{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:15:02Z","timestamp":1783379702966,"version":"3.54.6"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Thalamic hemorrhage is a severe subtype of intracerebral hemorrhage in which secondary neuroinflammation contributes to tissue injury and neurological deterioration. N-acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine writer, has been implicated in inflammatory regulation and neurological disorders. However, inflammation-related transcriptomic changes associated with Remodelin treatment after thalamic hemorrhage remain unclear\n                      <jats:bold>.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>mRNA transcriptome sequencing was performed on perilesional thalamic tissues from control, thalamic hemorrhage model, and Remodelin-treated mice. Differentially expressed genes were identified for the Model versus Control and Remodelin Intervention versus Model comparisons. Genes showing opposite directions of regulation across the two comparisons were defined as Remodelin-reversed differentially expressed genes. GeneCards-derived inflammation-related genes were converted to mouse orthologs and intersected with Remodelin-reversed genes. Protein-protein interaction analysis, Gene Ontology and KEGG enrichment analyses, gene set enrichment analysis, immune-cell signature estimation, and transcription factor\/miRNA regulatory network prediction were performed. Key candidates were validated by quantitative RT-PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNA-seq identified 499 differentially expressed genes in the Model versus Control comparison and 664 in the Remodelin Intervention versus Model comparison. Among 46 shared differentially expressed genes, 42 showed opposite-direction regulation. Ortholog-corrected screening identified 9 Remodelin-reversed inflammation-related candidates:\n                      <jats:italic>Cxcl1<\/jats:italic>\n                      ,\n                      <jats:italic>Ccl2<\/jats:italic>\n                      ,\n                      <jats:italic>Ncf4<\/jats:italic>\n                      ,\n                      <jats:italic>Ptx3<\/jats:italic>\n                      ,\n                      <jats:italic>Pomc<\/jats:italic>\n                      ,\n                      <jats:italic>Masp2<\/jats:italic>\n                      ,\n                      <jats:italic>Tnfrsf8<\/jats:italic>\n                      ,\n                      <jats:italic>Card9<\/jats:italic>\n                      , and\n                      <jats:italic>Gpr84<\/jats:italic>\n                      . Enrichment analyses linked these genes mainly to leukocyte- and neutrophil-mediated immunity, tumor necrosis factor production, cytokine-cytokine receptor interaction, IL-17 signaling, TNF signaling, chemokine signaling, and NOD-like receptor signaling. Protein-protein interaction analysis highlighted\n                      <jats:italic>Ccl2<\/jats:italic>\n                      ,\n                      <jats:italic>Cxcl1<\/jats:italic>\n                      , and\n                      <jats:italic>Pomc<\/jats:italic>\n                      as prominent candidate nodes. qRT-PCR using independent biological samples provided preliminary transcript-level support for Remodelin-associated changes in\n                      <jats:italic>Cxcl1<\/jats:italic>\n                      and\n                      <jats:italic>Pomc<\/jats:italic>\n                      expression, whereas\n                      <jats:italic>Ccl2<\/jats:italic>\n                      was increased after hemorrhage but was not significantly reduced by Remodelin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies Remodelin-reversed inflammation-related transcriptomic signatures in experimental thalamic hemorrhage.\n                      <jats:italic>Cxcl1<\/jats:italic>\n                      and\n                      <jats:italic>Pomc<\/jats:italic>\n                      represent the most consistently supported Remodelin-responsive transcriptomic candidates, whereas\n                      <jats:italic>Ccl2<\/jats:italic>\n                      appears to be a hemorrhage-associated inflammatory hub without robust reversal at the examined time point. These findings provide an exploratory neurogenomic framework for investigating inflammation-related transcriptional remodeling associated with Remodelin treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1874675","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:41:29Z","timestamp":1783377689000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Remodelin treatment reshapes inflammation-related transcriptomic signatures in experimental thalamic hemorrhage"],"prefix":"10.3389","volume":"17","author":[{"given":"Zi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinggang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianfeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]},{"name":"Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People\u2019s Hospital Affiliated to Yangzhou University","place":["Yangzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102207","DOI":"10.1016\/j.gde.2024.102207","article-title":"NAT10 and cytidine acetylation in mRNA: intersecting paths in development and disease","volume":"87","author":"Achour","year":"2024","journal-title":"Curr. Opin. Genet. Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1016\/j.cell.2018.10.030","article-title":"Acetylation of cytidine in mRNA promotes translation efficiency","volume":"175","author":"Arango","year":"2018","journal-title":"Cell."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A distinct function of regulatory T cells in tissue protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1471-2105-4-2","article-title":"An automated method for finding molecular complexes in large protein interaction networks","volume":"4","author":"Bader","year":"2003","journal-title":"BMC Bioinforma."},{"key":"B5","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"W244","DOI":"10.1093\/nar\/gkaa467","article-title":"miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology","volume":"48","author":"Chang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-020-01853-x","article-title":"TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K\/Akt pathway after intracerebral hemorrhage in mice","volume":"17","author":"Chen","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8886004","DOI":"10.1155\/2021\/8886004","article-title":"Ultrarapid endoscopic-aided hematoma evacuation in patients with thalamic hemorrhage","volume":"2021","author":"Chen","year":"2021","journal-title":"Behav. Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"De Filippo","year":"2013","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1161\/STROKEAHA.121.034173","article-title":"FTO (fat-mass and obesity-associated protein) participates in hemorrhage-induced thalamic pain by stabilizing toll-like receptor 4 expression in thalamic neurons","volume":"52","author":"Fu","year":"2021","journal-title":"Stroke"},{"key":"B11","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.brainresbull.2022.05.004","article-title":"Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors","volume":"185","author":"Guo","year":"2022","journal-title":"Brain Res. Bull."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.1523\/JNEUROSCI.4070-13.2014","article-title":"CCR2+Ly6Chi inflammatory monocyte recruitment exacerbates acute disability following intracerebral hemorrhage","volume":"34","author":"Hammond","year":"2014","journal-title":"J. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","article-title":"TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.1152\/physrev.00024.2017","article-title":"POMC: the physiological power of hormone processing","volume":"98","author":"Harno","year":"2018","journal-title":"Physiol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e139987","DOI":"10.1172\/jci.insight.139987","article-title":"Fgr contributes to hemorrhage-induced thalamic pain by activating NF-kappaB\/ERK1\/2 pathways","volume":"5","author":"Huang","year":"2020","journal-title":"JCI Insight"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1007\/s12035-024-04454-4","article-title":"The cytidine N-acetyltransferase NAT10 promotes thalamus hemorrhage-induced central poststroke pain by stabilizing Fn14 expression in thalamic neurons","volume":"62","author":"Huang","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/S1474-4422(12)70104-7","article-title":"Intracerebral haemorrhage: mechanisms of injury and therapeutic targets","volume":"11","author":"Keep","year":"2012","journal-title":"Lancet Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1126\/science.1252651","article-title":"Chemical inhibition of NAT10 corrects defects of laminopathic cells","volume":"344","author":"Larrieu","year":"2014","journal-title":"Science"},{"key":"B19","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.3233\/JAD-220564","article-title":"Comprehensive analysis of long non-coding RNAs N4-acetylcytidine in alzheimer's disease mice model using high-throughput sequencing","volume":"90","author":"Ma","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3109\/09638289709166839","article-title":"Functional outcome following thalamic haemorrhage: relationship between motor and cognitive functions and ADL","volume":"19","author":"Maeshima","year":"1997","journal-title":"Disabil. Rehabil."},{"key":"B22","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/S0140-6736(09)60371-8","article-title":"Intracerebral haemorrhage","volume":"373","author":"Qureshi","year":"2009","journal-title":"Lancet"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-Sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1001\/archneur.1992.00530310045011","article-title":"Thalamic stroke: presentation and prognosis of infarcts and hemorrhages","volume":"49","author":"Steinke","year":"1992","journal-title":"Arch. Neurol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards suite: from gene data mining to disease genome sequence analyses","volume":"54","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinforma."},{"key":"B29","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B30","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.chom.2020.05.011","article-title":"Acetylation of cytidine residues boosts HIV-1 gene expression by increasing viral RNA stability","volume":"28","author":"Tsai","year":"2020","journal-title":"Cell. Host Microbe"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e2106058","DOI":"10.1002\/advs.202106058","article-title":"PIWI-Interacting RNA HAAPIR regulates cardiomyocyte death after myocardial infarction by promoting NAT10-mediated ac4C acetylation of tfec mRNA","volume":"9","author":"Wang","year":"2022","journal-title":"Adv. Sci. (Weinh.)"},{"key":"B33","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B34","doi-asserted-by":"publisher","first-page":"119521","DOI":"10.1016\/j.bbamcr.2023.119521","article-title":"NAT10 regulates the LPS-Induced inflammatory response via the NOX2-ROS-NF-kappaB pathway in macrophages","volume":"1870","author":"Zhang","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1874675\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T22:41:30Z","timestamp":1783377690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1874675\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":34,"alternative-id":["10.3389\/fgene.2026.1874675"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1874675","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"article-number":"1874675"}}