{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:29:25Z","timestamp":1792132165865,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fibromyalgia (FM) is a common chronic pain syndrome that affects 1% to 5% of the population. We aimed to investigate the role of endothelial dysfunction and autophagy in fibromyalgia-related vascular and cerebral cortical changes in a reserpine-induced rat model of fibromyalgia at the histological and molecular levels and to study the ameliorative effect of fisetin. Forty adult female albino rats were divided into four groups (10 each): two control groups, the reserpine-induced fibromyalgia group, and the fisetin-treated group. The carotid arteries and brains of the animals were dissected. Frozen tissue samples were used for total RNA extraction and qPCR analysis of eNOS, caspase-3, Bcl-2, LC-3, BECN-1, CHOP, and TNF-\u03b1 expression. Histological, immunohistochemical (eNOS), and ultrastructure studies were conducted. The carotid arteries revealed excessive autophagy and endothelial, vascular, and apoptotic changes. The cerebral cortex showed similar findings apart from endoplasmic reticulum stress. Additionally, there was decreased gene expression of eNOS and Bcl-2 and increased expression of caspase-3, LC-3, BECN-1, CHOP, and TNF-\u03b1. In the fisetin-treated rats, improvements in the histological and molecular results were detected. In conclusion, oxidative stress, enhanced apoptosis, and excessive autophagy are fundamental pathophysiologic mechanisms of reserpine-induced fibromyalgia. Moreover, fisetin has an ameliorative effect against fibromyalgia.<\/jats:p>","DOI":"10.3390\/cells11010048","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T08:38:46Z","timestamp":1640335126000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Evaluation of Endothelial Dysfunction and Autophagy in Fibromyalgia-Related Vascular and Cerebral Cortical Changes and the Ameliorative Effect of Fisetin"],"prefix":"10.3390","volume":"11","author":[{"given":"Fatma Mohamed","family":"Ghoneim","sequence":"first","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-2723","authenticated-orcid":false,"given":"Salwa Mohamed","family":"Abo-Elkhair","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-6184","authenticated-orcid":false,"given":"Ayman Zaky","family":"Elsamanoudy","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"},{"name":"Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21465, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia A.","family":"Shabaan","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/art.38905","article-title":"The prevalence of fibromyalgia in the general population: A comparison of the American College of Rheumatology 1990, 2010, and modified 2010 classification criteria","volume":"67","author":"Jones","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3904\/kjim.2015.30.4.531","article-title":"Quantitative analysis of nailfold capillary morphology in patients with fibromyalgia","volume":"30","author":"Choi","year":"2015","journal-title":"Korean J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.3904\/kjim.2015.196","article-title":"A neurometabolite study of chronic daily headache in patients with systemic lupus erythematosus using magnetic resonance spectroscopy: Comparison with fibromyalgia patients and healthy controls","volume":"31","author":"Son","year":"2016","journal-title":"Korean J. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.amjmed.2009.09.008","article-title":"Pathophysiology of fibromyalgia","volume":"122","author":"Bradley","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/ehf2.12633","article-title":"Peripheral endothelial dysfunction in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"7","author":"Scherbakov","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.7754\/Clin.Lab.2017.171024","article-title":"Could Endocan, a Marker of Inflammation and Endothelial Dysfunction, be a New Diagnostic Marker for Fibromyalgia?","volume":"64","author":"Mertoglu","year":"2018","journal-title":"Clin. Lab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/path.2697","article-title":"Autophagy: Cellular and molecular mechanisms","volume":"2010","author":"Glick","year":"2010","journal-title":"J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.tcb.2003.12.002","article-title":"Autophagy: In sickness and in health","volume":"14","author":"Cuervo","year":"2004","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2147\/OARRR.S257470","article-title":"Mitochondrial Imbalance as a New Approach to the Study of Fibromyalgia","volume":"12","year":"2020","journal-title":"Open Access Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1007\/s10350-003-0119-1","article-title":"Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: Results of a randomized, controlled, clinical trial","volume":"47","author":"Nicolai","year":"2004","journal-title":"Dis. Colon Rectum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1093\/hmg\/ddq460","article-title":"ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington\u2019s disease","volume":"20","author":"Maher","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","first-page":"1343","article-title":"Attenuation of reserpine-induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol","volume":"19","author":"Yao","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.bbr.2011.09.023","article-title":"Different pathophysiology underlying animal models of fibromyalgia and neuropathic pain: Comparison of reserpine-induced myalgia and chronic constriction injury rats","volume":"226","author":"Nagakura","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.fitote.2012.01.010","article-title":"Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy","volume":"83","author":"Kandhare","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gamble, M. (2008). The Hematoxylins and Eosin. Theory and Practice of Histological Techniques, Elsevier.","DOI":"10.1016\/B978-0-443-10279-0.50016-6"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bancroft, J.D., and Gamble, M. (2008). Electron microscopy. Theory and Practice of Histological Techniques, Churchill Livingstone Elsevier. [6th ed.].","DOI":"10.1016\/B978-0-443-10279-0.50010-5"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s11418-008-0228-1","article-title":"Antihyperglycemic and antioxidative potential of Matricaria chamomilla L. in streptozotocin-induced diabetic rats","volume":"62","author":"Cemek","year":"2008","journal-title":"J. Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xie, Y., Li, J., Fan, G., Qi, S., and Li, B. (2014). Reperfusion promotes mitochondrial biogenesis following focal cerebral ischemia in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092443"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"604275","DOI":"10.1155\/2015\/604275","article-title":"A novel rat model of vitamin D deficiency: Safe and rapid induction of vitamin D and calcitriol deficiency without hyperparathyroidism","volume":"2015","author":"Stavenuiter","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_20","first-page":"873","article-title":"Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage","volume":"15","author":"He","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_21","first-page":"216","article-title":"Autophagy inhibitor 3-methyladenine regulates the expression of LC3, Beclin-1 and ZnTs in rat cerebral cortex following recurrent neonatal seizures","volume":"1","author":"Ni","year":"2010","journal-title":"World J. Emerg. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00418-019-01823-2","article-title":"Molecular and ultrastructure study of endoplasmic reticulum stress in hepatic steatosis: Role of hepatocyte nuclear factor 4\u03b1 and inflammatory mediators","volume":"153","author":"Ghoneim","year":"2020","journal-title":"Histochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0891-5849(93)90035-S","article-title":"Comparative evaluation of thiobarbituric acid methods for the determination of malondialdehydes in biological materials","volume":"15","author":"Draper","year":"1993","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pain.2009.05.024","article-title":"Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia","volume":"146","author":"Nagakura","year":"2009","journal-title":"Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1186\/ar4402","article-title":"Animal models of fibromyalgia","volume":"15","author":"DeSantana","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s11926-012-0277-z","article-title":"Peripheral and central mechanisms of fatigue in inflammatory and noninflammatory rheumatic diseases","volume":"14","author":"Staud","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jneuroim.2011.10.013","article-title":"Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels","volume":"242","author":"Kadetoff","year":"2012","journal-title":"J. Neuroimmunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Montoro, C.I., Duschek, S., Schuepbach, D., Gandarillas, M.A., and Reyes Del Paso, G.A. (2018). Cerebral blood flow variability in fi-bromyalgia syndrome: Relationships with emotional, clinical and functional variables. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204267"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ejpain.2007.07.007","article-title":"Attenuated adrenergic responses to exercise in women with fibromyalgia: A controlled study","volume":"12","author":"Giske","year":"2008","journal-title":"Eur. J. Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"596","DOI":"10.4070\/kcj.2011.41.10.596","article-title":"Arterial stiffness in female patients with fibromyalgia and its relationship to chronic emotional and physical stress","volume":"41","author":"Lee","year":"2011","journal-title":"Korean Circ. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/01.PSY.0000035720.08842.9F","article-title":"Associations between psychological traits and endothelial function in postmenopausal women","volume":"65","author":"Harris","year":"2003","journal-title":"Psychosom. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1161\/01.STR.31.5.1136","article-title":"Regional myocardial perfusion after experimental subarachnoid hemorrhage","volume":"31","author":"Zaroff","year":"2000","journal-title":"Stroke"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.3892\/mmr.2017.7395","article-title":"Association between endothelin 1 and fibromyalgia syndrome","volume":"16","author":"Nah","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fgene.2015.00112","article-title":"Age-related vascular stiffening causes and consequences","volume":"6","author":"Kohn","year":"2015","journal-title":"Front. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1161\/hc0202.101970","article-title":"Nitric oxide regulates local arterial distensibility in vivo","volume":"105","author":"Wilkinson","year":"2002","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mito.2015.01.010","article-title":"Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia","volume":"21","author":"Cordero","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_38","first-page":"165","article-title":"Nitric oxide, lipid peroxidation products, and antioxidants in primary fibromyalgia and correlation with disease severity","volume":"39","author":"Shukla","year":"2020","journal-title":"J. Med. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s00296-008-0738-x","article-title":"Serum antioxidants and nitric oxide levels in fibromyalgia: A controlled study","volume":"29","author":"Sendur","year":"2009","journal-title":"Rheumatol. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1124\/jpet.103.064154","article-title":"A Newly Identified Role for Superoxide in Inflammatory Pain","volume":"309","author":"Wang","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1526-4637.2009.00642.x","article-title":"Arginase, NOS activities, and clinical features in fibromyalgia patients","volume":"10","author":"Cimen","year":"2009","journal-title":"Pain Med."},{"key":"ref_42","first-page":"548","article-title":"Effects of Nitric Oxide Synthase Inhibition on Fiber-Type Composition, Mitochondrial Biogenesis, and SIRT1 Expression in Rat Skeletal Muscle","volume":"14","author":"Suwa","year":"2015","journal-title":"J. Sports Sci. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s00296-005-0079-y","article-title":"Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: Etiologic and therapeutic concerns","volume":"26","author":"Ozgocmen","year":"2006","journal-title":"Rheumatol. Int."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dolcino, M., Tinazzi, E., Puccetti, A., and Lunardi, C. (2020). Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061814"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1038\/s41598-017-17715-1","article-title":"Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R17","DOI":"10.1186\/ar2918","article-title":"Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: Implications in the pathogenesis of the disease","volume":"12","author":"Cordero","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"C104","DOI":"10.1152\/ajpcell.00313.2018","article-title":"Blocking the REDD1\/TXNIP axis ameliorates LPS-induced vascular endothelial cell injury through repressing oxidative stress and apoptosis","volume":"316","author":"Hou","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fncel.2019.00353","article-title":"Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome","volume":"13","author":"Theoharides","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00248","DOI":"10.1002\/prp2.248","article-title":"Fibromyalgia syndrome: Metabolic and autophagic processes in intermittent cold stress mice","volume":"4","author":"Oezel","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.bbamcr.2009.03.002","article-title":"Mitophagy","volume":"1793","author":"Tolkovsky","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_52","first-page":"233","article-title":"Hypoxia and related conditions","volume":"1","author":"Auer","year":"2002","journal-title":"Greenfield\u2019s Neuropathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.redox.2017.02.014","article-title":"Oxidative stress and apoptosis after acute respiratory hy-poxia and reoxygenation in rat brain","volume":"12","author":"Alva","year":"2017","journal-title":"Redox Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/ars.2014.5851","article-title":"Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease","volume":"21","author":"Cao","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"704334","DOI":"10.3389\/fncel.2021.704334","article-title":"Mechanism of Endoplasmic Reticulum Stress in Cerebral Ischemia","volume":"15","author":"Han","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegeneration","volume":"13","author":"Hetz","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"117847","DOI":"10.1016\/j.lfs.2020.117847","article-title":"Icariin protects neurons from endoplasmic reticulum stress-induced apoptosis after OGD\/R injury via suppressing IRE1\u03b1-XBP1 signaling pathway","volume":"255","author":"Mo","year":"2020","journal-title":"Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molcel.2017.06.017","article-title":"The unfolded protein response and cell fate control","volume":"69","author":"Hetz","year":"2018","journal-title":"Mol. Cell."},{"key":"ref_59","first-page":"4070","article-title":"Astragalin alleviates ischemia\/reperfusion-induced brain injury via suppression of endoplasmic reticulum stress","volume":"22","author":"Liu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9087873","DOI":"10.1155\/2020\/9087873","article-title":"Astragaloside IV reduces cerebral ischemia\/reperfusion-induced blood-brain barrier permeability in rats by inhibiting ER stress-mediated apoptosis","volume":"2020","author":"Hou","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-981-15-0602-4_8","article-title":"Endoplasmic Reticulum Stress and Autophagy","volume":"1206","author":"Qi","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","first-page":"20","article-title":"Fisetin protects against rotenone-induced neurotoxicity through signaling pathway","volume":"11","author":"Rajendran","year":"2019","journal-title":"Front. Biosci. (Elite Ed.)"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"162750","DOI":"10.1155\/2013\/162750","article-title":"Chemistry and biological activities of flavonoids: An overview","volume":"2013","author":"Kumar","year":"2013","journal-title":"Sci. World J."},{"key":"ref_64","first-page":"19","article-title":"Antioxidant and anti-inflammatory medicinal plants have potential role in the treatment of cardiovascular disease: A review","volume":"7","author":"Adegbola","year":"2017","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1038\/s41598-020-59894-4","article-title":"Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity","volume":"10","author":"Rodius","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_66","first-page":"65","article-title":"Fisetin inhibits inflammation and induces autophagy by mediating PI3K\/AKT\/mTOR signaling in LPS-induced RAW264.7 cells","volume":"25","author":"Sun","year":"2021","journal-title":"Food Nutr. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.abb.2014.06.034","article-title":"Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma","volume":"563","author":"Syed","year":"2014","journal-title":"Arch. Biochem. Biophys."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:57Z","timestamp":1760169177000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["cells11010048"],"URL":"https:\/\/doi.org\/10.3390\/cells11010048","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]}}}