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The role of ubiquitination and deubiquitination in the regulation of cell junctions

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Protein & Cell 2018年第9期9卷 754-769页

作者： Junting Cai Miranda K. Culley Yutong Zhao Jing Zhao Acute Lung Injury center of Excellence Division of Pulmonary Asthma and Critical Care Medicine Department of Medicine The University of Pittsburgh Pittsburgh PA 15213 USA Xiangya Hospital of Central South University Changsha 410008 China

Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, recep- tor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiq- uitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on inves- tigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases＇ biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.

关键词： cell-cell junctions protein stability ubiquitination deubiquitination Rho GTPases

Workup of difficult-to-treat asthma:implications from treatable

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Precision Clinical Medicine 2023年第1期6卷 30-37页

作者： Qing Zhang Wen Wen Wu Lei Li Vanessa M.McDonald Yu Cheng Chen Gang Wang Peter G.Gibson Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory DiseaseWest China HospitalSichuan UniversityChengdu 610041SichuanChina Laboratory of Pulmonary Immunology and Inflammation Frontiers Science Center for Disease-related Molecular NetworkSichuan UniversityChengdu 610041SichuanChina center of Excellence in Severe asthma and Priority Research center for asthma and Respiratory Disease the University of NewcastleNewcastle 2308Australia National Health and Medical Research Council center for Research Excellence in Severe asthma and Treatable Traits the University of NewcastleNewcastle 2308Australia Cardiology Division Department of MedicineWest China HospitalSichuan UniversityChengdu 610041SichuanChina Department of Respiratory and Sleep Medicine John Hunter HospitalHunter Medical Research InstituteNewcastle 2305Australia

Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma ***,due to the generalized heterogeneity and complexity of asthma,its therapeutic efficacy in difficultto-treat asthma is ***,a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to *** reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past *** complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other *** this patient have some potential treatable traits contributing to difficult-to-treat asthma?Through a multidimensional assessment of three domains including pulmonary,extrapulmonary,and behavioral/risk factors,15 treatable traits were identified in the patient,mainly including airflow limitation,eosinophilic airway inflammation,small airway dysfunction,exacerbation prone,dilated cardiomyopathy,diabetes mellitus,inhaler device polypharmacy,smoking,and the absence of an asthma action *** targeted treatment for these treatable traits,the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β_(2)-*** study shows that,in response to the limitation of a stepwise approach to therapy,treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems,and an individualized treatment program is developed and implemented based on this multidimensional assessment,especially for difficult-to-treat asthma.

关键词： difficult-to-treat asthma treatable traits multidimensional assessment comorbidity stepwise approach

Group 2 innate lymphoid cells can engulf and destroy bacteria

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Cellular & Molecular Immunology 2021年第11期18卷 2569-2571页

作者： Yiran Yang Yan Li Yingjie Xu Hanxiao Zhang Yuhan Diao Shihao Chen Ye Cui Chris J.Corrigan Wei Wang Sun Ying Department of Immunology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Department of Otorhinolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing Institute of OtorhinolaryngologyKey Laboratory of Otorhinolaryngology Head and Neck SurgeryMinistry of EducationBeijing Key Laboratory of Nasal DiseasesBeijing100730China School of Rehabilitation Capital Medical UniversityBeijing Bo’ai HospitalChina Rehabilitation Research CenterBeijingChina Division of asthma Allergy&Lung BiologyMRC&Asthma UK Centre in Allergic Mechanisms of AsthmaKing’s College LondonLondonUK

Group 2 innate lymphoid cells(ILC2s)are now known to play prominent roles in many inflammatory responses involving the production of Th2-type cytokines,which contribute to parasitic infections,tissue repair,and metabolic homeostasis[1].More recently,it has emerged that ILC2s may act as antigen-presenting cells,although corresponding evidence of phagocytic activity of these cells is currently scarce[2,3].Herein,we investigated whether ILC2s can phagocytose bacteria,through in vitro experiments.

关键词： lymphoid Th2 homeostasis

Inhibitory effect of Phlai capsules on skin test responses among allergic rhinitis patients:a randomized,three-way crossover study

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Journal of Integrative Medicine 2017年第6期15卷 462-468页

作者： Pattara Tanticharoenwiwat Prapasri Kulalert Thaweephol Dechatiwongse Na Ayudhya Sittichai Koontongkaew Weena Jiratchariyakul Ruedee Soawakontha Prakongsiri Booncong Orapan Poachanukoon center of excellence for allergy asthma and pulmonary diseasethammasat university hospitalPathumthani 12120Thailand department of pediatrics faculty of medicinethammasat universityPathumthani 12120Thailand medicinal herb research unit for asthma faculty of medicinethammasat universityPathumthani 12120Thailand faculty of dentistry thammasat universityPathumthani 12120Thailand faculty of pharmacy mahidol universityBangkok 10400Thailand faculty of pharmaceutical sciences huachiew chalermprekiet universitySamut Prakan 10540Thailand department for development of thai traditional and alternative medicine ministry of public healthNonthaburi 11000Thailand

BACKGROUND： Zingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease. OBJECTIVE： The purpose of this study was to assess the antihistaminic effect of Phlai on skin testing DESIGN, SETTING, PARTICIPANTS AND INTERVENTION： This was a randomized, open-label, three- way crossover study. Twenty allergic rhinitis （AR） patients were enrolled. In randomized sequence, patients received a single dose of Ph/ai capsules （100 or 200 mg） or Ioratadine （10 mg） with a washout period of 1 week between each treatment. MAIN OUTCOME MEASURES： Skin prick testing for histamine and common aeroallergen （house dust mite） were performed before treatment and after 1,2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment. RESULTS： Both 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that Ioratadine caused more wheal and flare suppression than Phial capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and Ioratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse ***： Both 100 mg （compound D 4 mg） when taken as a single therapeutic dose, inhibited AR patients. and 200 mg （compound D 8 mg） Phlai capsules, skin reactivity to histamine and mite skin prick tests in TRIAL REGISTRATION： Thai clinical trial registry （TCTR20160510001）

关键词： Zingiber cassumunac, Phlai antihistamine skin test rhinitis, allergic Ioratadine

Characteristics of Proinflammatory Cytokines and Chemokines in Airways of asthmatics： Relationships with Disease Severity and Infiltration of Inflammatory Cells

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Chinese Medical Journal 2017年第17期130卷 2033-2040页

作者： Ting Yang Yan Li Zhe Lyu Kewu Huang Chris J Corrigan Sun Ying Wei Wang Chen Wang National Clinical Research center for Respiratory Diseases Center for Respiratory Diseases China-Japan Friendship Hospital Capital Medical University Beijing 100029 China Department of Immunology School of Basic Medical Sciences Capital Medical University Beijing 100069 China Department of Respiratory and Critical Care Medicine Beijing Chao-Yang Hospital Capital Medical University and Beijing Institute of Respiratory Medicine Beijing 100020 China MRC and asthma UK Centre in Allergic Mechanisms of asthma Division of Asthma Allergy and Lung Biology King&#39 s College London London UK

Background：Increased proinflammatory cytokines and chemokines might contribute to infiltration of inflammatory cells and remodeling in airways of *** these molecules may be associated with asthma,there is lack of systemic evidence showing which and how important these events are in the *** aimed to analyze the concentrations of these molecules in the airways and relationships with disease severity and with airway infiltration of inflammatory cells in a large cohort of asthmatics （n =70,including 37 mild and 33 moderate/severe asthmatics） compared with controls （n =30）.Methods：Meso scale discovery system and commercial ELISA kits were used to measure the concentrations ofproinflammatory cytokines interleukin （IL）-1 β;tumor necrosis factor-alpha （TNF-α）;IL-6;and IL-17 and CC and CXC chemokines CCL2,CCL4,CCL 11,CCL 13,CCL17,CCL22,and CCL26 and CXCL8,CXCL9,CXCL10,and CXCL1 1 in bronchoalveolar lavage fluid of asthmatics and ***：The concentrations ofIL-1,TNF-α,IL-6,CXCL8 and CXCL 10,and CCL4,CCL 11,CCL 17,and CCL22 were significantly elevated in asthmatics compared with controls （P 〈 0.05）.The concentrations of TNF-α and CXCL8,but not others,were negatively correlated with severity of disease （lung function forced expiratory volume in 1 s）（TNF-α ***：r =-0.359,P =0.002 ***/severe：r =-0.541,P =0.001;CXCL8 ***：r =-0.327,P =0.006 ***/severe：r =-0.625,P =0.0001,respectively）.In addition,concentrations of these two molecules were also correlated with the absolute numbers of infiltrating eosinophils and neutrophils in asthmatic ***：Increased concentrations of TNF-α and CXCL8 are associated with pathogenesis of *** these molecules might provide an alternative therapeutic for this disease.

关键词： asthma Bronchoalveolar Lavage Chemokine Proinflammatory Cytokines

Low-intensity aerobic exercise training attenuates airway inflammation and remodeling in a rat model of steroid-resistant asthma

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Chinese Medical Journal 2014年第17期127卷 3058-3064页

作者： Qin Qingwu Chen Xi Feng Juntao Qin Ling Hu Chengping Department of Respiratory Medicine Xiangya Hospital Central South University National Clincial Research Center for Respirator3[ Disease Changsha Hunan 410008 China Bronchial asthma Research center of Hunan Province Changsha Hunan 410008 China

Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and ***,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma （SSA）.The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma （SRA） and to identify the potential mechanisms underlying these *** Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,*** hyperresponsiveness,inflammation,remodeling,expression of interleukin （IL）-25,IL-33,thymic stromal lymphopoietin （TSLP）,high mobility group box-1 （HMGB1）,and IL-17 in bronchoalveolar lavage fluid （BALF）,and the role of dexamethasone （DXM） were compared between these two asthmatic rat *** effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was *** SRA rats developed neutrophil-dominated airway inflammation （（29.5±4.1）％ of the total cell numbers in BALF）,whereas SSA rats developed eosinophil-dominated airway inflammation （（24.0±6.1）％ of the total cell numbers in BALF）.Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 （（33.6±10.3） vs.（104.8±24.9） pg/ml）,IL-33 （（87.5±25.0） vs.（226.6±40.7） pg/ml）,and TSLP （（1 933.2±899.5） vs.（7 224.0±992.1） pg/ml）,and higher levels of HMGB1 （（21.2±4.5） vs.（5.4±1.6） ng/ml） and IL-17 （（780.5±261.7） vs.（291.4±76.4） pg/ml） in BALF （all P ＜0.05）.However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two *** with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats were less sensitive t

关键词： aerobic exercise inflammation airway remodeling steroid-resistant asthma high mobility group box-1

Prevalence of asthma symptoms and smoking behavior among 20 - 44 years old adults in Tehran: A telephone survey

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Health 2013年第3期5卷 469-474页

作者： Behnaz Tazesh Azadeh Shaabani Mohammad Reza Fazlollahi Abbas Entezari Raheleh Dashti Zahra Pourpak Mostafa Moin Educational Developmental center Ministry of Health and Medical Education Tehran Iran. Immunology Asthma and Allergy Research Institute Tehran University of Medical Sciences Tehran Iran Immunology Asthma and Allergy Research Institute Tehran University of Medical Sciences Tehran Iran.

Background and Objective: asthma is a major health problem and a high-burden disease in the world. Unfortunately the prevalence of asthma in adult populations in Iran is not determined precisely. The aim of this study was to assess the prevalence of asthma symptoms and it’s relation with ages, gender and smoking behaviour in city of Tehran. Methods: A telephone interview survey was conducted among 7150 randomly selected telephone numbers in city of Tehran. A questionnaire adapted from The European Community Respiratory Health Survey (ECRHS) with additional two questions about smoking behaviour and hookah. Results: From 7150 eligible telephone numbers dialled there were 5500 responses (76.92%). The study populations included 3412 female (62%), 2088 men (38%) and the mean age of responder were 31.15 ± 7.33. Their smoking behaviour were;71.6% non smoker, 11.9% active smoker, 16.5% passive smoker and 7.8% used hookah. The prevalence of “wheezing in the last 12 months”, “dyspnea with wheezing” and “wheezing and two nocturnal symptoms” were 24%, 10.8% and 5% respectively. Prevalence of asthma symptoms was significantly greater in smokers than non-smokers groups. Conclusion: In this study by using symptom based questionnaire (ECRHS), we concluded the prevalence of asthma in Tehran adult population was between 5% to 10%. Also this study may made cross-national comparison of our findings with other ECRHS studies possible;rates of “wheezing in the last 12 months”, “dyspnea with wheezing” and “nocturnal dyspnea” were higher than the European Community Respiratory Health Survey median. Role of air pollution, smoking and other risk factors for asthma should be considered.

关键词： asthma Adult Prevalence Smoking Iran

E-waste environmental contamination and harm to public health in China

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Frontiers of Medicine 2015年第2期9卷 220-228页

作者： Xijin Xu Xiang Zeng H. Marike Boezen Xia Huo Laboratory of Environmental Medicine and Developmental Toxicology and Guangdong Provincial Key Laboratory oflnfectious Diseases' and Molecular Immunopathology Shantou University Medical College Shantou 515041 China Department of Cell Biology and Genetics Shantou University Medical College Shantou 515041 China Department of Epidemiology University Medical Center Groningen University of Groningen Groningen the Netherlands Groningen Research Institute for asthma and COPD (GRIAC) University Medical Center Groningen University of Groningen 1 Hanzeplein Groningen 970ORB the Netherlands

The adverse effects of electronic waste （e-waste） on the human body have stirred up concern in recent years. China is one of the countries that confront serious pollution and human exposure of e-waste, and the majority of the population is exposed to potentially hazardous substances that are derived from informal e-waste recycling processes. This study reviews recent reports on human exposure to e-waste in China, with particular focus on exposure routes （e.g., inhalation and ingestion） and several toxicities of human （e.g., endocrine system, respiratory system, reproductive system, developmental toxicity, neurotoxicity, and genetic toxicity）. Pieces of evidence that associate e-waste exposure with human health effects in China are assessed. The role of toxic heavy metals （e.g., lead, cadmium, chromium, mercury, and nickel） and organic pollutants （e.g., polybrominated diphenyl ethers （PBDEs）, polychlorinated biphenyl （PCBs）, polycyclic aromatic hydrocarbons （PAHs）, polybrominated biphenyls （PBBs）, polyhalogenated aromatic hydrocarbons （PHAHs）, bisphenol A （BPA）） on human health is also briefly discussed.

关键词： e-waste heavy metal organic pollutant hazardous toxicity human health China

Mapping and localization of susceptible genes in asthma

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Chinese Medical Journal 2011年第1期000卷 132-143页

作者： GU Ming-liang ZHAO Jing Beijing Institute of Genomics Key Laboratory of Genome Science and Information Chinese Academy of Sciences Beijing 100029 China center for asthma Prevention and Control Affiliated Children'sHospital Capital Institute of Pediatrics Beijing 100020 China

Objective To elucidate the development of mapping and localization of susceptible genes on chromosomes to asthma related phenotypes. Data sources Published articles about susceptibility genes for asthma related phenotypes were selected using PubMed. Study selection Using methods of candidate gene positional clone and genome-wide scan with linkage and association analysis to determine the location in the genome of susceptibility genes to asthma and asthma related phenotypes. Results There are multiple regions in the genome harboring susceptibility genes to asthma and asthma related phenotypes, including chromosomes 5, 11, 12, 6, 2, 3, 13, 7, 14, 9, 19 and 17. Many of these regions contain candidate genes involved in asthma development and progression. Some susceptible genes may affect the phenotype expression or response to therapy. In addition, the interaction of multiple genes with the environment may contribute to the susceptibility to asthma. Conclusions As an essential step toward cloning the susceptible genes to asthma, fine mapping and localization on chromosomes are definitely needed. Novel powerful tools for gene discovery and the integration of genetics, biology and bioinformatics should be pursued.

关键词： susceptible gene chromosome mapping localization asthma