{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:05:04Z","timestamp":1787882704459,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hypoxia\u2010ischemia (HI) of the brain not only impairs neurodevelopment but also causes pineal gland dysfunction, which leads to circadian rhythm disruption. However, the underlying mechanism of circadian rhythm disruption associated with HI\u2010induced pineal dysfunction remains unknown. The zinc finger protein repressor protein with a predicted molecular mass of 58\u2009kDa (\n                    <jats:italic>RP58<\/jats:italic>\n                    ) is involved in the development and differentiation of nerve cells. In this study, we established an HI model in neonatal rats to investigate the expression of\n                    <jats:italic>RP58<\/jats:italic>\n                    and its role in pineal dysfunction and circadian rhythm disruption induced by HI. We demonstrated that\n                    <jats:italic>RP58<\/jats:italic>\n                    was highly expressed in the pineal gland under normal conditions and significantly downregulated in the pineal gland and primary pinealocytes following HI. Knockdown of\n                    <jats:italic>RP58<\/jats:italic>\n                    decreased the expression of enzymes in the melatonin (Mel) synthesis pathway (tryptophan hydroxylase 1 [\n                    <jats:italic>TPH1<\/jats:italic>\n                    ], acetylserotonin\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methyltransferase [\n                    <jats:italic>ASMT<\/jats:italic>\n                    ], and arylalkylamine\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyltransferase [\n                    <jats:italic>AANAT<\/jats:italic>\n                    ]) and clock genes (circadian locomotor output cycles kaput [\n                    <jats:italic>CLOCK<\/jats:italic>\n                    ] and brain and muscle ARNT\u2010like 1 [\n                    <jats:italic>BMAL1<\/jats:italic>\n                    ]), and it also reduced the production of Mel, caused pineal cell injury, and disrupted circadian rhythms in vivo and in vitro. Similarly, HI reduced the expression of Mel synthesis enzymes (\n                    <jats:italic>TPH1<\/jats:italic>\n                    ,\n                    <jats:italic>ASMT<\/jats:italic>\n                    , and\n                    <jats:italic>AANAT<\/jats:italic>\n                    ) and clock genes (\n                    <jats:italic>CLOCK<\/jats:italic>\n                    and\n                    <jats:italic>BMAL1<\/jats:italic>\n                    ), and caused pineal injury and circadian rhythm disruption, which were exacerbated by\n                    <jats:italic>RP58<\/jats:italic>\n                    knockdown. The detrimental effect of\n                    <jats:italic>RP58<\/jats:italic>\n                    knockdown on pineal dysfunction and circadian rhythm disruption was reversed by the addition of exogenous Mel. Furthermore, exogenous Mel reversed HI\u2010induced pineal dysfunction and circadian rhythm disruption, as reflected by improvements in Mel production, voluntary activity periods, and activity frequency, as well as a diminished decrease in the expression of Mel synthesis enzymes and clock genes. The present study suggests that\n                    <jats:italic>RP58<\/jats:italic>\n                    is an endogenous source of protection against pineal dysfunction and circadian rhythm disruption after neonatal HI.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12885","type":"journal-article","created":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T23:34:38Z","timestamp":1684107278000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>RP58<\/i>\n                    knockdown contributes to hypoxia\u2010ischemia\u2010induced pineal dysfunction and circadian rhythm disruption in neonatal rats"],"prefix":"10.1111","volume":"75","author":[{"given":"Hui","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Research Institute Children's Hospital of Soochow University  Suzhou Jiangsu Province China"},{"name":"Department of Neonatology Tongren People's Hospital  Tongren Guizhou Province China"},{"name":"Department of Soochow Key Laboratory of Prevention and Treatment of Child Brain Injury Children's Hospital of Soochow University Suzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Research Institute Children's Hospital of Soochow University  Suzhou Jiangsu Province China"},{"name":"Department of Pharmacology, College of Pharmaceutical Sciences Soochow University Suzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Soochow Key Laboratory of Prevention and Treatment of Child Brain Injury Children's Hospital of Soochow University Suzhou Jiangsu Province 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