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https://www.readbyqxmd.com/read/29906536/mahuang-decoction-mitigates-airway-inflammation-and-regulates-il-21-stat3-signaling-pathway-in-rat-asthma-model
#1
Yu He, Xiaohui Lou, Zhan Jin, Li Yu, Ling Deng, Haitong Wan
ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, bronchial asthma is still a severe disease threatening human health, and it is incumbent upon us to seek effective therapeutic drugs. Mahuang decoction (MHD), a classic famous Chinese prescription, has been used for thousands of years to prevent phlegm from forming, stop coughing and relieve asthma, but the relevant mechanism has not been thoroughly clarified. This study aims to investigate the anti-airway inflammation effect of MHD and the possible molecular mechanism underlying IL21/STAT3 signaling pathway, so as to provide guidance for the treatment of MHD on bronchial asthma...
June 12, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29882755/hif-oxygen-sensing-pathways-in-lung-biology
#2
REVIEW
Andrés A Urrutia, Julián Aragonés
Cellular responses to oxygen fluctuations are largely mediated by hypoxia-inducible factors (HIFs). Upon inhalation, the first organ inspired oxygen comes into contact with is the lungs, but the understanding of the pulmonary HIF oxygen-sensing pathway is still limited. In this review we will focus on the role of HIF1α and HIF2α isoforms in lung responses to oxygen insufficiency. In particular, we will discuss novel findings regarding their role in the biology of smooth muscle cells and endothelial cells in the context of hypoxia-induced pulmonary vasoconstriction...
June 6, 2018: Biomedicines
https://www.readbyqxmd.com/read/29874617/effect-of-loading-history-on-airway-smooth-muscle-cell-matrix-adhesions
#3
Linda Irons, Markus R Owen, Reuben D O'Dea, Bindi S Brook
Integrin-mediated adhesions between airway smooth muscle (ASM) cells and the extracellular matrix (ECM) regulate how contractile forces generated within the cell are transmitted to its external environment. Environmental cues are known to influence the formation, size, and survival of cell-matrix adhesions, but it is not yet known how they are affected by dynamic fluctuations associated with tidal breathing in the intact airway. Here, we develop two closely related theoretical models to study adhesion dynamics in response to oscillatory loading of the ECM, representing the dynamic environment of ASM cells in vivo...
June 5, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29843083/sirt7-regulates-the-tgf-%C3%AE-1-induced-proliferation-and-migration-of-mouse-airway-smooth-muscle-cells-by-modulating-the-expression-of-tgf-%C3%AE-receptor-i
#4
Ping Fang, Yu Xue, Yonghong Zhang, Na Fan, Ling Ou, Lingjuan Leng, Jianli Pan, Xugeng Wang
Accumulating evidence shows that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays an important role in the pathogenesis of various diseases; however, little is known about the role of SIRT7 in asthma, which is characterized by airway remodeling. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of airway smooth muscle (ASM) cells, which are critical events during airway remodeling in asthmatic conditions. The results demonstrated that SIRT7 expression was significantly upregulated in ASM cells treated with transforming growth factor-beta 1 (TGF-β1)...
May 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29794201/clinical-pharmacology-of-bronchodilator-medications
#5
Dennis M Williams, Bruce K Rubin
Obstructive lung diseases, including asthma and COPD, are characterized by air-flow limitation. Bronchodilator therapy can often decrease symptoms of air-flow obstruction by relaxing airway smooth muscle (bronchodilation), decreasing dyspnea, and improving quality of life. In this review, we discuss the pharmacology of the β agonist and anticholinergic bronchodilators and their use, particularly in asthma and COPD. Expanding knowledge of receptor subtypes and G-protein signaling, agonist and antagonist specificity, and drug delivery have led to the introduction of safer medications with fewer off-target effects, medications with longer duration of action that may improve adherence, and more effective and efficient aerosol delivery devices...
June 2018: Respiratory Care
https://www.readbyqxmd.com/read/29792856/comparison-of-the-3-d-patterns-of-the-parasympathetic-nervous-system-in-the-lung-at-late-developmental-stages-between-mouse-and-chicken
#6
Tadayoshi Watanabe, Ryo Nakamura, Yuta Takase, Etsuo A Susaki, Hiroki R Ueda, Ryosuke Tadokoro, Yoshiko Takahashi
Although the basic schema of the body plan is similar among different species of amniotes (mammals, birds, and reptiles), the lung is an exception. Here, anatomy and physiology are considerably different, particularly between mammals and birds. In mammals, inhaled and exhaled airs mix in the airways, whereas in birds the inspired air flows unidirectionally without mixing with the expired air. This bird-specific respiration system is enabled by the complex tubular structures called parabronchi where gas exchange takes place, and also by the bellow-like air sacs appended to the main part of the lung...
May 21, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29785773/molecular-tension-probes-to-investigate-the-mechanopharmacology-of-single-cells-a-step-toward-personalized-mechanomedicine
#7
Kornelia Galior, Victor Pui-Yan Ma, Yang Liu, Hanquan Su, Nusaiba Baker, Reynold A Panettieri, Cherry Wongtrakool, Khalid Salaita
Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors...
May 22, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29775222/abca1-inhibits-pdgf-induced-proliferation-and-migration-of-rat-airway-smooth-muscle-cell-through-blocking-tlr2-nf-%C3%AE%C2%BAb-nfatc1-signaling
#8
Wei Cheng, Kun Yan, Yanni Chen, Wen Zhang, Zongzheng Ji, Chengxue Dang
Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP-binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)-induced primary rat ASMC proliferation and migration...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29765214/tiotropium-inhibits-methacholine-induced-extracellular-matrix-production-via-%C3%AE-catenin-signaling-in-human-airway-smooth-muscle-cells
#9
Yating Huo, Lili Guan, Jiawen Xu, Luqian Zhou, Rongchang Chen
Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29763833/%C3%AE-2-adrenoceptor-signalling-bias-in-asthma-and-copd-and-the-potential-impact-on-the-comorbidities-associated-with-these-diseases
#10
REVIEW
Maria Gabriella Matera, Clive Page, Barbara Rinaldi
Inhaled selective β2-agonists are the most widely used treatment for obstructive airway diseases. The classical mechanism of action of these drugs is considered as their ability to activate β2-adrenergic receptors (β2-AR) on airway smooth muscle leading to G-protein activation and subsequent generation of c-AMP causing bronchodilation. However, there is now growing evidence to suggest that binding of β2-agonists to β2-AR is pleotropically coupled to many intracellular pathways whereby depending on the state of the β2-AR when activated, a subset of different intracellular responses can be triggered...
May 12, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29763381/the-mfge8-%C3%AE-8%C3%AE-1-pten-pathway-regulates-airway-smooth-muscle-contraction-in-allergic-inflammation
#11
Amin Khalifeh-Soltani, Deepti Gupta, Arnold Ha, Michael J Podolsky, Ritwik Datta, Kamran Atabai
Asthma affects ∼300 million people worldwide. Despite multiple treatment options, asthma treatment remains unsatisfactory in a subset of patients. Airway obstruction is a hallmark of allergic asthma and is largely due to airway smooth muscle hypercontractility induced by airway inflammation. Identification of molecular pathways that regulate airway smooth muscle hypercontractility is of considerable therapeutic interest. We previously identified roles for milk fat globule epidermal growth factor-like 8 (Mfge8) in opposing the effects of allergic inflammation on increasing airway smooth muscle contractile force...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29760450/caveolin-3-differentially-orchestrates-cholinergic-and-serotonergic-constriction-of-murine-airways
#12
M Keshavarz, M Skill, M I Hollenhorst, S Maxeiner, M Walecki, U Pfeil, W Kummer, G Krasteva-Christ
The mechanisms of controlling airway smooth muscle (ASM) tone are of utmost clinical importance as inappropriate constriction is a hallmark in asthma and chronic obstructive pulmonary disease. Receptors for acetylcholine and serotonin, two relevant mediators in this context, appear to be incorporated in specialized, cholesterol-rich domains of the plasma membrane, termed caveolae due to their invaginated shape. The structural protein caveolin-1 partly accounts for anchoring of these receptors. We here determined the role of the other major caveolar protein, caveolin-3 (cav-3), in orchestrating cholinergic and serotonergic ASM responses, utilizing newly generated cav-3 deficient mice...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29757584/effects-of-nerve-growth-factor-shrna-inhibition-on-asthma-phenotypes-in-a-mouse-model-of-asthma
#13
Jinhong Wu, Bing Chen, Wenxian Li, Yanan Xiao
Nerve growth factor (NGF) plays an important role in airway hyper-responsiveness (AHR). In this study, we aimed at investigating the effect of NGF inhibition on AHR and other asthma phenotypes in a mouse model of asthma. 12 mice in each group were injected with lentiviral vectors expressing non-targeting shRNA (sham shRNA), targeting NGF (shRNA-1 and shRNA-2), or normal saline for control before the asthma models were established. Peak inspiratory pressure (PIP), NGF levels in bronchoalveolar lavage fluid (BALF), and bronchoconstriction in response to acetylcholine (ACh) were measured...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#14
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29743070/the-anti-proliferative-and-anti-inflammatory-response-of-copd-airway-smooth-muscle-cells-to-hydrogen-sulfide
#15
Mark M Perry, Bernadett Tildy, Alberto Papi, Paolo Casolari, Gaetano Caramori, Karen Limbert Rempel, Andrew J Halayko, Ian Adcock, Kian Fan Chung
BACKBROUND: COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H2 S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. METHODS: We examined the effect of H2 S upon ASM cells from COPD patients...
May 9, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29742412/traction-force-screening-enabled-by-compliant-pdms-elastomers
#16
Haruka Yoshie, Newsha Koushki, Rosa Kaviani, Mohammad Tabatabaei, Kavitha Rajendran, Quynh Dang, Amjad Husain, Sean Yao, Chuck Li, John K Sullivan, Magali Saint-Geniez, Ramaswamy Krishnan, Allen J Ehrlicher
Actomyosin contractility is an essential element of many aspects of cellular biology and manifests as traction forces that cells exert on their surroundings. The central role of these forces makes them a novel principal therapeutic target in diverse diseases. This requires accurate and higher-capacity measurements of traction forces; however, existing methods are largely low throughput, limiting their utility in broader applications. To address this need, we employ Fourier-transform traction force microscopy in a parallelized 96-well format, which we refer to as contractile force screening...
May 8, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29739412/immunohistological-features-related-to-functional-impairment-in-lymphangioleiomyomatosis
#17
Ellen Caroline Toledo do Nascimento, Bruno Guedes Baldi, Alessandro Wasum Mariani, Raquel Annoni, Ronaldo Adib Kairalla, Suzana Pinheiro Pimenta, Luiz Fernando Ferraz da Silva, Carlos Roberto Ribeiro Carvalho, Marisa Dolhnikoff
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients...
May 8, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29729548/pepducins-as-a-potential-treatment-strategy-for-asthma-and-copd
#18
REVIEW
Reynold A Panettieri, Tonio Pera, Stephen B Liggett, Jeffrey L Benovic, Raymond B Penn
Current therapies to treat asthma and other airway diseases primarily include anti-inflammatory agents and bronchodilators. Anti-inflammatory agents target trafficking and resident immunocytes and structural cells, while bronchodilators act to prevent or reverse shortening of airway smooth muscle (ASM), the pivotal tissue regulating bronchomotor tone. Advances in our understanding of the biology of G protein-coupled receptors (GPCRs) and biased agonism offers unique opportunities to modulate GPCR function that include the use of pepducins and allosteric modulators...
May 2, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29722559/mir-142-3p-is-associated-with-aberrant-wingless-integrase-i-wnt-signaling-during-airway-remodeling-in-asthma
#19
Sabine Bartel, Gianni Carraro, Francesca Alessandrini, Susanne Krauss-Etschmann, Fabio L M Ricciardolo, Saverio Bellusci
BACKGROUND: Asthma is characterized by a chronic inflammation and remodeling of the airways. While inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms in order to develop novel therapies. OBJECTIVE: we previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle precursor (ASM) cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling...
May 3, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29722436/cigarette-smoke-upregulates-pde3-and-pde4-to-decrease-camp-in-airway-cells
#20
Haoxiao Zuo, Bing Han, Wilfred J Poppinga, Lennard Ringnalda, Loes E M Kistemaker, Andrew J Halayko, Reinoud Gosens, Viacheslav O Nikolaev, Martina Schmidt
BACKGROUND AND PURPOSE: 3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood...
May 3, 2018: British Journal of Pharmacology
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