Alcohol (Hanover, York County, Pa.)最新文献

{"title":"Effect of aging on the development and progression of alcohol-associated liver disease.","authors":"Ramesh Bellamkonda, Sundararajan Mahalingam, Ojeshvi Ethiraj, Sathish Kumar Perumal, Madan Kumar Arumugam, Daren L Knoell, Kurt W Fisher, Carol A Casey, Kusum K Kharbanda, Karuna Rasineni","doi":"10.1111/acer.70086","DOIUrl":"https://doi.org/10.1111/acer.70086","url":null,"abstract":"<p><strong>Background: </strong>There is a robust link between chronic alcohol intake and the development of alcohol-associated liver disease (ALD). Over 90% of excessive alcohol drinkers develop hepatic steatosis that can progress to an advanced liver injury state. However, this progression depends on many extrahepatic factors including age, which is also a predictor of ALD-related mortality. This study aimed to identify selected pathological changes in rats of different ages with chronic ethanol administration for the same duration to gain insights into the effects of aging in the development and progression of ALD.</p><p><strong>Methods: </strong>Male Wistar rats of young (4 months), middle (8-12 months), and older (24 months) age were pair-fed for 6 weeks with Lieber-DeCarli control or ethanol diet. At the end of the experimental period, rats were euthanized and serum and tissues (liver, gut, and adipose) were collected for analyses.</p><p><strong>Results: </strong>Chronic ethanol feeding increased serum hepatic injury markers, circulating nonesterified free fatty acids, and hepatic triglycerides across the different age groups compared to their respective controls, with the higher levels seen in the middle-aged and old ethanol-fed rats compared to young ethanol-fed rats. Further, histopathological evaluation and quantitative analysis of inflammatory and fibrotic markers revealed more progressive liver injury in older ethanol-fed rats compared to young and middle-aged counterparts. We also observed increased intestinal permeability, as indicated by lower ileal expression of tight junction proteins and higher serum endotoxin levels in older ethanol-fed rats. Aging alone adversely affected several of these injury markers in older control-fed rats compared to middle-aged and young control-fed rats.</p><p><strong>Conclusion: </strong>Our findings indicate that aging significantly influences the development of liver injury after chronic alcohol intake.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are online norms-based alcohol interventions efficacious for college students with higher social anxiety?","authors":"Katherine Walukevich-Dienst, Scott Graupensperger, Marilyn L Piccirillo, Kirstyn N Smith-LeCavalier, Jessica Acolin, Mary E Larimer","doi":"10.1111/acer.70077","DOIUrl":"https://doi.org/10.1111/acer.70077","url":null,"abstract":"<p><strong>Background: </strong>Undergraduates with higher social anxiety symptoms are at risk for co-occurring substance misuse, heavier drinking in certain contexts, and experiencing more negative alcohol-related consequences. Among undergraduates broadly, online norms-based interventions provide consistent and cost-effective reductions in alcohol use and related risks. However, research on norms-based interventions for undergraduates with higher social anxiety symptoms is limited, and less is known about the longitudinal impacts of social anxiety symptoms on the efficacy of online, norms-based alcohol interventions.</p><p><strong>Methods: </strong>Secondary analyses were conducted on data from a large randomized controlled trial (RCT) with undergraduates who reported past-month heavy episodic drinking and were randomized to an attention control or a norms-based intervention. Generalized linear models tested whether baseline social anxiety symptoms moderated the efficacy of receiving a norms-based intervention versus a nonalcohol-focused attention control condition at 3-, 6-, and 12-month follow-up.</p><p><strong>Results: </strong>Social anxiety symptoms moderated intervention efficacy on the number of typical drinks consumed and descriptive norms at 3 months, as well as injunctive norms at 3 and 12 months. However, these effects appeared to be primarily driven by the individuals with higher social anxiety symptoms in the attention control group. Overall, norms-based interventions demonstrated efficacy in reducing the number of typical drinks consumed, descriptive and injunctive norms, and negative consequences up to 12 months later, regardless of social anxiety symptoms.</p><p><strong>Conclusions: </strong>Results demonstrated that online norms-based interventions were similarly efficacious for reducing drinking, negative consequences, and normative beliefs for undergraduates, regardless of social anxiety symptoms. Further, effects were maintained up to 12 months. Thus, existing alcohol-focused brief interventions are efficacious for those with higher social anxiety symptoms, even without adaptation for social anxiety-specific concerns. Individuals with higher social anxiety symptoms who did not receive an active intervention reduced drinking beliefs and behaviors, although reductions were not maintained over time.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls.","authors":"Kaitlin R McManus, Erica N Grodin, Elizabeth Burnette, Yenashi Castillo, Karen Miotto, Michael R Irwin, Naomi Eisenberger, Lara A Ray","doi":"10.1111/acer.70090","DOIUrl":"https://doi.org/10.1111/acer.70090","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical research reveal associations between chronic alcohol use, increases in proinflammatory cytokines (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α]), and increases in alcohol consumption, alcohol craving, and negative mood. However, these findings remain largely correlational in clinical samples. Therefore, we conducted a preliminary inflammatory challenge using endotoxin in individuals with alcohol use disorder (AUD) to investigate the immune, behavioral, and brain responses to the inflammatory challenge.</p><p><strong>Methods: </strong>Participants were randomly assigned to receive a bolus intravenous injection of either low-dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Blood samples, sickness symptoms, physiology, mood, and alcohol craving were collected at baseline and hourly for 4 h postbaseline, with a neuroimaging scan occurring at 3 h postbaseline. Matched control data were used to validate the endotoxin challenge in comparison to the AUD sample.</p><p><strong>Results: </strong>Endotoxin led to an acute blunted pro-inflammatory (i.e., TNF-α, IL-6, and IL-8) response in individuals with AUD compared to controls (all p's < 0.039). Endotoxin led to decreased cue-induced craving in both the behavioral human laboratory (p = 0.03) and neuroimaging (p's < 0.01) assays. Moreover, higher levels of endotoxin-induced IL-6 were most negatively associated with decreased self-reported craving following baseline (p < 0.05) in comparison with lower levels of endotoxin-induced IL-6.</p><p><strong>Conclusions: </strong>This preliminary study provides an acute experimental manipulation of inflammatory processes associated with AUD and suggests that the short-term effects of inflammation in AUD phenomenology are multifaceted and dose-dependent.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moderation of treatment outcomes by polygenic risk for alcohol-related traits in placebo-controlled trials of topiramate","authors":"Henry R. Kranzler,&nbsp;Zeal Jinwala,&nbsp;Christal N. Davis,&nbsp;Heng Xu,&nbsp;Joanna M. Biernacka,&nbsp;Hang Zhou,&nbsp;Rachel L. Kember,&nbsp;Joel Gelernter,&nbsp;Richard Feinn","doi":"10.1111/acer.70052","DOIUrl":"10.1111/acer.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In two 12-week, randomized, placebo-controlled trials (RCTs) in individuals with alcohol use disorder (AUD), topiramate significantly reduced heavy drinking days (HDDs), and alcohol-related problems. In a secondary analysis of those findings, we examined four broad measures of genetic risk—polygenic scores (PGS)—of problematic alcohol use (PAU), drinks per week (DPW), and time to relapse to any drinking (TR) and heavy drinking (THR) as moderators of topiramate's effect on HDDs and alcohol-related problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 285 individuals with AUD (65.6% male) of European-like ancestry, who were treated with either topiramate (49.1%) or placebo (50.9%). All patients underwent genome-wide array genotyping, and PGS were calculated using summary statistics from genome-wide association studies of PAU, DPW, and TR and THR (two time-to-event outcomes among patients treated in AUD pharmacotherapy trials). We hypothesized an interaction effect in which greater genetic risk—particularly for PAU—would be associated with a greater therapeutic response to topiramate than placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As shown previously, topiramate significantly reduced both HDDs (odds ratio [OR] = 0.50, <i>p</i> &lt; 0.001) and Short Index of Problems (SIP) scores (<i>b</i> = −3.04, <i>p</i> &lt; 0.001) more than placebo. There were nonsignificant associations of higher PGS with more HDDs (OR = 1.17, 95% CI = 0.98–1.41, <i>p</i> = 0.091) and a greater reduction in HDDs in the topiramate group (OR = 0.80, 95% CI = 0.62–1.03, <i>p</i> = 0.089). There were also significant interaction effects with treatment on SIP score by PGS for PAU (<i>b</i> = −1.64, SE = 0.78, <i>p</i> = 0.033), TR (<i>b</i> = −2.16, SE = 0.72, <i>p</i> = 0.003), and TRH (<i>b</i> = −2.17, SE = 0.72, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide proof of principle for the use of alcohol-related PGS as moderators of the effects of topiramate for treating AUD. Larger RCTs of topiramate are needed to provide adequate statistical power to validate this pharmacogenetic approach to precision AUD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1297-1305"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Drinking Dashboard for alcohol-induced blackout: A randomized pilot trial","authors":"Mary Beth Miller,&nbsp;Angelo M. DiBello,&nbsp;Jennifer E. Merrill,&nbsp;Sydney D. Shoemaker,&nbsp;Katie R. Moskal,&nbsp;Kate B. Carey","doi":"10.1111/acer.70042","DOIUrl":"10.1111/acer.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol-induced “blackouts,” or memory loss for events that occur while drinking, are prevalent and problematic among young adults. They also increase motivation to change. This study developed and pilot-tested a theoretically informed digital health intervention (“Drinking Dashboard”) for alcohol-induced blackouts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were collected using qualitative (Study 1) and quantitative (Study 2) methods. Participants in both studies were young adults (ages 18–30 years) across the United States who reported alcohol-induced blackout(s) in the past month. Study 1 participants (<i>N</i> = 22, 82% female) piloted the intervention for 1 week and then completed exit interviews to refine the intervention. In Study 2 (<i>N</i> = 169, 57% female), participants were randomly assigned (1:1 ratio) to the dashboard (<i>n</i> = 87) or screen time control (<i>n</i> = 82). Research staff were masked to trial outcomes. Participants in both groups completed baseline measures, 30 days of morning reports, and a three-month follow-up. Primary outcomes included high-intensity drinking, estimated peak blood alcohol concentration (BAC), blackout frequency, and alcohol-related consequences. Analyses were conducted using multilevel generalized linear models. This study aimed to prepare for a future trial of the Drinking Dashboard intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Four of five intervention participants accessed the dashboard, and half viewed it on ≥3 weeks. Per-protocol analyses compared the 74 who accessed the dashboard to 82 control participants (<i>N</i> = 156, 58% female). Overall, 83% of participants rated the dashboard as “good” or “excellent,” and 85% recommended it for friends who need help with drinking. Both groups reported decreases in estimated peak BAC, blackouts, and consequences, with no significant group differences over time. However, dashboard participants reported greater decreases in high-intensity drinking at 3 months [est = 0.93, 95% CI (0.04, 1.82)]. No adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The Drinking Dashboard is feasible and acceptable and may reduce high-intensity drinking among young adults who experience blackouts. Results support a future trial.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1273-1285"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive changes in employment status are associated with reduced alcohol use frequency at discharge from outpatient specialty treatment","authors":"Nicholas L. Bormann,&nbsp;Tyler S. Oesterle,&nbsp;Andrea N. Weber,&nbsp;Doo-Sup Choi,&nbsp;Victor Karpyak,&nbsp;Stephan Arndt","doi":"10.1111/acer.70044","DOIUrl":"10.1111/acer.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Workforce engagement can provide structure, income, feelings of accomplishment, and personal contacts, growing an individual's recovery capital (RC). Employed individuals are also more likely to complete addiction treatment. We sought to investigate whether changes in employment status from alcohol treatment admission to discharge correlated with changes in alcohol use frequency over those time points.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Treatment Episode Dataset—Discharges (2017–2021) provided the data. Employment status (full-time, part-time, unemployed, and not in labor force) and alcohol use frequency (daily use, some use, and no use in past month) were assessed at treatment admission and discharge. Changes in alcohol use frequency during treatment were recorded as Reduction or No reduction. Logistic regression using reduced alcohol use frequency as the dependent variable included employment status at admission and discharge separately. A second analysis included employment status at both admission and discharge and their interaction term. An adjusted model included all covariates (race, ethnicity, age, education, and referral source), with its results being used to derive the marginal probabilities of reduced alcohol use frequency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 856,085 alcohol treatment admissions over the 5 years, with 221,724 (25.9%) first admissions. Transitioning from not in the labor force or unemployed to full-time saw the largest percentage of encounters decreasing alcohol use frequency: 71.9% (95% CI: 70.0–73.7) and 69.3% (95% CI: 68.1–70.5), respectively. Those remaining unemployed had the lowest reduction at 26.7% (95% CI: 26.3–27.1), with a sample reduction of 42.7% (95% CI: 42.5–42.9) overall. Far more people (60.4%) completed treatment within the Reduction group than in the No reduction group (30.2%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Findings suggest that improving employment status may be relevant for reducing alcohol use frequency. This aligns with past work showing overall improved health outcomes with lower unemployment levels. Incorporating vocational training and workforce engagement activities into outpatient treatment may help augment traditional approaches to improve an individual's RC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1286-1296"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple network dynamics and future alcohol consumption in adolescents","authors":"Clayton C. McIntyre,&nbsp;Mohammadreza Khodaei,&nbsp;Robert G. Lyday,&nbsp;Jeffrey L. Weiner,&nbsp;Paul J. Laurienti,&nbsp;Heather M. Shappell","doi":"10.1111/acer.70043","DOIUrl":"10.1111/acer.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The human brain is a highly interconnected and dynamic system. The study of neuroimaging indicators of future teen drinking has primarily focused on the activation of individual brain regions. We applied novel methodology to identify relationships between functional brain network dynamics and future drinking outcomes in non/low drinking teens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Resting-state functional magnetic resonance imaging (fMRI) time series from 17-year-old non-/low drinking participants (<i>n</i> = 295) of the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study were used to fit a Hidden semi-Markov Model (HSMM). Regions of the default mode network (DMN), salience network (SN), and central executive network (CEN), collectively known as the Triple Network, were included in modeling. The HSMM identified each participant's most likely brain state sequence through five brain states. Poisson regression models assessed relationships between occupancy time in brain states and future drinking frequency/intensity. Sex differences were assessed with permutation testing and interaction terms in regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No sex differences in network dynamics were observed. However, the relationship between occupancy times and future drinking frequency differed by sex for three brain states. Occupancy time in a state characterized by high activation in the DMN and SN, but low activation in the CEN, was negatively associated with future drinking in both sexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Brain network dynamics may be useful neural markers of teen drinking predisposition. Brain dynamics that make teens vulnerable or resilient to drinking may differ between sexes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1206-1220"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethanol-induced Nrf2 suppression in the lung is mediated by AP-1-driven expression of miR-144.","authors":"Viranuj Sueblinvong, Xian Fan, Justin Guo, Hui Tao, David M Guidot","doi":"10.1111/acer.70088","DOIUrl":"https://doi.org/10.1111/acer.70088","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorders (AUD) increase susceptibility to lung diseases. Ethanol suppresses nuclear factor erythroid 2-related factor 2 (Nrf2), impairing pulmonary antioxidant and immune defenses. We showed that HIV-mediated Nrf2 suppression in the lung is driven by miR-144. We hypothesized that ethanol similarly suppresses Nrf2 by inducing miR-144 in the lung.</p><p><strong>Methods: </strong>miR-144 expression was quantified in lungs from rats chronically fed an ethanol-containing diet and in rat alveolar epithelial cells (AEC), alveolar macrophages (AMs), and lung fibroblasts (PLF) treated with ethanol. The levels of the AP-1 subunits c-Fos and c-Jun, both total and phosphorylated, were quantified by western immunoblotting in rat PLF. The link between ethanol-induced AP-1 activation and miR-144 expression on Nrf2 and Nrf2-regulated antioxidants was then assessed using c-Fos silencing RNA and AP-1 inhibitors. The impact of manipulating miR-144 expression and/or activity on the expression of Nrf2 and two key Nrf2-dependent antioxidants in ethanol-treated PLF was evaluated.</p><p><strong>Results: </strong>miR-144 expression was increased in the lungs of chronic ethanol-fed rats, and ethanol exposure increased miR-144 expression in AEC and PLF, with a trend toward increased expression in AM. Ethanol induced both total and phosphorylated c-Fos protein and total c-Jun protein in PLF. Inhibiting AP-1 with c-Fos silencing RNA or AP-1 inhibitors blocked ethanol-induced miR-144 expression in PLF. Furthermore, RNA silencing of c-Fos or inhibiting miR-144 restored the expression of Nrf2 and the Nrf2-dependent antioxidants GCLC and NQO-1 in ethanol-treated PLF. In contrast, direct overexpression of miR-144 suppressed Nrf2, GCLC, and NQO-1, thereby reproducing the pathophysiological effects of ethanol.</p><p><strong>Conclusions: </strong>Ethanol induces miR-144 expression in the lung, mediated by AP-1 activation. These steps can be implicated in the ethanol-mediated inhibition of Nrf2 and the downstream suppression of Nrf2-dependent antioxidant and immune defenses. These results suggest that miR-144 could be a novel therapeutic target to mitigate susceptibility to acute inflammatory lung diseases in individuals with AUD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the predictive validity of alcohol-seeking following punishment-imposed abstinence in mice","authors":"Linh Tran,&nbsp;Maria Kuznetsova,&nbsp;Elizabeth E. Manning,&nbsp;Erin J. Campbell","doi":"10.1111/acer.70057","DOIUrl":"10.1111/acer.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A defining feature of alcohol use disorder that has captured the attention of fundamental researchers is “persistent use despite negative consequences.” The last two decades have seen the preclinical field adopt the use of punishment to model the adverse consequences associated with alcohol use. However, existing research has focused on rats as the model of choice and alcohol consumption as the prevailing outcome measure. Additionally, the predictive validity of these models, that is, testing currently approved FDA treatments, is yet to be realized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we examined punishment-imposed abstinence in mice using foot shock and measured reinstatement of alcohol-seeking following exposure to alcohol-associated cues and environmental contexts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We showed that mice voluntarily abstain from alcohol use when it is paired with a foot shock. Alcohol-associated cues and environmental contexts produced reinstatement of alcohol-seeking behavior. Finally, the predictive validity of our model was tested using naltrexone and varenicline, two medications to treat alcohol use disorder. Both naltrexone and varenicline reduced reinstatement of alcohol-seeking in male and female mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, these data suggest that mice can display reinstatement of alcohol-seeking behavior following voluntary abstinence, and this model could be used to identify new medications for relapse prevention induced by environmental cues and contexts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1337-1350"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docosahexaenoic acid protects against alcohol-induced constriction of cerebral arteries and inhibition of vascular smooth muscle BK channels.","authors":"Shiwani Thapa, Rika Morales, Steven Mysiewicz, Sydney Hawks, Elizabeth Tolley, Alex M Dopico, Anna N Bukiya","doi":"10.1111/acer.70073","DOIUrl":"https://doi.org/10.1111/acer.70073","url":null,"abstract":"<p><strong>Background: </strong>Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid used as a dietary supplement with health benefits. Alcohol in moderate-to-high concentrations constricts cerebral arteries and triggers brain ischemia. Here, we probed the ability of DHA to protect against alcohol action on cerebral artery diameter and on the activity of calcium-/voltage-gated potassium channels of large conductance (BKs) in vasculature.</p><p><strong>Methodology: </strong>Adult Sprague-Dawley rats received daily oral DHA supplementation for up to 18-23 weeks. Constriction of middle cerebral artery (MCA) pial branches was probed using a cranial window upon infusion of 50 mM alcohol into the cerebral circulation. DHA and alcohol were also probed ex vivo in MCAs upon vessel pressurization at 60 mmHg. DHA's effect on alcohol-induced inhibition of BK channels in MCA myocytes was probed using patch-clamp recording of BK currents at physiological membrane voltage and intracellular calcium.</p><p><strong>Results: </strong>DHA protected males but not females against alcohol-induced vasoconstriction in vivo. Oral DHA increased DHA levels in the MCA of male but not female rats. Arteries from male rats on control chow that were pressurized ex vivo and perfused with 3 μM DHA lost their constriction by alcohol. Incubation of freshly isolated myocytes of male MCAs in DHA prevented alcohol-induced inhibition of BK channels. However, DHA protection was absent when DHA was perfused to excised patches. DHA did not alter the amount of BK channel subunits within the myocyte plasmalemma of male MCAs. DHA protection against alcohol-induced constriction persisted in arteries expressing BK channel with a mutation on a previously identified fatty acid-sensing site.</p><p><strong>Conclusions: </strong>DHA protects against alcohol-induced cerebral artery constriction and BK channel inhibition in a sexually dimorphic manner via cellular mechanisms in vascular myocytes. This action of DHA is independent of changes in BK subunit membrane levels and of a previously identified fatty acid-sensing site in the BK channel.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}