CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity
•CK2 is overactivated in RA FLS.•CK2 specific inhibitor CX-4945 improves the pathogenic phenotypes of RA FLS.•CK2-p53 axis controls RA FLS proliferation and cytokines secretion.•CX-4945 might be a potential therapeutic drug in RA. Fibroblast-like synoviocytes (FLS) mediate many pathological processe...
Gespeichert in:
| Veröffentlicht in: | International immunopharmacology 2023-06, Vol.119, p.110163-110163, Article 110163 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 110163 |
|---|---|
| container_issue | |
| container_start_page | 110163 |
| container_title | International immunopharmacology |
| container_volume | 119 |
| creator | Luo, Yanping Lei, Yunxuan Guo, Xin Zhu, Dehao Zhang, Haiyang Guo, Zizhen Xu, Zichong Zhao, Hanqing Xi, Yebin Peng, Xiaochun Xiao, Lianbo Wang, Zhaojun Niu, Xiaoyin Chen, Guangjie |
| description | •CK2 is overactivated in RA FLS.•CK2 specific inhibitor CX-4945 improves the pathogenic phenotypes of RA FLS.•CK2-p53 axis controls RA FLS proliferation and cytokines secretion.•CX-4945 might be a potential therapeutic drug in RA.
Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA. |
| doi_str_mv | 10.1016/j.intimp.2023.110163 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2801981572</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1567576923004848</els_id><sourcerecordid>2801981572</sourcerecordid><originalsourceid>FETCH-LOGICAL-c362t-cfea9a09ba82bf38910132b0c0a0bc2e4311aab4820c5ad70774167e33cbc7863</originalsourceid><addsrcrecordid>eNp9kE9v1DAQxS0EakvpN0DIRy5Z_CeJnQsSWtFStRIXkLhZtjNhZ0nixXZW7I2PjlcpHDnN6L3fzGgeIa8523DG23f7Dc4Zp8NGMCE3_KzJZ-SKa6UrrljzvPRNq6pGtd0leZnSnrGi1_yCXErFWqaZviK_t9-quqsbivMOHeZEB3QxuNGmXI34A2g6zeGIwZ8yFHOZfcYwJ5p3MSzfd6UC3T6I6tBIan9hMQKN0C8eaNzBMtkcsKc2Fh5zsXtMYFNZC0coyukVeTHYMcHNU70mX28_ftl-qh4_391vPzxWXrYiV34A21nWOauFG6Tuyr9SOOaZZc4LqCXn1rpaC-Yb2yumVM1bBVJ655Vu5TV5u-49xPBzgZTNhMnDONoZwpKM0Ix3mjdKFLReUR9DShEGc4g42XgynJlzzmZv1uzNOXuzZl_G3jxdWNwE_b-hv2EX4P0KQPnziBBN8gizhx4j-Gz6gP-_8Afp7JiX</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2801981572</pqid></control><display><type>article</type><title>CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Luo, Yanping ; Lei, Yunxuan ; Guo, Xin ; Zhu, Dehao ; Zhang, Haiyang ; Guo, Zizhen ; Xu, Zichong ; Zhao, Hanqing ; Xi, Yebin ; Peng, Xiaochun ; Xiao, Lianbo ; Wang, Zhaojun ; Niu, Xiaoyin ; Chen, Guangjie</creator><creatorcontrib>Luo, Yanping ; Lei, Yunxuan ; Guo, Xin ; Zhu, Dehao ; Zhang, Haiyang ; Guo, Zizhen ; Xu, Zichong ; Zhao, Hanqing ; Xi, Yebin ; Peng, Xiaochun ; Xiao, Lianbo ; Wang, Zhaojun ; Niu, Xiaoyin ; Chen, Guangjie</creatorcontrib><description>•CK2 is overactivated in RA FLS.•CK2 specific inhibitor CX-4945 improves the pathogenic phenotypes of RA FLS.•CK2-p53 axis controls RA FLS proliferation and cytokines secretion.•CX-4945 might be a potential therapeutic drug in RA.
Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2023.110163</identifier><identifier>PMID: 37060808</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Arthritis, Rheumatoid - metabolism ; Casein kinase 2 ; Casein Kinase II - metabolism ; Casein Kinase II - pharmacology ; Casein Kinase II - therapeutic use ; Cell Proliferation ; Cells, Cultured ; CX-4945 ; Fibroblast-like synoviocytes ; Fibroblasts ; Interleukin-6 - metabolism ; Matrix Metalloproteinase 3 - metabolism ; Mice ; p53 signaling pathway ; Patient Acuity ; Proteomics ; Rheumatoid arthritis ; Synovial Membrane - pathology ; Synoviocytes ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>International immunopharmacology, 2023-06, Vol.119, p.110163-110163, Article 110163</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-cfea9a09ba82bf38910132b0c0a0bc2e4311aab4820c5ad70774167e33cbc7863</citedby><cites>FETCH-LOGICAL-c362t-cfea9a09ba82bf38910132b0c0a0bc2e4311aab4820c5ad70774167e33cbc7863</cites><orcidid>0000-0002-5446-6784</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2023.110163$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37060808$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Yanping</creatorcontrib><creatorcontrib>Lei, Yunxuan</creatorcontrib><creatorcontrib>Guo, Xin</creatorcontrib><creatorcontrib>Zhu, Dehao</creatorcontrib><creatorcontrib>Zhang, Haiyang</creatorcontrib><creatorcontrib>Guo, Zizhen</creatorcontrib><creatorcontrib>Xu, Zichong</creatorcontrib><creatorcontrib>Zhao, Hanqing</creatorcontrib><creatorcontrib>Xi, Yebin</creatorcontrib><creatorcontrib>Peng, Xiaochun</creatorcontrib><creatorcontrib>Xiao, Lianbo</creatorcontrib><creatorcontrib>Wang, Zhaojun</creatorcontrib><creatorcontrib>Niu, Xiaoyin</creatorcontrib><creatorcontrib>Chen, Guangjie</creatorcontrib><title>CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•CK2 is overactivated in RA FLS.•CK2 specific inhibitor CX-4945 improves the pathogenic phenotypes of RA FLS.•CK2-p53 axis controls RA FLS proliferation and cytokines secretion.•CX-4945 might be a potential therapeutic drug in RA.
Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.</description><subject>Animals</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Casein kinase 2</subject><subject>Casein Kinase II - metabolism</subject><subject>Casein Kinase II - pharmacology</subject><subject>Casein Kinase II - therapeutic use</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>CX-4945</subject><subject>Fibroblast-like synoviocytes</subject><subject>Fibroblasts</subject><subject>Interleukin-6 - metabolism</subject><subject>Matrix Metalloproteinase 3 - metabolism</subject><subject>Mice</subject><subject>p53 signaling pathway</subject><subject>Patient Acuity</subject><subject>Proteomics</subject><subject>Rheumatoid arthritis</subject><subject>Synovial Membrane - pathology</subject><subject>Synoviocytes</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9v1DAQxS0EakvpN0DIRy5Z_CeJnQsSWtFStRIXkLhZtjNhZ0nixXZW7I2PjlcpHDnN6L3fzGgeIa8523DG23f7Dc4Zp8NGMCE3_KzJZ-SKa6UrrljzvPRNq6pGtd0leZnSnrGi1_yCXErFWqaZviK_t9-quqsbivMOHeZEB3QxuNGmXI34A2g6zeGIwZ8yFHOZfcYwJ5p3MSzfd6UC3T6I6tBIan9hMQKN0C8eaNzBMtkcsKc2Fh5zsXtMYFNZC0coyukVeTHYMcHNU70mX28_ftl-qh4_391vPzxWXrYiV34A21nWOauFG6Tuyr9SOOaZZc4LqCXn1rpaC-Yb2yumVM1bBVJ655Vu5TV5u-49xPBzgZTNhMnDONoZwpKM0Ix3mjdKFLReUR9DShEGc4g42XgynJlzzmZv1uzNOXuzZl_G3jxdWNwE_b-hv2EX4P0KQPnziBBN8gizhx4j-Gz6gP-_8Afp7JiX</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Luo, Yanping</creator><creator>Lei, Yunxuan</creator><creator>Guo, Xin</creator><creator>Zhu, Dehao</creator><creator>Zhang, Haiyang</creator><creator>Guo, Zizhen</creator><creator>Xu, Zichong</creator><creator>Zhao, Hanqing</creator><creator>Xi, Yebin</creator><creator>Peng, Xiaochun</creator><creator>Xiao, Lianbo</creator><creator>Wang, Zhaojun</creator><creator>Niu, Xiaoyin</creator><creator>Chen, Guangjie</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5446-6784</orcidid></search><sort><creationdate>202306</creationdate><title>CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity</title><author>Luo, Yanping ; Lei, Yunxuan ; Guo, Xin ; Zhu, Dehao ; Zhang, Haiyang ; Guo, Zizhen ; Xu, Zichong ; Zhao, Hanqing ; Xi, Yebin ; Peng, Xiaochun ; Xiao, Lianbo ; Wang, Zhaojun ; Niu, Xiaoyin ; Chen, Guangjie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-cfea9a09ba82bf38910132b0c0a0bc2e4311aab4820c5ad70774167e33cbc7863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Casein kinase 2</topic><topic>Casein Kinase II - metabolism</topic><topic>Casein Kinase II - pharmacology</topic><topic>Casein Kinase II - therapeutic use</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>CX-4945</topic><topic>Fibroblast-like synoviocytes</topic><topic>Fibroblasts</topic><topic>Interleukin-6 - metabolism</topic><topic>Matrix Metalloproteinase 3 - metabolism</topic><topic>Mice</topic><topic>p53 signaling pathway</topic><topic>Patient Acuity</topic><topic>Proteomics</topic><topic>Rheumatoid arthritis</topic><topic>Synovial Membrane - pathology</topic><topic>Synoviocytes</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Yanping</creatorcontrib><creatorcontrib>Lei, Yunxuan</creatorcontrib><creatorcontrib>Guo, Xin</creatorcontrib><creatorcontrib>Zhu, Dehao</creatorcontrib><creatorcontrib>Zhang, Haiyang</creatorcontrib><creatorcontrib>Guo, Zizhen</creatorcontrib><creatorcontrib>Xu, Zichong</creatorcontrib><creatorcontrib>Zhao, Hanqing</creatorcontrib><creatorcontrib>Xi, Yebin</creatorcontrib><creatorcontrib>Peng, Xiaochun</creatorcontrib><creatorcontrib>Xiao, Lianbo</creatorcontrib><creatorcontrib>Wang, Zhaojun</creatorcontrib><creatorcontrib>Niu, Xiaoyin</creatorcontrib><creatorcontrib>Chen, Guangjie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Yanping</au><au>Lei, Yunxuan</au><au>Guo, Xin</au><au>Zhu, Dehao</au><au>Zhang, Haiyang</au><au>Guo, Zizhen</au><au>Xu, Zichong</au><au>Zhao, Hanqing</au><au>Xi, Yebin</au><au>Peng, Xiaochun</au><au>Xiao, Lianbo</au><au>Wang, Zhaojun</au><au>Niu, Xiaoyin</au><au>Chen, Guangjie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>119</volume><spage>110163</spage><epage>110163</epage><pages>110163-110163</pages><artnum>110163</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•CK2 is overactivated in RA FLS.•CK2 specific inhibitor CX-4945 improves the pathogenic phenotypes of RA FLS.•CK2-p53 axis controls RA FLS proliferation and cytokines secretion.•CX-4945 might be a potential therapeutic drug in RA.
Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>37060808</pmid><doi>10.1016/j.intimp.2023.110163</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5446-6784</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1567-5769 |
| ispartof | International immunopharmacology, 2023-06, Vol.119, p.110163-110163, Article 110163 |
| issn | 1567-5769 1878-1705 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2801981572 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Animals Arthritis, Rheumatoid - metabolism Casein kinase 2 Casein Kinase II - metabolism Casein Kinase II - pharmacology Casein Kinase II - therapeutic use Cell Proliferation Cells, Cultured CX-4945 Fibroblast-like synoviocytes Fibroblasts Interleukin-6 - metabolism Matrix Metalloproteinase 3 - metabolism Mice p53 signaling pathway Patient Acuity Proteomics Rheumatoid arthritis Synovial Membrane - pathology Synoviocytes Tumor Suppressor Protein p53 - metabolism |
| title | CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T18%3A03%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CX-4945%20inhibits%20fibroblast-like%20synoviocytes%20functions%20through%20the%20CK2-p53%20axis%20to%20reduce%20rheumatoid%20arthritis%20disease%20severity&rft.jtitle=International%20immunopharmacology&rft.au=Luo,%20Yanping&rft.date=2023-06&rft.volume=119&rft.spage=110163&rft.epage=110163&rft.pages=110163-110163&rft.artnum=110163&rft.issn=1567-5769&rft.eissn=1878-1705&rft_id=info:doi/10.1016/j.intimp.2023.110163&rft_dat=%3Cproquest_cross%3E2801981572%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2801981572&rft_id=info:pmid/37060808&rft_els_id=S1567576923004848&rfr_iscdi=true |