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Reticulocalbin 3 deficiency in alveolar epithelium attenuated LPS-induced ALI via NFκB signaling Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-24 Xiaoqian Shi; Xiaojie An; Liu Yang; Zhipeng Wu; Danni Zan; Zhaohong Li; Baosen Pang; Yan Chen; Jiujie Li; PingPing Tan; Runlin Z. Ma; Qiuhong Fang; Yingmin Ma; Jiawei Jin
Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury-repair process
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Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-24 Eric Leslie; Vanessa Lopez; Nana A.O. Anti; Rafael Alvarez; Isaac Kafeero; Donald G. Welsh; Monica Romero; Shawn Kaushal; Catherine M. Johnson; Remy Bosviel; Ivana Blazenovic; Rui Song; Alex Brito; Michael R. La Frano; Lubo Zhang; John W. Newman; Oliver Fiehn; Sean M. Wilson
Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity
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Disease Specific Platelet Signaling Defects in Idiopathic Pulmonary Arterial Hypertension Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-17 Kulwant Singh Aulak; Sami AI Abdi; Ling Li; Jack S Crabb; Arnab Ghosh; Belinda Belle Willard; Dennis J. Stuehr; John W. Crabb; Raed A. Dweik; Adriano R. Tonelli
Background Idiopathic pulmonary arterial hypertension (IPAH) is a rapidly progressive disease with several treatment options. Long-term mortality remains high with great heterogeneity in treatment response. Even though most of the pathology of IPAH is observed in the lung, there is systemic involvement. Platelets from IPAH patients have characteristic metabolic shifts and defects in activation, therefore
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Alexander von Humboldt (1769-1859): early high altitude explorer and renowned plant naturalist Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-17 John B. West
Alexander von Humboldt (1769-1859) was one of the most distinguished German scientists of the late 18th and early 19th centuries. His fame came chiefly from his extensive explorations in South America, and his eminence as a plant naturalist. He attempted to climb the inactive volcano, Chimborazo, in Ecuador, which was thought to be the highest mountain in the world at the time, and he reached an altitude
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Altered lung metabolism and mitochondrial DAMPs in lung injury due to acute kidney injury Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-10 Mark Hepokoski; Jing Wang; Kefeng Li; Ying Li; Purva Gupta; Tina Mai; Alex Moshensky; Mona Alotaibi; Laura E. Crotty Alexander; Atul Malhotra; Prabhleen Singh
Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but
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Adhatoda Vasica rescues the hypoxia dependent severe asthma symptoms and mitochondrial dysfunction Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-10 Atish Gheware; Lipsa Panda; Kritika Khanna; Naveen Kumar Bhatraju; Vaibhav Jain; Shakti Sagar; Manish Kumar; Vijay Pal Singh; Sadasivam Kannan; Venkatesan Subramanian; Mitali Mukerji; Anurag Agrawal; Bhavana Prasher
Severe asthma is a chronic airway disease that exhibits poor response to conventional asthma therapies. Growing evidence suggests that elevated hypoxia increases the severity of asthmatic inflammation among patients and in model systems. In this study, we elucidate the therapeutic effects and mechanistic basis of Adhatoda Vasica (AV) aqueous extract on mouse models of acute allergic as well as severe
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YAP Expression in Endothelial Cells Prevents Ventilator-induced Lung Injury Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-10 Kai Su; Jianguo Wang; Yang Lv; Ming Tian; You-Yang Zhao; Richard D Minshall; Guochang Hu
Ventilator-induced lung injury is associated with an increase in mortality in patients with respiratory dysfunction, although mechanical ventilation is an essential intervention implemented in the intensive care unit. Intrinsic molecular mechanisms for minimizing lung inflammatory injury during mechanical ventilation remain poorly defined. We hypothesize that Yes-associated protein (YAP) expression
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Matrix Stiffening Induces a Pathogenic QKI-miR-7-SRSF1 Signaling Axis in Pulmonary Arterial Endothelial Cells Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-10 Chen-Shan Chen Woodcock; Neha Hafeez; Adam Handen; Ying Tang; Lloyd D Harvey; Leonard E Estephan; Gil Speyer; Seungchan Kim; Thomas Bertero; Stephen Y Chan
Pulmonary arterial hypertension (PAH) refers to a set of heterogeneous vascular diseases defined by elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), leading to right ventricular (RV) remodeling and often death. Early increases in pulmonary artery stiffness in PAH drive pathogenic alterations of pulmonary arterial endothelial cells (PAECs), leading to vascular
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Carrageenan containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-09 Desiree Schütz; Carina Conzelmann; Giorgio Fois; Rüdiger Groß; Tatjana Weil; Lukas Wettstein; Steffen Stenger; Alexander Zelikin; Thomas K Hoffmann; Manfred Frick; Janis A Müller; Jan Münch
Pharmaceutical interventions are urgently needed to prevent SARS-CoV-2 infection and transmission. As SARS-CoV-2 infects and spreads via the nasopharyngeal airways, we analyzed the antiviral effect of selected nasal and oral sprays on virus infection in vitro. Two nose sprays showed virucidal activity but were cytotoxic precluding further analysis in cell culture. One nasal and one mouth spray suppressed
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Exercise-Induced Alterations in Phospholipid Hydrolysis, Airway Surfactant and Eicosanoids and their Role in Airway Hyperresponsiveness in Asthma Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-03 Ryan Conrad Murphy; Ying Lai; James D Nolin; Robier A Aguillon Prada; Arindam Chakrabarti; Michael V Novotny; Michael C Seeds; William Altemeier; Michael H. Gelb; Robert Duncan Hite; Teal S. Hallstrand
The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (n=18) and bronchoalveolar lavage
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Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-02-03 Joseph J. Mackel; Jaleesa M. Garth; MaryJane Jones; Diandra A. Ellis; Jonathan P. Blackburn; Zhihong Yu; Sadis Matalon; Miranda Curtiss; Frances E Lund; Annette T Hastie; Deborah A Meyers; Chad Steele
Exposure to fungi can result in a wide range of comorbidities depending on the immune status of the host. Chronic exposure and reactivity to fungi such as Aspergillus fumigatus can result in conditions such as severe asthma with fungal sensitization (SAFS) or allergic bronchopulmonary aspergillosis (ABPA). However, the pathophysiology of SAFS and ABPA are not well understood. Here, we report that the
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A Shift from Glycolytic and Fatty Acid Derivatives toward One-Carbon Metabolites in the Developing Lung During Transitions of the Early Postnatal Period Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-27 Daniel D. Lee; Sang Jun Park; Kirsten Zborek; Margaret A. Schwarz
During postnatal lung development, metabolic changes that coincide with stages of alveolar formation are poorly understood. Responding to developmental and environmental factors, metabolic changes can be rapidly and adaptively altered. The objective of the present study was to determine biological and technical determinants of metabolic changes during postnatal lung development. Over 118 metabolic
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Glucose-6 Phosphate dehydrogenase deficiency contributes to metabolic abnormality and pulmonary hypertension Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-27 Mathews Valuparampil Varghese; Joel James; Olga Rafikova; Ruslan Rafikov
We have previously reported that several patients with idiopathic pulmonary hypertension (PH) had different types of G6PD deficiency. However, the role of G6PD in PH is multifactorial because G6PD is involved in controlling oxidative stress, metabolic switch, and red blood cell fragility. To delineate the contribution of G6PD in PH pathogenesis, we utilized a mouse line with decreased expression of
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Intratracheal administration of mesenchymal stem cell-derived extracellular vesicles reduces lung injuries in a chronic rat model of bronchopulmonary dysplasia Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-27 Andrea Porzionato; Patrizia Zaramella; Arben Dedja; Diego Guidolin; Luca Bonadies; Veronica Macchi; Michela Pozzobon; Marcin Jurga; Giorgio Perilongo; Raffaele De Caro; Eugenio Baraldi; Maurizio Muraca
Early therapeutic effect of intratracheally (IT)-administered extracellular vesicles secreted by mesenchymal stem cells (MSC-EVs) has been demonstrated in a rat model of bronchopulmonary dysplasia (BPD) involving hyperoxia exposure in the first 2 postnatal weeks. The aim of this study was to evaluate the protective effects of IT-administered MSC-EVs in the long term. EVs were produced from MSCs following
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Recent updates on biomarkers of exposure and systemic toxicity in e-cigarette users and EVALI Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-27 Samantha R McDonough; Irfan Rahman; Isaac Kirubakaran Sundar
Electronic nicotine delivery systems (ENDS), or e-cigarettes, are emerging tobacco products that produce aerosols by heating e-liquids, which most often consist of propylene glycol and vegetable glycerin along with various flavoring compounds, bypassing the combustion that occurs in the use of traditional tobacco cigarettes. These products have seen a drastic increase in popularity in recent years
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Insulin acutely increases agonist-induced airway smooth muscle contraction in human and rat Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-27 Becky J. Proskocil; Gina N. Calco; Zhenying Nie
Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced bronchoconstriction in obese rats. Since bronchoconstriction results from airway smooth muscle contraction, we tested whether insulin changed agonist-induced airway smooth muscle contraction. Obesity prone and resistant rats were fed a low-fat diet
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CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-20 Katja Koeppen; Amanda B Nymon; Roxanna Barnaby; Zhongyou Li; Thomas H Hampton; Alix Ashare; Bruce A Stanton
Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response
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Sodium coupled neutral amino acid transporter SNAT2 counteracts cardiogenic pulmonary edema by driving alveolar fluid clearance Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-13 Sarah Weidenfeld; Cécile Chupin; Delia Isabel Langner; Tamador Zetoun; Simon Rozowsky; Wolfgang M. Kuebler
The constant transport of ions across the alveolar epithelial barrier regulates alveolar fluid homeostasis. Dysregulation or inhibition of Na+ transport causes fluid accumulation in the distal airspaces resulting in impaired gas exchange and respiratory failure. Previous studies have primarily focused on the critical role of amiloride-sensitive epithelial sodium channel (ENaC) in alveolar fluid clearance
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SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-12 Reem Abdel Hameid; Estelle Cormet-Boyaka; Wolfgang M. Kuebler; Mohammed Uddin; Bakhrom K Berdiev
The tropism of SARS-CoV-2, a virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, towards the host cells is determined, at least in part, by the expression and distribution of its cell surface receptor, angiotensin-converting enzyme 2 (ACE2). The virus further exploits the host cellular machinery to gain access into the cells; its spike protein is cleaved by a host cell surface
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UCHL1, a Deubiquitinating Enzyme, Regulates Lung Endothelial Cell Permeability In Vitro and In Vivo Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-13 Sumegha Mitra; Yulia Epshtein; Saad Sammani; Hector Quijada; Weiguo Chen; Mounica Bandela; Ankit A Desai; Joe G.N. Garcia; Jeffrey R Jacobson
Increasing evidence suggests an important role for deubiquitinating enzymes (DUBs) in modulating a variety of biological functions and diseases. We previously identified the upregulation of the DUB, ubiquitin carboxyl terminal hydrolase 1 (UCHL1) in murine ventilator-induced lung injury (VILI). However, the role of UCHL1 in modulating vascular permeability, a cardinal feature of acute lung injury (ALI)
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Variability in tracheal mucociliary transport is not controlled by beating cilia in lambs in vivo during ventilation with humidified and non-humidified air Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-13 Susyn Joan Kelly; Vojta Brodecky; Elizabeth M. Skuza; Philip Berger; Stanislav Tatkov
Mucociliary transport in the respiratory epithelium depends on beating of cilia to move a mucus layer containing trapped inhaled particles towards the mouth. Little is known about the relationship between cilia beat frequency (CBF) and mucus transport velocity (MTV) in vivo under normal physiological conditions and when inspired air is dry or not fully humidified. This study was designed to use video-microscopy
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The RNA-binding protein Quaking regulates multiciliated and basal cell abundance in the developing lung Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-13 Dustin Ameis; Franklin Liu; Eimear Kirby; Daywin Patel; Richard Keijzer
RNA-binding proteins (RBPs) form complexes with RNA, changing how the RNA is processed and thereby regulating gene expression. RBPs are important sources of gene regulation during organogenesis, including the development of the lungs. The RBP called Quaking (QK) is critical for embryogenesis, yet has not been studied in the developing lung. Here, we show that QK is widely expressed during rat lung
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Low concentration of polyethylene glycol facilitates separation of extracellular vesicles from bronchoalveolar lavage fluid Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-13 Heedoo Lee; Xue He; Kareemah Ni; Jonathan M Carnino; Yang Jin
Extracellular vesicles (EVs) in bodily fluids play an essential role in cell-cell crosstalk and potentially serve as novel biomarkers in "liquid biopsy". It is crucial to have a consistent, efficient, and reliable method to separate EVs from bodily fluids. Currently, there is no universally accepted, "best" method to separate EVs. Besides differential ultracentrifugation (UC), polyethylene glycol (PEG)
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Kinins and Chymase: The Forgotten Components of the Renin angiotensin system and their implications in COVID-19 Disease Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-06 Zaid Abassi; Karl Skorecki; Dalit Ben Hamo-Giladi; Etty Kruzel-Davila; Samuel N Heyman
The unique clinical features of COVID-19 disease present a formidable challenge in the understanding of its pathogenesis. Within a very short time, our knowledge regarding basic physiologic pathways that participate in SARS CoV-2 invasion and subsequent organ damage have been dramatically expanded. In particular, we now better understand the complexity of the renin-angiotensin-aldosterone system (RAAS)
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Cellular Clocks in Hyperoxia Effects on [Ca2+]i Regulation in Developing Human Airway Smooth Muscle Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-06 Colleen M Bartman; Aleksey Matveyenko; Christina M Pabelick; Y. S. Prakash
Supplemental O2 (hyperoxia) is necessary for preterm infant survival but is associated with development of bronchial airway hyperreactivity and childhood asthma. Understanding early mechanisms that link hyperoxia to altered airway structure and function are key to developing advanced therapies. We previously showed that even moderate hyperoxia (50% O2) enhances intracellular calcium ([Ca2+]i) and proliferation
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Remote ischemic conditioning for acute respiratory distress syndrome in COVID-19 Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-06 Anthony V. Incognito; Philip J. Millar; W. Glen Pyle
Acute respiratory distress syndrome and subsequent respiratory failure remains the leading cause of death (>80%) in patients severely impacted by COVID-19. The lack of clinically effective therapies for COVID-19 calls for the consideration of novel adjunct therapeutic approaches. Though novel antiviral treatments and vaccination hold promise in control and prevention of early disease, it is noteworthy
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A rapid dynamic in vivo near-infrared fluorescence imaging assay to track lung vascular permeability after acute radiation injury Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2021-01-06 Jaidip Manikrao Jagtap; Said H. Audi; Mir Hadi Razeghi-Kondelaji; Brian L Fish; Christopher P Hansen; Jayashree Narayanan; Feng Gao; Gayatri Sharma; Abdul K Parchur; Anjishnu Banerjee; Carmen Bergom; Meetha M. Medhora; Amit Joshi
Purpose: Develop an in vivo near-infrared (NIR) fluorescence imaging assay to quantify sequential changes in lung vascular permeability-surface area product (PS) in rodents. Methods: Dynamic NIR imaging methods for determining lung vascular permeability-surface area product were developed and tested on non-irradiated and 13 Gy irradiated rats with/without treatment with lisinopril. A physiologically-based
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Healing after Covid-19: Are Survivors at Risk for Development of Pulmonary Fibrosis? Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-23 Lindsay T McDonald
The novel SARS-CoV-2 coronavirus, responsible for Covid-19 disease, was first reported in Wuhan, China in December of 2019. The virus rapidly spread, and the World Health Organization declared a pandemic by March 2020. With millions of confirmed cases world-wide, there is growing concern and considerable debate regarding the potential for coronavirus infection to contribute to an appreciable burden
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A Neutrophil Subset Defined by Intracellular Olfactomedin 4 is Associated with Mortality in Sepsis Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-23 Kirsten Neudoerffer Kangelaris; Regina Clemens; Xiaohui Fang; Alejandra Jauregui; Tom Liu; Kathryn Vessel; Thomas Deiss; Pratik Sinha; Aleksandra Leligdowicz; Kathleen D Liu; Hanjing Zhuo; Matthew N Alder; Hector R Wong; Carolyn S Calfee; Clifford A. Lowell; Michael A Matthay
Sepsis is a heterogeneous syndrome clinically and biologically but biomarkers of distinct host response pathways for early prognostic information and testing targeted treatments are lacking. We hypothesized that Olfactomedin 4 (OLFM4), a matrix glycoprotein of neutrophil specific granules defines a distinct neutrophil subset that may be an independent risk factor for poor outcomes in sepsis. In a single-center
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Retraction Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-18
American Journal of Physiology-Lung Cellular and Molecular Physiology, Volume 319, Issue 6, Page L1062-L1062, December 2020.
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Retraction Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-18
American Journal of Physiology-Lung Cellular and Molecular Physiology, Volume 319, Issue 6, Page L1061-L1061, December 2020.
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Corrigendum Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-18
American Journal of Physiology-Lung Cellular and Molecular Physiology, Volume 319, Issue 6, Page L1063-L1064, December 2020.
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Profibrotic epithelial TGF-β1 signaling involves NOX4-mitochondria cross-talk and redox-mediated activation of the tyrosine kinase FYN Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-16 Carmen Veith; Milena Hristova; Karamatullah Danyal; Aida Habibovic; Christopher M. Dustin; John E. McDonough; Bart M. Vanaudenaerde; Michael Kreuter; Marc A. Schneider; Nicolas Kahn; Frederik Jan van Schooten; Agnes W. Boots; Albert van der Vliet
Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed redox balance and increased production of reactive oxygen species (ROS), which is believed to contribute to epithelial injury and fibrotic lung scarring. The main pulmonary sources of ROS include mitochondria and NADPH oxidases (NOXs), of which the NOX4 isoform has been implicated in IPF. Non-receptor SRC tyrosine kinases (SFK) are
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The chemokine CX3CL1/fractalkine regulates immunopathogenesis during fungal-associated allergic airway inflammation Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-16 Matthew S. Godwin; MaryJane Jones; Jonathan P. Blackburn; Zhihong Yu; Sadis Matalon; Annette T Hastie; Deborah A Meyers; Chad Steele
Individuals that present with difficult-to-control asthma and sensitivity to one or more fungal species are categorized as a subset of severe asthma patients belonging to a group herein referred to as severe asthma with fungal sensitization (SAFS). We have previously reported the identification of numerous cytokines and chemokines that were elevated in human asthmatics that were sensitized to fungi
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E-cigarettes and health risks: more to the flavour than just the name Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-09 Miranda P. Ween; Alex Moshensky; Leigh L. Thredgold; Nicole A. Bastian; Rhys Hamon; Arash Badiei; Phan Tien Nguyen; Kirsty Herewane; Hubertus Jersmann; Christine M. Bojanowski; John Shin; Paul N. Reynolds; Laura E. Crotty Alexander; Sandra J. Hodge
Rationale: The growing interest in regulating flavoured E-liquids must incorporate understanding of the "flavouring profile" of each E-liquid - which flavourants (flavouring chemicals) are present and at what concentrations not just focussing on the flavour on the label. Methods: We investigated the flavouring profile of 10 different flavoured E-liquids. We assessed bronchial epithelial cell viability
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Inflammasome Activation in Acute Lung Injury Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-09 Mark John McVey; Benjamin Ethan Steinberg; Neil M Goldenberg
Inflammasomes are multi-protein complexes tasked with sensing endogenous or exogenous inflammatory signals, and integrating this signal into a downstream response. Inflammasome activation has been implicated in a variety of pulmonary diseases, including pulmonary hypertension, bacterial pneumonia, COPD and asthma. Of increasing interest is the contribution of inflammasome activation in the context
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Clinical and molecular characterisation of the R751L-CFTR mutation Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-09 Iram J Haq; Mike Althaus; Aaron Ions Gardner; Hui Ying Yeoh; Urjita Joshi; Vinciane Saint-Criq; Bernard Verdon; Jennifer Townshend; Christopher O'Brien; Mahfud Ben-Hamida; Matthew Thomas; Stephen Bourke; Peter van der Sluijs; Ineke Braakman; Chris Ward; Michael A Gray; Malcolm Brodlie
Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterised. Our aims were to describe the clinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individuals harbouring R751L
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Role of the COX2-PGE2 axis in S. pneumoniae induced exacerbation of experimental fibrosis Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-09 Tina Bormann; Regina Maus; Jennifer Stolper; Danny Jonigk; Tobias Welte; Jack Gauldie; Martin RJ Kolb; Ulrich A. Maus
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) associated with high morbidity and mortality. Patients with ILD frequently develop an acute exacerbation of their disease, which may be triggered by viral and/or bacterial infections. Prostaglandin E2 (PGE2) is an eicosanoid released in a cyclooxygenase-2 (COX2) dependent manner and is considered to contribute to regulation of
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Platelet activation contributes to hypoxia-induced inflammation Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-02 Cassidy Delaney; Pavel Davizon-Castillo; Ayed Allawzi; Janelle Posey; Aneta Gandjeva; Keith Neeves; Rubin M. Tuder; Jorge Di Paola; Kurt R Stenmark; Eva S. Nozik
Inflammation is central to the pathogenesis of pulmonary vascular remodeling and pulmonary hypertension (PH). Inflammation precedes remodeling in preclinical models, thus supporting the concept that changes in immunity drive remodeling in PH. Platelets are recognized as mediators of inflammation, but whether platelets contribute to hypoxia-driven inflammation has not been studied. We utilized a murine
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Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients. Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-02 Ariana Centa; Aline S. Fonseca; Solange G. da Silva Ferreira; Marina Luise V. Azevedo; Caroline B. Vaz de Paula; Seigo Nagashima; Cleber Machado-Souza; Anna Flavia R. dos Santos Miggiolaro; Cristina P. Baena; Lucia de Noronha; Luciane R. Cavalli
MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including the ones caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional
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Obesity and diabetes: similar respiratory mechanical, but different gas exchange defects Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-12-02 Roberta Sudy; Ferenc Petak; Liliana Kiss; Adam Laszlo Balogh; Gergely H. Fodor; Anita Korsos; Almos Schranc; Barna Babik
Diabetes mellitus increases smooth muscle tone and causes tissue remodelling affecting elastin and collagen. Since lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body
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Call for Papers: "Morphology is the link between genetics and function": A tribute to Ewald R. Weibel Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-25 Christian Mühlfeld; Connie C.W. Hsia; George D Leikauf; Sandra Orgeig; Louise V. Wain; Matthias Ochs
American Journal of Physiology-Lung Cellular and Molecular Physiology, Ahead of Print.
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Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients with COVID-19 Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-25 Faeq Husain-Syed; István Vadász; Jochen Wilhelm; Hans-Dieter Walmrath; Werner Seeger; Horst-Walter Birk; Birgit Jennert; Hartmut Dietrich; Susanne Herold; Janina Trauth; Khodr Tello; Michael Sander; Rory E. Morty; Heiko Slanina; Christian G. Schüttler; John Ziebuhr; Shadi Kassoumeh; Claudio Ronco; Fiorenza Ferrari; Klaus Warnatz; Klaus Stahl; Benjamin Seeliger; Marius M. Hoeper; Tobias Welte; Sascha
Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critical ill COVID-19 patients admitted to two German ICUs (72.6% male, median age: 61 years). 13 (21.0%)
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Angiotensin-Converting Enzyme 2 and COVID-19: Patients, Comorbidities, and Therapies Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-25 Girish Pathangey; Priyal Praful Fadadu; Alexandra Raye Hospodar; Amr Abbas
On March 11, 2020, the World Health Organization declared COVID-19 a pandemic, and the reality of the situation has finally caught up to the widespread reach of the disease. The presentation of the disease is highly variable, ranging from asymptomatic carriers to critical COVID-19. The availability of angiotensin-converting enzyme 2 (ACE2) receptors may reportedly increase the susceptibility and/or
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Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-25 Chloé Grebert; Frederic Becq; Clarisse Vandebrouck
Chloride secretion by airway epithelial cells is primordial for water and ion homeostasis and airways surface prevention of infections. This secretion is impaired in several human diseases, including cystic fibrosis, a genetic pathology due to CFTR gene mutations leading to chloride channel defects. A potential therapeutic approach is aiming at increasing chloride secretion either by correcting the
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The aryl hydrocarbon receptor reduces LC3II expression and controls endoplasmic reticulum stress Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-25 Necola Guerrina; Noof Aloufi; Fangyi Shi; Kashmira Prasade; Caitlin Mehrotra; Hussein Traboulsi; Jason Matthews; David H. Eidelman; Qutayba Hamid; Carolyn J Baglole
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor whose physiological function is poorly understood. The AhR is highly expressed in barrier organs such as the skin, intestine and lung. The lungs are continuously exposed to environmental pollutants such as cigarette smoke (CS) that can induce cell death mechanisms such as apoptosis, autophagy and endoplasmic reticulum (ER)
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Cigarette Smoke Preparations, Not Electronic Nicotine Delivery Systems (ENDS) Preparations, Induce Features of Lung Disease in a 3D Lung Repeat-Dose Model Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-18 Rachael E Rayner; Patrudu Makena; Gaddamanugu L Prasad; Estelle Cormet-Boyaka
Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare
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Strain-specific differences in lung tissue viscoelasticity of mechanically ventilated infant Sprague Dawley and Wistar rats Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-18 Philipp Baumann; Susanne Wiegert; Francesco Greco; Jörg Ersch; Vincenzo Cannizzaro
Rats are often used in ventilator-induced lung injury (VILI) models. However, strain-specific susceptibility for VILI has not been elucidated yet. The aim of this study was to demonstrate strain-specific differences in VILI in infant Sprague Dawley and Wistar rats. VILI was compared in two week old pups after 8 hours of protective or injurious ventilation. Pups were ventilated with tidal volumes (VT)
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Looking at the Developing Lung in Single-cell Resolution Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-18 Ivana Mižíková; Bernard Thébaud
Lung development is a complicated and delicate process, facilitated by spatially and temporarily coordinated crosstalk of up to 40 cell types. Developmental origin and heterogeneity of lung cell lineages in context of lung development have been a focus of research efforts for decades. Bulk RNA and protein measurements, RNA and protein labelling, and lineage tracing techniques have been traditionally
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Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-11 Mathew Suji Eapen; Wenying Lu; Tillie-Louise Hackett; Gurpreet K Singhera; Isobel E. Thompson; Kielan Darcy McAlinden; Ashutosh Hardikar; Heinrich C. Weber; Greg Haug; Peter A. B. Wark; Collin Chia; Sukhwinder Singh Sohal
Lungs of smokers and COPD are severely compromised and are susceptible to SARS-CoV-2 attack. The lethal combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2)
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In well-differentiated primary human bronchial epithelial cells, TGF-β1 and TGF-β2 induce expression of furin Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-11 Michael J O'Sullivan; Jennifer A Mitchel; Chimwemwe Mwase; Maureen McGill; Phyllis Kanki; Jin-Ah Park
Background: The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, the disease caused by SARS-CoV-2, no drugs have been developed to specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding of cellular mechanisms underlying SARS-CoV-2 infection is required. To fill this knowledge gap, researchers require reliable
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Why New Biology Must Be Uncovered to Advance Therapeutic Strategies for Chronic Obstructive Pulmonary Disease Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-11 Jennifer My Kieu Nguyen; Douglas N. Robinson; Venkataramana K. Sidhaye
Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar tissue (in emphysema) and airway remodeling (leading to chronic bronchitis) which cause difficulties in breathing. It is a growing public health concern with few therapeutic options that can reverse disease progression or mortality. This is in part because current treatments mainly focus on ameliorating symptoms
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Neuropilin-1 directs PDGFRα-entry into lung fibroblasts and signaling from very early endosomes Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-11 Stephen E McGowan; Diann M. McCoy
Platelet-derived growth factor receptor alpha (PDGFRα) is absolutely required for the development of secondary pulmonary alveolar septa. Our earlier observations indicated that PDGFRα resides intracellularly as well as on the plasma membrane of murine lung fibroblasts (LF). We have examined how neuropilin-1 (Nrp1), a surface receptor without kinase activity, regulates the intracellular trafficking
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Stabilizing mast cells improves acute lung injury after orthotopic liver transplantation via promotion of apoptosis in polymorphonuclear neutrophils Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-11 Chaojin Chen; Zheng Zhang; Fang Tan; Fanbing Meng; Lifei Lai; Xinjin Chi; Qianqian Zhu
Aims: Postoperative pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome have contributed to the mortality and morbidity of orthotopic liver transplantation (OLT) with unclear mechanisms. Mast cells (MCs) and polymorphonuclear neutrophils (PMNs) are the main inflammatory cells and participants in the process of ALI. The present study was designed to investigate
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Depletion of pulmonary intravascular macrophages rescues inflammation-induced delayed neutrophil apoptosis in horses Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-04 Stacy L. Anderson; Tanya Duke-Novakovski; Alexandra R Robinson; Hugh G.G. Townsend; Baljit Singh
The objective of this study was to determine the effect of pulmonary intravascular macrophage depletion on systemic inflammation and ex vivo neutrophil apoptosis, using an experimental model of intestinal ischemia and reperfusion injury in horses. Neutrophils were isolated before and after surgery from horses that were randomized to 3 treatment groups: sham celiotomy (CEL, n=4), intestinal ischemia
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Microvesicles in bronchoalveolar lavage as a potential biomarker of COPD. Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-04 Erica Bazzan; Claudia Maria Radu; Mariaenrica Tinè; Tommaso Neri; Davide Biondini; Umberto Semenzato; Alvise Casara; Elisabetta Balestro; Paolo Simioni; Alessandro Celi; Manuel G Cosio; Marina Saetta
Background. Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. Aims. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without COPD compared to non-smoking controls.
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High-dimensional single-cell analysis reveals the immune characteristics of COVID-19 Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-04 Wen Shi; Xiuxing Liu; Qiqi Cao; Pengjuan Ma; Wenqing Le; Lihui Xie; JinGuo Ye; Wen Wen; Hao Tang; Wenru Su; Yingfeng Zheng; Yizhi Liu
Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is now declared a global pandemic. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry
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TNFα Induces Mitochondrial Fragmentation and Biogenesis in Human Airway Smooth Muscle Am. J. Physiol. Lung Cell Mol. Physiol. (IF 4.406) Pub Date : 2020-11-04 Philippe F. Delmotte; Natalia Marin Mathieu; Gary C. Sieck