Long-term Alcohol Research Articles

The Alleviated Effect of α-Pinene on Amidst Alcoholic Liver Injury Pathology Through Autophagy Activation in Mice

Background: Alcoholic liver damage is caused by long-term and heavy alcohol consumption, which leads to many diseases and even cancer. α-Pinene has been shown to have antioxidant and anti-inflammatory activity, however, it is still unclear the relationship between α-Pinene and alcohol-induced liver injury. The potential molecular mechanisms of α-pinene in reducing alcohol-induced liver injury in mice were investigated in this study. Materials and methods: The C57BL/6 mice were randomly divided into five groups, which were the control groups (physiological saline, 0.2mL per days), alcohol group (50% alcohol, 5 mL/kg bw/day), alcohol with low/medium/high dosage α-pinene treatment group ((7.2 mg/kg bw, 14.4 mg/kg bw, 28.8 mg/kg bw, dissolved in 50% alcohol, Separately). The dosing method for mice is via oral gavage. After 8 weeks of experimentation, mouse serum and liver were collected for further testing. Result: The increased antioxidant enzyme activities demonstrated the alleviated effect of α-pinene against alcohol-induced mouse liver injury. Moreover, in liver tissues, α-pinene promoted nucleus translocation of nuclear factor-erythroid-2-related factor 2 (NRF2) and transcription of antioxidant target genes, including heme oxygenase 1 (HMOX-1 / HO-1), NAD[P]H quinone dehydrogenase 1 (NQO-1), and glutathione S-transferase alpha 1 (Gsta-1). Meanwhile, α-pinene promoted the protein expression of autophagy-related proteins and inhibited the increase of inflammatory factors caused by chronic alcohol intake. Furthermore, α-pinene partially inhibited the activation of apoptotic signaling pathways by increasing the expression of Bcl-2 and decreasing Bax and cleaved caspase-3 proteins. Conclusion: Taken together, our results indicated that α-pinene might alleviate alcoholic liver injury by reducing lipid accumulation, enhancing anti-oxidative stress and anti-inflammatory, activating autophagy, and inhibiting cell apoptosis.

Detection of alcoholism by combining EEG local activations with brain connectivity features and Graph Neural Network

Of late, Machine Learning (ML) and Deep Learning (DL) based techniques have become popular for automated screening of long-term alcoholism using Electroencephalogram (EEG) signals. However, most of the ML and DL-based methods for alcoholism detection rely upon the features extracted from individual EEG electrodes’ signals. In fact, the existing methods do not fully exploit the inherent topological structure of brain activity. On the other hand, Brain Connectivity Analysis (BCA) being an advanced approach provides an efficient way to express the brain topology and more significantly has the capability of synchronizing the co-activation between different brain regions in the form of a brain network. In the present study, synergistic integration of individual EEG electrodes’ features relevant to alcoholism and knowledge of inherent connectivity patterns between spatially distributed electrodes were performed. This work combined both the information in the form of a graph, where the individual electrodes’ features were embedded as node features and the edges represent the connectivity information. After that, the generated alcoholic and non-alcoholic graphs were classified using Graph Neural Network (GNN). A publicly available alcoholism dataset was used to validate the proposed framework. Based on the Phase Lag Index (PLI) connectivity estimator and Graph Convolution Neural Network (GCNN) classifier, the 10-fold cross-validation substantiated the highest classification accuracy of 93.28%. Further, the effects of alcoholism in different EEG sub-bands were also investigated, where the Beta band exhibited the highest classification accuracy of 81.76% among the sub-bands. Lastly, the different aspects and design considerations of the proposed framework were analyzed thoroughly by conducting multiple experiments.

Profiling the oxylipidome in aged mice after chronic ethanol feeding: Identifying lipid metabolites as drivers of hepatocyte stress.

The global population of people over the age of 65 is increasing and expected to reach 1.5 billion by 2050. While aging is associated with a number of chronic illnesses including dementia, the underlying contribution of alcohol misuse in the elderly is understudied. Long-term chronic alcohol misuse can lead to alcohol-associated liver disease, consisting of a spectrum of pathologies, including steatosis and cirrhosis; liver disease can be rapidly accelerated by non-resolving inflammation. Despite this knowledge, the mechanistic underpinnings of dysregulated host immunity and accelerated liver disease progression in the aged by alcohol is unknown. Alcohol misuse in the elderly is on the rise and aging is associated with progressive increases in pro-inflammatory cytokine production. The goals of the current study are to characterize bioactive lipid mediators of inflammation by making use of a murine model of ethanol-induced liver disease in 3-month-old and 20-month-old mice by quantitatively profiling selected oxylipins in liver, brain and plasma. Following chronic ethanol exposure, liver injury, steatosis, and senescence markers were robustly increased in aged mice compared to young adult mice. Expression of proinflammatory cytokines and lipid metabolizing enzymes were increased in liver by both age and ethanol feeding. Lipoxygenase-derived lipid metabolites 9- and 13-hydroxy-octadecadienoic acid and 15-hydroxyeicosatetraenoic acid were increased in liver and plasma in ethanol-fed aged mice and positively correlated with liver injury. In plasma, 9,10-dihydroxy-octadecenoic acid/epoxy-octadecenoic acid plasma ratios correlated with liver injury in ethanol-fed aged mice. Finally, 15-hydroxyeicosatetraenoic acid and 9,10-dihydroxy-octadecenoic acid positively correlated between liver and plasma. Importantly, leukotriene E4, 9,10-dihydroxy-octadecenoic acid and 15-hydroxyeicosatetraenoic acid increased lipid accumulation and ER stress in cultured AML12 hepatocytes. These data highlight the complexity of lipid metabolite networks but identify key mediators that may be used for diagnostic and prognostic markers in early stages of alcohol-related liver disease in patients of all ages.

Chronic ethanol exposure induces mitochondrial dysfunction and alters gene expression and metabolism in human cardiac spheroids.

Chronic alcohol consumption in adults can induce various cardiac toxicities such as arrhythmias, cardiomyopathy, and heart failure. Prenatal alcohol exposure can increase the risk of developing congenital heart defectsamongoffspring. Understandingthe molecular mechanisms underlying long-term alcohol exposure-induced cardiotoxicity canhelpguidethedevelopmentof therapeutic strategies. Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) were engineered into cardiac spheroids and treated with clinically relevant concentrations of ethanol (17 and 50 mM) for 5 weeks. The cells were then analyzed for changes in mitochondrial features, transcriptomic and metabolomic profiles, and integrated omics outcomes. Following chronic ethanol treatment of hiPSC-CMs, a decrease in mitochondrial membrane potential and respiration and changes in expression of mitochondrial function-related genes were observed. RNA-sequencing analysis revealed changes in various metabolic processes, heart development, response to hypoxia, and extracellular matrix-related activities. Metabolomic analysis revealed dysregulation of energy metabolism and increased metabolites associated with theupregulation of inflammation. Integrated omics analysis further identified functional subclusters and revealed potentially affected pathways associated with cardiac toxicities. Chronic ethanol treatment of hiPSC-CMs resulted in overall decreased mitochondrial function, increased glycolysis, disrupted fatty acid oxidation, and impaired cardiac structural development.

Does ethyl glucuronide in hair correlate with alcohol consumption? A comparative study with other traditional biomarkers among individuals with alcohol dependence syndrome.

Ethyl glucuronide (EtG) in hair is a direct biomarker proven to be useful for the detection of chronic excessive alcohol use. This study investigated the association of self-reported alcohol consumption with traditional biomarkers: GGT, AST, ALT, CDT, and MCV in blood and a direct biomarker, hair EtG, in a total of 122 patients with alcohol dependence syndrome. The diagnostic accuracy of the biomarkers to differentiate heavy from non-heavy drinkers was also evaluated. GGT, AST, and ALT in serum were measured by Automated Chemistry Analyzer, MCV in blood was measured by Haematology Analyzer, serum CDT was analyzed by ELISA, and EtG in hair was evaluated by gas chromatography-mass spectrometry. The association between the biomarkers and the amount of alcohol consumed (self-reported) was determined using Spearman's rank correlation. All participants showed EtG level above the cut-off (0.03ng/mg). Hair EtG showed a statistically significant linear and positive correlation with the amounts (in grams) of alcohol consumed (r=0.60; p<0.001). No correlation was observed among the traditional biomarkers and the quantity of alcohol consumed. Also, EtG showed an excellent receiver operating characteristic (ROC) curve (98%) with good sensitivity (85%) and specificity (60%) to classify heavy drinkers among individuals with alcohol dependence syndrome. Hair EtG can be helpful to estimate retrospective alcohol consumption in long-term chronic alcohol consumption cases. Hair EtG also provides a reliable diagnostic test to detect heavy drinkers among individuals with alcohol dependence syndrome.

Central markers of neuroinflammation in alcohol use disorder: A meta-analysis of neuroimaging, cerebral spinal fluid, and postmortem studies.

There is emerging evidence that heavy long-term alcohol consumption may alter the neuroimmune profile. We conducted a meta-analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta-AnalysisProtocols(PRISMA-P) for AUD-related terms in combination with neuroinflammatory markers and cytokine- and chemokine-related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on postmortem and PET studies. Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (𝑄 (14)=62.02, 𝑝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (𝑑=1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11 C] PBR28 total volume of distribution (V T ) for translocator protein in the hippocampus (g=-1.95 [95% CI -2.72, -1.18], p < 0.001) of the alcohol group compared to controls. There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain.

1-Methylnicotinamide promotes hepatic steatosis in mice: A potential mechanism in chronic alcohol-induced fatty liver disease

Alcohol abuse and its related diseases are the major risk factors for human health. Alcohol-related liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Although the mechanism of ALD has been widely investigated, liver metabolites associated with long-term alcohol intake-induced hepatic steatosis have not been well explored. In this study, we aimed to investigate the role and mechanisms of 1-methylnicotinamide (1-MNA), a metabolite during nicotinamide adenine dinucleotide (NAD+) metabolism, in the pathogenesis of ALD. C57BL/6 wild-type mice were subjected to chronic alcohol feeding with or without 1-MNA (50 mg/kg/day). Our data showed that 1-MNA administration significantly enhanced chronic alcohol consumption-induced hepatic steatosis. Mechanistic studies revealed that alcohol-increased hepatic protein levels of sterol regulatory element-binding transcription factor (SREBP-1c), a key enzyme that regulates lipid lipogenesis, were enhanced in mice administered with 1-MNA, regardless of alcohol feeding. Consistently, alcohol-increased mRNA and protein levels of hepatic diacylglycerol o-acyltransferase 2 (DGAT2) and very low-density lipoprotein receptor (VLDLR) were also exacerbated by 1-MNA administration. Alcohol-induced hepatic endoplasmic reticulum (ER) stress was enhanced by 1-MNA administration, which was evidenced by increased protein levels of binding immunoglobulin protein (BIP), phosphorylated- protein kinase r-like ER kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP-homologous protein (CHOP) in the mouse liver. Overall, this study demonstrated that 1-MNA serves as a pathogenic factor in the development of ALD. Targeting liver 1-MNA levels may serve as a promising therapeutic approach for improving hepatic steatosis in ALD.

Prolonged alcohol consumption influences microRNA expression in the nucleus accumbens of the rat brain.

The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression levels of miR-let7b, miR-96, miR-182, miR-155, and the mRNA content of HMGB1, TLR3, TLR4 in the nucleus accumbens (NAc) of the brain of rats exposed to long-term alcoholization. The long-term alcoholization caused a decrease in miR-let7b, miR-96, miR-182, and TLR7 mRNA levels; this was accompanied by an increase in miR-155, TLR4, and Hmgb1 mRNA levels in the NAc of rat brain. TLR7 is functionally linked to miR-let7b. The data of a simultaneous decrease in miR-let7b and TLR7 mRNA are of interest for further studies; they may indicate on the lack of functionally significant links between Hmgb1 and the miR-let7b-TLR7 system in NAc. The existing evidence of a functional relationship between TLR4 with miR-155 and miR-182 and our observations on their expression changes during chronic alcoholization are very interesting and require further investigation. The suggestion about the development of neuroinflammatory process in NAc under prolonged alcohol exposure are relevant for studying the level of TLR gene expression in NAc, as well as the expression of miR species, which may have a functional relationship with the TLR system.

Histopathological Changes in the Myocardium Caused by Energy Drinks and Alcohol in the Mid-term and Their Effects on Skeletal Muscle Following Ischemia-reperfusion in a Rat Model.

Although energy drinks have been consumed for many years, their effects on the cardiovascular system continue to be investigated. Today, the most frequently used area of energy drinks is the entertainment sector, and this study investigates the effects of energy drinks and alcohol consumption on rats' limb and myocardium tissue. Forty Wistar Albino rats were used and divided into 4 groups. Energy drinks were given to the first group (the energy drink group), alcohol was given to the second group, and energy drinks and alcohol were given to the third group Redbull-Alcohol (RA). Blood samples, leg muscles, and heart tissues were studied after the ischemia-reperfusion model was created at the infrarenal level. In the histopathological examination of heart muscles, the damage was significantly more severe in the RA group than in the control group (P <.05). There was no significant change in the RA group in the limb muscle; however, muscle fiber abnormality was higher. The energy drink group was more prone to carbon dioxide retention and hypoxia, resulting in respiratory acidosis. (P =.05). Lactate was significantly higher in the energy drink group (P =.002). Glucose concentrations of energy drink and RA groups were higher (P =.02). The high lactate values of the energy drink group and more damaged fibers in the striated muscles in the RA group showed that they are more susceptible to ischemia. Long-term energy drinks and alcohol use may cause damage to the heart muscle and endothelium. Also, the effects of long-term alcohol and energy drink use on the respiratory system should be investigated with more specific studies.

Miniature mass spectrometer-based point-of-care assay for measuring phosphatidylethanol in blood.

We demonstrate proof-of-concept for point-of-care assessment of long-term alcohol consumption by measuring phosphatidylethanol in blood/dried blood spots with nano-electrospray ionization and MS/MS using a miniature mass spectrometer. 'Abstinence', 'moderate', and 'chronic' consumption could be distinguished rapidly for both sample types, and quantitative performance was obtained with blood (LoQ-100 ng mL-1).

The conceptual basis of addiction memory, allostasis and dual processes, and the classical therapy of addiction.

In recent years, research has yielded new information regarding the impact of intense, long-term alcohol consumption on the development of permanent changes in the central nervous system. The present study examines the mechanisms related to the existence of addiction memory, sensitization and allostasis. A dual-process model was also created, which analyses the role of conscious and automatic mechanisms in the functioning of addicts. The aim of the article is to present these mechanisms and to consider the implications of their existence for the course of therapy. The mechanisms analysed shed new light on some of the negative phenomena occurring during and after therapy, such as frequent abstinence after treatment, switching addictions, and returning to drinking after a long period of abstinence. The existence of these mechanisms should also change the character of addiction therapy, which has so far focused mainly on conscious aspects and ignored the existence of automatic ones. Attempts are already being made to implement the dual-process model in addiction therapy. A better understanding of the mechanisms resulting from the dual-process model can significantly influence perspectives regarding functioning in addiction and the course of therapy. These processes merit further research, as do possible therapeutic interventions based on them.

Cognitive deficits in alcohol dependence—A case–control analytical study

Background: Use and abuse of alcohol is well known. Its abuse, predominantly its dependence, can cause medical, psychological, and social issues. Excessive alcohol intake over time is linked to cognitive problems, including memory loss. Excessive alcohol use has been linked to significant cognitive deficits that can last even after the person stops drinking. Executive functioning impairments are most likely to impact rehabilitation outcomes in people with cognitive impairment. Aim: To study the cognitive impairments in alcohol dependence and comparing with healthy individuals. Methods: An observational, analytical case–control study was done on 30 alcohol-dependent patients after stabilization and 25 healthy individuals from July 2019 to July 2021 in a tertiary care center in Pune; all subjects after diagnosis were assessed with Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Barratt Impulsiveness Scale, Stroop Test, and the Wisconsin card sorting test (WCST). Results: The mean score on MMSE of the case group was 28.60 and the controls—29.72. The mean score on FAB of the case group was 16.45 and the controls—17.4. The mean score on BIS of the case group was 16.45 and in control 17.4. Stroop Effect score of the case group was 187.16 seconds and in control it was 146.92 seconds, all being statically significant in comparison. On the WCST, all the findings were statistically significant. Conclusion: Long-term alcohol consumption affects executive functions considerably. The current study showed significant cognitive deficits in individuals with alcohol dependence mainly in executive functions, working memory, and high impulsiveness.

LONG-TERM ALCOHOL CONSUMPTION AND STABILITY OF DAILY WORKING MEMORY PERFORMANCE IN OLD AGE

Abstract Mixed evidence of associations of alcohol consumption with cognitive aging suggested that low to moderate alcohol consumption predicts more favorable cognitive outcomes than abstinence, whereas higher consumption operates as risk factor for cognitive decline. Daily short-term fluctuations of cognitive performance have also been established as risk factor for subsequent cognitive decline. Bringing these two lines of research together, our study analyzed associations of long-term trajectories of alcohol consumption with ambulatory assessments (7 days, 6 beeps per day) of working memory (WM) performance in participants (N = 155, aged 66-69 and 86-89) followed-up from a long-term (&amp;gt;20 years) longitudinal aging study. Overall, the findings do not support the “risk-view”, because long-term alcohol consumption patterns were not found to be predictive of either individual levels or intra-individual momentary fluctuations of WM performance. Follow-up analyses will examine the combined effects of alcohol consumption with further risk factors, such as long-term declines in health.

Association of the Quantity, Duration, and Type of Alcohol Consumption on the Development of Gouty Tophi.

To examine the association of alcohol consumption with the presence and development of ultrasound (US)-detected tophi and subcutaneous tophi in a Chinese gout population. A total of 554 patients with gout who underwent US and physical examination of the most frequently involved joints in gout were included in this study. Multivariable analysis was performed to assess the associations of the duration, quantity, and type of alcohol consumption with the presence, size, and number of US-detected tophi and subcutaneous tophi. Compared to non-drinkers, excessive drinkers (>70 gm/week), long-term drinkers (≥10 years), and spirits drinkers had a greater proportion, size, and number of US-detected tophi and subcutaneous tophi (all P < 0.05). After adjusting for confounders, excessive drinking (>70 gm/week) (odds ratio [OR] 1.79 [2.00 after adjustment]), long-term alcohol consumption (≥10 years) (OR 1.96 [2.17 after adjustment]), and spirits consumption of (OR 1.81 [2.10 after adjustment]) were significantly associated with the presence of US-detected tophi and subcutaneous tophi (all P < 0.05), with the highest ORs among the identified risk factors. Among patients who already had US-detected tophi or subcutaneous tophi, moderate drinking (≤70 gm/week) was associated with larger or multiple tophi (all P < 0.05). Longer duration and higher quantity of alcohol consumption as well as spirits consumption are predictors for the development of US-detected tophi and subcutaneous tophi in patients with gout. Among individuals who have US-detected tophi and subcutaneous tophi, weekly alcohol consumption leads to the development of tophi regardless of amount consumed.

Structure and hepatoprotective activity of Usp10/NF-κB/Nrf2 pathway-related Morchella esculenta polysaccharide

The water-soluble Morchella esculenta polysaccharide 2 (MEP2) was purified and isolated from an aqueous extract of the Morchella esculenta fruiting bodies. MEP2, having a molecular weight of 959 kDa, has a →4)-α-D-Glcp-(1→ glucan backbone, and this branch was substituted at the H-6 position by an α-D-Glcp-(1 → 4)-α-D-Glcp-(1→ residue and an α-D-Glcp-(1→ residue. The hepatoprotective activity and potential mechanism of action of MEP2 were also investigated. MEP2 ameliorated severe liver damage and regulated the liver function indicators and the alcohol-related enzyme levels in chronic alcohol-induced mice. Combined with biochemical detection, the gut microbiota, metabolites, and proteomics results revealed that MEP2 regulates the levels of hepatic cytokines related to inflammatory response and oxidative stress, as well as those of intestinal Bacteroides, Oscillospira, Parabacteroides, Alistipes, and Prevotella, through the ubiquitin-specific peptidase 10 (Usp10)/nuclear factor κB (NF-κB)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway in the liver of mice induced by long-term alcohol intake. These data provide experimental evidence for the application of MEP2 in chronic alcohol-induced liver injury.

Експериментально-клінічне дослідження перебігу запального процесу м'яких тканин щелепно-лицевої ділянки на тлі хронічної алкогольної інтоксикації

The purpose of the study was to investigate, under experimental conditions, the peculiarities of the healing of infected wounds in experimental animals with long-term alcohol consumption; in patients with phlegmons of maxillofacial region against the background of alcohol intoxication, to evaluate the dynamics of hematological indices for determining the activity of the inflammatory process, predicting the course of the pathological process. Materials and methods. Experimental studies were conducted on 16 female Wistar rats weighing 80 g. The animals were divided into 2 equal groups: group I – experimental, group II – control. The water for the rats of the experimental group was replaced with beer, the alcohol content of which did not exceed 6%. 6 weeks after the start of the experiment, 2 rats from each group were removed from the experiment and material was taken for histological examination, the remaining 12 rats were anesthetized and wounds were created on the lower lip by cutting out a fragment of the mucous membrane measuring 0.4 x 0.3 cm. After the wounds were created, the animals were removed from the experiment by overdose with ether anesthesia on the 3rd and 7th day, the wounds were photographed, the mucous membrane of the lower lip was taken for histological examination. Results. In the experiment, during the histological examination of the tissues of the lower lip of rats with a model process of beer alcoholism, deformation of the sweat and sebaceous glands of the lower lip, and thinning of the epithelial layer were revealed. The healing of infected wounds of the lower lip in experimental animals was slowed down against the background of replacing drinking water with beer, and an objective decrease in proliferative processes was established. In particular, on the 7th day in the subepithelial layer, mixed cellular infiltration with lymphocytes, single leukocytes and macrophages was maintained, at the same time foci of young granulation tissue appeared in animals of the control group, which indicated the healing process. A retrospective analysis of 50 case histories of patients with odontogenic phlegmons of the maxillofacial region, localized in one topographical and anatomical space, was conducted, 16 of them abused alcoholic beverages. Before the phlegmon opening operation, on the 5th and 9th days, hematological indices of activity were determined – the lymphocyte-granulocyte index, the leukocyte to erythrocyte sedimentation rate ratio. The lymphocyte-granulocyte index was significantly lower (by 3.3 times) in patients who abused alcohol. On the 5th day, a significant increase in the lymphocyte-granulocyte index was found in the group of patients who abused alcohol. The analysis of the leukocyte to erythrocyte sedimentation rate ratio showed an increase in indicators in patients with phlegmons from the normal level. In patients with alcohol intoxication, on the 9th day, a 2.6-fold increase in the leukocyte to erythrocyte sedimentation rate ratio was found compared to the indicators of practically healthy individuals and 2-fold compared to the group of patients without harmful habits (p&lt;0.05). Conclusion. According to hematological indices of inflammatory activity, it is possible to determine the degree of activation of the pathological process in patients, in particular, those who abuse alcohol, and to choose the tactics of treatment of phlegmon of maxillofacial region

Effects of Long-Term Ethanol Consumption on Learning-Memory Functions in Mice and the Mechanisms Involved

To investigate the effect of long-term ethanol consumption on learning-memory functions in mice and the mechanisms involved. Thirty male C57BL6/J mice were randomly assigned to 3 groups, with 10 mice in each group. The three groups included a control group in which the mice were given water ad libitum for 30 days, a long-term ethanol consumption group, or the EtOH group, in which the mice were given 6% (volume fraction) ethanol ad libitum for 30 days, and a long-term alcoholism group, or the EtOH+G group, in which the mice were given 5% (volume fraction) ethanol ad libitum for 30 days plus intermittent intragastric gavage of 20% ethanol at 3.5 g per kilogram body mass once every three days. After 30 days, the learning-memory functions of the mice were evaluated. At the conclusion of the experiment, the brain tissue of the mice was collected in order to examine the oxygen consumption rate (OCR) of mitochondria, the levels of pan-acetylation and protein oxidative stress in the hippocampal tissue, and the expression of sirtuin-3 (SIRT3) in hippocampus. Morris water maze test showed that, compared with those of the control group, the times of crossing the platform and the percentage of platform time in the EtOH group and the EtOH+G group were both lower, and the EtOH+G group had the lowest results ( P<0.05). Western blot results showed that long-term ethanol intake increased the levels of protein oxidative stress and pan-acetylation in the hippocampal tissue and down-regulated SIRT3 expression of hippocampal mitochondria. The results of mitochondrial complex Ⅱ respiration showed that the brain mitochondrial 3-state respiration in the EtOH group and the EtOH+G group was lower than that in the control group ( P<0.05). Compared that with the control group, the mitochondrial maximum respiration in EtOH+G group was decreased ( P<0.05). Both long-term ethanol consumption and long-term alcoholism can reduce learning-memory functions and long-term alcoholism has the greater impact of the two. The potential mechanism may involve the down-regulation of the expression of SIRT3 protein in the hippocampus, which results in an increased level of pan-acetylation and enhanced expression of oxidative stress protein in the hippocampus, affects the mitochondrial functions of the brain, inhibits the oxidative phosphorylation capacity of mitochondrial complex Ⅱ, reduces the ATP energy supply of the brain tissue, and thus affects the learning-memory function.

Association between long-term alcohol consumption and insomnia symptoms in civil servants: Aichi Workers' Cohort Study.

The influence of habitual alcohol consumption on insomnia symptoms in healthy workers remains unclear. In this study, we evaluated the association between habitual alcohol consumption among civil servants and insomnia symptoms such as difficulty falling asleep, difficulty staying asleep, and tiredness after sleep, using longitudinal data. We enrolled civil servants in a prospective cohort study who completed questionnaires at baseline. Of those, 2861 participants were revaluated in a 5-year follow-up survey. Insomnia symptoms during the past month were assessed using self-reporting. Alcohol drinking habits were assessed by querying the frequency of drinking alcohol as well as the amount of alcohol usually consumed per one occasion. Drinking alcohol every day was less likely to have difficulty falling asleep (odds ratio, 0.42 95% confidence interval, 0.20-0.89), and drinking alcohol 3 or more days a week was associated with difficulty staying asleep (odds ratio, 1.48; 95% confidence interval, 1.16-1.90). Drinking alcohol every day may produce subjective improvement in sleep onset. However, drinking alcohol 3 or more days a week may increase arousal during sleep, which contributes to reduced sleep quality. These results suggest the possibility that long-term daily habitual drinking may reinforce a sense of improvement in subjective sleep onset but may possibly induce sleep disturbance.

Effectiveness of Psychosocial Intervention in the Management of Alcohol Dependence Syndrome with Poor Marital Adjustment: A Case Report

Aim: Globally, it has been found that the mean lifetime prevalence of alcohol use is 80% and for alcohol use disorder (AUD) is 8.6%, and AUD has an adverse impact on an individual as well as on the person’s family. In view of the same, we choose a case of alcohol dependence syndrome (ADS) to investigate the effect of long-term alcohol use on family dynamics, marital adjustment, interpersonal relationship, and motivational level of the individual with ADS, as well as the effectiveness of pre- and post- brief psychosocial intervention in the treatment outcome of the individual with ADS by involving his family and strengthening his interpersonal relationships.&#x0D; Presentation of the Case: The client had a history of alcohol use for 22 years. Gradually, his alcohol intake was increased from 100 ml/day to 2-5 litres/day in the last few years. Due to his worsening condition, he was admitted to hospital in 2016 and diagnosed with ADS. He remained abstinent for the next 5–6 months after discharge, but had poor treatment compliance. For the past 2.5 years (2016– 2019), the client again started drinking and the symptoms recurred. He was admitted there again on May 30, 2019. It was found that the prolonged alcohol use of the client had an adverse impact on his spouse’s wellbeing and also on his interpersonal relationships with his parents and siblings. Further, it was found that the client had a lower level of motivation, poor adaptive patterns, inadequate social support, and poor marital adjustment.&#x0D; Discussion: This study discovered a significant difference between pre- and post-psychosocial intervention in the management of ADS. After our intervention, the client has been doing well. His marital adjustment has increased with his improvement in quality of life, family dynamics, and adaptive patterns.&#x0D; Conclusion: It was found that psychosocial intervention with the person with alcohol dependence as well as his family is effective and plays a very crucial role in treatment and wellbeing.

Comprehensive analysis of transcriptomics and metabolomics to understand chronic ethanol induced murine cardiotoxicity.

Alcohol abuse has attracted public attention and long-term alcohol exposure can lead to alcohol-featured non-ischemic dilated cardiomyopathy. However, the precise underlying mechanisms of alcoholic cardiomyopathy remain to be elucidated. This study aimed to comprehensively characterize alcohol abuse-mediated effects on downstream metabolites and genes transcription using a multi-omics strategy. We established chronic ethanol intoxication model in adult male C57BL/6 mice through 8weeks of 95% alcohol vapor administration and performed metabolomics analysis, mRNA-seq and microRNA-seq analysis with myocardial tissues. Firstly, ethanol markedly induced ejection fraction reductions, cardiomyocyte hypertrophy, and myocardial fibrosis in mice with myocardial oxidative injury. In addition, the omics analysis identified a total of 166 differentially expressed metabolites (DEMs), 241 differentially expressed genes (DEGs) and 19 differentially expressed microRNAs (DEmiRNAs), respectively. The results highlighted that alcohol abuse mainly interfered with endogenous lipids, amino acids and nucleotides production and the relevant genes transcription in mice hearts. Based on KEGG database, the affected signaling pathways are primarily mapped to the antigen processing and presentation, regulation of actin cytoskeleton, AMPK signaling pathway, tyrosine metabolism and PPAR signaling pathway, etc. Furthermore, 9 hub genes related to oxidative stress from DEGs were selected based on function annotation, and potential alcoholic cardiotoxic oxidative stress biomarkers were determined through establishing PPI network and DEmiRNAs-DEGs cross-talk. Altogether, our data strongly supported the conclusion that ethanol abuse characteristically affected amino acid and energy metabolism, nucleotide metabolism and especially lipids metabolism in mice hearts, and underlined the values of lipids signaling and oxidative stress in the treatment strategies.