{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:50Z","timestamp":1790776730679,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":272,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parkinson's Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accumulating evidence implicates peripheral immune dysregulation in the pathogenesis of Parkinson\u2019s disease (PD). High\u2010mobility group box 1 (HMGB1), a key alarmin released during mitochondrial stress, has been reported to be upregulated in the peripheral blood of PD patients, yet its precise role remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed an integrated analysis of multiple transcriptomic datasets from peripheral blood mononuclear cells (PBMCs) of PD patients. Using a combination of methods including machine learning, cell\u2013cell communication analysis, in silico gene perturbation, and pathway enrichment analysis, we systematically investigated the expression and regulation of\n                      <jats:italic>HMGB1<\/jats:italic>\n                      in peripheral immune cells in PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:italic>HMGB1<\/jats:italic>\n                      mRNA expression was significantly downregulated in PBMCs from PD patients. A machine learning model identified\n                      <jats:italic>HMGB1<\/jats:italic>\n                      as a potential predictive signature (AUC\u2009=\u20090.685). Single\u2010cell transcriptomic analysis revealed immune cell heterogeneity and identified CD8\n                      <jats:sup>+<\/jats:sup>\n                      T and CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells as central hubs in the cellular communication network. In silico perturbation analysis suggested that\n                      <jats:italic>HMGB1<\/jats:italic>\n                      may be associated with the expression of\n                      <jats:italic>S100A8<\/jats:italic>\n                      and\n                      <jats:italic>S100A9<\/jats:italic>\n                      , which are enriched in the IL\u201017 signaling pathway. Drug enrichment analysis identified potential therapeutic agents, including TPEN, hydrocotarnine, and phorbol 12\u2010myristate 13\u2010acetate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our analysis revealed a distinct downregulation of\n                      <jats:italic>HMGB1<\/jats:italic>\n                      within the peripheral immune compartment of PD, a change that was decoupled from the overall proinflammatory state. Observing the concomitant upregulation of the S100 gene family and activation of the IL\u201017 pathway, we propose a putative pathogenic axis based on computational findings:\n                      <jats:italic>HMGB1<\/jats:italic>\n                      downregulation is linked to S100 gene family upregulation and IL\u201017 pathway activation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/padi\/2128634","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:23:55Z","timestamp":1790774635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral\n                    <i>HMGB1<\/i>\n                    Downregulation Is Associated With the S100\u2013IL\u201017 Axis in Parkinson\u2019s Disease: An Integrated Bulk and Single\u2010Cell Transcriptomic Analysis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0354-1239","authenticated-orcid":false,"given":"Shuning","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University  Changchun Jilin China  jlu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5306-5885","authenticated-orcid":false,"given":"Hang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology Changchun Central Hospital  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6841-749X","authenticated-orcid":false,"given":"Xiangjun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology Liaoyuan Central Hospital  Liaoyuan Jilin 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