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Significant differences in expression were observed between samples before and after rapamycin treatment in nineteen miRNAs in TSC1, five miRNAs in TSC2 and seven miRNAs in controls. Of miRNAs dysregulated before rapamycin treatment, three normalized after treatment in the TSC1 group (miR-21-3p, miR-433-3p, let-7g-3p) and one normalized in the TSC2 group (miR-1224-3p). Of the miRNAs dysregulated before rapamycin treatment in the TSC1 and TSC2 groups, two did not normalize after treatment (miR-33a-3p, miR-29a-3p). The results of the possible targets indicated that there are four common genes with seed regions susceptible to regulation by those miRNAs: ZBTB20, PHACTR2, PLXNC1 and ATP1B4. Our data show no changes in mRNA expression of these targets after rapamycin treatment. In conclusion, results of our study indicate the involvement of miRNA dysregulation in the pathogenesis of TSC. Some of the miRNA might be used as markers of treatment efficacy and autonomic miRNA as a target for future therapy.<\/jats:p>","DOI":"10.3390\/ijms232214493","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T03:02:16Z","timestamp":1669086136000},"page":"14493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["MicroRNA Expression Profile in TSC Cell Lines and the Impact of mTOR Inhibitor"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-1033","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Pawlik","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Sporna 36\/50, 91-738 Lodz, Poland"},{"name":"Postgraduate School of Molecular Medicine, Medical University of Warsaw, \u017bwirki i Wigury 81, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-5833","authenticated-orcid":false,"given":"Szymon","family":"Grabia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-457X","authenticated-orcid":false,"given":"Urszula","family":"Smyczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Fendler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine, Medical University of Lodz, Mazowiecka 15, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1956-5063","authenticated-orcid":false,"given":"Izabela","family":"Dr\u00f3\u017cd\u017c","sequence":"additional","affiliation":[{"name":"Department of Clinical and Laboratory Genetics, Medical University of Lodz, Pomorska 251, 92-231 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Liszewska","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kotulska","sequence":"additional","affiliation":[{"name":"Department of Neurology & Epileptology and Pediatric Rehabilitation, The Children\u2019s Memorial Health Institute, Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-6326","authenticated-orcid":false,"given":"Sergiusz","family":"J\u00f3\u017awiak","sequence":"additional","affiliation":[{"name":"The Children\u2019s Memorial Health Institute, Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-4274","authenticated-orcid":false,"given":"Joanna","family":"Treli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Sporna 36\/50, 91-738 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jdermsci.2015.04.005","article-title":"Mammalian Target of Rapamycin and Tuberous Sclerosis Complex","volume":"79","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 Complex: A Molecular Switchboard Controlling Cell Growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","article-title":"The Tuberous Sclerosis Complex","volume":"355","author":"Crino","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","article-title":"Efficacy and Safety of Everolimus for Subependymal Giant Cell Astrocytomas Associated with Tuberous Sclerosis Complex (EXIST-1): A Multicentre, Randomised, Placebo-Controlled Phase 3 Trial","volume":"381","author":"Franz","year":"2013","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","article-title":"Everolimus for Angiomyolipoma Associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis (EXIST-2): A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial","volume":"381","author":"Bissler","year":"2013","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa063564","article-title":"Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis","volume":"358","author":"Bissler","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","article-title":"Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis","volume":"363","author":"Krueger","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/ana.20784","article-title":"Rapamycin Causes Regression of Astrocytomas in Tuberous Sclerosis Complex","volume":"59","author":"Franz","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00467-014-2949-6","article-title":"The Effects of Everolimus on Tuberous Sclerosis-Associated Lesions Can Be Dramatic but May Be Impermanent","volume":"30","author":"Miller","year":"2015","journal-title":"Pediatr. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6335","DOI":"10.1073\/pnas.1320577111","article-title":"MicroRNAs Are Critical Regulators of Tuberous Sclerosis Complex and MTORC1 Activity in the Size Control of the Xenopus Kidney","volume":"111","author":"Romaker","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fncel.2014.00182","article-title":"MiR-7 and MiR-153 Protect Neurons against MPP+-Induced Cell Death via Upregulation of MTOR Pathway","volume":"8","author":"Fragkouli","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.3390\/ijms14023874","article-title":"Chemical Inhibitors and MicroRNAs (MiRNA) Targeting the Mammalian Target of Rapamycin (MTOR) Pathway: Potential for Novel Anticancer Therapeutics","volume":"14","author":"AlQurashi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pawlik, B., Smyczy\u0144ska, U., Grabia, S., Fendler, W., Dr\u00f3\u017cd\u017c, I., B\u0105bol-Pokora, K., Kotulska, K., J\u00f3\u017awiak, S., Borkowska, J., and M\u0142ynarski, W. (2022). MTOR Inhibitor Treatment in Patients with Tuberous Sclerosis Complex Is Associated with Specific Changes in MicroRNA Serum Profile. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123395"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-016-0512-1","article-title":"Abnormal Serum MicroRNA Profiles in Tuberous Sclerosis Are Normalized during Treatment with Everolimus: Possible Clinical Implications","volume":"11","author":"Trelinska","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Trindade, A.J., Medvetz, D.A., Neuman, N.A., Myachina, F., Yu, J., Priolo, C., and Henske, E.P. (2013). MicroRNA-21 Is Induced by Rapamycin in a Model of Tuberous Sclerosis (TSC) and Lymphangioleiomyomatosis (LAM). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060014"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1093\/nar\/gkg605","article-title":"Identification of Patterns in Biological Sequences at the ALGGEN Server: PROMO and MALGEN","volume":"31","author":"Roset","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Franz, D.N., Belousova, E., Sparagana, S., Bebin, E.M., Frost, M.D., Kuperman, R., Witt, O., Kohrman, M.H., Flamini, J.R., and Wu, J.Y. (2016). Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158476"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00467-017-3806-1","article-title":"The Effect of Everolimus on Renal Angiomyolipoma in Pediatric Patients with Tuberous Sclerosis Being Treated for Subependymal Giant Cell Astrocytoma","volume":"33","author":"Bissler","year":"2018","journal-title":"Pediatr. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1212\/CPJ.0000000000000514","article-title":"Everolimus for Treatment-Refractory Seizures in TSC: Extension of a Randomized Controlled Trial","volume":"8","author":"Franz","year":"2018","journal-title":"Neurol. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/pbc.25368","article-title":"Factors Affecting Response to Everolimus Therapy for Subependymal Giant Cell Astrocytomas Associated with Tuberous Sclerosis","volume":"62","author":"Trelinska","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.7150\/thno.35458","article-title":"Integrative Multi-Omics Analysis Identifies a Prognostic MiRNA Signature and a Targetable MiR-21-3p\/TSC2\/ MTOR Axis in Metastatic Pheochromocytoma\/ Paraganglioma","volume":"9","author":"Calsina","year":"2019","journal-title":"Theranostics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11807","DOI":"10.2147\/OTT.S274451","article-title":"MiR-1224-5p Activates Autophagy, Cell Invasion and Inhibits Epithelial-to-Mesenchymal Transition in Osteosarcoma Cells by Directly Targeting PLK1 Through PI3K\/AKT\/MTOR Signaling Pathway","volume":"13","author":"Jin","year":"2020","journal-title":"Onco. Targets Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.3892\/ol.2020.11835","article-title":"Role of MicroRNA-33a in Malignant Cells (Review)","volume":"20","author":"Gao","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/bioinformatics\/18.2.333","article-title":"PROMO: Detection of Known Transcription Reg-ulatory Elements Using Species-Tailored Searches","volume":"18","author":"Messeguer","year":"2002","journal-title":"Bioinform. Appl. Note"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11477","DOI":"10.2147\/CMAR.S265579","article-title":"CircPVT1 Promoted the Progression of Breast Cancer by Regulating MiR-29a-3p-Mediated AGR2-HIF-1\u03b1 Pathway","volume":"12","author":"Wang","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20534","DOI":"10.1074\/jbc.M611782200","article-title":"Hypoxia-Inducible Factor 1\u03b1 Is Regulated by the Mammalian Target of Rapamycin (MTOR) via an MTOR Signaling Motif","volume":"282","author":"Land","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1758835920937890","DOI":"10.1177\/1758835920937890","article-title":"Long Non-Coding RNA LINC00473 Acts as a MicroRNA-29a-3p Sponge to Promote Hepatocellular Carcinoma Development by Activating Robo1-Dependent PI3K\/AKT\/MTOR Signaling Pathway","volume":"12","author":"Song","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_28","first-page":"22395","article-title":"Evolutionary Diversification of the BetaM Interactome Acquired through Co-Option of the ATP1B4 Gene in Placental Mammals","volume":"6","author":"Korneenko","year":"2016","journal-title":"Nat. Publ. Gr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s12035-018-1104-y","article-title":"Zbtb20 Regulates Developmental Neurogenesis in the Olfactory Bulb and Gliogenesis After Adult Brain Injury","volume":"56","author":"Doeppner","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1242\/dev.000265","article-title":"Hippocampus-like Corticoneurogenesis Induced by Two Isoforms of the BTB-Zinc Finger Gene Zbtb20 in Mice","volume":"134","author":"Nielsen","year":"2007","journal-title":"Development"},{"key":"ref_31","unstructured":"Chabrat, A., Brisson, G., Doucet-Beaupr\u00e9, H., Salesse, C., Profes, M.S., Dovonou, A., Akitegetse, C., Charest, J., Lemstra, S., and C\u00f4t\u00e9, D. Transcriptional Repression of Plxnc1 by Lmx1a and Lmx1b Directs Topographic Dopaminergic Circuit Formation. Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1002\/eji.201343968","article-title":"The Plexin C1 Receptor Promotes Acute Inflammation","volume":"44","author":"Marth","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_33","unstructured":"Walzer, T., Galibert, L., and De Smedt, T. Dendritic Cell Function in Mice Lacking Plexin C1. Int. Immunology."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuroscience.2012.06.059","article-title":"Different Expression Patterns of Phactr Family Members in Normal and Injured Mouse Brain","volume":"221","author":"Kim","year":"2012","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neulet.2009.02.009","article-title":"Phactr2 and Parkinson\u2019s Disease","volume":"453","author":"Wider","year":"2010","journal-title":"Neurosci Lett."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Goldstein, B.A., Hubbard, A.E., Cutler, A., and Barcellos, L.F. (2010). An Application of Random Forests to a Genome-Wide Association Dataset: Methodological Considerations and New Findings. BMC Genet., 11.","DOI":"10.1186\/1471-2156-11-49"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/jb\/mvaa082","article-title":"Long Non-Coding RNA PHACTR2-AS1 Promotes Tongue Squamous Cell Carcinoma Metastasis by Regulating Snail","volume":"168","author":"Yuan","year":"2020","journal-title":"J. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1158\/0008-5472.CAN-19-3326","article-title":"The EZH2-PHACTR2-AS1-Ribosome Axis Induces Genomic Instability and Promotes Growth and Metastasis in Breast Cancer","volume":"80","author":"Chu","year":"2020","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/cmi.2015.43","article-title":"TSC1 Controls IL-1\u03b2 Expression in Macrophages via MTORC1-Dependent C\/EBP\u03b2 Pathway","volume":"13","author":"Yang","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/nature21026","article-title":"Corrigendum: PI3K\u03b3 Is a Molecular Switch That Controls Immune Suppression","volume":"542","author":"Kaneda","year":"2017","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.toxlet.2019.05.003","article-title":"Involvement of C\/EBP\u03b2-Related Signaling Pathway in Methamphetamine-Induced Neuronal Autophagy and Apoptosis","volume":"312","author":"Huang","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4812","DOI":"10.1038\/sj.emboj.7601900","article-title":"Constitutive MTOR Activation in TSC Mutants Sensitizes Cells to Energy Starvation and Genomic Damage via P53","volume":"26","author":"Lee","year":"2007","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1073\/pnas.0502857102","article-title":"The Coordinate Regulation of the P53 and MTOR Pathways in Cells","volume":"102","author":"Feng","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.scr.2021.102225","article-title":"Establishment of Two HiPSC Lines (IIMCBi001-A and IIMCBi002-A) from Dermal Fibroblasts of Healthy Donors and Characterization of Their Cell Cycle","volume":"52","author":"Liszewska","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Robak, P., Dr\u00f3, I., Jarych, D., Mikulski, D., Siemieniuk-Ry, M., Misiewicz, M., Stawiski, K., Fendler, W., Szemraj, J., and Smolewski, P. (2020). The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients. Cancers, 12.","DOI":"10.3390\/cancers12092569"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-020-03743-8","article-title":"NormiRazor: Tool Applying GPU-Accelerated Computing for Determination of Internal References in MicroRNA Transcription Studies","volume":"21","author":"Grabia","year":"2020","journal-title":"BMC Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sticht, C., De La Torre, C., Parveen, A., and Gretz, N. (2018). MiRWalk: An Online Resource for Prediction of MicroRNA Binding Sites. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206239"},{"key":"ref_50","first-page":"D148","article-title":"MiRTarBase 2020: Updates to the Experimentally Validated MicroRNA-Target Interaction Database","volume":"48","author":"Huang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D127","DOI":"10.1093\/nar\/gkz757","article-title":"MiRDB: An Online Database for Prediction of Functional MicroRNA Targets","volume":"48","author":"Chen","year":"2020","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:23:12Z","timestamp":1760145792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,21]]},"references-count":51,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214493"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214493","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,21]]}}}