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.

scholarly journals Chronic respiratory diseases at primary health care level in Georgia: the results of the pilot study

2016 ◽  
Vol 71 (4) ◽  
Author(s):  
I. Chkhaidze ◽  
T. Maglakelidze ◽  
N. Khaltaev
Keyword(s):  
Allergic Rhinitis ◽  
Respiratory Diseases ◽  
Chronic Obstructive ◽  
Official Statistics ◽  
Global Alliance ◽  
Care Level ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Chronic Morbidity ◽  
Official Data

Background and aim. Millions of people suffer from chronic respiratory diseases (CRD). To address this serious global health problem WHO formed the Global Alliance against Chronic Respiratory Diseases (GARD). Chronic obstructive pulmonary disease (COPD) is a major priority of GARD due to high chronic morbidity and mortality; however, there is still little prevalence data available. The prevalence of COPD in Georgia, as well as other CRD, is suspected to be high. Methods. GARD Pilot Survey (GAPS) in Georgia had been carried out by the Georgian Respiratory Association. The survey was conducted in the Sagarejo and Mtskheta districts with total population of about 70.000. All subjects provided information on asthma, bronchitis, respiratory symptoms, smoking, allergic conditions, CRD comorbidity and lifestyle via an interviewer-administered questionnaire. A total of 3,646 questionnaires were analysed. Results. It was discovered that official data concerning allergic rhinitis, TB and asthma are almost equal, but readings in relation to CRD are about five times lower according to official data of the Ministry of Health of Georgia. The data results: for allergic rhinitis - 218 in GAPS vs. 177 in the official statistics (for 100.000 population); for TB -105 in GAPS vs. 147 in the official statistics; for asthma -250 in GAPS vs. 374 in the official statistics; the data about CRD according to our survey is almost five times higher - 365 in GAPS vs. 84 in the official statistics (for 100.000 population). Conclusions. It is necessary to expand the survey to the entire country population. Country results are likely to be useful and interesting for local doctors and managers, as well as for officials.

scholarly journals Evidence for pulmonary rehabilitation in chronic respiratory diseases in sub-Saharan Africa: a systematic review

2020 ◽  
Vol 24 (10) ◽  
pp. 991-999
Author(s):  
F. M. Bickton ◽  
C. Fombe ◽  
E. Chisati ◽  
J. Rylance
Keyword(s):  
Pulmonary Rehabilitation ◽  
Respiratory Diseases ◽  
Sub Saharan Africa ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Exercise Regimen ◽  
Home Based ◽  
Sub Saharan ◽  
Randomised Controlled

BACKGROUND: Pulmonary rehabilitation (PR) is a highly effective non-pharmacological treatment for patients with chronic respiratory diseases.OBJECTIVE: To synthesise the evidence for PR practice and efficacy in sub-Saharan Africa.METHODS: We searched in PubMed and Scopus for relevant studies and scanned reference lists of relevant studies from these databases for additional studies. Articles meeting the inclusion criteria were included. Pre-determined data were extracted independently by two reviewers. A narrative synthesis approach was used in the interpretation of findings.RESULTS: Six studies were included, totalling 275 participants. Indications for PR were chronic obstructive pulmonary disease, asthma, pulmonary tuberculosis and post-tuberculosis lung disease. Programmes ran for 6–12 weeks, universally incorporated exercise, and variously used home-based and hospital-based delivery models. All were interventional studies, of which two were randomised controlled trials, and primarily reported pulmonary function and exercise tolerance endpoints. Evidence for individualising the exercise regimen was available in three studies.CONCLUSIONS: There is limited evidence on PR design and efficacy in sub-Saharan Africa, but available data support its use in a variety of chronic respiratory conditions. Future studies should report core outcome sets and their individualised exercise and education regimens.

scholarly journals The microbiome in respiratory medicine: current challenges and future perspectives

2017 ◽  
Vol 49 (4) ◽  
pp. 1602086 ◽  
Author(s):  
Rosa Faner ◽  
Oriol Sibila ◽  
Alvar Agustí ◽  
Eric Bernasconi ◽  
James D. Chalmers ◽  
...  
Keyword(s):  
Respiratory Diseases ◽  
Future Research ◽  
Chronic Obstructive ◽  
Gene Expressions ◽  
Obstructive Pulmonary Disease ◽  
Bacterial Gene ◽  
Chronic Respiratory Diseases ◽  
Culture Techniques ◽  
Negative Results ◽  
Cultivable Bacteria

The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease. In all of these diseases, a loss of diversity, paralleled by an over-representation of Proteobacteria (dysbiosis), has been related to disease severity and exacerbations. However, it is unknown whether dysbiosis is a cause or a consequence of the damage to bronchoalveolar surfaces.Finally, little is known about bacterial functionality and the interactions between viruses, fungi and bacteria. It is expected that future research in bacterial gene expressions, metagenomics longitudinal analysis and host–microbiome animal models will help to move towards targeted microbiome interventions in respiratory diseases.

scholarly journals Tanimilast, A Novel Inhaled Pde4 Inhibitor for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabrizio Facchinetti ◽  
Maurizio Civelli ◽  
Dave Singh ◽  
Alberto Papi ◽  
Aida Emirova ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Side Effects ◽  
Pulmonary Disease ◽  
Respiratory Diseases ◽  
Pde4 Inhibitor ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Copd Patients ◽  
Anti Inflammatory

Chronic respiratory diseases are the third leading cause of death, behind cardiovascular diseases and cancer, affecting approximately 550 million of people all over the world. Most of the chronic respiratory diseases are attributable to asthma and chronic obstructive pulmonary disease (COPD) with this latter being the major cause of deaths. Despite differences in etiology and symptoms, a common feature of asthma and COPD is an underlying degree of airways inflammation. The nature and severity of this inflammation might differ between and within different respiratory conditions and pharmacological anti-inflammatory treatments are unlikely to be effective in all patients. A precision medicine approach is needed to selectively target patients to increase the chance of therapeutic success. Inhibitors of the phosphodiesterase 4 (PDE4) enzyme like the oral PDE4 inhibitor roflumilast have shown a potential to reduce inflammatory-mediated processes and the frequency of exacerbations in certain groups of COPD patients with a chronic bronchitis phenotype. However, roflumilast use is dampened by class related side effects as nausea, diarrhea, weight loss and abdominal pain, resulting in both substantial treatment discontinuation in clinical practice and withdrawal from clinical trials. This has prompted the search for PDE4 inhibitors to be given by inhalation to reduce the systemic exposure (and thus optimize the systemic safety) and maximize the therapeutic effect in the lung. Tanimilast (international non-proprietary name of CHF6001) is a novel highly potent and selective inhaled PDE4 inhibitor with proven anti-inflammatory properties in various inflammatory cells, including leukocytes derived from asthma and COPD patients, as well as in experimental rodent models of pulmonary inflammation. Inhaled tanimilast has reached phase III clinical development by showing promising pharmacodynamic results associated with a good tolerability and safety profile, with no evidence of PDE4 inhibitors class-related side effects. In this review we will discuss the main outcomes of preclinical and clinical studies conducted during tanimilast development, with particular emphasis on the characterization of the pharmacodynamic profile that led to the identification of target populations with increased therapeutic potential in inflammatory respiratory diseases.

scholarly journals The Underappreciated Role of Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease and Its Strong Link to Lung Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1394
Author(s):  
Malik Quasir Mahmood ◽  
Shakti D. Shukla ◽  
Chris Ward ◽  
Eugene Haydn Walters
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
World Health ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition

The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality. The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression. Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking. In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions. We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer. As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications.

scholarly journals Ginsenoside Rg1 Attenuates Cigarette Smoke-Induced Pulmonary Epithelial-Mesenchymal Transition via Inhibition of the TGF-β1/Smad Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sibin Guan ◽  
Weiguo Xu ◽  
Fengfeng Han ◽  
Wen Gu ◽  
Lin Song ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Epithelial Mesenchymal Transition ◽  
Airway Remodeling ◽  
Smooth Muscle Actin ◽  
Chronic Obstructive ◽  
Ginsenoside Rg1 ◽  
Active Components ◽  
Obstructive Pulmonary Disease ◽  
Smad Pathway ◽  
Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD), which leads to progressive pulmonary destruction.Panax ginsengis a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD. Ginsenoside Rg1 is one of the main active components and was shown to inhibit oxidative stress and inflammation. The present study investigated the hypothesis that ginsenoside Rg1 attenuates EMT in COPD rats induced by cigarette smoke (CS) and human bronchial epithelial (HBE) cells exposed to cigarette smoke extract (CSE). Our data showed that CS or CSE exposure increased expression of the mesenchymal markerα-smooth muscle actin (α-SMA) and decreased expression of the epithelial marker epithelial cadherin (E-cad) in both lung tissues and HBE cells, which was markedly suppressed by ginsenoside Rg1. Importantly, CS-induced upregulation of TGF-β1/Smad pathway components, including TGF-β1, TGF-βR1, phospho-Smad2, and phospho-Smad3, was also inhibited by ginsenoside Rg1. Additionally, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-βR1-Smad2/3 inhibitor, on suppression of EMT in CSE-induced HBE cells. Collectively, we concluded that ginsenoside Rg1 alleviates CS-induced pulmonary EMT, in both COPD rats and HBE cells, via inhibition of the TGF-β1/Smad pathway.

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