{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:10:39Z","timestamp":1792789839133,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guilin Sanjin Pharmaceutical Co., Ltd.","award":["BUCM-2023-JS-FW-060"],"award-info":[{"award-number":["BUCM-2023-JS-FW-060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Meniere\u2019s disease (MD) is a rare inner ear disorder characterized by endolymphatic hydrops and symptoms such as vertigo and hearing loss, with no curative treatment currently available. XuanYunNing tablets (XYN) have been clinically used to treat MD, but their molecular mechanisms remain unclear. Objective: This study aimed to systematically evaluate the pharmacological effects of XYN in a guinea pig model of MD and to elucidate the underlying molecular mechanisms of both MD pathogenesis and XYN intervention through integrated multi-omics analyses, including transcriptomics, proteomics, and bioinformatics. Methods: A guinea pig model of endolymphatic hydrops was induced by intraperitoneal injection of desmopressin acetate (dDAVP). Pharmacodynamic efficacy was evaluated via behavioral scoring and histopathological analysis. The differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) modulated by XYN treatment were identified using high-throughput transcriptomic and proteomic sequencing. These data were integrated through multi-omics bioinformatic analysis. Key molecular targets and signaling pathways were further validated using RT-qPCR and Western blotting. Results: Pharmacological evaluations showed that guinea pigs in the model group exhibited a 26% increase in endolymphatic hydrops area, while high-dose XYN treatment reduced this area by 19% and significantly improved functional parameters, including overall physiological condition (e.g., weight and general appearance), auricular reflexes to low-, medium-, and high-frequency sound stimuli, nystagmus, and the righting reflex. High-throughput sequencing combined with integrative omics analysis identified 513 potential molecular targets of XYN. Subsequent network and module analyses pinpointed the JAK-STAT signaling pathway as the central axis. Mendelian randomization (MR) analysis further supported a causal relationship between MD and metabolic, immune, and inflammatory traits, reinforcing the central role of JAK-STAT signaling in both MD progression and XYN-mediated intervention. Mechanistic studies confirmed that XYN downregulated IFNG, IFNGR1, JAK1, p-STAT3\/STAT3, and AOX at both mRNA and protein levels, thereby inhibiting aberrant JAK-STAT pathway activation in MD model animals. In addition, a total of 125 chemical constituents were identified in XYN by UHPLC-MS analysis. ZBTB20 and other molecules were identified as potential blood-based biomarkers for MD. Conclusions: This study reveals that XYN alleviates MD symptoms by disrupting a pathological cycle driven by JAK-STAT signaling, inflammation, and metabolic dysfunction. These findings support the clinical potential of XYN in the treatment of Meniere\u2019s disease and may inform the development of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ph18091266","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:57Z","timestamp":1756189557000},"page":"1266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Systems Network Integration of Transcriptomic, Proteomic, and Bioinformatic Analyses Reveals the Mechanism of XuanYunNing Tablets in Meniere\u2019s Disease via JAK-STAT Pathway Modulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhengsen","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanqi","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyan","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"Guilin Sanjin Pharmaceutical Co., Ltd., Guilin 541004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Guilin Sanjin Pharmaceutical Co., Ltd., Guilin 541004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zou","sequence":"additional","affiliation":[{"name":"Guilin Sanjin Pharmaceutical Co., Ltd., Guilin 541004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-6110","authenticated-orcid":false,"given":"Jiarui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","unstructured":"(2023, November 22). \u201cMeniere\u2019s Disease\u2014Symptoms and Causes.\u201d Mayo Clinic. Available online: https:\/\/www.mayoclinic.org\/diseases-conditions\/menieres-disease\/symptoms-causes\/syc-20374910."},{"key":"ref_2","unstructured":"(2023, November 22). \u201cMeniere\u2019s Disease.\u201d American Hearing Research Foundation. Available online: https:\/\/www.american-hearing.org\/disease\/menieres-disease\/."},{"key":"ref_3","first-page":"286","article-title":"Regulatory Effect of Acetic Desmopressin on the Expression of Aquaporin-2 in the Cochlea of Guinea Pigs","volume":"22","author":"Ma","year":"2014","journal-title":"J. Audiol. Speech Pathol."},{"key":"ref_4","first-page":"138","article-title":"Current Understanding and Clinical Management of Meniere\u2019s Disease: A Systematic Review","volume":"40","year":"2019","journal-title":"Semin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kwon, M.J., Kang, H.S., Kim, J., Kim, J.H., Bang, W.J., Yoo, D.M., Lee, N.-E., Han, K.M., Kim, N.Y., and Choi, H.G. (2024). Epidemiological Evidence for Upper Respiratory Infections as a Potential Risk Factor for Meniere\u2019s Disease: A Korean National Health Sample Cohort Study. Microorganisms, 12.","DOI":"10.3390\/microorganisms12102047"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.otc.2010.05.001","article-title":"Current Epidemiology of Meniere\u2019s Syndrome","volume":"43","author":"Alexander","year":"2010","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_7","unstructured":"Koenen, L., and Andaloro, C. (2023). Meniere Disease. StatPearls, StatPearls Publishing."},{"key":"ref_8","first-page":"S1","article-title":"Clinical Practice Guideline: M\u00e9ni\u00e8re\u2019s Disease","volume":"162","author":"Basura","year":"2020","journal-title":"Otolaryngol. \u2014Head Neck Surg."},{"key":"ref_9","first-page":"h6816","article-title":"Efficacy and Safety of Betahistine Treatment in Patients with Meniere\u2019s Disease: Primary Results of a Long-Term, Multicentre, Double-Blind, Randomised, Placebo-Controlled, Dose-Defining Trial (BEMED Trial)","volume":"352","author":"Adrion","year":"2016","journal-title":"Br. Med. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000515821","article-title":"Betahistine in M\u00e9ni\u00e8re\u2019s Disease or Syndrome: A Systematic Review","volume":"27","author":"Esch","year":"2022","journal-title":"Audiol. Neurotol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e7068","DOI":"10.5867\/medwave.2017.08.7068","article-title":"Is Betahistine Effective for M\u00e9ni\u00e8re\u2019s Disease?","volume":"17","author":"Rosenbaum","year":"2017","journal-title":"Medwave"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, P., Zhang, D., Zhou, W., Wang, L., Wang, B., Zhang, T., and Li, S. (2023). Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbad518"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.5582\/irdr.2025.01028","article-title":"Traditional Chinese medicine for intractable and rare diseases: Research progress and future strategies","volume":"14","author":"Liu","year":"2025","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_14","first-page":"611","article-title":"Clinical Study on Treating 120 Cases of Meniere\u2019s Disease with XYN","volume":"10","author":"Zhao","year":"2012","journal-title":"China Med. Her."},{"key":"ref_15","unstructured":"Wang, Z. (1996). Efficacy Analysis of XYN Decoction in Treating 200 Cases of Meniere\u2019s Disease. Hebei J. Tradit. Chin. Med., 7\u20138. Available online: https:\/\/kns.cnki.net\/kcms2\/article\/abstract?v=QUtgg5W7F1-o_g7KacxiiNnCXc20HBS_LCLGP4hYvJnmpdqV0UlYmLh-5qgZpMxOheNkzmC0Zn6FipoyiJfU68dZChYEz4pFsV8v124MbjKd6SGYn9V8DzM7QyGihFesk0iU_5EuVv44bRCwXgiROHVIhRPf1nVpfwYfbl2h2iM=&uniplatform=NZKPT&language=CHS."},{"key":"ref_16","first-page":"124","article-title":"Observation of the Efficacy of XYN in Treating Vertigo Caused by Meniere\u2019s Disease","volume":"12","author":"Shi","year":"2010","journal-title":"Chin. Community Dr. Med."},{"key":"ref_17","first-page":"196","article-title":"Research Review on the Advantages of Traditional Chinese Medicine in Treating Aural Vertigo and Meniere\u2019s Disease","volume":"29","author":"Wu","year":"2023","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref_18","first-page":"862","article-title":"Treatment of 36 Cases of Meniere\u2019s Disease with XYN Tablets","volume":"24","author":"Zhai","year":"2009","journal-title":"Guangming J. Chin. Med."},{"key":"ref_19","first-page":"97","article-title":"Treatment of 72 Cases of Meniere\u2019s Syndrome with XYN Tablets","volume":"3","author":"Gu","year":"2011","journal-title":"Clin. Res. Tradit. Chin. Med."},{"key":"ref_20","unstructured":"Luo, Y., Tang, X., Zhou, H., Liu, T., and Zhong, S.J. (2002). Analysis of TCM Syndrome Patterns in 632 Emergency Patients with Vertigo. New Chin. Med., 29\u201330."},{"key":"ref_21","first-page":"149","article-title":"Exploring the Treatment of Meniere\u2019s Disease from the Perspective of Spleen and Stomach Theory","volume":"17","author":"Fu","year":"2020","journal-title":"China Med. Her."},{"key":"ref_22","first-page":"571","article-title":"TCM Differentiation and Treatment During the Attack Phase of Meniere\u2019s Disease","volume":"29","author":"Zhang","year":"2009","journal-title":"Jilin J. Tradit. Chin. Med."},{"key":"ref_23","first-page":"88","article-title":"Exploring the Etiology and Treatment of Meniere\u2019s Disease Based on the \u201cPhlegm-Retention Causing Dizziness\u201d Theory","volume":"36","author":"Li","year":"2022","journal-title":"Pract. J. Tradit. Chin. Intern. Med."},{"key":"ref_24","first-page":"143","article-title":"Overview of Commonly Used Oral Chinese Patent Medicines for Treating Vertigo","volume":"14","author":"Wang","year":"2016","journal-title":"Mod. Distance Educ. Chin. Tradit. Med."},{"key":"ref_25","first-page":"149","article-title":"Clinical Study on XYN in Treating Meniere\u2019s Disease","volume":"48","author":"Ding","year":"2010","journal-title":"China Mod. Dr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42751","DOI":"10.1021\/acsami.5c08068","article-title":"Medicinal Plant-Derived Carbon Dots Nanozymes Ameliorate Ulcerative Colitis via Anti-inflammatory, Antioxidant, and Gut Barrier-Protective Effects","volume":"17","author":"Li","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ullah, A., Sun, Q., Li, J., Li, J., Khatun, P., Kou, G., and Lyu, Q. (2024). Bioactive Compounds in Citrus reticulata Peel Are Potential Candidates for Alleviating Physical Fatigue through a Triad Approach of Network Pharmacology, Molecular Docking, and Molecular Dynamics Modeling. Nutrients, 16.","DOI":"10.3390\/nu16121934"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112837","DOI":"10.1016\/j.jep.2020.112837","article-title":"A lipid-soluble extract of Pinellia pedatisecta Schott orchestrates intratumoral dendritic cell-driven immune activation through SOCS1 signaling in cervical cancer","volume":"267","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","first-page":"145","article-title":"Research Progress on the Relationship Between Sodium Channels, Aquaporins in Inner Ear Epithelium and Endolymph Metabolism","volume":"33","author":"Huang","year":"2019","journal-title":"J. Otolaryngol. Ophthalmol. Shandong Univ."},{"key":"ref_30","unstructured":"Tan, C., Cao, Y., Liu, H., Zhu, J., He, X., Du, C., and Zhou, M. (1998). Study on Immune-Related Factors in Meniere\u2019s Disease. J. Clin. Otorhinolaryngol., 208\u2013210. Available online: https:\/\/kns.cnki.net\/kcms2\/article\/abstract?v=QUtgg5W7F18cQxpAgp1u6W3b1cob5s2YJC8bkhFPYQ9sNNnsSBjfQiOd6jNKHCoGksBX33yUl-qawNWB3AAu06uFhX2sXvFbYNcixIVIrx-VnMBdg7r8BlHbDn-TIgh1vumY6dXNeFa79xTgzdjVuavRxP1dfCOG_Z-41nbcNbTz2K1Et3AN85lNDCNj5ySxHJFrZmcHMMhad7rusOwf62ePm-ndVK5S-wk7q0599b4=&uniplatform=NZKPT."},{"key":"ref_31","first-page":"CD015249","article-title":"Surgical Interventions for M\u00e9ni\u00e8re\u2019s Disease","volume":"2","author":"Lee","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116972","DOI":"10.1016\/j.envres.2023.116972","article-title":"Meniere\u2019s Disease: Pathogenesis, Treatments, and Emerging Approaches for an Idiopathic Bioenvironmental Disorder","volume":"238","author":"Falahati","year":"2023","journal-title":"Environ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S0140-6736(08)61161-7","article-title":"Meniere\u2019s Disease","volume":"372","author":"Sajjadi","year":"2008","journal-title":"Lancet"},{"key":"ref_34","first-page":"e7325","article-title":"Use of Mendelian Randomisation to Assess Potential Benefit of Clinical Intervention","volume":"345","author":"Burgess","year":"2012","journal-title":"BMJ Clin. Res. Ed."},{"key":"ref_35","first-page":"n2233","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomisation (STROBE-MR): Explanation and Elaboration","volume":"375","author":"Skrivankova","year":"2021","journal-title":"BMJ Clin. Res. Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.8197455","article-title":"Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins","volume":"264","author":"Darnell","year":"1994","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving Cognition of the JAK-STAT Signaling Pathway: Autoimmune Disorders and Cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s12964-023-01240-y","article-title":"Double-Edged Sword of JAK\/STAT Signaling Pathway in Viral Infections: Novel Insights into Virotherapy","volume":"21","author":"Mahjoor","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12950-023-00360-z","article-title":"Advances in the Study of Macrophage Polarization in Inflammatory Immune Skin Diseases","volume":"20","author":"Xia","year":"2023","journal-title":"J. Inflamm."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sarapultsev, A., Gusev, E., Komelkova, M., Utepova, I., Luo, S., and Hu, D. (2023). JAK-STAT Signaling in Inflammation and Stress-Related Diseases: Implications for Therapeutic Interventions. Mol. Biomed., 4.","DOI":"10.1186\/s43556-023-00151-1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41392-023-01331-9","article-title":"Signaling Pathways in Rheumatoid Arthritis: Implications for Targeted Therapy","volume":"8","author":"Ding","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"tkad050","DOI":"10.1093\/burnst\/tkad050","article-title":"The cGAS-STING Pathway: A Therapeutic Target in Diabetes and Its Complications","volume":"12","author":"He","year":"2024","journal-title":"Burn. Trauma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41577-021-00524-z","article-title":"The cGAS\u2013STING Pathway as a Therapeutic Target in Inflammatory Diseases","volume":"21","author":"Decout","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zatterale, F., Longo, M., Naderi, J., Raciti, G.A., Desiderio, A., Miele, C., and Beguinot, F. (2019). Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01607"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1038\/s41467-024-48471-2","article-title":"Liver ACOX1 Regulates Levels of Circulating Lipids That Promote Metabolic Health Through Adipose Remodeling","volume":"15","author":"Lu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1055\/s-0038-1673698","article-title":"Meni\u00e8re\u2019s Disease and Disorders of the Carbohydrate Metabolism Involving the Inner Ear","volume":"23","author":"Albernaz","year":"2019","journal-title":"Int. Arch. Otorhinolaryngol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rossmeisl, M., Jilkova, Z.M., Kuda, O., Jelenik, T., Medrikova, D., Stankova, B., Kristinsson, B., Haraldsson, G.G., Svensen, H., and Stoknes, I. (2012). Metabolic Effects of n-3 PUFA as Phospholipids Are Superior to Triglycerides in Mice Fed a High-Fat Diet: Possible Role of Endocannabinoids. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038834"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1517\/17425255.4.6.697","article-title":"Non-P450 Aldehyde Oxidizing Enzymes: The Aldehyde Dehydrogenase Superfamily","volume":"4","author":"Marchitti","year":"2008","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5377","DOI":"10.1074\/jbc.REV119.007741","article-title":"Evolution, Expression, and Substrate Specificities of Aldehyde Oxidase Enzymes in Eukaryotes","volume":"295","author":"Terao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/ohn.1085","article-title":"Dissecting the Circadian Clock and Toll-like Receptor Gene Alterations in Meniere\u2019s Disease and Vestibular Migraine","volume":"172","author":"Yang","year":"2025","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"49","DOI":"10.21053\/ceo.2021.00920","article-title":"Cytokines and Inflammation in Meniere Disease","volume":"15","author":"Frejo","year":"2022","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Teraoka, M., Hato, N., Inufusa, H., and You, F. (2024). Role of Oxidative Stress in Sensorineural Hearing Loss. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084146"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2220867120","DOI":"10.1073\/pnas.2220867120","article-title":"ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice","volume":"120","author":"Xie","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.otc.2010.05.007","article-title":"Endolymphatic Hydrops: Pathophysiology and Experimental Models","volume":"43","author":"Salt","year":"2010","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11097","DOI":"10.1073\/pnas.1301257110","article-title":"Zinc Finger Protein ZBTB20 Promotes Toll-like Receptor-Triggered Innate Immune Responses by Repressing I\u03baB\u03b1 Gene Transcription","volume":"110","author":"Liu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"53","DOI":"10.7874\/jao.2020.00115","article-title":"Experimental Animal Models for Meniere\u2019s Disease: A Mini-Review","volume":"24","author":"Seo","year":"2020","journal-title":"J. Audiol. Otol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kakigi, A., Egami, N., Uehara, N., Fujita, T., Nibu, K.I., Yamashita, S., and Yamasoba, T. (2020). Live imaging and functional changes of the inner ear in an animal model of Meniere\u2019s disease. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-68352-0"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1038\/s41380-020-0697-5","article-title":"Genomic Analysis of Diet Composition Finds Novel Loci and Associations with Health and Lifestyle","volume":"26","author":"Meddens","year":"2021","journal-title":"Mol. Psychiatry"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1266\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:32:42Z","timestamp":1760034762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/9\/1266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":58,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ph18091266"],"URL":"https:\/\/doi.org\/10.3390\/ph18091266","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]}}}