{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:56:01Z","timestamp":1782701761929,"version":"3.54.5"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study sought to investigate the therapeutic effects and mechanisms of cryptotanshinone (CT) on unexplained recurrent spontaneous abortion (URSA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The DBA\/2 male and CBA\/J female mice were caged together to construct a URSA model before treatment with high and medium\u2010low doses of CT. Enzyme\u2010linked immunosorbent assay (ELISA) was used to detect levels of interleukin (IL)\u20101 beta (\u03b2), IL\u201017, and IL\u201022 in serum in each category of mice. Hematoxylin\u2013eosin (HE) pathology was employed to detect decidua and uterine tissues, while polymerase chain reaction (PCR) was utilized to ascertain relative expression levels of serum messenger ribonucleic acid (mRNA) of IL\u201017, IL\u201022, and IL\u20101\u03b2. The effects of CT on H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2010induced HTR\u20108\/SVneo cells were investigated using cell counting kit\u20108 (CCK\u20108) assays and cell migration assays, while flow cytometry was used for the detection of apoptosis. Network pharmacology was used to analyze the mechanism of CT in the treatment of URSA. The repair effects and underlying mechanisms of the tumor protein 53 (p53) inhibitor and signal and transducer of transcription 3 small interfering RNA (STAT3 siRNA) were evaluated using ELISA assays, CCK\u20108, cell migration assays, flow cytometry, immunofluorescence, and Western blot techniques.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Different doses of CT exerted protective effects on the uterine tissues of URSA. Also, CT could reduce levels of IL\u201017, IL\u201022, and IL\u20101\u03b2 and their relative mRNA content in the serum of URSA mice, as well as increase the activity and migration rate of HTR\u20108\/SVneo cells, and reduce the rate of apoptosis. Using p53 and STAT3 as mechanistic targets, we found that the p53 inhibitor, STAT3 siRNA, and CT restored the migratory activity of HTR\u20108\/SVneo cells, reduced their apoptotic rate, and simultaneously downregulated the expression of retinoic acid receptor\u2010related orphan receptor \u03b3t (ROR\u03b3t) and vascular endothelial growth factor (VEGF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The mechanism by which CT regulated the activity of HTR\u20108\/SVneo cells involved the inhibition of p\u2010p53, with STAT3, ROR\u03b3t, and VEGF functioning as downstream targets of the p53 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70163","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T13:18:52Z","timestamp":1759151932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of Cryptotanshinone Regulates HTR\u20108\/SVneo Cells Activity Through the p53\/STAT3 Pathway in Unexplained Recurrent Spontaneous Abortion"],"prefix":"10.1111","volume":"94","author":[{"given":"Lidan","family":"Lu","sequence":"first","affiliation":[{"name":"The Third Clinical Medical College Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"Department of Gynecology Changshu Hospital Affiliated to Nanjing University of Chinese Medicine  Changshu Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Gynecology Changshu Hospital Affiliated to Nanjing University of 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