{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:11:47Z","timestamp":1792102307586,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health and Wealth Project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg\/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.<\/jats:p>","DOI":"10.3390\/ijms232214489","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T02:59:22Z","timestamp":1669085962000},"page":"14489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Essential Hypertension and Oxidative Stress: Novel Future Perspectives"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-0436","authenticated-orcid":false,"given":"Caterina","family":"Franco","sequence":"first","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Sciatti","sequence":"additional","affiliation":[{"name":"Cardiology Unit 1, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6895-7106","authenticated-orcid":false,"given":"Gaia","family":"Favero","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-0308","authenticated-orcid":false,"given":"Francesca","family":"Bonomini","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"},{"name":"Interdepartmental University Center of Research \u201cAdaption and Regeneration of Tissues and Organs-(ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"},{"name":"Italian Society of Orofacial Pain (SISDO), 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-6104","authenticated-orcid":false,"given":"Enrico","family":"Vizzardi","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Diseases, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-5846","authenticated-orcid":false,"given":"Rita","family":"Rezzani","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"},{"name":"Interdepartmental University Center of Research \u201cAdaption and Regeneration of Tissues and Organs-(ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"},{"name":"Italian Society of Orofacial Pain (SISDO), 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153701","DOI":"10.1016\/j.prp.2021.153701","article-title":"MicroRNAs and exosomes: Cardiac stem cells in heart diseases","volume":"229","author":"Maleki","year":"2022","journal-title":"Pathol.-Res. Pract."},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2021, August 25). Blood Pressure. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hypertension."},{"key":"ref_3","unstructured":"World Health Organization (WHO) (2021, August 25). Raised Blood Pressure. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hypertension."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2014, January 10). A Global Brief on Hypertension. Available online: www.who.int\/cardiovascular_diseases\/publications\/global_brief_hypertension\/en\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/1440-1681.12942","article-title":"Role of melatonin in blood pressure regulation: An adjunct anti-hypertensive agent","volume":"45","author":"Baker","year":"2018","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1111\/joim.13352","article-title":"Hypertension genetics past, present and future applications","volume":"290","author":"Olczak","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1136\/heartjnl-2016-309573","article-title":"Trends in the epidemiology of cardiovascular disease in the UK","volume":"102","author":"Bhatnagar","year":"2016","journal-title":"Heart"},{"key":"ref_8","unstructured":"Iqbal, A.M., and Jamal, S.F. (2022). Essential Hypertension. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0146-2806(03)00017-3","article-title":"The heart, kidney, and brain as target organs in hypertension","volume":"28","author":"Mensah","year":"2003","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1177\/1074248416660622","article-title":"Melatonin and Human Cardiovascular Disease","volume":"22","author":"Bahammam","year":"2017","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kostov, K. (2021). The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation. Life, 11.","DOI":"10.3390\/life11090986"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chen, S., Chen, R., Zhang, T., Shaowei, L., Zhou, C., Bi, Z., Huangyuan, L., and Siying, W. (2018). Relationship of cardiovascular disease risk factors and noncoding RNAs with hypertension: A case-control study. BMC Cardiovasc. Disord., 18.","DOI":"10.1186\/s12872-018-0795-3"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gavrilova, A., Bandere, D., Rutkovska, I., \u0160mits, D., Mauri\u0146a, B., Poplavska, E., and Urt\u0101ne, I. (2019). Knowledge about Disease, Medication Therapy, and Related Medication Adherence Levels among Patients with Hypertension. Medicina, 55.","DOI":"10.3390\/medicina55110715"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hsu, C.N., and Tain, Y.L. (2020). Early Origins of Hypertension: Should Prevention Start Before Birth Using Natural Antioxidants?. Antioxidants, 9.","DOI":"10.3390\/antiox9111034"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1152\/physrev.00016.2005","article-title":"Hypertension, Kidney, and Transgenics: A Fresh Perspective","volume":"86","author":"Mullins","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_16","first-page":"547809","article-title":"Essential hypertension: An approach to its etiology and neurogenic pathophysiology","volume":"2013","year":"2013","journal-title":"Int. J. Hypertens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2183\/pjab.82.17","article-title":"Endothelin and endothelial dysfunction","volume":"82","author":"Masaki","year":"2006","journal-title":"Proc. Jpn. Acad. Ser. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/5584_2016_90","article-title":"Endothelial Dysfunction and Hypertension","volume":"956","author":"Konukoglu","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fcvm.2019.00169","article-title":"Measuring the Interaction Between the Macro- and Micro-Vasculature","volume":"6","author":"Climie","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1093\/brain\/awr253","article-title":"Arterial stiffness, pressure and flow pulsatility and brain structure and function: The Age, Gene\/Environment Susceptibility\u2013Reykjavik Study","volume":"134","author":"Mitchell","year":"2011","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4330\/wjc.v6.i6.353","article-title":"Essential hypertension and oxidative stress: New insights","volume":"6","author":"Valls","year":"2014","journal-title":"World J. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11883-017-0678-6","article-title":"Oxidative Stress in Atherosclerosis","volume":"19","author":"Kattoor","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fphys.2018.00258","article-title":"The Antioxidant Therapy: New Insights in the Treatment of Hypertension","volume":"9","author":"Sorriento","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Senoner, T., and Dichtl, W. (2019). Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target?. Nutrients, 11.","DOI":"10.3390\/nu11092090"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1089\/ars.2020.8112","article-title":"Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension","volume":"34","author":"Wu","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2174\/1573402115666191011111402","article-title":"Nantes University Hospital Working Group On Hypertension. Resistant Hypertension: Novel Insights","volume":"16","author":"Lamirault","year":"2020","journal-title":"Curr. Hypertens. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/HYPERTENSIONAHA.120.15781","article-title":"Adherence to Single-Pill Versus Free-Equivalent Combination Therapy in Hypertension: A Systematic Review and Meta-Analysis","volume":"77","author":"Parati","year":"2021","journal-title":"Hypertension"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"472","DOI":"10.20945\/2359-3997000000066","article-title":"A brief review about melatonin, a pineal hormone","volume":"62","author":"Amaral","year":"2018","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3389\/fphar.2018.01086","article-title":"Promising Antineoplastic Actions of Melatonin","volume":"9","author":"Favero","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110260","DOI":"10.1016\/j.biopha.2020.110260","article-title":"Cardioprotective effects of melatonin: Focusing on its roles against diabetic cardiomyopathy","volume":"128","author":"Song","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.amjhyper.2005.07.013","article-title":"Potential Use of Melatonin as Adjunct Antihypertensive Therapy","volume":"18","author":"Scheer","year":"2005","journal-title":"Am. J. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17920","DOI":"10.3390\/ijms151017920","article-title":"Peripheral and Central Effects of Melatonin on Blood Pressure Regulation","volume":"15","author":"Pechanova","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1600-079X.2007.00436.x","article-title":"Melatonin as a potential antihypertensive treatment","volume":"42","author":"Simko","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.3389\/fcvm.2022.888319","article-title":"Evidence for the Benefits of Melatonin in Cardiovascular Disease","volume":"9","author":"Tobeiha","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1557988320946592","DOI":"10.1177\/1557988320946592","article-title":"Total Antioxidant Capacity and Frailty in Older Men","volume":"14","author":"Tembo","year":"2020","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.atherosclerosis.2015.05.007","article-title":"The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society","volume":"241","author":"Vlachopoulos","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s11906-013-0340-9","article-title":"High Blood Pressure: The Leading Global Burden of Disease Risk Factor and the Need for Worldwide Prevention Programs","volume":"15","author":"Bromfield","year":"2013","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/a-0841-6638","article-title":"Effects of Melatonin Supplementation On Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"51","author":"Hadi","year":"2019","journal-title":"Horm. Metab. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120870","DOI":"10.1016\/j.lfs.2022.120870","article-title":"Modulation of autophagy by melatonin via sirtuins in stroke: From mechanisms to therapies","volume":"307","author":"Azedi","year":"2022","journal-title":"Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e12829","DOI":"10.1111\/jpi.12829","article-title":"Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction","volume":"73","author":"Jiao","year":"2022","journal-title":"J. Pineal Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2174\/157015910792246236","article-title":"Neurotoxins: Free Radical Mechanisms and Melatonin Protection","volume":"8","author":"Reiter","year":"2010","journal-title":"Curr. Neuropharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0079-6123(08)81008-4","article-title":"Melatonin: A Multitasking Molecule","volume":"181","author":"Reiter","year":"2010","journal-title":"Prog. Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115263","DOI":"10.1016\/j.bcp.2022.115263","article-title":"Endothelial and vascular smooth muscle dysfunction in hypertension","volume":"205","author":"Nadruz","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/ajh\/hpaa137","article-title":"Aldosterone, Inflammation, Immune System, and Hypertension","volume":"34","author":"Ferreira","year":"2022","journal-title":"Am. J. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41573-021-00198-1","article-title":"Targeting inflammation in atherosclerosis\u2014From experimental insights to the clinic","volume":"20","author":"Soehnlein","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41440-018-0163-9","article-title":"Inappropriate left ventricular mass after preeclampsia: Another piece of the puzzle Inappropriate LVM and PE","volume":"42","author":"Orabona","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e2963","DOI":"10.1097\/MD.0000000000002963","article-title":"Relationship Between Determinants of Arterial Stiffness Assessed by Diastolic and Suprasystolic Pulse Oscillometry: Comparison of Vicorder and Vascular Explorer","volume":"95","author":"Teren","year":"2016","journal-title":"Medicine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/uog.14838","article-title":"Elastic properties of ascending aorta in women with previous pregnancy complicated by early- or late-onset pre-eclampsia","volume":"47","author":"Orabona","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/uog.15893","article-title":"Endothelial dysfunction and vascular stiffness in women with a previous pregnancy complicated by early or late pre-eclampsia","volume":"49","author":"Orabona","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/HJH.0000000000001888","article-title":"Elastic properties of ascending aorta and ventricular\u2013arterial coupling in women with previous pregnancy complicated by HELLP syndrome","volume":"37","author":"Sciatti","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1111\/echo.14375","article-title":"Elastic aortic properties in cystic fibrosis adults without cardiovascular risk factors: A case-control study","volume":"36","author":"Vizzardi","year":"2019","journal-title":"Echocardiography"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1046\/j.1365-2265.2001.01204.x","article-title":"Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: Role of hormone replacement therapy","volume":"54","author":"Cagnacci","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ramiro-Cortijo, D., Calle, M., Rodr\u00edguez-Rodr\u00edguez, P., Pablo, \u00c1.L.L., L\u00f3pez-Gim\u00e9nez, M.R., Aguilera, Y., Mart\u00edn-Cabrejas, M.A., Gonz\u00e1lez, M.D.C., and Arribas, S.M. (2020). Maternal Antioxidant Status in Early Pregnancy and Development of Fetal Complications in Twin Pregnancies: A Pilot Study. Antioxidants, 9.","DOI":"10.3390\/antiox9040269"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gali\u00f1anes, M., Cas\u00f3s, K., Blasco-Lucas, A., Permanyer, E., M\u00e1\u00f1ez, R., Le Tourneau, T., Barquinero, J., Schwartz, S., Bottio, T., and Roussel, J.C. (2022). Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study. Biomolecules, 12.","DOI":"10.3390\/biom12111606"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zujko, M.E., Wa\u015bkiewicz, A., Witkowska, A.M., Cicha-Miko\u0142ajczyk, A., Zujko, K., and Drygas, W. (2022). Dietary Total Antioxidant Capacity\u2014A New Indicator of Healthy Diet Quality in Cardiovascular Diseases: A Polish Cross-Sectional Study. Nutrients, 14.","DOI":"10.3390\/nu14153219"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s11739-019-02261-7","article-title":"Evaluation of systo-diastolic cardiac function and arterial stiffness in subjects with new diagnosis of coeliac disease without cardiovascular risk factors","volume":"15","author":"Sciatti","year":"2020","journal-title":"Intern. Emerg. Med."},{"key":"ref_58","first-page":"5560","article-title":"PPG-Based Blood Pressure Monitoring by Pulse Wave Analysis: Calibration Parameters are Stable for Three Months","volume":"2019","author":"Proenca","year":"2019","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1161\/hy1001.096106","article-title":"Prospective Evaluation of a Method for Estimating Ascending Aortic Pressure From the Radial Artery Pressure Waveform","volume":"38","author":"Pauca","year":"2001","journal-title":"Hypertension"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000452448","article-title":"Large Artery Stiffness Assessment Using SphygmoCor Technology","volume":"4","author":"Butlin","year":"2017","journal-title":"Pulse"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14489\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:04Z","timestamp":1760145784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,21]]},"references-count":60,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214489"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214489","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,21]]}}}