{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:36:55Z","timestamp":1776753415987,"version":"3.51.2"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Oxidative stress and inflammation are interconnected drivers of cellular damage in pathologies ranging from neurodegenerative disorders to sensorineural hearing loss. We aimed to develop a chitosan-Prussian blue nanozyme (CS-PB) to target these processes in sensorineural hearing loss. CS-PB (35 \u03bcg\/mL) pretreatment of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -injured HEI-OC1 cochlear cells for 4\u00a0h markedly decreased the levels of reactive oxygen species (ROS) inside cells (from 3.8 to 2.4 relative fluorescence intensity) by approximately 37% (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.001)-and concomitantly significantly decreased expression of the oxidative damage markers 4-HNE and 3-NT (both\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.001). The rate of apoptosis decreased from 27.5% in the H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -treated group to 14.1% following CS-PB treatment (P &amp;lt; 0.01). This reduction was accompanied by a significant downregulation of the pro-apoptotic proteins Bax (P &amp;lt; 0.05) and Cleaved-caspase-3 (P &amp;lt; 0.001), as well as an upregulation of the anti-apoptotic protein Bcl-XL (P &amp;lt; 0.01).Western blot analysis confirmed that CS\u2013PB significantly downregulated TLR4 expression and inhibited downstream phosphorylation of p-P65\/P65, while upregulating p-I\u03baB\u03b1\/I\u03baB\u03b1 protein (all\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.01) associated with reduction in the production of inflammatory cytokines like TNF-\u03b1, IL-1\u03b2, and IL-6. Treatment with the specific TLR4 antagonist TAK-242 (2 \u03bcM) mimicked the effect of CS-PB, with coadministration showing no additional ant-inflammatory effect (although HEI-OC1 viability was additionally increased), indicating that the anti-inflammatory properties of CS-PB were facilitated via the TLR4\/NF-\u03baB signaling pathway.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , CS-PB pretreatment (2 mg\/mL, 2 \u03bcL) was administered by carefully applying the solution to the round window membrane (RWM) using a microsyringe in a noise-induced hearing loss rat model, which significantly curtailed the noise-induced activation of the TLR4\/NF-\u03baB pathway in the cochlea. After 24 hours, the levels of p-P65\/P65 and TLR4 decreased by 54% and 50%, respectively. (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.001), and levels of the inflammatory cytokines IL-6, TNF-\u03b1 and IL-1\u03b2 were decreased by 53%, 48%, and 51% (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.001). Furthermore, the degree of pathway inhibition showed a strong correlation with cytokine reduction (r = 0.87\u20130.89, all\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&amp;lt;\u00a00.001). CS-PB showed no significant cytotoxicity\n                    <jats:italic>in vitro<\/jats:italic>\n                    or\n                    <jats:italic>in vivo<\/jats:italic>\n                    , suggesting that its combined ROS-scavenging and TLR4\/NF-\u03baB\u2013modulating properties may represent a potential therapeutic strategy, pending further mechanistic and translational validation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1758392","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:37:09Z","timestamp":1776749829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Studies of chitosan-Prussian blue nanozyme in auditory protection: from cellular mechanisms to in vivo validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Hebei Medical 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