{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:02:43Z","timestamp":1785391363097,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cirrhosis encephalopathy (CE) is a severe neuropsychiatric complication of liver cirrhosis, characterized by cognitive decline. While circadian rhythm (CR) disruption and astrocyte dysfunction are independently implicated, their integrated role in CE pathogenesis remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Limma and WGCNA analysis were performed for identification of CR and astrocyte (CA)-associated DEGs in CE patient bulk data (GSE41919 and GSE53808). Next, in 2 dependent CE patient bulk data (GSE184220 and GSE149741), we pinpointed CA-associated hub gene and nominated its corresponding diagnostic potential for CE patients via random forest (RF) machine learning algorithm. Next, molecular and immune patterns of hub gene in CE were examined in GSE184220 via single-gene GSEA and CIBERSORT analysis. Single-cell RNA-seq (GSE163577) from cognitive impairment patients was used to validate the cellular specificity of the hub gene and its functional implications in astrocyte via cutting-edge analytical framework, such as monocle2 and scTenifoldKnk analysis. Artificial intelligence (AI)-driven framework (DrugReflector) coupled with molecular docking identified a therapeutic compound in GSE41919 for the treatment of CE. Finally, an\n                      <jats:italic>in vitro<\/jats:italic>\n                      CE model using SVGp12 cells was used for the examination of hub gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IL8 can be considered as up-regulated CA-associated pathogenic factor involved in the pathogenesis of CE, which was predominantly active in astrocytes and related to neuroinflammation and CR regulation. AI-based drug screening nominated BRD-K11973162 as a potential therapeutic compound.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study discovered CA-related molecular patterns CE. IL18 emerges as a central pathogenic factor within astrocytes, providing a novel framework for risk stratification and targeted therapy for this debilitating condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1897110","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:40:00Z","timestamp":1785390000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and validation of circadian rhythm and astrocyte-associated diagnostic and therapeutic model for cirrhosis encephalopathy patients via integrative bioinformatic pipelines and in vitro validation"],"prefix":"10.3389","volume":"20","author":[{"given":"Nianshan","family":"Ji","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Cheng","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Peng","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Sun","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.cmet.2020.11.007","article-title":"SCENITH: A flow cytometry-based method to functionally profile energy metabolism with single-cell resolution.","volume":"32","author":"Arg\u00fcello","year":"2020","journal-title":"Cell. 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