{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:34:32Z","timestamp":1788885272048,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM121307"],"award-info":[{"award-number":["P20GM121307"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103424"],"award-info":[{"award-number":["P20GM103424"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"IDeA Center of Biomedical Research Excellence","doi-asserted-by":"publisher","award":["P20GM121307"],"award-info":[{"award-number":["P20GM121307"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"IDeA Center of Biomedical Research Excellence","doi-asserted-by":"publisher","award":["P20GM103424"],"award-info":[{"award-number":["P20GM103424"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine \u03b3-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-\u03b1 (TNF-\u03b1) and interferon-\u03b3 (IFN-\u03b3). CSE was increased in MPs and cells by exposure to TNF-\u03b1\/IFN-\u03b3; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction\/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, \u201cliquid biopsy\u201d can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.<\/jats:p>","DOI":"10.3390\/pathophysiology29030044","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T04:49:22Z","timestamp":1663562962000},"page":"570-582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9545-3616","authenticated-orcid":false,"given":"Pooja","family":"Veerareddy","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Dao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmi W.","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Y.","family":"Stokes","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"},{"name":"Center for Brain Health, LSU Health Shreveport, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Disbrow","sequence":"additional","affiliation":[{"name":"Center for Brain Health, LSU Health Shreveport, Shreveport, LA 71130, USA"},{"name":"Department of Neurology, LSU Health Shreveport, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Kevil","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"},{"name":"Department of Pathology, LSU Health Shreveport, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2042-6415","authenticated-orcid":false,"given":"Urska","family":"Cvek","sequence":"additional","affiliation":[{"name":"Department of Computer Science, LSU-Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Trutschl","sequence":"additional","affiliation":[{"name":"Department of Computer Science, LSU-Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Kilgore","sequence":"additional","affiliation":[{"name":"Department of Computer Science, LSU-Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7799-1485","authenticated-orcid":false,"given":"Robert","family":"Zivadinov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA"},{"name":"Department of Neurology, Buffalo Neuroimaging and Sciences (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-3711","authenticated-orcid":false,"given":"Jonathan S.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, LSU Health Shreveport, Shreveport, LA 71103, USA"},{"name":"Center for Brain Health, LSU Health Shreveport, Shreveport, LA 71130, USA"},{"name":"Department of Neurology, LSU Health Shreveport, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1172\/JCI58649","article-title":"Multiple Sclerosis","volume":"122","author":"Nylander","year":"2012","journal-title":"J. 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