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https://www.readbyqxmd.com/read/28420758/the-foxm1-inhibitor-rcm-1-suppresses-goblet-cell-metaplasia-and-prevents-il-13-and-stat6-signaling-in-allergen-exposed-mice
#1
Lifeng Sun, Xiaomeng Ren, I-Ching Wang, Arun Pradhan, Yufang Zhang, Hannah M Flood, Bo Han, Jeffrey A Whitsett, Tanya V Kalin, Vladimir V Kalinichenko
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation of goblet cells in response to allergens. We identified RCM-1, a nontoxic small molecule that inhibited goblet cell metaplasia and excessive mucus production in mice after exposure to allergens...
April 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28408202/airway-clearance-techniques-for-primary-ciliary-dyskinesia-is-the-cystic-fibrosis-literature-portable
#2
REVIEW
Lynne Marie Schofield, Alistair Duff, Cathy Brennan
Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired mucociliary clearance. Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group. Current physiotherapy practice in PCD is based on evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses on the available evidence and outlines challenges in extrapolating evidence between the conditions for best clinical practice.
March 16, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28405161/mucoactive-and-antioxidant-medicines-for-copd-consensus-of-a-group-of-chinese-pulmonary-physicians
#3
REVIEW
Xixin Yan, Yuanlin Song, Ce Shen, Wenbing Xu, Liangan Chen, Jian Zhang, Huiguo Liu, Mao Huang, Guoxiang Lai, Guishen Qian, Jing Wang, Xianwei Ye, Jinping Zheng, Chunxue Bai
Airway mucus hypersecretion is a frequent symptom associated with acute and chronic airway disease. Inhibition of mucus production or promotion of mucolysis not only relieved symptoms but also improved disease outcomes. There are numerous available mucoactive medicines for prescription, and how to select them properly for different diseases is important for clinical practice. So far, there is no one consensus or guideline reported. A group of Chinese pulmonary physicians worked together to complete this consensus based on literature review, summarized mechanism and usage of each classical mucoactive medicine...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28401936/bmal1-links-the-circadian-clock-to-viral-airway-pathology-and-asthma-phenotypes
#4
A Ehlers, W Xie, E Agapov, S Brown, D Steinberg, R Tidwell, G Sajol, R Schutz, R Weaver, H Yu, M Castro, L B Bacharier, X Wang, M J Holtzman, J A Haspel
Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical to the generation of circadian rhythms in mammals. Here, we used a viral model of acute and chronic airway disease to examine how circadian clock disruption affects asthmatic lung phenotypes. Deletion of the core clock gene bmal1 or environmental disruption of circadian function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus (SeV) and influenza A virus in mice...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#5
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393183/anti%C3%A2-inflammatory-effects-of-dihydromyricetin-in-a-mouse-model-of-asthma
#6
Bin Xu, Shuran Huang, Caiying Wang, Haitao Zhang, Shengcun Fang, Yingming Zhang
Dihydromyricetin (DHM) is a plant flavonoid and is the primary active ingredient isolated from the medicinal herb, Ampelopsis grossedentata. DHM has been shown to possess various pharmacological activities, including anti‑inflammatory effects. However, the possible role of DHM in asthma treatment remains to be elucidated. The present study aimed to investigate its anti‑inflammatory properties in mice with symptoms of allergic asthma. The C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma...
April 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28390837/the-influence-of-mannitol-on-morphology-and-disintegration-of-spray-dried-nano-embedded-microparticles
#7
Afra Torge, Philipp Grützmacher, Frank Mücklich, Marc Schneider
Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles...
April 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28389622/il-4r%C3%AE-on-dendritic-cells-in-neonates-and-th2-immunopathology-in-respiratory-syncytial-virus-infection
#8
Bishwas Shrestha, Dahui You, Jordy Saravia, David T Siefker, Sridhar Jaligama, Greg I Lee, Asmaa A Sallam, Jeffrey N Harding, Stephania A Cormier
Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children, and severe RSV infection early in life has been associated with asthma development. Using a neonatal mouse model, we have shown that down-regulation of IL-4 receptor α (IL-4Rα) with antisense oligonucleotides in the lung during neonatal infection protected from RSV immunopathophysiology. Significant down-regulation of IL-4Rα was observed on pulmonary CD11b(+) myeloid dendritic cells (mDCs) suggesting a role for IL-4Rα on mDCs in the immunopathogenesis of neonatal RSV infection...
April 7, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28373109/modelling-the-bronchial-barrier-in-pulmonary-drug-delivery-a-human-bronchial-epithelial-cell-line-supplemented-with-human-tracheal-mucus
#9
Xabi Murgia, Hanzey Yasar, Cristiane Carvalho-Wodarz, Brigitta Loretz, Sarah Gordon, Konrad Schwarzkopf, Ulrich Schaefer, Claus-Michael Lehr
The airway epithelium together with the mucus layer coating it forms a protective system that efficiently filters and removes potentially harmful particles contained in inhaled air. The same mechanism, however, serves to entrap particulate drug carriers, precluding their interaction with their target. The mucus barrier is often neglected in in vitro testing setups employed for the assessment of pulmonary drug delivery strategies. Therefore, our aim was to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus...
April 1, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28361885/exposure-to-ambient-particulate-matter-induced-copd-in-a-rat-model-and-a-description-of-the-underlying-mechanism
#10
Fang He, Baoling Liao, Jinding Pu, Chenglong Li, Mengning Zheng, Lingmei Huang, Yumin Zhou, Dongxing Zhao, Bing Li, Pixin Ran
While the health effects of air pollution have been an international public health concern since at least the 1950s, recent research has focused on two broad sources of air pollution, namely, biomass fuel (BMF) and motor vehicle exhaust (MVE). Many studies have shown associations between air pollution PM and exacerbations of pre-existing COPD, but the role of air pollution PM in the development and progression of COPD is still uncertain. The current study indicates that rats can develop pronounced COPD following chronic exposure to air pollution PM (BMF and MVE), as characterized by lung function reduction, mucus metaplasia, lung and systemic inflammation, emphysema, and small airway remodeling...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361060/bioaerosols-in-the-lungs-of-subjects-with-different-ages-part-2-clearance-modeling
#11
Robert Sturm
BACKGROUND: The present contribution deals with theoretical aspects regarding biogenic particle clearance from various lung structures of probands with different ages (1, 5, 15, 20 y). With reference to part 1 of the study, particles varying in size and shape are subject to a detailed analysis. The main goal of the investigation consists in an increase of our knowledge concerning the clearance behaviour of bioparticles and its dependence upon various physiological and anatomical factors...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28358158/direct-monitoring-of-pulmonary-disease-treatment-biomarkers-using-plasmonic-gold-nanorods-with-diffusion-sensitive-oct
#12
R L Blackmon, S M Kreda, P R Sears, B S Chapman, D B Hill, J B Tracy, L E Ostrowski, A L Oldenburg
The solid concentration of pulmonary mucus (wt%) is critical to respiratory health. In patients with respiratory disease, such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disorder (COPD), mucus hydration is impaired, resulting in high wt%. Mucus with high wt% is a hallmark of pulmonary disease that leads to obstructed airways, inflammation, and infection. Methods to measure mucus hydration in situ and in real-time are needed for drug development and personalized therapy. We employed plasmonic gold nanorod (GNR) biosensors that intermittently collide with macromolecules comprising the mucus mesh as they self-diffuse, such that GNR translational diffusion (DT) is sensitive to wt%...
March 30, 2017: Nanoscale
https://www.readbyqxmd.com/read/28357473/effect-of-anaerobiasis-or-hypoxia-on-pseudomonas-aeruginosa-inhibition-of-aspergillus-fumigatus-biofilm
#13
Rajesh Anand, Karl V Clemons, David A Stevens
Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) are the major bacterial and fungal pathogens in the airways of cystic fibrosis (CF) patients. This is likely related to their ability to form biofilms. Both microbes have been associated with CF disease progression. The interplay between these two pathogens has been studied under aerobic conditions, though accumulating data indicates that much of the CF airway is hypoxic or anaerobic. We studied the microbial interaction in these latter environments...
March 29, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28352653/defective-postsecretory-maturation-of-muc5b-mucin-in-cystic-fibrosis-airways
#14
Lubna H Abdullah, Jessica R Evans, T Tiffany Wang, Amina A Ford, Alexander M Makhov, Kristine Nguyen, Raymond D Coakley, Jack D Griffith, C William Davis, Stephen T Ballard, Mehmet Kesimer
In cystic fibrosis (CF), airway mucus becomes thick and viscous, and its clearance from the airways is impaired. The gel-forming mucins undergo an ordered "unpacking/maturation" process after granular release that requires an optimum postsecretory environment, including hydration and pH. We hypothesized that this unpacking process is compromised in the CF lung due to abnormal transepithelial fluid transport that reduces airway surface hydration and alters ionic composition. Using human tracheobronchial epithelial cells derived from non-CF and CF donors and mucus samples from human subjects and domestic pigs, we investigated the process of postsecretory mucin unfolding/maturation, how these processes are defective in CF airways, and the probable mechanism underlying defective unfolding...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28341820/il-23-gene-and-protein-expression-in-childhood-asthma
#15
Soheila Alyasin, Reza Amin, Ali Fazel, Mohammad Hossein Karimi, Seyed Hesamedin Nabavizadeh, Hossein Esmaeilzadeh, Maryam Babaei
BACKGROUND: Asthma is the chronic inflammation of airways characterized by eosinophilic infiltration, mucus overproduction, airway hyper-responsiveness and airway remodeling. These changes are induced mostly by cytokines which are produced by T helper (Th) 2 cells. Recently, the role of interleukin-23 (IL-23) in the pathogenesis of adult allergic asthma has been studied. OBJECTIVE: To explore IL-23 serum levels and its expression in persistent asthma compared with healthy children younger than five years old...
March 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28332107/mechanisms-driving-gender-differences-in-asthma
#16
REVIEW
Hubaida Fuseini, Dawn C Newcomb
PURPOSE OF REVIEW: Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis...
March 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28327162/biological-effects-of-carbon-black-nanoparticles-are-changed-by-surface-coating-with-polycyclic-aromatic-hydrocarbons
#17
Karina Lindner, Michael Ströbele, Sandra Schlick, Sina Webering, André Jenckel, Johannes Kopf, Olga Danov, Katherina Sewald, Christian Buj, Otto Creutzenberg, Thomas Tillmann, Gerhard Pohlmann, Heinrich Ernst, Christina Ziemann, Gereon Hüttmann, Holger Heine, Henning Bockhorn, Tanja Hansen, Peter König, Heinz Fehrenbach
BACKGROUND: Carbon black nanoparticles (CBNP) are mainly composed of carbon, with a small amount of other elements (including hydrogen and oxygen). The toxicity of CBNP has been attributed to their large surface area, and through adsorbing intrinsically toxic substances, such as polycyclic aromatic hydrocarbons (PAH). It is not clear whether a PAH surface coating changes the toxicological properties of CBNP by influencing their physicochemical properties, through the specific toxicity of the surface-bound PAH, or by a combination of both...
March 21, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28323735/covered-balloon-expanding-stents-in-airway-stenosis
#18
Adnan Majid, Fayez Kheir, Jey Chung, Daniel Alape, Bryan Husta, Scott Oh, Erik Folch
BACKGROUND: The balloon-expanding stents are widely available but rarely described for use within the tracheobronchial tree. This report describes our experience with these stents in airway stenosis particularly as a lobar salvage therapy. METHODS: This was a retrospective review of all records in which the balloon-expanding stents were used at a tertiary medical center. Ages, sex, location of stenosis, etiology of stenosis, stent size, duration of stent placement and associated interventions for airway stenosis were recorded...
April 2017: Journal of Bronchology & Interventional Pulmonology
https://www.readbyqxmd.com/read/28322599/dissolvit-an-in-vitro-method-for-simulating-the-dissolution-and-absorption-of-inhaled-dry-powder-drugs-in-the-lungs
#19
Per Gerde, Maria Malmlöf, Lina Havsborn, Carl-Olof Sjöberg, Pär Ewing, Stefan Eirefelt, Katarina Ekelund
The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second purpose was to evaluate this method. DissolvIt(®) was developed as a simulation of the air-blood barrier of the upper airways, constituting: "airborne" particles deposited on a glass cover slip, a mucus simulant, a polycarbonate (basal) membrane, and a pumped albumin buffer simulating the pulmonary blood flow. The PreciseInhale(®) exposure system was used to aerosolize and deposit test formulations onto cover slips...
February 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28299285/a-genetic-screen-reveals-novel-targets-to-render-pseudomonas-aeruginosa-sensitive-to-lysozyme-and-cell-wall-targeting-antibiotics
#20
Kang-Mu Lee, Keehoon Lee, Junhyeok Go, In Ho Park, Jeon-Soo Shin, Jae Young Choi, Hyun Jik Kim, Sang Sun Yoon
Pseudomonas aeruginosa is capable of establishing airway infections. Human airway mucus contains a large amount of lysozyme, which hydrolyzes bacterial cell walls. P. aeruginosa, however, is known to be resistant to lysozyme. Here, we performed a genetic screen using a mutant library of PAO1, a prototype P. aeruginosa strain, and identified two mutants (ΔbamB and ΔfabY) that exhibited decrease in survival after lysozyme treatment. The bamB and fabY genes encode an outer membrane assembly protein and a fatty acid synthesis enzyme, respectively...
2017: Frontiers in Cellular and Infection Microbiology
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