{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:47:11Z","timestamp":1785757631706,"version":"3.56.0"},"reference-count":154,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Star Project for Outstanding Graduate Students of the Gansu Provincial Department of Education","award":["2026CXZX-922"],"award-info":[{"award-number":["2026CXZX-922"]}]},{"DOI":"10.13039\/501100009590","name":"Excellent Doctoral Student Program of Gansu Province","doi-asserted-by":"publisher","award":["25JRRA258"],"award-info":[{"award-number":["25JRRA258"]}],"id":[{"id":"10.13039\/501100009590","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Traditional Chinese Medicine Service Capacity Building Project","award":["2023ZY010"],"award-info":[{"award-number":["2023ZY010"]}]},{"name":"Key Research and Development and Transformation Key Special Project of the Tibet Autonomous Region Science and Technology Plan","award":["XZ202601ZY0218"],"award-info":[{"award-number":["XZ202601ZY0218"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is an important endogenous gaseous signaling molecule that regulates diverse physiological and pathological processes through protein persulfidation. As a central regulator of inflammation and immune responses, NF-\u03baB signaling is precisely controlled by post-translational modifications, and its dysregulation contributes to various inflammatory diseases. Recent studies reveal that H2S-mediated persulfidation is a key mechanism for fine-tuning NF-\u03baB activity by targeting critical components, including p65, IKK\u03b2, I\u03baB\u03b1, and upstream regulators. Through site-specific S-sulfhydration, H2S modulates IKK activation, I\u03baB\u03b1 degradation, and p65 nuclear translocation, thereby limiting excessive NF-\u03baB activation and inflammatory cytokine production. This review provides an integrated view of how endogenous H2S production and persulfidation-dependent signaling regulate inflammatory responses. Rather than simply summarizing individual pathways, we focus on the molecular mechanisms underlying H2S-mediated regulation of NF-\u03baB-associated networks, including TLR4\/NF-\u03baB, PI3K\/Akt\/NF-\u03baB, and MAPK\/NF-\u03baB pathways, and highlight its roles in oxidative stress, apoptosis, pyroptosis, and tissue repair. We further discuss current challenges in identifying persulfidation sites, understanding endogenous H2S regulation, and improving detection technologies. By proposing H2S as a precision modulator of inflammatory signaling, this review provides new insights into H2S biology and highlights future opportunities for developing targeted H2S-based therapeutic strategies.<\/jats:p>","DOI":"10.3390\/biom16081130","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"1130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen Sulfide-Regulated NF-\u03baB Signaling via Persulfidation: A Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Liang","family":"Xu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5799-0231","authenticated-orcid":false,"given":"Keke","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Ta","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongrun","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-3694","authenticated-orcid":false,"given":"Xianxie","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengrong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China"},{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13098","DOI":"10.1096\/fj.201901304R","article-title":"Hydrogen Sulfide Signaling in Mitochondria and Disease","volume":"33","author":"Murphy","year":"2019","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.7150\/ijbs.38315","article-title":"Hydrogen Sulfide Treatment Alleviated Ventilator-Induced Lung Injury through Regulation of Autophagy and Endoplasmic Reticulum Stress","volume":"15","author":"Ge","year":"2019","journal-title":"Int. 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