{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:06:46Z","timestamp":1779944806461,"version":"3.53.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune and inflammatory disease, and circular RNAs (circRNAs) are widely involved in its progression. Baicalin, a naturally derived small molecule, has been shown to improve inflammatory responses in RA by regulating circRNAs; however, the underlying regulatory mechanism remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate how circ_0000734 participates in the inflammatory response of RA-FLS through the miR-197-5p\/IKBKB axis and to clarify the intervention effect of baicalin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression level of circ_0000734 in peripheral blood mononuclear cells (PBMCs) from RA patients was detected by qRT-PCR. Correlation analysis was performed to evaluate the associations between circ_0000734 expression and clinical indicators, including rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28 scores. The downstream targets miR-197-5p and IKBKB were predicted using bioinformatics databases. Dual-luciferase reporter assays were performed to verify the targeting relationship between circ_0000734 and miR-197-5p, as well as the binding relationship between miR-197-5p and IKBKB. Subsequently, circ_0000734 and miR-197-5p were silenced or overexpressed in a TNF-\u03b1-stimulated RA fibroblast-like synoviocyte (RA-FLS) model to validate their regulatory relationship. Flow cytometry (FCM), Cell Counting Kit-8 (CCK-8), reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and enzyme-linked immunosorbent assay (ELISA) were used to determine the effects of circ_0000734 and miR-197-5p silencing\/overexpression, as well as baicalin treatment, on RA-FLS cell viability, cell cycle progression, the NF-\u03baB signaling pathway, and the expression of inflammatory factors, including IL-17, IL-23, IL-4, and IL-10.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>circ_0000734 was highly expressed in PBMCs from RA patients and was positively correlated with disease activity indicators, including RF, CCP, CRP, ESR, and DAS28 scores. In the TNF-\u03b1-stimulated RA-FLS cell model, overexpression of circ_0000734 promoted RA-FLS cell proliferation, activated the NF-\u03baB pathway, and disrupted the balance between pro-inflammatory and anti-inflammatory factors, whereas circ_0000734 silencing exerted the opposite effects. Dual-uciferase reporter assays confirmed the targeting relationship between circ_0000734 and miR-197-5p. Overexpression of miR-197-5p reversed the effects of circ_0000734 overexpression on RA-FLS cell viability, the downstream target gene IKBKB, the NF-\u03baB pathway, and inflammatory factors. In addition, baicalin treatment downregulated circ_0000734 expression, thereby inhibiting the activation of the NF-\u03baB pathway, improving the inflammatory cytokine profile, and reversing the adverse phenotype induced by circ_0000734 overexpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Highly expressed circ_0000734 in RA promotes NF-\u03baB pathway activation by inhibiting miR-197-5p expression, thereby enhancing RA-FLS cell viability and promoting inflammatory cytokine secretion. Baicalin may inhibit the high expression of circ_0000734 and activation of the NF-\u03baB signaling pathway, ultimately alleviating the inflammatory response in RA-FLS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1828868","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:56:45Z","timestamp":1779944205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Baicalin improves the inflammatory response of RA-FLS by targeting the circ_0000734\/miR-197-5p\/IKBKB axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanqiu","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Rheumatism Immunity, The First Affiliated Hospital, Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Anhui Provincial Key Laboratory for Applied Basic and Clinical Translational Research on Rheumatologic Diseases in Traditional 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