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Here, we investigated the protective effects and molecular mechanisms of SA4503, a selective Sigmar1 agonist, on Adriamycin (ADR)-induced renal glomerular injury. Methods: Using in vitro and in vivo models, we evaluated the effects of SA4503 on ADR-induced podocyte injury, including podocyte survival, albumin permeability, urinary albumin levels, and Sigmar1-nephrin interactions. NE-100, a Sigmar1 antagonist, was co-administered to validate the specificity of the effects of SA4503. Results: Sigmar1 was highly expressed in podocytes and mouse kidney tissues. SA4503 significantly reduced ADR-induced podocyte injury and urinary albumin leakage in mice. Mechanistically, SA4503 preserved Sigmar1-nephrin interactions, which were disrupted in ADR-treated kidneys. This protective effect was abolished by NE-100 co-treatment, confirming the Sigmar1-dependency of SA4503\u2019s action. Conclusions: These findings demonstrate that the activation of Sigmar1 by SA4503 protects against ADR-induced podocyte injury and glomerular damage, likely by stabilizing Sigmar1-nephrin interactions. Therefore, Sigmar1 represents a promising therapeutic target for glomerular diseases such as nephrotic syndrome.<\/jats:p>","DOI":"10.3390\/ph18020172","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T04:59:10Z","timestamp":1737953950000},"page":"172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SA4503 Mitigates Adriamycin-Induced Nephropathy via Sigma-1 Receptor in Animal and Cell-Based Models"],"prefix":"10.3390","volume":"18","author":[{"given":"Hideaki","family":"Tagashira","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita 010-8543, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Chida","sequence":"additional","affiliation":[{"name":"Bioscience Education and Research Support Center, Akita University, Akita 010-8543, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0073-3071","authenticated-orcid":false,"given":"Md. Shenuarin","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA"},{"name":"Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohji","family":"Fukunaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-4884","authenticated-orcid":false,"given":"Tomohiro","family":"Numata","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita 010-8543, Akita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000481633","article-title":"A Review of Podocyte Biology","volume":"47","author":"Garg","year":"2018","journal-title":"Am. J. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s001090050206","article-title":"Regulation of podocyte structure during the development of nephrotic syndrome","volume":"76","author":"Smoyer","year":"1998","journal-title":"J. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1681\/ASN.2017090958","article-title":"Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach","volume":"29","author":"Sethi","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8072","DOI":"10.1073\/pnas.93.15.8072","article-title":"Purification, molecular cloning, and expression of the mammalian sigma1-binding site","volume":"93","author":"Hanner","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","first-page":"517","article-title":"The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog","volume":"197","author":"Martin","year":"1976","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/0006-8993(90)91143-5","article-title":"A sigma-like binding site in rat pheochromocytoma (PC12) cells: Decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain","volume":"527","author":"Hellewell","year":"1990","journal-title":"Brain Res."},{"key":"ref_7","first-page":"284","article-title":"Evidence for sigma opioid receptor: Binding of [3H]SKF-10047 to etorphine-inaccessible sites in guinea-pig brain","volume":"223","author":"Su","year":"1982","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hayashi, T. (2019). The Sigma-1 Receptor in Cellular Stress Signaling. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00733"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43156","DOI":"10.1074\/jbc.M112.380444","article-title":"The lifetime of UDP-galactose:ceramide galactosyltransferase is controlled by a distinct endoplasmic reticulum-associated degradation (ERAD) regulated by sigma-1 receptor chaperones","volume":"287","author":"Hayashi","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.cell.2007.08.036","article-title":"Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival","volume":"131","author":"Hayashi","year":"2007","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Aishwarya, R., Abdullah, C.S., Morshed, M., Remex, N.S., and Bhuiyan, M.S. (2021). Sigmar1\u2019s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.705575"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.tips.2010.08.007","article-title":"The sigma-1 receptor chaperone as an inter-organelle signaling modulator","volume":"31","author":"Su","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/s41594-018-0137-2","article-title":"Structural basis for \u03c3(1) receptor ligand recognition","volume":"25","author":"Schmidt","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/nature17391","article-title":"Crystal structure of the human \u03c31 receptor","volume":"532","author":"Schmidt","year":"2016","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"H1535","DOI":"10.1152\/ajpheart.00198.2010","article-title":"Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice","volume":"299","author":"Tagashira","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173614","DOI":"10.1016\/j.ejphar.2020.173614","article-title":"Chronic sigma-1 receptor activation ameliorates ventricular remodeling and decreases susceptibility to ventricular arrhythmias after myocardial infarction in rats","volume":"889","author":"Fo","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Munguia-Galaviz, F.J., Miranda-Diaz, A.G., Cardenas-Sosa, M.A., and Echavarria, R. (2023). Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031997"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.lfs.2013.12.019","article-title":"Fluvoxamine rescues mitochondrial Ca2+ transport and ATP production through \u03c3(1)-receptor in hypertrophic cardiomyocytes","volume":"95","author":"Tagashira","year":"2014","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/sj.bjp.0705605","article-title":"Antitussive activity of sigma-1 receptor agonists in the guinea-pig","volume":"141","author":"Brown","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00406-020-01231-x","article-title":"Repurposing of CNS drugs to treat COVID-19 infection: Targeting the sigma-1 receptor","volume":"271","author":"Hashimoto","year":"2021","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharmthera.2009.07.001","article-title":"The pharmacology of sigma-1 receptors","volume":"124","author":"Maurice","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/0014-2999(94)90453-7","article-title":"NE-100, a novel potent sigma ligand, preferentially binds to sigma 1 binding sites in guinea pig brain","volume":"251","author":"Chaki","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0014-2999(96)00201-4","article-title":"Binding properties of SA4503, a novel and selective sigma 1 receptor agonist","volume":"306","author":"Matsuno","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1172\/JCI69557","article-title":"KLF4-dependent epigenetic remodeling modulates podocyte phenotypes and attenuates proteinuria","volume":"124","author":"Hayashi","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2016.02.013","article-title":"Three-dimensional podocyte-endothelial cell co-cultures: Assembly, validation, and application to drug testing and intercellular signaling studies","volume":"86","author":"Li","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/ki.2014.67","article-title":"Matrix metalloproteinase-9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation","volume":"86","author":"Li","year":"2014","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhong, F., Wang, W., Lee, K., He, J.C., and Chen, N. (2016). Role of C\/EBP-\u03b1 in Adriamycin-induced podocyte injury. Sci. Rep., 6.","DOI":"10.1038\/srep33520"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1016\/j.ymthe.2023.09.003","article-title":"Asparagine endopeptidase protects podocytes in adriamycin-induced nephropathy by regulating actin dynamics through cleaving transgelin","volume":"31","author":"Qiu","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1038\/ki.2008.413","article-title":"Podocyte foot process effacement as a diagnostic tool in focal segmental glomerulosclerosis","volume":"74","author":"Deegens","year":"2008","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"F333","DOI":"10.1152\/ajprenal.00478.2012","article-title":"The podocyte\u2019s response to stress: The enigma of foot process effacement","volume":"304","author":"Kriz","year":"2013","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Gaja-Capdevila, N., Hern\u00e1ndez, N., Zamanillo, D., Vela, J.M., Merlos, M., Navarro, X., and Herrando-Grabulosa, M. (2021). Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136956"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1161\/STROKEAHA.114.005835","article-title":"Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke","volume":"45","author":"Urfer","year":"2014","journal-title":"Stroke"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0006-2952(01)00666-9","article-title":"Molecular cloning and pharmacological characterization of the rat sigma1 receptor","volume":"62","author":"Mei","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1258\/ebm.2009.009177","article-title":"Stimulation of Sigma-1 receptor by dehydroepiandrosterone ameliorates hypertension-induced kidney hypertrophy in ovariectomized rats","volume":"235","author":"Bhuiyan","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1681\/ASN.2015070772","article-title":"\u03c31-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury","volume":"28","author":"Hosszu","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1007\/s11033-023-08303-w","article-title":"PRE-084 ameliorated kidney injury by reducing endoplasmic reticulum stress in the rat model of adenine-induced chronic kidney disease","volume":"50","author":"Kumaran","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/syn.20253","article-title":"Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503","volume":"59","author":"Lever","year":"2006","journal-title":"Synapse"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1016\/j.bbagen.2012.12.029","article-title":"Stimulation of \u03c31-receptor restores abnormal mitochondrial Ca\u00b2\u207a mobilization and ATP production following cardiac hypertrophy","volume":"1830","author":"Tagashira","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41398-024-03185-3","article-title":"Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids","volume":"14","author":"Izumi","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ejphar.2019.03.032","article-title":"Sertraline inhibits nerve growth factor-induced neurite outgrowth in PC12 cells via a mechanism involving the sigma-1 receptor","volume":"853","author":"Matsushima","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Voronin, M.V., Shangin, S.V., Litvinova, S.A., Abramova, E.V., Kurbanov, R.D., Rybina, I.V., Vakhitova, Y.V., and Seredenin, S.B. (2023). Pharmacological Analysis of GABA(A) Receptor and Sigma1R Chaperone Interaction: Research Report I-Investigation of the Anxiolytic, Anticonvulsant and Hypnotic Effects of Allosteric GABA(A) Receptors\u2019 Ligands. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119580"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1046\/j.1523-1755.2000.07505.x","article-title":"Glomerular hypertension, abnormal glomerular growth, and progression of renal diseases","volume":"75","author":"Fogo","year":"2000","journal-title":"Kidney Int. Suppl."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1523-1755.2005.67097.x","article-title":"Pathways to nephron loss starting from glomerular diseases-insights from animal models","volume":"67","author":"Kriz","year":"2005","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10157-020-01854-3","article-title":"New insight into podocyte slit diaphragm, a therapeutic target of proteinuria","volume":"24","author":"Kawachi","year":"2020","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41581-021-00427-1","article-title":"Therapeutic trials in adult FSGS: Lessons learned and the road forward","volume":"17","author":"Wetzels","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/10.1.1","article-title":"The murine nephrin gene is specifically expressed in kidney, brain and pancreas: Inactivation of the gene leads to massive proteinuria and neonatal death","volume":"10","author":"Putaala","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1681\/ASN.2014040405","article-title":"Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult Kidneys","volume":"26","author":"Li","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/S0002-9440(10)64128-4","article-title":"Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome","volume":"158","author":"Doublier","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cell.2012.12.004","article-title":"Dynamic interaction between sigma-1 receptor and Kv1.2 shapes neuronal and behavioral responses to cocaine","volume":"152","author":"Kourrich","year":"2013","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s44161-021-00016-2","article-title":"Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome","volume":"1","author":"Song","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev-physiol-031522-100639","article-title":"Mechanisms of Protein Trafficking and Quality Control in the Kidney and Beyond","volume":"85","author":"Shaw","year":"2023","journal-title":"Annu. Rev. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41419-023-05905-x","article-title":"Research progress on endoplasmic reticulum homeostasis in kidney diseases","volume":"14","author":"Wu","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_53","first-page":"297","article-title":"ER-associated degradation of nephrin","volume":"17","author":"Allison","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Yoshida, S., Wei, X., Zhang, G., O\u2019Connor, C.L., Torres, M., Zhou, Z., Lin, L., Menon, R., Xu, X., and Zheng, W. (2021). Endoplasmic reticulum-associated degradation is required for nephrin maturation and kidney glomerular filtration function. J. Clin. Investig., 131.","DOI":"10.1172\/JCI143988"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15577","DOI":"10.1096\/fj.202000078RR","article-title":"Suppressed ER-associated degradation by intraglomerular cross talk between mesangial cells and podocytes causes podocyte injury in diabetic kidney disease","volume":"34","author":"Fujimoto","year":"2020","journal-title":"Faseb. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/sj.npp.1301047","article-title":"Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of fluvoxamine: Role of sigma-1 receptors","volume":"32","author":"Hashimoto","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1167\/iovs.61.13.3","article-title":"Comparison of Sigma 1 Receptor Ligands SA4503 and PRE084 to (+)-Pentazocine in the rd10 Mouse Model of RP","volume":"61","author":"Wang","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Numata, T., Sato-Numata, K., Hermosura, M.C., Mori, Y., and Okada, Y. (2021). TRPM7 is an essential regulator for volume-sensitive outwardly rectifying anion channel. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02127-9"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Tagashira, H., Abe, F., Sato-Numata, K., Aizawa, K., Hirasawa, K., Kure, Y., Iwata, D., and Numata, T. (2023). Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1264076"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Iacobini, C., Vitale, M., Sentinelli, F., Haxhi, J., Pugliese, G., and Menini, S. (2024). Renal Expression and Localization of the Receptor for (Pro)renin and Its Ligands in Rodent Models of Diabetes, Metabolic Syndrome, and Age-Dependent Focal and Segmental Glomerulosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042217"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.yexcr.2006.01.004","article-title":"Silencing of sigma-1 receptor induces cell death in human lens cells","volume":"312","author":"Wang","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"288","DOI":"10.7150\/jca.20499","article-title":"Genistein Promotes Proliferation of Human Cervical Cancer Cells Through Estrogen Receptor-Mediated PI3K\/Akt-NF-\u03baB Pathway","volume":"9","author":"Chen","year":"2018","journal-title":"J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jphs.2022.12.005","article-title":"Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca(2+) homeostasis in cardiomyocytes","volume":"151","author":"Tagashira","year":"2023","journal-title":"J. Pharmacol. 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