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Diseases
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Epigenetics and Disease II
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Epigenetics and Disease II

A special issue of Diseases (ISSN 2079-9721).

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 12226

Special Issue Editor

Dr. Mark A. Brown

E-Mail Website
Guest Editor
College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1005 Campus Delivery, Fort Collins, CO 80523, USA
Interests: targeted therapy; oncology; small molecular inhibitors; monoclonal antibodies; gene targeting; protein targeting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

This Special Issue builds from the 2020 issue on the topic of “Epigenetics and Disease.” Epigenetic mechanisms regulate the broad synchronization in patterns of gene expression that ultimately dictate cellular consequences. Aberrations in these epigenetic mechanisms are known to be associated with a range of diseases. This correlation between epigenetic aberrations and disease is the continued focus of this 2021 Special Issue of Diseases. For this issue, we invite papers related to the molecular, cellular, and clinical significance of epigenetic aberrations as well as treatments based on the modulation of epigenetic mechanisms in the clinical management of disease.

Dr. Mark Brown
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diseases is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • epigenetics
  • molecular genetics
  • molecular basis of disease
  • chromatin modifications

Published Papers (4 papers)

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Editorial

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3 pages, 1344 KiB  
Editorial
Targeting NSP16 Methyltransferase for the Broad-Spectrum Clinical Management of Coronaviruses: Managing the Next Pandemic
by Ilham M. Alshiraihi, Gerald L. Klein and Mark A. Brown
Diseases 2021, 9(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9010012 - 01 Feb 2021
Cited by 3 | Viewed by 1921
Abstract
With the approval and distribution of demonstrably safe COVID-19 vaccines bearing exceptionally high efficacy profiles, it may be tempting to envision a return to “normal” in the coming months. However, if there is one lesson to be learned from the ongoing pandemic, it [...] Read more.
With the approval and distribution of demonstrably safe COVID-19 vaccines bearing exceptionally high efficacy profiles, it may be tempting to envision a return to “normal” in the coming months. However, if there is one lesson to be learned from the ongoing pandemic, it is that, in a world of evolving zoonotic viruses, we must be better prepared for the next deadly outbreak. While the acute nature of the COVID-19 pandemic demanded a highly specific approach, it is advisable to consider the breadth of seemingly endless possibilities in our approach to managing the next inevitable occurrence of an outbreak. Though there is little chance of discovering a “magic pill” to combat all future pathogens, the highly conserved nature of non-surface viral proteins exposes an “Achilles’ heel” in the structural genome of viral pathogens. Herein, we consider the potential of targeting such proteins to develop broad-spectrum therapeutics for the future. To illustrate this point, we outline the therapeutic potential of targeting the nonstructural protein 16 methyltransferase, which is conserved across most coronaviruses. Full article
(This article belongs to the Special Issue Epigenetics and Disease II)
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Research

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11 pages, 8169 KiB  
Article
Structural Analysis of SMYD3 Lysine Methyltransferase for the Development of Competitive and Specific Enzyme Inhibitors
by Dillon K. Jarrell, Kelly N. Hassell, Ilham Alshiraihi, Debbie C. Crans and Mark A. Brown
Diseases 2022, 10(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases10010004 - 29 Dec 2021
Cited by 4 | Viewed by 2651
Abstract
Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, [...] Read more.
Lysine methylation is among the key posttranslational modifications to histones that contribute to epigenetic regulation. SMYD3 is a lysine methyltransferase that is essential for the proliferation of a range of tumorigenic cells. The findings that SMYD3 is significantly upregulated in most colorectal carcinomas, hepatocellular carcinomas, and breast cell carcinomas support a model in which its aberrant expression modifies established patterns of gene expression, ultimately driving unrestrained proliferation. Herein, we dissect the unique structural features of SMYD3 relative to other SET enzymes, with an emphasis on the implications for selective design of therapeutics for the clinical management of cancer. Further, we illustrate the ability of inhibitors targeting the SET domain of SMYD3 to reduce the viability of colorectal and lung carcinoma cells. Full article
(This article belongs to the Special Issue Epigenetics and Disease II)
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16 pages, 3790 KiB  
Article
Anticancer Impact of Nitric Oxide (NO) and NO Combination with SMYD-3 Inhibitor on Breast Carcinomas
by Jenna L. Gordon, Kristin J. Hinsen, Melissa M. Reynolds and Mark A. Brown
Diseases 2021, 9(4), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040082 - 12 Nov 2021
Viewed by 2132
Abstract
Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating [...] Read more.
Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating the potential of nitric oxide (NO) and SMYD-3 inhibition, this work sought to expand upon these concepts and combine the two approaches. Both NO (from S-Nitrosoglutathione (GSNO)), termed Group 1, and a combination therapeutic, inhibitor-4 (SMYD-3 inhibitor) plus NO (from GSNO), termed Group 2, were evaluated for their efficacy on breast carcinoma cell lines MCF7 and MDA-MB-231, and the normal MCF10A breast cell line, using cellular viability, colony formation capacity, cytotoxicity, and cellular apoptosis analysis. These results indicated that, in Group 1, breast carcinoma lines MCF7 and MDA-MB-231, cells experienced a moderate reduction in cellular viability (~20–25%), a large reduction in colony formation capacity (~80–90%), a moderate increase in the relative number of dead cells, and a moderate increase in cellular apoptosis. Group 2 was significantly more impactful, with a ~50% knockdown in cellular viability, a 100% reduction in colony formation capacity, a large increase in the relative number of dead cells, and a large increase in cellular apoptosis. Additionally, Group 2 induced a very small impact on the normal MCF10A cell line. Cumulatively, this work revealed the exciting impact of this combination therapeutic, indicating its potential for clinical application and further research. Full article
(This article belongs to the Special Issue Epigenetics and Disease II)
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Other

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9 pages, 1582 KiB  
Opinion
Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics
by Abdelaziz Ghanemi, Mayumi Yoshioka and Jonny St-Amand
Diseases 2021, 9(4), 87; https://0-doi-org.brum.beds.ac.uk/10.3390/diseases9040087 - 29 Nov 2021
Cited by 16 | Viewed by 4583
Abstract
In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and [...] Read more.
In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and health problems. Both of these health problems also share exercise and a healthy lifestyle as the best therapeutic options. Importantly, ageing and obesity also have common epigenetic changes (histone modification, DNA methylation, noncoding RNAs, and chromatin remodeling) that are also impacted by exercise. This suggests that epigenetic pathways are among the mechanisms via which exercise induces its benefits, including ageing and obesity improvements. Exploring these interrelations and based on the fact that both ageing and obesity represent risk factors for each other, would lead to optimizing the available therapeutic approaches towards improved obesity management and healthy ageing. Full article
(This article belongs to the Special Issue Epigenetics and Disease II)
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