Alcohol (Fayetteville, N.Y.)最新文献

Alcohol-related brain damage (ARBD) constitutes a major global public health issue and is often comorbid with neuropsychiatric disorders such as Alzheimer's and Parkinson's diseases. Ferroptosis, a form of regulated cell death characterized by iron dependency and lipid peroxidation, has been implicated in the pathogenesis of various neurodegenerative disorders. However, the role and underlying mechanisms of ferroptosis in mediating ARBD and its associated neuropsychiatric dysfunctions remain largely unexplored. This study aimed to investigate whether chronic alcohol exposure induces neurodegenerative-like behavioral phenotypes in mice and to identify associated molecular alterations using a multi-omics approach. Behavioral assessments demonstrated that chronic alcohol exposure led to impairments in memory, exploratory activity, and motor coordination. Histopathological analysis revealed significant neuronal damage in the hippocampus and prefrontal cortex. Integrated proteomic and metabolomic profiling identified a significant enrichment of pathways related to ferroptosis and neurodegenerative diseases in alcohol-exposed mice. Additionally, biochemical assays further confirmed alcohol induced disruption of iron homeostasis, elevated reactive oxygen species, and disruption of lipid peroxidation-key features consistent with ferroptosis activation. Taken together, these findings indicate that chronic alcohol exposure induces behavioral deficits and neuronal injury in mice, and is associated with molecular and biochemical changes indicative of ferroptosis. This multi-omics evidence suggests ferroptosis as a plausible contributing pathway in alcohol-related brain damage, offering new directions for understanding its pathophysiology.

Alcohol withdrawal syndrome (AWS) and its severe complication, delirium tremens (DT), pose significant clinical challenges due to their unpredictable course and potential life-threatening consequences. This study aimed to evaluate serum S100B protein as a candidate biomarker for AWS, with a focus on its relationship to coexisting mental and somatic disorders, as well as the presence or absence of DT. The study included 47 male patients (age range 23-69 years, mean 44) diagnosed with AWS according to ICD-10 criteria (psychiatric evaluation) and confirmed with DSM-V diagnostic standards, alongside a control group (CG) of 40 healthy males (age range 25-62 years, mean 35). Blood samples were collected at hospital admission and after resolution of withdrawal symptoms (7days), to quantify S100B concentrations. Mental and somatic health status, as well as withdrawal severity, were assessed using validated clinical scales, including the Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar). Serum S100B levels were measured via enzyme-linked immunosorbent assay (ELISA). Notably, contrary to our initial hypothesis, higher S100B concentrations were detected in the CG compared to patients with AWS at the conclusion of the study. Additionally, patients without somatic comorbidities exhibited significantly elevated S100B levels compared to those with somatic illnesses. No significant association was observed between S100B levels and CIWA-Ar scores. These findings highlight the limited but potentially informative clinical utility of serum S100B as a biomarker for monitoring AWS progression and severity. Despite the small sample size and exploratory design, S100B measurement could contribute to more precise risk stratification and personalized management strategies in patients undergoing alcohol withdrawal. Further large-scale studies are warranted to validate these preliminary observations and explore their implications for improving clinical outcomes in AWS and DT.

Alcohol misuse is frequently linked to emotional factors such as loneliness and anxiety, with individuals often using alcohol as a coping mechanism. Difficulties in emotional regulation may further exacerbate alcohol consumption; however, the pathways connecting loneliness, anxiety, and alcohol use remain unclear. This study examines these relationships across gender and age groups. A total of 302 participants were divided into young adults (n = 164, mean age = 23.13) and older adults (n = 138, mean age = 58.21). Participants completed measures of alcohol use (AUDIT), loneliness (UCLA), trait anxiety (STAI-T), and emotional regulation difficulties (DERS). We employed t-tests, correlations, linear regression, and mediation analyses to identify predictors of alcohol use and assess the mediating role of emotional regulation. Results indicated that loneliness did not directly predict alcohol use overall but had an indirect association with alcohol consumption through emotional regulation, notably among women. In older men, loneliness directly predicted alcohol use, while no significant associations were observed in younger men. Anxiety showed both direct and indirect associations with alcohol use via emotional regulation. Among younger women, anxiety showed significant direct and indirect relationships with alcohol use, suggesting partial mediation; in older women, the association between anxiety and alcohol use was fully mediated by emotional regulation. Notably, anxiety was not significantly associated with alcohol consumption among men. These findings underscore the key role of emotional regulation in mediating the relationships of loneliness and anxiety with alcohol use, with differences by gender and age. They highlight the need for targeted interventions to enhance emotional regulation and reduce hazardous drinking, particularly among women and older adults.

East Asians can be more susceptible to heavy alcohol consumption than others, due to genetic variations. In addition, alcohol drinking has been suspected as a cause of type 2 diabetes (T2D). To clarify the integrated toxic mechanisms of alcohol on T2D in East Asians, we performed epigenome-wide association studies using methylation profiling arrays among four groups of South Korean men (N = 80): drinking (DK), diabetic (DM), both drinking and diabetic (DK + DM), and non-drinking and non-diabetic controls (Con). We screened hypermethylated or hypomethylated sites in both DK and DM, compared to Con, and found 15 more and 10 fewer methylated sites in DK + DM than in DK or DM among the screened sites. Furthermore, we confirmed the involvement of SLC8A1, IGFBP7, ZBED3, etc., in alcohol-related diseases and T2D and observed that these epigenetic sites were related to the negative regulation of chemokines, response to hexose, transport, glucose, regulation of cell communication, response to insulin, sodium ion transmembrane transport, and sodium ion transport. MUL1, GPLD1, ZBED3, and SLC8A1 showed multiple associations with these pathways. Finally, we found that some of the 25 epigenetic sites, including CCRL2 for inflammation, ACTG1 for cell shape, and NDUFB9 for oxidoreduction, were hubs of the STRING network. In conclusion, our findings suggest that alcohol-induced T2D development involves two interconnected pathophysiological mechanisms, mitochondrial dysfunction and errors in cell communication and ion transport that contribute to pancreatic β-cell failure.

Background and aims: Alcohol-associated liver disease (ALD) is a growing public health concern, and outcomes may be influenced by social determinants of health. Although social disadvantage has been linked to adverse outcomes in other diseases, its specific association with ALD-related complications is not well defined.

Approach: We conducted a retrospective cohort study using the TriNetX research network. Adults with ALD were classified as experiencing documented social deprivation based on International Classification of Diseases, 10th Revision, Clinical Modification codes for extreme poverty (Z59.5), low income (Z59.6), or living alone (Z60.2). A 1:1 propensity score matching approach balanced baseline clinical covariates. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for acute and chronic outcomes.

Results: The matched cohort included 998 patients (499 socially deprived, 499 non-deprived). Median follow-up was 1469 days in the documented social deprivation group and 1166 days in the non-deprived group. Documented social deprivation was not associated with all-cause mortality, major adverse liver outcomes, or acute pancreatitis. Socially deprived patients had higher risks of acute complications, including major adverse cardiovascular events (20.6% vs. 11.4%; HR 1.76, 95% CI 1.22-2.56), arrhythmia (24.6% vs. 15.7%; HR 1.58, 95% CI 1.13-2.22), heart failure (13.5% vs. 6.2%; HR 2.15, 95% CI 1.34-3.43), alcohol-associated hepatitis (AH) (24.7% vs. 16.2%; HR 1.44, 95% CI 1.09-1.90), and sepsis (21.8% vs. 10.2%; HR 2.03, 95% CI 1.41-2.93).

Conclusions: Documented social deprivation was associated with increased risk of acute cardiovascular, infectious, and AH complications, but not chronic liver progression or mortality, suggesting that social vulnerability differentially affects acute versus chronic outcomes in ALD.

Objectives: Binge drinking (BD) increases the risk for alcohol use disorders and other psychopathological disorders later in life. Emotion regulation (ER) deficits have been identified as a transdiagnostic risk factor, yet their role in risk trajectories is not well established. This is especially relevant in young BDs initially free of psychopathology, where emerging symptoms may shape risk trajectories toward severe alcohol use. Thus, this study examined whether ER difficulties mediate the link between BD and later alcohol severity, and whether emerging psychopathology moderates these associations during the critical developmental period of late adolescence.

Methods: A total of 192 university students (53% female) were followed over two years, from ages 18 to 20. Individuals with psychopathological symptoms or alcohol-related problems were excluded at baseline. Alcohol consumption patterns were assessed together with ER (Difficulties in Emotion Regulation Scale), and psychopathology (Brief Symptom Inventory). Mediation and moderated mediation analyses were conducted using PROCESS in SPSS.

Results: BD was associated with ER difficulties, particularly problems engaging in goal-directed behaviour. ER difficulties partially mediated the relationship between BD and later alcohol severity. Emerging psychopathological symptoms amplified both the direct effect of BD and the indirect effect through ER. Specifically, ER difficulties predicted alcohol severity only among individuals with elevated psychopathological symptoms.

Conclusions: Findings suggest that ER difficulties, especially goal-directed behaviour, mediate the progression from BD to alcohol severity, and that emerging psychopathology during late adolescence heightens this risk. Preventive interventions should target both BD and ER skills in youth, particularly those developing early psychopathological symptoms.

With its carcinogenic properties and ability to adversely affect skeletal muscle, alcohol intake before and during the development of cancer may exacerbate skeletal muscle complications like cancer cachexia. Any sex-specific effects of alcohol consumption before and during cancer also remain undefined. Presently, male and female mice were treated with a control alcohol-free liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 7 weeks. Cancer groups (either CON or ETOH), were then inoculated with C26 colon cancer cells and gastrocnemius muscles were collected ∼ 2 weeks later. Alcohol decreased bodyweight and adipose tissue weight at euthanasia in male cancer mice, but this alcohol effect was absent in females. Cancer-induced muscle atrophy was evident in the soleus, plantaris, gastrocnemius and quadriceps muscle of both male and female mice, with alcohol only augmenting these effects in the gastrocnemius of male mice. In the gastrocnemius, AMPK T172 phosphorylation (Thr172) and REDD1 content was higher with cancer in males, while in females, alcohol and cancer increased AMPK T172 and alcohol alone augmented REDD1 content. Peptide chain elongation was likely impaired by alcohol and cancer only in males as eEF2 Thr56 was elevated. Cancer, but not alcohol, led to lower phosphorylation of proteins in the mTORC1 pathway in female, but not male muscle. Protein ubiquitination was higher in alcohol-treated females but not males. Overall, male and female mice displayed divergent responses relative to their same sex controls in response to alcohol consumption before and during cancer.

Binge drinking is a drinking pattern that results in a blood alcohol concentration (BAC) of 0.08 g/dL or higher in a 2-hour period. Binge drinking rates are often highest in adolescents. Persistent adolescent binge drinking has unique consequences and can produce social, cognitive, and executive function deficits. Most of what we know about the mechanisms underlying the effects of adolescent alcohol exposure comes from rodent studies. We developed an adolescent alcohol consumption paradigm in ferrets termed Intermittent One-Bottle (IOB). Ferrets received a bottle of 5% alcohol for 24 hours (no water). Following this alcohol only day, ferrets had ad-lib access to both water and 5% alcohol (2-bottle choice) for the remaining days of the week. This 7-day cycle was repeated for 9 weeks. Animal BACs were assessed. After the drinking period, ex vivo electrophysiology recordings were collected from layer V medial prefrontal cortex (mPFC) pyramidal neurons. Average alcohol consumption on two-bottle and one-bottle days was significantly higher in males than females. Average BAC for males was above the level of legal intoxication. Males were split between heavy and light drinkers, with heavy drinkers having significantly higher alcohol consumption, BAC levels, and mPFC excitability. Despite low consumption in females, they displayed significant changes in action potential latency, onset time, and width. Our findings show for the first time that ferrets can drink voluntarily at physiological doses. Intermittent one-bottle drinking results in moderate to heavy alcohol consumption with significant sex differences.