{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:26:23Z","timestamp":1778617583401,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["22K16497"],"award-info":[{"award-number":["22K16497"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["19K16564"],"award-info":[{"award-number":["19K16564"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["23K19900"],"award-info":[{"award-number":["23K19900"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"MEXT KAKENHI","doi-asserted-by":"publisher","award":["20K21659"],"award-info":[{"award-number":["20K21659"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anticancer agents are playing an increasing role in the treatment of gastric cancer (GC); however, novel anticancer agents have not been fully developed. Therefore, it is important to investigate compounds that improve sensitivity to the existing anticancer drugs. We have reported that pterostilbene (PTE), a plant stilbene, enhances the antitumor effect of low doses of sunitinib in gastric cancer cells accumulating mitochondrial iron (II) (mtFe) at low doses. In this study, we investigated the relationship between the mtFe deposition and the synergistic effect of PTE and different anticancer drugs. For this study, we used 5-fluorouracil (5FU), cisplatin (CPPD), and lapatinib (LAP), which are frequently used in the treatment of GC, and doxorubicin (DOX), which is known to deposit mtFe. A combination of low-dose PTE and these drugs suppressed the expression of PDZ domain-containing 8 (PDZD8) and increased mtFe accumulation and mitochondrial H2O2. Consequently, reactive oxygen species-associated hypoxia inducible factor-1\u03b1 activation induced endoplasmic reticulum stress and led to apoptosis, but not ferroptosis. In contrast, 5FU and CDDP did not show the same changes as those observed with PTE and DOX or LAP, and there was no synergistic effect with PTE. These results indicate that the combination of PTE with iron-accumulating anticancer drugs exhibits a strong synergistic effect. These findings would help in developing novel therapeutic strategies for GC. However, further clinical investigations are required.<\/jats:p>","DOI":"10.3390\/ijms25052611","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T07:33:56Z","timestamp":1708673636000},"page":"2611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pterostilbene Induces Apoptosis from Endoplasmic Reticulum Stress Synergistically with Anticancer Drugs That Deposit Iron in Mitochondria"],"prefix":"10.3390","volume":"25","author":[{"given":"Yukiko","family":"Nishiguch","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Fujiwara-Tani","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Nukaga","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiori","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiko","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"},{"name":"Pathology Laboratory, Research Institute, Tokushukai Nozaki Hospital, 2-10-50 Tanigawa, Daito 574-0074, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yudai","family":"Hojo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Sho","sequence":"additional","affiliation":[{"name":"Department of Surgery, Nara Medical University, Kashihara 634-8522, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-8825","authenticated-orcid":false,"given":"Hiroki","family":"Kuniyasu","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Nara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","unstructured":"Statistics Bureau Ministry of Internal Affairs and Communications Japan (2023, December 07). Statistical Handbook of Japan 2017, Available online: https:\/\/www.stat.go.jp\/english\/data\/handbook\/pdf\/2017all.pdf."},{"key":"ref_2","unstructured":"International Agency for Research on Cancer (2023, December 07). Globocan 2018 Latest Global Cancer Data. Available online: https:\/\/www.iarc.who.int\/infographics\/globocan-2018-latest-global-cancer-data\/."},{"key":"ref_3","unstructured":"Mikami, H., and Nagase, H. (2023, December 08). Cancer Survival Rates at Japanese Association of Clinical Cancer Centers. Available online: https:\/\/kapweb.chiba-cancer-registry.org\/."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Japanese Gastric Cancer Association (2011). Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer, 14, 101\u2013112.","DOI":"10.1007\/s10120-011-0041-5"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.cell.2017.11.009","article-title":"Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy","volume":"171","author":"Palmer","year":"2017","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1007\/s00268-009-0142-z","article-title":"Comparative study on overexpression of HER2\/neu and HER3 in gastric cancer","volume":"33","author":"Zhang","year":"2009","journal-title":"World J. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1002\/jcb.26495","article-title":"Pterostilbene down-regulates hTERT at physiological concentrations in breast cancer cells: Potentially through the inhibition of cMyc","volume":"119","author":"Daniel","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_9","first-page":"1384","article-title":"Pterostilbene (3\u2032,5\u2032-dimethoxy-resveratrol) exerts potent antitumor effects in HeLa human cervical cancer cells via disruption of mitochondrial membrane potential, apoptosis induction and targeting m-TOR\/PI3K\/Akt signalling pathway","volume":"23","author":"Da","year":"2018","journal-title":"J. BUON"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jss.2012.04.027","article-title":"Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro","volume":"180","author":"Moon","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mori, S., Kishi, S., Honoki, K., Fujiwara-Tani, R., Moriguchi, T., Sasaki, T., Fujii, K., Tsukamoto, S., Fujii, H., and Kido, A. (2020). Anti-Stem Cell Property of Pterostilbene in Gastrointestinal Cancer Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249347"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hojo, Y., Kishi, S., Mori, S., Fujiwara-Tani, R., Sasaki, T., Fujii, K., Nishiguchi, Y., Nakashima, C., Luo, Y., and Shinohara, H. (2022). Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074002"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.tips.2021.05.001","article-title":"Iron metabolism: Pathophysiology and pharmacology","volume":"42","author":"Roemhild","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.14740\/wjon1739","article-title":"Oxygen and Iron Availability Shapes Metabolic Adaptations of Cancer Cells","volume":"15","author":"Wang","year":"2024","journal-title":"World J. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1038\/cdd.2012.74","article-title":"PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress","volume":"19","author":"Verfaillie","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_17","first-page":"1631","article-title":"Pterostilbene inhibits lung squamous cell carcinoma growth in vitro and in vivo by inducing S phase arrest and apoptosis","volume":"18","author":"Tan","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1080\/01635581.2020.1817513","article-title":"Pterostilbene as a Phytochemical Compound Induces Signaling Pathways Involved in the Apoptosis and Death of Mutant P53-Breast Cancer Cell Lines","volume":"73","author":"Elsherbini","year":"2021","journal-title":"Nutr. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shin, H.J., Han, J.M., Choi, Y.S., and Jung, H.J. (2020). Pterostilbene Suppresses both Cancer Cells and Cancer Stem-Like Cells in Cervical Cancer with Superior Bioavailability to Resveratrol. Molecules, 25.","DOI":"10.3390\/molecules25010228"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6381","DOI":"10.1038\/s41598-021-85908-w","article-title":"Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells","volume":"11","author":"Gao","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"37417","DOI":"10.1038\/srep37417","article-title":"Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells","volume":"6","author":"Kong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chen, R.J., Lyu, Y.J., Chen, Y.Y., Lee, Y.C., Pan, M.H., Ho, Y.S., and Wang, Y.J. (2021). Chloroquine Potentiates the Anticancer Effect of Pterostilbene on Pancreatic Cancer by Inhibiting Autophagy and Downregulating the RAGE\/STAT3 Pathway. Molecules, 26.","DOI":"10.3390\/molecules26216741"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1126\/science.aan6009","article-title":"ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons","volume":"358","author":"Hirabayashi","year":"2017","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"jcs255026","DOI":"10.1242\/jcs.255026","article-title":"PDZD8-mediated lipid transfer at contacts between the ER and late endosomes\/lysosomes is required for neurite outgrowth","volume":"135","author":"Gao","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19924","DOI":"10.1073\/pnas.1908271116","article-title":"Redox-dependent gating of VDAC by mitoNEET","volume":"116","author":"Lipper","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.bbrc.2016.01.040","article-title":"His-87 ligand in mitoNEET is crucial for the transfer of iron sulfur clusters from mitochondria to cytosolic aconitase","volume":"470","author":"Tan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e65158","DOI":"10.7554\/eLife.65158","article-title":"Augmenter of liver regeneration regulates cellular iron homeostasis by modulating mitochondrial transport of ATP-binding cassette B8","volume":"10","author":"Chang","year":"2021","journal-title":"eLife"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.isci.2018.12.005","article-title":"Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress","volume":"11","author":"Issitt","year":"2019","journal-title":"iScience"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lin, Y., Jiang, M., Chen, W., Zhao, T., and Wei, Y. (2019). Cancer and ER stress: Mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109249"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1091\/mbc.e10-01-0025","article-title":"Hypoxia-inducible factor-1 activation in nonhypoxic conditions: The essential role of mitochondrial-derived reactive oxygen species","volume":"21","author":"Patten","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1128\/MCB.25.12.4853-4862.2005","article-title":"Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling","volume":"25","author":"Emerling","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cmet.2005.05.001","article-title":"Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing","volume":"1","author":"Guzy","year":"2005","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.cmet.2005.05.002","article-title":"Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation","volume":"1","author":"Brunelle","year":"2005","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.canlet.2007.08.001","article-title":"Inhibitory effects of nitric oxide on invasion of human cancer cells","volume":"257","author":"Wang","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1073\/pnas.0400265101","article-title":"A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression","volume":"101","author":"Liu","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.yexcr.2015.10.014","article-title":"Plant stilbenes induce endoplasmic reticulum stress and their anti-cancer activity can be enhanced by inhibitors of autophagy","volume":"339","author":"Papandreou","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1254\/jphs.14028FP","article-title":"Involvement of the Nrf2 pathway in the regulation of pterostilbene-induced apoptosis in HeLa cells via ER stress","volume":"126","author":"Zhang","year":"2014","journal-title":"J. Pharmacol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17939","DOI":"10.1038\/s41598-018-36063-2","article-title":"HIF-1\u03b1 triggers ER stress and CHOP-mediated apoptosis in alveolar epithelial cells, a key event in pulmonary fibrosis","volume":"8","author":"Delbrel","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kim, C., and Kim, B. (2018). Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review. Nutrients, 10.","DOI":"10.3390\/nu10081021"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-cellbio-101011-155826","article-title":"Structural basis of the unfolded protein response","volume":"28","author":"Korennykh","year":"2012","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1016\/j.bbamcr.2013.06.028","article-title":"ER stress-induced cell death mechanisms","volume":"1833","author":"Sano","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.mito.2015.01.005","article-title":"Inhibition of mitochondrial genome expression triggers the activation of CHOP-10 by a cell signaling dependent on the integrated stress response but not the mitochondrial unfolded protein response","volume":"21","author":"Michel","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/ncb2738","article-title":"ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death","volume":"15","author":"Han","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","article-title":"Roles of CHOP\/GADD153 in endoplasmic reticulum stress","volume":"11","author":"Oyadomari","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","article-title":"HER2-targeted therapies\u2014A role beyond breast cancer","volume":"17","author":"Oh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_47","first-page":"364","article-title":"Adriamycin (doxorubicin) cardiotoxicity: A review","volume":"131","author":"Chlebowski","year":"1979","journal-title":"West. J. Med."},{"key":"ref_48","first-page":"1064","article-title":"Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1","volume":"76","author":"Ochiai","year":"1985","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_49","first-page":"65","article-title":"Comparison of seven cell lines derived from human gastric carcinomas","volume":"36","author":"Motoyama","year":"1986","journal-title":"Acta Pathol. Jpn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1046\/j.1440-1827.2000.01117.x","article-title":"Molecular characteristics of eight gastric cancer cell lines established in Japan","volume":"50","author":"Yokozaki","year":"2000","journal-title":"Pathol. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/path.1031","article-title":"Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer","volume":"196","author":"Kuniyasu","year":"2002","journal-title":"J. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/pros.1114","article-title":"Interferon-alpha prevents selection of doxorubicin-resistant undifferentiated-androgen-insensitive metastatic human prostate cancer cells","volume":"49","author":"Kuniyasu","year":"2001","journal-title":"Prostate"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:03:52Z","timestamp":1760105032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25052611"],"URL":"https:\/\/doi.org\/10.3390\/ijms25052611","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]}}}