Computational Studies and Scaffold Search for APOE4 as Coronary Artery Disease Target by Virtual Screening
Lima Hazarika,
Supriyo Sen,
Jitesh Doshi
Issue:
Volume 10, Issue 2, December 2022
Pages:
49-59
Received:
17 July 2022
Accepted:
4 August 2022
Published:
17 August 2022
Abstract: Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer’s Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.
Abstract: Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is...
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Citizen Science: A Significant Contribution to Biodiversity Monitoring and Conservation
Issue:
Volume 10, Issue 2, December 2022
Pages:
60-67
Received:
15 July 2022
Accepted:
29 July 2022
Published:
24 August 2022
Abstract: The term "biodiversity" refers to the diverse variety of living things that exist in our natural environment including not just plants and animals, but also fungi and even microscopic organisms such as bacteria. Since there are still millions of species that have not been identified, the overall biodiversity of our world is immense. The biodiversity of our planet plays a significant role in ensuring the health of our ecosystems. Because of habitat destruction, industrialization, urbanization, and the ever-increasing population of humans, many animal and plant species are classified as being either vulnerable, endangered, or in imminent danger of becoming extinct. In addition, there is a high risk of extinction for a large number of species in the event that management and conservation strategies are not immediately put into effect. The goal of the initiative known as "citizen science" is to increase scientific understanding by encouraging collaboration and participation from the general public in scientific research. Individual people have the opportunity to nurture their scientific temperament in the field through involvement in citizen science, which also allows communities an ability to study nature and protect it through collective efforts. In order to monitor and conserve biodiversity together with professionals in the scientific and academic communities to develop solutions to environmental problems, it is important to establish additional citizen science projects for citizen scientists.
Abstract: The term "biodiversity" refers to the diverse variety of living things that exist in our natural environment including not just plants and animals, but also fungi and even microscopic organisms such as bacteria. Since there are still millions of species that have not been identified, the overall biodiversity of our world is immense. The biodiversit...
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Age in Impacting the Occurrence of Chronic Diseases: Case of Recurrently Diagnosed Diseases at Korhogo Regional Hospital in Northern of Cote d’Ivoire
Dago Dougba Noel,
Daramcoum Wentoin Alimata Marie-Pierre,
Dagnogo Olefongo,
Kouadio Kouassi Joel,
Kimou Adjiman Florent
Issue:
Volume 10, Issue 2, December 2022
Pages:
68-79
Received:
3 October 2022
Accepted:
26 October 2022
Published:
15 December 2022
Abstract: Background: Our previous study suggested Korhogo district as strongly influenced by parasitical and infectious diseases and as well high blood pressure (HBP) troubles. In the same study, we shown that recurrently diagnosed diseases at Korhogo Regional Hospital (KRH) clustered in two group, depending on the regular and/or irregular dynamism of their increasing. Diseases with regular increasing dynamism (i.e. hypertension) claiming to be chronic diseases were controlled by patients’ anthropomorphic parameters such as age and weight as opposite to diseases with irregular increasing frequency dynamism dominated by malaria and influenza (infectious and tropical diseases). Basing on these results, we embarked here in assessing the relationship between age anthropomorphic parameter and the occurrence of recurrently diagnosed diseases at KRH. Methods: Patients clinical and anthropomorphic parameters data (i.e. age and weight), collected from 2014 to 2018 at the general medicine division of KRH, were subsequently structured and submitted to a multivariate computational statistical analysis in R programming environment. Results: Our findings showed the strong influence of aging on the occurrence of all recurrent listed and analyzed pathologies recorded at KRH from 2014 to 2018 and in particular, on chronic diseases such as cardiovascular troubles dominated by high blood pressure (HBP), osteo-articular/muscular, metabolic diseases (diabetes) and digestive troubles. Conclusion: Considering as a whole, even if our study supported a high concordance between aging and occurrence of diseases recurrently recorded at KRH, it is noteworthy to underline the significant correlation between aging (age increasing) and chronic diseases occurrence. This trend results accentuated for chronic diseases, i.e. high blood pressure, osteo-articular and muscular diseases for age over 50 years.
Abstract: Background: Our previous study suggested Korhogo district as strongly influenced by parasitical and infectious diseases and as well high blood pressure (HBP) troubles. In the same study, we shown that recurrently diagnosed diseases at Korhogo Regional Hospital (KRH) clustered in two group, depending on the regular and/or irregular dynamism of their...
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