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https://www.readbyqxmd.com/read/29778504/solitary-chemosensory-cells-are-a-primary-epithelial-source-of-interleukin-25-in-chronic-rhinosinusitis-with-nasal-polyps
#1
Michael A Kohanski, Alan D Workman, Neil N Patel, Li-Yin Hung, Julie P Shtraks, Bei Chen, Mariel Blasetti, Laurel Doghramji, David W Kennedy, Nithin D Adappa, James N Palmer, De'Broski R Herbert, Noam A Cohen
BACKGROUND: IL-25 can function as an early signal for the respiratory Type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive. OBJECTIVE: In this study, we sought to determine if the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29778213/nitric-oxide-an-old-molecule-with-noble-functions-in-pseudomonas-aeruginosa-biology
#2
Masanori Toyofuku, Sang-Sun Yoon
Pseudomonas aeruginosa, a Gram-negative bacterium, is characterized by its versatility that enables persistent survival under adverse conditions. It can grow on diverse energy sources and readily acquire resistance to antimicrobial agents. As an opportunistic human pathogen, it also causes chronic infections inside the anaerobic mucus airways of cystic fibrosis patients. As a strict respirer, P. aeruginosa can grow by anaerobic nitrate ( [Formula: see text] ) respiration. Nitric oxide (NO) produced as an intermediate during anaerobic respiration exerts many important effects on the biological characteristics of P...
2018: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/29767240/munc13%C3%A2-4-mediates-human-neutrophil-elastase%C3%A2-induced-airway-mucin5ac-hypersecretion-by-interacting-with-syntaxin2
#3
Rui Xu, Jia Zhou, Xiang-Dong Zhou, Qi Li, Juliy M Perelman, Victor P Kolosov
The overexpression and hypersecretion of mucus is a hallmark of chronic pulmonary inflammatory disease. Mucin5AC (MUC5AC) is a major component of airway gel‑forming mucin. Members of the Unc13 (Munc13) protein family act as important activators of granule exocytosis from various types of mammalian cells. The present study aimed to determine the role of Munc13 family proteins in MUC5AC secretion via an in vitro study with BEAS‑2B and Calu‑3 cell lines. Reverse transcription‑quantitative polymerase chain reaction and western blotting indicated that stimulation of the cells with 100 nM human neutrophil elastase (hNE) for 1 h did not affect the expression of either unc13 homolog B (Munc13‑2) or unc13 homolog D (Munc13‑4), but immunofluorescence analysis demonstrated that hNE treatment was associated with the recruitment of Munc13‑4 to the plasma membrane...
May 14, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29750543/a-disintegrin-and-a-metalloproteinase-domain-8-adam8-a-novel-protective-proteinase-in-copd
#4
Francesca Polverino, Joselyn Rojas-Quintero, Xiaoyun Wang, Hans Petersen, Li Zhang, Xiaoyan Gai, Andrew Higham, Duo Zhang, Kushagra Gupta, Amit Rout, Ilyas Yambayev, Victor Pinto-Plata, Lynette M Sholl, Danen Cunoosamy, Bartolomé R Celli, James Goldring, Dave Singh, Yohannes Tesfaigzi, Jadwiga Wedzicha, Henric Olsson, Caroline A Owen
RATIONALE: A disintegrin and metalloproteinase-8 (ADAM8) is expressed by leukocytes and epithelial cells in health, but its contribution to the pathogenesis of COPD is unknown. OBJECTIVES: ADAM8 levels were measured in lung, sputum, plasma, and/or bronchoalveolar lavage fluid (BALF) samples from COPD patients, smokers, and non-smokers, and wild-type (WT) mice exposed to cigarette smoke (CS) versus air. COPD-like lung pathologies were compared in CS-exposed WT versus Adam8-/- mice...
May 11, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29748385/activation-of-airway-epithelial-bitter-taste-receptors-by-pseudomonas-aeruginosa-quinolones-modulates-calcium-cyclic-amp-and-nitric-oxide-signaling
#5
Jenna R Freund, Corrine J Mansfield, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Danielle R Reed, Peihua Jiang, Robert J Lee
Bitter taste receptors (T2Rs), discovered in many tissues outside the tongue, have recently become potential therapeutic targets. We showed previously that airway epithelial cells express several T2Rs that activate innate immune responses that may be important for treatment of airway diseases such as chronic rhinosinusitis. It is imperative to more clearly understand what compounds activate airway T2Rs as well as their full range of functions. T2R isoforms in airway motile cilia (T2Rs 4, 14, 16, and 38) produce bactericidal levels of nitric oxide (NO) that also increase ciliary beating, promoting clearance of mucus and trapped pathogens...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29748250/effective-silencing-of-enac-by-sirna-delivered-with-epithelial-targeted-nanocomplexes-in-human-cystic-fibrosis-cells-and-in-mouse-lung
#6
Aristides D Tagalakis, Mustafa M Munye, Rositsa Ivanova, Hanpeng Chen, Claire M Smith, Ahmad M Aldossary, Luca Z Rosa, Dale Moulding, Josephine L Barnes, Konstantinos N Kafetzis, Stuart A Jones, Deborah L Baines, Guy W J Moss, Christopher O'Callaghan, Robin J McAnulty, Stephen L Hart
INTRODUCTION: Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport...
May 10, 2018: Thorax
https://www.readbyqxmd.com/read/29747753/dehydrocostus-lactone-a-sesquiterpene-from-saussurea-lappa-clarke-suppresses-allergic-airway-inflammation-by-binding-to-dimerized-translationally-controlled-tumor-protein
#7
Haejun Pyun, Unwoo Kang, Eun Kyoung Seo, Kyunglim Lee
BACKGROUND: We previously reported that the biologically active form of histamine releasing factor (HRF) is dimerized translationally controlled tumor protein (dTCTP) which is involved in a number of allergic diseases. HYPOTHESIS/PURPOSE: Hoping that agents that modulate dTCTP may provide new therapeutic targets to allergic inflammatory diseases, we screened a library of natural products for substances that inhibit dTCTP. One such inhibitor we found was dehydrocostus lactone (DCL), a natural sesquiterpene present in rhizome of Saussurea lappa Clarke, the subject of this study...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29747318/-effects-of-glycyrrhizic-acid-on-erk1-2-and-p38-mapk-signaling-pathway-in-a-murine-model-of-asthma
#8
W Y Zhang, Y C Gu, Y Tang, Q Z Wu
Objective: To explore the effects of glycyrrhizic acid (GA) on Extracellular regulated protein kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) signaling pathways in a murine model of asthma. Methods: Sixty female BALB/c mice were randomly divided into 6 groups ( n =10 each): a control group, an asthmatic group, two treatment groups with low and high doses of GA, U0126 group and SB203580 group. Within 24 hours after the last OVA challenge, histological studies of lung were conducted with the hematoxylin and eosin staining (HE) and alcian blue-periodic acid-Schiff (AB-PAS), the relative protein expression of ERK1/2 and p38 MAPK were detected by immunohistochemistry and Western blotting in vivo ...
April 24, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29732561/small-rna-and-transcriptome-sequencing-reveal-the-role-of-mir-199a-3p-in-inflammatory-processes-in-cystic-fibrosis-airways
#9
Pauline Bardin, Emmeline Marchal-Duval, Florence Sonneville, Sabine Blouquit-Laye, Nathalie Rousselet, Philippe Le Rouzic, Harriet Corvol, Olivier Tabary
Cystic fibrosis (CF) is the most common lethal genetic disease, caused by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations. CF is characterized by an ionic imbalance and thickened mucus, which impair mucociliary clearance, promote bacterial colonization, and the establishment of infection/inflammation cycles. However, the origin of this inflammation remains unclear, although microRNA (miRNA) are suspected to be involved. MiRNA are small non-coding RNA that bind to the 3'-untranslated regions (UTR) of target gene mRNA, thereby repressing their translation and/or inducing their degradation...
May 7, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29729496/progressive-increase-in-allergen-concentration-abrogates-immune-tolerance-in-ovalbumin-induced-murine-model-of-chronic-asthma
#10
Gurupreet S Sethi, Amarjit S Naura
Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week...
May 2, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29724394/enhancing-our-understanding-of-computerised-adventitious-respiratory-sounds-in-different-copd-phases-and-healthy-people
#11
Ana Oliveira, João Rodrigues, Alda Marques
BACKGROUND: Timely diagnosis of acute exacerbations of COPD (AECOPD) is challenging as it depends on patients' reports. AECOPD are characterised by increased airway obstruction, mucus and air trapping, which results in changes in lung acoustics. Thus, adventitious respiratory sounds (ARS) may be useful to detect/monitor AECOPD. OBJECTIVE: To evaluate computerised ARS changes during AECOPD. METHODS: 25 non-hospitalised patients with AECOPD (16♂, 70 [62...
May 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29698781/in-vivo-and-in-vitro-investigation-of-anti-inflammatory-and-mucus-regulatory-activities-of-a-fixed-combination-of-thyme-and-primula-extracts
#12
Jan Seibel, Kirill Kryshen, Judit E Pongrácz, Martin D Lehner
Hypersecretion of viscous mucus is one of the hallmark symptoms of acute and chronic bronchitis and typically develops secondary to an inflammation of the airway epithelium. Bronchipret® TP film-coated tablets (BRO), an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts, has been successfully used clinically for the treatment of acute bronchitis for more than two decades. However, the underlying pharmacological mechanisms of action have not been fully understood so far...
April 23, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29692622/identifying-agents-triggering-bronchiolitis-in-the-state-of-qatar
#13
Mohamed A Hendaus, Ahmed H Alhammadi, Prem Chandra, Eshan Muneer, Mohamed S Khalifa
Background: Bronchiolitis is considered as the most frequent lower respiratory tract infection in infants and young children. This disorder is marked by acute inflammation, edema, damage of epithelial cells lining small airways, and augmentation of mucus production. Objective: The goal of the study was to identify agents triggering bronchiolitis in the State of Qatar. Materials and methods: A cross-sectional retrospective study was performed at Hamad Medical Corporation, the only tertiary and academic medical center in the State of Qatar...
2018: International Journal of General Medicine
https://www.readbyqxmd.com/read/29688496/zmapptm-reinforces-the-airway-mucosal-barrier-against-ebola-virus
#14
Bing Yang, Alison Schaefer, Ying-Ying Wang, Justin McCallen, Phoebe Lee, Jay M Newby, Harendra Arora, Priya A Kumar, Larry Zeitlin, Kevin J Whaley, Scott A McKinley, William A Fischer, Dimple Harit, Samuel K Lai
Filoviruses, including Ebola, have the potential to be transmitted via virus-laden droplets deposited onto mucus membranes. Protecting against such emerging pathogens will require understanding how they may transmit at mucosal surfaces and developing strategies to reinforce the airway mucus barrier.Here, we prepared Ebola pseudovirus (with Zaire strain glycoproteins) and employed high resolution multiple particle tracking to track the motions of hundreds of individual pseudoviruses in fresh and undiluted human airway mucus isolated from extubated endotracheal tubes...
April 24, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29680833/lps-exposure-in-early-life-protects-against-mucus-hypersecretion-in-ovalbumin-induced-asthma-by-down-regulation-of-the-il-13-and-jak-stat6-pathways
#15
Fengxia Ding, Bo Liu, Wenjing Zou, Daiyin Tian, Qubei Li, Jihong Dai, Zhengxiu Luo, Zhou Fu
BACKGROUND/AIMS: Previous studies have shown that lipopolysaccharide (LPS) exposure may have a protective effect on asthma by reducing airway hyper-responsiveness, airway inflammation and serum IgE levels. However, there are few studies investigating the effect of LPS on mucous secretion in asthma. In this study, we evaluate the relationship between LPS pre-treatment in infant mice and airway mucus hypersecretion in an OVA (ovalbumin)-induced asthma model, and further explore the mechanisms behind this effect...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29678545/preparation-of-drug-loaded-small-unilamellar-liposomes-and-evaluation-of-their-potential-for-the-treatment-of-chronic-respiratory-diseases
#16
Vincenzo De Leo, Silvia Ruscigno, Adriana Trapani, Sante Di Gioia, Francesco Milano, Delia Mandracchia, Roberto Comparelli, Stefano Castellani, Angela Agostiano, Giuseppe Trapani, Lucia Catucci, Massimo Conese
The aim of the present investigation was to evaluate the influence of liposome formulation on the ability of vesicles to penetrate a pathological mucus model obtained from COPD affected patients in order to assess the potential of such vesicles for the treatment of chronic respiratory diseases by inhalation. Therefore, Small Unilamellar Liposomes (PLAIN-LIPOSOMEs), Pluronic® F127-surface modified liposomes (PF-LIPOSOMEs) and PEG 2000PE-surface modified liposomes (PEG-LIPOSOMEs) were prepared using the micelle-to-vesicle transition (MVT) method and beclomethasone dipropionate (BDP) as model drug...
April 17, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29676620/interleukin-13-stimulation-reveals-the-cellular-and-functional-plasticity-of-the-airway-epithelium
#17
Max A Seibold
About 50% of patients with asthma exhibit chronic airway inflammation driven by the type 2 cytokines interleukin (IL)-4, IL-5, and IL-13. These patients with type 2-high asthma experience more allergic symptoms, greater airway hyperresponsiveness, and more severe mucus obstruction than patients with type 2-low asthma. Mouse models of asthma have shown that much of the airway dysfunction in these models can be generated by IL-13 stimulation of the airway epithelium alone. Both in vivo mouse model studies and in vitro studies of human mucociliary airway epithelial cultures have shown that IL-13 induces cellular remodeling of the airway epithelium through proliferation-independent transdifferentiation processes...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29667749/effect-of-lysm-macrophage-depletion-on-lung-pathology-in-mice-with-chronic-bronchitis
#18
Yogesh Saini, Brandon W Lewis, Dongfang Yu, Hong Dang, Alessandra Livraghi-Butrico, Fabio Del Piero, Wanda K O'Neal, Richard C Boucher
Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29667580/severe-asthma-phenotypes-classified-by-site-of-airway-involvement-and-remodeling-via-chest-ct-scan
#19
S Kim, K Nam Jin, S H Cho, C Hyun Lee, H R Kang
BACKGROUND AND OBJECTIVE: This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualized by computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. METHODS: Chest CT images of severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed...
April 18, 2018: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/29658455/-efficacy-of-early-treatment-via-fiber-bronchoscope-in-children-with-mycoplasma-pneumoniae-pneumonia-complicated-by-airway-mucus-obstruction
#20
Li-Jie Cao, Jian-Hua Liu, Jin-Feng Shuai, Bo Niu, Su-Kun Lu, Kun-Ling Huang
OBJECTIVE: To study the efficacy of early treatment via fiber bronchoscope in children with Mycoplasma pneumoniae pneumonia (MPP) complicated by airway mucus obstruction. METHODS: According to the time from admission to the treatment via fiber bronchoscope, the children with MPP who were found to have airway mucus obstruction under a fiber bronchoscope were randomly divided into early intervention group (≤3 days; n=40) and late intervention group (>3 days; n=56)...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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