{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:19:36Z","timestamp":1787775576247,"version":"build-2784847793"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Cytokine storms and inflammation lead to heart failure (HF). Bioactive compounds, as complementary medicine, can be the primary source of compounds with anti-inflammatory properties.\n                      <jats:italic toggle=\"yes\">Linum usitatissimum<\/jats:italic>\n                      (LiU) has antioxidant capacity and anti-inflammatory activity. Here, candidate hugeness was selected based on the\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      studies, bio-cheminformatics, and bioinformatic analysis for excremental validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We selected the vital genes with differential expression from the GSE26887 dataset. Based on the bioinformatics analysis, several parameters are determined to choose switchable genes involved in diabetic HF (DHF). We designed the protein\u2013protein interactions network to consider the nodes\u2019 degree, modularity, and betweenness centrality. Hence, we selected the interleukin (IL)-6 protein as a target for drug design and discovery to reduce diabetes complications in the heart. Here, H9c2 cell lines of rat embryonic cardiomyocytes induce HF using hyperglycemic and hyperlipidemic conditions. Real-time polymerase chain reaction evaluated the relative expression of SMAD7\/NRF-2\/STAT3. Furthermore, we assessed the concentration of IL-6 using the enzyme-linked immunosorbent assay technique.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Based on the bioinformatic analysis, we found that IL-6 with the highest network parameters score might be presented as a druggable protein in the DHF. Bioactive compounds and phytochemicals have potential strategies to manage DHF. LiUs decreased the expression level of the SMAD7 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001) and STAT3 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001), and increased the expression level of the NRF2 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001). In addition, LiUs significantly reduced the concentration of IL-6 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data proposed that LiUs regulated inflammation and triggered the antioxidant defense in HF. Moreover, LiUs could have potential approaches to managing and preventing DHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jmss.jmss_4_24","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T05:44:30Z","timestamp":1725342270000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics and Chemoinformatics Analysis Explored the Role of Linum usitatissimum in Diabetic Heart Conditions: Experimental Analysis in H9c2 Rat Embryonic Cardiomyocytes Cell Lines"],"prefix":"10.4103","volume":"14","author":[{"given":"Kamran","family":"Safavi","sequence":"first","affiliation":[{"name":"Department of Plant Biotechnology, Medicinal Plants Research Centre, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Hajibabaie","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran"},{"name":"Department of Physiology, Medicinal Plants Research Centre, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Abedpoor","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medicinal Plants Research Centre, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,9]]},"reference":[{"key":"R1-20240903","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF diabetes atlas:Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"R2-20240903","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/S0140-6736(12)60283-9","article-title":"Prediabetes: A high-risk state for diabetes development","volume":"379","author":"Tab\u00e1k","year":"2012","journal-title":"Lancet"},{"key":"R3-20240903","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.amjcard.2018.10.032","article-title":"Prevention of diabetes mellitus in patients with prediabetes","volume":"123","author":"Carris","year":"2019","journal-title":"Am J Cardiol"},{"key":"R4-20240903","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF diabetes atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"R5-20240903","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41581-020-0278-5","article-title":"Genetics of diabetes mellitus and diabetes complications","volume":"16","author":"Cole","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"R6-20240903","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","article-title":"The role of inflammation in diabetes: Current concepts and future perspectives","volume":"14","author":"Tsalamandris","year":"2019","journal-title":"Eur Cardiol Rev"},{"key":"R7-20240903","doi-asserted-by":"crossref","first-page":"151844","DOI":"10.1016\/j.acthis.2022.151844","article-title":"Physical activity ameliorates the function of organs via adipose tissue in metabolic diseases","volume":"124","author":"Abedpoor","year":"2022","journal-title":"Acta Histochem"},{"key":"R8-20240903","doi-asserted-by":"crossref","first-page":"e14480","DOI":"10.1111\/jfbc.14480","article-title":"Natural remedies medicine derived from flaxseed (secoisolariciresinol diglucoside, lignans, and ?-linolenic acid) improve network targeting efficiency of diabetic heart conditions based on computational chemistry techniques and pharmacophore modeling","volume":"46","author":"Hajibabaie","year":"2022","journal-title":"J Food Biochem"},{"key":"R9-20240903","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3892\/mmr.2020.11104","article-title":"Ischemic postconditioning attenuates the inflammatory response in ischemia\/reperfusion myocardium by upregulating miR-499 and inhibiting TLR2 activation","volume":"22","author":"Zhang","year":"2020","journal-title":"Mol Med Rep"},{"key":"R10-20240903","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/fsn3.2714","article-title":"Novel prevention insights into depletion of oxidative stress status through regular exercise and grape seed effective substance in heart ischemia rat model","volume":"10","author":"Zarei","year":"2022","journal-title":"Food Sci Nutr"},{"key":"R11-20240903","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1161\/CIRCRESAHA.114.300559","article-title":"Cardiac mitochondria and reactive oxygen species generation","volume":"114","author":"Chen","year":"2014","journal-title":"Circ Res"},{"key":"R12-20240903","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12933-015-0288-y","article-title":"Circulating interleukin-1? promotes endoplasmic reticulum stress-induced myocytes apoptosis in diabetic cardiomyopathy via interleukin-1 receptor-associated kinase-2","volume":"14","author":"Liu","year":"2015","journal-title":"Cardiovasc Diabetol"},{"key":"R13-20240903","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.2337\/db15-0568","article-title":"Methylglyoxal-induced endothelial cell loss and inflammation contribute to the development of diabetic cardiomyopathy","volume":"65","author":"Vulesevic","year":"2016","journal-title":"Diabetes"},{"key":"R14-20240903","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: From inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ Res"},{"key":"R15-20240903","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1093\/cvr\/cvx011","article-title":"An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy","volume":"113","author":"Frati","year":"2017","journal-title":"Cardiovasc Res"},{"key":"R16-20240903","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1161\/CIRCULATIONAHA.106.679597","article-title":"Diabetic cardiomyopathy revisited","volume":"115","author":"Boudina","year":"2007","journal-title":"Circulation"},{"key":"R17-20240903","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s12031-022-02086-8","article-title":"A cocktail of polyherbal bioactive compounds and regular mobility training as senolytic approaches in age-dependent Alzheimer's: The in silico analysis, lifestyle intervention in old age","volume":"73","author":"Hajibabaie","year":"2023","journal-title":"J Mol Neurosci"},{"key":"R18-20240903","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.nutres.2022.12.008","article-title":"Flaxseed supplementation significantly reduces hemoglobin A1C in patients with type 2 diabetes mellitus: A systematic review and meta-analysis","volume":"110","author":"Xi","year":"2023","journal-title":"Nutr Res"},{"key":"R19-20240903","doi-asserted-by":"crossref","first-page":"104622","DOI":"10.1016\/j.phrs.2019.104622","article-title":"Effect of flaxseed supplementation on lipid profile: An updated systematic review and dose-response meta-analysis of sixty-two randomized controlled trials","volume":"152","author":"Hadi","year":"2020","journal-title":"Pharmacol Res"},{"key":"R20-20240903","doi-asserted-by":"crossref","first-page":"95","DOI":"10.38001\/ijlsb.690295","article-title":"The important in terms of health of flax (Linum usitatissimum L.)","volume":"3","author":"Arslano\u011flu","year":"2020","journal-title":"Int J Life Sci Biotechnol"},{"key":"R21-20240903","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/AJRIMPS\/2018\/45045","article-title":"Anti hyperglycemic and anti hyperlipidemic activity of Linum usitatissimum and Glycyrrhiza glabra extracts in streptozotocin-induced diabetic rats","volume":"5","author":"Qureshi","year":"2018","journal-title":"Asian J Res Med Pharm Sci"},{"key":"R22-20240903","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ejlt.201600219","article-title":"The lignan (+)-secoisolariciresinol extracted from flax hulls is an effective protectant of linseed oil and its emulsion against oxidative damage","volume":"119","author":"Hano","year":"2017","journal-title":"Eur J Lipid Sci Technol"},{"key":"R23-20240903","first-page":"16","article-title":"Flaxseed: Medicinal Importance","author":"Patil","year":"2017","journal-title":"Dnyanamay J"},{"key":"R24-20240903","first-page":"43","article-title":"Flaxseed lignans and polyphenols enhanced activity in streptozotocin-induced diabetic rats","volume":"10","author":"Draganescu","year":"2021","journal-title":"Biology (Basel)"},{"key":"R25-20240903","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1089\/jmf.2011.0228","article-title":"Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms","volume":"15","author":"Colli","year":"2012","journal-title":"J Med Food"},{"key":"R26-20240903","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3390\/nu11051171","article-title":"Dietary flaxseed as a strategy for improving human health","volume":"11","author":"Parikh","year":"2019","journal-title":"Nutrients"},{"key":"R27-20240903","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/gme.0b013e318223b021","article-title":"Aphase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North central cancer treatment group N08C7","volume":"19","author":"Pruthi","year":"2012","journal-title":"Menopause"},{"key":"R28-20240903","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3945\/jn.109.113886","article-title":"Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women","volume":"140","author":"Simbalista","year":"2010","journal-title":"J Nutr"},{"key":"R29-20240903","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/02763869.2015.1082382","article-title":"Natural medicines: A complementary and alternative medicines tool combining natural standard and the natural medicines comprehensive database","volume":"34","author":"Vardell","year":"2015","journal-title":"Med Ref Serv Q"},{"key":"R30-20240903","doi-asserted-by":"crossref","first-page":"D488","DOI":"10.1093\/nar\/gkac1077","article-title":"RCSB Protein Data Bank (RCSB.org): Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence\/machine learning","volume":"51","author":"Burley","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"R31-20240903","doi-asserted-by":"crossref","first-page":"D1373","DOI":"10.1093\/nar\/gkac956","article-title":"PubChem 2023 update","volume":"51","author":"Kim","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"R32-20240903","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open babel: An open chemical toolbox","volume":"3","author":"O'Boyle","year":"2011","journal-title":"J Cheminform"},{"key":"R33-20240903","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera \u2013 A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"R35-20240903","doi-asserted-by":"crossref","first-page":"e1298","DOI":"10.1002\/wcms.1298","article-title":"Using PyMOL as a platform for computational drug design","volume":"7","author":"Yuan","year":"2017","journal-title":"Wiley Interdiscip Rev Comput Mol Sci"},{"key":"R36-20240903","first-page":"114","article-title":"Decrease in the inflammatory marker TNF-? after consumption of flaxseed by hypercholesterolemic rabbits","volume":"31","author":"Martins","year":"2018","journal-title":"Int J Cardiovasc Sci"},{"key":"R37-20240903","doi-asserted-by":"crossref","first-page":"154922","DOI":"10.1016\/j.cyto.2019.154922","article-title":"Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis","volume":"126","author":"Askarpour","year":"2020","journal-title":"Cytokine"},{"key":"R38-20240903","first-page":"1","article-title":"Dietary consumption on glycemic control among prediabetes: A review of the literature","volume":"9","author":"Thipsawat","year":"2023","journal-title":"SAGE Open Nurs"},{"key":"R39-20240903","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12986-021-00619-3","article-title":"Comparisons of the effects of different flaxseed products consumption on lipid profiles, inflammatory cytokines and anthropometric indices in patients with dyslipidemia related diseases: Systematic review and a dose-response meta-analysis of randomized controlled trials","volume":"18","author":"Yang","year":"2021","journal-title":"Nutr Metab (Lond)"},{"key":"R40-20240903","doi-asserted-by":"crossref","first-page":"102852","DOI":"10.1016\/j.ctim.2022.102852","article-title":"Effect of flaxseed (Linum usitatissimum) supplementation on glycemic control and insulin resistance in prediabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials","volume":"70","author":"Villarreal-Renteria","year":"2022","journal-title":"Complement Ther Med"},{"key":"R41-20240903","doi-asserted-by":"crossref","first-page":"6820","DOI":"10.1002\/fsn3.3662","article-title":"Pharmacological, nutraceutical, and nutritional properties of flaxseed (Linum usitatissimum): An insight into its functionality and disease mitigation","volume":"11","author":"Noreen","year":"2023","journal-title":"Food Sci Nutr"},{"key":"R42-20240903","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s13197-016-2477-4","article-title":"Therapeutic effect of Linum usitatissimum L. in STZ-nicotinamide induced diabetic nephropathy via inhibition of AGE's and oxidative stress","volume":"54","author":"Kaur","year":"2017","journal-title":"J Food Sci Technol"},{"key":"R43-20240903","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1055\/s-0039-1678691","article-title":"Importance of flaxseed and its components in the management of hypertension","volume":"28","author":"Prasad","year":"2019","journal-title":"Int J Angiol"},{"key":"R44-20240903","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijbiomac.2020.06.270","article-title":"Purification and characterization of non-enzymatic glycoprotein (NEGp) from flax seed buffer extract that exhibits anticoagulant and antiplatelet activity","volume":"163","author":"Nandish","year":"2020","journal-title":"Int J Biol Macromol"},{"key":"R45-20240903","first-page":"16","article-title":"Antimicrobial effect of flaxseed (Linum usitatissimum) on periodontal pathogens: An in vitro study","volume":"7","author":"Badiger","year":"2019","journal-title":"Int J Herb Med"},{"key":"R46-20240903","doi-asserted-by":"crossref","first-page":"892","DOI":"10.3390\/antiox11050892","article-title":"Flaxseed ethanol extracts'antitumor, antioxidant, and anti-inflammatory potential","volume":"11","author":"Chera","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"R47-20240903","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1161\/CIRCRESAHA.118.314555","article-title":"Metabolic syndrome exacerbates pulmonary hypertension due to left heart disease","volume":"125","author":"Ranchoux","year":"2019","journal-title":"Circ Res"},{"key":"R48-20240903","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1074\/jbc.M607622200","article-title":"Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between keap1 and cullin3","volume":"282","author":"Gao","year":"2007","journal-title":"J Biol Chem"},{"key":"R49-20240903","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.fsi.2017.06.036","article-title":"\u03b1-lipoic acid ameliorates n-3 highly-unsaturated fatty acids induced lipid peroxidation via regulating antioxidant defenses in grass carp (Ctenopharyngodon idellus)","volume":"67","author":"Shi","year":"2017","journal-title":"Fish Shellfish Immunol"}],"container-title":["Journal of Medical Signals &amp; Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/jmss.jmss_4_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:32:49Z","timestamp":1787772769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/jmss.jmss_4_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.4103\/jmss.jmss_4_24","relation":{},"ISSN":["2228-7477"],"issn-type":[{"value":"2228-7477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-01-08","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}