Alcoholic Injury Research Articles

Alcoholic brain injury via 8-layer customized deep convolution neural network

Alcohol can act quickly in the human body and alter mood and behavior. If alcohol is consumed in excess, it will accumulate in the organs of the body, especially in the liver and brain. To a certain extent, the symptoms of alcoholism will appear. So far, the main method of diagnosis of alcoholic brain injury is through MRI images by radiologists. However, this is a very subjective diagnosis. Radiologists may be affected by external factors, such as physical discomfort, lack of rest, inattention, etc., resulting in diagnostic errors. In this paper, we proposed a novel 8-layer customized deep convolution neural network for alcoholic brain injury detection, which contains five convolution layers, five pooling layers, and three fully connected layers. There are three improvements in this paper, (i) Based on deep learning, we proposed a method for automatic diagnosis of alcoholic brain injury; (ii) We introduced Dropout to the proposed structure to improve robustness; (iii) Compared with other state-of-the-art approaches, the proposed structure is more efficient. The experimental results showed that the sensitivity, specificity, precision, accuracy, F1, MCC and FMI were 96.14±1.99, 96.20±1.47, 95.98±1.54, 96.17±1.55, 96.05±1.62, 93.34±3.11, 96.06±1.62 respectively. According to comparison results, our method performed the best. The proposed model is effective in detecting alcoholic brain injury based on MRI images.

Pterostilbene attenuates RIPK3-dependent hepatocyte necroptosis in alcoholic liver disease via SIRT2-mediated NFATc4 deacetylation

Receptor-interacting protein kinase (RIPK) 3-dependent necroptosis plays a critical role in alcoholic liver disease. RIPK3 also facilitates steatosis, oxidative stress, and inflammation. Pterostilbene (PTS) has favorable hepatoprotective activities. The present study was aimed to reveal the therapeutic effects of PTS on ethanol-induced hepatocyte necroptosis and further illustrate possible molecular mechanisms. Human hepatocytes LO2 were incubated with 100 mM ethanol for 24 h to mimic alcoholic hepatocyte injury. Results showed that PTS at 20 μM reduced damage-associated molecular patterns (DAMPs) release, including IL-1α and high-mobility group box 1 (HMGB1), and blocked necroptotic signaling, evidenced by decreased RIPK1 and RIPK3 expression. Trypan blue staining visually showed that PTS reduced nonviable hepatocytes after ethanol exposure, which was counteracted by adenovirus-mediated ectopic overexpression of RIPK3 but not RIPK1. Besides, PTS inhibited ethanol-induced hepatocyte steatosis via restricting lipogenesis and enhancing lipolysis, decreased oxidative stress via rescuing mitochondrial membrane potential, reducing oxidative system, and enhancing antioxidant system, and relieved inflammation evidenced by decreased expression of proinflammatory factors. Notably, RIPK3 overexpression diminished these protective effects of PTS. Subsequent work indicated that PTS suppressed the expression and nuclear translocation of nuclear factor of activated T-cells 4 (NFATc4), an acetylated protein, in ethanol-exposed hepatocytes, while NFATc4 overexpression impaired the negative regulation of PTS on RIPK3 and DAMPs release. Further, PTS rescued sirtuin 2 (SIRT2) expression, and SIRT2 knockdown abrogated the inhibitory effects of PTS on nuclear translocation and acetylation status of NFATc4 in ethanol-incubated hepatocytes. In conclusion, PTS attenuated RIPK3-dependent hepatocyte necroptosis after ethanol exposure via SIRT2-mediated NFATc4 deacetylation.

Protective effect and mechanism of Wangshi Baochi Pills against acute alcoholic liver/stomach injury in mice

As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.

Bioengineered 3D electrospun nanofibrous scaffold with human liver cells to study alcoholic liver disease in vitro.

Alcohol injury induces hepatic fibrosis which gradually progresses to cirrhosis, sometimes may lead to liver cancer. Animal models are less efficient in mimicking responses of human liver cells, whereas in vitro models discussed so far are majorly based on rodent cells. In this work, a coculture of primary human hepatocytes (PHHs) with LX-2 cells was established on the unmodified (C:F_0:0), collagen-I modified (C:F_1:0), fibronectin modified (C:F_0:1) and 3:1 collagen-I to fibronectin modified (C:F_3:1) 3D electrospun fibrous scaffolds. The effect of alcohol injury was evaluated on this cell-scaffold model at 0-40μl/ml alcohol concentrations over 14days of culture period by using the gold standard sandwich culture as the control. Among all the culture groups, C:F_3:1 scaffold was able to maintain translational and transcriptional properties of human liver cells at all concentrations of alcohol treatment. The study reveals that, PHHs on C:F_3:1 were able to maintain ~4-fold and ~1.6-fold higher secretion of albumin than the gold standard sandwich culture on Day 3 and Day 7, respectively. When treated with alcohol, at concentrations of 20 and 40μl/ml, albumin secretion was also observed to be higher (~2-fold) when compared to the gold standard sandwich culture. Again as expected, in C:F_3:1 culture group on 40μl/ml alcohol treatment, albumin gene expression decreased by ~2-fold due to alcohol toxicity, whereas CYP2C9, CYP3A4, CYP2E1 and CYP1A2 gene expressions upregulated by ~3.5, ~~4, ~5 and ~15-fold, respectively in response to the alcohol injury. LX-2 cells also acquire more quiescent phenotype on C:F_3:1 scaffolds when compared to the gold standard sandwich culture upon alcohol treatment. Thus, C:F_3:1 scaffold with human liver cells was established as the potential platform to scan alcohol toxicity at varied alcohol concentrations. Thus, it can pave a promising path not only to support functional healthy human liver cells for liver tissue engineering but also to examine potential drugs to study the progression or inhibition of alcoholic liver fibrosis in vitro.

Abstract #1000943: Hidden In Plain Sight: The Complexity of Euglycemic DKA Induced by Severe Alcoholic Pancreatitis

The diagnostic challenge of euglycemic diabetic ketoacidosis (EDKA) is attributed to its relatively uncommon presentation and similarity to other forms of ketoacidosis. Often unrecognized at initial presentation, appropriate treatment for this life-threatening complication is delayed and potentially fatal. To emphasize EDKA as a differential diagnosis in severe metabolic derangement and highlight the complexity of ketoacidosis with alcoholic pancreatic injury, we describe a case of EDKA with severe acute pancreatitis in a patient without known diabetes.

The role of alcohol and other drugs on emergency department traumatic injury mortality in the United States

BackgroundAlcohol and other drugs (AOD) increase the risk of traumatic injury occurring, but data suggest a protective benefit in preventing trauma-related mortality. The objective of this study is to describe the epidemiology of AOD-related traumatic injury in the US over a recent 7 year period and assess the interaction of traumatic injury and AOD on pre-admission fatality on both an additive scale using incidence contrasts and on a statistical multiplicative scale using survey-adjusted logistic regression. MethodsUsing the National Emergency Department Sample (NEDS), we describe the epidemiology of alcohol and substance-related emergency department traumatic injury over a recent period. AOD-related injury was assessed using survey-adjusted counts and means. Ratio estimates and differences were calculated using simulations based on survey-adjusted counts and standard errors. Differences in trends over time were evaluated by comparing the slopes of linear regression equations with year as the predictor variable. ResultsAlcohol and substance-related emergency department injury discharges increased 9.8 % during the study period. There was a statistically significant interaction between traumatic injury death and AOD on both an additive scale and multiplicative scale. (Odds Ratio for interaction term = 1.76, 95 % CI = 1.53, 2.03). ConclusionsAOD use does not provide a protective benefit in the setting of trauma, but rather is an important contributor to traumatic injury mortality.

Blood alcohol screening and outcomes in trauma team activation patients at a level 1 trauma centre in New Zealand.

A causal relationship between alcohol consumption and injury exists and the prevalence of harmful alcohol intakes in New Zealand adults is high. The present study investigates compliance to blood alcohol (BA) screening policy and the epidemiological profile and hospital-related outcomes of trauma team activation (TTA) patients with positive BA at a New Zealand level 1 trauma centre. A retrospective review of Midland Trauma Registry hospitalisation data between January 2012 and December 2019 was conducted. Eligible patients (n=2168) were ≥15 years who received TTA at Waikato Hospital. BA screening rates, demographic and event information, injury severity and hospital-related outcomes were examined. The average BA screening rate was 94.0% (95% confidence interval 92.9-95.0%) and 17.9% of screened patients were BA+ . BA+ patients were younger than BA- (34.7 and 40.5 years, P< 0.0001). More males than females (20.6 and 12.4%, P< 0.0001), Māori (30.8%) compared to non-Māori (<16.0%) and unemployed/beneficiaries (33.4%) compared to employed patients (15.5%) were BA+ . Road transport crashes accounted for the highest proportion (45.2%) but, in comparison there were higher odds of BA+ from interpersonal violence (odds ratio 4.48, P< 0.0001). No difference between BA+ and BA- was observed in survival rate, injury severity scores, length of intensive care and total hospital stay. Between 2012 and 2019, Waikato Hospital demonstrated high compliance to BA screening policy for TTA patients. Appropriate alcohol awareness initiatives that focus on road safety and interpersonal violence are required to reduce the preventable prevalence and burden of alcohol-related trauma in the Waikato region.

Harnessing Artificial Intelligence to Expedite Identification of Therapeutic Phytochemical Combination for Alcoholic Hepatic Injury

AbstractPlant‐originated compounds, also known as phytochemicals, could improve health through either daily consumption or medical treatments. Conventional developments of phytochemical therapies are often based on the action mechanism of single compounds. However, compounds within a plant or across different plants are numerous, and their interactions potentially mold its therapeutic effect, which is hard to explore with conventional approaches. To address such challenges, an Artificial Intelligence (AI) platform featuring Monte Carlo method‐based modeling (MCM2) for rapid identification of the optimal dose combinations is devised. MCM2 utilizes both the mean and variances within multiple replicates, and thus maximizes the optimization efficiency. MCM2 is applied to optimize the therapeutic effect on alcoholic hepatic injury of a quaternary dose combination of products from Gynostemma pentaphyllum and Lotus leaf, which are identified through in vitro screening of 50 products extracted from 24 herbal medicine candidates. The optimal combination identified by MCM2 is then tested on murine model. Both in vitro and in vivo results confirmed the AI‐optimized phytochemical combination significantly reduced acute alcoholic liver injury. The AI platform introduced in this study could serve to promptly identify optimal combinatorial regimens with potential synergy, which enhances the efficiency during the development of compound medicine.

Lactobacillus plantarum ZS62 Alleviates Alcohol-Induced Gastric Injury in Mice via an Anti-Oxidative Mechanism.

AimGastric mucosal injury is a typical characteristic of gastric diseases. The prevalence of gastric mucosal injury caused by alcohol has been on the rise, which has been considered a serious problem. The purpose of this study is to explore the protective effect on gastric injury of Lactobacillus plantarum ZS62 (LP-ZS62) isolated from naturally fermented yak yoghurt.MethodsWe established a gastric injury model through alcohol and evaluated the protective effect of LP-ZS62 on gastric injury in mice. The injury to the gastric mucosa, histopathological sections, related biochemical indicators, and related genes were examined to evaluate the protective effect of LP-ZS62.ResultsLP-ZS62 effectively alleviated alcohol-induced gastric injury according to visual observations of gastric tissue and pathological tissue sections. The experimental results revealed that LP-ZS62 decreased malondialdehyde (MDA) level, and elevated superoxide dismutase (SOD) and glutathione (GSH) levels in gastric tissues. Additionally, LP-ZS62 increased glutathione peroxidase (GSH-Px), prostaglandin E2 (PGE2), and somatostatin (SS) levels. LP-ZS62 also decreased inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 levels, and increased the anti-inflammatory cytokine IL-10 level. The quantitative polymerase chain reaction results showed that LP-ZS62 upregulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2), copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), gamma-glutamylcysteine synthetase (GSH1), and glutathione peroxidase (GSH-Px).ConclusionThis study confirmed that LP-ZS62 alleviated alcohol-induced gastric injury by regulating antioxidant capacity. Therefore, LP-ZS62 could be developed as a probiotic product to treat alcoholic gastric injury.

The association between the time of alcohol drinking and injury risk in Thailand: a cross\u2010sectional emergency department study

BackgroundAlthough the relationship between acute alcohol consumption and injuries is well recognized, studies exploring how the time of day the drinking commences affects alcohol-related injuries have been scarce. This contribution examines the associations between the time at which the drinking began and the duration of the drinking, the volume of alcohol consumed, the injury type, and the blood alcohol concentration (BAC) level.MethodThis study employed a cross-sectional survey, which was conducted in two hospital emergency departments (ED) in Chiangmai Province, Thailand. The sample was composed of 519 injured patients aged 18 years and older. Outcome measures included the BAC and type of injury. Exposures included the quantity of alcohol consumed, the time the drinking commenced, and the pattern of drinking involved. ResultsThe injured patients who drank alcohol within six hours prior to sustaining their injury were more likely to get injured and present themselves at the ED at night (20:00–04:00) compared to those who sustained an injury but did not drink in the hours prior. However, this relationship was only true for unintentional injuries, not intentional ones. The majority of participants consumed their first drink between 16:00 and 20:00. On average, among the 104 patients who drank prior to sustaining an injury, the total amount of alcohol consumed was 6.9 drinks, the duration of drinking was 2.6 h, the rate of drinking was 6.0 drinks/hour, and the BAC was 0.119 gm%. Every drink increased the BAC by 0.012 gm% and each year of increasing age increased the BAC by 0.003 gm%. People who were older, less educated, and drank more frequently tended to have their first drink earlier than other drinkers. An earlier start to their drinking resulted in a faster pace of drinking and a higher BAC.ConclusionsBAC increased with the total amount of alcohol consumed and the age of the drinker. Different groups of people had their first drink at different times of the day, resulting in differences in the rate of drinking, the BAC, the time of injury, and the time they presented to the ED after injury.

Alcohol and acute traumatic brain injury in the emergency department.

There is limited research from Australasian EDs describing the demographic make-up, injury severity and impact of alcohol in patients requiring computed tomography (CT) for suspected traumatic brain injury (TBI). The present study aims to review the frequency and presenting patterns of patients who consume alcohol prior to presenting with suspected TBI. Retrospective observational study of patients referred for head CT to exclude TBI from a major referral centre and regional ED in New Zealand, between 1 September 2018 and 31 August 2019. Comparison groups were defined as 'alcohol involved' or 'no alcohol involved'. 97/425 (22.8% [95% CI 18.3-27.4]) of included TBI presentations involved alcohol. 73/97 (75.3% [95% CI 58.6-93.5]) were male and 41/97 (42.3% [95% CI 29.3-55.2]) were aged 18-30 years. The alcohol group were more likely to report assault as the injury mechanism (19.6% [95% CI 10.8-28.4] vs 5.2% [95% CI 2.7-7.7], P< 0.05) and have Glasgow Coma Scale scores reflecting more moderate (13.5% [95% CI 5.9-21.1] vs 3.5% [95% CI 1.5-5.6]) and severe (5.6% [95% CI 0.7-10.5] vs 3.2% [95% CI 1.2-5.2] TBI. Presentation times post-injury were delayed compared to the no alcohol group (3.4h [interquartile range 1.9-14.8] vs 2.8 h [interquartile range 1.8-6.6], P< 0.05). One quarter of patients with suspected TBI had consumed alcohol prior to their injury. Predominantly, those affected were young males who reported higher rates of assault; however, alcohol use was recorded in all age groups and sex. Alcohol-affected patients presented later, potentially delaying time to diagnosis. The present study supports the call for public health interventions that aim to reduce alcohol misuse.

Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis

Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis.

Preventive and Regenerative Effect of Glutamine and Probiotics on Gastric Mucosa in an Experimental Model of Alcohol-Induced Injury in Male Holtzman Rats

Aims: The purpose of this study was to measure the preventive and regenerative effect of glutamine and probiotics in holtzman rats induced by alcohol injury. Methods: Analytical, experimental and prospective study. The population consisted of 56 male rats between 300 and 350 g, distributed in three phases: Pre-pilot phase PPP (6 rats), Pilot phase PP (10 rats), and Experimental phase EP (40 rats). In the pilot phase, 10 rats were subjected to damage with 8.5% ethanol, which was given intragastrically (3 ml/kg). The dosage was calculated for 10 rats in two groups: the first with 7.5 ml/kg in 5 rats and the second with 8.5 ml/kg in 5 rats. The experimental phase was performed in 40 rats divided into 6 groups, the negative control group (healthy), positive control group (damage), preventive experimental group (glutamine and glutamine with probiotic) and regenerative experimental group (glutamine and glutamine with probiotic). At the end of each phase the rats were sacrificed with sodium pentobarbital (Halathal) and a portion of their stomachs were stored in formol for macroscopic examination and for its corresponding processing and histopathological analysis. Results: The evaluation of stomach tissue samples (desquamation, erythema, hyperemia) showed that in the preventive phase glutamine shows effectiveness in comparison to glutamine with probiotic. In the regenerative phase, glutamine shows better effectiveness than glutamine plus probiotic. Conclusion: Glutamine and probiotics can potentially serve as a therapy for the treatment for gastritis.

Mulberry leaves extract ameliorates alcohol-induced liver damages through reduction of acetaldehyde toxicity and inhibition of apoptosis caused by oxidative stress signals.

Mulberry leaves (Morus alba L.), which are traditional Chinese herbs, exert several biological functions, such as antioxidant, anti-inflammation, antidiabetic, and antitumor. Alcohol intake increases inflammation and oxidative stress, and this increase causes liver injury and leads to liver steatosis, cirrhosis, and hepatocellular carcinoma, which are major health problems worldwide. Previous report indicated that mulberry leaf extract (MLE) exited hepatoprotection effects against chronic alcohol-induced liver damages. In this present study, we investigated the effects of MLE on acute alcohol and liver injury induced by its metabolized compound called acetaldehyde (ACE) by using in vivo and in vitro models. Administration of MLE reversed acute alcohol-induced liver damages, increased acetaldehyde (ACE) level, and decreased aldehyde dehydrogenase activity in a dose-dependent manner. Acute alcohol exposure-induced leukocyte infiltration and pro-inflammation factors, including cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were blocked by MLE in proportion to MLE concentration. MLE prevented alcohol-induced liver apoptosis via enhanced caveolin-1 expression and attenuated EGFR/STAT3/iNOS pathway using immunohistochemical analysis. ACE induced proteins, such as iNOS, COX-2, TNF-α, and IL-6, and inhibited superoxide dismutase expression, whereas co-treated with MLE reversed these proteins expression. MLE also recovered alcohol-induced apoptosis in cultured Hep G2 cells. Overall, our findings indicated that MLE ameliorated acute alcohol-induced liver damages by reducing ACE toxicity and inhibiting apoptosis caused by oxidative stress signals. Our results implied that MLE might be a potential agent for treating alcohol liver disease.

The impact of alcohol use and withdrawal on trauma outcomes: A case control study

IntroductionMany patients admitted to hospitals with acute trauma have positive serum blood alcohol levels. Published associations between alcohol use, injury patterns, and outcomes are inconsistent. We sought to further delineate the impact of alcohol use and alcohol withdrawal on hospital outcomes amongst acute trauma patients. MethodsWe performed a retrospective analysis of adult trauma patients hospitalized at a suburban level 1 trauma center between January 2015 and September 2019 with a blood alcohol level measurement and/or classification as alcohol withdrawal syndrome (AWS). Patients were separated into three groups: BAL ≤10 mg/dL, BAL >10 mg/dL, and alcohol withdrawal syndrome (AWS). ResultsOverall, 3896 patients met study criteria with 75.6% BAL ≤10, 23.2% BAL >10, and 1.2% AWS. The median age was significantly different (BAL ≤ 10: 59 years, BAL > 10: 44 years, AWS: 53.5 years). Alcohol withdrawal was experienced by patients with BAL ≤10 and BAL >10. While injury severity and mortality were similar across all 3 groups, AWS patients experienced significantly longer hospital and ICU lengths of stay, unplanned ICU admission, need for mechanical ventilation, and higher rates of complications. Patients with AWS had high rates of acute neuropsychiatric symptoms, complicating their management. ConclusionsExcept for mortality, AWS patients experienced worse outcomes. The complex nature of alcohol withdrawal cases, including the possibility of developing AWS despite a negative BAL on admission, emphasizes the need for early assessment for alcohol withdrawal risk factors and input from specialists.

Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury.

Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0–100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota—increased Lactobacillus and decreased Lachnospiraceae species—were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy.

Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism

Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1β, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.

Strength training protects against prostate injury in alcoholic rats.

Alcoholic injury can alter the hormonal signaling pathway and lead to glucose and lipid metabolism disorders. In this study, we investigated whether the strength training could exert protective effects against the alterations caused by ethanol consumption on prostatic metabolism. A UChB, ethanol-preferring rats were used in this study. Strength training was conducted for 3 days per week for 13 weeks, rats performed jumps in water carrying a weight load strapped to their chests as part of a strength training protocol. The reduced alcohol consumption by strength training was accompanied by increased glucose, serum lipid profile, total protein levels, and reduced hormonal levels. The results of protein expression of prostatic tissues in the ethanol- and strength training-treated groups indicated that "steroidal hormone receptors," "fatty acid translocation," and "cell regulation" were significantly different between ethanol- and strength training-treated groups. Taken together, these findings show that strength training effectively ameliorated prostatic injuries in alcoholic rats at least partially by acting on lipids receptors and steroidal hormone receptors pathway, suggesting the strength training as a potential novel therapeutic strategy for treating prostate injuries caused by ethanol.

DNA methylation of FTO promotes renal inflammation by enhancing m6A of PPAR-α in alcohol-induced kidney injury

Alcohol consumption is one of the risk factors for kidney injury. The underlying mechanism of alcohol-induced kidney injury remains largely unknown. We previously found that the kidney in a mouse model of alcoholic kidney injury had severe inflammation. In this study, we found that the administration of alcohol was associated with the activation of NLRP3 inflammasomes and NF-κB signaling, and the production of pro-inflammatory cytokines. Whole-genome methylation sequencing (WGBS) showed that the DNA encoding fat mass and obesity-associated protein (FTO) was significantly methylated in the alcoholic kidney. This finding was confirmed with the bisulfite sequencing (BSP), which showed that alcohol increased DNA methylation of FTO in the kidney. Furthermore, inhibition of DNA methyltransferases (DNMTs) by 5-azacytidine (5-aza) reversed alcohol-induced kidney injury and decreased the mRNA and protein levels of FTO. Importantly, we found that FTO, the m6A demethylase, epigenetically modified peroxisome proliferator activated receptor-α (PPAR-α) in a YTH domain family 2 (YTHDF2)-dependent manner, which resulted in inflammation in alcoholic kidney injury models. In conclusion, our findings indicate that alcohol increases the methylation of PPAR-α m6A by FTO-mediated YTHDF2 epigenetic modification, which ultimately leads to the activation of NLRP3 inflammasomes and NF-κB-driven renal inflammation in the kidney. These findings may provide novel strategies for preventing and treating alcoholic kidney diseases.

Research progress on anti-alcoholic gastric injury active components and mechanisms of Chinese herbal medicine

Alcohol is considered to be one of the main causes for gastric injury, and alcoholic gastric injury has been becoming one of the global health problems, which seriously affects the quality of human life. Many studies suggest that the active components extracted from Chinese herbal medicine can effectively reduce the degree of alcohol-induced gastric injury. The active components and its mechanism of anti-alcoholic gastric injury of Chinese herbal medicine reported in recent five years were preliminarily summarized according to the classification of terpenoids, flavonoids, polyphenols, polysaccharides, volatile oils, phenylpropanoids and alkaloids in this paper. The terpenoids could improve oxidative stress and inflammatory response by regulating relevant signaling pathways. The flavonoids are mainly related to antioxidant and anti-inflammatory properties. The polyphenols mainly regulate the level of relevant factors involved in inflammatory pathway, oxidative stress and apoptosis pathway. The polysaccharides could enhance the ability of gastric mucosal defense factor by inhibiting oxidative stress injury and inflammatory response. Phenylpropanoids could enhance the gastric mucosal defense factor. The volatile oils mainly inhibit H~+/K~+-ATPase activity or inflammatory reaction. Alkaloids are closely related to the inhibition of inflammatory response and the improvement of antioxidant system. This paper aims to provide reference for further research and development of Chinese herbal medicine against alcoholic gastric injury.