{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:26:18Z","timestamp":1753878378107,"version":"3.41.2"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060294"],"award-info":[{"award-number":["82060294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions in the first 24 weeks of pregnancy. However, the detailed molecular mechanisms behind RSA remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>We used bioinformatics and systems biology approaches to analyze the underlying molecular mechanisms to provide new insights into the biology of M1 macrophage exosome differentially expressed genes (DEGs) in RSA patients and to identify potential drugs to treat RSA. The trophoblast (HTR\u20108) was co\u2010cultured with the M1 macrophage exosomes induced by THP\u20101, and the cell model was constructed for transcriptome sequencing analysis and data source construction. Functional enrichment and pathway analysis of DEGs among the three groups were performed. In addition, differential expression of key genes was verified by RT\u2010qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We obtained 172 DEGs from the sequencing data. Metabolic and immune\u2010related pathways and functions are the main pathways of its enrichment. FOCX1, GATA2, YY1, TFAP2A, MEFF2A, and STAT3 are the major transcription factors (TFs) of M1 macrophage exosomes in RSA. Hsa\u2010mir\u2010106b\u20105p, hsa\u2010mir\u2010149\u20103p, and hsa\u2010mir\u2010520a\u20103p are associated with RSA. Finally, the DEGS\u2010disease and DEGS\u2010drug interaction networks are predicted. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) enrichment analysis revealed clusters and targets associated with maternal and fetal interface immune tolerance in RSA M1 macrophage exosomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The candidate targets and drugs obtained from M1\u2010type macrophage exosomes in this study may contribute to the effective treatment of RSA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70115","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T17:57:12Z","timestamp":1750355832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Therapeutic Targets and Drugs for Recurrent Spontaneous Abortion by M1 Macrophage Exosome Sequencing Analysis: A Bioinformatic and Vitro Study"],"prefix":"10.1111","volume":"93","author":[{"given":"Cen","family":"Tang","sequence":"first","affiliation":[{"name":"Obstetrics Department Kunming Medical University Second Affiliated Hospital  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqin","family":"Hu","sequence":"additional","affiliation":[{"name":"Obstetrics Department Kunming Medical University Second Affiliated Hospital  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Obstetrics Department Kunming Medical University Second Affiliated Hospital  Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00682-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmaa017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.642392"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.58731"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4146"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.46144"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2016.10.007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01334-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2012-3354"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjab232.176"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01094-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01084"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700673r"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12024"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202204826"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752\u20100509\u20108\u2010S4\u2010S11"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbab115"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2239606"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1107"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.860676"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv313"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz1021"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184331"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01906-4"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.994888"},{"key":"e_1_2_9_31_1","unstructured":"Identifying Central Genes From Common DEGs Helps Us Gain More Key Features to Uncover Potential Biomarkers. 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