{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:32:11Z","timestamp":1789471931210,"version":"build-2803163510"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Asthma, a chronic inflammatory respiratory disease with significant global health burden, faces limitations in current therapies, necessitating novel therapeutic strategies. The plant\n                      <jats:italic>Geranium wilfordii<\/jats:italic>\n                      Maxim. (GWM), a traditional Chinese herbal medicine with diverse pharmacological activities and clinical applications, has been traditionally used in the treatment of rheumatism, numbness, infectious diseases, dermatosis, tumors and other disease by the Bai, Miao, Yi minority people of Southwest China for generations. Earlier research in our lab also demonstrated that GWM exhibits anti-asthmatic activity, but the mechanism of action remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the anti-asthmatic mechanisms of GWM by identifying compounds and elucidating key molecular targets involved in immune cell regulation through integrated computational and experimental approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed UPLC-QE-Orbitrap-MS to identify active compounds. Network pharmacology and machine learning analyses were conducted to identify key hub genes, followed by validation through Mendelian randomization analysis, molecular docking, and animal models. Immune infiltration and single-cell RNA sequencing analyses using publicly available Gene Expression Omnibus (GEO) datasets, combined with mediation Mendelian randomization (MR), were performed to elucidate the underlying cellular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 43 compounds were identified in GWM. Network pharmacology and machine learning prioritized NOTCH2, HDAC2, and MAPK1 as hub targets, validated using MR and molecular docking. Subsequent\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments validated the regulatory effects of GWM on the expression levels of these hub genes and demonstrated its therapeutic efficacy in asthma. Further analysis showed that GWM regulation of these hub genes may subsequently affect the activity of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and regulatory T cells, potentially contributing to its therapeutic effects against asthma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides novel evidence for the potential therapeutic activity of GWM in asthma. By targeting key hub genes such as NOTCH2, HDAC2, and MAPK1, GWM may modulate immune cell activity, thereby contributing to its anti-asthmatic effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1761424","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:04:45Z","timestamp":1774418685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Multifaceted mechanistic exploration of Geranium wilfordii Maxim. in asthma treatment: integrating network pharmacology, machine learning, Mendelian randomization and experimental validation"],"prefix":"10.3389","volume":"14","author":[{"given":"Yingxiang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]},{"name":"School of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan (Cultivation), Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"He","sequence":"additional","affiliation":[{"name":"Basic Medical College, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan (Cultivation), Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan (Cultivation), Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan (Cultivation), Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengle","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Traditional Chinese Medicine Hospital of Dali Bai Autonomous Prefecture","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Dali University","place":["Dali, Yunnan, China"]},{"name":"Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from Western Yunnan (Cultivation), Dali University","place":["Dali, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.immuni.2007.05.021","article-title":"Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch","volume":"27","author":"Amsen","year":"2007","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1016\/j.jaip.2024.07.031","article-title":"Adherence challenges and strategies in specific groups with asthma: adolescents, pregnancy, and older adults","volume":"12","author":"Anderson","year":"2024","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.2147\/JAA.S395490","article-title":"Role of chemokines and inflammatory cells in respiratory allergy","volume":"15","author":"Bao","year":"2022","journal-title":"J. Asthma Allergy"},{"key":"B4","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.jaci.2012.12.1564","article-title":"Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease","volume":"131","author":"Barnes","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40169-020-0262-5","article-title":"PI3K inhibitor treatment ameliorates the glucocorticoid insensitivity of PBMCs in severe asthma","volume":"9","author":"Bi","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2174\/157488610791698316","article-title":"Evaluating safety of long-acting beta agonists (LABAs) in patients with asthma","volume":"5","author":"Bian","year":"2010","journal-title":"Curr. Drug Saf."},{"key":"B7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","article-title":"Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants","volume":"28","author":"Burgess","year":"2017","journal-title":"Epidemiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1182\/blood-2005-11-007237","article-title":"CD45RA on human CD8 T cells is sensitive to the time elapsed since the last antigenic stimulation","volume":"108","author":"Carrasco","year":"2006","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1165\/rcmb.2019-0257OC","article-title":"Antisense oligonucleotides targeting Jagged 1 reduce house dust mite\u2013induced goblet cell metaplasia in the adult murine lung","volume":"63","author":"Carrer","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"524","DOI":"10.23736\/S0026-4806.19.06319-5","article-title":"Supplementary prevention and management of asthma with quercetin phytosome: a pilot registry","volume":"110","author":"Cesarone","year":"2019","journal-title":"Minerva Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"100106","DOI":"10.1016\/j.medidd.2021.100106","article-title":"Suppressive effects of rutin, quercitrin, and isoquercitrin on atypical allergic asthma in an animal model","volume":"12","author":"Chen","year":"2021","journal-title":"Med. Drug Discov."},{"key":"B12","doi-asserted-by":"publisher","first-page":"410","DOI":"10.13286\/j.1001-5213.2025.04.07","article-title":"Composition analysis of seeds of Petroselinum crispum(Mill.)Fuss by UPLC-QE-Orbitrap-MS","volume":"45","author":"Chen","year":"2025","journal-title":"Chin. J. Hosp."},{"key":"B13","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3390\/ijms25010182","article-title":"Personalized medicine in severe asthma: from biomarkers to biologics","volume":"25","author":"Chen","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.1016\/j.cell.2024.02.034","article-title":"Flexible scaffold-based cheminformatics approach for polypharmacological drug design","volume":"187","author":"Chen","year":"2024","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1164\/rccm.200305-659OC","article-title":"Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma","volume":"170","author":"Cos\u00edo","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10654-020-00622-7","article-title":"Mendel\u2019s laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues","volume":"35","author":"Davey Smith","year":"2020","journal-title":"Eur. J. Epidemiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e2102050118","DOI":"10.1073\/pnas.2102050118","article-title":"Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing","volume":"118","author":"Deshmukh","year":"2021","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5590","DOI":"10.1111\/dom.15925","article-title":"Causal relationship between key genes and metabolic dysfunction\u2010associated fatty liver disease risk mediated by immune cells: a Mendelian randomization and mediation analysis","volume":"26","author":"Feng","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.3390\/ijms26167741","article-title":"Single cell RNA sequencing and its impact on understanding human embryo development","volume":"26","author":"Gul","year":"2025","journal-title":"Diabetes Obes. Metab."},{"key":"B20","doi-asserted-by":"publisher","first-page":"114907","DOI":"10.1016\/j.jep.2021.114907","article-title":"Geranium wilfordii maxim.: a review of its traditional uses, phytochemistry, pharmacology, quality control and toxicology","volume":"285","author":"He","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1630708","DOI":"10.3389\/fcell.2025.1630708","article-title":"Investigating the metabolic reprogramming mechanisms in diabetic nephropathy: a comprehensive analysis using bioinformatics and machine learning","volume":"13","author":"He","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"Hemani","year":"2017","journal-title":"PLOS Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4260","DOI":"10.1182\/blood-2006-06-027409","article-title":"Only the CD45RA+ subpopulation of CD4+ CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion","volume":"108","author":"Hoffmann","year":"2006","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/ni1075","article-title":"Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo","volume":"5","author":"Hozumi","year":"2004","journal-title":"Nat. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.21037\/atm-22-2835","article-title":"Research advances in airway remodeling in asthma: a narrative review","volume":"10","author":"Huang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1186\/s12906-015-0665-9","article-title":"Identification of anti-inflammatory fractions of Geranium wilfordii using tumor necrosis factor-alpha as a drug target on Herbochip\u00ae\u2013an array-based high throughput screening platform","volume":"15","author":"Huang","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"102005","DOI":"10.1016\/j.pupt.2021.102005","article-title":"Epimedin C modulates the balance between Th9 cells and Treg cells through negative regulation of noncanonical NF-\u03baB pathway and MAPKs activation to inhibit airway inflammation in the ovalbumin\u2013induced murine asthma model","volume":"65","author":"Huang","year":"2020","journal-title":"Pulm. Pharmacol. Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.3389\/fimmu.2020.01023","article-title":"Role of regulatory T cells in regulating fetal-maternal immune tolerance in healthy pregnancies and reproductive diseases","volume":"11","author":"Huang","year":"2020","journal-title":"Front. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3389\/fped.2017.00162","article-title":"Oxidative stress and bronchial asthma in children\u2014causes or consequences?","volume":"5","author":"Jesenak","year":"2017","journal-title":"Front. Pediatr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"860915","DOI":"10.3389\/fimmu.2022.860915","article-title":"Antigen presentation in the lung","volume":"13","author":"Kawasaki","year":"2022","journal-title":"Front. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/toxsci\/kfj063","article-title":"Gallic acid inhibits histamine release and pro-inflammatory cytokine production in mast cells","volume":"91","author":"Kim","year":"2006","journal-title":"Toxicol. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"7422","DOI":"10.3390\/ijms26157422","article-title":"Supervised machine-based learning and computational analysis to reveal unique molecular signatures associated with wound healing and fibrotic outcomes to lens injury","volume":"26","author":"Lalman","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B33","unstructured":"dian nan ben cao\n          \n          \n            \n              Lan\n              M.\n            \n          \n          \n          1959"},{"key":"B34","doi-asserted-by":"publisher","first-page":"38","DOI":"10.14348\/molcells.2020.0188","article-title":"Transforming growth factor \u03b2 inhibits muc5ac expression by smad3\/hdac2 complex formation and nf-\u03bab deacetylation at k310 in nci-h292 cells","volume":"44","author":"Lee","year":"2021","journal-title":"Mol. Cells"},{"key":"B35","doi-asserted-by":"publisher","first-page":"637948","DOI":"10.3389\/fimmu.2021.637948","article-title":"Modulating Th2 cell immunity for the treatment of asthma","volume":"12","author":"Le\u00f3n","year":"2021","journal-title":"Front. Immunol."},{"key":"B36","volume-title":"An application study of comprehensive quality evaluation on Magnolia liliflora by near-infrared spectroscopy","author":"Li","year":"2020"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1545392","DOI":"10.3389\/fphar.2025.1545392","article-title":"Integrating traditional omics and machine learning approaches to identify microbial biomarkers and therapeutic targets in pediatric inflammatory bowel disease","volume":"16","author":"Li","year":"","journal-title":"Front. Pharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"118936","DOI":"10.1016\/j.jep.2024.118936","article-title":"Exploiting omic-based approaches to decipher Traditional Chinese medicine","volume":"337","author":"Li","year":"","journal-title":"J. Ethnopharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.4314\/tjpr.v22i9.9","article-title":"MAPK1 knockdown ameliorated immune and inflammatory abnormalities in a mouse model of refractory asthma","volume":"22","author":"Lin","year":"2023","journal-title":"Trop. J. Pharm. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6943135","DOI":"10.1155\/2016\/6943135","article-title":"Herbal medicines for asthmatic inflammation: from basic researches to clinical applications","volume":"2016","author":"Liu","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1625286","DOI":"10.3389\/fphar.2025.1625286","article-title":"Huangkui capsule combined with finerenone attenuates diabetic nephropathy by regulating the JAK2\/STAT3 signaling pathway based on network pharmacology, molecular docking, and experimental verification","volume":"16","author":"Liu","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1007\/s10753-021-01466-3","article-title":"PI3K\/AKT\/mTOR and TLR4\/MyD88\/NF-\u03baB signaling inhibitors attenuate pathological mechanisms of allergic asthma","volume":"44","author":"Ma","year":"2021","journal-title":"Inflammation"},{"key":"B43","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00005-008-0005-6","article-title":"Expression of naive\/memory (CD45RA\/CD45RO) markers by peripheral blood CD4+ and CD8+ T cells in children with asthma","volume":"56","author":"Machura","year":"2008","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"B44","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.pharmthera.2017.08.011","article-title":"Oxidative stress and cellular pathways of asthma and inflammation: therapeutic strategies and pharmacological targets","volume":"181","author":"Mishra","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1016\/j.jaci.2018.06.052","article-title":"Epidemiology and risk factors of asthma-chronic obstructive pulmonary disease overlap in low-and middle-income countries","volume":"143","author":"Morgan","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2103179","DOI":"10.1183\/13993003.03179-2021","article-title":"Asthma management in low and middle income countries: case for change","volume":"60","author":"Mortimer","year":"2022","journal-title":"Eur. Respir. J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/MCP.0000000000000337","article-title":"Glucocortiosteroid subsensitivity and asthma severity","volume":"23","author":"Mukherjee","year":"2017","journal-title":"Curr. Opin. Pulm. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e13444","DOI":"10.7717\/peerj.13444","article-title":"IL-4\/IL-13 axis as therapeutic targets in allergic rhinitis and asthma","volume":"10","author":"Nur Husna","year":"2022","journal-title":"PeerJ"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1038\/s41588-020-0684-4","article-title":"Complex genetic signatures in immune cells underlie autoimmunity and inform therapy","volume":"52","author":"Orr\u00f9","year":"2020","journal-title":"Nat. Genet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"4879","DOI":"10.1002\/clt2.12172","article-title":"A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-\u03b21 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation","volume":"13","author":"Panek","year":"2016","journal-title":"Clin. Transl. Allergy"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e12172","DOI":"10.3892\/mmr.2016.5104","article-title":"New insights into the regulation of TGF\u2010\u03b2\/Smad and MPK signaling pathway gene expressions by nasal allergen and methacholine challenge test in asthma","volume":"12","author":"Panek","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","volume":"22","author":"Pishesha","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1159\/000536460","article-title":"Recent developments in the role of histone acetylation in asthma","volume":"185","author":"Potaczek","year":"2024","journal-title":"Int. Arch. Allergy Immunol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"472","DOI":"10.13313\/j.issn.1673-4890.20240717003","article-title":"Rapid identification of components in houyanqing oral liquid by UHPLC Q-Exactive orbitrap MS and molecular networking","volume":"27","author":"Quan","year":"2025","journal-title":"Mod. Chin. Med."},{"key":"B55","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s13312-024-3260-7","article-title":"Global initiative for asthma guidelines 2024: an update","volume":"61","author":"Rajvanshi","year":"2024","journal-title":"Indian Pediatr."},{"key":"B56","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cytogfr.2016.03.011","article-title":"T helper 2 and T follicular helper cells: regulation and function of interleukin-4","volume":"30","author":"Sahoo","year":"2016","journal-title":"Cytokine Growth Factor Rev."},{"key":"B57","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/S1074-7613(03)00111-0","article-title":"Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development","volume":"18","author":"Saito","year":"2003","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","first-page":"108960","DOI":"10.1016\/j.clim.2022.108960","article-title":"The safety of long-term use of inhaled corticosteroids in patients with asthma: a systematic review and meta-analysis","volume":"236","author":"Shang","year":"2022","journal-title":"Clin. Immunol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/all.14543","article-title":"Th2 cell markers in peripheral blood increase during an acute asthma exacerbation","volume":"76","author":"Shrestha Palikhe","year":"2021","journal-title":"Allergy"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4606","DOI":"10.1007\/s12325-023-02590-2","article-title":"Understanding the clinical implications of individual patient characteristics and treatment choice on the risk of exacerbation in asthma patients with moderate\u2013severe symptoms","volume":"40","author":"Singh","year":"2023","journal-title":"Adv. Ther."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2102583","DOI":"10.1183\/13993003.02583-2021","article-title":"Asthma remission: what is it and how can it be achieved?","volume":"60","author":"Thomas","year":"2022","journal-title":"Eur. Respir. J."},{"key":"B62","doi-asserted-by":"publisher","first-page":"8068","DOI":"10.3390\/ijms22158068","article-title":"CD39 regulation and functions in T cells","volume":"22","author":"Timperi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.jaci.2018.09.012","article-title":"Increased surface expression of NOTCH on memory T cells in peripheral blood from patients with asthma","volume":"143","author":"Tindemans","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.1172\/JCI128310","article-title":"Notch signaling licenses allergic airway inflammation by promoting Th2 cell lymph node egress","volume":"130","author":"Tindemans","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B65","doi-asserted-by":"publisher","first-page":"113988","DOI":"10.1016\/j.envres.2022.113988","article-title":"Climatotherapy for asthma: research progress and prospect","volume":"214","author":"Tong","year":"2022","journal-title":"Environ. Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3390\/biology12010133","article-title":"Oxidative stress, environmental pollution, and lifestyle as determinants of asthma in children","volume":"12","author":"Vincenzo","year":"2023","journal-title":"Biology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"69","DOI":"10.11124\/jbisrir-2015-2335","article-title":"The effectiveness of school-based family asthma educational programs on the quality of life and number of asthma exacerbations of children aged five to 18 years diagnosed with asthma: a systematic review protocol","volume":"13","author":"Walter","year":"2015","journal-title":"JBI Evid. Synth."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1125233","DOI":"10.3389\/fcell.2023.1125233","article-title":"Systemic inflammatory regulators and risk of acute-on-chronic liver failure: a bidirectional mendelian-randomization study","volume":"11","author":"Wang","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"437","DOI":"10.2147\/JAA.S504925","article-title":"Notch signaling pathway interfering as a possible asthma treatment: a narrative review","volume":"18","author":"Wang","year":"2025","journal-title":"J. Asthma Allergy"},{"key":"B70","doi-asserted-by":"publisher","first-page":"5871","DOI":"10.2147\/DDDT.S518115","article-title":"Cornus officinalis protects against steroid-induced osteonecrosis of the femoral head through inhibiting inflammatory responses and apoptosis via network pharmacology and experimental validation","volume":"19","author":"Wang","year":"2025","journal-title":"DDDT"},{"key":"B71","doi-asserted-by":"publisher","first-page":"pe55","DOI":"10.1126\/scisignal.1.51.pe55","article-title":"Untangling the complex web of IL-4\u2013and IL-13\u2013mediated signaling pathways","volume":"1","author":"Wills-Karp","year":"2008","journal-title":"Sci. Signal."},{"key":"B72","doi-asserted-by":"publisher","first-page":"09603271221121320","DOI":"10.1177\/09603271221121320","article-title":"Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14","volume":"41","author":"Xia","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"B73","unstructured":"The clinical applications of Geranium wilfordii maxim. in Pediatrics., (Chinese Society of pediatrics)\n          \n          \n            \n              Xing\n              Y.\n            \n            \n              Zhang\n              J.\n            \n          \n          \n          2012"},{"key":"B74","doi-asserted-by":"publisher","first-page":"09603271231154227","DOI":"10.1177\/09603271231154227","article-title":"Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy","volume":"42","author":"Xu","year":"2023","journal-title":"Hum. Exp. Toxicol."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2021.1978785","article-title":"The role of the ubiquitin-proteasome pathway in skin cancer development: 26S proteasome-activated NF-\u03baB signal transduction","author":"Yaagoubi","year":"2021","journal-title":"Cancer Biol. Ther."},{"key":"B76","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/imr.12548","article-title":"Recent advances in understanding basophil\u2010mediated Th2 immune responses","volume":"278","author":"Yamanishi","year":"2017","journal-title":"Immunol. Rev."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1111\/all.16353","article-title":"Medical algorithm: diagnosis and treatment of drug hypersensitivity reactions to biologicals, 2024 update","volume":"75","author":"Yang","year":"2024","journal-title":"Allergy"},{"key":"B78","doi-asserted-by":"publisher","first-page":"270","DOI":"10.14159\/j.cnki.0441-3776.2011.03.013","article-title":"Synthesis of 5,6-Epoxy-\u03b2-ionol","volume":"74","author":"Yang","year":"2011","journal-title":"Chem. Bull."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.2147\/DDDT.S124971","article-title":"Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch\/snail pathway in diabetic nephropathy model KKAy mice","volume":"11","author":"Yang","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"B80","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2147\/OTT.S486300","article-title":"Integrated network pharmacology, machine learning and experimental validation to identify the key targets and compounds of TiaoShenGongJian for the treatment of breast cancer","volume":"18","author":"Ying","year":"2025","journal-title":"Oncotargets Ther."},{"key":"B81","doi-asserted-by":"publisher","first-page":"628453","DOI":"10.3389\/fimmu.2021.628453","article-title":"Butyrate shapes immune cell fate and function in allergic asthma","volume":"12","author":"Yip","year":"2021","journal-title":"Front. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"103051","DOI":"10.1016\/j.eclinm.2024.103051","article-title":"Global, regional, national burden of asthma from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021","volume":"80","author":"Yuan","year":"2025","journal-title":"EClinicalMedicine"},{"key":"B83","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13020-025-01075-4","article-title":"A new paradigm for drug discovery in the treatment of complex diseases: drug discovery and optimization","volume":"20","author":"Yuan","year":"2025","journal-title":"Chin. Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.19378\/j.issn.1003-9783.2023.09.008","article-title":"A serum pharmacochemical study on the pharmacodynamic substances basis of the Anti- ischemic injury of Buyang Huanwu decoction","volume":"34","author":"Zeng","year":"2023","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"902318","DOI":"10.3389\/fimmu.2022.902318","article-title":"Regulatory T cells, a viable target against airway allergic inflammatory responses in asthma","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Immunol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"230","DOI":"10.14715\/cmb\/2023.69.15.39","article-title":"Effects of simvastatin on immunoreaction and inflammation in rats with asthma by regulating NOTCH signaling pathway","volume":"69","author":"Zhang","year":"2023","journal-title":"Cell. Mol. Biol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1519998","DOI":"10.3389\/fimmu.2025.1519998","article-title":"Epithelial-mesenchymal transition in asthma: its role and underlying regulatory mechanisms","volume":"16","author":"Zhang","year":"2025","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1761424\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:04:56Z","timestamp":1774418696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1761424\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":87,"alternative-id":["10.3389\/fcell.2026.1761424"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1761424","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1761424"}}