{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:25:04Z","timestamp":1782789904276,"version":"3.54.5"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Arch Otorhinolaryngol"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>To investigate the therapeutic effect of Bicalutamide, an androgen receptor antagonist on the onset and development of allergic rhinitis in an animal model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>40 male BALB\/c mice were randomly divided into five groups (eight mice per group). Aluminum hydroxide powder was used as an adjuvant, combined with Ovalbumin (OVA) to establish the mouse model of allergic rhinitis via ultrasonic nebulization of OVA to stimulate the nasal cavity. Mice in Bica#1 group were intraperitoneally injected with 0.02\u00a0mg Bicalutamide\/0.5\u00a0ml of normal saline daily for 7 consecutive days; mice in Bica#2 group were administered 0.02\u00a0mg Bicalutamide\/0.5\u00a0ml of normal saline via intraperitoneal injection for 5 consecutive days, and then the same amount of normal saline was injected intraperitoneally for 2 consecutive days. Enzyme-linked immunosorbent assay was adopted to detect the serological levels of IgE, IL-4, and IL-6 production. Eosinophil infiltration was observed under microscope after hematoxylin and eosin staining of nasal mucosa. Quantitative PCR and Western blot were employed for determination of histamine receptors mRNA expression and PI3K\/PKB associated protein levels, respectively.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Histological analysis shown that allergic lesion was induced after OVA sensitization. Intraperitoneal injection with 0.02\u00a0mg Bicalutamide daily for 7 consecutive days significantly reduced the allergic lesion; however, mice injected with the same amount of normal saline at the same time demonstrated no allergic rhinitis symptoms. In addition, there was a significant reduction in eosinophils number in Bicalutamide treated mice (<jats:italic>n<\/jats:italic>\u2009=\u20098) compared to the OVA group (<jats:italic>n<\/jats:italic>\u2009=\u20098) (OVA: 19.6\u2009\u00b1\u20095.3 vs. Bica#1: 7.7\u2009\u00b1\u20090.8 vs. Bica#2: 9.4\u2009\u00b1\u20091.2, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Furthermore, ELISA results revealed that the serological levels of IgE (OVA: 17.3\u2009\u00b1\u20091.7\u00a0\u00b5g\/ml vs. Bica#1: 9.2\u2009\u00b1\u20090.6 vs. Bica#2: 10.4\u2009\u00b1\u20092.3, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), IL-4 (OVA: 164.3\u2009\u00b1\u20095.1\u00a0pg\/ml vs. Bica#1: 110.2\u2009\u00b1\u20093.1 vs. Bica#2: 115.3\u2009\u00b1\u20094.1, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and IL-6 (OVA: 167.3\u2009\u00b1\u20093.7\u00a0pg\/ml vs. Bica#1: 117.5\u2009\u00b1\u20096.5 vs. Bica#2: 114.8\u2009\u00b1\u20092.4, both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) were significantly decreased after two different dosage of Bicalutamide treatment. Similarly, histamine receptors in mast cells were significantly reduced after two different dosage of Bicalutamide treatment. More importantly, p-PKB protein was notably reduced after two different dosage of Bicalutamide treatment compared to the OVA group, mTOR protein levels were also down regulated after two different dosage of Bicalutamide treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our data demonstrated that androgen receptor antagonist Bicalutamide can significantly alleviate allergic rhinitis lesion in the animal model. PI3K\/PKB activity in mast cells was suppressed after Bicalutamide injection. Our results provide important implication in allergic rhinitis prevention and treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00405-022-07538-w","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T16:16:24Z","timestamp":1657728984000},"page":"703-711","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bicalutamide, an androgen receptor antagonist, effectively alleviate allergic rhinitis via suppression of PI3K\u2013PKB activity"],"prefix":"10.1007","volume":"280","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-0716","authenticated-orcid":false,"given":"Geping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingkai","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"7538_CR1","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/nri2327","volume":"8","author":"SJ Galli","year":"2008","unstructured":"Galli SJ, Grimbaldeston M, Tsai M (2008) Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol 8:478\u2013486. https:\/\/doi.org\/10.1038\/nri2327","journal-title":"Nat Rev Immunol"},{"key":"7538_CR2","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.3389\/fimmu.2018.01873","volume":"9","author":"EB Thangam","year":"2018","unstructured":"Thangam EB, Jemima EA, Singh H, Baig MS, Khan M, Mathias CB, Church MK, Saluja R (2018) The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: the hunt for new therapeutic targets. Front Immunol 9:1873. https:\/\/doi.org\/10.3389\/fimmu.2018.01873","journal-title":"Front Immunol"},{"key":"7538_CR3","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.trsl.2016.02.011","volume":"174","author":"BD Modena","year":"2016","unstructured":"Modena BD, Dazy K, White AA (2016) Emerging concepts: mast cell involvement in allergic diseases. Transl Res 174:98\u2013121. https:\/\/doi.org\/10.1016\/j.trsl.2016.02.011","journal-title":"Transl Res"},{"key":"7538_CR4","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/MPH.0000000000000329","volume":"37","author":"D King","year":"2015","unstructured":"King D, Yeomanson D, Bryant HE (2015) PI3King the lock: targeting the PI3K\/Akt\/mTOR pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol 37:245\u2013251. https:\/\/doi.org\/10.1097\/MPH.0000000000000329","journal-title":"J Pediatr Hematol Oncol"},{"key":"7538_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023414","volume":"6","author":"L Ojeda","year":"2011","unstructured":"Ojeda L, Gao J, Hooten KG, Wang E, Thonhoff JR, Dunn TJ, Gao T, Wu P (2011) Critical role of PI3K\/Akt\/GSK3beta in motoneuron specification from human neural stem cells in response to FGF2 and EGF. PLoS ONE 6:e23414. https:\/\/doi.org\/10.1371\/journal.pone.0023414","journal-title":"PLoS ONE"},{"key":"7538_CR6","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/nature02991","volume":"431","author":"K Ali","year":"2004","unstructured":"Ali K, Bilancio A, Thomas M, Pearce W, Gilfillan AM, Tkaczyk C, Kuehn N, Gray A, Giddings J, Peskett E, Fox R, Bruce I, Walker C et al (2004) Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature 431:1007\u20131011. https:\/\/doi.org\/10.1038\/nature02991","journal-title":"Nature"},{"key":"7538_CR7","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1016\/j.jaci.2015.12.1313","volume":"137","author":"F Horak","year":"2016","unstructured":"Horak F, Puri KD, Steiner BH, Holes L, Xing G, Zieglmayer P, Zieglmayer R, Lemell P, Yu A (2016) Randomized phase 1 study of the phosphatidylinositol 3-kinase delta inhibitor idelalisib in patients with allergic rhinitis. J Allergy Clin Immunol 137:1733\u20131741. https:\/\/doi.org\/10.1016\/j.jaci.2015.12.1313","journal-title":"J Allergy Clin Immunol"},{"key":"7538_CR8","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.aller.2019.11.005","volume":"48","author":"G Wu","year":"2020","unstructured":"Wu G, Zhu H, Wu X, Liu L, Ma X, Yuan Y, Fu X, Zhang L, Lv Y, Li D, Liu J, Lu J, Yu Y et al (2020) Anti-allergic function of alpha-Tocopherol is mediated by suppression of PI3K-PKB activity in mast cells in mouse model of allergic rhinitis. Allergol Immunopathol (Madr) 48:395\u2013400. https:\/\/doi.org\/10.1016\/j.aller.2019.11.005","journal-title":"Allergol Immunopathol (Madr)"},{"key":"7538_CR9","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1158\/1541-7786.MCR-08-0342","volume":"7","author":"M Yoeli-Lerner","year":"2009","unstructured":"Yoeli-Lerner M, Chin YR, Hansen CK, Toker A (2009) Akt\/protein kinase b and glycogen synthase kinase-3beta signaling pathway regulates cell migration through the NFAT1 transcription factor. Mol Cancer Res 7:425\u2013432. https:\/\/doi.org\/10.1158\/1541-7786.MCR-08-0342","journal-title":"Mol Cancer Res"},{"key":"7538_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9040034","author":"M Crumbaker","year":"2017","unstructured":"Crumbaker M, Khoja L, Joshua AM (2017) AR signaling and the PI3K pathway in prostate cancer. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers9040034","journal-title":"Cancers (Basel)."},{"key":"7538_CR11","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.ccr.2011.04.008","volume":"19","author":"BS Carver","year":"2011","unstructured":"Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, Scardino PT, Rosen N, Sawyers CL (2011) Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19:575\u2013586. https:\/\/doi.org\/10.1016\/j.ccr.2011.04.008","journal-title":"Cancer Cell"},{"key":"7538_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ejca.2017.01.024","volume":"76","author":"C Massard","year":"2017","unstructured":"Massard C, Chi KN, Castellano D, de Bono J, Gravis G, Dirix L, Machiels JP, Mita A, Mellado B, Turri S, Maier J, Csonka D, Chakravartty A et al (2017) Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer. Eur J Cancer 76:36\u201344. https:\/\/doi.org\/10.1016\/j.ejca.2017.01.024","journal-title":"Eur J Cancer"},{"key":"7538_CR13","first-page":"664","volume":"44","author":"EZ Fan","year":"2009","unstructured":"Fan EZ, Xi L, Han DM, Zhang SZ, Li Y, Zhang L (2009) Evaluation of the safety of aluminium adjuvant in the preparation of allergic rhinitis animal model. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 44:664\u2013668","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"7538_CR14","doi-asserted-by":"publisher","first-page":"300","DOI":"10.4168\/aair.2018.10.4.300","volume":"10","author":"L Cheng","year":"2018","unstructured":"Cheng L, Chen J, Fu Q, He S, Li H, Liu Z, Tan G, Tao Z, Wang D, Wen W, Xu R, Xu Y, Yang Q et al (2018) Chinese Society of allergy guidelines for diagnosis and treatment of allergic rhinitis. Allergy Asthma Immunol Res 10:300\u2013353. https:\/\/doi.org\/10.4168\/aair.2018.10.4.300","journal-title":"Allergy Asthma Immunol Res"},{"key":"7538_CR15","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.phymed.2018.06.044","volume":"55","author":"TT Bui","year":"2019","unstructured":"Bui TT, Kwon DA, Choi DW, Jung SY, Lee SY, Piao CH, Hyeon E, Fan Y, Yeon SH, Son RH, Shon DH, Song CH, Shin HS et al (2019) Rosae multiflorae fructus extract and its four active components alleviate ovalbumin-induced allergic inflammatory responses via regulation of Th1\/Th2 imbalance in BALB\/c rhinitis mice. Phytomedicine 55:238\u2013248. https:\/\/doi.org\/10.1016\/j.phymed.2018.06.044","journal-title":"Phytomedicine"},{"key":"7538_CR16","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.intimp.2019.02.025","volume":"70","author":"Y Fan","year":"2019","unstructured":"Fan Y, Piao CH, Hyeon E, Jung SY, Eom JE, Shin HS, Song CH, Chai OH (2019) Gallic acid alleviates nasal inflammation via activation of Th1 and inhibition of Th2 and Th17 in a mouse model of allergic rhinitis. Int Immunopharmacol 70:512\u2013519. https:\/\/doi.org\/10.1016\/j.intimp.2019.02.025","journal-title":"Int Immunopharmacol"},{"key":"7538_CR17","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1002\/cne.23580","volume":"522","author":"LA Wyatt","year":"2014","unstructured":"Wyatt LA, Filbin MT, Keirstead HS (2014) PTEN inhibition enhances neurite outgrowth in human embryonic stem cell-derived neuronal progenitor cells. J Comp Neurol 522:2741\u20132755. https:\/\/doi.org\/10.1002\/cne.23580","journal-title":"J Comp Neurol"},{"key":"7538_CR18","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/s41389-017-0007-5","volume":"6","author":"DA Dart","year":"2017","unstructured":"Dart DA, Uysal-Onganer P, Jiang WG (2017) Prostate-specific PTen deletion in mice activates inflammatory microRNA expression pathways in the epithelium early in hyperplasia development. Oncogenesis 6:400. https:\/\/doi.org\/10.1038\/s41389-017-0007-5","journal-title":"Oncogenesis"},{"issue":"1698\u2013700","key":"7538_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.014","volume":"136","author":"X Wu","year":"2015","unstructured":"Wu X, Wang S, Han M, Song B, Ye P, Ma S, Li J, Chen F, Xu G, Ding Q, Xia J, Li H (2015) Critical link between glycogen synthase kinase 3beta and forkhead box P3 in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 136(1698\u2013700):e12. https:\/\/doi.org\/10.1016\/j.jaci.2015.08.014","journal-title":"J Allergy Clin Immunol"},{"key":"7538_CR20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092912","volume":"9","author":"R Fu","year":"2014","unstructured":"Fu R, Li J, Zhong H, Yu D, Zeng X, Deng M, Sun Y, Wen W, Li H (2014) Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3beta-related T regulatory cell insufficiency. PLoS ONE 9:e92912. https:\/\/doi.org\/10.1371\/journal.pone.0092912","journal-title":"PLoS ONE"},{"key":"7538_CR21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jbior.2017.06.003","volume":"65","author":"MA Hermida","year":"2017","unstructured":"Hermida MA, Dinesh Kumar J, Leslie NR (2017) GSK3 and its interactions with the PI3K\/AKT\/mTOR signalling network. Adv Biol Regul 65:5\u201315. https:\/\/doi.org\/10.1016\/j.jbior.2017.06.003","journal-title":"Adv Biol Regul"}],"container-title":["European Archives of Oto-Rhino-Laryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-022-07538-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00405-022-07538-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00405-022-07538-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T07:04:27Z","timestamp":1674025467000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00405-022-07538-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["7538"],"URL":"https:\/\/doi.org\/10.1007\/s00405-022-07538-w","relation":{},"ISSN":["0937-4477","1434-4726"],"issn-type":[{"value":"0937-4477","type":"print"},{"value":"1434-4726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]},"assertion":[{"value":"1 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was approved by the research committee of Zhangjiagang Hospital affiliated to Soochow University, China. Bicalutamide, an androgen receptor antagonist, effectively alleviate allergic rhinitis via suppression of PI3K\u2013PKB activity.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}}]}}