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1.
Epigenetics/epigenomics and prevention by curcumin of early stages of inflammatory-driven colon cancer.
Wu, R, Wang, L, Yin, R, Hudlikar, R, Li, S, Kuo, HD, Peter, R, Sargsyan, D, Guo, Y, Liu, X, et al
Molecular carcinogenesis. 2020;(2):227-236
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Abstract
Colorectal cancer (CRC) is associated with significant morbidity and mortality in the US and worldwide. CRC is the second most common cancer-related death in both men and women globally. Chronic inflammation has been identified as one of the major risk factors of CRC. It may drive genetic and epigenetic/epigenomic alterations, such as DNA methylation, histone modification, and non-coding RNA regulation. Current prevention modalities for CRC are limited and some treatment regimens such as use the nonsteroidal anti-inflammatory drug aspirin may have severe side effects, namely gastrointestinal ulceration and bleeding. Therefore, there is an urgent need of developing alternative strategies. Recently, increasing evidence suggests that several dietary cancer chemopreventive phytochemicals possess anti-inflammation and antioxidative stress activities, and may prevent cancers including CRC. Curcumin (CUR) is the yellow pigment that is found in the rhizomes of turmeric (Curcuma longa). Many studies have demonstrated that CUR exhibit strong anticancer, antioxidative stress, and anti-inflammatory activities by regulating signaling pathways, such as nuclear factor erythroid-2-related factor 2, nuclear factor-κB, and epigenetics/epigenomics pathways of histones modifications, and DNA methylation. In this review, we will discuss the latest evidence in epigenetics/epigenomics alterations by CUR in CRC and their potential contribution in the prevention of CRC.
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Mechanisms and individuality in chromium toxicity in humans.
Pavesi, T, Moreira, JC
Journal of applied toxicology : JAT. 2020;(9):1183-1197
Abstract
With regards to health, chromium (Cr) is an ambiguous chemical element. Although it is considered to be an important micronutrient, it also is connected with several pathologies, including carcinogenicity. The mechanism of action of Cr and its compounds in humans is not yet fully understood. Currently, three possible mechanisms have been proposed for carcinogenesis: Cr(VI)-induced multistage carcinogenesis, genomic instability, and epigenetic modification. Therefore, in addition to the toxicity of this metal and its ions, human susceptibility to Cr-induced pathologies depends on external factors and individual characteristics, such as enzymatic polymorphisms, carriers, endogenous reducing system, adduct formation and stability, and efficiency of DNA repair mechanisms, among other factors. In fact, the variability of individual molecular constitutive factors, such as individual polymorphisms, creates an individualized environment for Cr toxicity. This mini-review contemplates the essential variables in this process.
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Maternal Prenatal Exposures in Pregnancy and Autism Spectrum Disorder: An Insight into the Epigenetics of Drugs and Diet as Key Environmental Influences.
Bastaki, KN, Alwan, S, Zahir, FR
Advances in neurobiology. 2020;:143-162
Abstract
Autism spectrum disorder (ASD) is a rapidly growing global pandemic that affects an estimated 1 in 59-68 children. It is a complex disease with both genetic and environmental etiologies. Due to the rapid increase in the incidence of ASD, environmental causes for ASD are gaining attention. Efforts to probe several environmental exposures that could contribute to causing ASD are underway. In this regard, this chapter is directed towards understanding prenatal exposure to key environmental factors i.e., drugs and dietary nutrients that may act via the same molecular pathway - epigenetics as a potential etiological factor for ASD. Epigenetic regulation is a molecular mechanism known to be a significant contributor to neurodevelopmental disorders. It also offers a means to explain how environmental exposures can impact genetics. We discuss the impact of maternal exposures to certain drugs, and dietary intake, on the developing fetus during pregnancy. Maternal Exposure to some drugs during gestation are associated with a higher risk of ASD, while exposure to other dietary compounds may offer promise to rescue epigenetic regulatory insults related to ASD. However, more work in this important area is still required, nevertheless preliminary research already has important implications in the understanding, prevention and treatment of ASD.
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Epigenetic Patterns in Five-Year-Old Children Exposed to a Low Glycemic Index Dietary Intervention during Pregnancy: Results from the ROLO Kids Study.
Geraghty, AA, Sexton-Oates, A, O'Brien, EC, Saffery, R, McAuliffe, FM
Nutrients. 2020;(12)
Abstract
A range of in utero and early-life factors can influence offspring epigenetics, particularly DNA methylation patterns. This study aimed to investigate the influence of a dietary intervention and factors in pregnancy on offspring epigenetic profile at five years of age. We also explored associations between body composition and methylation profile in a cross-sectional analysis. Sixty-three five-year-olds were selected from the ROLO Kids Study, a Randomized controlled trial Of a LOw glycemic index dietary intervention from the second trimester of pregnancy. DNA methylation was investigated in 780,501 CpG sites in DNA isolated from saliva. Principal component analysis identified no association between maternal age, weight, or body mass index (BMI) during pregnancy and offspring DNA methylation (p > 0.01). There was no association with the dietary intervention during pregnancy, however, gene pathway analysis identified functional clusters involved in insulin secretion and resistance that differed between the intervention and control. There were no associations with child weight or adiposity at five years of age; however, change in weight from six months was associated with variation in methylation. We identified no evidence of long-lasting influences of maternal diet or factors on DNA methylation at age five years. However, changes in child weight were associated with the methylome in childhood.
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Wandering along the epigenetic timeline.
Topart, C, Werner, E, Arimondo, PB
Clinical epigenetics. 2020;(1):97
Abstract
BACKGROUND Increasing life expectancy but also healthspan seems inaccessible as of yet but it may become a reality in the foreseeable future. To extend lifespan, it is essential to unveil molecular mechanisms involved in ageing. As for healthspan, a better understanding of the mechanisms involved in age-related pathologies is crucial. MAIN BODY We focus on the epigenetic side of ageing as ageing is traced by specific epigenetic patterns and can be measured by epigenetic clocks. We discuss to what extent exposure to environmental factor, such as alcohol use, unhealthy diet, tobacco and stress, promotes age-related conditions. We focused on inflammation, cancer and Alzheimer's disease. Finally, we discuss strategies to reverse time based on epigenetic reprogramming. CONCLUSIONS Reversibility of the epigenetic marks makes them promising targets for rejuvenation. For this purpose, a better understanding of the epigenetic mechanisms underlying ageing is essential. Epigenetic clocks were successfully designed to monitor these mechanisms and the influence of environmental factors. Further studies on age-related diseases should be conducted to determine their epigenetic signature, but also to pinpoint the defect in the epigenetic machinery and thereby identify potential therapeutic targets. As for rejuvenation, epigenetic reprogramming is still at an early stage.
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Epigenetic Regulators of Mesenchymal Stem/Stromal Cell Lineage Determination.
Cakouros, D, Gronthos, S
Current osteoporosis reports. 2020;(5):597-605
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Abstract
PURPOSE OF REVIEW Although many signalling pathways have been discovered to be essential in mesenchymal stem/stromal (MSC) differentiation, it has become increasingly clear in recent years that epigenetic regulation of gene transcription is a vital component of lineage determination, encompassing diet, lifestyle and parental influences on bone, fat and cartilage development. RECENT FINDINGS This review discusses how specific enzymes that modify histone methylation and acetylation or DNA methylation orchestrate the differentiation programs in lineage determination of MSC and the epigenetic changes that facilitate development of bone related diseases such as osteoporosis. The review also describes how environmental factors such as mechanical loading influence the epigenetic signatures of MSC, and how the use of chemical agents or small peptides can regulate epigenetic drift in MSC populations during ageing and disease. Epigenetic regulation of MSC lineage commitment is controlled through changes in enzyme activity, which modifies DNA and histone residues leading to alterations in chromatin structure. The co-ordinated epigenetic regulation of transcriptional activation and repression act to mediate skeletal tissue homeostasis, where deregulation of this process can lead to bone loss during ageing or osteoporosis.
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Germ cell-mediated mechanisms of epigenetic inheritance.
Lempradl, A
Seminars in cell & developmental biology. 2020;:116-122
Abstract
It is well established that lifestyle and other environmental factors have the potential to shape our own health and future. Research from the last two decades, however, provides mounting evidence that parental exposures or experiences such as dietary challenges, toxin exposure, or stress can impact the health and future of our offspring. There are indications that both the paternal and maternal germline are able to store information of the parental environment and pass certain information on to their progeny. These intergenerational effects are mediated by epigenetic mechanisms. This review summarizes and discusses insights into germline epigenetic plasticity caused by environmental stimuli and how such alterations are transmitted to induce a stable phenotype in the offspring.
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Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer.
Selvakumar, P, Badgeley, A, Murphy, P, Anwar, H, Sharma, U, Lawrence, K, Lakshmikuttyamma, A
Nutrients. 2020;(3)
Abstract
Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid's anti-cancer action in breast cancer. The dose is another key factor, with research showing that approximately 10 mg/day of isoflavones is required to inhibit breast cancer occurrence. In addition, flavonoids also influence the epigenetic machinery in breast cancer, with research demonstrating that epigallocatechin, genistein, and resveratrol all inhibited DNA methyltransferase and altered chromatin modification in breast cancer. These flavonoids can induce the expression of different tumor suppressor genes that may contribute to decreasing breast cancer progression and metastasis. Additional studies are required to confirm the contribution of epigenetic modifications by flavonoids to breast cancer prevention.
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Reduced Calcium Sensing Receptor (CaSR) Expression Is Epigenetically Deregulated in Parathyroid Adenomas.
Singh, P, Bhadada, SK, Dahiya, D, Arya, AK, Saikia, UN, Sachdeva, N, Kaur, J, Brandi, ML, Rao, SD
The Journal of clinical endocrinology and metabolism. 2020;(9):3015-24
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Abstract
AIM: Reduced calcium sensing receptor (CaSR) expression has been implicated in parathyroid tumorigenesis, but the underlying mechanism remains elusive. Accordingly, we aimed to explore the epigenetic changes (DNA methylation and histone modifications) involved in CaSR regulation in sporadic parathyroid adenomas and correlate epigenetic state with disease indices. EXPERIMENTAL DESIGN Forty sporadic parathyroid adenomas and 10 control parathyroid tissues were studied. Real-time quantitative PCR (qPCR) for mRNA and immunohistochemistry for protein expression of CaSR were performed. The methylation status of the CaSR promoter 2 was determined by bisulphite sequencing analysis of sodium bisulphite-converted DNA. To determine the role of histone modifications in the CaSR regulation, chromatin immunoprecipitation-qPCR assay was performed. RESULTS Real-time qPCR revealed reduced CaSR mRNA expression with a fold reduction of 0.12 (P < 0.0001) in parathyroid adenomas. Immunohistochemistry revealed reduced protein expression of CaSR in 90% (36/40) of adenomas. The promoter 2 region of CaSR displayed significant hypermethylation in 45% (18/40) of the adenomas compared with the controls (6.7%; 1 of 10) (P < 0.002). Bisulphite sequencing analysis revealed maximum methylated CpG at glial cell missing 2 binding site on the CaSR promoter 2 compared to other CpG sites. The methylation status of CaSR correlated directly with plasma intact parathyroid hormone levels in patients with parathyroid adenoma. With chromatin immunoprecipitation-qPCR analysis, H3K9me3 levels showed increased enrichment by 10-fold in adenomas and correlated with CaSR-mRNA expression (r = 0.61; P < 0.003). Treatment with 5-aza-2'deoxycytidine restored the expression of CaSR in a parathyroid cell line. CONCLUSION Our data suggest that hypermethylation and increased H3K9me3 of the CaSR promoter 2 are involved in silencing CaSR expression in sporadic parathyroid adenoma.
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Epigenetic regulation in plant abiotic stress responses.
Chang, YN, Zhu, C, Jiang, J, Zhang, H, Zhu, JK, Duan, CG
Journal of integrative plant biology. 2020;(5):563-580
Abstract
In eukaryotic cells, gene expression is greatly influenced by the dynamic chromatin environment. Epigenetic mechanisms, including covalent modifications to DNA and histone tails and the accessibility of chromatin, create various chromatin states for stress-responsive gene expression that is important for adaptation to harsh environmental conditions. Recent studies have revealed that many epigenetic factors participate in abiotic stress responses, and various chromatin modifications are changed when plants are exposed to stressful environments. In this review, we summarize recent progress on the cross-talk between abiotic stress response pathways and epigenetic regulatory pathways in plants. Our review focuses on epigenetic regulation of plant responses to extreme temperatures, drought, salinity, the stress hormone abscisic acid, nutrient limitations and ultraviolet stress, and on epigenetic mechanisms of stress memory.