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1.
Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition.
Fabianowska-Majewska, K, Kaufman-Szymczyk, A, Szymanska-Kolba, A, Jakubik, J, Majewski, G, Lubecka, K
Nutrients. 2021;(2)
Abstract
One of the most systematically studied bioactive nutraceuticals for its benefits in the management of various diseases is the turmeric-derived compounds: curcumin. Turmeric obtained from the rhizome of a perennial herb Curcuma longa L. is a condiment commonly used in our diet. Curcumin is well known for its potential role in inhibiting cancer by targeting epigenetic machinery, with DNA methylation at the forefront. The dynamic DNA methylation processes serve as an adaptive mechanism to a wide variety of environmental factors, including diet. Every healthy tissue has a precise DNA methylation pattern that changes during cancer development, forming a cancer-specific design. Hypermethylation of tumor suppressor genes, global DNA demethylation, and promoter hypomethylation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer, including breast cancer. Curcumin has been shown to modulate epigenetic events that are dysregulated in cancer cells and possess the potential to prevent cancer or enhance the effects of conventional anti-cancer therapy. Although mechanisms underlying curcumin-mediated changes in the epigenome remain to be fully elucidated, the mode of action targeting both hypermethylated and hypomethylated genes in cancer is promising for cancer chemoprevention. This review provides a comprehensive discussion of potential epigenetic mechanisms of curcumin in reversing altered patterns of DNA methylation in breast cancer that is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Insight into the other bioactive components of turmeric rhizome as potential epigenetic modifiers has been indicated as well.
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Prenatal Air Pollution Exposure and Placental DNA Methylation Changes: Implications on Fetal Development and Future Disease Susceptibility.
Ghazi, T, Naidoo, P, Naidoo, RN, Chuturgoon, AA
Cells. 2021;(11)
Abstract
The Developmental Origins of Health and Disease (DOHaD) concept postulates that in utero exposures influence fetal programming and health in later life. Throughout pregnancy, the placenta plays a central role in fetal programming; it regulates the in utero environment and acts as a gatekeeper for nutrient and waste exchange between the mother and the fetus. Maternal exposure to air pollution, including heavy metals, can reach the placenta, where they alter DNA methylation patterns, leading to changes in placental function and fetal reprogramming. This review explores the current knowledge on placental DNA methylation changes associated with prenatal air pollution (including heavy metals) exposure and highlights its effects on fetal development and disease susceptibility. Prenatal exposure to air pollution and heavy metals was associated with altered placental DNA methylation at the global and promoter regions of genes involved in biological processes such as energy metabolism, circadian rhythm, DNA repair, inflammation, cell differentiation, and organ development. The altered placental methylation of these genes was, in some studies, associated with adverse birth outcomes such as low birth weight, small for gestational age, and decreased head circumference. Moreover, few studies indicate that DNA methylation changes in the placenta were sex-specific, and infants born with altered placental DNA methylation patterns were predisposed to developing neurobehavioral abnormalities, cancer, and atopic dermatitis. These findings highlight the importance of more effective and stricter environmental and public health policies to reduce air pollution and protect human health.
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3.
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.
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4.
Ten Years of EWAS.
Wei, S, Tao, J, Xu, J, Chen, X, Wang, Z, Zhang, N, Zuo, L, Jia, Z, Chen, H, Sun, H, et al
Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021;(20):e2100727
Abstract
Epigenome-wide association study (EWAS) has been applied to analyze DNA methylation variation in complex diseases for a decade, and epigenome as a research target has gradually become a hot topic of current studies. The DNA methylation microarrays, next-generation, and third-generation sequencing technologies have prepared a high-quality platform for EWAS. Here, the progress of EWAS research is reviewed, its contributions to clinical applications, and mainly describe the achievements of four typical diseases. Finally, the challenges encountered by EWAS and make bold predictions for its future development are presented.
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5.
Maternal Dietary Quality and Dietary Inflammation Associations with Offspring Growth, Placental Development, and DNA Methylation.
Lecorguillé, M, Teo, S, Phillips, CM
Nutrients. 2021;(9)
Abstract
The 'Developmental Origins of Health and Diseases' hypothesis posits that prenatal maternal diet influences offspring growth and later life health outcomes. Dietary assessment has focused on selected nutrients. However, this approach does not consider the complex interactions between foods and nutrients. To provide a more comprehensive approach to public health, dietary indices have been developed to assess dietary quality, dietary inflammation and risk factors for non-communicable diseases. Thus far, their use in the context of placental development is limited and associations with offspring outcomes have been inconsistent. Although epidemiological studies have focused on the role of maternal diet on foetal programming, the underlying mechanisms are still poorly understood. Some evidence suggests these associations may be driven by placental and epigenetic changes. In this narrative review, we examine the current literature regarding relationships between key validated diet quality scores (Dietary Inflammatory Index [DII], Mediterranean diet [MD], Healthy Eating Index [HEI], Alternative Healthy Eating Index [AHEI], Dietary Approaches to Stop Hypertension [DASH], Glycaemic Index [GI] and Glycaemic Load [GL]) in pregnancy and birth and long-term offspring outcomes. We summarise findings, discuss potential underlying placental and epigenetic mechanisms, in particular DNA methylation, and highlight the need for further research and public health strategies that incorporate diet quality and epigenetics.
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6.
How Dietary Factors Affect DNA Methylation: Lesson from Epidemiological Studies.
Maugeri, A, Barchitta, M
Medicina (Kaunas, Lithuania). 2020;(8)
Abstract
Over the past decades, DNA methylation has been proposed as a molecular mechanism underlying the positive or negative effects of diet on human health. Despite the number of studies on this topic is rapidly increasing, the relationship between dietary factors, changes in DNA methylation and health outcomes remains unclear. In this review, we summarize the literature from observational studies (cross-sectional, retrospective, or prospective) which examined the association of dietary factors (nutrients, foods, and dietary patterns) with DNA methylation markers among diseased or healthy people during the lifetime. Next, we discuss the methodological pitfalls by examining strengths and limitations of published studies. Finally, we close with a discussion on future challenges of this field of research, raising the need for large-size prospective studies evaluating the association between diet and DNA methylation in health and diseases for appropriate public health strategies.
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7.
Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.
Cappuccilli, M, Bergamini, C, Giacomelli, FA, Cianciolo, G, Donati, G, Conte, D, Natali, T, La Manna, G, Capelli, I
Nutrients. 2020;(5)
Abstract
Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.
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8.
RNA directed DNA methylation and seed plant genome evolution.
Wambui Mbichi, R, Wang, QF, Wan, T
Plant cell reports. 2020;(8):983-996
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Abstract
RNA Directed DNA Methylation (RdDM) is a pathway that mediates de novo DNA methylation, an evolutionary conserved chemical modification of cytosine bases, which exists in living organisms and utilizes small interfering RNA. Plants utilize DNA methylation for transposable element (TE) repression, regulation of gene expression and developmental regulation. TE activity strongly influences genome size and evolution, therefore making DNA methylation a key component in understanding divergence in genome evolution among seed plants. Multiple proteins that have extensively been studied in model plant Arabidopsis thaliana catalyze RNA dependent DNA Methylation pathway along with small interfering RNA. Several developmental functions have also been attributed to DNA methylation. This review will highlight aspects of RdDM pathway dynamics, evolution and functions in seed plants with focus on recent findings on conserved and non-conserved attributes between angiosperms and gymnosperms to potentially explain how methylation has impacted variations in evolutionary and developmental complexity among them and advance current understanding of this crucial epigenetic pathway.
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Flavonoids as Epigenetic Modulators for Prostate Cancer Prevention.
Izzo, S, Naponelli, V, Bettuzzi, S
Nutrients. 2020;(4)
Abstract
Prostate cancer (PCa) is a multifactorial disease with an unclear etiology. Due to its high prevalence, long latency, and slow progression, PCa is an ideal target for chemoprevention strategies. Many research studies have highlighted the positive effects of natural flavonoids on chronic diseases, including PCa. Different classes of dietary flavonoids exhibit anti-oxidative, anti-inflammatory, anti-mutagenic, anti-aging, cardioprotective, anti-viral/bacterial and anti-carcinogenic properties. We overviewed the most recent evidence of the antitumoral effects exerted by dietary flavonoids, with a special focus on their epigenetic action in PCa. Epigenetic alterations have been identified as key initiating events in several kinds of cancer. Many dietary flavonoids have been found to reverse DNA aberrations that promote neoplastic transformation, particularly for PCa. The epigenetic targets of the actions of flavonoids include oncogenes and tumor suppressor genes, indirectly controlled through the regulation of epigenetic enzymes such as DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC). In addition, flavonoids were found capable of restoring miRNA and lncRNA expression that is altered during diseases. The optimization of the use of flavonoids as natural epigenetic modulators for chemoprevention and as a possible treatment of PCa and other kinds of cancers could represent a promising and valid strategy to inhibit carcinogenesis and fight cancer.
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The Impact of Natural Dietary Compounds and Food-Borne Mycotoxins on DNA Methylation and Cancer.
Ghazi, T, Arumugam, T, Foolchand, A, Chuturgoon, AA
Cells. 2020;(9)
Abstract
Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.