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PBX/Knotted 1 homeobox-2(PKNOX2)is a novel regulator of myocardial fibrosis

Signal Transduction and Targeted Therapy 2024年第5期9卷 2231-2249页

作者： Liang Chen Haotong Li Xiaorui Liu Ningning Zhang Kui Wang Anteng Shi Hang Gao Deniz akdis Ardan mSaguner Xinjie Xu Elena Osto Willem Van de Veen Guangyu Li Antoni Bayés-Genís Firat Duru Jiangping Song Xiangjie Li Shengshou Hu State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China School of Statistics and Data Science Nankai UniversityTianjinChina Department of Cardiology University Heart CenterUniversity Hospital Zurich and University of ZurichZurichSwitzerland Institute for Clinical Chemistry University Hospital Zurich and University of ZürichZurichSwitzerland Swiss Institute of Allergy and Asthma Research(SIAF) University of ZurichDavosSwitzerland Heart Institute Hospital Universitari Germans Trias i PujolBadalonaCIBERCVSpain

much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA ***,the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription *** this study,we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription *** this unbiased protocol,we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell *** in fibroblasts,a novel regulator,PKNOX2,was identified as being associated with physiological fibroblast activation in healthy *** validate the roles of these transcription factors in maintaining homeostasis,we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast *** trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast *** gain-and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis ***,fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis,*** summary,this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart *** this optimized protocol,we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.

关键词： NOX2 homeostasis fibrosis

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Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma

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Chinese medical Journal 2022年第5期135卷 519-531页

作者： Xiang Dong mei Ding Jinjin Zhang Ismail Ogülür Yagiz Pat m.beccel akdis Yadong Gao Cezmi A.akdis Department of Allergology Zhongnan Hospital of Wuhan UniversityHubei Province Key Laboratory of Allergy and ImmunologyWuhanHubei 430071China Swiss Institute of Allergy and Asthma Research(SIAF) University of ZurichHerman-Burchard Strasse 9DavosSwitzerland.

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis,allergic asthma,atopic dermatitis,and chronic rhinosinusitis with nasal *** is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their *** studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma,which may partly explain the increasing prevalence of asthma in China and around the *** epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific *** development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter-and sub-epithelial areas and the development of epithelial tissue ***,preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of *** review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma,the structure and molecular composition of the airway epithelial barrier,and the assessment of epithelial barrier *** role of airway epithelial barrier disruption in the pathogenesis of asthma will be *** addition,the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants,and current treatments to restore the airway epithelial barrier are reviewed.

关键词： Airway epithelial barrier Type 2 inflammation Asthma Allergen Environmental pollutants

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Primary adenoid cystic carcinoma of the lung:A case report

Primary adenoid cystic carcinoma of the lung:A case report

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2009年世界肿瘤介入学术大会

作者： Rahsan Habiboglu Ilknur Aytas Ferit Cetinyokus Zeynep Dogan Haluk Sayan Sercan zyurt Leyla Kayaaslan Nalan Aslan Ferdi Aksaray m.beccel Tümz ankara numune education and research hospital radiation oncology clinic

＜正＞Pulmonary adenoid cystic carcinomas typically arise from central extra-pulmonary airways and lung involvement is *** the other hand,this entity should be kept in mind because it has a more favorable clinical course compared to the primary lung *** cytology is seldom useful in the diagnosis of primary bronchial adenoid cystic carcinoma,because these neoplasms usually have a submucosal location with often intact *** most endobronchial adenoid cystic carcinomas are endoscopically visible,bronchoscope-guided fine-needle aspiration constitutes an excellent approach to establish a pathologic diagnosis.

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