{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:32:23Z","timestamp":1788877943212,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2014R1A1A4A01007858, 2016R1D1A3B03931424, and NRF-2017R1A2B4002675"],"award-info":[{"award-number":["NRF-2014R1A1A4A01007858, 2016R1D1A3B03931424, and NRF-2017R1A2B4002675"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study focuses on the effect of honokiol (HON) on glucose homeostasis, insulin resistance, dyslipidemia, hepatic steatosis, and inflammation in type 2 diabetic db\/db mice. Male C57BL\/KsJ-db\/db mice were fed a normal diet with or without HON (0.02%, w\/w) or pioglitazone (PIO, anti-diabetic agent, 0.01%, w\/w) for 5 weeks. Blood biomarker, tissue morphology and enzymatic and genetic parameters were determined. PIO significantly decreased food intake, fasting blood glucose, and glycosylated hemoglobin (HbA1c) levels, but markedly increased body weight, adipose tissue weight, and plasma leptin levels. HON did not significantly affect food intake, body weight, or levels of plasma leptin and blood glucose. However, HON led to significant decreases in adipose tissue weight, plasma insulin, blood HbA1c and HOMA-IR levels and improved glucose tolerance. The anti-diabetic and anti-adiposity effects of HON were partially related to the inhibition of gluconeogenic enzymes and their mRNA expression in the liver; and the inhibition of lipogenic enzymes in adipose tissue, respectively. Unlike PIO, HON did not affect dyslipidemia, but ameliorated hepatic steatosis by inhibiting hepatic lipogenic enzymes activity. Moreover, HON exhibited anti-inflammatory effects similar to PIO. These results suggest that HON can protect against type 2 diabetes by improving insulin resistance, glucose and lipid metabolism, and inflammation.<\/jats:p>","DOI":"10.3390\/ijms20092303","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T11:22:35Z","timestamp":1557400955000},"page":"2303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 Diabetic db\/db Mice"],"prefix":"10.3390","volume":"20","author":[{"given":"Young-Je","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Un Ju","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global aetiology and epidemiology of type 2 diabetes mellitus and its complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1172\/JCI10842","article-title":"Obesity and insulin resistance","volume":"106","author":"Kahn","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.2460\/javma.1996.209.05.943","article-title":"Pretreatment clinical and laboratory evaluation of cats with diabetes mellitus: 104 cases (1992-1994)","volume":"209","author":"Crenshaw","year":"1996","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.soard.2010.05.013","article-title":"Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity","volume":"7","author":"Hardy","year":"2011","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1172\/JCI88876","article-title":"Role of innate and adaptive immunity in obesity-associated metabolic disease","volume":"127","author":"McLaughlin","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1172\/JCI96139","article-title":"Insulin resistance causes inflammation in adipose tissue","volume":"128","author":"Shimobayashi","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrendo.2015.189","article-title":"Regulation of metabolism by the innate immune system","volume":"12","author":"Lackey","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1210\/jcem.87.7.8638","article-title":"Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men","volume":"87","author":"Vehkavaara","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2337\/diabetes.49.5.749","article-title":"Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients","volume":"49","author":"Ryysy","year":"2000","journal-title":"Diabetes"},{"key":"ref_10","first-page":"906","article-title":"Fatty liver in type 2 diabetes mellitus: Relation to regional adiposity, fatty acids, and insulin resistance","volume":"285","author":"Kelley","year":"2003","journal-title":"Am. J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1159\/000028324","article-title":"Antiarrhythmic effect of magnolol and honokiol during acute phase of coronary occlusion in anesthetized rats: Influence of L-NAME and aspirin","volume":"59","author":"Tsai","year":"1999","journal-title":"Pharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/ptr.736","article-title":"Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis","volume":"15","author":"Ho","year":"2001","journal-title":"Phytother. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/sj.ki.5001617","article-title":"Honokiol, a small molecular weight natural product, alleviates experimental mesangial proliferative glomerulonephritis","volume":"70","author":"Chiang","year":"2006","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1182\/blood-2005-01-0346","article-title":"Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis","volume":"06","author":"Ishitsuka","year":"2005","journal-title":"Blood"},{"key":"ref_15","first-page":"1529","article-title":"Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest","volume":"30","author":"Wolf","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.biopha.2017.11.063","article-title":"Honokiol protects pancreatic \u03b2 cell against high glucose and intermittent hypoxia-induced injury by activating Nrf2\/ARE pathway in vitro and in vivo","volume":"97","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","first-page":"3159801","article-title":"Honokiol Ameliorates Myocardial Ischemia\/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway","volume":"2018","author":"Zhang","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_18","first-page":"6327","article-title":"Hypoglycemic effect and mechanism of honokiol on type 2 diabetic mice","volume":"9","author":"Sun","year":"2015","journal-title":"Drug. Des. Devel. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/ilar.47.3.186","article-title":"Animal models of type 2 diabetes: Clinical presentation and pathophysiological relevance to the human condition","volume":"47","author":"Cefalu","year":"2006","journal-title":"ILAR. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.lfs.2010.08.002","article-title":"Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db\/db mice","volume":"87","author":"Yang","year":"2010","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.2337\/db12-0428","article-title":"Pioglitazone acutely reduces energy metabolism and insulin secretion in rats","volume":"62","author":"Lamontagne","year":"2013","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.4137\/BMI.S38440","article-title":"Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients","volume":"11","author":"Sherwani","year":"2016","journal-title":"Biomark. Insights"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1128\/MCB.01321-14","article-title":"Lipid-overloaded enlarged adipocytes provoke insulin resistance independent of inflammation","volume":"35","author":"Kim","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"533","DOI":"10.4314\/ahs.v14i3.6","article-title":"Association of glycosylated hemoglobin (HbA1c) levels with Iinsulin resistance in obese children","volume":"14","author":"Onal","year":"2014","journal-title":"Afr. Health Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1464-5491.2012.03667.x","article-title":"High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: The Toranomon Hospital Health Management Center Study 8","volume":"29","author":"Heianza","year":"2012","journal-title":"Diabet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.2337\/diab.43.11.1271","article-title":"Tumor necrosis factor alpha: A key component of the obesity-diabetes link","volume":"43","author":"Hotamisligil","year":"1994","journal-title":"Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1210\/en.2004-1468","article-title":"Interleukin-6 depletion selectively improves hepatic insulin action in obesity","volume":"146","author":"Klover","year":"2005","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1126\/science.1160794","article-title":"A stress signaling pathway in adipose tissue regulates hepatic insulin resistance","volume":"322","author":"Sabio","year":"2008","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.cmet.2015.02.006","article-title":"Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance","volume":"21","author":"Kraakman","year":"2015","journal-title":"Cell. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.metabol.2018.03.002","article-title":"Depletion of dendritic cells in perivascular adipose tissue improves arterial relaxation responses in type 2 diabetic mice","volume":"85","author":"Qiu","year":"2018","journal-title":"Metabolism"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.2337\/db12-0868","article-title":"Reduced adipose tissue macrophage content is associated with improved insulin sensitivity in thiazolidinedione-treated diabetic humans","volume":"62","author":"Koppaka","year":"2013","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1172\/JCI34260","article-title":"Insulin sensitivity: Modulation by nutrients and inflammation","volume":"118","author":"Schenk","year":"2008","journal-title":"J. Clin. Invest."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2337\/diabetes.48.2.292","article-title":"Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting","volume":"48","author":"Ekberg","year":"1999","journal-title":"Diabetes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3945\/an.112.002089","article-title":"Regulation of hepatic glucose uptake and storage in vivo","volume":"3","author":"Moore","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1172\/JCI200525152","article-title":"The role of hepatic insulin receptors in the regulation of glucose production","volume":"115","author":"Cherrington","year":"2005","journal-title":"J. Clin. Invest."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26972707","DOI":"10.2337\/db10-1032","article-title":"Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: Implications for therapy","volume":"59","author":"Rizza","year":"2010","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2337\/diacare.15.3.369","article-title":"Molecular physiology and genetics of NIDDM. Importance of metabolic staging","volume":"15","author":"Granner","year":"1992","journal-title":"Diabetes Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1515\/JBCPP.1999.10.2.119","article-title":"Insulin regulates expression of metabolic genes through divergent signaling pathways","volume":"10","author":"Hall","year":"1999","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1210\/jc.2003-031361","article-title":"Promoter polymorphism in PCK1 (phosphoenolpyruvate carboxykinase gene) associated with type 2 diabetes mellitus","volume":"89","author":"Cao","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.2337\/db07-1087","article-title":"Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db\/db mice","volume":"57","author":"Blasco","year":"2008","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23301","DOI":"10.1074\/jbc.M200964200","article-title":"Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice","volume":"277","author":"Sun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1093\/hmg\/ddv230","article-title":"Mice expressing reduced levels of hepatic glucose-6-phosphatase-\u03b1 activity do not develop age-related insulin resistance or obesity","volume":"24","author":"Kim","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1053\/j.gastro.2008.01.075","article-title":"Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects","volume":"134","author":"Korenblat","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s00125-005-0132-0","article-title":"Insulin glargine or NPH combined with metformin in type 2 diabetes: The LANMET study","volume":"49","author":"Tiikkainen","year":"2006","journal-title":"Diabetologia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.2337\/diabetes.54.12.3541","article-title":"Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients","volume":"54","author":"Targher","year":"2005","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1007\/s10620-015-3564-5","article-title":"Prevalence of Insulin Resistance in Subjects with Nonalcoholic Fatty Liver Disease and Its Predictors in a Chinese Population","volume":"60","author":"Li","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1172\/JCI24930","article-title":"Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease","volume":"115","author":"Tamura","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cmet.2007.12.009","article-title":"Selective versus total insulin resistance: A pathogenic paradox","volume":"7","author":"Brown","year":"2008","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1161\/ATVBAHA.108.168633","article-title":"Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db\/db mice","volume":"28","author":"Tamura","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.3892\/ijmm.2016.2799","article-title":"Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db\/db mice","volume":"38","author":"Kong","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nm1166","article-title":"Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB","volume":"11","author":"Cai","year":"2005","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1002\/mnfr.201300113","article-title":"Long-term supplementation of honokiol and magnolol ameliorates body fat accumulation, insulin resistance, and adipose inflammation in high-fat fed mice","volume":"57","author":"Kim","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for isolation and purification of total lipids from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/mnfr.200700315","article-title":"Dietary docosahexaenoic acid-rich diacylglycerols ameliorate hepatic steatosis and alter hepatic gene expressions in C57BL\/6J-Lep(ob\/ob) mice","volume":"52","author":"Kim","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1016\/S0021-9258(17)33478-6","article-title":"Interaction of anions and divalent metal ions with phosphopyruvate carboxykinase","volume":"251","author":"Bentle","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0003-2697(88)90176-5","article-title":"Determination of glucose-6-phosphatase activity using the glucose dehydrogenase-coupled reaction","volume":"173","author":"Alegre","year":"1988","journal-title":"Anal. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/0003-9861(87)90648-5","article-title":"Factors underlying significant underestimations of glucokinase activity in crude liver extracts: Physiological implications of higher cellular activity","volume":"253","author":"Davidson","year":"1987","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0076-6879(75)35136-7","article-title":"Fatty-acid synthase from rat liver","volume":"35","author":"Nepokroeff","year":"1975","journal-title":"Methods Enzymol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/0076-6879(55)01129-4","article-title":"Malic enzyme","volume":"1","author":"Ochoa","year":"1955","journal-title":"Methods Enzymol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1016\/S0021-9258(19)43946-X","article-title":"The subcellular distribution of carnitine acyltransferases in mammalian liver and kidney","volume":"248","author":"Markwell","year":"1973","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0076-6879(81)72021-4","article-title":"Assay of peroxisomal \u03b2-oxidation of fatty acids","volume":"72","author":"Lazarow","year":"1981","journal-title":"Methods Enzymol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_64","first-page":"191","article-title":"The estimation of glycogen with the anthrone reagent","volume":"25","author":"Seifter","year":"1950","journal-title":"Arch. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:50:36Z","timestamp":1760187036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,9]]},"references-count":65,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijms20092303"],"URL":"https:\/\/doi.org\/10.3390\/ijms20092303","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,9]]}}}