{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:31:53Z","timestamp":1786649513848,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Efferocytosis plays a vital role in mitigating inflammation and subsequent tissue damage by clearing dying cells after intracerebral hemorrhage, but its underlying mechanism remains poorly understood. In this study, programmed cell death 4 (PDCD4) exhibited upregulated expression and localization to microglia following intracerebral hemorrhage. Targeted adenoviral-mediated\n                    <jats:italic toggle=\"yes\">Pdcd4<\/jats:italic>\n                    knockdown\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    markedly improved neurological recovery and enhanced microglial efferocytosis in intracerebral hemorrhage model mice. These effects were further validated in\n                    <jats:italic toggle=\"yes\">Pdcd4<\/jats:italic>\n                    knockout mice. In an\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    intracerebral hemorrhage model using oxyhemoglobin-treated microglia,\n                    <jats:italic toggle=\"yes\">Pdcd4<\/jats:italic>\n                    knockdown notably increased the expression of efferocytosis-related molecules AXL receptor tyrosine kinase (AXL) and MER proto-oncogene, tyrosine kinase (MERTK). Mechanistically, an interaction between PDCD4 and signal transducer and activator of transcription 3 (STAT3) identified under basal conditions was amplified following intracerebral hemorrhage.\n                    <jats:italic toggle=\"yes\">Pdcd4<\/jats:italic>\n                    knockdown also promoted Janus kinase 2 (JAK2)-mediated STAT3 phosphorylation and nuclear translocation, driving\n                    <jats:italic toggle=\"yes\">Mertk<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Axl<\/jats:italic>\n                    transcription to facilitate microglial efferocytosis. Furthermore,\n                    <jats:italic toggle=\"yes\">Pdcd4<\/jats:italic>\n                    knockdown markedly reduced proinflammatory factor expression while enhancing anti-inflammatory factor levels, thereby mitigating the neuronal apoptosis induced by conditioned medium. These findings indicate that PDCD4 blockade enhances microglial efferocytosis by activating the JAK2-STAT3-Mertk\/Axl pathway and promotes post-intracerebral hemorrhage neurological recovery, identifying PDCD4 as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-25-01622","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:00:15Z","timestamp":1776142815000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Downregulation of PDCD4 contributes to microglial efferocytosis and neurological function recovery following intracerebral hemorrhage"],"prefix":"10.4103","author":[{"given":"Mengqi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Zai","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengwei","family":"Duan","sequence":"additional","affiliation":[{"name":"Medical Research Center, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit, Medical Research Center, Nantong First People\u2019s Hospital, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Research Center, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit, Medical Research Center, Nantong First People\u2019s Hospital, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7377-8879","authenticated-orcid":false,"given":"Hongjian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Nantong First People\u2019s Hospital, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu Province, China"},{"name":"Department of Nursing and Rehabilitation, Medical College, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,4,14]]},"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-01622","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T18:54:55Z","timestamp":1786647295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-01622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.4103\/nrr.nrr-d-25-01622","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"2025-10-25","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}