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1.
An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions.
Mahmoud, AM
International journal of molecular sciences. 2022;(3)
Abstract
Obesity has become a global epidemic that has a negative impact on population health and the economy of nations. Genetic predispositions have been demonstrated to have a substantial role in the unbalanced energy metabolism seen in obesity. However, these genetic variations cannot entirely explain the massive growth in obesity over the last few decades. Accumulating evidence suggests that modern lifestyle characteristics such as the intake of energy-dense foods, adopting sedentary behavior, or exposure to environmental factors such as industrial endocrine disruptors all contribute to the rising obesity epidemic. Recent advances in the study of DNA and its alterations have considerably increased our understanding of the function of epigenetics in regulating energy metabolism and expenditure in obesity and metabolic diseases. These epigenetic modifications influence how DNA is transcribed without altering its sequence. They are dynamic, reflecting the interplay between the body and its surroundings. Notably, these epigenetic changes are reversible, making them appealing targets for therapeutic and corrective interventions. In this review, I discuss how these epigenetic modifications contribute to the disordered energy metabolism in obesity and to what degree lifestyle and weight reduction strategies and pharmacological drugs can restore energy balance by restoring normal epigenetic profiles.
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2.
Resolving trained immunity with systems biology.
Koeken, VACM, van Crevel, R, Netea, MG, Li, Y
European journal of immunology. 2021;(4):773-784
Abstract
Trained immunity is characterized by long-term functional reprogramming of innate immune cells following challenge with pathogens or microbial ligands during infection or vaccination. This cellular reprogramming leads to increased responsiveness upon restimulation, and is mediated through epigenetic and metabolic modifications. In this review, we describe how molecular mechanisms underlying trained immunity, for example, induced by β-glucan or Bacille Calmette-Guérin (BCG) vaccination, can be investigated by using and integrating different layers of information including genome, epigenome, transcriptome, proteome, metabolome, microbiome, immune cell phenotyping, and function. We also describe the most commonly used experimental and computational techniques. Finally, we provide a number of examples of how a systems biology approach was applied to study trained immunity to understand interindividual variation or the complex interplay between molecular layers. In conclusion, trained immunity represents an opportunity for regulating innate immune function, and understanding the complex interplay of mechanisms that mediate trained immunity might enable us to employ it as a clinical tool in the future.
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3.
Plant flavone Chrysin as an emerging histone deacetylase inhibitor for prosperous epigenetic-based anticancer therapy.
Ganai, SA, Sheikh, FA, Baba, ZA
Phytotherapy research : PTR. 2021;(2):823-834
Abstract
Aberrations in epigenetic mechanisms provide a fertile platform for tumour initiation and progression. Thus, agents capable of modulating the epigenetic environment of neoplasms will be a valuable addition to the anticancer therapeutics. Flavones are emerging as befitting anticancer agents due to their inherent antioxidant activity and the ability to restrain epi-targets namely histone deacetylases (HDACs). HDACs have broader implications in pathogenesis of various cancers. Chrysin, a flavone possessing the ability to inhibit HDACs could prove as a potential anticancer drug. Thus, in this article we focussed on Chrysin and its distinct antineoplastic effect against bellicose malignancies including lung, colorectal, cervical, gastric, melanoma, hepatocellular carcinoma and breast cancer. The underlying signalling cascades triggered by Chrysin for inducing cytotoxic effect in these cancer models are discussed. Importantly, approaches towards combinatorial treatments by Chrysin and commercial anticancer agents are taken into account. The downstream molecular mechanism aroused by combined therapy for abrogating onerous cancer chemoresistance is delineated as well. Moreover, the nano-combinatorial approach involving co-encapsulation of Chrysin with other herbal and non-herbal agents for clinical excellence is elucidated.
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4.
Role of Phytonutrients in Nutrigenetics and Nutrigenomics Perspective in Curing Breast Cancer.
Bhattacharya, T, Dutta, S, Akter, R, Rahman, MH, Karthika, C, Nagaswarupa, HP, Murthy, HCA, Fratila, O, Brata, R, Bungau, S
Biomolecules. 2021;(8)
Abstract
Breast cancer (BC) is one of the most common type of cancer and an important contributor to female mortality. Several genes and epigenetic modifications are involved in the development and progression of BC. Research in phytochemistry, nutrigenomics, and nutrigenetics has provided strong evidence that certain phytonutrients are able to modulate gene expression at transcriptional and post-transcriptional levels. Such phytonutrients may also be beneficial to prevent and treat BC. In this review, we will focus on the nutrigenomic effects of various phytochemicals including polyphenols, phytosterols, terpenoids, alkaloids, and other compounds from different sources. Overall, these phytonutrients are found to inhibit BC cell proliferation, differentiation, invasion, metastasis, angiogenesis, and induce apoptotic cell death by targeting various molecular pathways. They also alter epigenetic mechanisms and enhance the chemosensitivity and radiosensitivity of cancer cells. Such phytochemicals may be used for the effective management of BC patients in the clinical setting in the future. The present article aims to summarize the specific molecular pathways involved in the genetic effects of phytochemicals in BC.
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5.
Potential effects of nutrition-based weight loss therapies in reversing obesity-related breast cancer epigenetic marks.
Lorenzo, PM, Crujeiras, AB
Food & function. 2021;(4):1402-1414
Abstract
Obesity is a modifiable risk factor of breast cancer and epigenetic marks were proposed as a relevant mechanistic link. These mechanisms can be remodelled by modifying lifestyle factors and this fact could be useful in the treatment of obesity-related breast cancer. This review aimed to reveal the current evidence on the effects of differences in body composition and lifestyle factors on the risk, treatment, and survival of breast cancer with a focus on the effects of weight loss therapies based on different nutrients, bioactive compounds, and Mediterranean and ketogenic diets to counteract obesity-related breast cancer epigenetic marks. This review was framed on the most relevant and recently published articles and abstracts selected in PubMed using key words related to epigenetics, lifestyle, dietary habits, nutrients, bioactive compounds, ketone bodies, and weight loss treatments in obesity and breast cancer. Several studies have demonstrated that lifestyle interventions, including dietary modifications towards a healthy diet pattern, are effective therapies to prevent the onset of breast cancer and to improve the survival after treatment. These therapies reduce the main factors associated with obesity that are links between adiposity and cancer, including oxidative stress, inflammation and epigenetic mechanisms. However, although sufficient evidence exists regarding the effects of nutrients, dietary patterns, and weight loss therapies to prevent breast cancer or to improve survival, the effects of these strategies on the oncological treatment response were less studied. This review summarises the current scientific evidence regarding these nutritional strategies as adjuvant therapies in the management of obesity-related breast cancer by remodelling epigenetic marks related to carcinogenesis.
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6.
The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation.
Sartorius, K, An, P, Winkler, C, Chuturgoon, A, Li, X, Makarova, J, Kramvis, A
Frontiers in immunology. 2021;:661204
Abstract
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication and survival. A key tool in its arsenal, is the HBx protein which can manipulate the epigenetic landscape to decrease its own viral load and enhance persistence, as well as manage host genome epigenetic responses to the presence of viral infection. The HBx protein can initiate epigenetic modifications to dysregulate miRNA expression which, in turn, can regulate downstream epigenetic changes in HBV-HCC pathogenesis. We attempt to link the HBx and miRNA induced epigenetic modulations that influence both the HBV and host genome expression in HBV-HCC pathogenesis. In particular, the review investigates the interplay between CHB infection, the silencing role of miRNA, epigenetic change, immune system expression and HBV-HCC pathogenesis. The review demonstrates exactly how HBx-dysregulated miRNA in HBV-HCC pathogenesis influence and are influenced by epigenetic changes to modulate both viral and host genome expression. In particular, the review identifies a specific subset of HBx induced epigenetic miRNA pathways in HBV-HCC pathogenesis demonstrating the complex interplay between HBV infection, epigenetic change, disease and immune response. The wide-ranging influence of epigenetic change and miRNA modulation offers considerable potential as a therapeutic option in HBV-HCC.
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7.
Brain on food: The neuroepigenetics of nutrition.
Vaziri, A, Dus, M
Neurochemistry international. 2021;:105099
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Abstract
Humans have known for millennia that nutrition has a profound influence on health and disease, but it is only recently that we have begun mapping the mechanisms via which the dietary environment impacts brain physiology and behavior. Here we review recent evidence on the effects of energy-dense and methionine diets on neural epigenetic marks, gene expression, and behavior in invertebrate and vertebrate model organisms. We also discuss limitations, open questions, and future directions in the emerging field of the neuroepigenetics of nutrition.
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8.
ABA and Bud Dormancy in Perennials: Current Knowledge and Future Perspective.
Pan, W, Liang, J, Sui, J, Li, J, Liu, C, Xin, Y, Zhang, Y, Wang, S, Zhao, Y, Zhang, J, et al
Genes. 2021;(10)
Abstract
Bud dormancy is an evolved trait that confers adaptation to harsh environments, and affects flower differentiation, crop yield and vegetative growth in perennials. ABA is a stress hormone and a major regulator of dormancy. Although the physiology of bud dormancy is complex, several advancements have been achieved in this field recently by using genetics, omics and bioinformatics methods. Here, we review the current knowledge on the role of ABA and environmental signals, as well as the interplay of other hormones and sucrose, in the regulation of this process. We also discuss emerging potential mechanisms in this physiological process, including epigenetic regulation.
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9.
Epigenetic Therapies for Heart Failure: Current Insights and Future Potential.
Napoli, C, Bontempo, P, Palmieri, V, Coscioni, E, Maiello, C, Donatelli, F, Benincasa, G
Vascular health and risk management. 2021;:247-254
Abstract
Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy ("epidrugs") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.
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10.
COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks.
Kgatle, MM, Lawal, IO, Mashabela, G, Boshomane, TMG, Koatale, PC, Mahasha, PW, Ndlovu, H, Vorster, M, Rodrigues, HG, Zeevaart, JR, et al
Frontiers in immunology. 2021;:752380
Abstract
The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID-19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation, and progression.