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After discovering in 1811 that alcohol existed as a discrete chemical substance in all intoxicating drinks, physicians reconsidered the individual's responsibility for becoming a compulsive drinker. Looking to science and medicine for legitimacy, temperance reformers ascribed a deleterious agency to alcohol and personified it as an agent of physiological destruction. Alcohol destroyed the body and transformed natural alimentary desires into a compulsive artificial appetite for alcohol. Reformers, prohibitionists, and physicians were troubled that alcohol possessed the ability to destroy the physical capacity for the power of choice. Ascribing agency to alcohol destabilized long-standing understandings of intemperance as a vice and imbued habitual drunkenness with medical meanings. However, most professionals remained anxious about absolving the habitual drunkard of all responsibility, especially for taking the first drink. An inchoate attempt to capture the medical and moral dilemmas of compulsion, habitual drunkenness represents a conceptual missing link in the genealogy of addiction. [ABSTRACT FROM AUTHOR]

Abstract Alcohol and cocaine (COC) are commonly co-used drugs that cause addiction and have harmful effects. Their abuse may threaten the health of the abuser and public safety by causing serious accidents or crimes. The recidivism rate of drug-related crimes closely correlates with alcoholism. Several incidences of alcohol consumption in combination with drug abuse have been reported. Here, liquid chromatography tandem mass spectrometric method was developed to simultaneously analyze ethyl glucuronide (EtG), a metabolite of ethanol; COC; cocaethylene (CE), an alcohol-derived metabolite of COC; and benzoylecgonine (BZE), a major metabolite of COC, to determine the concurrent use of alcohol with COC. For pre-treatment, ultracentrifugation (5 min, 50,000 g) and mixed-mode anion exchange solid-phase extraction were used to increase the recovery of target compounds and minimize the matrix effect of hair. The lower limits of quantification were: 7 pg/mg (EtG), 2 pg/mg (COC), 10 pg/mg (CE), and 1 pg/mg (BZE). The correlation coefficient (r) of the calibration curve within the quantified range of target compounds was ≥ 0.9978. The intra- and inter-day accuracies were − 6.1–9.7% and − 9.3–8.3%, and intra- and inter-day precisions were 0.5–10.3% and 0.6–14.4%, respectively. The recovery, matrix effect, process efficiency, and autosampler stability were 89.2–104.8%, 81.6–105.4%, 81.5–107.1%, and 96.6–109.7%, respectively. The novel analytical method was validated with hair samples from individuals suspected of alcohol and COC use, and the method could distinguish between independent and concurrent use. Based on the findings, the analytical approach developed in this study is anticipated to be valuable in drug and alcohol dependence tests that require the simultaneous detection of alcohol and COC abuse.

ABSTRACTA practical colorimetric analysis for alcohol determination was devised using a composite of food colorants, specifically a green solution of brilliant blue FCF and tartrazine at a ratio of 1:5 v/v. This colorimetric method was characterized by its simplicity, user-friendliness, environmental compatibility, cost-effectiveness, and suitability for self-measurement through visual examination. The colorimetric procedure entails admixture 1 mL of the alcohol sample with 50 µL of the green test solution and 250 µL of a 30% NaOH solution at ambient temperature. The ensuing color changes were visually assessed within 5 min. Through color sensing, methanol, ethanol, and isopropanol were identified by the manifestation of lemon yellow, orange, and biphasic solutions, respectively. Ethanol was semi-quantified based on color sensing from green to orange, with corresponding concentration ranges. The limit of detection for both methanol and ethanol was determined to be 30% v/v. The developed method demonstrated an accuracy of 93%, with the error range of 1 − 10% v/v and standard deviation of 3.9% v/v, as confirmed by the analysis of 100 commercially available alcohol-based hand sanitizers. This methodology has the potential for further expansion to encompass a wide range of rapid colorimetric analyses of products containing alcohol, including food items, alcohol raw materials, and cosmetics.

Carbon number upgrading of bio-furans by coupling with other renewable feedstocks is an attractive approach for producing renewable fuel and polymer feedstocks. In this work, used Li-ion battery waste based low cost catalyst was shown as an alternative to expensive noble metal catalysts for coupling furfural with alcohols to give 2-alkyl-3-(2-furyl) acroleins. The catalyst was prepared by pyrolyzing the black electrode coating from 18650 Li-ion cells in a used laptop battery at 600 °C in air. Highest furfural conversions of 72.6, 83.6, 100.0 and 95.4 % were observed for 1-propanol, 1-butanol, 1-pentanol and 1-hexanol respectively, using 0.6 mmol LiOH/mmol of furfural and using 25 mg/mmol of furfural catalyst loading, 0.345 MPa O2, 110 °C for 4.0 h. However, recycling of LiNiaMnbCocOd/graphite catalyst showed significant loss in catalytic activity in four cycles of reuse. A reaction scheme involving oxidation of alcohols to aldehydes followed by base catalyzed aldol condensation was proposed to explain the coupling to give 2-alkyl-3-(2-furyl) acroleins.

We first report a novel solvent, base free synthesis of carbonyl compound catalyst by FeCl3/TEMPO at 40 °C with high-rate. In this article, we examine the mechanism of this catalytic system and compare the reactivity of aromatic alcohols. Furthermore, the efficacy of 3-(2-aminoethyl)-1-methyl-1H-imidazol-3-ium bromide [Aemim]Br could be maintained after seven recycling cycles. High catalyst productivity and reaction rate (5.53 to 22.50) have been accomplished with the use of an enhanced procedure.

The use of Liquid Organic Hydrogen Carriers (LOHC) is one of the potential options to store hydrogen. Today, the vast majority of compounds used as LOHC come from the oil industry. Using biosourced LOHC would be a step forward in the development of this CO2-free solution. This article looks at LOHC candidates that can be obtained from biomass. The special case of formic acid and methanol, which do not fall within the definition of LOHC, is also considered. The synthesis of alcohols, polyols, amines, aminoalcohols and N-heterocyclic compounds from biosourced compounds is reviewed.

Identifying the concentration of alcohol compounds in postmortem analysis of biological fluids can help the investigation, just as postmortem analysis of gastric juices can reveal the concentrations of alcohol consumed. However, an efficient and effective combination of extraction and measurement methods is required when looking at complex postmortem samples. Therefore, a headspace-solid phase microextraction (HS-SPME) method was developed using gas chromatography with a flame ionization detector (GC-FID) to identify postmortem alcohol concentrations. This present study optimizes and validates an effective and efficient method for postmortem alcohol extraction and quantification in gastric fluid. The optimal conditions for HS-SPME extraction using 65μm Polydimethy lsiloxane Divinyl benzene (PDMS/DVB) fiber for analyte isolation were 15 minutes. at 60°C and an exposure time of 1 minute. The validation investigation shows that the suggested approach satisfies the criteria for linearity, precision, accuracy, LOD, and LOQ for postmortem measurement of alcohol in gastric fluid.

This paper investigates the factors influencing the probability of fatality in various types of maritime accidents, including grounding, capsizing, sinking, man overboard incidents, and fatal falls, with a focus on several contributing factors—alcohol consumption, meteorological conditions, and visibility. Through comprehensive analysis, the alcohol consumption was examined in order to show how it impairs judgment and physical abilities, significantly increasing the risk of fatal outcomes in these accidents. The paper explores the interplay between alcohol consumption and other contributing factors, such as time of day (daytime/night) and weather conditions, providing a comprehensive understanding of how these variables collectively influence fatality rates in EU maritime transportation. The findings underscore the critical need for stringent alcohol regulations and enhanced safety protocols to mitigate the heightened risks associated with alcohol-impaired maritime operations.

Chronic alcohol use leads to metabolic dysfunction in adipose tissue. The underlying mechanisms and the contribution of alcohol-induced adipose tissue dysfunction to systemic metabolic dysregulation are not well understood. In our previous studies, we found that chronic alcohol feeding induces mesenteric lymphatic leakage, perilymphatic adipose tissue (PLAT) inflammation, and local insulin resistance in rats. The goal of this study was to further explore the link between alcohol-induced lymphatic leakage and PLAT immunometabolic dysregulation, locally and systemically, using in vivo and ex vivo approaches. Male rats received a Lieber–DeCarli liquid diet, of which 36% of the calories were from alcohol, for 10 weeks. Time-matched control animals were pair-fed. Adipokine levels were measured in PLAT, subcutaneous fat, plasma, and mesenteric lymph samples. Glucose tolerance was assessed after 10 weeks. Further, we used a novel ex vivo lymph-stimulated naïve PLAT explant approach to modeling lymph leakage to assess changes in adipokine secretion and expression of proinflammatory markers after stimulation with lymph from alcohol- or pair-fed animals. Our data show that chronic alcohol-fed rats presented PLAT-specific decreases in adiponectin and leptin levels, alterations in the expression of genes involved in lipid metabolic pathways, and associated impaired whole-body glucose homeostasis. Further, we found that direct naïve PLAT stimulation with lymph contents from alcohol-fed animals increased IL-6 expression in demonstrating the ability of lymph contents to differentially impact naïve adipose tissue. Overall, chronic alcohol feeding leads to depot-specific alterations in metabolic profile, impaired systemic glucose tolerance, and lymph-induced adipose tissue inflammation. The specific lymph components leading to PLAT immunometabolic dysregulation remain to be determined.

While the number of publications on wine and health is steadily increasing, ranging from a molecular level to epidemiological studies, often with contradictory results, little attention has been given to a holistic approach to research, starting from the molecular level to arrive at pharmacological and medical conclusions. In this review, some unusual concepts are considered, such as the phytocomplex, the vehicle, and the Matrix effect. The concept of the phytocomplex is discussed, specifically the biological activities of Tyrosol, Hydroxytyrosol, and Resveratrol; indeed, the interactions among different molecules in herbal matrices provide a specific response. This is often markedly different from the response evoked by single constituents in the modulation of microbial populations in the gut, in intestinal stability and bioaccessibility, and, obviously, in inducing biological responses. Among the many alcoholic beverages which contain these molecules, wine has the most peculiar Matrix effect, which can heavily influence the bioavailability of the phytocomplex obtained by the fermentation processes that produce this beverage. Wine’s Matrix effect plays an instrumental role in improving the beneficial compounds’ bioavailability and/or in inhibiting alcohol metabolites’ carcinogenicity. Underestimation of the wine Matrix effect could lead to deceiving results, as in the case of dealcoholized wine or wine-compound-based nutritional supplements; alternatively, this can occur in the emphasis of a single component’s toxic activity, in this case, alcohol, ignoring the specific molecular-level protective action of other compounds (polyphenols) that are present in the same matrix. The dark side of the Matrix effect is also discussed. This review confirms the research recommendations made by the WHO Scientific Group, which suggests it is important “to investigate the possible protective effects of ingredients other than alcohol in alcoholic beverages”, considering that most recent studies seem not only relevant but also capable of directing future research towards innovative points of view that have so far been too neglected.

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1β, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse.

Clinical studies demonstrate that the risk of developing neurological disorders is increased by overconsumption of the commonly used drugs, alcohol, nicotine and cannabis. These drug-induced neurological disorders, which include substance use disorder (SUD) and its co-occurring emotional conditions such as anxiety and depression, are observed not only in adults but also with drug use during adolescence and after prenatal exposure to these drugs, and they are accompanied by long-lasting disturbances in brain development. This report provides overviews of clinical and preclinical studies, which confirm these adverse effects in adolescents and the offspring prenatally exposed to the drugs and include a more in-depth description of specific neuronal systems, their neurocircuitry and molecular mechanisms, affected by drug exposure and of specific techniques used to determine if these effects in the brain are causally related to the behavioral disturbances. With analysis of further studies, this review then addresses four specific questions that are important for fully understanding the impact that drug use in young individuals can have on future pregnancies and their offspring. Evidence demonstrates that the adverse effects on their brain and behavior can occur: (1) at low doses with short periods of drug exposure during pregnancy; (2) after pre-conception drug use by both females and males; (3) in subsequent generations following the initial drug exposure; and (4) in a sex-dependent manner, with drug use producing a greater risk in females than males of developing SUDs with emotional conditions and female offspring after prenatal drug exposure responding more adversely than male offspring. With the recent rise in drug use by adolescents and pregnant women that has occurred in association with the legalization of cannabis and increased availability of vaping tools, these conclusions from the clinical and preclinical literature are particularly alarming and underscore the urgent need to educate young women and men about the possible harmful effects of early drug use and to seek novel therapeutic strategies that might help to limit drug use in young individuals.

In the contemporary era, youthful and healthy skin is a pivotal determinant of beauty. Choices pertaining to one’s dietary and lifestyle practices wield substantial influence over skin health. Currently, the focal point of attention lies in strategies that delay skin aging and maintain skin quality. Remarkably, the skin, the body’s largest organ, serves as the primary defense barrier against external elements. Skin aging encompasses intrinsic and extrinsic categories, both susceptible to genetic, lifestyle, and environmental factors. Given the strides in science and technology, the pursuit of effective and safe interventions for skin aging assumes paramount importance. Thus, this review delves into the intricate relationship between diet, lifestyle, and skin aging, culminating in an exploration of the crucial role played by excess iron in this intricate nexus. Understanding these dynamics holds promise for advancing our knowledge of skincare and the quest for timeless vitality.

It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the BDNF gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait (p < 0.0001) and neuroticism (p < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A (p < 0.0001) and G/G (p = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A (p < 0.0001) and G/G (p < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the BDNF gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.

This work was done due to a need of developing a facile detection platform of ethanol (EtOH) type of alcohol for various reasons from the police uses up to the medical and industrial uses. To this aim, a representative model of fullerene (FULL) was doped by each of the beryllium (Be), magnesium (Mg), and calcium (Ca) alkali-earth atoms to produce MFULL counterparts including BeFULL, MgFULL, and CaFULL to be examined towards the adsorption of EtOH substance. Accordingly, the models were stabilized and their structural features were evaluated in addition to the evaluation of electronic based frontier molecular orbital features. The results showed possibility of formation of EtOH@FULL and EtOH@MFULL complexes by a priority of formation of the doped models, in which the formation of EtOH@BeFULL complex was found at the highest level of suitability regarding the energy terms and integration details. Subsequently, the electronic features indicated measurable variation of molecular orbital levels to approach a point of detection of adsorbed EtOH by the assistance of fullerenes. Meaningful results were found by performing density functional theory (DFT) calculations for showing the stability of EtOH@MFULL complexes besides evaluating measurable electronic features. Accordingly, the idea of developing a facile detection of EtOH by the Be/Mg/Ca-enhanced fullerenes was affirmed.

Binge alcohol consumption during adolescence can produce lasting deficits in learning and memory while also increasing the susceptibility to substance use disorders. The adolescent intermittent ethanol (AIE) rodent model mimics human adolescent binge drinking and has identified the nucleus basalis magnocellularis (NbM) as a key site of pathology. The NbM is a critical regulator of prefrontal cortical (PFC) cholinergic function and attention. The cholinergic phenotype is controlled pro/mature neurotrophin receptor activation. We sought to determine if p75NTR activity contributes to the loss of cholinergic phenotype in AIE by using a p75NTR modulator (LM11A-31) to inhibit prodegenerative signaling during ethanol exposure. Male and female rats underwent 5 g/kg ethanol (AIE) or water (CON) exposure following 2-day-on 2-day-off cycles from postnatal day 25–57. A subset of these groups also received a protective dose of LM11A-31 (50 mg/kg) during adolescence. Rats were trained on a sustained attention task (SAT) and behaviorally relevant acetylcholine (ACh) activity was recorded in the PFC with a fluorescent indicator (AChGRAB 3.0). AIE produced learning deficits on the SAT, which were spared with LM11A-31. In addition, PFC ACh activity was blunted by AIE, which LM11A-31 corrected. Investigation of NbM ChAT+ and TrkA+ neuronal expression found that AIE led to a reduction of ChAT+TrkA+ neurons, which again LM11A-31 protected. Taken together, these findings demonstrate the p75NTR activity during AIE treatment is a key regulator of cholinergic degeneration.

Relapse to alcohol abuse, often caused by cue-induced alcohol craving, is a major challenge in alcohol addiction treatment. Therefore, disrupting the cue-alcohol memories can suppress relapse. Upon retrieval, memories transiently destabilize before they reconsolidate in a process that requires protein synthesis. Evidence suggests that the mammalian target of rapamycin complex 1 (mTORC1), governing the translation of a subset of dendritic proteins, is crucial for memory reconsolidation. Here, we explored the involvement of two regulatory pathways of mTORC1, phosphoinositide 3-kinase (PI3K)-AKT and extracellular regulated kinase 1/2 (ERK1/2), in the reconsolidation process in a rat (Wistar) model of alcohol self-administration. We found that retrieval of alcohol memories using an odor-taste cue increased ERK1/2 activation in the amygdala, while the PI3K-AKT pathway remained unaffected. Importantly, ERK1/2 inhibition after alcohol memory retrieval impaired alcohol-memory reconsolidation and led to long-lasting relapse suppression. Attenuation of relapse was also induced by post-retrieval administration of lacosamide, an inhibitor of collapsin response mediator protein-2 (CRMP2)—a translational product of mTORC1. Together, our findings indicate the crucial role of ERK1/2 and CRMP2 in the reconsolidation of alcohol memories, with their inhibition as potential treatment targets for relapse prevention.

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.

Traumatic brain injury (TBI) is associated with alcohol abuse and higher ethanol sensitivity later in life. Currently, it is poorly understood how ethanol sensitivity changes with time after TBI and whether there are sex-dependent differences in the relationship between TBI and ethanol sensitivity. This study uses the fruit fly Drosophila melanogaster to investigate how TBI affects alcohol sensitivity and whether the effects are sex-specific. Our results indicate that flies have a significantly higher sensitivity to the intoxicating levels of ethanol during the acute phase post-TBI, regardless of sex. The increased ethanol sensitivity decreases as time progresses; however, females take longer than males to recover from the heightened ethanol sensitivity. Dietary restriction does not improve the negative effects of alcohol post-TBI. We found that tau mutant flies exhibit a similar ethanol sensitivity to TBI flies. However, TBI increased the ethanol sensitivity of dtauKO mutants, suggesting that TBI and dtau loss of function have additive effects on ethanol sensitivity.

Alcohol use disorders (AUDs) frequently co-occur with negative mood disorders, such as anxiety and depression, exacerbating relapse through dopaminergic dysfunction. Stress-related neuropeptides play a crucial role in AUD pathophysiology by modulating dopamine (DA) function. The rostromedial tegmental nucleus (RMTg), which inhibits midbrain dopamine neurons and signals aversion, has been shown to increase ethanol consumption and negative emotional states during abstinence. Despite some stress-related neuropeptides acting through the RMTg to affect addiction behaviors, their specific roles in alcohol-induced contexts remain underexplored. This study utilized an intermittent voluntary drinking model in mice to induce negative effect behavior 24 h into ethanol (EtOH) abstinence (post-EtOH). It examined changes in pro-stress (Pnoc, Oxt, Npy) and anti-stress (Crf, Pomc, Avp, Orx, Pdyn) neuropeptide-coding genes and analyzed their correlations with aversive behaviors. We observed that adult male C57BL/6J mice displayed evident anxiety, anhedonia, and depression-like symptoms at 24 h post-EtOH. The laser-capture microdissection technique, coupled with or without retrograde tracing, was used to harvest total ventral tegmental area (VTA)-projecting neurons or the intact RMTg area. The findings revealed that post-EtOH consistently reduced Pnoc and Orx levels while elevating Crf levels in these neuronal populations. Notably, RMTg Pnoc and Npy levels counteracted ethanol consumption and depression severity, while Crf levels were indicative of the mice’s anxiety levels. Together, these results underscore the potential role of stress-related neuropeptides in the RMTg in regulating the negative emotions related to AUDs, offering novel insights for future research.

The main aims of the present study were to explore the relationship of the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women with their personality traits and to try to find out whether any specific features may influence alcohol cravings and be a prognostic for alcohol dependency and treatment in AUD women. Our study found a notable correlation between openness and the interaction of the ORIM1 gene and AUD. The alcohol use disorder subjects with genotype AG showed a higher level of openness compared to the control group with genotypes AG (p = 0.0001) and AA (p = 0.0125). The alcohol use disorder subjects with the AA genotype displayed higher levels of openness than the control group with genotype AG (p = 0.0271). However, the alcohol use disorder subjects with the AA genotype displayed lower levels of openness than the control group with genotype GG (p = 0.0212). Our study indicates that openness as a personality trait is correlated with the OPRM1 gene rs1074287 polymorphism in alcohol-dependent women. These are the first data and results exploring such a relationship between opioid and alcohol pathways and the mental construction of AUD women. Personality traits such as openness to experience and neuroticism might play major roles in the addiction mechanism, especially in genetically predisposed females, independent of the reward system involved in the emotional disturbances that coexist with anxiety and depression.

The design and fabrication of highly efficient, cheap, and stable heterogeneous catalyst for the advancement of sustainable organic transformation is a crucial goal in both academic research and industry. Herein, an efficient catalyst based on Cu-decorating on a N, P-codoped porous carbon(Cu/NPC) derived from wheat straw was successfully synthesized by a cost-effective method. The as-prepared Cu/NPC showed superior catalytic activity for the N-alkylation of amines with alcohols via the borrowing hydrogen strategy. A variety of aromatic amines were converted into the corresponding secondary amines in moderate to excellent yields. Noted that, such catalyst can be easily prepared, recovered and recycled four times without obvious loss in both activity and selectivity.

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon—previously existing hepatic disorder or acute liver failure due to SARS-CoV-2—is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

Fetal alcohol spectrum disorders (FASD) are leading causes of neurodevelopmental disability. The mechanisms by which alcohol (EtOH) disrupts fetal brain development are incompletely understood, as are the genetic factors that modify individual vulnerability. Because the phenotype abnormalities of FASD are so varied and widespread, we investigated whether fetal exposure to EtOH disrupts ribosome biogenesis and the processing of pre-ribosomal RNAs and ribosome assembly, by determining the effect of exposure to EtOH on the developmental expression of 18S rRNA and its cleaved forms, members of a novel class of short non-coding RNAs (srRNAs). In vitro neuronal cultures and fetal brains (11–22 weeks) were collected according to an IRB-approved protocol. Twenty EtOH-exposed brains from the first and second trimester were compared with ten unexposed controls matched for gestational age and fetal gender. Twenty fetal-brain-derived exosomes (FB-Es) were isolated from matching maternal blood. RNA was isolated using Qiagen RNA isolation kits. Fetal brain srRNA expression was quantified by ddPCR. srRNAs were expressed in the human brain and FB-Es during fetal development. EtOH exposure slightly decreased srRNA expression (1.1-fold; p = 0.03). Addition of srRNAs to in vitro neuronal cultures inhibited EtOH-induced caspase-3 activation (1.6-fold, p = 0.002) and increased cell survival (4.7%, p = 0.034). The addition of exogenous srRNAs reversed the EtOH-mediated downregulation of srRNAs (2-fold, p = 0.002). EtOH exposure suppressed expression of srRNAs in the developing brain, increased activity of caspase-3, and inhibited neuronal survival. Exogenous srRNAs reversed this effect, possibly by stabilizing endogenous srRNAs, or by increasing the association of cellular proteins with srRNAs, modifying gene transcription. Finally, the reduction in 18S rRNA levels correlated closely with the reduction in fetal eye diameter, an anatomical hallmark of FASD. The findings suggest a potential mechanism for EtOH-mediated neurotoxicity via alterations in 18S rRNA processing and the use of FB-Es for early diagnosis of FASD. Ribosome biogenesis may be a novel target to ameliorate FASD in utero or after birth. These findings are consistent with observations that gene–environment interactions contribute to FASD vulnerability.

Native amine dehydrogenases (nat-AmDHs) catalyze the (S)-stereoselective reductive amination of various ketones and aldehydes in the presence of high concentrations of ammonia. Based on the structure of CfusAmDH from Cystobacter fuscus complexed with Nicotinamide adenine dinucleotide phosphate (NADP+) and cyclohexylamine, we previously hypothesized a mechanism involving the attack at the electrophilic carbon of the carbonyl by ammonia followed by delivery of the hydride from the reduced nicotinamide cofactor on the re-face of the prochiral ketone. The direct reduction of carbonyl substrates into the corresponding alcohols requires a similar active site architecture and was previously reported as a minor side reaction of some native amine dehydrogenases and variants. Here we describe the ketoreductase (KRED) activity of a set of native amine dehydrogenases and variants, which proved to be significant in the absence of ammonia in the reaction medium but negligible in its presence. Conducting this study on a large set of substrates revealed the heterogeneity of this secondary ketoreductase activity, which was dependent upon the enzyme/substrate pairs considered. In silico docking experiments permitted the identification of some relationships between ketoreductase activity and the structural features of the enzymes. Kinetic studies of MsmeAmDH highlighted the superior performance of this native amine dehydrogenases as a ketoreductase but also its very low activity towards the reverse reaction of alcohol oxidation.

In this work, a convenient and greener procedure for synthesizing 1,2-diarylethane-1,2-dione derivatives as well as the oxidation of primary and secondary alcohols was explored using an oxidizing agent (KMnO4) in a basic ionic liquid of 1-butyl-3-methylimidazolium hydroxide ([Bmim]OH) as greener medium. The selective oxidation of α-hydroxy ketone compounds together with primary and secondary alcohols in the presence of KMnO4 in [Bmim]OH afforded corresponding carbonyl compounds of 1,2-diarylethane-1,2-dione derivatives and aldehydes or ketones in high yields (85-97% and 83-97%, respectively). The reactions are mild, fast, and efficient. Moreover, KMnO4 in [Bmim]OH medium was easily recovered and reused for at least four additional reactions without significant loss of efficiency with a consistent yield of about 80%.

Abstract The DHBD quantity represents the hydroxyl group density of alcoholic solvents or water. DHBD is purely physically defined by the product of molar concentration of the solvent (N) and the factor Σn=n×f which reflects the number n and position (f‐factor) of the alcoholic OH groups per molecule. Whether the hydroxyl group is either primary, secondary or tertiary is taken into account by f. Σn is clearly linearly correlated with the physical density or the refractive index of the alcohol derivative. Relationships of solvent‐dependent UV/Vis absorption energies as ET(30) values, 129Xe NMR shifts and kinetic data of 2‐chloro‐2‐methylpropane solvolysis with DHBD are demonstrated. It can be shown that the ET(30) solvent parameter reflects the global polarity of the hydrogen bond network rather than specific H‐bond acidity. Significant correlations of the log k1 rate constants of the solvolysis reaction of 2‐chloro‐2‐methylpropane with DHBD show the physical reasoning of the approach.

Alginate organohydrogels prepared in water/alcohol mixtures play an important role in electronic and superconductor applications in low-temperature environments. The study deals with the preparation of Ca-alginate organohydrogels and the analysis of their equilibrium swelling and mechanical properties at sub-zero temperatures. It is shown that the equilibrium degree of swelling at room temperature is noticeably affected by the concentration of co-solvents (methanol, ethanol, and 2-propanol) in the mixtures and the number of carbon atoms in the co-solvent molecules. Mechanical properties are studied in small-amplitude oscillatory tests. The data are fitted with a model that involves three material parameters. The influence of temperature is investigated in temperature-sweep oscillatory tests under a cooling-heating program, where a noticeable difference is observed between the storage and loss moduli under cooling and heating (the hysteresis curves). The hysteresis areas are affected by the cooling/heating rate and the number of carbon atoms in the co-solvents.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Excessive drinking damages the central nervous system of individuals and can even cause alcohol use disorder (AUD). AUD is regulated by both genetic and environmental factors. Genes determine susceptibility to alcohol, and the dysregulation of epigenome drives the abnormal transcription program and promotes the occurrence and development of AUD. DNA methylation is one of the earliest and most widely studied epigenetic mechanisms that can be inherited stably. In ontogeny, DNA methylation pattern is a dynamic process, showing differences and characteristics at different stages. DNA dysmethylation is prevalent in human cancer and alcohol-related psychiatric disorders, resulting in local hypermethylation and transcriptional silencing of related genes. Here, we summarize recent findings on the roles and regulatory mechanisms of DNA methylation, the development of methyltransferase inhibitors, methylation alteration during alcohol exposure at different stages of life, and possible therapeutic options for targeting methylation in human and animal studies.

Fischer–Tropsch synthesis (FTS) produces hundreds of hydrocarbons and oxygenates by simple reactants (CO + H2) and the detailed chain propagation mechanism is still in dispute. An industrial iron-based catalyst was used to further clarify the mechanism by adding aldehyde, alcohol and alkene species into a fixed-bed tubular reactor. The added species were investigated in H2 and syngas atmospheres, respectively. 1-alkene in the H2 atmosphere presented an obvious hydrogenolysis, in which the produced C1 species participated in C–C bond formation simultaneously. Co-feeding Cn alkene with syngas showed remarkable Cn+1 alcohol selectivity compared to the normal FTS reaction. In addition, the carbonyl group of aldehyde was extremely unstable over the iron-based catalyst and could easily be hydrogenated to an alcohol hydroxyl group, which could even undergo dehydration for hydrocarbon species formation. Experimental data confirmed that both heavier alkenes and alcohols added can be converted to chain growth intermediates and then undergo monomer insertion for chain propagation. These results provide strong evidence that the chain propagation in the FTS reaction is simultaneously controlled by the surface carbide mechanism and the CO insertion mechanism, with surface CHx species and CO as monomers, respectively. The study is of guiding significance for FTS mechanism understanding and kinetic modeling.

It is one of the critical fields of green chemistry to catalyze the selective conversion of biomass-derived alcohol and ammonia to primary amines with extensive application. Recently, catalytic systems consisting of non-noble metal nickel- and cobalt-based catalysts have been developed for catalytic alcohol amination. This paper reviewed these two types of catalytic systems, which are classified as skeleton Co and Ni catalytic systems, supported and modified Co and Ni catalytic systems, emphasized on catalysts and catalysis, and clearly explained where zero-valent cobalt or nickel is active species for catalytic reaction. In supported catalysts, the catalytic active sites constituted by the catalytic active species and its micro-environment can regulate the efficiency of catalytic the reaction. While in modified catalysts, modifiers such as metal Fe, Re and Bi may modulate the catalytic active sites and change the catalytic selectivity. There are differences in structure and size between catalysts prepared by different methods, resulting in distinct interface and electronic properties for alcohol amination, which determines the structure–activity relationships of the catalytic system.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can modulate cerebral AD pathology include Toll-like receptors, protein kinase-B (Akt)/mammalian target of rapamycin (mTOR) pathway, cyclic adenosine monophosphate (cAMP) response element-binding protein phosphorylation pathway, glycogen synthase kinase 3-β, cyclin-dependent kinase-5, insulin-like growth factor type-1 receptor, modulation of β-amyloid (Aβ) synthesis and clearance, microglial mediated, and brain endothelial alterations. Besides these brain-centric pathways, alcohol-mediated liver injury may significantly affect brain Aβ levels through alterations in the peripheral-to-central Aβ homeostasis. This article reviews published experimental studies (cell culture and AD rodent models) to summarize the scientific evidence and probable mechanisms (both cerebral and hepatic) by which alcohol promotes or protects against AD progression.

Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such as ATP synthesis and initiation of apoptosis. However, current research has provided evidence that mitochondria participate in myriad cellular processes, including immune activation, nutrient sensing in pancreatic β-cells, and skeletal muscle stem and progenitor cell differentiation. The literature indicates that alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation and disrupting mitochondrial dynamics, leading to dysfunctional mitochondria accumulation. As discussed in this review, mitochondrial dyshomeostasis emerges at a nexus between alcohol-disrupted cellular energy metabolism and tissue injury. Here, we highlight this link and focus on alcohol-mediated disruption of immunometabolism, which refers to two distinct, yet interrelated processes. Extrinsic immunometabolism involves processes whereby immune cells and their products influence cellular and/or tissue metabolism. Intrinsic immunometabolism describes immune cell fuel utilization and bioenergetics that affect intracellular processes. Alcohol-induced mitochondrial dysregulation negatively impacts immunometabolism in immune cells, contributing to tissue injury. This review will present the current state of literature, describing alcohol-mediated metabolic and immunometabolic dysregulation from a mitochondrial perspective.

Cervical cancer causes malignant tumors in females and threatens the physical and mental health of women. Current research shows that persistent infection of high-risk HPV is the main cause of cervical cancer. However, not all cervical cancer is caused by HPV infection, which may also be related to other factors, such as nutritional status and lifestyle. This study focuses on the effect of alcohol consumption on the methylation status of cervical cancer from the perspective of methyl donors. We established a mouse tumor-bearing model with cervical cancer SiHa cells, and at the same time, we cultured SiHa cells in vitro. Different concentrations of ethanol were administered to the model mice and SiHa cells. Then, we detected the levels of the methyl-donor folate and methionine and their metabolite homocysteine levels in mice serum, tumor tissues, and SiHa cells. Furthermore, we determined the expression of the members of the DNA methyltransferase family (DNMT1, DNMT3a, and DNMT3b) in tumor tissue by immunohistochemistry. qRT-PCR and Western blotting analysis were used to detect the mRNA and protein levels of members of the DNA methyltransferase family in cervical cancer SiHa cells. Our results show that the levels of the methyl donor (folate and methionine) decreased with the increase of ethanol concentration (p < 0.05), and the homocysteine level increased significantly (p < 0.05). In SiHa cells, the mRNA and protein levels of the DNMT family members and their receptors were significantly higher than those in the control group (p < 0.05). Collectively, these results suggest that ethanol could influence DNMT expression by inducing methyl donor consumption, thereby causing cervical cancer cells to exhibit genome-wide hypomethylation.

Liver disease is one of the leading comorbidities in HIV infection. The risk of liver fibrosis development is potentiated by alcohol abuse. In our previous studies, we reported that hepatocytes exposed to HIV and acetaldehyde undergo significant apoptosis, and the engulfment of apoptotic bodies (ABs) by hepatic stellate cells (HSC) potentiates their pro-fibrotic activation. However, in addition to hepatocytes, under the same conditions, ABs can be generated from liver-infiltrating immune cells. The goal of this study is to explore whether lymphocyte-derived ABs trigger HSC profibrotic activation as strongly as hepatocyte-derived ABs. ABs were generated from Huh7.5-CYP2E1 (RLW) cells and Jurkat cells treated with HIV+acetaldehyde and co-culture with HSC to induce their pro-fibrotic activation. ABs cargo was analyzed by proteomics. ABs generated from RLW, but not from Jurkat cells activated fibrogenic genes in HSC. This was driven by the expression of hepatocyte-specific proteins in ABs cargo. One of these proteins is Hepatocyte-Derived Growth Factor, for which suppression attenuates pro-fibrotic activation of HSC. In mice humanized with only immune cells but not human hepatocytes, infected with HIV and fed ethanol, liver fibrosis was not observed. We conclude that HIV+ABs of hepatocyte origin promote HSC activation, which potentially may lead to liver fibrosis progression.

Catalytic nitrobenzene reduction is crucial for the synthesis of 4,4-methylene diphenyl diisocyanate, which is used to produce polyurethane foams, thermoplastic elastomers, and adhesives. The stability and activity of nanoparticle catalysts are affected by surface ligands and stabilizers. We established the complete composition of 7.0 ± 1.1 nm iridium oxide nanoparticles that were stabilized by polyvinylpyrrolidone (PVP[Ir]). PVP[Ir] and its surface stabilizers were characterized using elemental analysis (EA), high-resolution X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD), FT-IR, and UV-vis spectroscopy. Notably, PVP[Ir] contained 33.8 ± 0.4% Ir. XPS binding energy analyses suggest that 7% of the Ir is Ir(0) and 93% is IrO2. Using formic acid as the source of hydrogen, PVP[Ir] catalyzed the selective hydrogenation of nitrobenzene to give aniline as the only product in 66% yield in 1 h at 160 °C in a high-pressure metal reactor. Less than 1% of the side products (azobenzene and azoxybenzene) were detected. In contrast, using alcohol as the hydrogen source led to a low yield and a poor selectivity for aniline.

In this study, a reduced graphene oxide (rGO)@sodium lignosulfonate (NaLS) composite material was fabtricated using a one-step method and then mixed with natural polysaccharide calcium alginate (CaAlg) to prepare the rGO@NaLS/CaAlg pervaporation membrane. The appearance and physical properties of the rGO@NaLS/CaAlg membrane were characterized by scanning electron microscopy and water contact angle. The swelling performance of the membrane and its dehydration performance to organic solvents were evaluated. The results indicate that the addition of rGO@NaLS can increase the hydrophilicity of the rGO@NaLS/CaAlg membrane and reduce its degree of swelling in the ethanol solution. The membrane incorporated with 6 wt% rGO@NaLS exhibits the best pervaporation performance, and ethanol can be purified to 99.8%.

Alcohol abuse accounts for 3.3 million deaths annually, rendering it a global health issue. Recently, fibroblast growth factor 2 (FGF-2) and its target, fibroblast growth factor receptor 1 (FGFR1), were discovered to positively regulate alcohol-drinking behaviors in mice. We tested whether alcohol intake and withdrawal alter DNA methylation of Fgf-2 and Fgfr1 and if there is a correlation regarding mRNA expression of these genes. Blood and brain tissues of mice receiving alcohol intermittently over a six-week period were analyzed using direct bisulfite sequencing and qRT-PCR analysis. Assessment of Fgf-2 and Fgfr1 promoter methylation revealed changes in the methylation of cytosines in the alcohol group compared with the control group. Moreover, we showed that the altered cytosines coincided with binding motives of several transcription factors. We also found that Fgf-2 and Fgfr1 gene expression was significantly decreased in alcohol-receiving mice compared with control littermates, and that this effect was specifically detected in the dorsomedial striatum, a brain region involved in the circuitry of the reward system. Overall, our data showed alcohol-induced alterations in both mRNA expression and methylation pattern of Fgf-2 and Fgfr1. Furthermore, these alterations showed a reward system regional specificity, therefore, resembling potential targets for future pharmacological interventions.

Alcoholic liver disease (ALD) is a consequence of excessive alcohol use. According to many studies, alcohol represents a significant socioeconomic and health risk factor in today’s population. According to data from the World Health Organization, there are about 75 million people who have alcohol disorders, and it is well known that its use leads to serious health problems. ALD is a multimodality spectrum that includes alcoholic fatty liver disease (AFL) and alcoholic steatohepatitis (ASH), consequently leading to liver fibrosis and cirrhosis. In addition, the rapid progression of alcoholic liver disease can lead to alcoholic hepatitis (AH). Alcohol metabolism produces toxic metabolites that lead to tissue and organ damage through an inflammatory cascade that includes numerous cytokines, chemokines, and reactive oxygen species (ROS). In the process of inflammation, mediators are cells of the immune system, but also resident cells of the liver, such as hepatocytes, hepatic stellate cells, and Kupffer cells. These cells are activated by exogenous and endogenous antigens, which are called pathogen and damage-associated molecular patterns (PAMPs, DAMPs). Both are recognized by Toll-like receptors (TLRs), which activation triggers the inflammatory pathways. It has been proven that intestinal dysbiosis and disturbed integrity of the intestinal barrier perform a role in the promotion of inflammatory liver damage. These phenomena are also found in chronic excessive use of alcohol. The intestinal microbiota has an important role in maintaining the homeostasis of the organism, and its role in the treatment of ALD has been widely investigated. Prebiotics, probiotics, postbiotics, and symbiotics represent therapeutic interventions that can have a significant effect on the prevention and treatment of ALD.

This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D invasion assay using Matrigel was performed to validate the model. RNA was extracted and subjected to transcriptomic analysis to validate the model and assess carcinogen-induced changes. The VEGF inhibitors pazopanib and lenvatinib were tested in the model and were validated by a 3D invasion assay, which demonstrated that changes induced by the carcinogen in spheroids were consistent with a malignant phenotype. Further validation was obtained by bioinformatic analyses, which showed the enrichment of pathways associated with hallmarks of cancer and VEGF signalling. Overexpression of common genes associated with tobacco-induced oral squamous cell carcinoma (OSCC), such as MMP1, MMP3, MMP9, YAP1, CYP1A1, and CYP1B1, was also observed. Pazopanib and lenvatinib inhibited the invasion of transformed spheroids. In summary, we successfully established a 3D spheroid model of oral carcinogenesis for biomarker discovery and drug testing. This model is a validated preclinical model for OSCC development and would be suitable for testing a range of chemotherapeutic agents.

Microbiome alterations are emerging as one of the most important factors that influence the course of alcohol use disorder (AUD). Recent advances in bioinformatics enable more robust and accurate characterization of changes in the composition of the microbiome. In this study, our objective was to provide the most comprehensive and up-to-date evaluation of microbiome alterations associated with AUD and alcoholic liver disease (ALD). To achieve it, we have applied consistent, state of art bioinformatic workflow to raw reads from multiple 16S rRNA sequencing datasets. The study population consisted of 122 patients with AUD, 75 with ALD, 54 with non-alcoholic liver diseases, and 260 healthy controls. We have found several microbiome alterations that were consistent across multiple datasets. The most consistent changes included a significantly lower abundance of multiple butyrate-producing families, including Ruminococcaceae, Lachnospiraceae, and Oscillospiraceae in AUD compared to HC and further reduction of these families in ALD compared with AUD. Other important results include an increase in endotoxin-producing Proteobacteria in AUD, with the ALD group having the largest increase. All of these alterations can potentially contribute to increased intestinal permeability and inflammation associated with AUD and ALD.

Binge Drinking (BD) corresponds to episodes of ingestion of large amounts of ethanol in a short time, typically ≤2 h. BD occurs across all populations, but young and sports-related people are especially vulnerable. However, the short- and long-term effects of episodic BD on skeletal muscle function have been poorly explored. Young rats were randomized into two groups: control and episodic Binge-Like ethanol protocol (BEP) (ethanol 3 g/kg IP, 4 episodes of 2-days ON-2-days OFF paradigm). Muscle function was evaluated two weeks after the last BEP episode. We found that rats exposed to BEP presented decreased muscle strength and increased fatigability, compared with control animals. Furthermore, we observed that skeletal muscle from rats exposed to BEP presented muscle atrophy, evidenced by reduced fiber size and increased expression of atrophic genes. We also observed that BEP induced fibrotic and inflammation markers, accompanied by mislocalization of nNOSµ and high levels of protein nitration. Our findings suggest that episodic binge-like ethanol exposure alters contractile capacity and increases fatigue by mechanisms involving atrophy, fibrosis, and inflammation, which remain for at least two weeks after ethanol clearance. These pathological features are common to several neuromuscular diseases and might affect muscle performance and health in the long term.

Prenatal alcohol exposure can cause developmental abnormalities (fetal alcohol spectrum disorders; FASD), including small eyes, face and brain, and neurobehavioral deficits. These cannot be detected early in pregnancy with available imaging techniques. Early diagnosis could facilitate development of therapeutic interventions. Banked human fetal brains and eyes at 9–22 weeks’ gestation were paired with maternal blood samples, analyzed for morphometry, protein, and RNA expression, and apoptotic signaling. Alcohol (EtOH)-exposed (maternal self-report) fetuses were compared with unexposed controls matched for fetal age, sex, and maternal race. Fetal brain-derived exosomes (FB-E) were isolated from maternal blood and analyzed for protein, RNA, and apoptotic markers. EtOH use by mothers, assessed by self-report, was associated with reduced fetal eye diameter, brain size, and markers of synaptogenesis. Brain caspase-3 activity was increased. The reduction in eye and brain sizes were highly correlated with amount of EtOH intake and caspase-3 activity. Levels of several biomarkers in FB-E, most strikingly myelin basic protein (MBP; r > 0.9), correlated highly with morphological abnormalities. Reduction in FB-E MBP levels was highly correlated with EtOH exposure (p < 1.0 × 10−10). Although the morphological features of FAS appear long before they can be detected by live imaging, FB-E in the mother’s blood may contain markers, particularly MBP, that predict FASD.

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was inhibited in the presence of PGE1; AC7 KO BV-2 cells showed lower and PGE1-insensitive phagocytic activity. Innate immune activities of the parental BV-2 cells, including bacterial killing, nitric oxide synthesis, and expression of arginase 1 and interleukin 10 were activated as expected with small effects of ethanol. However, the innate immune activities of AC7 KO cells were either drastically diminished or not detected. The data presented suggest that AC7 has an important role in the innate immune functions of microglial cells. AC7’s involvement in ethanol’s effects on immune functions remains unclear. Further studies are needed.

Recreational use of alcohol is a social norm in many communities worldwide. Alcohol use in moderation brings pleasure and may protect the cardiovascular system. However, excessive alcohol consumption or alcohol abuse are detrimental to one’s health. Three million deaths due to excessive alcohol consumption were reported by the World Health Organization. Emerging evidence also revealed the danger of moderate consumption, which includes the increased risk to cancer. Alcohol abuse and periods of withdrawal have been linked to depression and anxiety. Here, we present the effects of alcohol consumption (acute and chronic) on important brain structures—the frontal lobe, the temporal lobe, the limbic system, and the cerebellum. Apart from this, we also present the link between alcohol abuse and withdrawal and mood disorders in this review, thus drawing a link to oxidative stress. In addition, we also discuss the positive impacts of some pharmacotherapies used. Due to the ever-rising demands of life, the cycle between alcohol abuse, withdrawal, and mood disorders may be a never-ending cycle of destruction. Hence, through this review, we hope that we can emphasise the importance and urgency of managing this issue with the appropriate approaches.

Alcohol use disorder (AUD) is a global public health problem and is frequently comorbid with mental disorders, including anxiety and depression. Ferroptosis is an iron-dependent cell death, which is involved in the pathological process of various diseases such as neurodegenerative diseases, but the role of ferroptosis in the mediation of AUD and its induced mental disorders is unclear. In this study, we aimed to investigate whether ferroptosis was involved in alcohol-induced depressive and anxiety-like behaviors in mice. Following an 8-week period of intermittent alcohol exposure, the alcohol group showed noticeable depressive and anxiety-like behaviors. In addition, nissl staining revealed that alcohol exposure induced neuron damage in the hippocampus (Hip) and prefrontal cortex (PFC) of mice. The levels of synapse-related proteins were significantly reduced in the alcohol group. Iron staining demonstrated that alcohol increased the number of iron-positive staining cells. The protein expression of the transferrin receptor (TFRC) was increased, and the expression of glutathione peroxidase 4 (GPX4) was decreased, respectively, in the alcohol group. Furthermore, the ferroptosis inhibitor ferrostatin-1 significantly prevented alcohol-induced neuron damage and enhanced the expression of N-methyl-d-aspartic acid (NMDA) receptor 2B (NR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor 1 (GluA1) and GPX4 in vitro. These results indicated that alcohol exposure could induce depressive and anxiety-like behaviors, and that this effect may occur via activating ferroptosis.

Alcohol abuse is a significant public health problem. While considerable research has shown that alcohol use affects sleep, little is known about the role of sleep deprivation in alcohol toxicity. We investigated sleep as a factor modulating alcohol toxicity using Drosophila melanogaster, a model for studies of sleep, alcohol, and aging. Following 24 h of sleep deprivation using a paradigm that similarly affects males and females and induces rebound sleep, flies were given binge-like alcohol exposures. Sleep deprivation increased mortality, with no sex-dependent differences. Sleep deprivation also abolished functional tolerance measured at 24 h after the initial alcohol exposure, although there was no effect on alcohol absorbance or clearance. We investigated the effect of chronic sleep deprivation using mutants with decreased sleep, insomniac and insulin-like peptide 2, finding increased alcohol mortality. Furthermore, we investigated whether pharmacologically inducing sleep prior to alcohol exposure using the GABAA-receptor agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) mitigated the effects of alcohol toxicity on middle-aged flies, flies with environmentally disrupted circadian clocks, and flies with short sleep. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality. Thus, sleep prior to binge-like alcohol exposure affects alcohol-induced mortality, even in vulnerable groups such as aging flies and those with circadian dysfunction.

Therapeutic activation of mechanoreceptors (MStim) in osteopathy, chiropractic and acupuncture has been in use for hundreds of years with a myriad of positive outcomes. It has been previously shown to modulate the firing rate of neurons in the ventral tegmental area (VTA) and dopamine (DA) release in the nucleus accumbens (NAc), an area of interest in alcohol-use disorder (AUD). In this study, we examined the effects of MStim on VTA GABA neuron firing rate, DA release in the NAc, and behavior during withdrawal from chronic EtOH exposure in a rat model. We demonstrate that concurrent administration of MStim and EtOH significantly reduced adaptations in VTA GABA neurons and DA release in response to a reinstatement dose of EtOH (2.5 g/kg). Behavioral indices of EtOH withdrawal (rearing, open-field crosses, tail stiffness, gait, and anxiety) were substantively ameliorated with concurrent application of MStim. Additionally, MStim significantly increased the overall frequency of ultrasonic vocalizations, suggesting an increased positive affective state.

Recent data show that young people, mainly due to the pressure of some risk factors or due to disrupted interpersonal relationships, utilise greater reward value and display greater sensitivity to the reinforcing properties of “pleasurable stimuli”, specifically in those situations in which an enhanced dopamine release is present. Alcoholic beverages, foods rich in sugar and fat, and illicit drug use are pleasurable feelings associated with rewards. Research shows that there is a link between substance abuse and obesity in brain functioning. Still, alcohol excess is central in leading to obesity and obesity-related morbidities, such as hepatic steatosis, mainly when associated with illicit drug dependence and negative eating behaviours in young people. It is ascertained that long-term drinking causes mental damage, similarly to drug abuse, but also affects liver function. Indeed, beyond the pharmacokinetic interactions of alcohol with drugs, occurring in the liver due to the same metabolic enzymes, there are also pharmacodynamic interactions of both substances in the CNS. To complicate matters, an important noxious effect of junk foods consists of inducing obesity and obesity-related NAFLD. In this review, we focus on some key mechanisms underlying the impact of these addictions on the liver, as well as those on the CNS.