{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:53Z","timestamp":1783660433749,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Hypervirulent\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (hv\n                      <jats:italic>K<\/jats:italic>\n                      p) is an important pathogen causing central nervous system infections, including meningitis; however, the mechanisms by which it disrupts the blood-brain barrier remain unclear. Niacin, a vitamin B3 compound related to NAD+ metabolism, has the potential to regulate redox homeostasis. This study aimed to investigate the mechanism of hv\n                      <jats:italic>K<\/jats:italic>\n                      p-induced injury in human cerebral microvascular endothelial cell (HCMEC) and to evaluate the protective effects of niacin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A GFP-labeled hv\n                      <jats:italic>K<\/jats:italic>\n                      p ATCC 43816 strain was used to establish an HCMEC infection model, and an hv\n                      <jats:italic>K<\/jats:italic>\n                      p mouse meningitis model was also constructed. Live-cell imaging was performed to monitor infection dynamics. Flow cytometry was used to assess infection rate, reactive oxygen species (ROS) levels, and Annexin V-FITC\/PI-labeled apoptosis, while Western blotting was used to analyze apoptosis-related pathways. The experimental groups included a control group, an hv\n                      <jats:italic>K<\/jats:italic>\n                      p infection group, an hv\n                      <jats:italic>K<\/jats:italic>\n                      p plus niacin treatment group, and a niacin pretreatment group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      hv\n                      <jats:italic>K<\/jats:italic>\n                      p caused time- and dose-dependent injury to HCMEC, characterized by intracellular proliferation followed by apoptosis induction. Mechanistically, hv\n                      <jats:italic>K<\/jats:italic>\n                      p promoted mitochondrial ROS accumulation and activated the p53-associated mitochondrial apoptotic pathway. Niacin reduced ROS levels, inhibited apoptosis, and alleviated HCMEC injury.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , niacin preserved blood-brain barrier integrity, reduced central nervous system inflammation and hv\n                      <jats:italic>K<\/jats:italic>\n                      p colonization, and improved survival in infected mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      hv\n                      <jats:italic>K<\/jats:italic>\n                      p damages cerebral microvascular endothelial cells and disrupts the blood-brain barrier through the ROS-p53-mitochondrial apoptosis axis. Niacin exerts protective effects by regulating redox homeostasis, suggesting that it may serve as a host-directed adjunctive therapeutic strategy for hv\n                      <jats:italic>K<\/jats:italic>\n                      p-associated central nervous system infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1867024","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:43Z","timestamp":1783657543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Niacin alleviates cerebral microvascular endothelial cell apoptosis induced by hypervirulent Klebsiella Pneumoniae by reducing the accumulation of reactive oxygen species"],"prefix":"10.3389","volume":"16","author":[{"given":"Yinghai","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Jingjiang People\u2019s Hospital Affiliated to Yangzhou University, Jingjiang","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1073\/pnas.87.4.1620","article-title":"Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide","volume":"87","author":"Beckman","year":"1990","journal-title":"Proc. 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