{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:17:46Z","timestamp":1790255866552,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T00:00:00Z","timestamp":1569628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R37CA215427"],"award-info":[{"award-number":["R37CA215427"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastric cancer remains an unmet clinical problem in urgent need of newer and effective treatments. Here we show that the nuclear export protein, Exportin 1 (XPO1, chromosome region maintenance 1 or CRM1), is a promising molecular target in gastric cancer. We demonstrate significant overexpression of XPO1 in a cohort of histologically diverse gastric cancer patients with primary and metastatic disease. XPO1 RNA interference suppressed gastric cancer cell growth. Anti-tumor activity was observed with specific inhibitor of nuclear export (SINE) compounds (selinexor\/XPOVIO), second-generation compound KPT-8602\/eltanexor, KPT-185 and +ve control Leptomycin B in three distinct gastric cancer cell lines. SINE compounds inhibited gastric cancer cell proliferation, disrupted spheroid formation, induced apoptosis and halted cell cycle progression at the G1\/S phase. Anti-tumor activity was concurrent with nuclear retention of tumor suppressor proteins and inhibition of colony formation. In combination studies, SINE compounds enhanced the efficacy of nab-paclitaxel in vitro and in vivo. More significantly, using non-coding RNA sequencing studies, we demonstrate for the first time that SINE compounds can alter the expression of non-coding RNAs (microRNAs and piwiRNAs). SINE treatment caused statistically significant downregulation of oncogenic miR-33b-3p in two distinct cell lines. These studies demonstrate the therapeutic significance of XPO1 in gastric cancer that warrants further clinical investigation.<\/jats:p>","DOI":"10.3390\/ijms20194826","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T05:58:33Z","timestamp":1569823113000},"page":"4826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Targeting Nuclear Exporter Protein XPO1\/CRM1 in Gastric Cancer"],"prefix":"10.3390","volume":"20","author":[{"given":"Rachel","family":"Sexton","sequence":"first","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Emory Winship Cancer Institute, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahman","family":"Chaudhury","sequence":"additional","affiliation":[{"name":"Detroit Medical Center, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafic","family":"Beydoun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amro","family":"Aboukameel","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9161-1514","authenticated-orcid":false,"given":"Husain Y.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkan","family":"Baloglu","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics Inc., Newton, MA 02459, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Senapedis","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics Inc., Newton, MA 02459, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosef","family":"Landesman","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics Inc., Newton, MA 02459, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anteneh","family":"Tesfaye","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-1232","authenticated-orcid":false,"given":"Steve","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"Philip","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-9505","authenticated-orcid":false,"given":"Asfar S.","family":"Azmi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,28]]},"reference":[{"key":"ref_1","unstructured":"(2019, January 02). World Health Organization. Available online: https:\/\/gco.iarc.fr\/today\/fact-sheets-populations."},{"key":"ref_2","unstructured":"(2019, January 02). AmericanCancerSociety. Available online: https:\/\/www.cancer.org\/cancer\/stomach-cancer\/detection-diagnosis-staging\/survival-rates.html."},{"key":"ref_3","first-page":"1286","article-title":"Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology","volume":"14","author":"Ajani","year":"2016","journal-title":"JNCCN"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3748\/wjg.v12.i3.354","article-title":"Epidemiology of Gastric Cancer","volume":"12","author":"Crew","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1634\/theoncologist.2018-0143","article-title":"Comparative Molecular Analyses of Esophageal Squamous Cell Carcinoma, Esophageal Adenocarcinoma and Gastric Adenocarcinoma","volume":"23","author":"Salem","year":"2018","journal-title":"Oncologist"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s10689-018-0080-8","article-title":"Germline CDH1 mutations are a significant contributor to the high frequency of early diffuse gastric cancer cases in New Zealand Maori","volume":"18","author":"Hakkaart","year":"2018","journal-title":"Fam. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1245\/s10434-018-6502-x","article-title":"Rates of TP53 Mutation are significantly elevated in African American Patients with Gastric Cancer","volume":"25","author":"Hernandez","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/S0092-8674(00)80370-0","article-title":"Exportin 1 (Crm1p) is an essential Nuclear Export Factor","volume":"90","author":"Stade","year":"2017","journal-title":"Cell"},{"key":"ref_9","first-page":"137","article-title":"The CRM1 nuclear export protein in normal development and disease","volume":"3","author":"Nguyen","year":"2012","journal-title":"Int. J. Biochem. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1053\/j.gastro.2012.10.036","article-title":"Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice","volume":"144","author":"Azmi","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.clml.2018.03.003","article-title":"Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma","volume":"18","author":"Gandhi","year":"2018","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1016\/j.jtho.2017.06.013","article-title":"Therapeutic Targeting of Nuclear Export Inhibition in Lung Cancer","volume":"12","author":"Gupta","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1158\/1078-0432.CCR-16-1333","article-title":"Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer","volume":"23","author":"Chen","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"78883","DOI":"10.18632\/oncotarget.12428","article-title":"Selinexor, a Selective Inhibitor of Nuclear Export (SINE) compound, acts through NF-kB deactivation and combines with proteasome inhibitors to synergistically induce tumor cell death","volume":"7","author":"Kashyap","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1200\/JCO.2016.67.5066","article-title":"Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination with Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia","volume":"34","author":"Alexander","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78896","DOI":"10.18632\/oncotarget.12969","article-title":"XPO1 inhibition combination therapy with bortezomib or carfilzomib induces nuclear localization of IkBa and overcomes acquired proteasome inhibitor resistance in human multiple myeloma","volume":"7","author":"Turner","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"30773","DOI":"10.18632\/oncotarget.25637","article-title":"Selinexor reduces the expression on DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents","volume":"9","author":"Kashyap","year":"2018","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.canlet.2016.09.016","article-title":"Anti-tumor activity of selective inhibitor of nuclear export (SINE) compounds, is enhanced in non-Hodgkin lymphoma through combination with mTOR inhibitor and dexamethasone","volume":"383","author":"Muqbil","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_19","unstructured":"(2019, August 01). Bortezomib, Selinexor and Dexamethasone in Patients with Multiple Myeloma (BOSTON), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03110562."},{"key":"ref_20","unstructured":"(2019, August 01). A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients with Relapsed\/Refractory Diffuse Large B-cell Lymphoma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02227251."},{"key":"ref_21","unstructured":"(2019, August 01). Selinexor and Backbone Treatments of Multiple Myeloma Patients (STOMP), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02343042."},{"key":"ref_22","unstructured":"(2019, August 01). Selinexor in Advanced Liposarcoma (SEAL), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02606461."},{"key":"ref_23","unstructured":"(2019). XPO1 Inhibitor Approved for Multiple Myeloma. Cancer Discov."},{"key":"ref_24","unstructured":"(2019, August 01). XPO1 Survival Curves Figure 1A-1C, XPO1, Female\/Male\/Overall Data\/All Stages\/Stage 1\/ Stage 4, dataavailablefrom88.83. Available online: https:\/\/www.proteinatlas.org\/ENSG00000082898-XPO1\/pathology\/tissue\/stomach+cancer."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21037\/sci.2019.02.03","article-title":"The past, present, and future of CRM1\/XPO1 inhibitors","volume":"6","author":"Wang","year":"2019","journal-title":"Stem Cell Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/pros.10197","article-title":"Leptomycin B stabilizes and activates p53 in primary prostatic epithelial cells and induces apoptosis in the LNCaP cell line","volume":"54","author":"Lecane","year":"2003","journal-title":"Prostate."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1038\/emboj.2010.82","article-title":"The nuclear export receptor XPO-1 supports primary miRNA processing in C. elegans and Drosophilia","volume":"29","author":"Bussing","year":"2010","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s10120-015-0487-y","article-title":"An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence","volume":"19","author":"Martinez","year":"2016","journal-title":"Gastric. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gpb.2017.09.004","article-title":"The Role of Exportin-5 in MicroRNA Biogenesis and Cancer","volume":"16","author":"Wu","year":"2018","journal-title":"Genom. Proteom. Bioinform."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.2174\/1389450111314100002","article-title":"Nuclear export mediated regulation of microRNAs: potential target for drug intervention","volume":"14","author":"Muqbil","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.fob.2014.04.010","article-title":"Small RNA expression and deep sequencing analyses of the nucleolus reveal the presence of nucleolus-associated miRNAs","volume":"4","author":"Bai","year":"2014","journal-title":"FEBS Open Bio."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"82144","DOI":"10.18632\/oncotarget.19285","article-title":"Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration","volume":"8","author":"Azmi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.cell.2019.07.007","article-title":"A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production","volume":"178","author":"ElMaghraby","year":"2019","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1158\/1535-7163.MCT-17-1303","article-title":"The XPO1 inhibitor Selinexor Inhibits Translation and Enhances the Radiosensitivity of Glioblastoma Cells Growth In Vitro and In Vivo","volume":"17","author":"Wahba","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_35","first-page":"961","article-title":"Radiation Response enhanced by inhibition of XPO1 in preclinical rectal cancer models","volume":"192","author":"Depping","year":"2016","journal-title":"Strahlenther Onkol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s10120-016-0650-0","article-title":"Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: abhorrent DNA methylation pathway","volume":"20","author":"Maeda","year":"2017","journal-title":"Gastric. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"31691","DOI":"10.1007\/s11356-018-3080-1","article-title":"Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk","volume":"25","author":"Yadav","year":"2018","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.3390\/v4123420","article-title":"Epstein-Barr virus (EBV) associated gastric Carcinoma","volume":"4","author":"Iizasa","year":"2012","journal-title":"Viruses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3174","DOI":"10.1136\/bmj.g3174","article-title":"Helicobacter pylori eradication therapy to prevent gastric cancer in healthy asymptomatic infected individuals: systematic review and meta-analysis of randomized controlled trials","volume":"348","author":"Ford","year":"2014","journal-title":"Bmj"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1038\/cti.2014.27","article-title":"Epstein-barr virus vaccines","volume":"4","author":"Cohen","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12943-018-0859-0","article-title":"E-Cadherin signal sequence disruption: a novel mechanism underlying hereditary cancer","volume":"17","author":"Figueiredo","year":"2018","journal-title":"Mol Cancer."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13053-015-0038-x","article-title":"The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers","volume":"13","author":"Cavanagh","year":"2015","journal-title":"Hered. Cancer Clin. Pr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1053\/j.gastro.2009.10.051","article-title":"Risk and epidemiological time treads of gastric cancer in Lynch syndrome carriers in the Netherlands","volume":"132","author":"Capelle","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.11648\/j.ab.20150305.11","article-title":"Environmental Factors in Etiology of Gastric Cancer","volume":"3","author":"Bhat","year":"2015","journal-title":"Adv. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4103\/ijc.IJC_665_17","article-title":"Radical gastrectomy for gastric cancer at Tata Memorial Hospital","volume":"54","author":"Bhandare","year":"2017","journal-title":"Indian J. Cancer."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/S0140-6736(18)32557-1","article-title":"Preoperative chemotherapy with fluorouracil plus leucovorin, Oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2\/3 trial","volume":"393","author":"Homann","year":"2019","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1182\/blood.V128.22.4509.4509","article-title":"A Phase 1\/2 Study of the Second Generation Selective inhibitor of Nuclear Export (SINE) Compound, KPT-8602, in Patients with Relapsed Refractory Multiple Myeloma","volume":"128","author":"Cornell","year":"2016","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1038\/leu.2016.136","article-title":"Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies","volume":"30","author":"Hing","year":"2016","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12248","DOI":"10.1038\/s41598-018-30686-1","article-title":"Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor","volume":"8","author":"Subhash","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.3748\/wjg.v20.i18.5411","article-title":"Non-coding RNAs in gastric cancer","volume":"20","author":"Li","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1053\/j.gastro.2018.10.054","article-title":"Long Noncoding RNA GMAN, Up-regulated in Gastric Cancer Tissues, Is Associated with Metastasis in Patients and Promotes Translation of Ephrin A1 by Competitively Binding GMAN-AS","volume":"156","author":"Zhuo","year":"2019","journal-title":"Gastroenterol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Xu, Z., Yu, Z., Tan, Q., Wei, C., Tang, Q., Wang, L., and Hong, Y. (2019). MIR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190066"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1038\/s41598-018-22858-w","article-title":"TDP43 nuclear export and neurodegeneration in models of amyotrophic lateral sclerosis and frontotemporal dementia","volume":"8","author":"Archbold","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Caceres-Gorriti, K.Y., Carmona, E., Barres, V., Rahimi, K., Letourneau, I.J., Tonin, P.N., Provencher, D., and Mes-Masson, A.M. (2014). RAN nucleo-cytoplasmic transport and mitotic spindle assembly partners XPO7 and TPX2 are new prognostic biomarkers in serous epithelial ovarian cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091000"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.3892\/or.2012.2060","article-title":"Taxol-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1\/CIP1, in human breast cancer cells","volume":"28","author":"Chou","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1182\/blood-2017-07-793398","article-title":"Balancing the yin and yang of SINE","volume":"130","author":"Pluthero","year":"2017","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2144\/btn-2018-0046","article-title":"Isolation of Spheroid-forming single cells from gastric cancer cell lines: enrichment of cancer stem-like cells","volume":"65","author":"Lee","year":"2018","journal-title":"Biotechniques"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/19\/4826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:31Z","timestamp":1760189131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/19\/4826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,28]]},"references-count":57,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["ijms20194826"],"URL":"https:\/\/doi.org\/10.3390\/ijms20194826","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,28]]}}}