{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:06:27Z","timestamp":1767179187280,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010774","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000}}],"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004607","name":"Guangxi Natural Science Foundation","doi-asserted-by":"crossref","award":["2018GXNSFBA050070"],"award-info":[{"award-number":["2018GXNSFBA050070"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31900681"],"award-info":[{"award-number":["31900681"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National College Students\u2019 innovation and entrepreneurship training program","award":["202010598028"],"award-info":[{"award-number":["202010598028"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Currently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD.\n                      <jats:italic>Clonorchis sinensis<\/jats:italic>\n                      (\n                      <jats:italic>C<\/jats:italic>\n                      .\n                      <jats:italic>sinensis<\/jats:italic>\n                      ) mainly elicit Th2\/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease (\n                      <jats:italic>Cs<\/jats:italic>\n                      CP) and adult crude antigen (\n                      <jats:italic>Cs<\/jats:italic>\n                      CA) of\n                      <jats:italic>C<\/jats:italic>\n                      .\n                      <jats:italic>sinensis<\/jats:italic>\n                      , and\n                      <jats:italic>C<\/jats:italic>\n                      .\n                      <jats:italic>sinensis<\/jats:italic>\n                      (\n                      <jats:italic>Cs<\/jats:italic>\n                      ) infection on DSS-induced colitis mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BALB\/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP,\n                      <jats:italic>Cs<\/jats:italic>\n                      CA or dexamethasone (DXM) every day, or\n                      <jats:italic>Cs<\/jats:italic>\n                      infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with\n                      <jats:italic>Cs<\/jats:italic>\n                      infection, r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP and\n                      <jats:italic>Cs<\/jats:italic>\n                      CA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP was superior to\n                      <jats:italic>Cs<\/jats:italic>\n                      CA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that\n                      <jats:italic>Cs<\/jats:italic>\n                      CA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1\/Th17 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Both r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP and\n                      <jats:italic>Cs<\/jats:italic>\n                      CA showed good therapeutic effects on the treatment of acute colitis, but r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP is a better choice. r\n                      <jats:italic>Cs<\/jats:italic>\n                      CP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12\/IL-23r axis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0010774","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T17:03:20Z","timestamp":1662743000000},"page":"e0010774","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in 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