{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:04:24Z","timestamp":1785791064153,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselleria de Educaci\u00f3n of Valencia, Spain","award":["5\/2007"],"award-info":[{"award-number":["5\/2007"]}]},{"name":"Ministerio de Econom\u00eda of the Spanish Government, the Fundaci\u00f3n Genoma Espa\u00f1a","award":["5\/2007"],"award-info":[{"award-number":["5\/2007"]}]},{"name":"Conselleria de Econom\u00eda of Valencia, Spain","award":["5\/2007"],"award-info":[{"award-number":["5\/2007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myotonic dystrophy type 1 (DM1) is a complex rare disorder characterized by progressive muscle dysfunction, involving weakness, myotonia, and wasting, but also exhibiting additional clinical signs in multiple organs and systems. Central dysregulation, caused by an expansion of a CTG trinucleotide repeat in the DMPK gene\u2019s 3\u2019 UTR, has led to exploring various therapeutic approaches in recent years, a few of which are currently under clinical trial. However, no effective disease-modifying treatments are available yet. In this study, we demonstrate that treatments with boldine, a natural alkaloid identified in a large-scale Drosophila-based pharmacological screening, was able to modify disease phenotypes in several DM1 models. The most significant effects include consistent reduction in nuclear RNA foci, a dynamic molecular hallmark of the disease, and noteworthy anti-myotonic activity. These results position boldine as an attractive new candidate for therapy development in DM1.<\/jats:p>","DOI":"10.3390\/ijms24129820","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T02:28:45Z","timestamp":1686104925000},"page":"9820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Natural Compound Boldine Lessens Myotonic Dystrophy Type 1 Phenotypes in DM1 Drosophila Models, Patient-Derived Cell Lines, and HSALR Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Mari Carmen","family":"\u00c1lvarez-Abril","sequence":"first","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Garc\u00eda-Alcover","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"},{"name":"Human Translational Genomics Group, Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, 46100 Burjasot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Colonques-Bellmunt","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Garijo","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"P\u00e9rez-Alonso","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"},{"name":"Human Translational Genomics Group, Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, 46100 Burjasot, Spain"},{"name":"Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-047X","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Artero","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"},{"name":"Human Translational Genomics Group, Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, 46100 Burjasot, Spain"},{"name":"Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-2635","authenticated-orcid":false,"given":"Arturo","family":"L\u00f3pez-Castel","sequence":"additional","affiliation":[{"name":"Valentia BioPharma S.L., 46980 Paterna, Spain"},{"name":"Human Translational Genomics Group, Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia, 46100 Burjasot, Spain"},{"name":"Incliva Biomedical Research Institute, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.ncl.2014.04.011","article-title":"Myotonic dystrophy","volume":"32","author":"Thornton","year":"2014","journal-title":"Neurol. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1159\/000524734","article-title":"Global prevalence of myotonic dystrophy: An updated systematic review and meta-analysis","volume":"56","author":"Liao","year":"2022","journal-title":"Neuroepidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1045","DOI":"10.1212\/WNL.0000000000011425","article-title":"Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program","volume":"96","author":"Johnson","year":"2021","journal-title":"Neurology"},{"key":"ref_4","unstructured":"Saunders, W.B. (2001). Myotonic Dystrophy, OUP Oxford. [3rd ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00418-015-1315-5","article-title":"Dynamic changes of nuclear RNA foci in proliferating DM1 cells","volume":"143","author":"Xia","year":"2015","journal-title":"Histochem. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/dvdy.24240","article-title":"Developmental insights into the pathology of and therapeutic strategies for DM1: Back to the basics","volume":"244","author":"Chau","year":"2015","journal-title":"Dev. Dyn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41467-018-04892-4","article-title":"miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models","volume":"9","author":"Moreno","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103489","DOI":"10.1016\/j.drudis.2023.103489","article-title":"The myotonic dystrophy type 1 drug development pipeline: 2022 edition","volume":"28","author":"Artero","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e228","DOI":"10.1212\/WNL.0000000000011002","article-title":"Mexiletine in Myotonic Dystrophy Type 1. A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"96","author":"Heatwole","year":"2021","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1093\/brain\/awy231","article-title":"Improved mobility with metformin in patients with myotonic dystrophy type 1: A randomized controlled trial","volume":"141","author":"Bassez","year":"2018","journal-title":"Brain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/acn3.271","article-title":"Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy","volume":"3","author":"Nakamori","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.pediatrneurol.2020.08.001","article-title":"A Phase 2 Study of AMO-02 (Tideglusib) in Congenital and Childhood-Onset Myotonic Dystrophy Type 1 (DM1)","volume":"112","author":"Horrigan","year":"2020","journal-title":"Pediatr. Neurol."},{"key":"ref_13","unstructured":"Pascual-Gilabert, M. (2022). Nutritional Management of Myotonic Dystrophy Type 1. [Ph.D. Thesis, Universitat de Barcelona]."},{"key":"ref_14","unstructured":"Myogem Health Company (2023, April 26). CORDIS EU Research Results. Available online: https:\/\/cordis.europa.eu\/project\/id\/875615\/reporting."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2005.09.002","article-title":"Boldine and its antioxidant or health-promoting properties","volume":"159","author":"Speisky","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/1043-6618(94)80093-6","article-title":"Boldo and boldine: An emerging case of natural drug development","volume":"29","author":"Speisky","year":"1994","journal-title":"Pharmacol. Res."},{"key":"ref_17","first-page":"593672","article-title":"Boldine prevents renal alterations in diabetic rats","volume":"2013","author":"Vielma","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.2042-7158.1993.tb05572.x","article-title":"Different mechanism of relaxation induced by aporphine alkaloids in rat uterus","volume":"45","author":"Ivorra","year":"1993","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_19","first-page":"1297","article-title":"Development of a Drosophila melanogaster spliceosensor system for in vivo high-throughput screening in myotonic dystrophy type 1","volume":"7","author":"Garijo","year":"2014","journal-title":"Dis. Model. Mech."},{"key":"ref_20","unstructured":"(2023, April 22). Drug Bank. Available online: https:\/\/go.drugbank.com\/categories\/DBCAT000691."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.fitote.2018.02.020","article-title":"Variation of the alkaloid content of Peumus boldus (boldo)","volume":"127","author":"Liberona","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_22","first-page":"487","article-title":"Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds","volume":"10","author":"Arandel","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1093\/hmg\/ddi223","article-title":"Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic\/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1","volume":"14","author":"Kimura","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1093\/hmg\/ddl132","article-title":"Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy","volume":"15","author":"Lin","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","unstructured":"\u00c1lvarez-Abril, M.C., Garc\u00eda-Alcover, I., Colonques-Bellmunt, J., Garijo, R., P\u00e9rez-Alonso, M., Artero, R., and L\u00f3pez-Castel, A. AS modulation in patient-derived cells. Personal communication."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1126\/science.289.5485.1769","article-title":"Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat","volume":"289","author":"Mankodi","year":"2000","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1085\/jgp.200609635","article-title":"Muscle chloride channel dysfunction in two mouse models of myotonic dystrophy","volume":"129","author":"Lueck","year":"2007","journal-title":"J. Gen. Physiol."},{"key":"ref_28","unstructured":"\u00c1lvarez-Abril, M.C., Garc\u00eda-Alcover, I., Colonques-Bellmunt, J., Garijo, R., P\u00e9rez-Alonso, M., Artero, R., and L\u00f3pez-Castel, A. AS modulation in HSALR mouse model. Personal communication."},{"key":"ref_29","unstructured":"\u00c1lvarez-Abril, M.C., Garc\u00eda-Alcover, I., Colonques-Bellmunt, J., Garijo, R., P\u00e9rez-Alonso, M., Artero, R., and L\u00f3pez-Castel, A. Myotonia quantification in HSALR mouse model after 5 days of treatment. Personal communication."},{"key":"ref_30","unstructured":"\u00c1lvarez-Abril, M.C., Garc\u00eda-Alcover, I., Colonques-Bellmunt, J., Garijo, R., P\u00e9rez-Alonso, M., Artero, R., and L\u00f3pez-Castel, A. Myotonia quantification in HSALR mouse model after 21 days of treatment. Personal communication."},{"key":"ref_31","first-page":"CD004762","article-title":"Drug treatment for myotonia","volume":"2006","author":"Trip","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0896-6273(03)00168-5","article-title":"Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1","volume":"38","author":"Schroeder","year":"2003","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuropharm.2012.09.006","article-title":"In vivo evaluation of anti-myotonic efficacy of \u03b2-adrenergic drugs in a rat model of myotonia","volume":"65","author":"Desaphy","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18551","DOI":"10.1073\/pnas.0903234106","article-title":"Pentamidine reverses the splicing defects associated with myotonic dystrophy","volume":"106","author":"Warf","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.ab.2005.12.010","article-title":"Analysis of RNA-protein interactions by a microplate-based fluorescence anisotropy assay","volume":"350","author":"Mao","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Garcia-Lopez, A., Monferrer, L., Garcia-Alcover, I., Vicente-Crespo, M., Alvarez-Abril, M.C., and Artero, R.D. (2008). Genetic and chemical modifiers of a CUG toxicity model in Drosophila. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001595"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Neault, N., O\u2019Reilly, S., Baig, A.T., Plaza-Diaz, J., Azimi, M., Farooq, F., Baird, S.D., and MacKenzie, A. (2021). High-throughput kinome-RNAi screen identifies protein kinase R activator (PACT) as a novel genetic modifier of CUG foci integrity in myotonic dys-trophy type 1 (DM1). PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256276"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-0716-0771-8_7","article-title":"Degradation of Toxic RNA in Myotonic Dystrophy Using Gapmer Antisense Oligonucleotides","volume":"2176","author":"Nguyen","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.3389\/fmicb.2018.01659","article-title":"Boldine-Derived Alkaloids Inhibit the Activity of DNA Topoisomerase I and Growth of Mycobacterium tuberculosis","volume":"9","author":"Rodrigues","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.3390\/molecules20033730","article-title":"Dose-dependent cytotoxic effects of boldine in HepG-2 cells-telomerase inhibition and apoptosis induction","volume":"20","author":"Noureini","year":"2015","journal-title":"Molecules"},{"key":"ref_41","first-page":"719","article-title":"Evaluation of cytotoxic and chemotherapeutic properties of boldine in breast cancer using in vitro and in vivo models","volume":"8","author":"Paydar","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"36.e1","DOI":"10.1016\/j.urolonc.2013.02.012","article-title":"Boldine induces cell cycle arrest and apoptosis in T24 human bladder cancer cell line via regulation of ERK, AKT, and GSK-3\u03b2","volume":"32","author":"Gerhardt","year":"2014","journal-title":"Urol. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"D\u2019Ambrosio, E.S., Chuang, K., David, W.S., Amato, A.A., and Gonzalez-Perez, P. (2023). Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study. Muscle Nerve.","DOI":"10.1002\/mus.27801"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e159357","DOI":"10.1172\/jci.insight.159357","article-title":"Senescence plays a role in myotonic dystrophy type 1","volume":"7","author":"Gerenu","year":"2022","journal-title":"JCI Insight"},{"key":"ref_45","first-page":"125","article-title":"Muscle wasting in myotonic dystrophies: A model of premature aging","volume":"7","author":"Goicoechea","year":"2015","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Toro, C.A., Johnson, K., Hansen, J., Siddiq, M.M., V\u00e1squez, W., Zhao, W., Graham, Z.A., S\u00e1ez, J.C., Iyengar, R., and Cardozo, C.P. (2023). Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury. bioRxiv.","DOI":"10.1101\/2023.02.15.528337"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/brv.12674","article-title":"The hallmarks of myotonic dystrophy type 1 muscle dysfunction","volume":"96","author":"Ozimski","year":"2021","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.celrep.2017.10.018","article-title":"Aberrant Myokine Signaling in Congenital Myotonic Dystrophy","volume":"21","author":"Nakamori","year":"2017","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1248\/cpb.52.696","article-title":"Reactive oxygen species (ROS) generation inhibited by aporphine and phenanthrene alkaloids semi-synthesized from natural boldine","volume":"52","author":"Abarca","year":"2004","journal-title":"Chem. Pharm. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3109\/10715762.2014.887847","article-title":"Imbalanced oxidant and antioxidant ratio in myotonic dystrophy type 1","volume":"48","author":"Kumar","year":"2014","journal-title":"Free Radic. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3389\/fncel.2015.00156","article-title":"ClC-1 chloride channels: State-of-the-art research and future challenges","volume":"9","author":"Imbrici","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1085\/jgp.201611582","article-title":"Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle","volume":"147","author":"Pedersen","year":"2016","journal-title":"J. Gen. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.biocel.2019.02.008","article-title":"Conserved functions of RNA-binding proteins in muscle","volume":"110","author":"Nikonova","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bcp.2012.11.010","article-title":"Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism","volume":"85","author":"Lau","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S214","DOI":"10.1016\/j.nmd.2012.10.010","article-title":"Fatigue in muscular dystrophies","volume":"22","author":"Angelini","year":"2012","journal-title":"Neuromuscul. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Liguori, S., Moretti, A., Toro, G., Paoletta, M., Palomba, A., Barra, G., Gimigliano, F., and Iolascon, G. (2023). Pain and Motor Function in Myotonic Dystrophy Type 1: A Cross-Sectional Study. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20075244"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cea, L.A., Fern\u00e1ndez, G., Arias-Bravo, G., Castillo-Ruiz, M., Escamilla, R., Bra\u00f1es, M.C., and S\u00e1ez, J.C. (2020). Blockade of Hemichannels Normalizes the Differentiation Fate of Myoblasts and Features of Skeletal Muscles from Dysferlin-Deficient Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176025"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/glia.23182","article-title":"Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer\u2019s disease","volume":"65","author":"Yi","year":"2017","journal-title":"Glia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"fcac154","DOI":"10.1093\/braincomms\/fcac154","article-title":"Cell type-specific abnormalities of central nervous system in myotonic dystrophy type 1","volume":"4","author":"Nakamori","year":"2022","journal-title":"Brain Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1152\/physrev.1984.64.4.1103","article-title":"Adrenal medullary chromaffin cells in vitro","volume":"64","author":"Livett","year":"1984","journal-title":"Physiol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0003-2697(90)90287-J","article-title":"Separation and culture of living adrena-line- and noradrenaline-containing cells from bovine adrenal medullae","volume":"185","author":"Moro","year":"1990","journal-title":"Anal. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF00656997","article-title":"Improved patch-clamp techniques for high-resolution current recording from cells and cell free membrane patches","volume":"391","author":"Hamill","year":"1981","journal-title":"Pfluguers Arch. Eur. J. Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/9820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:49:24Z","timestamp":1760125764000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/12\/9820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,6]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["ijms24129820"],"URL":"https:\/\/doi.org\/10.3390\/ijms24129820","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,6]]}}}