannus formation via decreasing connective tissue growth factor caused by upregulation of Mirna-146a-5p in rheumatoid arthritis","volume":"22","author":"Sun","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B22","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41419-021-03562-6","article-title":"Protectin Dx restores Treg\/T(H)17 cell balance in rheumatoid arthritis by inhibiting Nlrp3 inflammasome via Mir-20a","volume":"12","author":"Jin","year":"2021","journal-title":"Cell Death Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"17312","DOI":"10.1038\/s41598-021-96530-1","article-title":"Effect of resolvin D5 on T cell differentiation and osteoclastogenesis analyzed by lipid mediator profiling in the experimental arthritis","volume":"11","author":"Yamada","year":"2021","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/jci131609","article-title":"Gpr101 mediates the pro-resolving actions of Rvd5n-3 Dpa in arthritis and infections","volume":"130","author":"Flak","year":"2020","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-023-03172-2","article-title":"Omega-3 polyunsaturated fatty acids improve intestinal barrier integrity-albeit to a lesser degree than short-chain fatty acids: an exploratory analysis of the randomized controlled libre trial","volume":"62","author":"Seethaler","year":"2023","journal-title":"Eur J Nutr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3504","DOI":"10.3390\/nu12113504","article-title":"Diet as a modulator of intestinal microbiota in rheumatoid arthritis","volume":"12","author":"Dourado","year":"2020","journal-title":"Nutrients"},{"key":"B27","doi-asserted-by":"publisher","first-page":"892","DOI":"10.2174\/1386207325666220701121025","article-title":"N-3 polyunsaturated fatty acids and gut microbiota","volume":"26","author":"Jayapala","year":"2023","journal-title":"Comb Chem High Throughput Screen"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/md17060374","article-title":"Effects of fish N-3 Pufas on intestinal microbiota and immune system","volume":"17","author":"Parolini","year":"2019","journal-title":"Mar Drugs"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/nu14112265","article-title":"Synbiotic compositions of bacillus megaterium and polyunsaturated fatty acid salt enable self-sufficient production of specialized pro-resolving mediators","volume":"14","author":"Speckmann","year":"2022","journal-title":"Nutrients"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.3390\/nu16091354","article-title":"Synbiotic bacillus megaterium Dsm 32963 and N-3 Pufa salt composition elevates pro-resolving lipid mediator levels in healthy subjects: A randomized controlled study","volume":"16","author":"Speckmann","year":"2024","journal-title":"Nutrients"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927","article-title":"Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis","volume":"386","author":"Ytterberg","year":"2022","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.209304","article-title":"Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis","volume":"348","author":"Dowty","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"key":"B33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J Basic Clin Pharm"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1504s19","article-title":"Adjuvant arthritis in the rat","author":"van Eden","year":"2001","journal-title":"Curr Protoc Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.8.1964","article-title":"Lactobacillus gg bacteria ameliorate arthritis in lewis rats","volume":"134","author":"Baharav","year":"2004","journal-title":"J Nutr"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1177\/019262339702500103","article-title":"Clinical and histological assessment of collagen-induced arthritis progression in the diabetes-resistant Bb\/Wor rat","volume":"25","author":"Knoerzer","year":"1997","journal-title":"Toxicol Pathol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0003-2697(79)90043-5","article-title":"Sensitive substrates for human leukocyte and porcine pancreatic elastase: A study of the merits of various chromophoric and fluorogenic leaving groups in assays for serine proteases","volume":"99","author":"Castillo","year":"1979","journal-title":"Anal Biochem"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.218","article-title":"The role of mitogen-activated protein kinase-activated protein kinase 2 in the P38\/Tnf-alpha pathway of systemic and cutaneous inflammation","volume":"130","author":"Schottelius","year":"2010","journal-title":"J Invest Dermatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802509R","article-title":"Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome","volume":"33","author":"Werner","year":"2019","journal-title":"FASEB J"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2023.106798","article-title":"The role of specialized pro-resolving mediators (Spms) in inflammatory arthritis: A therapeutic strategy","volume":"170","author":"Natami","year":"2024","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2023.106726","article-title":"Formation of lipoxins and resolvins in human leukocytes","volume":"166","author":"Kahnt","year":"2023","journal-title":"Prostaglandins Other Lipid Mediators"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.631319","article-title":"A new E-series resolvin: Rve4 stereochemistry and function in efferocytosis of inflammation-resolution","volume":"11","author":"Libreros","year":"2020","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.8.1197","article-title":"Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing","volume":"192","author":"Serhan","year":"2000","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/698313","article-title":"Interleukin 6 and rheumatoid arthritis","volume":"2014","author":"Yoshida","year":"2014","journal-title":"BioMed Res Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00958","article-title":"C-reactive protein promotes the activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis","volume":"11","author":"Fang","year":"2020","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415823","article-title":"Methods for the assessment of net formation: from neutrophil biology to translational research","volume":"23","author":"Stoimenou","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B47","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.nut.2017.06.023","article-title":"Intake of \u03a9-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: A systematic review and meta-analysis","volume":"45","author":"Gioxari","year":"2018","journal-title":"Nutrition"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.121.055654","article-title":"Effect of long-term marine \u0277-3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes: A systematic review and meta-analysis","volume":"144","author":"Gencer","year":"2021","journal-title":"Circulation"},{"key":"B49","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s40168-019-0719-1","article-title":"A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis","volume":"7","author":"Pan","year":"2019","journal-title":"Microbiome"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00393-020-00775-6","article-title":"Management of early rheumatoid arthritis: interdisciplinary guideline","volume":"79","author":"Schneider","year":"2020","journal-title":"Z Rheumatol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3181\/00379727-91-22179","article-title":"Development of arthritis, periarthritis and periostitis in rats given adjuvants","volume":"91","author":"Pearson","year":"1956","journal-title":"Proc Soc Exp Biol Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.076430","article-title":"Utility of animal models for identification of potential therapeutics for rheumatoid arthritis","volume":"67","author":"Hegen","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"B53","article-title":"Animal models of rheumatoid arthritis","volume":"1","author":"Bendele","year":"2001","journal-title":"J Musculoskelet Neuronal Interact"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2147\/jir.S301076","article-title":"Preclinical characterization of the selective Jak1 inhibitor Lw402 for treatment of rheumatoid arthritis","volume":"14","author":"Zhang","year":"2021","journal-title":"J Inflammation Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41927-018-0031-x","article-title":"In vitro and in vivo characterization of the Jak1 selectivity of upadacitinib (Abt-494)","volume":"2","author":"Parmentier","year":"2018","journal-title":"BMC Rheumatol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/art.27503","article-title":"Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis","volume":"62","author":"Bevaart","year":"2010","journal-title":"Arthritis Rheum"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/569068","article-title":"Rodent preclinical models for developing novel antiarthritic molecules: comparative biology and preferred methods for evaluating efficacy","volume":"2011","author":"Bolon","year":"2011","journal-title":"J BioMed Biotechnol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1080\/08923973.2018.1434793","article-title":"Experimental animal models for rheumatoid arthritis","volume":"40","author":"Choudhary","year":"2018","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"B59","article-title":"Animal models of rheumatoid arthritis: correlation and usefulness with human rheumatoid arthritis","volume":"3","author":"Ghosh","year":"2013","journal-title":"Indo-American J Pharm Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175490","article-title":"Comparison of the effects of peficitinib and tofacitinib in the adjuvant-induced arthritis rat model","volume":"941","author":"Ishikawa","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.03.034","article-title":"Fish oil attenuates persistent inflammatory pain in rats through modulation of Tnf-A and resolvins","volume":"152","author":"Lobo","year":"2016","journal-title":"Life Sci"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-11-136","article-title":"Supplementation of diet with krill oil protects against experimental rheumatoid arthritis","volume":"11","author":"Ierna","year":"2010","journal-title":"BMC Musculoskelet Disord"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0658-4","article-title":"Docosahexaenoic acid reduces inflammation and joint destruction in mice with collagen-induced arthritis","volume":"62","author":"Olson","year":"2013","journal-title":"Inflammation Res"},{"key":"B64","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13075-015-0653-y","article-title":"Eicosapentaenoic acid and docosapentaenoic acid monoglycerides are more potent than docosahexaenoic acid monoglyceride to resolve inflammation in a rheumatoid arthritis model","volume":"17","author":"Morin","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.680073","article-title":"Lactobacillus Casei Ccfm1074 alleviates collagen-induced arthritis in rats via balancing Treg\/Th17 and modulating the metabolites and gut microbiota","volume":"12","author":"Fan","year":"2021","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28010297","article-title":"Enhanced anti-inflammatory effect of the combination of lactiplantibacillus plantarum Ls\/07 with methotrexate compared to their monotherapies studied in experimental arthritis","volume":"28","author":"Pru\u017einsk\u00e1","year":"2022","journal-title":"Molecules"},{"key":"B67","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1093\/rheumatology\/key377","article-title":"Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model","volume":"58","author":"Vidal","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B68","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10067-016-3436-1","article-title":"Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group","volume":"36","author":"Fleischmann","year":"2017","journal-title":"Clin Rheumatol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2016-000262","article-title":"Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis","volume":"2","author":"Fleischmann","year":"2016","journal-title":"RMD Open"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-021-05871-0","article-title":"Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis","volume":"32","author":"Hamar","year":"2021","journal-title":"Osteoporos Int"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-019-09864-2","article-title":"Prophylactic effects of probiotic Bifidobacterium spp. In the resolution of inflammation in arthritic rats","volume":"103","author":"Achi","year":"2019","journal-title":"Appl Microbiol Biotechnol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.168728","article-title":"Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis","volume":"8","author":"Norling","year":"2023","journal-title":"JCI Insight"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4301072","article-title":"Prostanoid receptor subtypes and its endogenous ligands with processing enzymes within various types of inflammatory joint diseases","volume":"2020","author":"Al-Madol","year":"2020","journal-title":"Mediators Inflammation"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/1jlh15","article-title":"Role of prostaglandins in rheumatoid arthritis","volume":"39","author":"Ma","year":"2021","journal-title":"Clin Exp Rheumatol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2667","article-title":"Phenotypic characterization of type ii collagen-induced arthritis in Wistar rats","volume":"10","author":"Song","year":"2015","journal-title":"Exp Ther Med"},{"key":"B76","article-title":"Effect of losartan in complete Freund\u2019s adjuvant -induced arthritis in rats","volume":"17","author":"Abdel El-Gaphar","year":"2018","journal-title":"Iran J Pharm Res"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-006-6026-x","article-title":"Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats","volume":"55","author":"Cai","year":"2006","journal-title":"Inflammation Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-eular.1468","article-title":"Ab0358 reduction of white blood cell count predicts the efficacy of baricitinib, does not of tofacitinib for rheumatoid arthritis","volume":"79","author":"Sugihara","year":"2020","journal-title":"Ann Rheumatic Dis"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/art.40780","article-title":"Evaluation of the short-, mid-, and long-term effects of tofacitinib on lymphocytes in patients with rheumatoid arthritis","volume":"71","author":"van Vollenhoven","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1093\/rheumatology\/kew329","article-title":"Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies","volume":"56","author":"Schulze-Koops","year":"2017","journal-title":"Rheumatol (Oxford)"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2021.111282","article-title":"Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative\/nitrosative profile in people with rheumatoid arthritis","volume":"89","author":"Cannarella","year":"2021","journal-title":"Nutrition"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1002\/art.34649","article-title":"Jak inhibition with tofacitinib suppresses arthritic joint structural damage through decreased Rankl production","volume":"64","author":"LaBranche","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B83","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1186\/s12891-015-0802-0","article-title":"Improvement of spontaneous locomotor activity with Jak inhibition by Jte-052 in rat adjuvant-induced arthritis","volume":"16","author":"Tanimoto","year":"2015","journal-title":"BMC Musculoskelet Disord"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxac085","article-title":"Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response","volume":"210","author":"Valli","year":"2022","journal-title":"Clin Exp Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12234","article-title":"Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid a and interleukin-6 during treatment for rheumatoid arthritis","volume":"175","author":"Migita","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"B86","article-title":"Serum and synovial fluid levels of serum amyloid a protein and C-reactive protein in inflammatory and noninflammatory arthritis","volume":"15","author":"Sukenik","year":"1988","journal-title":"J Rheumatol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.clim.2017.04.015","article-title":"Tofacitinib attenuates arthritis manifestations and reduces the pathogenic cd4 T cells in adjuvant arthritis rats","volume":"184","author":"Gertel","year":"2017","journal-title":"Clin Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/art.39996","article-title":"Brief report: remission rates with tofacitinib treatment in rheumatoid arthritis: A comparison of various remission criteria","volume":"69","author":"Smolen","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934664","article-title":"Treatment with coenzyme Q10, omega-3-polyunsaturated fatty acids and their combination improved bioenergetics and levels of coenzyme Q9 and Q10 in skeletal muscle mitochondria in experimental model of arthritis","volume":"70","author":"Kucharsk\u00e1","year":"2021","journal-title":"Physiol Res"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3390\/nu14051030","article-title":"The relationship between fatty acids and the development, course and treatment of rheumatoid arthritis","volume":"14","author":"Ta\u0144ski","year":"2022","journal-title":"Nutrients"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.711788","article-title":"Probiotic supplementation for rheumatoid arthritis: A promising adjuvant therapy in the gut microbiome era","volume":"12","author":"Ferro","year":"2021","journal-title":"Front Pharmacol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.961325","article-title":"Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials","volume":"13","author":"Zeng","year":"2022","journal-title":"Front Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker338","article-title":"Analysis of Sf and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy","volume":"51","author":"Wright","year":"2012","journal-title":"Rheumatol (Oxford)"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113126","article-title":"Anti-rheumatoid drugs advancements: new insights into the molecular treatment of rheumatoid arthritis","volume":"151","author":"Ben Mrid","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003668","article-title":"Modulation of innate and adaptive immune responses by tofacitinib (Cp-690,550)","volume":"186","author":"Ghoreschi","year":"2011","journal-title":"J Immunol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2021.151812","article-title":"The effect of association of aspirin and omega 3 in rat temporomandibular joint with induced arthritis","volume":"239","author":"Ceotto","year":"2022","journal-title":"Ann Anat"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01345.x","article-title":"The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats","volume":"164","author":"Lima-Garcia","year":"2011","journal-title":"Br J Pharmacol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.584116","article-title":"Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species, and neutrophil extracellular traps","volume":"11","author":"Wright","year":"2020","journal-title":"Front Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.578129","article-title":"Neutrophil extracellular traps tied to rheumatoid arthritis: points to ponder","volume":"11","author":"Song","year":"2020","journal-title":"Front Immunol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.phrs.2016.01.027","article-title":"Neutrophils and arthritis: role in disease and pharmacological perspectives","volume":"112","author":"Fattori","year":"2016","journal-title":"Pharmacol Res"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1134\/s0006297920100065","article-title":"Netosis: molecular mechanisms, role in physiology and pathology","volume":"85","author":"Vorobjeva","year":"2020","journal-title":"Biochem (Mosc)"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2018","article-title":"The neutrophil\u2019s role during health and disease","volume":"99","author":"Liew","year":"2019","journal-title":"Physiol Rev"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.013","article-title":"The neutrophil life cycle","volume":"40","author":"Hidalgo","year":"2019","journal-title":"Trends Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/jci84538","article-title":"Neutrophil extracellular traps - the dark side of neutrophils","volume":"126","author":"S\u00f8rensen","year":"2016","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cellimm.2017.05.002","article-title":"Myeloperoxidase: A new player in autoimmunity","volume":"317","author":"Strzepa","year":"2017","journal-title":"Cell Immunol"},{"key":"B107","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jaut.2017.04.007","article-title":"Diagnostic potential of netosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in rheumatoid arthritis patients","volume":"82","author":"P\u00e9rez-S\u00e1nchez","year":"2017","journal-title":"J Autoimmun"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.06.006","article-title":"Neutrophils: novel key players in rheumatoid arthritis. Current and future therapeutic targets","volume":"17","author":"Cecchi","year":"2018","journal-title":"Autoimmun Rev"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12070650","article-title":"Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by Jak inhibition","volume":"12","author":"Chokesuwattanaskul","year":"2022","journal-title":"Metabolites"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(62)90321-1","article-title":"Myeloperoxidase of the leucocyte of normal human blood. I. Content and localization","volume":"96","author":"Schultz","year":"1962","journal-title":"Arch Biochem Biophys"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26226970","article-title":"Role of specialized pro-resolving mediators in modifying host defense and decreasing bacterial virulence","volume":"26","author":"Thornton","year":"2021","journal-title":"Molecules"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-015-0252-8","article-title":"Fish oil and adjuvant-induced arthritis: inhibitory effect on leukocyte recruitment","volume":"39","author":"Estev\u00e3o-Silva","year":"2016","journal-title":"Inflammation"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85922","article-title":"Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis","volume":"1","author":"Norling","year":"2016","journal-title":"JCI Insight"},{"key":"B114","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13075-018-1645-5","article-title":"Prediction of primary non-response to methotrexate therapy using demographic, clinical and psychosocial variables: results from the UK rheumatoid arthritis medication study (Rams)","volume":"20","author":"Sergeant","year":"2018","journal-title":"Arthritis Res Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1540878\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:10:47Z","timestamp":1748232647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1540878\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":114,"alternative-id":["10.3389\/fimmu.2025.1540878"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1540878","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,5,26]]},"article-number":"1540878"}}