{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:57:09Z","timestamp":1771649829532,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["BT\/COE\/34\/SP15138\/2015"],"award-info":[{"award-number":["BT\/COE\/34\/SP15138\/2015"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>The objective of this study was to study the altered proteome in the frontal lobe of patients with CM. Unbiased analysis of differentially abundant proteins could lead to identification of host responses against<jats:italic>Plasmodium falciparum<\/jats:italic>infection, which will aid in better understanding of the molecular mechanism of pathophysiology in CM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental design<\/jats:title><jats:p>TMT\u2010based quantitative proteomic analysis using high\u2010resolution mass spectrometry is employed. In brief, proteins are isolated from frontal lobe samples, which are collected at autopsy from three cases of CM and three control subjects. Equal amounts of protein from each case are digested using trypsin and labeled with different TMT reagents. The pooled sample is fractionated using strong cation exchange chromatography and analyzed on Orbitrap Fusion in triplicates. For accurate quantitation of peptides, the samples are analyzed in MS3 mode. The data is searched against a combined database of human and<jats:italic>P. falciparum<\/jats:italic>proteins using Sequest and Mascot search engines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 4174 proteins are identified, of which, 107 are found to be differentially abundant in the test samples with significant<jats:italic>p<\/jats:italic>\u2010value (&lt;0.05). Proteins associated with biological processes such as innate immune response, complement system, coagulation, and platelet activation are found to be elevated in CM cases. In contrast, proteins associated with myelination, oxidative phosphorylation, regulation of reactive oxygen species, and sodium and calcium ions transport are found to be depleted in response to CM. In addition, three<jats:italic>P. falciparum<\/jats:italic>proteins exclusively in CM brain samples are also identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>The study signifies neuronal assault due to axonal injury, altered sodium and calcium ion channels, deregulated inflammation and demyelination as a part of host response to CM. Enhanced oxidative stress, repressed oxidative phosphorylation, and demyelination of axons may contribute to the severity of the disease. Further validation of these results on a large cohort can provide leads in the development of neuroprotective therapies for CM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.201600187","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T16:22:34Z","timestamp":1517502154000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Identification of Host\u2010Response in Cerebral Malaria Patients Using Quantitative Proteomic Analysis"],"prefix":"10.1002","volume":"12","author":[{"given":"Manish","family":"Kumar","sequence":"first","affiliation":[{"name":"Institute of Bioinformatics International Technology Park Bangalore India"},{"name":"Manipal Academy of Higher Education Manipal Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chakrakodi N.","family":"Varun","sequence":"additional","affiliation":[{"name":"Department of Neuromicrobiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gourav","family":"Dey","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics International Technology Park Bangalore India"},{"name":"Manipal Academy of Higher Education Manipal Karnataka India"},{"name":"Center for Systems Biology and Molecular Medicine Yenepoya (Deemed to be University) Mangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raju","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Department of Neuromicrobiology National Institute of Mental Health and Neuro Sciences Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Department of Neuropathology National Institute of Mental Health and Neurosciences Bangalore India"},{"name":"Human Brain Tissue Repository Neurobiology Research Centre National Institute of Mental Health and Neurosciences Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susarla Krishna","family":"Shankar","sequence":"additional","affiliation":[{"name":"Department of Neuropathology National Institute of Mental Health and Neurosciences Bangalore India"},{"name":"Human Brain Tissue Repository Neurobiology Research Centre National Institute of Mental Health and Neurosciences Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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