Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(10), P. 5170 - 5170

Published: May 13, 2021

Alcohol-related liver disease (ALD) refers to the damage occurring due excessive alcohol consumption and involves a broad spectrum of diseases that includes steatosis, steatohepatitis, hepatitis, cirrhosis, hepatocellular carcinoma (HCC). The progression ALD is mainly associated with amount duration usage; however, it also influenced by genetic, epigenetic, environmental factors. definite diagnosis based on biopsy, although several non-invasive diagnostic tools serum biomarkers have emerging roles in early detection ALD. While abstinence nutritional support remain cornerstone treatment, growing evidence has revealed therapeutic agents target oxidative stress or gut-liver axis, inflammatory response inhibition, regeneration enhancement play role management. Furthermore, microRNAs modulation mesenchymal stem cell-based therapy potential as options. This review summarizes updated understanding pathophysiology, diagnosis, novel approaches for

Language: Английский

---

Alcohol and Human Health: What Is the Evidence?

Annual Review of Food Science and Technology, Journal Year: 2020, Volume and Issue: 11(1), P. 1 - 21

Published: March 25, 2020

Alcohol consumption has long been a part of human culture. However, alcohol levels and patterns are associated with chronic diseases. Overall, light moderate (up to 14 g per day for women up 28 men) may be reduced mortality risk, mainly due risks cardiovascular disease type-2 diabetes. heavy abuse lead alcohol-use disorder, which results in physical mental diseases such as liver disease, pancreatitis, dementia, various types cancer. Risk factors disorder largely unknown. Alcohol-use frequent drinking have detrimental effects on personal health.

Language: Английский

---

Epigenetic basis of the dark side of alcohol addiction

Neuropharmacology, Journal Year: 2017, Volume and Issue: 122, P. 74 - 84

Published: Feb. 4, 2017

Language: Английский

---

The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention

Clinical Psychology Review, Journal Year: 2020, Volume and Issue: 77, P. 101830 - 101830

Published: Feb. 4, 2020

Mental disorders are highly complex and multifactorial in origin, comprising an elaborate interplay of genetic environmental factors. Epigenetic mechanisms such as DNA modifications (e.g. CpG methylation), histone acetylation) microRNAs function a translator between genes the environment. Indeed, influences exposure to stress shape epigenetic patterns, lifetime experiences continue alter genome throughout lifespan. Here, we summarize recently burgeoning body research regarding involvement aberrant signatures mediating increased vulnerability wide range mental disorders. We review current knowledge changes constitute useful markers predicting clinical response psychotherapeutic interventions, psychotherapy - potentially reverse risk patterns. Given first evidence pointing transgenerational transmission information, alterations arising from successful might be transferred future generations thus contribute prevention Findings integrated into multi-level framework highlighting challenges pertaining action implications research. Promising directions prediction, prevention, personalized treatment line with 'precision medicine' approach discussed.

Language: Английский

---

Histone Methylation Regulation in Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4654 - 4654

Published: April 28, 2021

Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation histone posttranslational modifications, which are critical for gene expression in almost all tissues brain health disease. These advances influenced much interest understanding the dysregulation of mechanisms neurodegenerative disorders. Although these disorders diverge their fundamental causes pathophysiology, several involve methylation-mediated expression. Interestingly, remodeling via specific regions has been suggested play a function neurobiology psychiatric disorders, including that related diseases. Prominently, currently brings considerable an essential player Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), Amyotrophic lateral sclerosis (ALS) drugs abuse, alcohol abuse disorder, where it may facilitate connections between genetic environmental risk factors or directly influence disease-specific pathological factors. We discussed current state methylation, therapeutic strategies, future perspectives While not somatically heritable, enzymes responsible regulation, methyltransferases demethylases neurons, dynamic reversible. They become promising potential targets treat prevent findings, along clinical data, provide links molecular-level changes behavioral differences novel avenues through epigenome be targeted early on people at

Language: Английский

---

NLRP3: a new therapeutic target in alcoholic liver disease

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 13, 2023

The liver is in charge of a wide range critical physiological processes and it plays an important role activating the innate immune system which elicits inflammatory events. Chronic ethanol exposure disrupts hepatic mechanism leads to release proinflammatory mediators such as chemokines, cytokines activation inflammasomes. fibrosis/cirrhosis involve NLRP3 inflammasome, leading destruction hepatocytes subsequent metabolic dysregulation humans. In addition, increasing evidence suggests that alcohol intake significantly modifies epigenetics, promoting development alcoholic disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, DNA methylation are crucial alcohol-evoked cell signaling affects gene expression system. Though we at beginning stage without having entire print epigenetic signature, time focus more on inflammasome modifications. Here review novel aspect ALD pathology linking inflammation highlighting modification associated with how could be therapeutic target ALD.

Language: Английский

---

Blood-based epigenome-wide association study and prediction of alcohol consumption

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 25, 2025

Abstract Alcohol consumption is an important risk factor for multiple diseases. It typically assessed via self-report, which open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used derive a more objective measure of alcohol by incorporating information from cytosine-phosphate-guanine (CpG) sites known linked the trait. Here, we explore epigenetic architecture self-reported weekly units in Generation Scotland study. We first create score (EpiScore) using elastic net penalized linear regression. effect pre-filtering CpG features ahead net, well differential patterns sex and consumed last week relative average week. The final EpiScore was trained on 16,717 individuals tested four external cohorts: Lothian Birth Cohorts (LBC) 1921 1936, Sister Study, Avon Longitudinal Study Parents Children (total N across studies > 10,000). maximum Pearson correlation between within cohort ranged 0.41 0.53. In LBC1936, higher levels had significant associations with poorer global brain imaging metrics, whereas did not. Finally, identified two novel loci Bayesian regression epigenome-wide association study consumption. Together, these findings show how DNAm can objectively characterize that associate health, unlike estimates.

Language: Английский

---

Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross‐sectional and longitudinal data

Addiction Biology, Journal Year: 2019, Volume and Issue: 26(1)

Published: Dec. 2, 2019

Abstract DNA methylation may be one of the mechanisms by which alcohol consumption is associated with risk disease. We conducted a large‐scale, cross‐sectional, genome‐wide association study and longitudinal analysis repeated measurements taken several years apart. Using Illumina HumanMethylation450 BeadChip, was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 them, these measures were using collected median 11 later. Associations between intake assessed linear mixed‐effects regression models. Independent data London Life Sciences Prospective Population (LOLIPOP) (N = 4042) Cooperative Health Research Augsburg Region (KORA) 1662) cohorts used to replicate associations discovered MCCS. Cross‐sectional analyses identified 1414 CpGs at P < 10 −7 , 1243 had not been reported previously. Of novel associations, 1078 replicated ( .05) LOLIPOP KORA data. MCCS data, we also 403 518 previously associations. Interaction suggested that stronger for women, non‐smokers, participants genetically predisposed consume less alcohol. CpGs, 530 differentially methylated former compared current drinkers. Longitudinal change observed 513 cross‐sectional Our indicates widespread changes across genome. showed status alcohol‐associated adulthood.

Language: Английский

---

Genome-wide methylation in alcohol use disorder subjects: implications for an epigenetic regulation of the cortico-limbic glucocorticoid receptors (NR3C1)

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 26(3), P. 1029 - 1041

Published: June 25, 2019

Abstract Environmental factors, including substance abuse and stress, cause long-lasting changes in the regulation of gene expression brain via epigenetic mechanisms, such as DNA methylation. We examined genome-wide methylation patterns prefrontal cortex (PFC, BA10) 25 pairs control individuals with alcohol use disorder (AUD), using Infinium ® MethylationEPIC BeadChip. identified 5254 differentially methylated CpGs ( p nominal < 0.005). Bioinformatic analyses highlighted biological processes containing genes related to stress adaptation, glucocorticoid receptor (encoded by NR3C1 ). Considering that is a stressor, we focused our attention on regions validated differential several network. Chronic drinking results significant increased exon variant 1 H , particular increase levels 5-hydroxymethylcytosine over 5-methylcytosine. These were associated reduced mRNA protein PFC, well other cortico-limbic AUD subjects when compared controls. Furthermore, show stress-responsive (e.g., CRF POMC FKBP5 ) altered PFC subjects. stress-response also changed hippocampus, region highly susceptible stress. data suggest alcohol-dependent aberrant consequent stress-related might be fundamental pathophysiology lay groundwork for treatments targeting mechanisms regulating AUD.

Language: Английский

---

Intergenerational Effects of Alcohol: A Review of Paternal Preconception Ethanol Exposure Studies and Epigenetic Mechanisms in the Male Germline

Alcoholism Clinical and Experimental Research, Journal Year: 2019, Volume and Issue: 43(6), P. 1032 - 1045

Published: March 25, 2019

While alcohol use disorder (AUD) is a highly heritable psychiatric disease, efforts to elucidate that heritability by examining genetic variation (e.g., single nucleotide polymorphisms) have been insufficient fully account for familial AUD risk. Perhaps not coincidently, there has burgeoning interest in novel nongenomic mechanisms of inheritance (i.e., epigenetics) are shaped the male or female germ cells significant lifetime experiences such as exposure chronic stress, malnutrition, drugs abuse. many epidemiological and preclinical studies long pointed role parental preconception environment offspring behavior, over last decade implicated causal relationship between environmentally sensitive sperm epigenome intergenerational phenotypes. This critical review will detail effects potential epigenetics.

Language: Английский

---