{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:41:38Z","timestamp":1792604498049,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute ischemic stroke remains a major cause of death and disability, underscoring the need for safe and effective neuroprotective strategies. Hydrogen sulfide (H\u2082S) exhibits dose-dependent neuroprotective effects but its therapeutic application is constrained by volatility and burst release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We synthesized low-solubility, slowly hydrolyzing calcium sulfide nanoparticles (CaS NPs) via a wet-chemistry route as an intrinsically slow-releasing H\u2082S donor. Their sustained release profile was characterized, and efficacy was evaluated in vitro using SH-SY5Y cells under oxygen-glucose deprivation\/reoxygenation (OGD\/R) and in BV2 microglia, and in vivo using a distal middle cerebral artery occlusion (dMCAO) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CaS NPs demonstrated sustained H\u2082S release over 48 h. In vitro, they enhanced SH-SY5Y cell viability under OGD\/R, decreased intracellular reactive oxygen species, suppressed TNF-\u03b1 and IL-1\u03b2 expression in BV2 cells, and reduced neuronal apoptosis. In the dMCAO model, CaS NPs increased cortical H\u2082S levels, improved 24-h neurological scores, reduced day-3 infarct area, preserved peri-infarct neurons, mitigated ROS accumulation, and attenuated astrocyte and microglia activation. Treatment consistently decreased Bax expression, increased Bcl-2 levels, and reduced pro-inflammatory cytokine expression. Short-term safety assessments indicated a favorable biosafety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings provide proof-of-concept support that CaS NPs can serve as a slow-releasing H\u2082S donor platform for further evaluation in experimental ischemic stroke.\"<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1746066","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:15:33Z","timestamp":1776399333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Calcium sulfide nanoparticles as sustained H2S donors with neuroprotective potential in ischemic stroke"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhen","family":"Lu","sequence":"first","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Bin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Stroke Center, The Affiliated Panyu Central Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaotao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second People\u2019s Hospital of Fujian Province, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Postgraduate Cultivation Base of Guangzhou University of Chinese Medicine, Panyu Central Hospital","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Neuroscience Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Neuroscience Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"School of Biomedical Engineering, Guangzhou Medical University","place":["Guangzhou, 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