{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:19:32Z","timestamp":1791339572553,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20220530162408019"],"award-info":[{"award-number":["JCYJ20220530162408019"]}],"id":[{"id":"10.13039\/501100017610","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study investigated the effects of lactate\u2010induced lactylation in the inflammatory microenvironment of pulpitis and further explored the mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Lactate levels in pulpitis samples were quantified using a high\u2010sensitivity assay. Histological, immunohistochemical, and immunofluorescence staining were conducted to evaluate lactylation, macrophage marker, pro\u2010inflammatory, and anti\u2010inflammatory markers. A time\u2010course murine experimental pulpitis model (0\u201372\u2009h) was established to characterise lactylation dynamics during inflammatory progression in pulpitis. An in\u00a0vitro inflammatory dental pulp microenvironment model of THP\u20101 macrophages cocultured with LPS\u2010pretreated dental pulp cells derived conditioned media (iCM) was developed to investigate lactate production and macrophage phenotypes. Transcriptomic profiling identified differentially expressed genes, with gene set enrichment analysis (GSEA) employed to assess the functions of differentially expressed genes. Transmission electron microscopy, quantitative real\u2010time PCR (qRT\u2010PCR), concurrent oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were measured to evaluate the mitochondrial activity of iCM\u2010pretreated macrophages. Mouse experimental pulpitis models treated with iCM were conducted to evaluate anti\u2010inflammation and pro\u2010healing properties by histological, immunohistochemical, and immunofluorescence staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Histological staining revealed that elevated lactate levels, increased Pan Kla expression, and upregulated extent of M2 phenotype macrophage infiltration in clinical pulpitis specimens. Notably, we identified a positive correlation between Pan Kla levels and M2 macrophage markers. In\u00a0vitro inflammatory dental pulp microenvironment model, we demonstrated that M1 macrophages actively uptake lactate from iCM, leading to increased lactylation and subsequent M2\u2010like polarisation. Importantly, we found that iCM could regulate polarisation of M1 macrophages via metabolic reprogramming, as evidenced by RNA sequencing. Our integrated analyses revealed significant mitochondrial structural remodelling, while metabolic flux assays demonstrated a characteristic shift from glycolytic metabolism to oxidative phosphorylation. This metabolic reprogramming was functionally linked to M2 polarisation, as evidenced by phenotypic marker analysis. Moreover, iCM treatment significantly downregulated pro\u2010inflammatory cytokine (IL\u20106) while upregulating anti\u2010inflammatory marker (CD206) in experimental pulpitis models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study revealed that elevated lactate production in the inflammatory microenvironment roles as a mediator of immunometabolic crosstalk, bridging dental pulp cells\u2010macrophage communication. And the mechanism involved in lactylation induced metabolic reprogramming. This helps to better understand the repair potential of inflamed dental pulp, supporting biologically\u2010based preservation approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70136","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:29:17Z","timestamp":1773030557000},"page":"1465-1478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lactylation\u2010Driven Macrophage Polarisation Regulates Pulp Inflammation"],"prefix":"10.1111","volume":"59","author":[{"given":"Ziting","family":"Wang","sequence":"first","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-0957","authenticated-orcid":false,"given":"Xiaolin","family":"Lyu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Yi","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5499-0693","authenticated-orcid":false,"given":"Buling","family":"Wu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7481-5283","authenticated-orcid":false,"given":"Wenan","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Clinical College of Stomatology, School of Stomatology Southern Medical University  Shenzhen Guangdong China"},{"name":"Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.688910"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001452\u20101"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102446"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020\u20100360OC"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg3505"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2015.09.001"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2023.08.019"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.09.010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/230251"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110986"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.117894"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2006.11.008"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2007.01.001"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12459"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221150383"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.21276\/ujds.2020.6.2.14"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001499\u20100"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123843"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010023\u201001335\u20107"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.23\u20100241"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.02.008"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2018.02.004"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2019.10.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016357809029086"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.013"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102846"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010101320\u2010031555"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.934040"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/10985549.2023.2253131"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.04.034"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.03.001"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.75434"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.03.015"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110328"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523\u20101755.2004.00786.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/php.13751"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2021.105136"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301300"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.949252"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010025\u201001268\u20109"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519894957"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101678\u20101"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.12.004"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.10.006"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.901495"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.103016"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010024\u201000866\u2010z"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.926802"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411408"}],"container-title":["International Endodontic Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iej.70136","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/iej.70136","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iej.70136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:17:12Z","timestamp":1780384632000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iej.70136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,8]]},"references-count":49,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/iej.70136"],"URL":"https:\/\/doi.org\/10.1111\/iej.70136","archive":["Portico"],"relation":{},"ISSN":["0143-2885","1365-2591"],"issn-type":[{"value":"0143-2885","type":"print"},{"value":"1365-2591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,8]]},"assertion":[{"value":"2025-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}