scholarly journals Role of Nrf2 and Its Activators in Respiratory Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Qinmei Liu ◽  
Yun Gao ◽  
Xinxin Ci
Keyword(s):  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Redox Balance ◽  
Antioxidant Response ◽  
Experimental Models ◽  
26S Proteasome ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Protective Effects ◽  
Obstructive Pulmonary Disease

Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant response element- (ARE-) driven cytoprotective protein expression. The activation of Nrf2 signaling plays an essential role in preventing cells and tissues from injury induced by oxidative stress. Under the unstressed conditions, natural inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), traps Nrf2 in the cytoplasm and promotes the degradation of Nrf2 by the 26S proteasome. Nevertheless, stresses including highly oxidative microenvironments, impair the ability of Keap1 to target Nrf2 for ubiquitination and degradation, and induce newly synthesized Nrf2 to translocate to the nucleus to bind with ARE. Due to constant exposure to external environments, including diverse pollutants and other oxidants, the redox balance maintained by Nrf2 is fairly important to the airways. To date, researchers have discovered that Nrf2 deletion results in high susceptibility and severity of insults in various models of respiratory diseases, including bronchopulmonary dysplasia (BPD), respiratory infections, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and lung cancer. Conversely, Nrf2 activation confers protective effects on these lung disorders. In the present review, we summarize Nrf2 involvement in the pathogenesis of the above respiratory diseases that have been identified by experimental models and human studies and describe the protective effects of Nrf2 inducers on these diseases.

scholarly journals An Update on the Role of Nrf2 in Respiratory Disease: Molecular Mechanisms and Therapeutic Approaches

2021 ◽  
Vol 22 (16) ◽  
pp. 8406
Author(s):  
Jooyeon Lee ◽  
Jimin Jang ◽  
Sung-Min Park ◽  
Se-Ran Yang
Keyword(s):  
Oxidative Stress ◽  
Respiratory Diseases ◽  
Molecular Mechanisms ◽  
Antioxidant Response ◽  
Atmospheric Environment ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Protective Effects ◽  
Cell Protection ◽  
Obstructive Pulmonary Disease

Nuclear factor erythroid 2-related factor (Nrf2) is a transcriptional activator of the cell protection gene that binds to the antioxidant response element (ARE). Therefore, Nrf2 protects cells and tissues from oxidative stress. Normally, Kelch-like ECH-associated protein 1 (Keap1) inhibits the activation of Nrf2 by binding to Nrf2 and contributes to Nrf2 break down by ubiquitin proteasomes. In moderate oxidative stress, Keap1 is inhibited, allowing Nrf2 to be translocated to the nucleus, which acts as an antioxidant. However, under unusually severe oxidative stress, the Keap1-Nrf2 mechanism becomes disrupted and results in cell and tissue damage. Oxide-containing atmospheric environment generally contributes to the development of respiratory diseases, possibly leading to the failure of the Keap1-Nrf2 pathway. Until now, several studies have identified changes in Keap1-Nrf2 signaling in models of respiratory diseases, such as acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and asthma. These studies have confirmed that several Nrf2 activators can alleviate symptoms of respiratory diseases. Thus, this review describes how the expression of Keap1-Nrf2 functions in different respiratory diseases and explains the protective effects of reversing this expression.

scholarly journals Role of Nrf2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches – Pulmonary Disease/Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
Camille Audousset ◽  
Toby McGovern ◽  
James G. Martin
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Disease ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Antioxidant Response ◽  
Protective Role ◽  
Experimental Models ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Obstructive Pulmonary Disease

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor involved in redox homeostasis and in the response induced by oxidative injury. Nrf2 is present in an inactive state in the cytoplasm of cells. Its activation by internal or external stimuli, such as infections or pollution, leads to the transcription of more than 500 elements through its binding to the antioxidant response element. The lungs are particularly susceptible to factors that generate oxidative stress such as infections, allergens and hyperoxia. Nrf2 has a crucial protective role against these ROS. Oxidative stress and subsequent activation of Nrf2 have been demonstrated in many human respiratory diseases affecting the airways, including asthma and chronic obstructive pulmonary disease (COPD), or the pulmonary parenchyma such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Several compounds, both naturally occurring and synthetic, have been identified as Nrf2 inducers and enhance the activation of Nrf2 and expression of Nrf2-dependent genes. These inducers have proven particularly effective at reducing the severity of the oxidative stress-driven lung injury in various animal models. In humans, these compounds offer promise as potential therapeutic strategies for the management of respiratory pathologies associated with oxidative stress but there is thus far little evidence of efficacy through human trials. The purpose of this review is to summarize the involvement of Nrf2 and its inducers in ARDS, COPD, asthma and lung fibrosis in both human and in experimental models.

scholarly journals The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L155-L162 ◽  
Author(s):  
Hailin Zhao ◽  
Shiori Eguchi ◽  
Azeem Alam ◽  
Daqing Ma
Keyword(s):  
Lung Injury ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Protective Role ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

scholarly journals Gender, Estrogen, and Obliterative Lesions in the Lung

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hamza Assaggaf ◽  
Quentin Felty
Keyword(s):  
Hormone Replacement ◽  
Experimental Models ◽  
Vascular Lesions ◽  
Chronic Obstructive ◽  
Protective Effects ◽  
Pulmonary Tissue ◽  
Obstructive Pulmonary Disease ◽  
Sex Steroid Hormone ◽  
And Migration ◽  
Context Specific

Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH). Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens.

scholarly journals Air pollution exposure—the (in)visible risk factor for respiratory diseases

2021 ◽  
Author(s):  
Gabriel-Petrică Bălă ◽  
Ruxandra-Mioara Râjnoveanu ◽  
Emanuela Tudorache ◽  
Radu Motișan ◽  
Cristian Oancea
Keyword(s):  
Air Pollution ◽  
Low Income ◽  
Air Pollutants ◽  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Low Income Countries ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Pollution Exposure

AbstractThere is increasing interest in understanding the role of air pollution as one of the greatest threats to human health worldwide. Nine of 10 individuals breathe air with polluted compounds that have a great impact on lung tissue. The nature of the relationship is complex, and new or updated data are constantly being reported in the literature. The goal of our review was to summarize the most important air pollutants and their impact on the main respiratory diseases (chronic obstructive pulmonary disease, asthma, lung cancer, idiopathic pulmonary fibrosis, respiratory infections, bronchiectasis, tuberculosis) to reduce both short- and the long-term exposure consequences. We considered the most important air pollutants, including sulfur dioxide, nitrogen dioxide, carbon monoxide, volatile organic compounds, ozone, particulate matter and biomass smoke, and observed their impact on pulmonary pathologies. We focused on respiratory pathologies, because air pollution potentiates the increase in respiratory diseases, and the evidence that air pollutants have a detrimental effect is growing. It is imperative to constantly improve policy initiatives on air quality in both high- and low-income countries.

scholarly journals Diagnostic accuracy of respiratory diseases in primary health units

2014 ◽  
Vol 60 (6) ◽  
pp. 599-612 ◽  
Author(s):  
Bruno Piassi de São José ◽  
Paulo Augusto Moreira Camargos ◽  
Álvaro Augusto Souza da Cruz Filho ◽  
Ricardo de Amorim Corrêa
Keyword(s):  
Diagnostic Accuracy ◽  
General Practitioners ◽  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Diagnostic Errors ◽  
Chronic Obstructive ◽  
World Population ◽  
Diagnostic Ability ◽  
Obstructive Pulmonary Disease ◽  
Primary Health

Respiratory diseases are responsible for about a fifth of all deaths worldwide and its prevalence reaches 15% of the world population. Primary health care (PHC) is the gateway to the health system, and is expected to resolve up to 85% of health problems in general. Moreover, little is known about the diagnostic ability of general practitioners (GPs) in relation to respiratory diseases in PHC. This review aims to evaluate the diagnostic ability of GPs working in PHC in relation to more prevalent respiratory diseases, such as acute respiratory infections (ARI), tuberculosis, asthma and chronic obstructive pulmonary disease (COPD). 3,913 articles were selected, totaling 30 after application of the inclusion and exclusion criteria. They demonstrated the lack of consistent evidence on the accuracy of diagnoses of respiratory diseases by general practitioners. In relation to asthma and COPD, studies have shown diagnostic errors leading to overdiagnosis or underdiagnosis depending on the methodology used. The lack of precision for the diagnosis of asthma varied from 54% underdiagnosis to 34% overdiagnosis, whereas for COPD this ranged from 81% for underdiagnosis to 86.1% for overdiagnosis. For ARI, it was found that the inclusion of a complementary test for diagnosis led to an improvement in diagnostic accuracy. Studies show a low level of knowledge about tuberculosis on the part of general practitioners. According to this review, PHC represented by the GP needs to improve its ability for the diagnosis and management of this group of patients constituting one of its main demands.

scholarly journals Infection-Associated Mechanisms of Neuro-Inflammation and Neuro-Immune Crosstalk in Chronic Respiratory Diseases

2021 ◽  
Vol 22 (11) ◽  
pp. 5699
Author(s):  
Belinda Camp ◽  
Sabine Stegemann-Koniszewski ◽  
Jens Schreiber
Keyword(s):  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Airflow Obstruction ◽  
Microbial Colonization ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Neuro Inflammation

Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.

scholarly journals Epidemiological evidence relating risk factors to chronic obstructive pulmonary disease in China: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261692
Author(s):  
Hong Chen ◽  
Xiang Liu ◽  
Xiang Gao ◽  
Yipeng Lv ◽  
Liang Zhou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chinese Population ◽  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Meta Analysis ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Early Prevention ◽  
Obstructive Pulmonary Disease ◽  
History Of

Background Chronic obstructive pulmonary disease (COPD), the most common chronic respiratory disease worldwide, not only leads to the decline of pulmonary function and quality of life consecutively, but also has become a major economic burden on individuals, families, and society in China. The purpose of this meta-analysis was to explore the risk factors for developing COPD in the Chinese population that resides in China and to provide a theoretical basis for the early prevention of COPD. Methods A total of 2457 cross-sectional, case-control, and cohort studies published related to risk factors for COPD in China were searched. Based on the inclusion and exclusion criteria, 20 articles were selected. Stata 11.0 was used for meta-analysis. After merging the data, the pooled effect and 95% confidence intervals (CIs) were calculated to assess the association between risk factors and COPD. Heterogeneity between studies was assessed using I2 and Cochran’s Q tests. Begg’s test was used to assess publication bias. Results Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) (pooled effect = 1.73; 95%CI: 1.16~2.58; P <0.01), smoking history (pooled effect = 2.58; 95%CI: 2.00~3.32; P <0.01), passive smoking history (pooled effect = 1.39; 95%CI: 1.03~1.87; P = 0.03), male sex(pooled effect = 1.70; 95%CI: 1.31~2.22; P <0.01), body mass index (BMI) <18.5 kg/m2 (pooled effect = 1.73; 95%CI: 1.32~2.25; P <0.01), exposure to biomass burning emissions (pooled effect = 1.65; 95%CI: 1.32~2.06; P <0.01), childhood respiratory infections (pooled effect = 3.44; 95%CI: 1.33~8.90; P = 0.01), residence (pooled effect = 1.24; 95%CI: 1.09~1.42; P <0.01), and a family history of respiratory diseases (pooled effect = 2.04; 95%CI: 1.53~2.71; P <0.01) were risk factors for COPD in the Chinese population. Conclusion Early prevention of COPD could be accomplished by quitting smoking, reducing exposure to air pollutants and biomass burning emissions, maintaining body mass index between 18.5 kg/m2 and 28 kg/m2, protecting children from respiratory infections, adopting active treatments to children with respiratory diseases, and conducting regular screening for those with family history of respiratory diseases.

Lower respiratory tract infections in patients with comorbidities

2020 ◽  
Vol 1 (1) ◽  
pp. 29-34
Author(s):  
Leonid Dvoretsky ◽  
Keyword(s):  
Respiratory Diseases ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Chronic Obstructive ◽  
Lower Respiratory Tract Infections ◽  
Obstructive Pulmonary Disease ◽  
Artery Disease ◽  
Tract Infections ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

Comorbidities are an important factor of the various infectious respiratory diseases emergence, complications development and prognosis. The most frequent comorbidities affecting the course and outcome of respiratory infections are the following: cardiovascular disease (heart failure, various types of coronary artery disease, cerebrovascular disease), chronic obstructive pulmonary disease, diabetes mellitus, obesity. The paper reports data on the discussed comorbidities impact on the course and outcome of bacterial and viral respiratory infections, inter alia in patients with COVID-19.

CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases

2020 ◽  
Vol 20 (5) ◽  
pp. 333-346
Author(s):  
Sadiya Bi Shaikh ◽  
Yashodhar Prabhakar Bhandary
Keyword(s):  
Respiratory Diseases ◽  
Gene Editing ◽  
Epithelial Mesenchymal Transition ◽  
Respiratory Health ◽  
Chronic Obstructive ◽  
Therapeutic Tool ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition ◽  
Chronic Respiratory Diseases ◽  
Promising Tool

Respiratory diseases are one of the prime topics of concern in the current era due to improper diagnostics tools. Gene-editing therapy, like Clustered regularly interspaced palindromic repeats- associated nuclease 9 (CRISPR/Cas9), is gaining popularity in pulmonary research, opening up doors to invaluable insights on underlying mechanisms. CRISPR/Cas9 can be considered as a potential gene-editing tool with a scientific community that is helping in the advancement of knowledge in respiratory health and therapy. As an appealing therapeutic tool, we hereby explore the advanced research on the application of CRISPR/Cas9 tools in chronic respiratory diseases such as lung cancer, Acute respiratory distress syndrome (ARDS) and cystic fibrosis (CF). We also address the urgent need to establish this gene-editing tool in various other lung diseases such as asthma, Chronic obstructive pulmonary disease (COPD) and Idiopathic pulmonary fibrosis (IPF). The present review introduces CRISPR/Cas9 as a worthy application in targeting epithelial-mesenchymal transition and fibrinolytic system via editing specific genes. Thereby, based on the efficiency of CRISPR/Cas9, it can be considered as a promising therapeutic tool in respiratory health research.

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