scholarly journals Mesenchymal WNT-5A/5B Signaling Represses Lung Alveolar Epithelial Progenitors

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1147 ◽  
Author(s):  
Wu ◽  
van Dijk ◽  
Ng-Blichfeldt ◽  
Bos ◽  
Ciminieri ◽  
...  
Keyword(s):  
Wnt Signaling Pathway ◽  
Disease Process ◽  
Alveolar Epithelium ◽  
Accelerated Ageing ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Epithelial ◽  
The Impact

Chronic obstructive pulmonary disease (COPD) represents a worldwide concern with high morbidity and mortality, and is believed to be associated with accelerated ageing of the lung. Alveolar abnormalities leading to emphysema are a key characteristic of COPD. Pulmonary alveolar epithelial type 2 cells (AT2) produce surfactant and function as progenitors for type 1 cells. Increasing evidence shows elevated WNT-5A/B expression in ageing and in COPD that may contribute to the disease process. However, supportive roles for WNT-5A/B in lung regeneration were also reported in different studies. Thus, we explored the role of WNT-5A/B on alveolar epithelial progenitors (AEPs) in more detail. We established a Precision-Cut-Lung Slices (PCLS) model and a lung organoid model by co-culturing epithelial cells (EpCAM+/CD45-/CD31-) with fibroblasts in matrigel in vitro to study the impact of WNT-5A and WNT-5B. Our results show that WNT-5A and WNT-5B repress the growth of epithelial progenitors with WNT-5B preferentially restraining the growth and differentiation of alveolar epithelial progenitors. We provide evidence that both WNT-5A and WNT-5B negatively regulate the canonical WNT signaling pathway in alveolar epithelium. Taken together, these findings reveal the functional impact of WNT-5A/5B signaling on alveolar epithelial progenitors in the lung, which may contribute to defective alveolar repair in COPD.

scholarly journals WNT5a-ROR Signaling Is Essential for Alveologenesis

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 384 ◽  
Author(s):  
Changgong Li ◽  
Susan M Smith ◽  
Neil Peinado ◽  
Feng Gao ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Type I ◽  
Loss Of Function ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Epithelial ◽  
Isolated Lung ◽  
And Migration

WNT5a is a mainly “non-canonical” WNT ligand whose dysregulation is observed in lung diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and asthma. Germline deletion of Wnt5a disrupts embryonic lung development. However, the temporal-specific function of WNT5a remains unknown. In this study, we generated a conditional loss-of-function mouse model (Wnt5aCAG) and examined the specific role of Wnt5a during the saccular and alveolar phases of lung development. The lack of Wnt5a in the saccular phase blocked distal airway expansion and attenuated differentiation of endothelial and alveolar epithelial type I (AT1) cells and myofibroblasts. Postnatal Wnt5a inactivation disrupted alveologenesis, producing a phenotype resembling human bronchopulmonary dysplasia (BPD). Mutant lungs showed hypoalveolization, but endothelial and epithelial differentiation was unaffected. The major impact of Wnt5a inactivation on alveologenesis was on myofibroblast differentiation and migration, with reduced expression of key regulatory genes. These findings were validated in vitro using isolated lung fibroblasts. Conditional inactivation of the WNT5a receptors Ror1 and Ror2 in alveolar myofibroblasts recapitulated the Wnt5aCAG phenotype, demonstrating that myofibroblast defects are the major cause of arrested alveologenesis in Wnt5aCAG lungs. Finally, we show that WNT5a is reduced in human BPD lung samples, indicating the clinical relevance and potential role for WNT5a in pathogenesis of BPD.

scholarly journals Impact of surgery on the mortality of infective endocarditis in a hospital without cardiac surgery

2020 ◽  
Vol 33 (6) ◽  
pp. 436-443
Author(s):  
Rosa Escudero-Sánchez ◽  
S. Scarleth Mendoza Lizardo ◽  
Elena Batlle López ◽  
Carolina Campelo Gutierrez ◽  
Juan Emilio Losa García ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cardiac Surgery ◽  
Infective Endocarditis ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease ◽  
The Poor ◽  
The Central Nervous System ◽  
The Impact ◽  
Valvular Insufficiency

Background. Infective endocarditis has a high morbidity and mortality and requires a coordinated medical-surgical management. The objective was to analyse the impact of surgery on mortality in a hospital without cardiac surgery. Material and methods. Evaluation of a prospective cohort of patients with infective endocarditis diagnosed between August 2011 and January 2016 according to modified Duke’s criteria. Results. Sixty-four patients were included, of whom seventeen patients were operated (26.6%). Mortality was 32.8% and it was associated with chronic obstructive pulmonary disease history, staphylococci coagulase-negative and the appearance of complications, as valvular insufficiency and embolisms in the central nervous system; cardiac surgery was not associated with mortality. Four patients (6,6%) were not operated despite indication of cardiac surgery. The main reason for not been intervened was the poor presurgical prognosis (44.7%). Conclusions. Mortality due to infective endocarditis in a hospital without cardiac surgery is high. The need for interhospital teams is strengthened.

scholarly journals The Impact of Lung Proteases on Snake-Derived Antimicrobial Peptides

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1106
Author(s):  
Shannice E. Creane ◽  
Simon R. Carlile ◽  
Damian Downey ◽  
Sinéad Weldon ◽  
John P. Dalton ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Therapeutic Potential ◽  
Respiratory Infections ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Peptide Cleavage ◽  
Therapeutic Development ◽  
Systemic Side Effects ◽  
The Impact

Respiratory infections are a leading cause of global morbidity and mortality and are of significant concern for individuals with chronic inflammatory lung diseases. There is an urgent need for novel antimicrobials. Antimicrobial peptides (AMPs) are naturally occurring innate immune response peptides with therapeutic potential. However, therapeutic development has been hindered by issues with stability and cytotoxicity. Availing of direct drug delivery to the affected site, for example the lung, can reduce unwanted systemic side effects and lower the required dose. As cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) lungs typically exhibit elevated protease levels, the aim of this study was to assess their impact on snake-derived AMPs. Peptide cleavage was determined using SDS-PAGE and antimicrobial and anti-inflammatory activities of neutrophil elastase (NE)-incubated peptides were assessed using a radial diffusion assay (RDA) and an in vitro LPS-induced inflammation model, respectively. Although the snake-derived AMPs were found to be susceptible to cleavage by lung proteases including NE, several retained their function following NE-incubation. This facilitated the design of novel truncated derivatives that retained functionality following NE incubation. Snake-derived AMPs are tractable candidate treatments for use in environments that feature elevated NE levels, such as the CF airways.

scholarly journals The PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in chronic obstructive pulmonary disease caused by PM2.5 particulate matter

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092791 ◽  
Author(s):  
Fang Zhang ◽  
Hui Ma ◽  
Zhong Lan Wang ◽  
Wei Hua Li ◽  
Hua Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Epithelial Cells ◽  
In Vitro Model ◽  
Mtor Pathway ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Epithelial ◽  
Vitro Model

Objective Many lung diseases are associated with changes in autophagic activity. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a key regulatory role in autophagy. Our aim was to explore the function of PI3K/AKT/mTOR pathway on autophagy in chronic obstructive pulmonary disease (COPD) caused by particulate matter with a diameter <2.5 µm (PM2.5). Methods Male C57BL/6 mice were randomly divided into sham, model, and PI3K inhibitor groups. Mice were exposed to PM2.5 for 4 weeks to establish an in vivo COPD model. Alveolar epithelial cells were stimulated with PM2.5 to establish an in vitro COPD model. Results In mice with COPD induced by PM2.5, the PI3K inhibitor PF-04979064 suppressed protein expression of PI3K, p-AKT, and p-mTOR to increase apoptosis of alveolar epithelial cells and reduce autophagy. Short interfering PI3K suppressed the PI3K/AKT/mTOR pathway to induce apoptosis and reduce autophagy of alveolar epithelial cells in an in vitro model of COPD. Activation of PI3K induced the PI3K/AKT/mTOR pathway to reduce apoptosis of alveolar epithelial cells in the in vitro model of COPD by promoting autophagy. Conclusions These data demonstrate that PI3K/AKT/mTOR pathway regulates autophagy to induce apoptosis of alveolar epithelial cells in COPD.

scholarly journals The impact of daily troponin-I and D-dimer serum levels on mortality of moderate-to-severe COVID-19 pneumonia patients

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
B Stavileci ◽  
E Ozdemir
Keyword(s):  
Intensive Care ◽  
Troponin I ◽  
Coronary Bypass ◽  
Serum Levels ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease ◽  
Funding Sources ◽  
The Impact ◽  
D Dimer

Abstract Introduction Coronavirus Disease 2019 (COVID-19) caused by that infection resulted in a very high morbidity and mortality rates globally. Purpose The aim of this study is to analyses the daily Troponin-I and D-dimer levels and their impact on the need for intensive care and mortality of the COVID-19 infected patients. Methods 206 patients who were hospitalized between 20.03.2020–05.05.2020 with a diagnosis of moderate-to-severe COVID-19 pneumonia were analyzed retrospectively. Serum Troponin-I and D-dimer levels were recorded at least 10 days. Results Average age was higher in mortality group compared to non-mortality group (respectively 67.79±14.9, 56.87±18.15, p:&lt;0.001). Presence of hypertension, diabetes mellitus, previous coronary bypass surgery, heart failure, chronic renal failure and chronic obstructive pulmonary disease were statistically significant affecting mortality (respectively p:0.003, p:0.004, p:0.045, p:0.02, p:0.003, p:0.007). First 10 days measurements of Troponin-I and D-dimer values was associated with mortality and intensive care requirement (p&lt;0.001). Both Troponin-I and D-dimer were higher in mortality group compared to the patients requiring intensive care. Troponin-I value on the 7th day ≥16.05 pg/ml was related with need for intensive care (AUC: 0.896, sensitivity: %78.6, specificity: %78.3, p&lt;0.001). Troponin-I value ≥30.25 pg/ml on the 9th day was related with mortality (AUC: 0.920, sensitivity: %89.5, specificity: %89.3, p&lt;0.001). D-dimer value ≥878 hg/ml on the 2nd day was associated with intensive care need (AUC: 0.896, sensitivity: %78.6, specificity %78.3, p&lt;0.001). D-dimer value ≥1106 hg/ml on the 10th day was associated with mortality (AUC: 0.817, sensitivity: %68.4, specificity: %65.2, p&lt;0.001). It was observed that hospitalization periods ≥9.5 days were associated with mortality (AUC: 0.738, sensitivity %68.4, specificity: %65.9, p&lt;0.001). Conclusion We observed that hospitalizations ≥9.5 days increased mortality. Troponin-I and D-dimer follow-ups in serum are more effective than other inflammatory markers to show the need for intensive care and mortality. A high Troponin-I value should alert the clinician in terms of clinical deterioration. FUNDunding Acknowledgement Type of funding sources: None.

Hazards for Construction Workers

2017 ◽  
Author(s):  
Gavin H. West ◽  
Laura S. Welch
Keyword(s):  
Heavy Metals ◽  
Prevention And Control ◽  
Respiratory Diseases ◽  
Noise Exposure ◽  
Engineered Nanomaterials ◽  
Construction Workers ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
And Control ◽  
The Impact

This chapter describes the hazards for construction workers, with a particular focus on injuries as well as exposures to hazardous chemicals and dusts. A section describes hazardous exposures to lead and other heavy metals. Another section describes noise exposure. The impact of musculoskeletal disorders among construction workers is then discussed. A section on respiratory diseases focuses on asbestosis, silicosis, chronic obstructive pulmonary disease, and asthma. Exposures known to cause dermatitis and cancer are reviewed. There is a discussion of engineered nanomaterials as a potential emerging hazard. Various approaches to prevention and control, including regulations and health services, are described.

scholarly journals The Impact of the COVID-19 Pandemic on Self-Reported Management of Chronic Conditions

2021 ◽  
Vol 8 ◽  
pp. 237437352110076
Author(s):  
Hyllore Imeri ◽  
Erin Holmes ◽  
Shane Desselle ◽  
Meagen Rosenthal ◽  
Marie Barnard
Keyword(s):  
Locus Of Control ◽  
Chronic Conditions ◽  
Online Survey ◽  
Health Locus Of Control ◽  
Patient Activation ◽  
Survey Study ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
The Impact

Chronic conditions (CCs) management during the COVID-19 pandemic and the impact of the pandemic on patient activation (PA) and health locus of control (HLOC) remain unknown. This cross-sectional online survey study examined the role of COVID-19 pandemic-related worry or fear in PA and HLOC among patients with CCs. Individuals with CCs (n = 300) were recruited through MTurk Amazon. The questionnaire included sociodemographic questions, the Patient Activation Measure, and the Multidimensional Health Locus of Control–Form B. Out of the 300 participants, 9.7% were diagnosed with COVID-19, and 7.3% were hospitalized. Patients with cancer, chronic kidney disease, chronic obstructive pulmonary disease, drug abuse/substance abuse, and stroke reported significant difficulties in managing their CCs due to worry or fear because of COVID-19. More than half of the sample (45.7%) reported COVID-19-related worry or fear about managing their CCs, and these patients had lower PA and lower external HLOC compared to patients not affected by COVID-19-related worry or fear. Health professionals should provide more support for patients facing difficulties in managing their CCs during the COVID-19 pandemic.

scholarly journals ‘I’m fine!’: Assertions of lack of support need among patients with chronic obstructive pulmonary disease: A mixed-methods study

2021 ◽  
pp. 174239532110003
Author(s):  
A Carole Gardener ◽  
Caroline Moore ◽  
Morag Farquhar ◽  
Gail Ewing ◽  
Efthalia Massou ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Mixed Method ◽  
Self Report ◽  
Design Stage ◽  
Chronic Obstructive ◽  
Support Needs ◽  
Obstructive Pulmonary Disease ◽  
Stage 1 ◽  
The Impact

Objectives To understand how people with Chronic Obstructive Pulmonary Disease (COPD) disavow their support needs and the impact on care. Methods Two stage mixed-method design. Stage 1 involved sub-analyses of data from a mixed-method population-based longitudinal study exploring the needs of patients with advanced COPD. Using adapted criteria from mental health research, we identified 21 patients who disavowed their needs from the 235 patient cohort. Qualitative interview transcripts and self-report measures were analysed to compare these patients with the remaining cohort. In stage 2 focus groups (n = 2) with primary healthcare practitioners (n = 9) explored the implications of Stage 1 findings. Results Patients who disavowed their support needs described non-compliance with symptom management and avoidance of future care planning (qualitative data). Analysis of self-report measures of mental and physical health found this group reported fewer needs than the remaining sample yet wanted more GP contact. The link between risk factors and healthcare professional involvement present in the rest of the sample was missing for these patients. Focus group data suggested practitioners found these patients challenging. Discussion This study identified patients with COPD who disavow their support needs, but who also desire more GP contact. GPs report finding these patients challenging to engage.

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