{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:04:07Z","timestamp":1780549447469,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disease-modifying therapies (DMT)s) for relapsing-remitting multiple sclerosis (RRMS) act through distinct immunological mechanisms, yet the within-patient molecular response programs associated with these therapies remain incompletely defined. Here, we reanalyzed publicly available peripheral blood mononuclear cell (PBMC) miRNA microarray data (GSE230064) using a longitudinal, robustness-focused framework to compare therapy-associated miRNA response patterns following cladribine versus ocrelizumab treatment. Baseline (t0) and 6-month post-treatment (t1) samples were paired within individuals and technical replicates consolidated prior to analysis, yielding a final paired cohort of four cladribine-treated and six ocrelizumab-treated patients. Within each treatment arm, we quantified per-patient \u0394-miRNA (t1 \u2212 t0) values and prioritized therapy-associated response features using a multi-evidence framework integrating effect direction, magnitude, directional consistency across individuals, and leave-one-out sensitivity. Cladribine treatment was associated with a highly coordinated, directionally concordant upregulation of five miRNAs including hsa-miR-27a-3p, hsa-miR-27b-3p, hsa-miR-503-5p, hsa-miR-148a-3p, and hsa-miR-26a-5p, all exhibiting 100% directional stability across patients and mean \u0394-expression values ranging from +0.77 to +1.38. These miRNAs target pathways relevant to MS pathophysiology, including Th17\/Treg balance, Wnt-\u03b2-catenin signaling, macrophage polarization, and epigenetic immune regulation. In contrast, ocrelizumab elicited a more selective response pattern, with five miRNAs including hsa-miR-100-5p, hsa-miR-410-3p, hsa-miR-432-5p, hsa-miR-296-5p, and hsa-miR-485-3p showing moderate directional stability (83%) and greater inter-individual heterogeneity, consistent with the more targeted mechanism of CD20+ B-cell depletion. Notably, the two treatment-associated signatures were non-overlapping, with hsa-miR-27b-3p representing the only miRNA shared with prior cross-sectional analyses of this dataset. The identified ocrelizumab-associated miRNAs implicate pathways including mTOR\/IGF1R signaling, NF-\u03baB regulation, RNA editing, and mitochondrial biogenesis, several of which are dysregulated in progressive MS. Together, these findings demonstrate that cladribine and ocrelizumab induce distinct, treatment-specific miRNA response architectures that reflect their divergent immunological mechanisms. This work establishes a stability-aware analytic template for extracting reproducible longitudinal miRNA signals from small paired RRMS cohorts and provides a ranked set of biologically plausible candidate miRNAs for prospective validation and mechanistic investigation.<\/jats:p>","DOI":"10.3390\/ijms27114935","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal and Stability-Aware Analysis Reveals Treatment-Specific MicroRNA Response Signatures Following Immune-Reconstitution and B-Cell-Targeted Therapies in Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Nasar","family":"Ata","sequence":"first","affiliation":[{"name":"Department of Neurology, Henry Ford Health, Detroit, MI 48202, USA"},{"name":"School of Life and Basic Science, Jaipur National University, Jaipur 302017, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4214-5674","authenticated-orcid":false,"given":"Joshua S.","family":"Mytych","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-6315","authenticated-orcid":false,"given":"Mirela","family":"Cerghet","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramandeep","family":"Rattan","sequence":"additional","affiliation":[{"name":"Women\u2019s Health Services, Henry Ford Health, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-8442","authenticated-orcid":false,"given":"Sumit","family":"Govil","sequence":"additional","affiliation":[{"name":"School of Life and Basic Science, Jaipur National University, Jaipur 302017, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-829X","authenticated-orcid":false,"given":"Shailendra","family":"Giri","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Mao-Draayer","sequence":"additional","affiliation":[{"name":"Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yauk, C.L., Rowan-Carroll, A., Stead, J.D., and Williams, A. (2010). Cross-platform analysis of global microRNA expression technologies. BMC Genom., 11.","DOI":"10.1186\/1471-2164-11-330"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3934\/Neuroscience.2025026","article-title":"A review of multiple sclerosis: From pathophysiology to latest therapeutic advances","volume":"12","author":"Arachchige","year":"2025","journal-title":"AIMS Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1212\/WNL.46.4.907","article-title":"Defining the clinical course of multiple sclerosis: Results of an international survey. National Multriple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis","volume":"46","author":"Lublin","year":"1996","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Brieva, L., Calles, C., Landete, L., and Oreja-Guevara, C. (2025). Current challenges in secondary progressive multiple sclerosis: Diagnosis, activity detection and treatment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1543649"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zabalza, A., Pappolla, A., Comabella, M., Montalban, X., and Malhotra, S. (2024). MiRNA-based therapeutic potential in multiple sclerosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1441733"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1373\/clinchem.2010.147405","article-title":"The microRNA spectrum in 12 body fluids","volume":"56","author":"Weber","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"de Faria, O., Moore, C.S., Kennedy, T.E., Antel, J.P., Bar-Or, A., and Dhaunchak, A.S. (2012). MicroRNA dysregulation in multiple sclerosis. Front. Genet., 3.","DOI":"10.3389\/fgene.2012.00311"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., Castelli, G., and Labbaye, C. (2017). miR-146 and miR-155: Two Key Modulators of Immune Response and Tumor Development. Non-Coding RNA, 3.","DOI":"10.3390\/ncrna3030022"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Emami Nejad, A., Mostafavi Zadeh, S.M., Nickho, H., Sadoogh Abbasian, A., Forouzan, A., Ahmadlou, M., Nedaeinia, R., Shaverdi, S., and Manian, M. (2023). The role of microRNAs involved in the disorder of blood-brain barrier in the pathogenesis of multiple sclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1281567"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/ane.12921","article-title":"Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients","volume":"138","author":"Vistbakka","year":"2018","journal-title":"Acta Neurol. Scand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12765","DOI":"10.1111\/nan.12765","article-title":"MiR-142-3p regulates synaptopathy-driven disease progression in multiple sclerosis","volume":"48","author":"Musella","year":"2022","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mancuso, R., Agostini, S., Hernis, A., Caputo, D., Galimberti, D., Scarpini, E., and Clerici, M. (2022). Alterations of the miR-126-3p\/POU2AF1\/Spi-B Axis and JCPyV Reactivation in Multiple Sclerosis Patients Receiving Natalizumab. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.819911"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12974-023-02811-z","article-title":"miRNA 548a-3p as biomarker of NEDA-3 at 2 years in multiple sclerosis patients treated with fingolimod","volume":"20","author":"Patel","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105751","DOI":"10.1016\/j.msard.2024.105751","article-title":"Real-world evidence from Germany and the United States: Treatment initiation on low-efficacy versus high-efficacy therapies in patients with multiple sclerosis","volume":"88","author":"Papukchieva","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_15","first-page":"35","article-title":"Cladribine tablets\u2019 potential role as a key example of selective immune reconstitution therapy in multiple sclerosis","volume":"8","author":"Boyko","year":"2018","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"765","DOI":"10.2147\/TCRM.S282390","article-title":"Ocrelizumab for the Treatment of Multiple Sclerosis: Safety, Efficacy, and Pharmacology","volume":"17","author":"Mancinelli","year":"2021","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Arisi, I., Malimpensa, L., Manzini, V., Brandi, R., Gosetti di Sturmeck, T., D\u2019Amelio, C., Crisafulli, S., Ferrazzano, G., Belvisi, D., and Malerba, F. (2023). Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing\u2013remitting multiple sclerosis patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1234869"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ben-Elazar, S., Aure, M.R., Jonsdottir, K., Leivonen, S.K., Kristensen, V.N., Janssen, E.A.M., Kleivi Sahlberg, K., Lingj\u00e6rde, O.C., and Yakhini, Z. (2021). miRNA normalization enables joint analysis of several datasets to increase sensitivity and to reveal novel miRNAs differentially expressed in breast cancer. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1008608"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yang, L., Liu, J., Lu, Q., Riggs, A.D., and Wu, X. (2017). SAIC: An iterative clustering approach for analysis of single cell RNA-seq data. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4019-5"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nrg2825","article-title":"Tackling the widespread and critical impact of batch effects in high-throughput data","volume":"11","author":"Leek","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhang, B., Wang, T., Bonni, A., and Zhao, G. (2020). Robust principal component analysis for accurate outlier sample detection in RNA-Seq data. BMC Bioinform., 21.","DOI":"10.1186\/s12859-020-03608-0"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fissolo, N., Calvo-Barreiro, L., Eixarch, H., Boschert, U., Villar, L.M., Costa-Frossard, L., Ferrer, M., Sanchez, A., Borr\u00e0s, E., and Sabid\u00f3, E. (2023). Molecular signature associated with cladribine treatment in patients with multiple sclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1233546"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ncrna.2025.05.009","article-title":"Role of Ocrelizumab in modulating gene and microRNA expression in multiple sclerosis","volume":"13","author":"Signoriello","year":"2025","journal-title":"Non-Coding RNA Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e200420","DOI":"10.1212\/NXI.0000000000200420","article-title":"Extracellular Vesicle-Derived MicroRNAs as a Biomarker for Therapeutic Response in Multiple Sclerosis","volume":"12","author":"Egido","year":"2025","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.21873\/invivo.13920","article-title":"B-Cell and T-Cell Populations in Peripheral Blood Linked to Ocrelizumab Treatment Efficacy in Multiple Sclerosis","volume":"39","author":"Akbayir","year":"2025","journal-title":"Vivo"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e360","DOI":"10.1212\/NXI.0000000000000360","article-title":"Both cladribine and alemtuzumab may effect MS via B-cell depletion","volume":"4","author":"Baker","year":"2017","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1021\/cr300362f","article-title":"MicroRNA: Function, detection, and bioanalysis","volume":"113","author":"Dong","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1091\/mbc.e10-01-0062","article-title":"MiR-322\/424 and -503 are induced during muscle differentiation and promote cell cycle quiescence and differentiation by down-regulation of Cdc25A","volume":"21","author":"Sarkar","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1186\/s13098-025-01982-4","article-title":"Systematic validation of miR-503-5p abnormal expression in diabetic vascular complications: A meta-analysis and exploration of its targeted regulatory mechanism in retinopathy","volume":"17","author":"Zhang","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.bbadis.2017.09.024","article-title":"Human miR-26a-5p regulates the glutamate transporter SLC1A1 (EAAT3) expression. Relevance in multiple sclerosis","volume":"1864","author":"Potenza","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"De Felice, B., Mondola, P., Sasso, A., Orefice, G., Bresciamorra, V., Vacca, G., Biffali, E., Borra, M., and Pannone, R. (2014). Small non-coding RNA signature in multiple sclerosis patients after treatment with interferon-\u03b2. BMC Med. Genom., 7.","DOI":"10.1186\/1755-8794-7-26"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mameli, G., Arru, G., Caggiu, E., Niegowska, M., Leoni, S., Madeddu, G., Babudieri, S., Sechi, G.P., and Sechi, L.A. (2016). Natalizumab Therapy Modulates miR-155, miR-26a and Proinflammatory Cytokine Expression in MS Patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157153"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13891","DOI":"10.1038\/s41598-019-50210-3","article-title":"MicroRNA-27a\/b-3p and PPARG regulate SCAMP3 through a feed-forward loop during adipogenesis","volume":"9","author":"Kwok","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e267","DOI":"10.1212\/NXI.0000000000000267","article-title":"Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis","volume":"3","author":"Regev","year":"2016","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.celrep.2019.09.020","article-title":"Oligodendrocyte Intrinsic miR-27a Controls Myelination and Remyelination","volume":"29","author":"Tripathi","year":"2019","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Manaster, I., Goldman-Wohl, D., Greenfield, C., Nachmani, D., Tsukerman, P., Hamani, Y., Yagel, S., and Mandelboim, O. (2012). MiRNA-mediated control of HLA-G expression and function. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033395"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e200069","DOI":"10.1212\/NXI.0000000000200069","article-title":"miRNA Signature in CSF From Patients With Primary Progressive Multiple Sclerosis","volume":"10","author":"Miguela","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102681","DOI":"10.1016\/j.redox.2023.102681","article-title":"MiR-27b attenuates mitochondrial oxidative stress and inflammation in endothelial cells","volume":"62","author":"Prattichizzo","year":"2023","journal-title":"Redox Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1093\/brain\/awr262","article-title":"Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity","volume":"134","author":"Smith","year":"2011","journal-title":"Brain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12951-024-02444-1","article-title":"Macrophage-derived mir-100-5p orchestrates synovial proliferation and inflammation in rheumatoid arthritis through mTOR signaling","volume":"22","author":"Liu","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pinheiro, A.H.G., Pereira, B.O., Silva, L.S.D., Melo, F.T.C., Souza, A., Leal, V.S.G., Figueiredo, P.B.B., Neto, J.F.A., Santos, M.C.D., and Queiroz, N.N.M. (2024). Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115663"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000445625","article-title":"MiR-410 Down-Regulates the Expression of Interleukin-10 by Targeting STAT3 in the Pathogenesis of Systemic Lupus Erythematosus","volume":"39","author":"Liu","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s10753-018-0896-2","article-title":"miR-410-3p Suppresses Cytokine Release from Fibroblast-Like Synoviocytes by Regulating NF-\u03baB Signaling in Rheumatoid Arthritis","volume":"42","author":"Wang","year":"2019","journal-title":"Inflammation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12974-015-0418-1","article-title":"Next-generation sequencing identifies altered whole blood microRNAs in neuromyelitis optica spectrum disorder which may permit discrimination from multiple sclerosis","volume":"12","author":"Keller","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/bpa.12800","article-title":"MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin-7","volume":"30","author":"Fritsche","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100396","DOI":"10.1016\/j.ynstr.2021.100396","article-title":"Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1","volume":"15","author":"Zhang","year":"2021","journal-title":"Neurobiol. Stress"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1177\/1352458516651141","article-title":"Circulating microRNAs as biomarkers in progressive multiple sclerosis","volume":"23","author":"Vistbakka","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/jb\/mvab097","article-title":"Circ_0000514 promotes breast cancer progression by regulating the miR-296-5p\/CXCL10 axis","volume":"170","author":"Li","year":"2022","journal-title":"J. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s10020-018-0012-y","article-title":"MicroRNA-296: A promising target in the pathogenesis of atherosclerosis?","volume":"24","author":"Li","year":"2018","journal-title":"Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102303","DOI":"10.1016\/j.msard.2020.102303","article-title":"Dysregulation of microRNAs regulating survivin in CD4+ T cells in multiple sclerosis","volume":"44","author":"Alian","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Koh, H.S., Lee, S., Lee, H.J., Min, J.W., Iwatsubo, T., Teunissen, C.E., Cho, H.J., and Ryu, J.H. (2021). Targeting MicroRNA-485-3p Blocks Alzheimer\u2019s Disease Progression. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313136"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ryu, I.S., Ha, D.I., Jung, Y.J., Lee, H.J., Kim, I., Lim, Y.N., Min, H.S., Kim, S.H., Yoon, I., and Cho, H.J. (2026). Modulation of the miR-485-3p\/PGC-1\u03b1 Pathway by ASO-Loaded Nanoparticles Attenuates ALS Pathogenesis. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020615"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11584","DOI":"10.1038\/s41598-018-29917-2","article-title":"MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer","volume":"8","author":"Kahraman","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1745-6150-2-9","article-title":"How high is the level of technical noise in microarray data?","volume":"2","author":"Klebanov","year":"2007","journal-title":"Biol. Direct"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41577-020-00446-2","article-title":"Transcriptional regulation of memory B cell differentiation","volume":"21","author":"Laidlaw","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.cell.2012.04.005","article-title":"Roles for microRNAs in conferring robustness to biological processes","volume":"149","author":"Ebert","year":"2012","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e182790","DOI":"10.1172\/JCI182790","article-title":"Transcriptomic profiling after B cell depletion reveals central and peripheral immune cell changes in multiple sclerosis","volume":"135","author":"Wei","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Holm Hansen, R., von Essen, M.R., Reith Mahler, M., Cobanovic, S., and Sellebjerg, F. (2024). Sustained effects on immune cell subsets and autoreactivity in multiple sclerosis patients treated with oral cladribine. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1327672"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e200565","DOI":"10.1212\/NXI.0000000000200565","article-title":"Dynamics of Spinal Fluid Immune Cell Alterations Following Cladribine Tablet Treatment in Multiple Sclerosis","volume":"13","author":"Smirnov","year":"2026","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Navon, R., Wang, H., Steinfeld, I., Tsalenko, A., Ben-Dor, A., and Yakhini, Z. (2009). Novel rank-based statistical methods reveal microRNAs with differential expression in multiple cancer types. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008003"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1093\/nar\/gkm1075","article-title":"Model-based variance-stabilizing transformation for Illumina microarray data","volume":"36","author":"Lin","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1038\/s41596-021-00579-1","article-title":"Statistical analysis in metabolic phenotyping","volume":"16","author":"Blaise","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"D138","DOI":"10.1093\/nar\/gkad965","article-title":"NCBI GEO: Archive for gene expression and epigenomics data sets: 23-year update","volume":"52","author":"Clough","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Stevens, J.R., Herrick, J.S., Wolff, R.K., and Slattery, M.L. (2018). Power in pairs: Assessing the statistical value of paired samples in tests for differential expression. BMC Genom., 19.","DOI":"10.1186\/s12864-018-5236-2"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4935\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:24:19Z","timestamp":1780547059000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114935"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114935","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}