{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:29:36Z","timestamp":1784366976461,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dr. Hans Messer Stiftung, Bad Soden, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation is intimately involved in the pathogenesis of diabetic kidney disease. Inhibition of SGLT-2 by a specific class of drugs, gliflozins, has been shown to reduce inflammation and attenuate the progression of diabetic nephropathy, in addition to its main effect of inhibiting renal glucose reabsorption. We used highly purified human renal proximal tubular epithelial cells (PTCs) as an in vitro model to study the cellular response to a diabetic (high glucose) and inflammatory (cytokines) microenvironment and the effect of gliflozins. In this context, we investigated the influence of SGLT-2 inhibition by empa- and dapagliflozin (500 nM) on the expression of pro-inflammatory factors (IL-1\u03b2, IL-6, TNF-\u03b1, MCP-1, and ICAM-1). The results clearly indicate an anti-inflammatory effect of both gliflozins. Although induced expression of the four cytokines was only slightly attenuated, there was a clear effect on the expression of the adhesion molecule ICAM-1, a master regulator of cellular responses in inflammation and injury resolution. The induced expression of ICAM-1 mRNA was significantly reduced by approximately 13.5% by empagliflozin and also showed an inhibitory trend with dapagliflozin. However, induced ICAM-1 protein expression was significantly inhibited from 24.71 \u00b1 1.0 ng\/mL to 18.81 \u00b1 3.9 (empagliflozin) and 19.62 \u00b1 2.1 ng\/mL (dapagliflozin). In conclusion, an additional anti-inflammatory effect of empa- and dapagliflozin in therapeutically observed concentrations was demonstrated in primary human PTCs in vitro.<\/jats:p>","DOI":"10.3390\/ijms24031811","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T03:41:52Z","timestamp":1673926912000},"page":"1811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gliflozins Have an Anti-Inflammatory Effect on Renal Proximal Tubular Epithelial Cells in a Diabetic and Inflammatory Microenvironment In Vitro"],"prefix":"10.3390","volume":"24","author":[{"given":"Benjamin","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Internal Medicine 4, Nephrology, University Hospital, Goethe-University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-9387","authenticated-orcid":false,"given":"Dominik C.","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry I, Faculty of Medicine, Goethe-University, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7124-0904","authenticated-orcid":false,"given":"Ralf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Division of Allergology, Pneumology and Cystic Fibrosis, Department for Children and Adolescents, University Hospital, Goethe-University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Geiger","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 4, Nephrology, University Hospital, Goethe-University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thimoteus","family":"Speer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 4, Nephrology, University Hospital, Goethe-University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-3312","authenticated-orcid":false,"given":"Patrick C.","family":"Baer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 4, Nephrology, University Hospital, Goethe-University, 60596 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.phrs.2016.07.001","article-title":"Pharmacological aspects of the safety of gliflozins","volume":"118","author":"Faillie","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1464-5491.2009.02894.x","article-title":"Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications","volume":"27","author":"Gerich","year":"2010","journal-title":"Diabet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tentolouris, A., Vlachakis, P., Tzeravini, E., Eleftheriadou, I., and Tentolouris, N. (2019). SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16162965"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic Kidney Disease: Challenges, Progress, and Possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","first-page":"191","article-title":"Tofogliflozin, a Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation","volume":"48","author":"Ishibashi","year":"2016","journal-title":"Horm. Metab. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Prandi, F.R., Barone, L., Lecis, D., Belli, M., Sergi, D., Milite, M., Lerakis, S., Romeo, F., and Barill\u00e0, F. (2022). Biomolecular Mechanisms of Cardiorenal Protection with Sodium-Glucose Co-Transporter 2 Inhibitors. Biomolecules, 12.","DOI":"10.3390\/biom12101349"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1053\/j.ajkd.2014.02.010","article-title":"Sodium\/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: Targeting the renal tubule in diabetes","volume":"64","author":"Gabbai","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Matoba, K., Takeda, Y., Nagai, Y., Kawanami, D., Utsunomiya, K., and Nishimura, R. (2019). Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143393"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Winiarska, A., Knysak, M., Nabrdalik, K., Gumprecht, J., and Stomp\u00f3r, T. (2021). Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910822"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1055\/s-0034-1395609","article-title":"Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis","volume":"47","author":"Ojima","year":"2015","journal-title":"Horm. Metab. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/s41569-020-0406-8","article-title":"SGLT2 inhibitors: Mechanisms of cardiovascular benefit beyond glycaemic control","volume":"17","author":"Cowie","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Baer, P.C., Koch, B., Freitag, J., Schubert, R., and Geiger, H. (2020). No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020391"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Feij\u00f3o-Band\u00edn, S., Arag\u00f3n-Herrera, A., Otero-Santiago, M., Anido-Varela, L., Mora\u00f1a-Fern\u00e1ndez, S., Taraz\u00f3n, E., Rosell\u00f3-Llet\u00ed, E., Portol\u00e9s, M., Gualillo, O., and Gonz\u00e1lez-Juanatey, J.R. (2022). Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105634"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ejphar.2013.05.014","article-title":"Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice","volume":"715","author":"Tahara","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1124\/jpet.116.235069","article-title":"Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation","volume":"359","author":"Benetti","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.freeradbiomed.2017.01.035","article-title":"Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts","volume":"104","author":"Lee","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zaibi, N., Li, P., and Xu, S.-Z. (2021). Protective effects of dapagliflozin against oxidative stress-induced cell injury in human proximal tubular cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247234"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109506","DOI":"10.1016\/j.cellsig.2019.109506","article-title":"Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition","volume":"68","author":"Das","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F67","DOI":"10.1152\/ajprenal.00402.2019","article-title":"Blockade of sodium-glucose cotransporter 2 suppresses high glucose-induced angiotensinogen augmentation in renal proximal tubular cells","volume":"318","author":"Satou","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Xu, J., Kitada, M., Ogura, Y., Liu, H., and Koya, D. (2021). Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells. Cells, 10.","DOI":"10.3390\/cells10061457"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e10615","DOI":"10.1016\/j.heliyon.2022.e10615","article-title":"Proximal tubular epithelia-specific transcriptomics of diabetic mice treated with dapagliflozin","volume":"8","author":"Nakamura","year":"2022","journal-title":"Heliyon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12933-021-01252-3","article-title":"Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: Protective effect of gliflozins","volume":"20","author":"Park","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mihaljevi\u0107, V., Zjali\u0107, M., Kizivat, T., Omanovi\u0107 Kolari\u0107, T., Smoli\u0107, M., Ro\u0111ak, E., \u010covi\u0107, M., Kuna, L., Smoli\u0107, R., and V\u010dev, A. (2022). Molecular Mechanisms Linking Empagliflozin to Renal Protection in the LLC-PK1 Model of Diabetic Nephropathy. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112983"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mal\u00ednsk\u00e1, H., H\u00fcttl, M., Markov\u00e1, I., Mikl\u00e1nkov\u00e1, D., Hojn\u00e1, S., Papou\u0161ek, F., \u0160ilhav\u00fd, J., Mlejnek, P., Zicha, J., and Hrdli\u010dka, J. (2022). Beneficial Effects of Empagliflozin Are Mediated by Reduced Renal Inflammation and Oxidative Stress in Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092066"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.2174\/0929867322666150415145814","article-title":"The Role and Predictive Value of Cytokines in Atherosclerosis and Coronary Artery Disease","volume":"22","author":"Tousoulis","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1093\/ndt\/gfy115","article-title":"Bone, inflammation and the bone marrow niche in chronic kidney disease: What do we know?","volume":"33","author":"Mazzaferro","year":"2018","journal-title":"Nephrol. Dial. Transplant"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s13205-022-03375-0","article-title":"Cytokine database of stress and metabolic disorders (CdoSM): A connecting link between stress and cardiovascular disease, hypertension, diabetes and obesity","volume":"12","author":"Bhasin","year":"2022","journal-title":"3 Biotech"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.3389\/fphar.2019.01192","article-title":"Inflammation in Renal Diseases: New and Old Players","volume":"10","author":"Watanabe","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.ekir.2021.04.023","article-title":"Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2","volume":"6","author":"Stenvinkel","year":"2021","journal-title":"Kidney Int. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","article-title":"ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis","volume":"108","author":"Bui","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_32","first-page":"3625","article-title":"Renoprotection of dapagliflozin in human renal proximal tubular cells via the inhibition of the high mobility group box 1-receptor for advanced glycation end products-nuclear factor-\u03baB signaling pathway","volume":"18","author":"Yao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lee, W.-C., Chau, Y.-Y., Ng, H.-Y., Chen, C.-H., Wang, P.-W., Liou, C.-W., Lin, T.-K., and Chen, J.-B. (2019). Empagliflozin Protects HK-2 Cells from High Glucose-Mediated Injuries via a Mitochondrial Mechanism. Cells, 8.","DOI":"10.3390\/cells8091085"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Panchapakesan, U., Pegg, K., Gross, S., Komala, M.G., Mudaliar, H., Forbes, J., Pollock, C., and Mather, A. (2013). Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054442"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/dom.13905","article-title":"Effect of Dapagliflozin, a Sodium-glucose Cotransporter-2 Inhibitor, on Gluconeogenesis in Proximal Renal Tubules","volume":"22","author":"Kim","year":"2019","journal-title":"Diabetes Obes. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"865","DOI":"10.33594\/000000178","article-title":"Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor \u03b1-Stimulated Human Coronary Arterial Endothelial Cells","volume":"53","author":"Uthman","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Heimke, M., Lenz, F., Rickert, U., Lucius, R., and Cossais, F. (2022). Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia. Cells, 11.","DOI":"10.3390\/cells11193107"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12681","DOI":"10.1038\/s41598-022-16763-6","article-title":"Empagliflozin mitigates endothelial inflammation and attenuates endoplasmic reticulum stress signaling caused by sustained glycocalyx disruption","volume":"12","author":"Campeau","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s10787-021-00797-9","article-title":"Anti-inflammatory potential of Empagliflozin","volume":"29","author":"Pirklbauer","year":"2021","journal-title":"Inflammopharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pirklbauer, M., Bernd, M., Fuchs, L., Staudinger, P., Corazza, U., Leierer, J., Mayer, G., and Schramek, H. (2020). Empagliflozin Inhibits Basal and IL-1\u03b2-Mediated MCP-1\/CCL2 and Endothelin-1 Expression in Human Proximal Tubular Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218189"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1038\/s41598-018-23420-4","article-title":"Canagliflozin inhibits interleukin-1\u03b2-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms","volume":"8","author":"Mancini","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9944880","DOI":"10.1155\/2021\/9944880","article-title":"Anti-inflammatory Effects of Empagliflozin and Gemigliptin on LPS-Stimulated Macrophage via the IKK\/NF-\u03baB, MKK7\/JNK, and JAK2\/STAT1 Signalling Pathways","volume":"2021","author":"Lee","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"879522","DOI":"10.3389\/fmolb.2022.879522","article-title":"Cell-Target-Specific Anti-Inflammatory Effect of Empagliflozin: In Vitro Evidence in Human Cardiomyocytes","volume":"9","author":"Giannattasio","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1093\/cvr\/cvaa323","article-title":"Off-target effects of sodium-glucose co-transporter 2 blockers: Empagliflozin does not inhibit Na+\/H+ exchanger-1 or lower Na+i in the heart","volume":"117","author":"Chung","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/cvr\/cvaa123","article-title":"Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase G\u03b1 oxidation","volume":"117","author":"Kolijn","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00018-022-04289-z","article-title":"Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin","volume":"79","author":"Olivieri","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Z\u00fcgner, E., Yang, H.-C., Kotzbeck, P., Boulgaropoulos, B., Sourij, H., Hagvall, S., Elmore, C.S., Esterline, R., Moosmang, S., and Oscarsson, J. (2022). Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation, Glucose Uptake and Cell Metabolism. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147966"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/ki.1997.457","article-title":"Isolation of proximal and distal tubule cells from human kidney by immunomagnetic separation. Technical note","volume":"52","author":"Baer","year":"1997","journal-title":"Kidney Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000096947","article-title":"Differentiation status of human renal proximal and distal tubular epithelial cells in vitro: Differential expression of characteristic markers","volume":"184","author":"Baer","year":"2006","journal-title":"Cells Tissues Organs (Print)"},{"key":"ref_51","unstructured":"EMA (2022, November 24). Assessment Report-Empagliflozin-EMA\/CHMP\/137741\/2014. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/jardiance-epar-public-assessment-report_en.pdf."},{"key":"ref_52","unstructured":"EMA (2022, November 24). Assessment Report-Dapagliflozin-EMA\/689976\/2012. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/forxiga-epar-public-assessment-report_en.pdf."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT\u2013PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1811\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:07:59Z","timestamp":1760119679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/1811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24031811"],"URL":"https:\/\/doi.org\/10.3390\/ijms24031811","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]}}}