{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:51:38Z","timestamp":1785919898424,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/1-151-07\/503-11-001-18"],"award-info":[{"award-number":["503\/1-151-07\/503-11-001-18"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/1-159-01\/503-11-001"],"award-info":[{"award-number":["503\/1-159-01\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"award":["503\/1-151-07\/503-11-001-18"],"award-info":[{"award-number":["503\/1-151-07\/503-11-001-18"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]},{"award":["503\/1-159-01\/503-11-001"],"award-info":[{"award-number":["503\/1-159-01\/503-11-001"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Atrial fibrillation (AF) is associated with oxidative stress and inflammation. Glutathione reductase (GR) and microRNA-144 (miR-144) may participate in redox-related pathways. This study aimed to evaluate relative GSR mRNA and miR-144 expression in peripheral blood samples from patients with and without AF and to explore their associations with selected clinical characteristics. Methods: This case\u2013control study included 189 hospitalized adults: 95 without AF and 94 with AF. Clinical, anthropometric, biochemical, and echocardiographic data were collected for all participants. GSR mRNA was assessed by quantitative real-time PCR in whole blood samples, whereas circulating miR-144 expression was evaluated in serum. Group differences were assessed using nonparametric tests, correlations were evaluated using Spearman\u2019s rank correlation coefficient, and multivariable logistic regression was used to identify variables independently associated with AF. Model stability was assessed using bootstrap internal validation. Results: Relative GSR mRNA expression was significantly lower in the AF group than in controls (0.1539 vs. 0.2058, p &lt; 0.001), whereas miR-144 expression was significantly higher in patients with AF (0.3636 vs. 0.2550, p = 0.0183). In multivariable logistic regression adjusted for clinical confounders, higher miR-144 (OR = 1.336, p = 0.048) and lower GSR (OR = 0.343, p &lt; 0.001) expression remained associated with AF. Bootstrap internal validation supported the statistical stability of the GSR association (optimism-corrected AUC = 0.709, bootstrapped 95% CI: 0.622\u20130.785), whereas miR-144 showed only a more modest and less stable association (optimism-corrected AUC = 0.598, bootstrapped 95% CI: 0.519\u20130.684); both signals remain exploratory and do not yet support routine clinical use as diagnostic or risk-stratification biomarkers in AF. Both markers showed exploratory correlations with selected clinical and biochemical variables. Given the cross-sectional design of the study, all reported relationships should be interpreted as statistical associations rather than as evidence of causality. The observed correlations between molecular markers and clinical parameters are hypothesis-generating and warrant further investigation.<\/jats:p>","DOI":"10.3390\/medsci14040456","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:14:46Z","timestamp":1785917686000},"page":"456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Expression Profiles of Glutathione Reductase and miR-144 in Patients with Atrial Fibrillation"],"prefix":"10.3390","volume":"14","author":[{"given":"Monika","family":"R\u00f3\u017cycka-Kosmalska","sequence":"first","affiliation":[{"name":"Department of Electrocardiology, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3529-1989","authenticated-orcid":false,"given":"Miko\u0142aj","family":"Grabarczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0704","authenticated-orcid":false,"given":"Agnieszka","family":"\u015aliwi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Koz\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-9657","authenticated-orcid":false,"given":"Marcin","family":"Kosmalski","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6335-0273","authenticated-orcid":false,"given":"Jerzy Krzysztof","family":"Wranicz","sequence":"additional","affiliation":[{"name":"Department of Electrocardiology, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6545-579X","authenticated-orcid":false,"given":"Izabela","family":"Szymczak-Pajor","sequence":"additional","affiliation":[{"name":"Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.cjco.2024.11.017","article-title":"Trends in Global Burden and Socioeconomic Profiles of Atrial Fibrillation and Atrial Flutter: Insights from the Global Burden of Disease Study 2021","volume":"7","author":"Tan","year":"2025","journal-title":"CJC Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1001\/jama.2024.22451","article-title":"Atrial Fibrillation: A Review","volume":"333","author":"Ko","year":"2025","journal-title":"JAMA"},{"key":"ref_3","first-page":"100786","article-title":"Atrial fibrillation: Epidemiology, screening and digital health","volume":"37","author":"Linz","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_4","first-page":"100785","article-title":"Atrial fibrillation: Pathophysiology, genetic and epigenetic mechanisms","volume":"37","author":"Vinciguerra","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Singh, H., Shahid, M.Z., Harrison, S.L., Lane, D.A., Lip, G.Y.H., and Logantha, S.J.R.J. (2024). Subclinical thyroid dysfunction and the risk of incident atrial fibrillation: A systematic review and meta-analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0296413"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1093\/eurheartj\/ehag044","article-title":"Atrial fibrillation: An underappreciated complication of diabetes","volume":"47","author":"Cai","year":"2026","journal-title":"Eur. Heart J."},{"key":"ref_7","first-page":"100784","article-title":"Atrial fibrillation: Comorbidities, lifestyle, and patient factors","volume":"37","author":"Shantsila","year":"2024","journal-title":"Lancet Reg. Health-Eur."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10654-022-00914-0","article-title":"Blood pressure, hypertension and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies","volume":"38","author":"Aune","year":"2023","journal-title":"Eur. J. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.yjmcc.2024.09.011","article-title":"Oxidative stress and atrial fibrillation","volume":"196","author":"Pfenniger","year":"2024","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104050","DOI":"10.1016\/j.redox.2026.104050","article-title":"NRF2: Master regulator of cellular homeostasis and therapeutic vulnerability in cancer","volume":"90","author":"Chen","year":"2026","journal-title":"Redox Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28063","DOI":"10.1074\/jbc.M704893200","article-title":"Atrial Glutathione Content, Calcium Current, and Contractility","volume":"282","author":"Carnes","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00424-021-02514-5","article-title":"Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage","volume":"473","author":"Rennison","year":"2021","journal-title":"Pfl\u00fcg. Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s00441-023-03823-0","article-title":"MicroRNAs in atrial fibrillation target genes in structural remodelling","volume":"394","author":"Kawasaki","year":"2023","journal-title":"Cell Tissue Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1016\/j.hrthm.2025.05.052","article-title":"MicroRNAs in cardiac arrhythmias: Mechanisms, biomarkers, and therapeutic frontiers","volume":"22","author":"Popat","year":"2025","journal-title":"Heart Rhythm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neulet.2017.06.045","article-title":"MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis","volume":"655","author":"Zhou","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.1182\/blood-2009-04-214817","article-title":"microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease","volume":"116","author":"Sangokoya","year":"2010","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ramos-Mondrag\u00f3n, R., Lozhkin, A., Vendrov, A.E., Runge, M.S., Isom, L.L., and Madamanchi, N.R. (2023). NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation. Antioxidants, 12.","DOI":"10.3390\/antiox12101833"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Han, C., Kim, M.-J., Ding, D., Park, H.-J., White, K., Walker, L., Gu, T., Tanokura, M., Yamasoba, T., and Linser, P. (2017). GSR is not essential for the maintenance of antioxidant defenses in mouse cochlea: Possible role of the thioredoxin system as a functional backup for GSR. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180817"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fujii, J., Osaki, T., Soma, Y., and Matsuda, Y. (2023). Critical Roles of the Cysteine\u2013Glutathione Axis in the Production of \u03b3-Glutamyl Peptides in the Nervous System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098044"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.hrthm.2017.07.028","article-title":"Association between oxidative stress and atrial fibrillation","volume":"14","author":"Sandesara","year":"2017","journal-title":"Heart Rhythm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e000713","DOI":"10.1161\/JAHA.113.000713","article-title":"Monoamine Oxidase is a Major Determinant of Redox Balance in Human Atrial Myocardium and is Associated with Postoperative Atrial Fibrillation","volume":"3","author":"Anderson","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1053\/j.semtcvs.2020.11.026","article-title":"Inflammatory and Antioxidant Gene Transcripts: A Novel Profile in Postoperative Atrial Fibrillation","volume":"33","author":"Watt","year":"2021","journal-title":"Semin. Thorac. Cardiovasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rubanenko, O., Rubanenko, A., and Davydkin, I. (2023). Comprehensive Analysis of Factors Associated with New Episode of Postoperative Atrial Fibrillation after Coronary Artery Bypass Graft Surgery. Life, 13.","DOI":"10.3390\/life13102035"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kiyosawa, N., Watanabe, K., Morishima, Y., Yamashita, T., Yagi, N., Arita, T., Otsuka, T., and Suzuki, S. (2020). Exploratory Analysis of Circulating miRNA Signatures in Atrial Fibrillation Patients Determining Potential Biomarkers to Support Decision-Making in Anticoagulation and Catheter Ablation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072444"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1038\/s41598-020-61322-6","article-title":"Serum microRNA in patients undergoing atrial fibrillation ablation","volume":"10","author":"Kiliszek","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"45","author":"Rienstra","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10654-020-00636-1","article-title":"Prediction meets causal inference: The role of treatment in clinical prediction models","volume":"35","author":"Swanson","year":"2020","journal-title":"Eur. J. Epidemiol."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/4\/456\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:38:51Z","timestamp":1785919131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/4\/456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["medsci14040456"],"URL":"https:\/\/doi.org\/10.3390\/medsci14040456","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}