Dysregulation of epigenetic mechanisms, including DNA methylation, hydroxymethylation, histone modifications, and the control of microRNAs and long non-coding RNAs, has been implicated in Alzheimer's disease. Subsequently, epigenetic mechanisms have proven to be fundamental in the development of memory, using DNA methylation and post-translational alterations to histone tails as the defining epigenetic markers. AD-related gene alterations are causal factors in the disease's pathogenesis, specifically impacting the transcriptional regulation of AD The current chapter provides an overview of the role of epigenetics in the onset and progression of Alzheimer's disease and the potential for epigenetic-based therapies to alleviate the difficulties associated with the disease.
Higher-order DNA structure and gene expression are dictated by epigenetic mechanisms, including DNA methylation and histone modifications. Epigenetic abnormalities are implicated in the development of various diseases, including the insidious onset of cancer. Chromatin irregularities were, in the past, deemed limited to specific DNA segments, often associated with unusual genetic conditions. However, present-day discoveries have unveiled widespread alterations in the epigenetic machinery, improving our grasp of the underlying mechanisms involved in both developmental and degenerative neuronal disorders associated with pathologies such as Parkinson's disease, Huntington's disease, epilepsy, and multiple sclerosis. Epigenetic variations in various neurological diseases are explored within this chapter, which then delves into their potential for shaping novel therapeutic interventions.
DNA methylation fluctuations, histone alterations, and the roles of non-coding RNAs (ncRNAs) are frequently observed across various diseases and epigenetic component mutations. By distinguishing the contributions of driving and passenger epigenetic factors, one can identify diseases where epigenetics has a critical impact on the assessment of disease, forecasting its progression, and guiding its treatment. Additionally, a combined intervention strategy will be formulated by investigating the intricate relationships between epigenetic components and other disease pathways. The cancer genome atlas project, a comprehensive study of specific cancer types, has uncovered a pattern of frequent mutations in genes linked to epigenetic components. Alterations in DNA methylase and demethylase activity, changes to the cytoplasm and its composition, and genes crucial for chromatin and chromosomal architecture are affected. The metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) further affect histone and DNA methylation, disrupting the 3D genome's structure, and ultimately impacting the metabolic genes IDH1 and IDH2. Cancerous growth can be triggered by the presence of recurring DNA motifs. The 21st century has seen a tremendous acceleration in epigenetic research, producing both genuine excitement and optimism, and a substantial feeling of anticipation. Preventive, diagnostic, and therapeutic markers can be facilitated by novel epigenetic tools. Gene expression is modulated by precise epigenetic mechanisms, which are the focus of drug development efforts aimed at increasing gene expression. The development and use of epigenetic tools constitute a suitable and effective strategy for clinical management of diverse diseases.
Decades of research have culminated in epigenetics becoming a prominent area of study, providing insights into gene expression and its regulation. The phenomenon of stable phenotypic changes, unaccompanied by DNA sequence alterations, is a direct result of epigenetic processes. Epigenetic adjustments, encompassing DNA methylation, acetylation, phosphorylation, and other analogous processes, can impact gene expression levels without directly altering the DNA. CRISPR-dCas9-facilitated epigenome modifications, enabling the regulation of gene expression, are explored in this chapter as potential therapies for human diseases.
Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from lysine residues, found in both histone and non-histone proteins. Cancer, neurodegeneration, and cardiovascular disease are just a few of the conditions potentially influenced by the presence of HDACs. Gene transcription, cell survival, growth, and proliferation are all impacted by HDAC activity, with histone hypoacetylation acting as a defining element in the downstream chain of events. HDAC inhibitors (HDACi) epigenetically adjust gene expression via the control of acetylation. Unlike many, only a select few HDAC inhibitors have been approved by the FDA, leaving the majority presently engaged in clinical trials to assess their effectiveness against disease. see more This book chapter provides a comprehensive listing of HDAC classes and elucidates their functional roles in driving diseases like cancer, cardiovascular disease, and neurodegenerative processes. We also examine novel and promising HDACi therapeutic avenues, in relation to the current clinical context.
Epigenetic inheritance relies on the interplay of DNA methylation, post-translational chromatin modifications, and the influence of non-coding RNAs. The manifestation of new traits in various organisms, a consequence of epigenetic modifications on gene expression, has implications for the development of various diseases, including cancer, diabetic kidney disease, diabetic nephropathy, and renal fibrosis. The field of bioinformatics offers a potent toolset for epigenomic profiling analysis. A multitude of bioinformatics tools and software can be employed to analyze these epigenomic data. An abundance of online databases contain detailed data on these modifications, a significant volume of information. Sequencing and analytical techniques have expanded the scope of recent methodologies, enabling the extraction of various epigenetic data types. This data holds the key to crafting drugs that target illnesses correlated with epigenetic modifications. This chapter succinctly presents various epigenetic databases, including MethDB, REBASE, Pubmeth, MethPrimerDB, Histone Database, ChromDB, MeInfoText database, EpimiR, Methylome DB, and dbHiMo, and accompanying tools such as compEpiTools, CpGProD, MethBlAST, EpiExplorer, and BiQ analyzer, which play a crucial role in data acquisition and mechanistic analysis of epigenetic modifications.
The European Society of Cardiology (ESC) has released a new guideline for managing patients with ventricular arrhythmias and preventing sudden cardiac death. This document, referencing the 2017 AHA/ACC/HRS guideline and the 2020 CCS/CHRS position paper, formulates evidence-based recommendations for clinical practice. Despite the regular updates reflecting current scientific understanding, many aspects of these recommendations share commonalities. Even though some key recommendations remain unchanged, significant differences appear due to varied research parameters, such as the research scope, publication dates, differences in data curation and interpretation, and regional variations in pharmaceutical market conditions. The objective of this paper is to compare various recommendations, noting similarities and differences, while offering a summary of current guidelines. Particular emphasis will be placed on gaps in the evidence and future research opportunities. A key focus of the recent ESC guidelines is the increased significance of cardiac magnetic resonance, genetic testing for cardiomyopathies and arrhythmia syndromes, and the use of risk calculators for risk stratification. In the realm of genetic arrhythmia syndromes, diagnostic criteria; hemodynamically well-tolerated ventricular tachycardia management; and primary preventive implantable cardioverter-defibrillator therapies, substantial variations exist.
Strategies aiming to prevent damage to the right phrenic nerve (PN) during catheter ablation can prove difficult to execute, unproductive, and dangerous. A prospective analysis of a novel technique in patients with multidrug-refractory periphrenic atrial tachycardia was conducted. This novel approach involved single-lung ventilation, followed by an intentional pneumothorax to spare the PN. The PHRENICS hybrid technique, employing phrenic nerve relocation via endoscopy and intentional pneumothorax with carbon dioxide and single-lung ventilation, consistently shifted the PN away from the ablation target, enabling successful AT catheter ablation without complications or arrhythmia recurrence. Employing the PHRENICS hybrid ablation technique, PN mobilization is achieved, obviating the need for excessive pericardium intrusion, consequently enhancing the safety profile of catheter ablation for periphrenic AT.
Prior research has shown that cryoballoon pulmonary vein isolation (PVI) and concomitant posterior wall isolation (PWI) can provide improvements in the clinical condition of patients experiencing persistent atrial fibrillation (AF). medication overuse headache Still, the utilization of this approach in patients affected by paroxysmal atrial fibrillation (PAF) is not presently clear.
The study scrutinized the effects of cryoballoon-deployed PVI and PVI+PWI procedures on symptomatic patients with paroxysmal atrial fibrillation, considering both immediate and long-term outcomes.
A retrospective, long-term follow-up study (NCT05296824) examined the comparative effectiveness of cryoballoon pulmonary vein isolation (PVI) (n=1342) versus cryoballoon PVI combined with pulmonary vein ablation (PWI) (n=442) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The nearest-neighbor method was used to assemble a group of 11 patients, divided into those who received PVI alone and those who received PVI+PWI, ensuring similar patient characteristics.
The matched cohort totaled 320 patients, sorted into two groups of 160 patients each: one group with PVI and the other with a co-occurrence of PVI and PWI. Angioimmunoblastic T cell lymphoma A noticeable association was observed between the presence of PVI+PWI and shorter durations of cryoablation (23 10 minutes versus 42 11 minutes) and procedure times (103 24 minutes versus 127 14 minutes; P<0.0001 for both).