{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:36:06Z","timestamp":1791228966909,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T00:00:00Z","timestamp":1585440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["10080691"],"award-info":[{"award-number":["10080691"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-\u03b1 or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-\u03b1 was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.<\/jats:p>","DOI":"10.3390\/nu12040947","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T10:29:38Z","timestamp":1585650578000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protective Mechanisms of Avocado Oil Extract Against Ototoxicity"],"prefix":"10.3390","volume":"12","author":[{"given":"Thu Nguyen Minh","family":"Pham","sequence":"first","affiliation":[{"name":"Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Yeon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Dongkook Pharm. Co., Ltd., Gyeonggi 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Hwa","family":"Park","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Dongkook Pharm. Co., Ltd., Gyeonggi 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Suk","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Dongkook Pharm. Co., Ltd., Gyeonggi 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kye Wan","family":"Lee","sequence":"additional","affiliation":[{"name":"R&amp;D Center, Dongkook Pharm. Co., Ltd., Gyeonggi 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Seok","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Young","family":"Choung","sequence":"additional","affiliation":[{"name":"Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4161-6798","authenticated-orcid":false,"given":"Tong Ho","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Oriental Medicine Biotechnology, College of Life Sciences and Graduate School of Biotechnology, Kyung Hee University, Global Campus, Gyeonggi 17104, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2258-8354","authenticated-orcid":false,"given":"Kwang Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1017\/S0022215118001275","article-title":"Global burden of hearing impairment and ear disease","volume":"133","author":"Graydon","year":"2019","journal-title":"J. Laryngol. Otol."},{"key":"ref_2","first-page":"385","article-title":"Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses. A comparative biochemical and morphometric study","volume":"54","author":"Toubeau","year":"1986","journal-title":"Lab. Investig. J. Tech. Methods Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1001\/archotol.1959.00730030400002","article-title":"Neomycin ototoxicity: Report of a case","volume":"69","author":"Greenwood","year":"1959","journal-title":"AMA Arch. Otolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000013861","article-title":"Aminoglycoside antibiotics","volume":"5","author":"Forge","year":"2000","journal-title":"Audiol. Neurotol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/cpt.603","article-title":"Drug-induced ototoxicity: Mechanisms, Pharmacogenetics, and protective strategies","volume":"101","author":"Ciarimboli","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1039\/c1ib00034a","article-title":"Intracellular mechanisms of aminoglycoside-induced cytotoxicity","volume":"3","author":"Karasawa","year":"2011","journal-title":"Integr. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/sj.emboj.7600951","article-title":"Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness","volume":"25","author":"Kharkovets","year":"2006","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"937861","DOI":"10.1155\/2011\/937861","article-title":"Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection","volume":"2011","author":"Huth","year":"2011","journal-title":"Int. J. Otolaryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000071059","article-title":"A cochlear cell line as an in vitro system for drug ototoxicity screening","volume":"8","author":"Kalinec","year":"2003","journal-title":"Audiol. Neurotol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/00005537-200003000-00024","article-title":"Characterization of an experimentally induced inner ear immune response","volume":"110","author":"Ma","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nam, Y.H., Rodriguez, I., Jeong, S.Y., Pham, T.N.M., Nuankaew, W., Kim, Y.H., Casta\u00f1eda, R., Jeong, S.Y., Park, M.S., and Lee, K.W. (2019). Avocado Oil Extract Modulates Auditory Hair Cell Function through the Regulation of Amino Acid Biosynthesis Genes. Nutrients, 11.","DOI":"10.3390\/nu11010113"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10151","DOI":"10.1021\/jf061809j","article-title":"Pigments in avocado tissue and oil","volume":"54","author":"Ashton","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1007\/s11746-011-1877-x","article-title":"Effect of varietal differences on composition and thermal characteristics of avocado oil","volume":"88","author":"Yanty","year":"2011","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Flores, M., Saravia, C., Vergara, C.E., Avila, F., Vald\u00e9s, H., and Ortiz-Viedma, J. (2019). Avocado oil: Characteristics, properties, and applications. Molecules, 24.","DOI":"10.3390\/molecules24112172"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.foodchem.2018.03.048","article-title":"Bioactive compounds and quality parameters of avocado oil obtained by different processes","volume":"257","author":"Krumreich","year":"2018","journal-title":"Food Chem."},{"key":"ref_16","first-page":"72","article-title":"A review on Persea americana Mill.(avocado)-its fruits and oil","volume":"8","author":"Ranade","year":"2015","journal-title":"Int. J. PharmTech Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jfda.2015.11.005","article-title":"Effect of an avocado oil-enhanced diet (Persea americana) on sucrose-induced insulin resistance in Wistar rats","volume":"24","year":"2016","journal-title":"J. Food Drug Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"123","DOI":"10.12968\/jowc.2008.17.3.28670","article-title":"Wound healing activity of Persea americana (avocado) fruit: A preclinical study on rats","volume":"17","author":"Nayak","year":"2008","journal-title":"J. Wound Care"},{"key":"ref_19","first-page":"485759","article-title":"Avocado oil improves mitochondrial function and decreases oxidative stress in brain of diabetic rats","volume":"2015","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1002\/ijc.31853","article-title":"Aberrant expression of SETD1A promotes survival and migration of estrogen receptor \u03b1-positive breast cancer cells","volume":"143","author":"Jin","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110555","DOI":"10.1016\/j.fct.2019.06.002","article-title":"Photoactivation of N-retinylidene-N-retinylethanolamine compromises autophagy in retinal pigmented epithelial cells","volume":"131","author":"Jeong","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3389\/fncel.2017.00338","article-title":"Mechanisms of cisplatin-induced ototoxicity and otoprotection","volume":"11","author":"Sheth","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.freeradbiomed.2006.01.018","article-title":"Heme oxygenase-1 attenuates the cisplatin-induced apoptosis of auditory cells via down-regulation of reactive oxygen species generation","volume":"40","author":"Kim","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-12073-0","article-title":"GSTA4 mediates reduction of cisplatin ototoxicity in female mice","volume":"10","author":"Park","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1021\/bi048016f","article-title":"Microsomal glutathione S-transferase 1 in the retinal pigment epithelium: Protection against oxidative stress and a potential role in aging","volume":"44","author":"Maeda","year":"2005","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000046818","article-title":"Overexpression of copper\/zinc-superoxide dismutase protects from kanamycin-induced hearing loss","volume":"6","author":"Sha","year":"2001","journal-title":"Audiol. Neurotol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.heares.2006.05.008","article-title":"Aspirin attenuates gentamicin ototoxicity: From the laboratory to the clinic","volume":"226","author":"Chen","year":"2007","journal-title":"Hear. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nrd4533","article-title":"New treatment options for hearing loss","volume":"14","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zong, S., Zeng, X., Liu, T., Wan, F., Luo, P., and Xiao, H. (2017). Association of polymorphisms in heat shock protein 70 genes with the susceptibility to noise-induced hearing loss: A meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188195"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/clpt.2013.80","article-title":"Replication of TPMT and ABCC3 genetic variants highly associated with cisplatin-induced hearing loss in children","volume":"94","author":"Pussegoda","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.heares.2017.12.009","article-title":"Immune cells and non-immune cells with immune function in mammalian cochleae","volume":"362","author":"Hu","year":"2018","journal-title":"Hear. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1121\/1.5132545","article-title":"Inflammation associated with noise-induced hearing loss","volume":"146","author":"Frye","year":"2019","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fujioka, M., Okamoto, Y., Shinden, S., Okano, H.J., Okano, H., Ogawa, K., and Matsunaga, T. (2014). Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall: A potential therapeutic target for sensorineural hearing loss. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090089"},{"key":"ref_35","unstructured":"Pear Oofa (2011). Extraction and characterization of oil from Avocado pear (Persea americana) and native pear (Dacryodes edulis) fruits. World, 3, 27\u201334."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"843908","DOI":"10.1155\/2014\/843908","article-title":"Characterization of fatty acid profile of argan oil and other edible vegetable oils by gas chromatography and discriminant analysis","volume":"2014","author":"Rueda","year":"2014","journal-title":"J. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.15252\/embj.201489363","article-title":"Unsaturated fatty acids induce non-canonical autophagy","volume":"34","author":"Malik","year":"2015","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14364","DOI":"10.1074\/jbc.M111.294157","article-title":"Induction of autophagy by palmitic acid via protein kinase C-mediated signaling pathway independent of mTOR (mammalian target of rapamycin)","volume":"287","author":"Tan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_39","first-page":"1","article-title":"Oleic acid induces apoptosis and autophagy in the treatment of Tongue Squamous cell carcinomas","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1089\/ars.2014.6004","article-title":"Autophagy attenuates noise-induced hearing loss by reducing oxidative stress","volume":"22","author":"Yuan","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cell.2010.01.028","article-title":"Methods in mammalian autophagy research","volume":"140","author":"Mizushima","year":"2010","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1080\/15548627.2017.1359449","article-title":"Autophagy protects auditory hair cells against neomycin-induced damage","volume":"13","author":"He","year":"2017","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.heares.2012.12.014","article-title":"A brief history of hair cell regeneration research and speculations on the future","volume":"297","author":"Rubel","year":"2013","journal-title":"Hear. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.neuroscience.2009.02.085","article-title":"Generation of highly-reactive oxygen species is closely related to hair cell damage in rat organ of Corti treated with gentamicin","volume":"161","author":"Choung","year":"2009","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"a033548","DOI":"10.1101\/cshperspect.a033548","article-title":"Aminoglycoside-and cisplatin-induced ototoxicity: Mechanisms and otoprotective strategies","volume":"9","author":"Kros","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fncel.2015.00276","article-title":"Age-related hearing impairment and the triad of acquired hearing loss","volume":"9","author":"Yang","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3389\/fphar.2014.00287","article-title":"Inflammatory and immune responses in the cochlea: Potential therapeutic targets for sensorineural hearing loss","volume":"5","author":"Fujioka","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/s10162-007-0084-9","article-title":"Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-\u03baB","volume":"8","author":"So","year":"2007","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/hed.20892","article-title":"Role of proinflammatory cytokines in cisplatin-induced vestibular hair cell damage","volume":"30","author":"Kim","year":"2008","journal-title":"Head Neck J. Sci. Spec. Head Neck"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"83","DOI":"10.23937\/2378-3001\/1410083","article-title":"Involvement of Oxidative Stress, Inflammation, and Glutamate in Ototoxici-ty, and their Attenuation by Simultaneous Activation of Nrf2 and Elevation of Antioxidant Compounds","volume":"6","author":"Prasad","year":"2019","journal-title":"Int. J. Neurol. Neurother."},{"key":"ref_51","first-page":"6053492","article-title":"Omega-9 oleic acid, the main compound of olive oil, mitigates inflammation during experimental sepsis","volume":"2018","author":"Kurz","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1476-511X-8-25","article-title":"Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-\u03b1 both in vitro and in vivo systems","volume":"8","author":"Vassiliou","year":"2009","journal-title":"Lipids Health Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2780","DOI":"10.1038\/cddis.2017.194","article-title":"Autophagy is essential for hearing in mice","volume":"8","author":"Fujimoto","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41356","DOI":"10.1038\/srep41356","article-title":"Autophagic flux, a possible mechanism for delayed gentamicin-induced ototoxicity","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1016\/j.ijporl.2015.08.012","article-title":"Role of autophagy in cisplatin-induced ototoxicity","volume":"79","author":"Youn","year":"2015","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1172\/JCI85052","article-title":"Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells","volume":"127","author":"Hailey","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0006-8993(97)00977-3","article-title":"Lysosomal targeting and accumulation of aminoglycoside antibiotics in sensory hair cells","volume":"777","author":"Hashino","year":"1997","journal-title":"Brain Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/4\/947\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:13:11Z","timestamp":1760173991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/4\/947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,29]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["nu12040947"],"URL":"https:\/\/doi.org\/10.3390\/nu12040947","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,29]]}}}