{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:15:42Z","timestamp":1785575742591,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["H30-Nanchitou (Nan)-Ippan- 016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan- 016"]}]},{"name":"Japan Society for the Promotion of Science KAKENHI","award":["0G20KA7383"],"award-info":[{"award-number":["0G20KA7383"]}]},{"name":"Health Labor Sciences Research grant","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Health Labor Sciences Research grant","award":["H30-Nanchitou (Nan)-Ippan- 016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan- 016"]}]},{"name":"Health Labor Sciences Research grant","award":["0G20KA7383"],"award-info":[{"award-number":["0G20KA7383"]}]},{"name":"Research Collaboration Fund with Universal Sound Design Inc.","award":["22K09668"],"award-info":[{"award-number":["22K09668"]}]},{"name":"Research Collaboration Fund with Universal Sound Design Inc.","award":["H30-Nanchitou (Nan)-Ippan- 016"],"award-info":[{"award-number":["H30-Nanchitou (Nan)-Ippan- 016"]}]},{"name":"Research Collaboration Fund with Universal Sound Design Inc.","award":["0G20KA7383"],"award-info":[{"award-number":["0G20KA7383"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.<\/jats:p>","DOI":"10.3390\/ijms25042113","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T08:12:03Z","timestamp":1707466323000},"page":"2113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Severe Type 2 Inflammation Leads to High Platelet-Activating-Factor-Associated Pathology in Chronic Rhinosinusitis with Nasal Polyps\u2014A Hierarchical Cluster Analysis Using Bulk RNA Barcoding and Sequencing"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-0839","authenticated-orcid":false,"given":"Takashi","family":"Ishino","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kawasumi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-7821","authenticated-orcid":false,"given":"Kota","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Horibe","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Chikuie","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Taruya","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-1264","authenticated-orcid":false,"given":"Takao","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-2501","authenticated-orcid":false,"given":"Sachio","family":"Takeno","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/all.12644","article-title":"Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC Study","volume":"70","author":"Tokunaga","year":"2015","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/jamaoto.2020.1453","article-title":"Contemporary Classification of Chronic Rhinosinusitis Beyond 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