{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:05:04Z","timestamp":1793412304878,"version":"4.5.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"4-6","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"\u201cTianshan Talents\u201d high-level medical and health talent training program","award":["TSYC202301B146"],"award-info":[{"award-number":["TSYC202301B146"]}]},{"name":"Natural Science Fund of Xinjiang Uygur Autonomous Region","award":["2025D01C46"],"award-info":[{"award-number":["2025D01C46"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Heat stroke causes life-threatening liver injury, but its molecular basis remains poorly understood. We investigated whether ALKBH5-mediated N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) demethylation stabilizes Hmgb1 transcripts and promotes hepatocyte pyroptosis through the NLRP3 inflammasome. We also developed mesenchymal stem cell membrane-coated glycyrrhizic acid liposomes (MMGLs) as a targeted therapeutic strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      RNA-seq of HS rat livers revealed significant enrichment of pyroptosis pathways, with ALKBH5 identified as a hub gene. Mechanistically, heat stress upregulated ALKBH5, which demethylated\n                      <jats:italic toggle=\"yes\">HMGB1<\/jats:italic>\n                      mRNA, preventing its degradation and enhancing transcript stability. This stabilization led to increased intracellular High-mobility group box 1 (HMGB1) abundance, nucleocytoplasmic translocation, and extracellular release, subsequently activating the NLRP3-Caspase-1-GSDMD axis. Alkbh5 knockdown shortened Hmgb1 half-life and attenuated pyroptosis, whereas HMGB1 supplementation restored it. To target this axis, we engineered MMGLs (encapsulation efficiency: 81.7%), which exhibited superior inflammatory homing compared to unmodified liposomes. In HS rats, MMGLs achieved rapid hepatic accumulation, significantly reduced serum alanine aminotransferase\/aspartate aminotransferase, and suppressed Interleukin-1 beta (IL-1\u03b2)\/IL-18. MMGLs restored redox homeostasis by decreasing reactive oxygen species\/malondialdehyde and boosting reduced glutathione\/superoxide dismutase, thereby preserving hepatocyte architecture and inhibiting pyroptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>This study identifies an epitranscriptomic mechanism in HS-induced liver injury, in which ALKBH5-dependent stabilization of Hmgb1 mRNA amplifies pyroptotic signaling. MMGLs provide a biomimetic nanotherapeutic strategy to interrupt this inflammatory cascade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      ALKBH5-mediated m\n                      <jats:sup>6<\/jats:sup>\n                      A demethylation stabilizes HMGB1 to drive hepatocyte pyroptosis during HS. MMGLs effectively target this axis, offering a promising therapeutic approach for acute liver damage.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 173\u2013197.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261449248","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:04:07Z","timestamp":1779242647000},"page":"173-197","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["ALKBH5-Mediated m\n                    <sup>6<\/sup>\n                    A Demethylation Stabilizes HMGB1 to Drive Hepatocyte Pyroptosis and Liver Injury in Heat Stroke: Targeting via Biomimetic Nanodelivery"],"prefix":"10.1177","volume":"45","author":[{"given":"Yanli","family":"Sun","sequence":"first","affiliation":[{"name":"School of Mechanical Engineering, Xinjiang University, \u00dcr\u00fcmqi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Emergency Trauma Surgery, The First Affiliated Hospital of Xinjiang Medical University, \u00dcr\u00fcmqi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1885-2829","authenticated-orcid":false,"given":"Fei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Emergency Trauma Surgery, The First Affiliated Hospital of Xinjiang Medical University, \u00dcr\u00fcmqi, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01500-4"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.02.003"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adq0703"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34910-5"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404171"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.216044"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123537"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044100"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15020157"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.14789\/ejmj.JMJ25-0023-P"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101079"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080784"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.04.010"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.07.045"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i7.679"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1109-9"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.07.020"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435889.2024.2369495"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.55460\/5P2Q-1MBQ"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01189"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00452.2019"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2437-9"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111305"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b00553"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/grp\/6864091"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.07.004"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-018-00965-x"},{"issue":"4","key":"e_1_3_2_29_1","first-page":"1","article-title":"Glycyrrhizic acid delivery system","volume":"69","author":"Naseriyeh T","year":"2023","unstructured":"Naseriyeh T, , Kahrizi D, , Alvandi H, et al. 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