Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease

Alcoholic liver disease (ALD) is characterized by the injury, inflammation, and scarring in the liver owing to excessive alcohol consumption. Currently, ALD is a leading cause for liver transplantation. Therefore, extensive studies (in vitro, in experimental ALD models and in humans) are needed to elucidate pathological features and pathogenic mechanisms underlying ALD. Notably, oxidative changes in the liver have been recognized as a signature trait of ALD. Progression of ALD is linked to the generation of highly reactive free radicals by reactions involving ethanol and its metabolites. Furthermore, hepatic oxidative stress promotes tissue injury and, in turn, stimulates inflammatory responses in the liver, forming a pathological loop that promotes the progression of ALD. Accordingly, accumulating further knowledge on the relationship between oxidative stress and inflammation may help establish a viable therapeutic approach for treating ALD.

Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.

Changes in Alcohol Consumption Among a Population Who Underwent Medical Checkups During the First Wave of the Coronavirus Disease 2019 Pandemic in Japan: A Single-Center Retrospective Study

Background: Movement restrictions during the coronavirus disease 2019 (COVID-19) pandemic have inflicted stress and affected drinking behavior. However, limited information is available on the changes in alcohol use among the Japanese population.Method: This retrospective study included 371 subjects aged 20–74 years who underwent medical checkups at Fuyoukai Murakami Hospital before (April 1, 2019 to December 31, 2019) and during the COVID-19 pandemic (April 1, 2020 to May 31, 2020). All data were extracted from medical records. Changes in alcohol consumption and severity were also investigated. A logistic regression model was used to identify the risk factors associated with increased drinking, and seven variables were sequentially introduced into the model—age (≤ 49 years), male sex, prior instructions for alcohol restriction, medication for lifestyle-related diseases (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, and hyperuricemia), depression or insomnia, essential workers, and smoking.Results: The median age was 46 years, and 81.7% subjects were men. In total, 25.1% subjects increased their alcohol intake, and 24.5% subjects reduced their alcohol intake. The rates of excessive alcohol consumption (≥ 60 g ethanol per day) were 15.9% and 16.7% in the pre-COVID-19 period and during the COVID-19 pandemic, respectively. Multivariate analysis identified only age ≤ 49 years as a risk factor for increased drinking (adjusted odds ratio, 2.20; 95% confidence interval, 1.22–3.99; p = 0.009).Conclusion: Approximately one-fourth of the subjects reported increased drinking, although the overall severity remained stable. The importance of alcohol reduction, particularly among young people, should be emphasized.

SARS-CoV-2, alcohol consumption, poor social behaviour, and the COVID-19 pandemic

Studies dealing with the SARS-CoV-2 virus and the COVID-19 disease have concentrated on the study of the virus and the disease themselves, but a knowledge of the causes responsible for the pandemic is still lacking. Crucial for effective decision making and control of the pandemic is a thorough and critical analysis of data regarding COVID-19, which shows an intimate relation between the number of cases/deaths and the consumption of alcohol. Ranked top 30 countries in COVID-19 cases/deaths and alcohol consumption coincide, with only a few exceptions. This coincidence is not fortuitous nor surprising, because excessive alcohol consumption is known to have pernicious effects on social behaviour, i.e. lead to deviant and irresponsible behaviour, which greatly promotes transmission

Association between road safety habits and risky health behaviours in Latvian adult population

The study examined the road safety habits of the adult population of Latvia in relation to risky health behaviours (smoking, excessive alcohol consumption, no regular health check-ups at the family doctor). Data of Health Behaviour among the Latvian Adult Population for five consecutive surveys for the years 2010–2018 were analysed. Results: The use of seat belts has increased slightly – from 93.5% to 95.6% in the front seat of the vehicle, from 52.4% to 56.3% in the rear seat of the vehicle (p < 0,001). Of the 10,731 respondents, 30.8% (N = 3309; 95% CI 30.0–31.7) were daily smokers, 14.8% (N = 1593; 95% CI 14.2–15.5) had excessive alcohol consumption habits, 25.9% (N = 2779; 95% CI 25.1–26.7) had not visited their family doctor during the last year. Higher odds for seat belt use were observed among respondents without excessive alcohol consumption (OR = 2.1), non-smokers (OR = 1.5–1.8), and those, who had visited their family doctor last year (OR = 1.2–1.3). Multivariate regression analysis showed risky behaviour is an independent factor associated with road safety habits.

Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis

Introduction: NAFLD is increasingly prevalent in Asia, where people suffer more metabolic comorbidities at a lower body mass index (BMI), suggesting potential differences in their clinical profile. Therefore, we attempted to characterize the clinical profile of Asians with NAFLD via a meta-analytic approach. Methods: We searched Pubmed, EMBASE, and Cochrane databases from January 1, 2000 to January 17, 2019. Two authors independently reviewed and selected 104 articles (2,247,754 persons) that identified NAFLD in Asians and reported relevant data, especially BMI and ALT, and excluded individuals with other liver disease and excessive alcohol consumption. Individual patient-level data were obtained from seven cohorts in Asia to complement meta-analyzed data. Results: Overall, the mean age was 52.07 (95%CI:51.28-52.85) years with those from Southeast Asia (42.66, 95%CI: 32.23-53.11) being significantly younger. The mean BMI was 26.2 kg/m2, higher in moderate-severe vs. mild hepatic steatosis (28.3 vs. 25.7) patients and NFS ≥-1.455 vs. <-1.455 (27.09 vs. 26.02), with 34% having non-obese NAFLD. The mean ALT was 31.74 U/L, higher in NFS <-1.455 vs. ≥-1.455 (33.74 vs. 27.83), though no differences were found by obesity or steatosis severity. The majority of males (85.7%) and females (60.7%) had normal to minimally elevated ALT (1-1.5x 95% ULN). Individual patient-level data analysis (N=7,668) demonstrated similar results. Conclusion: About one-third of Asians with NAFLD were non-obese and the majority did not have markedly elevated ALT. Therefore, abnormal ALT or BMI are not recommended as a criterion for NAFLD screening in this population. Additionally, there were significant differences in the clinical profiles of NAFLD among the different regions of Asia.

A Traditional Chinese Medicine Plant Extract Prevents Alcohol-Induced Osteopenia

Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including Astragalus, Cistanche deserticola, Dioscorea polystachya, Lycium barbarum, Epimedium, Cinnamomum cassia, Syzygium aromaticum, Angelica sinensis, and Curculigo orchioides. In this study, Balb/c male mice were orally administrated alcohol (3.2 g/kg/day) with/without TCM herbal extracts (0.125 g/kg, 0.25 g/kg, or 0.5 g/kg) by gavage. Our results showed that after 50 days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by μ-CT bone morphological analysis in young adults and middle-aged/old Balb/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates in vivo alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb/c male mice and in vitro ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.

Circulatory Glutathion S Transferases Estimation in Chronic Alcoholics Vising Urban and Rural Health Center

Introduction: Excessive alcohol consumption is a global healthcare problem with enormous social, economic, and clinical consequences, accounting for 3.3 million deaths in 2012. Glutathione (GSH) is tri-peptide thiol with chemical name γ glutamyl-cysteinyl-glycine the properties of glutathione are conferred to it by highly reactive thiol present in one of its constituent amino acids- cysteine, hence they referred as GSH. Xenobiotics form thioether (-S) linkage with GSH. The reaction is catalysed by enzyme known as glutathione S Transferases (GSTs). The cytoplasmic GSTs are important in the xenobiotic metabolism and are present in higher concentration in liver. Materials and Methods: The present study was conducted in the Dept. of Biochemistry in collaboration with Dept. of General Medicine at Datta Meghe Medical College, Nagpur. In present study includes 40 diagnosed alcoholic liver disease patients and 40 non-alcoholic healthy subjects as control group who are permanent nt of study area. Results: The level of GST was raised in chronic alcoholic patients i.e. study group (43.25±15.94) as compare to control group (1.57±0.55). At the other hand the level of total thiol were decreased in study group (3.12±0.55) as compare to control group. Conclusions: The strong negative association between glutathione-s-transferase (GST) and total thiol (T-SH) levels suggested that as the concentration of total thiol (T-SH) decreased, glutathione-s-transferase activity increased (GST). This may be attributed to an increase in alcohol-induced oxidative stress and increased T-SH utilization from thiols.

Modifiable Risk Factors for Dementia: The Role of Gut Microbiota

: Dementia is a syndrome resulting from chronic or progressive brain disease. Around 40% of worldwide dementia can be prevented or delayed by modifying 12 risk factors: low educational attainment in early life, mid-life hypertension, mid-life obesity, hearing loss, traumatic brain injury, excessive alcohol consumption, smoking, depression, physical inactivity, social isolation, diabetes mellitus, and air pollution. There is growing evidence that gastrointestinal tract microbiota may significantly contribute to dementia pathogenesis. In particular, gut dysbiosis can trigger metabolic diseases and the progression of low-grade systemic inflammation, being involved in much of the major modifiable risk factors. In this review, we focus on studies that have evaluated the association between modifiable risk factors for dementia and the role of gut microbiota. We also suggest clinical implications for researchers in dementia-gut microbiota related fields.