{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:24:18Z","timestamp":1783635858796,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060214"],"award-info":[{"award-number":["82060214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20212BAB206047"],"award-info":[{"award-number":["20212BAB206047"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD\u2010like complications of diabetes mellitus. This work further investigated its underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Diabetes mellitus rat model was constructed by a high\u2010fat and high\u2010sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro\u2010injected with LV\u2010TXNIP\u2010OE\/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFR\u03b2, tight junction proteins occludin and ZO\u20101, calpain\u20101, calpain\u20102, APP, A\u03b2, A\u03b2\u2010related, and TXNIP\/NLRP3 inflammasome\u2010related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood\u2013brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory\u2010related factors were assessed by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Calpeptin effectively reduced the expression of Calpain\u20102 and TXNIP\/NLRP3 inflammasome\u2010related proteins, improved the decreased pericyte marker (PDGFR\u2010\u03b2) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, A\u03b2 accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data demonstrated that calpeptin treatment alleviated AD\u2010like symptoms in DM rats through regulating TXNIP\/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD\u2010like complications of diabetes mellitus.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14292","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T19:38:53Z","timestamp":1724355533000},"page":"1365-1376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Calpeptin improves the cognitive function in Alzheimer's disease\u2010like complications of diabetes mellitus rats by regulating <scp>TXNIP<\/scp>\/<scp>NLRP3<\/scp> inflammasome"],"prefix":"10.1111","volume":"15","author":[{"given":"Luyao","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouqin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianpei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Neuroscience, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahui","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4728-3397","authenticated-orcid":false,"given":"Zhenyu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"xiii","DOI":"10.1016\/j.ecl.2016.09.002","article-title":"Diabetes mellitus","volume":"45","author":"Ben\u2010Shlomo A","year":"2016","journal-title":"Endocrinol Metab Clin North Am"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.151"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.10.2568"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-018-0703-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2020.06.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000499541"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11111016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093165"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.2c05609"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315287"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113306"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-96445-4_13"},{"key":"e_1_2_9_14_1","first-page":"125","article-title":"Diabetes mellitus and blood\u2010brain barrier dysfunction: An overview","volume":"2","author":"Prasad S","year":"2014","journal-title":"J Pharm"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-96445-4_14"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858416649178"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.04.004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21534"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-022-00561-z"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17784"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01524-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249357"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1327-16.2016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.007265"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12655"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2018.03.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13024"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1722-y"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.09.026"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146361"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317473"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9518"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0504-4"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox7050063"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871530319666191016103222"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40199-019-00302-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00129"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1195-5"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2020.1787624"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25173942"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.06.015"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104685"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102735"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.14292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T12:31:45Z","timestamp":1731501105000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.14292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,22]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/jdi.14292"],"URL":"https:\/\/doi.org\/10.1111\/jdi.14292","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,22]]},"assertion":[{"value":"2024-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}