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Forchlorfenuron (KT-30), a cytokinin-like plant growth regulator widely used on fruits such as kiwifruit, grapes, and watermelon, has been reported to elevate serum cholesterol levels, suggesting potential atherogenic effects. However, whether KT-30 induces oxidative stress and accelerates atherosclerosis remains unknown. Here, apolipoprotein E-deficient (apoE\u2212\/\u2212) mice were orally administered KT-30 (5 mg\/kg\/day) for four weeks. KT-30 significantly accelerated atherosclerotic lesion formation, elevated plasma cholesterol levels, upregulated scavenger receptors SR-A and CD36, and downregulated ABCA1 and LXR\u03b1, indicating impaired reverse cholesterol transport and enhanced foam cell formation. KT-30 also increased pro-inflammatory cytokines (IL-1\u03b2, IL-6, MIP-2) and aortic expression of F4\/80 and VCAM-1. Critically, KT-30 exposure was associated with elevated oxidative stress markers, as evidenced by elevated plasma MDA levels, increased aortic 4-HNE immunostaining, and upregulation of NOX-1\/4. In the liver, KT-30 induced lipid accumulation, characterized by elevated cholesterol and free fatty acids, accompanied by SREBP-1\/2-driven de novo lipogenesis and impaired lipoprotein uptake. Proteomic analysis revealed significant alterations in mitochondrial oxidative phosphorylation- and sirtuin signaling-related protein expression. Taken together, KT-30-associated oxidative stress, accompanied by upregulation of NOX-1\/4 and alterations in mitochondrial pathway-related protein expression, may represent an important mechanistic link between lipid homeostasis disruption and accelerated atherosclerosis in apoE\u2212\/\u2212 mice, highlighting the potential pro-atherogenic effects of KT-30 in a susceptible experimental model and providing mechanistic evidence that warrants further investigation of its possible cardiovascular implications.<\/jats:p>","DOI":"10.3390\/antiox15080953","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:55:11Z","timestamp":1785419711000},"page":"953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Plant Growth Regulator Forchlorfenuron (KT-30) Drives Atherosclerosis Progression via Lipid Homeostasis Disruption: Evidence from ApoE-Deficient Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Chia-Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-An","family":"Hu","sequence":"additional","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Sheng","family":"Chuang","sequence":"additional","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Yu","family":"Tang","sequence":"additional","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0748-0513","authenticated-orcid":false,"given":"Chiao-Po","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-4062","authenticated-orcid":false,"given":"Tzong-Shyuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12471-017-0959-2","article-title":"Pathophysiology and treatment of atherosclerosis: Current view and future perspective on lipoprotein modification treatment","volume":"25","author":"Bergheanu","year":"2017","journal-title":"Neth. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102108","DOI":"10.1016\/j.redox.2021.102108","article-title":"Hyperuricemia induces endothelial dysfunction and accelerates atherosclerosis by disturbing the asymmetric dimethylarginine\/dimethylarginine dimethylaminotransferase 2 pathway","volume":"46","author":"Lee","year":"2021","journal-title":"Redox Biol."},{"key":"ref_3","first-page":"927","article-title":"Atherosclerosis: Process, indicators, risk factors and new hopes","volume":"5","author":"Setorki","year":"2014","journal-title":"Int. J. Prev. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1161\/CIRCRESAHA.115.307611","article-title":"Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease","volume":"118","author":"Herrington","year":"2016","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13209","DOI":"10.1111\/apha.13209","article-title":"CCN family member 1 deregulates cholesterol metabolism and aggravates atherosclerosis","volume":"225","author":"Zhao","year":"2019","journal-title":"Acta Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev.bi.52.070183.001255","article-title":"Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis","volume":"52","author":"Brown","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1073\/pnas.84.9.2995","article-title":"Oxidatively modified low density lipoproteins: A potential role in recruitment and retention of monocyte\/macrophages during atherogenesis","volume":"84","author":"Quinn","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/apha.12005","article-title":"Essential role of transient receptor potential vanilloid type 1 in evodiamine--mediated protection against atherosclerosis","volume":"207","author":"Wei","year":"2013","journal-title":"Acta Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00204-014-1377-5","article-title":"Di-(2-ethylhexyl) phthalate accelerates atherosclerosis in apolipoprotein E-deficient mice","volume":"90","author":"Zhao","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/jcb.22667","article-title":"Anti-atherogenic effect of berberine on LXRa-ABCA1-dependent cholesterol efflux in macrophages","volume":"111","author":"Lee","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/cvr\/cvq226","article-title":"EGb761 ameliorates the formation of foam cells by regulating the expression of SR-A and ABCA1: Role of haem oxygenase-1","volume":"88","author":"Tsai","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chen, C.H., Hsia, C.C., Hu, P.A., Yeh, C.H., Chen, C.T., Peng, C.L., Wang, C.H., and Lee, T.S. (2022). Bromelain ameliorates atherosclerosis by activating the TFEB-mediated autophagy and antioxidant pathways. Antioxidants, 12.","DOI":"10.3390\/antiox12010072"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1055\/s-0032-1306423","article-title":"Dyslipidemia in patients with nonalcoholic fatty liver disease","volume":"32","author":"Chatrath","year":"2012","journal-title":"Semin. Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1463-1326.2010.01275.x","article-title":"Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c","volume":"12","author":"Foufelle","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.jhep.2008.12.016","article-title":"Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH","volume":"50","author":"Caballero","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"An, H.J., Kim, J.Y., Gwon, M.G., Gu, H., Kim, H.J., Leem, J., Youn, S.W., and Park, K.K. (2020). Beneficial effects of SREBP decoy oligodeoxynucleotide in an animal model of hyperlipidemia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020552"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/01140671.1992.10422328","article-title":"Effect of a forchlorfenuron dip on kiwifruit fruit size","volume":"20","author":"Blank","year":"1992","journal-title":"N. Z. J. Crop Hortic. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/03601230701551475","article-title":"Analysis and residue levels of forchlorfenuron (CPPU) in watermelons","volume":"42","author":"Valverde","year":"2007","journal-title":"J. Environ. Sci. Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.21273\/HORTSCI.43.1.173","article-title":"Effects of forchlorfenuron and abscisic acid on the quality of \u2018Flame Seedless\u2019 grapes","volume":"43","author":"Peppi","year":"2008","journal-title":"HortScience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10207","DOI":"10.1021\/acs.jafc.9b03855","article-title":"180 Day repeated-dose toxicity study on forchlorfenuron in Sprague-Dawley rats and its effects on the production of steroid hormones","volume":"67","author":"Bu","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112700","DOI":"10.1016\/j.ecoenv.2021.112700","article-title":"Dissipation and risk assessment of forchlorfenuron and its major metabolites in oriental melon under greenhouse cultivation","volume":"225","author":"Wang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_23","unstructured":"Australian Pesticides and Veterinary Medicines Authority (2005). Evaluation of the New Active Forchlorfenuron in the Product SITOFEX 10 EC Plant Growth Regulator."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"C7","DOI":"10.1016\/j.jacc.2005.09.068","article-title":"Pathogenesis of atherosclerosis","volume":"47","author":"Falk","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","first-page":"2758","article-title":"Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice","volume":"119","author":"Sundaresan","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1089\/ars.2012.4713","article-title":"SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a\/PGC-1\u03b1 complex","volume":"19","author":"Olmos","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1080\/17441692.2020.1808693","article-title":"Pesticide exposure and risk of cardiovascular disease: A systematic review","volume":"17","author":"Zago","year":"2022","journal-title":"Glob. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"592","DOI":"10.34172\/aim.2023.86","article-title":"Insights into organochlorine pesticides exposure in the development of cardiovascular diseases: A systematic review","volume":"26","author":"Mohammadkhani","year":"2023","journal-title":"Arch. Iran. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/28406","article-title":"Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis","volume":"394","author":"Shih","year":"1998","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/nprot.2006.468","article-title":"In-gel digestion for mass spectrometric characterization of proteins and proteomes","volume":"1","author":"Shevchenko","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/qjmed\/hci136","article-title":"Reverse cholesterol transport and cholesterol efflux in atherosclerosis","volume":"98","author":"Ohashi","year":"2005","journal-title":"QJM"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.2174\/0929867321666131227162950","article-title":"Obesity, hypertension and hypercholesterolemia as risk factors for atherosclerosis leading to ischemic events","volume":"21","author":"Pretorius","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1161\/ATVBAHA.107.154864","article-title":"Scavenger receptor A and CD36 are implicated in mediating platelet activation induced by oxidized low-density lipoproteins","volume":"27","author":"McGregor","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tem.2017.02.001","article-title":"SR-BI: A multifunctional receptor in cholesterol homeostasis and atherosclerosis","volume":"28","author":"Linton","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1097-2765(01)00164-2","article-title":"A PPAR\u03b3-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis","volume":"7","author":"Chawla","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_36","first-page":"736","article-title":"Liver X receptors (LXRs). Part I: Structure, function, regulation of activity, and role in lipid metabolism","volume":"61","author":"Horoszewicz","year":"2007","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.immunol.021908.132620","article-title":"Immune and inflammatory mechanisms of atherosclerosis","volume":"27","author":"Galkina","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/MOL.0b013e328363d298","article-title":"Myeloid cells in atherosclerosis: A delicate balance of anti-inflammatory and proinflammatory mechanisms","volume":"24","author":"Koltsova","year":"2013","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1161\/CIRCULATIONAHA.104.510073","article-title":"Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: Validation using a novel monocyte chemoattractant protein monoclonal antibody","volume":"111","author":"Lutgens","year":"2005","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/01.CIR.2.2.161","article-title":"Blood lipids and human atherosclerosis","volume":"2","author":"Gofman","year":"1950","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-3-319-22380-3_5","article-title":"Mechanistic role of microRNAs in coupling lipid metabolism and atherosclerosis","volume":"887","author":"Santulli","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.biochi.2004.09.018","article-title":"SREBP transcription factors: Master regulators of lipid homeostasis","volume":"86","author":"Hegarty","year":"2004","journal-title":"Biochimie"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1194\/jlr.C066712","article-title":"Srebp2: A master regulator of sterol and fatty acid synthesis","volume":"57","author":"Madison","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1194\/jlr.M048819","article-title":"High density lipoprotein metabolism in low density lipoprotein receptor-deficient mice","volume":"55","author":"Rinninger","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hu, P.A., Chen, C.H., Guo, B.C., Kou, Y.R., and Lee, T.S. (2020). Bromelain confers protection against the non-alcoholic fatty liver disease in male C57BL\/6 mice. Nutrients, 12.","DOI":"10.3390\/nu12051458"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12944-022-01629-7","article-title":"Correlation of cholesteryl ester metabolism to pathogenesis, progression and disparities in colorectal cancer","volume":"21","author":"Liu","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.atherosclerosis.2004.03.015","article-title":"Interactions between common genetic polymorphisms in ABCG5\/G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin","volume":"175","author":"Kajinami","year":"2004","journal-title":"Atherosclerosis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1194\/jlr.M400402-JLR200","article-title":"On the hepatic mechanism of HDL assembly by the ABCA1\/apoA-I pathway","volume":"46","author":"Tsujita","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1194\/jlr.M093112","article-title":"The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes","volume":"60","author":"Chitraju","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_50","first-page":"221","article-title":"Adipose triglyceride lipase regulation: An overview","volume":"19","author":"Cerk","year":"2018","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1194\/jlr.R200014-JLR200","article-title":"Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly","volume":"44","author":"Hussain","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"857142","DOI":"10.1155\/2012\/857142","article-title":"Protection from metabolic dysregulation, obesity, and atherosclerosis by citrus flavonoids: Activation of hepatic PGC1\u03b1-mediated fatty acid oxidation","volume":"2012","author":"Mulvihill","year":"2012","journal-title":"PPAR Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1476-511X-9-117","article-title":"The activation of CD14, TLR4, and TLR2 by mmLDL induces IL-1\u03b2, IL-6, and IL-10 secretion in human monocytes and macrophages","volume":"9","author":"Zenteno","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_54","first-page":"1358","article-title":"The role of cytokines in the development of atherosclerosis","volume":"81","author":"Fatkhullina","year":"2016","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.phrs.2016.10.015","article-title":"NADPH oxidases and vascular remodeling in cardiovascular diseases","volume":"114","author":"Aguado","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_56","first-page":"1","article-title":"Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis","volume":"131","author":"Busch","year":"2016","journal-title":"Adv. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.3748\/wjg.v13.i26.3540","article-title":"Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease","volume":"13","author":"Qureshi","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/nm.2297","article-title":"Brown adipose tissue activity controls triglyceride clearance","volume":"17","author":"Bartelt","year":"2011","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1152\/physrev.00015.2003","article-title":"Brown adipose tissue: Function and physiological significance","volume":"84","author":"Cannon","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ma, Y., Lee, G., Heo, S.Y., and Roh, Y.S. (2021). Oxidative stress is a key modulator in the development of nonalcoholic fatty liver disease. Antioxidants, 11.","DOI":"10.3390\/antiox11010091"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"30954","DOI":"10.1074\/jbc.M313571200","article-title":"Liver fatty acid-binding protein gene ablation inhibits branched-chain fatty acid metabolism in cultured primary hepatocytes","volume":"279","author":"Atshaves","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Khan, T., Waseem, R., Zehra, Z., Aiman, A., Bhardwaj, P., Ansari, J., Hassan, M.I., and Islam, A. (2022). Mitochondrial dysfunction: Pathophysiology and mitochondria-targeted drug delivery approaches. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122657"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Cojocaru, K.A., Luchian, I., Goriuc, A., Antoci, L.M., Ciobanu, C.G., Popescu, R., Vlad, C.E., Blaj, M., and Foia, L.G. (2023). Mitochondrial dysfunction, oxidative stress, and therapeutic strategies in diabetes, obesity, and cardiovascular disease. Antioxidants, 12.","DOI":"10.3390\/antiox12030658"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cortassa, S., Sollott, S.J., and Aon, M.A. (2017). Mitochondrial respiration and ROS emission during \u03b2-oxidation in the heart: An experimental-computational study. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005588"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41598-017-18530-4","article-title":"Loss of the mitochondrial fatty acid \u03b2-oxidation protein medium-chain acyl-coenzyme a dehydrogenase disrupts oxidative phosphorylation protein complex stability and function","volume":"8","author":"Lim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"28738","DOI":"10.1074\/jbc.M112.375915","article-title":"Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion","volume":"287","author":"Shrestha","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ravelojaona, M., Girouard, J., Kana Tsapi, E.S., Chambers, M., Vaillancourt, C., Van Themsche, C., Thornton, C.A., and Reyes-Moreno, C. (2024). Oncostatin M and STAT3 signaling pathways support human trophoblast differentiation by inhibiting inflammatory stress in response to IFN\u03b3 and GM-CSF. Cells, 13.","DOI":"10.3390\/cells13030229"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1186\/s13054-025-05628-9","article-title":"Cell-specific expression and signaling of glucocorticoid receptor isoforms over time in critically ill patients with a low inflammatory response","volume":"29","author":"Poupouzas","year":"2025","journal-title":"Crit. Care"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e13033","DOI":"10.1111\/pim.13033","article-title":"Unveiling the role of endoplasmic reticulum stress pathways in canine demodicosis","volume":"46","author":"Kelly","year":"2024","journal-title":"Parasite Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"120080","DOI":"10.1016\/j.envpol.2022.120080","article-title":"Ractopamine at legal residue dosage accelerates atherosclerosis by inducing endothelial dysfunction and promoting macrophage foam cell formation","volume":"313","author":"Chen","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"154847","DOI":"10.1016\/j.metabol.2021.154847","article-title":"Atypical antipsychotic drugs deregulate the cholesterol metabolism of macrophage-foam cells by activating NOX-ROS-PPAR\u03b3-CD36 signaling pathway","volume":"123","author":"Chen","year":"2021","journal-title":"Metabolism"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"117958","DOI":"10.1016\/j.biopha.2025.117958","article-title":"Atypical antipsychotics impair the lipid-lowering and pleiotropic effects of simvastatin via activation of the ADMA-NOX-ROS pathway","volume":"185","author":"Chen","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.atherosclerosis.2011.02.028","article-title":"Role for Nox1 NADPH oxidase in atherosclerosis","volume":"216","author":"Sheehan","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e000492","DOI":"10.1161\/JAHA.113.000492","article-title":"Bisphenol A increases atherosclerosis in pregnane X receptor-humanized ApoE deficient mice","volume":"3","author":"Sui","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"EFSA (European Food Safety Authority), Arena, M., Auteri, D., Barmaz, S., Bellisai, G., Brancato, A., Brocca, D., Bura, L., Byers, H., and Chiusolo, A. (2017). Peer review of the pesticide risk assessment of the active substance forchlorfenuron. 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