{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:43:20Z","timestamp":1791927800120,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370946"],"award-info":[{"award-number":["82370946"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501124"],"award-info":[{"award-number":["82501124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501127"],"award-info":[{"award-number":["82501127"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012401","name":"Beijing Science and Technology Planning Project","doi-asserted-by":"publisher","award":["Z211100002921042"],"award-info":[{"award-number":["Z211100002921042"]}],"id":[{"id":"10.13039\/501100012401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M760151"],"award-info":[{"award-number":["2024M760151"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Irreversible pulpitis poses a significant clinical burden due to progressive inflammatory pulp damage. While inflammatory mechanisms are central to its pathogenesis, they remain incompletely characterised. This study aims to elucidate the role of Nod\u2010like receptor thermal domain associated protein 1 (NLRP1) in irreversible pulpitis pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Transcriptomic analysis of public dataset GSE77459 identified dysregulated pyroptosis\u2010related genes (PRGs), with machine learning prioritising hub genes for experimental validation. Key targets were experimentally verified through an integrated approach: in\u00a0vitro models using lipopolysaccharide (LPS)\u2013stimulated human dental pulp cells (hDPCs) analysed by qRT\u2010PCR, ELISA and Western blot and specific pyroptosis assays (PI uptake, Caspase\u20101 cleavage); in\u00a0vivo rat pulpitis models; and clinically validation with human irreversible pulpitis tissues analysed via H&amp;E staining, immunohistochemistry (IHC) and immunofluorescence (IF). Functional roles were further assessed via NLRP1 knockdown and overexpression in hDPCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bioinformatics identified 11 differentially expressed PRGs, with machine learning highlighting six hub genes including unreported NLRP1. Specific pyroptosis assays confirmed that LPS induces membrane pore formation and Caspase\u20101 activation in hDPCs. Significant post\u2010transcriptional regulation of NLRP1 was demonstrated by pronounced protein upregulation in LPS\u2010stimulated hDPCs despite unaltered mRNA. Functional studies established NLRP1 as a positive regulator, where its knockdown attenuated the LPS\u2010induced inflammatory\u2010pyroptotic response, while its overexpression alone was sufficient to upregulate key mediators. Consistently, elevated NLRP1 expression was observed in rat models and human tissues, where IHC\/IF localised prominent expression to inflammatory infiltrates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NLRP1 is highlighted as a novel pyroptosis biomarker for irreversible pulpitis, with its dysregulation offering diagnostic value for inflammation. These findings suggest its potential involvement in the inflammatory mechanisms of pulpitis, providing a new molecular target for future therapeutic exploration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70084","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:24:44Z","timestamp":1765884284000},"page":"643-655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>NLRP1<\/scp>\n                    as a Novel Pyroptosis Biomarker in Irreversible Pulpitis: A Laboratory Investigation and Animal Model Study"],"prefix":"10.1111","volume":"59","author":[{"given":"Jilin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cariology and Endodontology Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-7138","authenticated-orcid":false,"given":"Churen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University  Xiamen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Stomatology Peking University Third Hospital  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1587-4128","authenticated-orcid":false,"given":"Siyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-9857","authenticated-orcid":false,"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatric Dentistry Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"},{"name":"Fourth Clinical Division, Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cariology and Endodontology Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.14036"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.04.025"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1702"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.02.006"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-019-02876-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13762"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13866"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-021-00724-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07710"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S507198"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2020.07.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-073119-095439"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2009.09.032"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13505"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101130"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146852"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/aej.12392"},{"issue":"1","key":"e_1_2_11_19_1","first-page":"128","article-title":"Symptom Correlation and Spatial Distribution of Inflammatory Mediators in Pulpitis\u2010A Preliminary Study","volume":"58","author":"Loo A. 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