{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:03:14Z","timestamp":1793696594281,"version":"4.5.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Nature Science funds of China","award":["81870708"],"award-info":[{"award-number":["81870708"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High mobility group box 1 (HMGB1) has been known to involve in the pathogenesis of many inflammatory diseases. The aim of this study was to establish animal model of acute rhinosinusitis (ARS), and determine whether ethyl pyruvate (EP) attenuate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in ARS animals. Thirty-six Sprague Dawley (SD) rat were used as follows: six normal controls without intervention (group 1); thirty rats were used for establishment of ARS rats model by nasal insertion of Merocel sponge, and model rats without any treatments (group 2), treated with nasal drops of sterile saline (group 3), 10\u00a0\u03bcl EP (group 4), and 20\u00a0\u03bcl EP (group 5), twice a day for 5\u00a0days, respectively. Bacterial culture was done regularly and the main bacterial strains were identified using matrix-assisted laser desorption\/ionization time of flight mass spectrometry. HMGB1 expression in sinonasal mucosa was detected by immunohistochemistry and RT-PCR. Serum levels of HMGB1, IL-6, and TNF-\u03b1 were determined by ELISA. Data from 29 of 36 rats that had completed research were analyzed. Bacterial colony formation unit (CFU) of nasal secretion was significantly higher in each group of ARS rats compared with controls (p\u2009&lt;\u20090.001). ARS rats treated with EP had only slightly decreased CFU, but significantly attenuated inflammatory response of sinonasal mucosa and decreased HMGB1 expression compared to those treated with saline alone (p\u2009&lt;\u20090.001). Serum levels of HMGB1, IL-6 and TNF-\u03b1 were significantly higher in ARS rats compared to controls, and decreased by EP treatments (p\u2009&lt;\u20090.001). Nasal sponge packing led to acute inflammatory response of nasal sinus in rats, and increased the expression of HMGB1, IL-6, and TNF-\u03b1. Nasal drops with EP could attenuate the inflammation of sinonasal mucosa through inhibiting the expression of HMGB1, IL-6 and TNF-\u03b1 in ARS rats.\n<\/jats:p>","DOI":"10.1038\/s41598-021-85785-3","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T16:48:15Z","timestamp":1616086095000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ethyl pyruvate ameliorate inflammatory response of sinonasal mucosa by inhibiting HMGB1 in rats with acute rhinosinusitis"],"prefix":"10.1038","volume":"11","author":[{"given":"Xiang","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxiang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"issue":"S29","key":"85785_CR1","first-page":"1","volume":"58","author":"WJ Fokkens","year":"2020","unstructured":"Fokkens, W. J. et al. EPOS 2020: European position paper on rhinosinusitis and nasal polyps. Rhinology 58(S29), 1\u2013464 (2020).","journal-title":"Rhinology"},{"issue":"5","key":"85785_CR2","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1177\/0194599813479768","volume":"148","author":"SS Smith","year":"2013","unstructured":"Smith, S. S. et al. Variations in antibiotic prescribing of acute rhinosinusitis in United States ambulatory settings. Otolaryngol. Head Neck Surg. 148(5), 852\u2013859 (2013).","journal-title":"Otolaryngol. Head Neck Surg."},{"issue":"2","key":"85785_CR3","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1007\/s11882-011-0180-0","volume":"11","author":"P Eloy","year":"2011","unstructured":"Eloy, P. et al. Actual concepts in rhinosinusitis: A review of clinical presentations, inflammatory pathways, cytokine profiles, remodeling, and management. Curr. Allergy Asthma Rep. 11(2), 146\u2013162 (2011).","journal-title":"Curr. Allergy Asthma Rep."},{"issue":"Suppl 1","key":"85785_CR4","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.2119\/molmed.2015.00087","volume":"21","author":"H Yang","year":"2015","unstructured":"Yang, H., Wang, H., Chavan, S. S. & Andersson, U. High mobility group box protein 1 (HMGB1): The prototypical endogenous danger molecule. Mol. Med. 21(Suppl 1), S6\u2013S12 (2015).","journal-title":"Mol. Med."},{"issue":"7","key":"85785_CR5","doi-asserted-by":"publisher","first-page":"E225","DOI":"10.1002\/lary.25172","volume":"125","author":"HJ Min","year":"2015","unstructured":"Min, H. J. et al. Level of secreted HMGB1 correlates with severity of inflammation in chronic rhinosinusitis. Laryngoscope 125(7), E225\u2013E230 (2015).","journal-title":"Laryngoscope"},{"key":"85785_CR6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12950-016-0144-1","volume":"13","author":"R Yang","year":"2016","unstructured":"Yang, R., Zhu, S. & Tonnessen, T. I. Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries. J. Inflamm. (Lond.) 13, 37 (2016).","journal-title":"J. Inflamm. (Lond.)"},{"issue":"11","key":"85785_CR7","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1177\/1535370214566563","volume":"240","author":"S Chen","year":"2015","unstructured":"Chen, S. et al. Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release. Exp. Biol. Med. (Maywood) 240(11), 1490\u20131499 (2015).","journal-title":"Exp. Biol. Med. (Maywood)"},{"issue":"6","key":"85785_CR8","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1111\/his.13470","volume":"72","author":"E Rrapaj","year":"2018","unstructured":"Rrapaj, E. et al. Expression analysis of HMGB1 in histological samples of malignant pleural mesothelioma. Histopathology 72(6), 1039\u20131050 (2018).","journal-title":"Histopathology"},{"issue":"6","key":"85785_CR9","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/s00405-011-1483-4","volume":"268","author":"M Jin","year":"2011","unstructured":"Jin, M. et al. Developing a mouse model of acute bacterial rhinosinusitis. Eur. Arch. Otorhinolaryngol 268(6), 857\u2013861 (2011).","journal-title":"Eur. Arch. Otorhinolaryngol"},{"issue":"1","key":"85785_CR10","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s00405-016-4189-9","volume":"274","author":"K Nomura","year":"2017","unstructured":"Nomura, K. et al. Predicting postoperative fever and bacterial colonization on packing material following endoscopic endonasal surgery. Eur. Arch. Otorhinolaryngol. 274(1), 167\u2013173 (2017).","journal-title":"Eur. Arch. Otorhinolaryngol."},{"issue":"4","key":"85785_CR11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.2500\/aap.2007.28.3017","volume":"28","author":"C Klemens","year":"2007","unstructured":"Klemens, C. et al. Mediators and cytokines in allergic and viral-triggered rhinitis. Allergy Asthma Proc. 28(4), 434\u2013441 (2007).","journal-title":"Allergy Asthma Proc."},{"issue":"9","key":"85785_CR12","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1111\/j.1398-9995.2009.02012.x","volume":"64","author":"A M\u00e5nsson","year":"2009","unstructured":"M\u00e5nsson, A., Bachar, O., Adner, M. & Cardell, L. O. Nasal CpG. oligodeoxynucleotide administration induces a local inflammatory response in nonallergic individuals. Allergy 64(9), 1292\u20131300 (2009).","journal-title":"Allergy"},{"issue":"9","key":"85785_CR13","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1111\/j.1365-2222.2005.02316.x","volume":"35","author":"H Riechelmann","year":"2005","unstructured":"Riechelmann, H. et al. Nasal biomarker profiles in acute and chronic rhinosinusitis. Clin. Exp. Allergy 35(9), 1186\u20131191 (2005).","journal-title":"Clin. Exp. Allergy"},{"issue":"11","key":"85785_CR14","doi-asserted-by":"publisher","first-page":"7718","DOI":"10.1128\/IAI.73.11.7718-7726.2005","volume":"73","author":"AMC van Rossum","year":"2005","unstructured":"van Rossum, A. M. C., Lysenko, E. S. & Weiser, J. N. Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model. Infect. Immun. 73(11), 7718\u20137726 (2005).","journal-title":"Infect. Immun."},{"issue":"1","key":"85785_CR15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1084\/jem.20141318","volume":"212","author":"H Yang","year":"2015","unstructured":"Yang, H. et al. MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J. Exp. Med. 212(1), 5\u201314 (2015).","journal-title":"J. Exp. Med."},{"issue":"4","key":"85785_CR16","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1055\/s-0036-1597665","volume":"21","author":"LM Bellussi","year":"2017","unstructured":"Bellussi, L. M., Cocca, S., Passali, G. C. & Passali, D. HMGB1 in the pathogenesis of nasal inflammatory diseases and its inhibition as new therapeutic approach: A review from liuterature. Int. Arch. Otorhinolaryngol. 21(4), 390\u2013398 (2017).","journal-title":"Int. Arch. Otorhinolaryngol."},{"issue":"4","key":"85785_CR17","doi-asserted-by":"publisher","first-page":"278","DOI":"10.2500\/ajra.2013.27.3909","volume":"27","author":"SM Hong","year":"2013","unstructured":"Hong, S. M. et al. Increased expression of high-mobility group protein B1 in chronic rhinosinusitis. Am. J. Rhinol. Allergy 27(4), 278\u2013282 (2013).","journal-title":"Am. J. Rhinol. Allergy"},{"issue":"3","key":"85785_CR18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2500\/ajra.2016.30.4300","volume":"30","author":"S Shimizu","year":"2016","unstructured":"Shimizu, S., Kouzaki, H., Kato, T., Tojima, I. & Shimizu, T. HMGB1-TLR4 signaling contributes to the secretion of interleukin 6 and interleukin 8 by nasal epithelial cells. Am. J. Rhinol. Allergy. 30(3), 167\u2013172 (2016).","journal-title":"Am. J. Rhinol. Allergy."},{"issue":"19","key":"85785_CR19","first-page":"4411","volume":"21","author":"A Ciofalo","year":"2017","unstructured":"Ciofalo, A. et al. Pathological and cytological changes of the nasal mucosa in acute rhinosinusitis: The role of hyaluronic acid as supportive therapy. Eur. Rev. Med. Pharmacol. 21(19), 4411\u20134418 (2017).","journal-title":"Eur. Rev. Med. Pharmacol."},{"issue":"2","key":"85785_CR20","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.bcp.2010.03.007","volume":"80","author":"KK Kao","year":"2010","unstructured":"Kao, K. K. & Fink, M. P. The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochem. Pharmacol. 80(2), 151\u2013159 (2010).","journal-title":"Biochem. Pharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85785-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85785-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85785-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T05:14:12Z","timestamp":1670044452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-85785-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["85785"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-85785-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"assertion":[{"value":"20 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6206"}}