scholarly journals Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 387 ◽  
Author(s):  
Haruka Fujikawa ◽  
Yuki Sakamoto ◽  
Natsuki Masuda ◽  
Kentaro Oniki ◽  
Shunsuke Kamei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Lung Function ◽  
Protective Factor ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Human Females ◽  
Lung Dysfunction ◽  
Endogenous Antioxidant

The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females.

scholarly journals SIRT1 Activity in Peripheral Blood Mononuclear Cells Correlates with Altered Lung Function in Patients with Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Valeria Conti ◽  
Graziamaria Corbi ◽  
Valentina Manzo ◽  
Paola Malangone ◽  
Carolina Vitale ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Chronic Obstructive ◽  
Peripheral Blood Mononuclear ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Blood Mononuclear Cells

Background. Oxidative stress is a recognized pathogenic mechanism in chronic obstructive pulmonary disease (COPD). Expression of the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), an antiaging molecule with a key role in oxidative stress response, has been described as decreased in the lung of COPD patients. No studies so far investigated whether systemic SIRT1 activity was associated to decreased lung function in this disease. Methods. We measured SIRT1 protein expression and activity in peripheral blood mononuclear cells (PBMCs) and total oxidative status (TOS), total antioxidant capacity (TEAC), and oxidative stress index (TOS/TEAC) in the plasma of 25 COPD patients, 20 healthy nonsmokers (HnS), and 20 healthy smokers (HS). Results. The activity of SIRT1 was significantly lower in COPD patients compared to both control groups while protein expression decreased progressively (HnS > HS > COPD). TOS levels were significantly lower in HnS than in smoke-associated subjects (COPD and HS), while TEAC levels were progressively lower according (HnS > HS > COPD). In COPD patients, SIRT1 activity, but not protein levels, correlated significantly with both lung function parameters (FEV1/FVC and FEV1) and TEAC. Conclusions. These findings suggest loss of SIRT1-driven antioxidant activity as relevant in COPD pathogenesis and identify SIRT1 activity as a potential convenient biomarker for identification of mild/moderate, stable COPD.

scholarly journals Loading of Beclomethasone in Liposomes and Hyalurosomes Improved with Mucin as Effective Approach to Counteract the Oxidative Stress Generated by Cigarette Smoke Extract

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 850
Author(s):  
Maria Letizia Manca ◽  
Maria Ferraro ◽  
Elisabetta Pace ◽  
Serena Di Vincenzo ◽  
Donatella Valenti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Room Temperature ◽  
Cigarette Smoke Extract ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Epithelial ◽  
Promising Tool ◽  
Next Generation Impactor

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomes modified with mucin to improve the ability of the payload to counteract the oxidative stress and involved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersing all components in the appropriate vehicle and sonicating them, thus avoiding the use of organic solvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed (polydispersity index lower than 0.22) and negatively charged (~−11 mV), were obtained. Moreover, these vesicle dispersions were stable for five months at room temperature (~25 °C). In vitro studies performed using the Next Generation Impactor confirmed the suitability of the formulations to be nebulized as they were capable of reaching the last stages of the impactor that mimic the deeper airways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibility studies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibility and safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes were capable of effectively counteracting the production of reactive oxygen species (ROS) induced by cigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce the damaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarette smoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer.

scholarly journals Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
◽  
Ying-Huang Tsai ◽  
Chin-Chou Wang ◽  
Shih-Feng Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Dna Methylations

AbstractWe hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

scholarly journals HIF-1α Contributes to the Progression of Chronic Obstructive Pulmonary Disease

2022 ◽  
Author(s):  
Kedong Zhang ◽  
Feng Zhou ◽  
Caixia Zhu ◽  
Liang Yuan ◽  
Defu Li ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
A549 Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tgf Β1

Background: Hypoxia-inducible factor-1α (HIF-1α) plays an important regulatory role in inflammatory and hypoxic diseases. Higher HIF-1α level was found in lungs of chronic obstructive pulmonary disease (COPD) patients, however, its role in cigarette smoke (CS)-induced COPD has not been fully studied. Digoxin has been showed to inhibit HIF-1α translation and block HIF-1α activity and thus is often used as the HIF-1α inhibitor. Therefore, in the present study, we chose digoxin as the inhibitor to investigate whether HIF-1α contributes to the progression of COPD and possible mechanism. Methods: CS-exposed mice were intragastrically treated with different doses of digoxin, and COPD-associated phenotypes such as pathological changes in lungs, inflammation, lung function and mucus secretion in airways were evaluated. Meanwhile, CSE-treated A549 cells were administrated with digoxin or S7959. Moreover, EMT-associated markers together with HIF-1α\TGF-β1\Smad3 signaling pathway were detected both in vivo and in vitro. Results: The level of HIF-1α was significantly increased in lungs of COPD mice and CSE-exposed A549 cells, which was markedly suppressed by digoxin. Moreover, digoxin inhibited CS-induced inflammatory responses, lung function decline, and mucus hyper-secretion in COPD mouse model. In in vitro studies, digoxin decreased CSE-induced pro-inflammatory cytokine release. Importantly, CS-induced or CSE-induced EMT and up-regulation of HIF-1α/TGF-β1/Smad pathway was inhibited by digoxin. Additionally, S7959 mitigated CSE-induced EMT in A549 cells. Conclusions: Digoxin can protect CS-induced COPD and prevent CS-induced EMT possibly through HIF-1α/TGF-β1/Smad3 signaling pathway. This study suggests HIF1-α could be a potential intervention target for COPD prevention and treatment, especially for EMT in CS-induced COPD.

Does physical inactivity cause chronic obstructive pulmonary disease?

2010 ◽  
Vol 118 (9) ◽  
pp. 565-572 ◽  
Author(s):  
Nicholas S. Hopkinson ◽  
Michael I. Polkey
Keyword(s):  
Oxidative Stress ◽  
Physical Activity ◽  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Activity Levels ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Physical Activity Levels

COPD (chronic obstructive pulmonary disease) is the most common pulmonary disease and is the only common cause of death in which mortality is presently rising. It is caused by the inhalation of smoke, which leads to oxidative stress and inflammation both in the lungs and systemically. Reduced physical activity is a well-recognized consequence of the condition, but we argue here that inactivity is itself an early cause of lung function decline and symptoms. This hypothesis is supported by data from population studies that link activity levels to decline in spirometric indices, both in smokers and non-smokers. In addition, smokers with low physical activity levels are more likely to be diagnosed subsequently with COPD. Physical exercise reduces oxidative stress, has an anti-inflammatory effect and reduces the frequency of upper respiratory tract infections, providing a number of mechanisms by which it could attenuate the harmful effects of smoking. There is sufficient evidence to justify population trials of lifestyle interventions aimed at improving physical activity levels and reducing lung function decline in people diagnosed with early COPD through spirometry screening.

scholarly journals Increased Serum ox-LDL Levels Correlated with Lung Function, Inflammation, and Oxidative Stress in COPD

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Yongchun Shen ◽  
Ting Yang ◽  
Shujin Guo ◽  
Xiao'ou Li ◽  
Lei Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Stress Studies ◽  
Copd Patients ◽  
And Oxidative Stress

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that oxidized low density lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and inflammation. However, no data on the possible relationship between COPD and ox-LDL are available. This study compared serum levels of ox-LDL in 48 COPD patients and 32 health controls and correlated them with lung function, systematic inflammation, and oxidative stress. Serum levels of ox-LDL, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Mean levels of serum ox-LDL were significantly higher in COPD patients than in controls (18.62±7.56versus12.57±5.90 mU/L,P<0.05). Serum levels of CRP and ROS were also significantly higher in COPD patients. Serum levels of ox-LDL in COPD patients correlated inversely with FEV1% predicted, an index of lung function (r=−0.347,P=0.016), while they correlated positively with CRP and ROS levels. These results suggest that serum levels of ox-LDL are increased in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD. Future studies are needed to determine whether and how ox-LDL plays a role in COPD.

Screening of High-risk Patients for Chronic Obstructive Pulmonary Disease in Primary Care: A Narrative Review (Preprint)

2020 ◽  
Author(s):  
Ponrathi Athilingam ◽  
Andrew Bugajski ◽  
Usha Menon
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Current Knowledge ◽  
Screening Tools ◽  
Chronic Obstructive ◽  
Early Screening ◽  
Obstructive Pulmonary Disease ◽  
Impaired Lung Function ◽  
Risk Patients

UNSTRUCTURED Chronic obstructive pulmonary disease (COPD) predominantly affects older adults, and claimed 3 million lives in 2016, making it the third leading cause of death worldwide. Over 35 million Americans aged 40 or older have lung function consistent with diagnosable COPD. COPD and cardiovascular disease (CVD) have a bidirectional relationship, in that one is a risk factor for developing the other. National and international consortiums recommend early screening of adults at risk of COPD, such as those with CVD. Recommended screening strategies include screening tools to assess symptoms, medical history, and handheld spirometry. Handheld spirometry has high diagnostic accuracy and if impaired lung function is indicated, these patients are referred for pulmonary function testing (PFT), the diagnostic gold standard for COPD. However, there is no clinical consensus for pulmonary screening in people with CVD. Current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence is key in combating the global burden of COPD.

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