scholarly journals Lung Disease Network Reveals the Impact of Comorbidity on SARS-CoV-2 Infection and Opportunities of Drug Repurposing

2020 ◽  
Author(s):  
ASIM BIKAS DAS
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Drug Repurposing ◽  
Functional Protein ◽  
Potential Threat ◽  
Protein Protein Interaction ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Clinical Conditions ◽  
The Impact

Abstract Higher mortality of COVID-19 patients with comorbidity is the formidable challenge faced by the health care system. In response to the present crisis, understanding the molecular basis of comorbidity is essential to accelerate the development of drugs. To address this, the genetic association between COVID-19 and various lung disorders was measured and notable molecular resemblance was observed. 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases topologically overlapped with COVID-19 module. This demonstrates the clustering of lung diseases with COVID-19 in the same network vicinity, indicating the potential threat for lung patients upon SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19, and clinical evidences suggest that shared molecular features probably the reason for comorbidity. Additionally, topological overlap with various lung disorders provides an opportunity to repurpose the drugs used for lung disease to hit the closely associated COVID-19 module. Further analysis showed that the functional protein-protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, were connected to several lung disorders. The network-based proximity measure identified the FDA approved targets in hijacked protein modules which can be hit by existing drugs to rescue these modules from viral possessions, and can lead to the improvement of clinical conditions.

scholarly journals Lung disease network reveals impact of comorbidity on SARS-CoV-2 infection and opportunities of drug repurposing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Asim Bikas Das
Keyword(s):  
Lung Disease ◽  
Drug Targets ◽  
Lung Diseases ◽  
Drug Repurposing ◽  
Pathway Enrichment Analysis ◽  
Functional Protein ◽  
Potential Threat ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Protein Modules

Abstract Background Higher mortality of COVID-19 patients with lung disease is a formidable challenge for the health care system. Genetic association between COVID-19 and various lung disorders must be understood to comprehend the molecular basis of comorbidity and accelerate drug development. Methods Lungs tissue-specific neighborhood network of human targets of SARS-CoV-2 was constructed. This network was integrated with lung diseases to build a disease–gene and disease-disease association network. Network-based toolset was used to identify the overlapping disease modules and drug targets. The functional protein modules were identified using community detection algorithms and biological processes, and pathway enrichment analysis. Results In total, 141 lung diseases were linked to a neighborhood network of SARS-CoV-2 targets, and 59 lung diseases were found to be topologically overlapped with the COVID-19 module. Topological overlap with various lung disorders allows repurposing of drugs used for these disorders to hit the closely associated COVID-19 module. Further analysis showed that functional protein–protein interaction modules in the lungs, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. FDA-approved targets in the hijacked protein modules were identified and that can be hit by exiting drugs to rescue these modules from virus possession. Conclusion Lung diseases are clustered with COVID-19 in the same network vicinity, indicating the potential threat for patients with respiratory diseases after SARS-CoV-2 infection. Pathobiological similarities between lung diseases and COVID-19 and clinical evidence suggest that shared molecular features are the probable reason for comorbidity. Network-based drug repurposing approaches can be applied to improve the clinical conditions of COVID-19 patients.

scholarly journals Lung Disease Network Reveals the Impact of Comorbidity on SARS-CoV-2 infection

2020 ◽  
Author(s):  
Asim Bikas Das
Keyword(s):  
Lung Diseases ◽  
Small World ◽  
Disease Association ◽  
Disease Network ◽  
Functional Protein ◽  
Protein Protein Interaction ◽  
Formidable Challenge ◽  
Small World Property ◽  
Clinical Conditions ◽  
The Impact

AbstractHigher mortality of COVID19 patients with comorbidity is the formidable challenge faced by the health care system. In response to the present crisis, understanding the molecular basis of comorbidity is essential to accelerate the development of potential drugs. To address this, we have measured the genetic association between COVID19 and various lung disorders and observed a remarkable resemblance. 141 lung disorders directly or indirectly linked to COVID19 result in a high-density disease-disease association network that shows a small-world property. The clustering of many lung diseases with COVID19 demonstrates a greater complexity and severity of SARS-CoV-2 infection. Furthermore, our results show that the functional protein-protein interaction modules involved RNA and protein metabolism, substantially hijacked by SARS-CoV-2, are connected to several lung disorders. Therefore we recommend targeting the components of these modules to inhibit the viral growth and improve the clinical conditions in comorbidity.

scholarly journals Study of the post tuberculosis lung diseases and the impact of various patient and disease related factors on its occurrence

2019 ◽  
Vol 6 (4) ◽  
pp. 1241
Author(s):  
Jayasri Helen Gali ◽  
Harsha Vardhana Varma ◽  
Aruna Kumari Badam
Keyword(s):  
Lung Disease ◽  
Urban Areas ◽  
Lung Diseases ◽  
Lung Damage ◽  
Common Symptom ◽  
Related Factors ◽  
Cross Sectional ◽  
Restrictive Lung Disease ◽  
Co Morbidity ◽  
The Impact

Background: More than fifty percent of the cured cases of pulmonary tuberculosis develop some form of chronic pulmonary dysfunction. It can present with varying degrees of lung damage, ranging from minimum functional abnormalities to severe forms of dysfunction that can be an important cause of death. Objective of the study to identify the various Post Tuberculosis Lung Diseases (PTBLDs) and to study impact of the patient and disease related factors on its occurrence.Methods: Cross-sectional, observational study was conducted in 134 adult, post tuberculosis patients, aged between 18-65 years, who have completed at least one year after the end of anti-tubercular treatment. All symptomatic post TB lung disease patients coming to the pulmonology out-patient clinic at the Apollo Institute of Medical sciences and Research were included in the study.Results: Majority were more than 50 years (35.3%) and males (59.4%). Majority were from urban areas (70.7%), low social class (72.2%), and unskilled workers (56.4%). Most common symptom was cough in 74.4% cases. Majority of the cases had symptoms from one week to one month i.e. 47.4%. Only eight cases were found out to be very prompt in reporting their symptoms. 39 cases had some or the other co-morbidity. Current chest X-ray status was normal in only three cases. Mean FEV1 was 1.38 which increased to 1.52; mean FVC was 1.23 which increased to 1.58; mean FEV1/FVC was 67.37 which increased to 72.76 after giving the bronchodilator. 78(58.6%) cases had obstructive and 27(20.3%) had restrictive lung disease. In 30 cases the disease was reversible. Majority of the cases were of pulmonary fibrosis followed by bronchiectasis.Conclusion: Further studies are needed to develop approaches for the prevention, care and treatment of patients with post TBLD.

scholarly journals Role of the Microbiome in Interstitial Lung Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Ozioma S. Chioma ◽  
Laura E. Hesse ◽  
Austin Chapman ◽  
Wonder P. Drake
Keyword(s):  
Immune Responses ◽  
Lung Disease ◽  
Microbial Communities ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Original Research ◽  
Inflammatory Conditions ◽  
Lung Health ◽  
The Impact

There are trillions of microorganisms in the human body, consisting of bacteria, viruses, fungi, and archaea; these collectively make up the microbiome. Recent studies suggest that the microbiome may serve as a biomarker for disease, a therapeutic target, or provide an explanation for pathophysiology in lung diseases. Studies describing the impact of the microorganisms found in the respiratory tract on lung health have been published and are discussed here in the context of interstitial lung diseases. Additionally, epidemiological and experimental evidence highlights the importance of cross-talk between the gut microbiota and the lungs, called the gut–lung axis. The gut-lung axis postulates that alterations in gut microbial communities may have a profound effect on lung disease. Dysbiosis in the microbial community of the gut is linked with changes in immune responses, homeostasis in the airways, and inflammatory conditions in the gastrointestinal tract itself. In this review, we summarize studies describing the role of the microbiome in interstitial lung disease and discuss the implications of these findings on the diagnosis and treatment of these diseases. This paper describes the impact of the microbial communities on the pathogenesis of lung diseases by assessing recent original research and identifying remaining gaps in knowledge.

scholarly journals Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1799
Author(s):  
Caspar Schiffers ◽  
Niki L. Reynaert ◽  
Emiel F. M. Wouters ◽  
Albert van der Vliet
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Responses ◽  
Related Disease ◽  
Age Related ◽  
The Impact ◽  
Important Enzyme

With a rapidly growing elderly human population, the incidence of age-related lung diseases such as chronic obstructive pulmonary disease (COPD) continues to rise. It is widely believed that reactive oxygen species (ROS) play an important role in ageing and in age-related disease, and approaches of antioxidant supplementation have been touted as useful strategies to mitigate age-related disease progression, although success of such strategies has been very limited to date. Involvement of ROS in ageing is largely attributed to mitochondrial dysfunction and impaired adaptive antioxidant responses. NADPH oxidase (NOX) enzymes represent an important enzyme family that generates ROS in a regulated fashion for purposes of oxidative host defense and redox-based signalling, however, the associations of NOX enzymes with lung ageing or age-related lung disease have to date only been minimally addressed. The present review will focus on our current understanding of the impact of ageing on NOX biology and its consequences for age-related lung disease, particularly COPD, and will also discuss the implications of altered NOX biology for current and future antioxidant-based strategies aimed at treating these diseases.

scholarly journals The Impact of the Synergistic Effect of Temperature and Air Pollutants on Chronic Lung Diseases in Subtropical Taiwan

2021 ◽  
Vol 11 (8) ◽  
pp. 819
Author(s):  
Da-Wei Wu ◽  
Szu-Chia Chen ◽  
Hung-Pin Tu ◽  
Chih-Wen Wang ◽  
Chih-Hsing Hung ◽  
...  
Keyword(s):  
Air Pollution ◽  
Lung Disease ◽  
Air Pollutants ◽  
Lung Diseases ◽  
Environmental Parameters ◽  
Effect Of Temperature ◽  
Cross Sectional ◽  
Chronic Lung Diseases ◽  
The Impact ◽  
The Relationship

Previous studies have suggested an association between air pollution and lung disease. However, few studies have explored the relationship between chronic lung diseases classified by lung function and environmental parameters. This study aimed to comprehensively investigate the relationship between chronic lung diseases, air pollution, meteorological factors, and anthropometric indices. We conducted a cross-sectional study using the Taiwan Biobank and the Taiwan Air Quality Monitoring Database. A total of 2889 participants were included. We found a V/U-shaped relationship between temperature and air pollutants, with significant effects at both high and low temperatures. In addition, at lower temperatures (<24.6 °C), air pollutants including carbon monoxide (CO) (adjusted OR (aOR):1.78/Log 1 ppb, 95% CI 0.98–3.25; aOR:5.35/Log 1 ppb, 95% CI 2.88–9.94), nitrogen monoxide (NO) (aOR:1.05/ppm, 95% CI 1.01–1.09; aOR:1.11/ppm, 95% CI 1.07–1.15), nitrogen oxides (NOx) (aOR:1.02/ppm, 95% CI 1.00–1.05; aOR:1.06/ppm, 95% CI 1.04–1.08), and sulfur dioxide (SO2) (aOR:1.29/ppm, 95% CI 1.01–1.65; aOR:1.77/ppm, 95% CI 1.36–2.30) were associated with restrictive and mixed lung diseases, respectively. Exposure to CO, NO, NO2, NOx and SO2 significantly affected obstructive and mixed lung disease in southern Taiwan. In conclusion, temperature and air pollution should be considered together when evaluating the impact on chronic lung diseases.

Decoding Protein-protein Interactions: An Overview

2020 ◽  
Vol 20 (10) ◽  
pp. 855-882
Author(s):  
Olivia Slater ◽  
Bethany Miller ◽  
Maria Kontoyianni
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Drug Repurposing ◽  
Protein Docking ◽  
Target Space ◽  
Protein Protein Interactions ◽  
X Ray Crystallography ◽  
Protein Protein Interaction ◽  
Interaction Sites ◽  
Long Time

Drug discovery has focused on the paradigm “one drug, one target” for a long time. However, small molecules can act at multiple macromolecular targets, which serves as the basis for drug repurposing. In an effort to expand the target space, and given advances in X-ray crystallography, protein-protein interactions have become an emerging focus area of drug discovery enterprises. Proteins interact with other biomolecules and it is this intricate network of interactions that determines the behavior of the system and its biological processes. In this review, we briefly discuss networks in disease, followed by computational methods for protein-protein complex prediction. Computational methodologies and techniques employed towards objectives such as protein-protein docking, protein-protein interactions, and interface predictions are described extensively. Docking aims at producing a complex between proteins, while interface predictions identify a subset of residues on one protein that could interact with a partner, and protein-protein interaction sites address whether two proteins interact. In addition, approaches to predict hot spots and binding sites are presented along with a representative example of our internal project on the chemokine CXC receptor 3 B-isoform and predictive modeling with IP10 and PF4.

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

scholarly journals Ageratina adenophora Inhibits Spleen Immune Function in Rats via the Loss of the FRC Network and Th1–Th2 Cell Ratio Elevation

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 309
Author(s):  
Zhihua Ren ◽  
Pei Gao ◽  
Samuel Kumi Okyere ◽  
Yujing Cui ◽  
Juan Wen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Immune Function ◽  
Tissue Sample ◽  
Th2 Cells ◽  
Sample Collection ◽  
Functional Protein ◽  
Th2 Cell ◽  
Ageratina Adenophora ◽  
Mrna And Protein Expression ◽  
The Impact

The objective of this study was to determine the impact of Ageratina adenophora (A. adenophora) on splenic immune function in a rat model. Rats were fed with 10 g/100 g normal feed and an experimental feed, which was composed of 3:7 A. adenophora powder and normal feed for 60 days. On days 14, 28, and 60, subsets of rats (n = 8 rats/group/time point) were selected for blood and spleen tissue sample collection. The results showed that the proportion of CD3+ T cells in the spleen was decreased at day 60 (vs. control). Also, mRNA and protein expression of chemokines CCL21 and CCL19 and functional protein gp38 in spleen decreased significantly versus the control at day 60. In addition, ER-TR7 antigen protein expression was also decreased at day 60. Levels of T-helper (Th)1 cells significantly increased, whereas those of Th2 cells decreased significantly versus the control at day 60 in spleen. The finding revealed that A. adenophora could affect splenic immune function in rats by altering the fibroblast reticulocyte (FRC) network, as well as by causing an imbalance in Th1/Th2 cell ratios. This research provides new insights into potential mechanisms of spleen immunotoxicity due to exposures to A. Adenophora.

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