4,951 results match your criteria American Journal of Physiology - Lung Cellular and Molecular Physiology[Journal]


Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 13. Epub 2019 Feb 13.

Research, Philips Research, Netherlands.

Introduction: Volatile organic compounds (VOCs) in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption - gas chromatography - mass-spectrometry (TD-GC-MS) and selected ion flow tube - mass spectrometry (SIFT-MS) of exhaled breath.

Methods: Male adult rats ( n=50) received an intra-tracheal inoculation of 1) 200 µL saline, 2) 1x10 colony forming units (CFU) of SP or 3) 1x10 CFU of PA. Read More

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http://dx.doi.org/10.1152/ajplung.00449.2018DOI Listing
February 2019

Extracellular vesicles: another compartment for the second messenger, cyclic adenosine monophosphate (cAMP).

Am J Physiol Lung Cell Mol Physiol 2019 Feb 13. Epub 2019 Feb 13.

Pharmacology/Center for Lung Biology, University of South Alabama., United States.

The second messenger, cAMP, is highly compartmentalized to facilitate signaling specificity. Extracellular vesicles (EVs) are submicron, intact vesicles released from many cell types that can act as biomarkers or be involved in cell-to-cell communication. While it is well recognized that EVs encapsulate functional proteins and RNAs/miRNAs, currently it is unclear whether cyclic nucleotides are encapsulated within EVs to provide an additional second messenger compartment. Read More

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http://dx.doi.org/10.1152/ajplung.00282.2018DOI Listing
February 2019
4.080 Impact Factor

Prostaglandin E2 inhibits pro-fibrotic function of human pulmonary fibroblasts by disrupting Ca2+-signaling.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 13. Epub 2019 Feb 13.

Medicine, McMaster University, Canada.

We have shown that calcium (Ca) oscillations in human pulmonary fibroblasts (HPFs) contribute to pro-fibrotic effects of TGFβ and that disruption of these oscillations blunts features of pulmonary fibrosis. Prostaglandin E (PGE) exerts anti-fibrotic effects in the lung but the mechanisms for this action are not well defined. We thus sought to explore interactions between PGE and the pro-fibrotic agent transforming growth factor beta (TGFβ) in pulmonary fibroblasts (PFs) isolated from patients with or without idiopathic pulmonary fibrosis (IPF). Read More

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https://www.physiology.org/doi/10.1152/ajplung.00403.2018
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http://dx.doi.org/10.1152/ajplung.00403.2018DOI Listing
February 2019
1 Read

Galectin-3 is Expressed in Vascular Smooth Muscle Cells and Promotes Pulmonary Hypertension through changes in Proliferation, Apoptosis and Fibrosis.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6. Epub 2019 Feb 6.

Augusta University, United States.

A defining characteristic of Pulmonary Hypertension (PH) is the extensive remodeling of pulmonary arteries (PA) that results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. There is no cure for PH and identification of novel molecular mechanisms that underlie increased proliferation, reduced apoptosis and excessive extracellular matrix production in pulmonary artery smooth muscle cells (PASMC) is a vital objective. Galectin-3 (Gal-3) is a chimeric lectin and potent driver of many aspects of fibrosis, but its role in regulating PASMC behavior in PH remains poorly understood. Read More

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http://dx.doi.org/10.1152/ajplung.00186.2018DOI Listing
February 2019
2 Reads

Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchanges disturbances: results from two randomized clinical trials.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6. Epub 2019 Feb 6.

Cardiology, Hôpital Saint-Pierre, Belgium.

Background: When heated by an electronic cigarette, propylene glycol and glycerol produce a nicotine-carrying-aerosol. This hygroscopic/hyperosmolar aerosol can deposit deep within the lung. Whether these deposits trigger local inflammation and disturb pulmonary gas exchanges is not known. Read More

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http://dx.doi.org/10.1152/ajplung.00492.2018DOI Listing
February 2019
1 Read

Resolvin D1 attenuates mechanical stretch-induced pulmonary fibrosis via epithelial-mesenchymal transition (EMT).

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6. Epub 2019 Feb 6.

Anesthesiology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Mechanical ventilation-induced pulmonary fibrosis plays an important role in the high mortality rate of acute respiratory distress syndrome (ARDS). Resolvin D1 (RvD1) displays potent proresolving activities. Epithelial-mesenchymal transition (EMT) has been proven to be an important pathological feature of lung fibrosis. Read More

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http://dx.doi.org/10.1152/ajplung.00415.2018DOI Listing
February 2019
1 Read

Regulation of Ovarian cancer G protein-coupled receptor (OGR1) expression and signaling.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6. Epub 2019 Feb 6.

Medicine, Director, Center for Translational Medicine, Thomas Jefferson University, United States.

Ovarian cancer G protein-coupled receptor 1 (OGR1) is a recently deorphanized G protein-coupled receptor shown to signal in response to low extracellular pH (↓pHo) or certain benzodiazepines. The pleiotropic nature of OGR1 signaling in human airway smooth muscle (HASM) cells suggests OGR1 is a potential therapeutic target for the management of obstructive lung diseases. However, the basic pharmacological and regulatory features of OGR1 remain poorly understood. Read More

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http://dx.doi.org/10.1152/ajplung.00426.2018DOI Listing
February 2019
1 Read

Mesothelial mobilization in the developing lung and heart differs in timing, quantity and pathway-dependency.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 31. Epub 2019 Jan 31.

Institut für Molekularbiologie, Medizinische Hochschule Hannover, Germany.

The mesothelial lining of the lung, the visceral pleura, and of the heart, the epicardium, derive from a common multi-potent precursor tissue, the mesothelium of the embryonic thoracic cavity that also contributes to organ-specific mesenchymal cell types. Insight into mesothelial mobilization and differentiation has prevailed in the developing heart while the mesenchymal transition and fate of the visceral pleura is poorly understood. Here, we use the fact that the early mesothelium of both the lung and the heart expresses the transcription factor gene Wt1, to comparatively analyze mesothelial mobilization in the two organs by a genetic cre-loxPbased conditional approach. Read More

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http://dx.doi.org/10.1152/ajplung.00212.2018DOI Listing
January 2019

Small hairpin RNA and pharmacological targeting of neutral sphingomyelinase prevents diaphragm weakness in rats with heart failure and reduced ejection fraction.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 31. Epub 2019 Jan 31.

Department of Applied Physiology and Kinesiology, University of Florida, United States.

Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity, mitochondrial reactive oxygen species emission (ROS), and causes diaphragm weakness. We tested whether a systemic pharmacologic NSMase inhibitor or short-hairpin RNA (shRNA) targeting NSMase isoform 3 (NSMase3) would prevent diaphragm abnormalities induced by HFREF caused by myocardial infarction. In the pharmacological intervention, we used intraperitoneal injection of GW4869 or vehicle. Read More

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http://dx.doi.org/10.1152/ajplung.00516.2018DOI Listing
January 2019
4.080 Impact Factor

Genetic inactivation of the phospholipase A2 activity of peroxiredoxin 6 in mice protects against LPS-induced acute lung injury.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 31. Epub 2019 Jan 31.

Physiology, University of Pennsylvania, United States.

Peroxiredoxin 6 (Prdx6) is a multi-functional enzyme that serves important anti-oxidant roles by scavenging hydroperoxides and reducing peroxidized cell membranes. Prdx6 also plays a key role in cell signaling by the activation of NADPH oxidase,type 2 (Nox2) through its phospholipase A2 (aiPLA2) activity. Nox2 generation of O2. Read More

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http://dx.doi.org/10.1152/ajplung.00344.2018DOI Listing
January 2019
1 Read
4.080 Impact Factor

Pharmacological activation of Liver X Receptor during cigarette smoke exposure adversely affects alveolar macrophages and pulmonary surfactant homeostasis.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 31. Epub 2019 Jan 31.

Medicine, Université Laval, Canada.

Background: Smoking alters pulmonary reverse lipid transport and leads to intracellular lipid accumulation in alveolar macrophages. We investigated whether stimulating reverse lipid transport with an agonist of the Liver X receptor (LXR) would help alveolar macrophages limit lipid accumulation and dampen lung inflammation in response to cigarette smoke.

Methods: Mice were exposed to cigarette smoke and treated intraperitonealy with the LXR agonist T0901317. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00482.2018
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http://dx.doi.org/10.1152/ajplung.00482.2018DOI Listing
January 2019
2 Reads

CD36 mediates albumin transcytosis by dermal but not lung microvascular endothelial cells - role in fatty acid delivery.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 31. Epub 2019 Jan 31.

Critical Care Medicine, St. Michael's Hospital, Canada.

In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin across primary human microvascular endothelial cells from both lung and skin. Read More

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http://dx.doi.org/10.1152/ajplung.00127.2018DOI Listing
January 2019
1 Read

LOCAL PULMONARY DRUG DELIVERY IN THE PRETERM RABBIT: FEASIBILITY AND EFFICACY OF DAILY INTRATRACHEAL INJECTIONS.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 24. Epub 2019 Jan 24.

Development and Regeneration, KU Leuven.

Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, in order to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required where intratracheal (IT) administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily IT surfactant, daily IT saline or no injections for 7 days. Read More

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http://dx.doi.org/10.1152/ajplung.00255.2018DOI Listing
January 2019
1 Read

Impact of aging on inflammatory and immune responses during elastin peptide-induced murine emphysema.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 24. Epub 2019 Jan 24.

EA4683, laboratoire d'Immunologie, UFR de Pharmacie, Université de Reims Champagne-Ardenne, France.

Deterioration of lung functions and degradation of elastin fibers with age are accelerated during chronic obstructive pulmonary disease (COPD). Excessive genesis of soluble elastin peptides (EP) is a key factor in the pathophysiology of COPD. We have previously demonstrated that 6-week old mice exhibited emphysematous structural changes associated with pro-inflammatory immune response after EP instillation. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00402.2018
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http://dx.doi.org/10.1152/ajplung.00402.2018DOI Listing
January 2019
3 Reads

The Tcf21 lineage constitutes the lung lipofibroblast population.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 24. Epub 2019 Jan 24.

Department of Medicine, University of Hawaii, United States.

Transcription factor 21 (Tcf21) is a bHLH transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. Read More

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http://dx.doi.org/10.1152/ajplung.00254.2018DOI Listing
January 2019

Inhibition of GGPPS1 attenuated LPS-induced acute lung injury and was associated with NLRP3 inflammasome suppression.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, China.

Inhibition of the mevalonate pathway using statins has been shown to be beneficial in the treatment of acute lung injury (ALI). Here, we investigated whether partial inhibition of this pathway by targeting Geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, was effective at treating lung inflammation in ALI. Lipopolysaccharide (LPS) was intra-tracheally instilled to induce ALI in lung specific GGPPS1 knockout and wild-type mice. Read More

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http://dx.doi.org/10.1152/ajplung.00190.2018DOI Listing
January 2019
1 Read

Acute and chronic changes in the control of breathing in a rat model of bronchopulmonary dysplasia.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Physiology, Medical College of Wisconsin, United States.

Infants born very prematurely (<28 weeks gestation) have immature lungs and often require supplemental oxygen. However, long-term hyperoxia exposure can arrest lung development leading to bronchopulmonary dysplasia (BPD), which increases acute and long-term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00086.2018
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http://dx.doi.org/10.1152/ajplung.00086.2018DOI Listing
January 2019
12 Reads

Decreased miR-29b expression is associated with airway inflammation in chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Chronic obstructive pulmonary disease (COPD) is a common chronic airway inflammatory disease. MicroRNAs are shown to be involved in the regulation of inflammation. We investigated the role of microRNA-29b (miR-29b) in the airway inflammation in COPD. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00436.2018
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http://dx.doi.org/10.1152/ajplung.00436.2018DOI Listing
January 2019
7 Reads

A Metagenomic Comparison of Tracheal Aspirate and Mini-Bronchial Alveolar Lavage for Assessment of Respiratory Microbiota.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Medicine, Infectious Diseases, Unviersity of California, San Francisco, United States.

Accurate and informative microbiologic testing is essential for guiding diagnosis and management of pneumonia in critically ill patients. Sampling of tracheal aspirate (TA) is less invasive compared to mini-bronchoalveolar lavage (mBAL) and is now recommended as a frontline diagnostic approach in mechanically ventilated patients, despite the historical belief that TA was suboptimal due to contamination from oral microbes. Advancements in metagenomic next generation sequencing (mNGS) now permit assessment of airway microbiota without a need for culture, and as such provide an opportunity to examine differences between mBAL and TA at a resolution previously unachievable. Read More

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http://dx.doi.org/10.1152/ajplung.00476.2018DOI Listing
January 2019
3 Reads

Three classical papers in respiratory physiology by Christian Bohr (1855-1911) whose work is frequently cited but seldom read.

Authors:
John B West

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Department of Medicine, University of California San Diego, United States.

History has been kind to Christian Bohr (1855-1911). His name is attached eponymously to three different areas of respiratory physiology. The first is the Bohr dead space which refers to the portion of the tidal volume that does not undergo gas exchange. Read More

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http://dx.doi.org/10.1152/ajplung.00527.2018DOI Listing
January 2019
1 Read

Simultaneous amplification and testing method for Mycobacterium Tuberculosis rRNA (SAT-TB) to differentiate sputum negative tuberculosis from sarcoidosis.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, China.

Objective: We use the simultaneous application and testing method to detect Mycobacterium Tuberculosis (MTB) rRNA (SAT-TB) with the EBUS-TBNA biopsy specimens to differentiate sputum negative tuberculosis from sarcoidosis.

Methods: In the first part, we validated the SAT-TB on the bronchial or EBUS-TBNA biopsy specimens from sputum smear-positive pulmonary tuberculosis. In the second part, all the EBUS-TBNA specimens for sputum smear-negative intrathoracic tuberculous lymphadenopathies or sarcoidosis were tested with the SAT-TB, acid-fast bacilli smear and culture . Read More

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http://dx.doi.org/10.1152/ajplung.00172.2018DOI Listing
January 2019
2 Reads
4.080 Impact Factor

Mesenchymal Stromal Cell-Derived Exosomes Improve Mitochondrial Health in Pulmonary Arterial Hypertension.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 17. Epub 2019 Jan 17.

Regenerative Medicine Lab, United Therapeutics, United States.

Secreted exosomes are bioactive particles that elicit profound responses in target cells. Using targeted metabolomics and global microarray analysis, we identified a role of exosomes in promoting mitochondrial function in the context of pulmonary arterial hypertension (PAH). While chronic hypoxia results in a glycolytic shift in pulmonary artery smooth muscle cells (PASMC), exosomes restore energy balance and improve O2 consumption. Read More

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http://dx.doi.org/10.1152/ajplung.00058.2018DOI Listing
January 2019
2 Reads

Lethal Avian Influenza A (H5N1) Virus Replicates in Pontomedullary Chemosensitive Neurons and Depresses Hypercapnic Ventilatory Response in Mice.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Pathophysiology, Lovelace Respiratory Research Institute, United States.

The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20%↓) at 2 days post-infection (dpi) and death at 7 dpi in mice, but the relevant mechanisms are not fully understood. Glomus cells in the carotid body and catecholaminergic neurons in locus coeruleus (LC), neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN), and serotonergic neurons in the raphe are chemosensitive and responsible for HCVR. We asked if the dHCVR became worse over the infection period with viral replication in these cells/neurons. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00324.2018
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http://dx.doi.org/10.1152/ajplung.00324.2018DOI Listing
January 2019
7 Reads

Subcutaneous administration of neutralizing antibodies to endothelial monocyte-activating protein II attenuates cigarette smoke-induced lung injury in mice.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Medicine, National Jewish Health, United States.

Pro-apoptotic and monocyte chemotactic endothelial monocyte activating protein 2 (EMAPII) is released extracellular during cigarette smoke (CS) exposure. We have previously demonstrated that, when administered intratracheally during chronic CS exposures, neutralizing rat antibodies to EMAPII inhibited endothelial cell apoptosis and lung inflammation and reduced airspace enlargement in mice (DBA/2J strain). Here we report further preclinical evaluation of EMAPII targeting using rat anti-EMAPII antibodies via either nebulization or subcutaneous (SQ) injection. Read More

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http://dx.doi.org/10.1152/ajplung.00409.2018DOI Listing
January 2019
5 Reads
4.080 Impact Factor

Deficiency of cationic amino acid transporter-2 protects mice from hyperoxia-induced lung injury.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, United States.

The pathology of acute lung injury (ALI) involves inducible nitric oxide synthase (iNOS) derived NO induced apoptosis of pulmonary endothelial cells. In vitro, iNOS-derived NO production has been shown to depend on the uptake of L-arginine by the cationic amino acid transporters (CAT). To test the hypothesis that mice deficient in CAT-2 ( slc7a2 on a C57BL/6 background) would be protected from hyperoxia-induced ALI, mice ( slc7a2 or wild-type) were placed in >95% oxygen (hyperoxia) or 21% oxygen (control) for 60 hours. Read More

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http://dx.doi.org/10.1152/ajplung.00223.2018DOI Listing
January 2019
1 Read
4.080 Impact Factor

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Department of Respiratory, the First Hospital of Qinhuangdao, China.

The involvement of several microRNAs (miRs) in the initiation and development of tumor through the suppression of the target gene expression has been highlighted. The aberrant expression of microRNA-181d-5p (miR-181d-5p) and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis, In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their role in NSCLC and the underlying mechanism. There was a high expression of CDKN3 while miR-181d-5p was down-regulated in NSCLC. Read More

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http://dx.doi.org/10.1152/ajplung.00334.2018DOI Listing
January 2019
5 Reads

Small Airway Hyperresponsiveness in COPD: Relationship Between Structure and Function in Lung Slices.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Dep of Molecular Pharmacology, University of Groningen, Netherlands.

The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear. We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients. Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline twice weekly for twelve weeks. Read More

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http://dx.doi.org/10.1152/ajplung.00325.2018DOI Listing
January 2019
3 Reads

Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages.

Am J Physiol Lung Cell Mol Physiol 2019 Mar 10;316(3):L418-L427. Epub 2019 Jan 10.

Department of Physiology, University of Kentucky , Lexington, Kentucky.

We previously showed that mice deficient in apoptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1β) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00199.2018
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http://dx.doi.org/10.1152/ajplung.00199.2018DOI Listing
March 2019
8 Reads

MiRNA let-7b promotes the development of hypoxic pulmonary hypertension by targeting ACE2.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 10. Epub 2019 Jan 10.

Department of Ultrasound, the Second Affiliated Hospital, Medical School of Zhejiang University, China.

Angiotensin-converting enzyme 2 (ACE2) protects against hypoxic pulmonary hypertension (HPH) by inhibiting the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Under hypoxia, the hypoxia-inducible factor 1α (HIF-1α) inhibits ACE2 indirectly, however the underlying mechanism is unclear. In the present study, we found that exposure to chronic hypoxia stimulated microRNA (miRNA) let-7b expression in rat lung via a HIF-1α dependent pathway. Read More

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http://dx.doi.org/10.1152/ajplung.00387.2018DOI Listing
January 2019
3 Reads

Cinnamaldehyde in Flavored E-Cigarette Liquids Temporarily Suppresses Bronchial Epithelial Cell Ciliary Motility by Dysregulation of Mitochondrial Function.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 3. Epub 2019 Jan 3.

Center for Environmental Medicine and Lung Biology, The The University of North Carolina at Chapel Hill, United States.

Aldehydes in cigarette smoke (CS) impair mitochondrial function and reduce ciliary beat frequency (CBF), leading to diminished mucociliary clearance (MCC). However, the effects of aldehyde e-cigarette flavorings on CBF is unknown. The purpose of this study was to investigate whether cinnamaldehyde, a flavoring agent commonly used in e-cigarettes, disrupts mitochondrial function and impairs CBF on well-differentiated human bronchial epithelial (hBE) cells. Read More

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http://dx.doi.org/10.1152/ajplung.00304.2018DOI Listing
January 2019
1 Read

Requirement for neuropeptide Y in the development of type 2 responses and allergen-induced airway hyperresponsiveness and inflammation.

Am J Physiol Lung Cell Mol Physiol 2019 Mar 3;316(3):L407-L417. Epub 2019 Jan 3.

Department of Hematology, Oncology, Allergy, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama , Japan.

Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y receptor. NPY modulates these cells via its Y receptor; however, involvement of NPY in the pathophysiology of bronchial asthma, particularly airway hyperresponsiveness (AHR), has not been defined. Read More

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http://dx.doi.org/10.1152/ajplung.00386.2018DOI Listing
March 2019
2 Reads

Pro-fibrotic effects of IL-17A and elevated IL-17RA in IPF and RA-ILD support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 3. Epub 2019 Jan 3.

Pulmonary/Critical Care Medicine, Mayo Medical Center, United States.

Interleukin-17 (IL-17) is a T helper 17 (Th17) cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, it's role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with idiopathic pulmonary fibrosis (IPF) and RA-ILD to determine IL-17RA receptor expression. Read More

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http://dx.doi.org/10.1152/ajplung.00301.2018DOI Listing
January 2019
5 Reads

Identification of CAV1 and DCN as potential predictive biomarkers for lung adenocarcinoma.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 3. Epub 2019 Jan 3.

Department of Pathology, Xiangya Hospital, Central South University, China.

Background Lung adenocarcinoma (LUAD) is the most common histological form of lung cancer that is clinically diagnosed. The aim of this study is to explore the novel genes associated with the LUAD tumorigenesis. Methods Comprehensive bioinformatics analyses of the data were obtained from several publicly available databases, such as the Gene Expression Omnibus, the Human Protein Atlas project and the Cancer Cell Line Encyclopedia. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00364.2018
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http://dx.doi.org/10.1152/ajplung.00364.2018DOI Listing
January 2019
4 Reads

Effect of cooling on lung secretory phospholipase A2 activity in vitro, ex vivo and in vivo.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 3. Epub 2019 Jan 3.

Pediatrics and Neonatal Critical Care, South Paris University Hospitals, France.

Background: Hypothermia can modify surfactant composition and function. Secretory phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respiratory disorders. We hypothesize that sPLA2 activity might be influenced by the temperature partially explaining surfactant changes. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00201.2018
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http://dx.doi.org/10.1152/ajplung.00201.2018DOI Listing
January 2019
16 Reads
4.080 Impact Factor

Inositol monophosphatase 1 as a novel interacting partner of RAGE in pulmonary hypertension.

Am J Physiol Lung Cell Mol Physiol 2019 Mar 3;316(3):L428-L444. Epub 2019 Jan 3.

Division of Endocrinology, Department of Medicine, University of Arizona , Tucson, Arizona.

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by progressive pulmonary vascular remodeling. The receptor for advanced glycation end products (RAGE) plays an important role in PAH by promoting proliferation of pulmonary vascular cells. RAGE is also known to mediate activation of Akt signaling, although the particular molecular mechanism remains unknown. Read More

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http://dx.doi.org/10.1152/ajplung.00393.2018DOI Listing
March 2019
1 Read

Th1 cytokines TNF-α and IFN-γ promote corticosteroid resistance in developing human airway smooth muscle.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 18;316(1):L71-L81. Epub 2018 Oct 18.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic , Rochester, Minnesota.

Corticosteroids (CSs) are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show CS resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNF-α and IFN-γ, promote CS resistance in adult human airway smooth muscle (ASM). Read More

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http://dx.doi.org/10.1152/ajplung.00547.2017DOI Listing
January 2019
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Functional interaction between PDGFβ and GluN2B-containing NMDA receptors in smooth muscle cell proliferation and migration in pulmonary arterial hypertension.

Am J Physiol Lung Cell Mol Physiol 2019 Mar 13;316(3):L445-L455. Epub 2018 Dec 13.

Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.

In this study, we explored the complex interactions between platelet-derived growth factor (PDGF) and N-methyl-d-aspartate receptor (NMDAR) and their effect on the excessive proliferation and migration of smooth muscle cells leading to obstructed arteries in pulmonary arterial hypertension (PAH). We report lower expression of glutamate receptor NMDA-type subunit 2B (GluN2B), a subunit composing NMDARs expected to affect cell survival/proliferation of pulmonary artery smooth muscle cells (PASMCs), in PAH patient lungs. PASMC exposure to PDGF-BB stimulated immediate increased levels of phosphorylated Src family kinases (SFKs) together with increased phosphorylated GluN2B (its active form) and cell surface relocalization, suggesting a cross talk between PDGFR-recruited SFKs and NMDAR. Read More

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http://dx.doi.org/10.1152/ajplung.00537.2017DOI Listing
March 2019
21 Reads

Regulators of A20 (TNFAIP3) - new drug-able targets in inflammation.

Am J Physiol Lung Cell Mol Physiol 2018 Dec 13. Epub 2018 Dec 13.

Centre for Experimental Medicine, Queen's University of Belfast, United Kingdom.

Persistent activation of the transcription factor Nuclear Factor-kappaB (NF-κB) is central to the pathogenesis of many inflammatory disorders, including those of the lung such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). Despite recent advances in treatment, management of the inflammatory component of these diseases still remains suboptimal. A20 is an endogenous negative regulator of NF-κB signaling, which has been widely described in several autoimmune and inflammatory disorders and more recently in terms of chronic lung disorders. Read More

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http://dx.doi.org/10.1152/ajplung.00335.2018DOI Listing
December 2018
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A functional macrophage migration inhibitory factor promoter polymorphism is associated with reduced diffusing capacity.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6;316(2):L400-L405. Epub 2018 Dec 6.

Department of Medicine, Yale School of Medicine , New Haven, Connecticut.

Cigarette smoke exposure is the leading modifiable risk factor for chronic obstructive pulmonary disease (COPD); however, the clinical and pathologic consequences of chronic cigarette smoke exposure are variable among smokers. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of COPD. Within the promoter of the MIF gene is a functional polymorphism that regulates MIF expression (-794 CATT microsatellite repeat) ( rs5844572 ). Read More

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http://dx.doi.org/10.1152/ajplung.00439.2018DOI Listing
February 2019
2 Reads

Impaired hypoxic pulmonary vasoconstriction in a mouse model of Leigh syndrome.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6;316(2):L391-L399. Epub 2018 Dec 6.

Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.

Hypoxic pulmonary vasoconstriction (HPV) is a physiological vasomotor response that maintains systemic oxygenation by matching perfusion to ventilation during alveolar hypoxia. Although mitochondria appear to play an essential role in HPV, the impact of mitochondrial dysfunction on HPV remains incompletely defined. Mice lacking the mitochondrial complex I (CI) subunit Ndufs4 ( Ndufs4) develop a fatal progressive encephalopathy and serve as a model for Leigh syndrome, the most common mitochondrial disease in children. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00419.2018
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http://dx.doi.org/10.1152/ajplung.00419.2018DOI Listing
February 2019
6 Reads

Oxidative stress and macrophages: driving forces behind exacerbations of asthma and chronic obstructive pulmonary disease?

Am J Physiol Lung Cell Mol Physiol 2019 Feb 6;316(2):L369-L384. Epub 2018 Dec 6.

Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen , Groningen , The Netherlands.

Oxidative stress is a common feature of obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Lung macrophages are key innate immune cells that can generate oxidants and are known to display aberrant polarization patterns and defective phagocytic responses in these diseases. Whether these characteristics are linked in one way or another and whether they contribute to the onset and severity of exacerbations in asthma and COPD remain poorly understood. Read More

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http://dx.doi.org/10.1152/ajplung.00456.2018DOI Listing
February 2019
4 Reads

Disruption of the airway epithelial barrier in a murine model of respiratory syncytial virus infection.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 29;316(2):L358-L368. Epub 2018 Nov 29.

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation , Cleveland, Ohio.

Respiratory syncytial virus (RSV) is a major cause of hospitalization for infants and young children worldwide. RSV is known to infect epithelial cells and increase the permeability of model airway epithelial monolayers in vitro. We hypothesized that RSV infection also induces airway barrier dysfunction in vivo. Read More

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http://dx.doi.org/10.1152/ajplung.00345.2018DOI Listing
February 2019
4 Reads

Molecular characterization of a precision-cut rat lung slice model for the evaluation of antifibrotic drugs.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 29;316(2):L348-L357. Epub 2018 Nov 29.

Department of Cardiovascular and Fibrotic Diseases Drug Discovery, Bristol-Myers Squibb, Pennington, New Jersey.

The translation of novel pulmonary fibrosis therapies from preclinical models into the clinic represents a major challenge demonstrated by the high attrition rate of compounds that showed efficacy in preclinical models but demonstrated no significant beneficial effects in clinical trials. A precision-cut lung tissue slice (PCLS) contains all major cell types of the lung and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study pulmonary fibrosis. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00339.2018
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http://dx.doi.org/10.1152/ajplung.00339.2018DOI Listing
February 2019
7 Reads
4.080 Impact Factor

A novel GABA receptor ligand MIDD0301 with limited blood-brain barrier penetration relaxes airway smooth muscle ex vivo and in vivo.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 29;316(2):L385-L390. Epub 2018 Nov 29.

Department of Anesthesiology, Vagelos College of Physicians and Surgeons, Columbia University , New York, New York.

Airway smooth muscle (ASM) cells express GABA A receptors (GABARs), and previous reports have demonstrated that GABAR activators relax ASM. However, given the activity of GABARs in central nervous system inhibitory neurotransmission, concern exists that these activators may lead to undesirable sedation. MIDD0301 is a novel imidazobenzodiazepine and positive allosteric modulator of the GABAR with limited brain distribution, thus eliminating the potential for sedation. Read More

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http://dx.doi.org/10.1152/ajplung.00356.2018DOI Listing
February 2019
3 Reads
4.080 Impact Factor

Tissue-informed engineering strategies for modeling human pulmonary diseases.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 21;316(2):L303-L320. Epub 2018 Nov 21.

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.

Chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), and chronic obstructive pulmonary disease (COPD), account for staggering morbidity and mortality worldwide but have limited clinical management options available. Although great progress has been made to elucidate the cellular and molecular pathways underlying these diseases, there remains a significant disparity between basic research endeavors and clinical outcomes. This discrepancy is due in part to the failure of many current disease models to recapitulate the dynamic changes that occur during pathogenesis in vivo. Read More

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http://dx.doi.org/10.1152/ajplung.00353.2018DOI Listing
February 2019
10 Reads

BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation.

Am J Physiol Lung Cell Mol Physiol 2019 Feb 21;316(2):L321-L333. Epub 2018 Nov 21.

Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine , New Haven, Connecticut.

Bpifa1 (BPI fold-containing group A member 1) is an airway host-protective protein with immunomodulatory properties that binds to LPS and is regulated by infectious and inflammatory signals. Differential expression of Bpifa1 has been widely reported in lung disease, yet the biological significance of this observation is unclear. We sought to understand the role of Bpifa1 fluctuations in modulating lung inflammation. Read More

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http://dx.doi.org/10.1152/ajplung.00056.2018DOI Listing
February 2019
8 Reads

Corrigendum.

Authors:

Am J Physiol Lung Cell Mol Physiol 2018 Nov;315(5):L919

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http://dx.doi.org/10.1152/ajplung.zh5-7547-corr.2018DOI Listing
November 2018
1 Read

Corrigendum.

Authors:

Am J Physiol Lung Cell Mol Physiol 2018 Nov;315(5):L920

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http://dx.doi.org/10.1152/ajplung.zh5-7548-corr.2018DOI Listing
November 2018
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High-mobility group box-1 protein from CC10 club cells promotes type 2 response in the later stage of respiratory syncytial virus infection.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 8;316(1):L280-L290. Epub 2018 Nov 8.

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University , Chongqing , China.

The type 2 immune response, induced by infection of respiratory syncytial virus (RSV), has been linked to asthma development, but it remains unclear how the response is initiated. Here, we reported that the high-mobility group box-1 (HMGB1) protein promotes the type 2 response in the later stage of RSV infection. In mice, we found that type 2 cytokines were elevated in the later stages, which were strongly diminished after administration of anti-HMGB1 antibodies. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00552.2017
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http://dx.doi.org/10.1152/ajplung.00552.2017DOI Listing
January 2019
11 Reads

Short-chain fatty acids increase TNFα-induced inflammation in primary human lung mesenchymal cells through the activation of p38 MAPK.

Am J Physiol Lung Cell Mol Physiol 2019 Jan 8;316(1):L157-L174. Epub 2018 Nov 8.

Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research, The University of Sydney , Sydney, New South Wales , Australia.

Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF)α-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. Read More

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https://www.physiology.org/doi/10.1152/ajplung.00306.2018
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http://dx.doi.org/10.1152/ajplung.00306.2018DOI Listing
January 2019
8 Reads