{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:52:50Z","timestamp":1753869170174,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["#2021R1I1A3044128","RS\u20102023\u201000219399"],"award-info":[{"award-number":["#2021R1I1A3044128","RS\u20102023\u201000219399"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Our previous study highlighted the anticancer potential of sea hare hydrolysate (SHH), particularly its role in regulating macrophage polarization and inducing pyroptotic death in lung cancer cells through the inhibition of signal transducer and activator of transcription 3 (STAT3). These findings prompted us to investigate additional features of immune\u2010oncology (I\u2010O) agents or adjuvants, such as programmed cell death protein 1 (PD\u20101)\/programmed death ligand 1 (PD\u2010L1) inhibition and their association with rheumatoid arthritis (RA) risk, to explore the potential of SHH as an I\u2010O agent or adjuvant. In this study, we investigated the effects of SHH on PD\u2010L1 levels in various cancer cell types and assessed its effectiveness in treating RA, a common side effect of I\u2010O agents. Our results showed a marked reduction in PD\u2010L1 levels in multiple cancer cell lines and decreased PD\u20101 and PD\u2010L1 levels in tumor\u2010associated macrophages. In a mouse model with collagen\u2010induced arthritis (CIA), SHH exhibited anti\u2010inflammatory effects comparable to methotrexate (MTX), a first\u2010line treatment for RA. Both the SHH and MTX groups had significantly lower arthritis scores and paw thickness compared to the CIA group. Additionally, SHH or MTX treatment effectively reduced elevated levels of anticollagen type II (CII) antibodies and proinflammatory cytokines (IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1). Histopathological analysis revealed that SHH and MTX treatments notably mitigated arthritic inflammation, synovial hyperplasia, and loss of articular cartilage and bone. Micro\u2010CT scans showed reduced articular destruction in the SHH and MTX groups. These findings indicate that SHH treatment decreases PD\u2010L1 levels in cancer cells and reduces the severity of CIA by exerting anti\u2010inflammatory effects. Therefore, SHH holds promise as an I\u2010O agent without side effects such as exacerbation of RA.<\/jats:p>","DOI":"10.1002\/fsn3.4644","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T10:35:28Z","timestamp":1733135728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sea Hare Hydrolysate Reduces <scp>PD<\/scp>\u2010<scp>L1<\/scp> Levels in Cancer Cells and Mitigates Rheumatoid Arthritis Ina Collagen\u2010Induced Arthritis Mouse Model"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-3108","authenticated-orcid":false,"given":"Ji Hyeon","family":"Ryu","sequence":"first","affiliation":[{"name":"Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan Hospital  Yangsan Republic of 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