Additional file 6 of Dissection of transcriptomic and epigenetic heterogeneity of grade 4 gliomas: implications for prognosis
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Additional file 6. Table S3. Component features in each module.Cardiovascular disease (CVD), the main complication of diabetes mellitus (DM), accounts for a high percentage of mortality in diabetic patients. Endothelial dysfunction is a major causative event in the pathogenesis of diabetes-related vascular disease and the earliest symptom of vascular injury. Epigenetic modification plays a key role in the initiation, maintenance, and progression of both endothelial dysfunction and diabetes. Epigenetic alterations respond to the environment and mediate the 'legacy effect' of uncontrolled hyperglycaemia early in the disease despite thorough glycaemic control in a phenomenon called metabolic memory. Therefore, an understanding of the integrated system of different epigenetic mechanisms in DM and its vascular complications is urgently needed. This review summarizes aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs). Understanding the connections between these processes and DM may reveal a novel potential therapeutic target for diabetic vascular complications.
Endothelial Dysfunction
Pathogenesis
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Epigenetic modifications play a fundamental role in the progression of coronary artery disease (CAD). This panoramic review aims to provide an overview of the current understanding of the epigenetic mechanisms involved in CAD pathogenesis and highlights the potential implications for personalized medicine approaches. Epigenetics is the study of heritable changes that do not influence alterations in the DNA sequence of the genome. It has been shown that epigenetic processes, including DNA/histone methylation, acetylation, and phosphorylation, play an important role. Additionally, miRNAs, lncRNAs, and circRNAs are also involved in epigenetics, regulating gene expression patterns in response to various environmental factors and lifestyle choices. In the context of CAD, epigenetic alterations contribute to the dysregulation of genes involved in inflammation, oxidative stress, lipid metabolism, and vascular function. These epigenetic changes can occur during early developmental stages and persist throughout life, predisposing individuals to an increased risk of CAD. Furthermore, in recent years, the concept of personalized medicine has gained significant attention. Personalized medicine aims to tailor medical interventions based on an individual’s unique genetic, epigenetic, environmental, and lifestyle factors. In the context of CAD, understanding the interplay between genetic variants and epigenetic modifications holds promise for the development of more precise diagnostic tools, risk stratification models, and targeted therapies. This review summarizes the current knowledge of epigenetic mechanisms in CAD and discusses the fundamental principles of personalized medicine.
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Abstract Age is well-known to be a significant factor in both disease pathology and response to treatment, yet the molecular changes that occur with age in humans remain ill-defined. Here, using transcriptome profiling of healthy human male skin, we demonstrate that there is a period of significantly elevated, transcriptome-wide expression changes occurring predominantly in middle age. Both pre and post this period, the transcriptome appears to undergo much smaller, linear changes with increasing age. Functional analysis of the transient changes in middle age suggest a period of heightened metabolic activity and cellular damage associated with NF-kappa-B and TNF signaling pathways. Through meta-analysis we also show the presence of global, tissue independent linear transcriptome changes with age which appear to be regulated by NF-kappa-B. These results suggest that aging in human skin is associated with a critical mid-life period with widespread transcriptome changes, both preceded and proceeded by a relatively steady rate of linear change in the transcriptome. The data provides insight into molecular changes associated with normal aging and will help to better understand the increasingly important pathological changes associated with aging.
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Epigenetics is a rapidly developing science that has gained a lot of interest in recent years due to the correlation between characteristic epigenetic marks and cardiovascular diseases (CVDs). Epigenetic modifications contribute to a change in gene expression while maintaining the DNA sequence. The analysis of these modifications provides a thorough insight into the cardiovascular system from its development to its further functioning. Epigenetics is strongly influenced by environmental factors, including known cardiovascular risk factors such as smoking, obesity, and low physical activity. Similarly, conditions affecting the local microenvironment of cells, such as chronic inflammation, worsen the prognosis in cardiovascular diseases and additionally induce further epigenetic modifications leading to the consolidation of unfavorable cardiovascular changes. A deeper understanding of epigenetics may provide an answer to the continuing strong clinical impact of cardiovascular diseases by improving diagnostic capabilities, personalized medical approaches and the development of targeted therapeutic interventions. The aim of the study was to present selected epigenetic pathways, their significance in cardiovascular diseases, and their potential as a therapeutic target in specific medical conditions.
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Abstract The human genome is thought to contain 100 000 genes of which a subset of approximately 15 000 to 20 000 genes is expressed in an individual cell. The set of genes expressed and the stoichiometry of the resulting messenger RNAs, together called a transcriptome, determine the phenotype of a cell, tissue, and whole organism. It is generally accepted that a transcriptome is largely determined by an interplay of hereditary and environmental factors. For example, in the CNS, a challenge from the environment, e.g. a learning or a traumatic experience may lead to an alteration of the transcriptome of target neurons. Thus, transcriptome analysis and subsequent transcriptome comparisons may reveal novel insights in the molecular mechanisms underlying complex processes such learning and memory formation.
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Epigenetic regulation of gene expression allows the organism to respond/adapt to environmental conditions without changing the gene coding sequence. Epigenetic modifications have also been found to control gene expression in various diseases, including diabetes. Epigenetic changes induced by hyperglycemia in multiple target organs contribute to metabolic memory of diabetic complications. The long-lasting development of diabetic complications even after achieving glucose control has been partly attributed to epigenetic changes in target cells. Specific epigenetic drugs might rescue chromatin conformation associated to hyperglycemia possibly slowing down the onset of diabetes-related complications. The current review will describe the updated epigenetics in diabetes that can be used to personalize a more focused treatment.
Epigenesis
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Epigenetic alterations during aging are manifested with altered gene expression linking it to lifespan regulation, genetic instability, and diseases. Diet and epigenetic modifiers exert a profound effect on the lifespan of an organism by modulating the epigenetic marks. However, our understanding of the multifactorial nature of the epigenetic process during aging and the onset of disease conditions as well as its reversal by epidrugs, diet, or environmental factors is still mystifying. This review covers the key findings in epigenetics related to aging and age-related diseases. Furthermore, it holds a discussion about the epigenetic clocks and their implications in various age-related disease conditions, including cancer. Although, epigenetics is a reversible process, how fast the epigenetic alterations can revert to normal is an intriguing question. Therefore, this article touches on the possibility of utilizing nutrition and mesenchymal stem cell secretome to accelerate the epigenetic reversal and emphasizes the identification of new therapeutic epigenetic modifiers to counter epigenetic alteration during aging.
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Epigenetic Therapy
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Epigenetics is the branch of molecular biology that studies modifications able to change gene expression without altering the DNA sequence. Epigenetic modulations include DNA methylation, histone modifications, and noncoding RNAs. These gene modifications are heritable and modifiable and can be triggered by lifestyle and nutritional factors. In recent years, epigenetic changes have been associated with the pathogenesis of several diseases such as diabetes, obesity, renal pathology, and different types of cancer. They have also been related with the pathogenesis of cardiovascular diseases including ischemic stroke. Importantly, since epigenetic modifications are reversible processes they could assist with the development of new therapeutic approaches for the treatment of human diseases. In the present review article, we aim to collect the most recent evidence concerning the impact of epigenetic modifications on the pathogenesis of ischemic stroke in both animal models and humans.
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The novel genome-wide assays of epigenetic marks have resulted in a greater understanding of how genetics and the environment interact in the development and inheritance of diabetes. Chronic hyperglycemia induces epigenetic changes in multiple organs, contributing to diabetic complications. Specific epigenetic-modifying compounds have been developed to erase these modifications, possibly slowing down the onset of diabetes-related complications. The current review is an update of the previously published paper, describing the most recent advances in the epigenetics of diabetes.
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