5,629 results match your criteria American Journal Of Physiology-Lung Cellular And Molecular Physiology[Journal]


Chemokines, Soluble PD-L1, and Immune Cell Hyporesponsiveness are Distinct Features of SARS-CoV-2 Critical Illness.

Am J Physiol Lung Cell Mol Physiol 2022 May 24. Epub 2022 May 24.

Benaroya Research Institute, Seattle, WA, United States.

Critically ill patients manifest many of the same immune features seen in COVID-19, including both "cytokine storm" and "immune suppression." However, direct comparisons of molecular and cellular profiles between contemporaneously enrolled critically ill patients with and without SARS-CoV-2 are limited. We sought to identify immune signatures specifically enriched in critically ill patients with COVID-19 compared to patients without COVID-19. Read More

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Single Cell RNA Sequencing and Binary Hierarchical Clustering Defines Lung Interstitial Macrophage Heterogeneity in Response to Hypoxia.

Am J Physiol Lung Cell Mol Physiol 2022 May 24. Epub 2022 May 24.

Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, United States.

Few studies have examined lung interstitial macrophage (IM) molecular phenotypes after being exposed to hypoxia in-vivo at the single-cell level, even though macrophages contribute to hypoxic pulmonary hypertension (PH). We aimed to determine IM diversity and its association with hypoxia-induced PH. We hypothesized that integrating single-cell RNA sequencing (scRNAseq) and binary hierarchal clustering (BHC) could resolve IM heterogeneity under normal homeostatic conditions and changes induced by hypoxia exposure. Read More

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Cellular mechanism underlying the facilitation of contractile response induced by IL-25 in mouse tracheal smooth muscle.

Am J Physiol Lung Cell Mol Physiol 2022 May 10. Epub 2022 May 10.

School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Asthma is a common heterogeneous respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR) which is associated with abnormality in smooth muscle contractility. The epithelial cell-derived cytokine IL-25 is implicated in type 2 immune pathology including asthma, whereas the underlying mechanisms have not been fully elucidated. This study aims to investigate the effects of IL-25 on mouse tracheal smooth muscle contractility and elucidate the cellular mechanisms. Read More

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Airway and parenchymal tissue resistance and elastance in ex vivo sheep lungs: Effects of bronchochallenge and deep inspiration.

Am J Physiol Lung Cell Mol Physiol 2022 May 10. Epub 2022 May 10.

The UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada.

Lung resistance (R) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in R, but the mechanism is not entirely clear. The first step towards understanding the effect of DI is to determine how each of the resistance components is affected by DI. Read More

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Cortactin Loss Protects Against Hemin-Induced Acute Lung Injury in Sickle Cell Disease.

Am J Physiol Lung Cell Mol Physiol 2022 May 3. Epub 2022 May 3.

ndiana University School of Medicine, Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Occupational Medicine, Indianapolis, IN, United States.

In patients with sickle cell disease (SCD), acute chest syndrome (ACS) is a major cause of morbidity and mortality. The pathophysiology of ACS is complex and hemin, the prosthetic moiety of hemoglobin, has been implicated in endothelial cell (EC) activation and subsequent ALI and ACS in vitro and in animal studies. Here, we examined the role of cortactin (CTTN), a cytoskeletal protein that regulates EC function, in response to hemin-induced ALI and ACS. Read More

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The impact of nebulized Epoprostenol and Iloprost on hemoglobin oxygen affinity - an ex-vivo experiment.

Am J Physiol Lung Cell Mol Physiol 2022 May 3. Epub 2022 May 3.

Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Austria.

Background Inhalational prostacyclins act as strong vasodilators, potentially improving oxygenation by reducing shunt fraction and ventilation-perfusion mismatch. As prostacyclin receptors are known to be present on human erythrocytes, possible direct effects on oxygenation were further explored by examining the sole in-vitro influence of prostacyclins on hemoglobin oxygen (Hb-O) affinity. Methods Venous blood samples from 20 healthy volunteers were exposed in-vitro to supramaximal doses of epoprostenol, iloprost, and control. Read More

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Racing Against Time: Leveraging Preclinical Models to Understand Pulmonary Susceptibility to Perinatal Acetaminophen Exposures.

Am J Physiol Lung Cell Mol Physiol 2022 May 3. Epub 2022 May 3.

Section of Neonatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, United States.

Over the past decade, clinicians have increasingly prescribed acetaminophen (APAP) for patients in the neonatal intensive care unit (NICU). Acetaminophen has been shown to reduce post-operative opiate burden, and may provide similar efficacy for closure of the patent ductus arteriosus (PDA) as nonsteroidal anti-inflammatory drugs (NSAIDs). Despite these potential benefits, APAP exposures have spread to increasingly less mature infants, a highly vulnerable population for whom robust pharmacokinetic and pharmacodynamic data for APAP are lacking. Read More

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Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 19;322(6):L866-L872. Epub 2022 Apr 19.

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Read More

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Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 19;322(6):L822-L841. Epub 2022 Apr 19.

The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.

Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. Read More

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One percent of the clinical dose used for antenatal steroid therapy is sufficient to induce lung maturation when administered directly to the preterm ovine fetus.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 19;322(6):L853-L865. Epub 2022 Apr 19.

Division of Obstetrics and Gynecology, Medical School, The University of Western Australia, Perth, Western Australia, Australia.

Antenatal steroids (ANSs) are routinely administered to women judged to be at imminent risk of preterm delivery. Their principal benefit is precocious functional maturation of the preterm fetal lung. Current dosing regimens expose the mother and fetus to high steroid levels that may be unnecessary, increasing the potential risks of disruption to the maternal and fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose regulation, alterations in placental function, and reduced fetal growth. Read More

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Chloride channel accessory 1 gene deficiency causes selective loss of mucus production in a new pig model.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 19;322(6):L842-L852. Epub 2022 Apr 19.

Drug Discovery Program, Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri.

Morbidity and mortality of respiratory diseases are linked to airway obstruction by mucus but there are still no specific, safe, and effective drugs to correct this phenotype. The need for better treatment requires a new understanding of the basis for mucus production. In that regard, studies of human airway epithelial cells in primary culture show that a mucin granule constituent known as chloride channel accessory 1 (CLCA1) is required for inducible expression of the inflammatory mucin MUC5AC in response to potent type 2 cytokines. Read More

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The ultrastructural heterogeneity of lung surfactant revealed by serial section electron tomography: Insights into the 3D architecture of human tubular myelin.

Am J Physiol Lung Cell Mol Physiol 2022 Apr 19. Epub 2022 Apr 19.

Institute of Functional Anatomy, Charité , Berlin, Germany.

Weibel's hypothetical 3D model in 1966 provided first ultrastructural details into tubular myelin (TM), a unique, complex surfactant subtype found in the hypophase of the alveolar lining layer. Although initial descriptions by electron microscopy (EM) were already published in the 1950s, a uniform morphological differentiation from other intraalveolar surfactant subtypes is still missing and potential structure-function relationships remain enigmatic. Technical developments in volume EM methods now allow a more detailed reinvestigation. Read More

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Moving bronchopulmonary dysplasia research from the bedside to the bench.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 19;322(6):L804-L821. Epub 2022 Apr 19.

Division of Neonatology, The Children's Regional Hospital at Cooper/Cooper Medical School of Rowan University, Camden, New Jersey.

Although advances in the respiratory management of extremely preterm infants have led to improvements in survival, this progress has not yet extended to a reduction in the incidence of bronchopulmonary dysplasia (BPD). BPD is a complex multifactorial condition that primarily occurs due to disturbances in the regulation of normal pulmonary airspace and vascular development. Preterm birth and exposure to invasive mechanical ventilation also compromises large airway development, leading to significant morbidity and mortality. Read More

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Pharmacological sphingosine-1 phosphate receptor 1 targeting in cigarette smoke-induced emphysema in mice.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 12;322(6):L794-L803. Epub 2022 Apr 12.

Department of Medicine, Division of Pulmonary and Critical Care, National Jewish Health, Denver, Colorado.

Primarily caused by chronic cigarette smoking (CS), emphysema is characterized by loss of alveolar cells comprising lung units involved in gas exchange and inflammation that culminate in airspace enlargement. Dysregulation of sphingolipid metabolism with increases of ceramide relative to sphingosine-1 phosphate (S1P) signaling has been shown to cause lung cell apoptosis and is emerging as a potential therapeutic target in emphysema. We sought to determine the impact of augmenting S1P signaling via S1P receptor 1 (S1P1) in a mouse model of CS-induced emphysema. Read More

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Continuous but not pulsed low-dose fetal betamethasone exposures extend the durability of antenatal steroid therapy.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 5;322(6):L784-L793. Epub 2022 Apr 5.

Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.

Antenatal steroid (ANS) therapy is the standard care for women at imminent risk of preterm labor. Despite extensive and long-standing use, 40%-50% of babies exposed antenatally to steroids do not derive benefit; remaining undelivered 7 days or more after ANS treatment is associated with a lack of treatment benefit and increased risk of harm. We used a pregnant sheep model to evaluate the impact of continuous versus pulsed ANS treatments on fetal lung maturation at an extended, 8-day treatment to delivery interval. Read More

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Exposure to the heated tobacco product IQOS generates apoptosis-mediated pulmonary emphysema in murine lungs.

Am J Physiol Lung Cell Mol Physiol 2022 05 5;322(5):L699-L711. Epub 2022 Apr 5.

Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Pulmonary emphysema is predominantly caused by chronic exposure to cigarette smoke (CS). Novel tobacco substitutes, such as heated tobacco products (HTPs), have emerged as healthier alternatives to cigarettes. IQOS, the most popular HTP in Japan, is advertised as harmless compared with conventional cigarettes. Read More

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Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract.

Am J Physiol Lung Cell Mol Physiol 2022 05 29;322(5):L683-L698. Epub 2022 Mar 29.

School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma. The current study investigated these nonantibiotic activities of azithromycin in mice exposed daily to intranasal house dust mite (HDM) extract for 10 days. Read More

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Reviewing the suitability of mitochondrial transplantation as therapeutic approach for pulmonary hypertension in the era of personalized medicine.

Authors:
Gerald J Maarman

Am J Physiol Lung Cell Mol Physiol 2022 05 23;322(5):L641-L646. Epub 2022 Mar 23.

CARMA: Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Stellenbosch University, Tygerberg, South Africa.

Pulmonary hypertension (PH) is a fatal disease, defined as a mean pulmonary artery pressure ≥25 mmHg. It is caused, in part, by mitochondrial dysfunction. Among the various biological therapies proposed to rescue mitochondrial dysfunction, evidence going back as far as 2009 suggests that mitochondrial transplantation is an alternative. Read More

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Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.

Am J Physiol Lung Cell Mol Physiol 2022 Jun 23;322(6):L771-L783. Epub 2022 Mar 23.

Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California.

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments. Read More

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Angiotensin-converting enzyme 2 in peripheral lung club cells modulates the susceptibility to SARS-CoV-2 in chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2022 05 23;322(5):L712-L721. Epub 2022 Mar 23.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.

Accumulating evidence has confirmed that chronic obstructive pulmonary disease (COPD) is a risk factor for development of severe pathological changes in the peripheral lungs of patients with COVID-19. However, the underlying molecular mechanisms remain unclear. Because bronchiolar club cells are crucial for maintaining small airway homeostasis, we sought to explore whether the altered susceptibility to SARS-CoV-2 infection of the club cells might have contributed to the severe COVID-19 pneumonia in COPD patients. Read More

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Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.

Am J Physiol Lung Cell Mol Physiol 2022 05 23;322(5):L737-L760. Epub 2022 Mar 23.

Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California.

Concentric pulmonary vascular wall thickening due partially to increased pulmonary artery (PA) smooth muscle cell (PASMC) proliferation contributes to elevating pulmonary vascular resistance (PVR) in patients with pulmonary hypertension (PH). Although pulmonary vasoconstriction may be an early contributor to increasing PVR, the transition of contractile PASMCs to proliferative PASMCs may play an important role in the development and progression of pulmonary vascular remodeling in PH. A rise in cytosolic Ca concentration ([Ca]) is a trigger for PASMC contraction and proliferation. Read More

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Cytokine signature clusters as a tool to compare changes associated with tobacco product use in upper and lower airway samples.

Am J Physiol Lung Cell Mol Physiol 2022 05 23;322(5):L722-L736. Epub 2022 Mar 23.

Curriculum in Toxicology and Environmental Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Inhalation exposure to cigarette smoke and e-cigarette aerosol is known to alter the respiratory immune system, particularly cytokine signaling. In assessments of health impacts of tobacco product use, cytokines are often measured using a variety of sample types, from serum to airway mucosa. However, it is currently unclear whether and how well cytokine levels from different sample types and the airway locations they represent are correlated, making comparing studies that utilize differing sample types challenging. Read More

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Lung-kidney interactions and their role in chronic kidney disease-associated pulmonary diseases.

Am J Physiol Lung Cell Mol Physiol 2022 05 10;322(5):L625-L640. Epub 2022 Mar 10.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.

Chronic illnesses rarely present in a vacuum, devoid of other complications, and chronic kidney disease is hardly an exception. Comorbidities associated with chronic kidney disease lead to faster disease progression, expedited dialysis dependency, and a higher mortality rate. Although chronic kidney disease is most commonly accompanied by cardiovascular diseases and diabetes, there is clear cross talk between the lungs and kidneys pH balance, phosphate metabolism, and immune system regulation. Read More

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Lung resistance and elastance are different in ex vivo sheep lungs ventilated by positive and negative pressures.

Am J Physiol Lung Cell Mol Physiol 2022 05 10;322(5):L673-L682. Epub 2022 Mar 10.

The UBC Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada.

Lung resistance () and elastance () can be measured during positive or negative pressure ventilation. Whether the different modes of ventilation produce different and is still being debated. Although negative pressure ventilation (NPV) is more physiological, positive pressure ventilation (PPV) is more commonly used for treating respiratory failure. Read More

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Actin-related protein 2/3 complex regulates neutrophil extracellular trap expulsion and lung damage in abdominal sepsis.

Am J Physiol Lung Cell Mol Physiol 2022 05 10;322(5):L662-L672. Epub 2022 Mar 10.

Department of Clinical Sciences, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.

Neutrophil extracellular trap (NET) formation is a key feature in sepsis. The aim of the present study was to examine the role of the actin cytoskeleton in regulating the expulsion of NETs. Actin-related protein 2/3 (Arp 2/3) complex is an important regulator of F-actin polymerization. Read More

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Intense light-elicited alveolar type 2-specific circadian PER2 protects from bacterial lung injury via BPIFB1.

Am J Physiol Lung Cell Mol Physiol 2022 05 10;322(5):L647-L661. Epub 2022 Mar 10.

Department of Anesthesiology, University of Colorado Denver School of Medicine, Aurora, Colorado.

Circadian amplitude enhancement has the potential to be organ protective but has not been studied in acute lung injury (ALI). Consistent light and dark cycles are crucial for the amplitude regulation of the circadian rhythm protein Period2 (PER2). Housing mice under intense instead of ambient light for 1 wk (light: dark cycle:14h:10h), we demonstrated a robust increase of pulmonary PER2 trough and peak levels, which is consistent with circadian amplitude enhancement. Read More

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Early humoral defense under the radar: microvascular-epithelial cooperation at airways infection in asthma and health.

Authors:
Carl Persson

Am J Physiol Lung Cell Mol Physiol 2022 03;322(3):L503-L506

Laboratory Medicine, University Hospital of Lund, Lund, Sweden.

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CD14-positive extracellular vesicles in bronchoalveolar lavage fluid as a new biomarker of acute respiratory distress syndrome.

Am J Physiol Lung Cell Mol Physiol 2022 04 2;322(4):L617-L624. Epub 2022 Mar 2.

Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, grid.6572.6University of Birmingham, Birmingham, United Kingdom.

Recent studies have indicated that extracellular vesicles (EVs) may play a role in the pathogenesis of acute respiratory distress syndrome (ARDS). EVs have been identified as potential biomarkers of disease severity and prognosis in other pulmonary diseases. We sought to characterize the EV phenotype within bronchoalveolar lavage (BAL) fluid of patients with ARDS, and to determine whether BAL EV could be used as a potential biomarker in ARDS. Read More

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Fibrinogen mediates cadmium-induced macrophage activation and serves as a predictor of cadmium exposure in chronic obstructive pulmonary disease.

Am J Physiol Lung Cell Mol Physiol 2022 04 24;322(4):L593-L606. Epub 2022 Feb 24.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

The etiologies of chronic obstructive pulmonary disease (COPD) remain unclear. Cadmium (Cd) causes both pulmonary fibrosis and emphysema; however, the predictors for Cd exposure and the mechanisms by which Cd causes COPD remain unknown. We demonstrated that Cd burden was increased in lung tissue from subjects with COPD and this was associated with cigarette smoking. Read More

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Effect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.

Am J Physiol Lung Cell Mol Physiol 2022 04 23;322(4):L607-L616. Epub 2022 Feb 23.

Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.

We previously showed that pericyte-like cells derived from the FoxD1-lineage contribute to myofibroblasts following bleomycin-induced lung injury. However, their functional significance in lung fibrosis remains unknown. In this study, we used a model of lung pericyte-like cell ablation to test the hypothesis that pericyte-like cell ablation attenuates lung fibrosis in bleomycin-induced lung injury. Read More

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