Long-term Alcohol Consumption Research Articles

Alcoholic Cardiomyopathy: a summary of current knowledge and possible future directions

Introduction and purpose: Ethanol is still one of the most frequently consumed drugs worldwide and is a strong risk factor for more than 60 illnesses including alcoholic cardiomyopathy which is a specific heart muscle disease caused by long-term excessive alcohol consumption. The review aims to gather available data and summarize it to give better understanding of the disease, to help select patients with the condition to implement proper treatment, and to present possible future directions as the incidence of the disease is projected to persist in the future. Brief description of the state of knowledge: Alcoholic cardiomyopathy (ACM) is characterized by dilation, increased mass of the left ventricle, and reduced ejection fraction leading to end-stage heart failure. It is caused by ethanol’s direct toxicity on myocytes disturbing many different metabolic pathways. The result is a decrease in both systolic and diastolic function of the heart. The ACM development depends on factors such as genetics, gender, dietary factors and the dosage of ethanol consumption. The goal of the treatment is total alcohol abstinence, but the reduction of ethanol intake may also be beneficial. Patients should obtain a complete pharmacological treatment for heart failure. Summary: Ethanol overconsumption remains an unresolved problem, with the incidence of ACM projected to persist in the future, especially among patients with alcohol use disorder (AUD). Efforts for prevention, early detection, and effective treatment of ACM need to be established. A primary focus should be on treating AUD because it is the most effective way to halt the progression of the disease. Further research should focus on both asymptomatic and symptomatic patients with AUD to better define clinical manifestations, diagnostic approaches, and the most effective treatments for ACM.

Fucoidan from Apostichopus japonicus ameliorates alcoholic liver disease by regulating gut-liver axis homeostasis

Long-term and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD), characterized by oxidative damage, intestinal barrier injury, and disruption of intestinal microbiota. In this study, we extracted fucoidan (Aj-FUC) from Apostichopus japonicus using enzymatic methods and characterized its structure. The ALD model was established in male Balb/c mice using 56° Baijiu, with silymarin as a positive control. Mice were orally administered 100 mg/kg·bw and 300 mg/kg·bw of Aj-FUC for 28 days to evaluate its effects on liver injury in ALD mice and explore its potential role in modulating the gut-liver axis. The results showed significant improvements in histopathological changes and liver disease in the Aj-FUC group. Aj-FUC treatment significantly increased the levels of glutathione (GSH) and glutathione peroxidase (GSH-Px) while weakly reduced the elevation of malondialdehyde (MDA) induced by ALD. It also regulated the Nrf2/HO-1 signaling pathway, collectively alleviating hepatic oxidative stress. Aj-FUC intervention upregulated the expression of ZO-1 and Occludin, thus contributing to repair the intestinal barrier. Additionally, Aj-FUC increased the content of short-chain fatty acids (SCFAs) and regulated the imbalance in gut microbiota. These results suggested that Aj-FUC alleviates ALD by modulating the gut-liver axis homeostasis. It may prove to be a useful dietary supplement in the treatment of alcoholic liver damage.

Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice.

Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae, meanwhile, the abundances of Bacteroides, Blautia, Collinsella, Escherichia-Shigella, Enterococcus, Prevotella, [Ruminococcus]_gnavus_group, Methylobacterium-Methylorubrum, Romboutsia, Streptococcus, Bilophila, were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.

Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke

Background and purposeMicrobial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics.MethodsBlood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining.Results16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10–9.27; p = 0.033).ConclusionBacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

Epigenetic Modulation of DDIT3 and MGMT Expression Acts Synergistically with Resistance to Imatinib towards CML Disease Progression: A Hospital based Study.

Imatinib Mesylate is an authenticated drug that aids in the treatment of Chronic Myeloid Leukaemia and Philadelphia patients which is recognized as a BCR-ABL tyrosine kinase inhibitor. Indeed, DNA Methylation occupies a key role in the stability of chromosomes. Changes in the methylation status of genes may impart to the advancement of Chronic Myeloid Leukaemia. The present investigation aims to assess the role of expression analysis and methylation status of DDIT3 and MGMT genes in imatinib-resistant and nonresistant cases. The Imatinib resistance was screened through RFLP. In this case maximum number of patients were recorded in the chronic phase belonging to the age group 40-59 and the accelerated and blast phase is more common in elderly patients showing the progressive nature of the disease with age. Hemoglobin and platelet count are found to be higher in cases where WBC count was minimal. A history of long-term alcohol consumption is found to be associated with the progression of the disease. The maximum level of expression of the DDIT3 gene was recorded in the chronic phase regardless of upstream (67.8%) and downstream (57.9%) regulation. The highest MGMT expression regulation was also observed in the case of chronic phase in both upstream (78.9%) and downstream (44%) regulation. Further, the MGMT gene showed the highest methylation of 6.6% and DDIT3 showed 3.3% in CML cases. In the present study notable depletion of survivality was established in the Imatinib resistance patients manifesting genetic malfunction of BCR-ABL transcripts among the North East Indian inhabitants and advocating for the expansion of the disease.

Circulating metabolites may illustrate relationship of alcohol consumption with cardiovascular disease

BackgroundMetabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.MethodsCumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).ResultsWe identified 60 metabolites associated with cumulative average alcohol consumption (p < 0.05/211 ≈ 0.00024). For example, 1 g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta = 0.023 ± 0.002, p = 6.3e − 45) and phosphatidylcholine (e.g., PC 32:1, beta = 0.021 ± 0.002, p = 3.1e − 38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11 (95% CI = [1.02, 1.21], p = 0.02) vs 0.88 (95% CI = [0.78, 0.98], p = 0.02).ConclusionsWe identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.

Evaluation of Raktadushti in Madatyaya Vyadhi: A Cross Sectional Observational Study

All over the world, alcohol consumption is becoming a lifestyle. The fashion of alcohol ingestion leads to habits of chronicalcoholism. Alcoholism (Madyapaan) is a behavioral disorder characterized by repetitive and excessive consumption of alcohol (Madya). It isobserved that long-term consumption of alcohol damages the liver to a very large extent, leading to either Alcoholic liver disease or livercirrhosis. In Ayurveda, this condition can be correlated with 'Madatyaya.' Madya is described as the main etiological factor of various diseasesat multiple places in Ayurvedic classics, but madatyaya is a primary one. Ayurved explains the etiology, pathogenesis, and treatment ofmadatyaya, but the specific srotodushti is not explained. When characteristics of madya and causative moolasthanavikruti (Hepatotoxicity) areconsidered, it is assumed that madya may cause raktadushti also. Hence this topic is an attempt to evaluate raktadushti in madatyaya vyadhi. Itis a cross-sectional observational study performed on 50 patients of Madatyaya. Patients were examined thoroughly, and all the details werenoted in a specially designed case record format. A comparative study of madatyaya and raktadushti was conducted; also assessment ofraktadushti was done based on symptoms of raktadushti observed in those patients. Collected data and the observations are then analyzed bystatistical tests such as the chi-square test and correlation regression. This study proves the positive correlation between madyatyaya andraktadushti. It may be the alcohol metabolized primarily in the liver, which is getting damaged by long-term consumption. Ayurveda explainsYakrita and pleeha as the moolasthana (roots) of Raktavaha srotas. This moolasthana dushti (damage to the root) causes damage to the wholesystem (Raktavaha srotas); hence madatyaya vyadhi can be labeled as a disease of Raktavaha srotas.

Alcohol consumption and epigenetic age acceleration across human adulthood.

The alcohol-associated biological aging remains to be studied across adulthood. We conducted linear regression analyses to investigate the associations between alcohol consumption and two DNA methylation-based biological age acceleration metrics in 3823 Framingham Heart Study participants (24-92 years and 53.8% women) adjusting for covariates. We also investigated whether the two epigenetic aging metrics mediated the association of alcohol consumption with hypertension. We found that higher long-term average alcohol consumption was significantly associated with biological age acceleration assessed by GrimAge acceleration (GAA) and PhenoAge acceleration (PAA) in middle-aged (45-64 years, n = 1866) and older (65-92 years, n = 1267) participants while not in young participants (24-44 years, n = 690). For example, one additional standard drink of alcohol (~14 grams of ethanol per day) was associated with a 0.71 ± 0.15-year (p = 2.1e-6) and 0.60 ± 0.18-year (p = 7.5e-4) increase in PAA in middle-aged and older participants, respectively, but the association was not significant in young participants (p = 0.23). One additional standard serving of liquor (~14 grams of ethanol) was associated with a greater increase in GAA (0.82-year, p = 4.8e-4) and PAA (1.45-year, p = 7.4e-5) than beer (GAA: 0.45-year, p = 5.2e-4; PAA: 0.48-year, p = 0.02) and wine (GAA: 0.51-year, p = 0.02; PAA: 0.91-year, p = 0.008) in middle-aged participant group. We observed that up to 28% of the association between alcohol consumption and hypertension was mediated by GAA or PAA in the pooled sample. Our findings suggest that alcohol consumption is associated with greater biological aging quantified by epigenetic aging metrics, which may mediate the association of alcohol consumption with quantitative traits, such as hypertension.

Age features of the correction of alcohol motivation and voluntary alcohol consumption by intranasal administration of dehydroepiandrosterone under long-term preventive alcoholization (experimental study)

We studied the effect of exogenous DHEA on the severity of alcohol motivation in animals of mature and adolescent-pubertal periods of ontogenesis using a model of voluntary ad libitum consumption of ethanol with determination of its level and preference index in a 2-bottle test. Course intranasal administration of DHEA under conditions of long-term preventive alcoholization, has a normalizing effect on emotional-motor activity and weakens anxiety-phobic reactions, which leads to the predominance of the sociocentric type in the structure of zoosocial behavior of animals. At the same time, there is a significant (by 74 %, p ≤ 0.001) decrease in the ethanol preference index in the situation of alcohol free choice, which reflects the suppression of alcohol motivation in mature adult male rats. Such effects of DHEA may indicate its certain therapeutic potential under psychoemotional disorders due to long-term alcohol consumption on the background of age-related peripheral neurosteroid hormone deficiency. In comparison, there were no found such properties during puberty, which is characterized by the highest intensity of endogenous DHEA production. Key words: periods of ontogenesis, disorders due to ethanol consumption, zoosocial behavior, intranasal administration of DHEA, correction of alcohol motivation

Lyso-phosphatidylethanol detected by LC-MS/MS as a potential new marker for alcohol consumption.

Alcohol biomarkers are able to reflect the degree of recent or long-term alcohol consumption, covering different windows of detection. Phosphatidylethanols (PEths) are an emerging group of direct alcohol biomarkers that are widely applied in clinical and forensic applications. Their quantification can provide insight into an individual's drinking behaviour. Here, we present a new sub-class of yet unknown PEth species, LysoPEths, which are structurally related to PEth, but miss one fatty acyl chain. LysoPEths can be either a degradation product of PEth or a product of transesterification of lyso-phosphatidylcholine (LysoPC) with ethanol. To set up an analytical method, LysoPEth 16:0 was synthesised from PC 16:0/18:1 and characterised by LC-MS/MS, using an enzymatic method: phospholipase D (PLD), followed by phospholipase A2 (PLA2). Then, an LC-MS/MS method in MRM mode for LysoPEth 16:0 with additional LysoPEth species (LysoPEth 18:1, LysoPEth 18:2, and LysoPEth 20:4) and PEth 16:0/20:4 was developed. By incubation of freshly sampled venous blood of a teetotaller with ethanol at different concentrations, the formation of LysoPEth in parallel to PEth was investigated. With increasing ethanol concentrations, LysoPEth 16:0 was formed besides the known PEth species (PEth 16:0/18:1, PEth 16:0/18:2) for up to 72 h with LysoPEth concentrations being about three times lower than PEth concentrations. Storage of ethanol-free PEth-positive blood of an alcohol consumer at 37 °C showed that LysoPEth 16:0 concentrations increased, while PEth 16:0/18:1 concentrations decreased in the first 24 h for frozen/thawed blood, however not for freshly collected blood. Furthermore, LysoPEth 16:0 was detected in venous as well as lyophilised blood from clinical and forensic case work alongside with PEth 16:0/18:1, 16:0/18:2, and other PEth and LysoPEth species (PEth 16:0/20:4, LysoPEth 18:1, LysoPEth 18:2, and LysoPEth 20:4). LysoPEth 16:0 concentrations were found to be in linear correlation with PEth 16:0/18:1 (r2 = 0.75).

Effects of alcohol on the symptoms of gouty arthritis and taxonomic structure of gut microbiota in C57BL/6 mice.

Gout is an acute arthritis caused by the elevated levels of serum uric acid (UA), and its prevalence has been rapidly increasing. Alcohol abuse could lead to a series of health problems. Multiple pieces of evidence suggest that alcohol intake affects the development and progression of gout, while the gut microbiota plays an important role in the development of gout and the long-term alcohol consumption could affect the stability of the gut microbiota. This study aimed to explore the effects of alcohol intake at different concentrations on gouty arthritis based on the gut microbiota. We investigated the effects of different concentrations of alcohol on gouty arthritis in mouse models of acute gouty arthritis established by injection of monosodium urate (MSU) crystals into C57BL/6 mice. The results indicated that the high-alcohol consumption not only exacerbated joint swelling and pain, increased the levels of UA, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), but also showed dramatic effects on the composition and structure of the gut microbiota in gouty mice. Two key microorganisms, Parasutterella and Alistipes, could aggravate gout symptoms through lipopolysaccharide biosynthesis, riboflavin metabolism, phenylalanine metabolism, and arginine and proline metabolisms. In conclusion, our study suggested that high-concentrations of alcohol altered the gut microbiota structure in gouty mice induced by MSU crystals, which could exacerbate gouty symptoms by enhancing pro-inflammatory pathways.

Long-Term Alcohol-Activated c-Jun N-terminal Kinase Isoform 2 Preserves Cardiac Function but Drives Ca2+-Triggered Arrhythmias.

Long-term alcohol consumption leads to cardiac arrhythmias including atrial fibrillation (AF), the most common alcohol-related arrhythmia. While AF significantly increases morbidity and mortality in patients, it takes years for an alcoholic individual undergoing an adaptive status with normal cardiac function to reach alcoholic cardiomyopathy. The underlying mechanism remains unclear to date. In this study, we assessed the functional role of JNK2 in long-term alcohol-evoked atrial arrhythmogenicity but preserved cardiac function. Wild-type (WT) mice and cardiac-specific JNK2dn mice (with an overexpression of inactive dominant negative (dn) JNK2) were treated with alcohol (2 g/kg daily for 2 months; 2 Mo). Confocal Ca2+ imaging in the intact mouse hearts showed that long-term alcohol prolonged intracellular Ca2+ transient decay, and increased pacing-induced Ca2+ waves, compared to that of sham controls, while cardiac-specific JNK2 inhibition in JNK2dn mice precluded alcohol-evoked Ca2+-triggered activities. Moreover, activated JNK2 enhances diastolic SR Ca2+ leak in 24 h and 48 h alcohol-exposed HL-1 atrial myocytes as well as HEK-RyR2 cells (inducible expression of human RyR2) with the overexpression of tGFP-tagged active JNK2-tGFP or inactive JNK2dn-tGFP. Meanwhile, the SR Ca2+ load and systolic Ca2+ transient amplitude were both increased in ventricular myocytes, along with the preserved cardiac function in 2 Mo alcohol-exposed mice. Moreover, the role of activated JNK2 in SR Ca2+ overload and enhanced transient amplitude was also confirmed in long-term alcohol-exposed HL-1 atrial myocytes. In conclusion, our findings suggest that long-term alcohol-activated JNK2 is a key driver in preserved cardiac function, but at the expense of enhanced cardiac arrhythmogenicity. Modulating JNK2 activity could be a novel anti-arrhythmia therapeutic strategy.

The Hepatic Nerves Regulated Inflammatory Effect in the Process of Liver Injury: Is Nerve the Key Treating Target for Liver Inflammation?

Liver injury is a common pathological basis for various liver diseases. Chronic liver injury is often an important initiating factor in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, hepatitis A and E infections are the most common causes of acute liver injury worldwide, whereas drug toxicity (paracetamol overdose) in the USA and part of Western Europe. In recent years, chronic liver injury has become a common disease that harms human health. Meanwhile, the main causes of chronic liver injury are viral hepatitis (B, C) and long-term alcohol consumption worldwide. During the process of liver injury, massive inflammatory cytokines are stimulated by these hazardous factors, leading to a systemic inflammatory response syndrome, followed by a compensatory anti-inflammatory response, which causes immune cell dysfunction and sepsis, subsequent multi-organ failure. Cytokine release and immune cell infiltration-mediated aseptic inflammation are the most important features of the pathobiology of liver failure. From this perspective, diminishing the onset and progression of liver inflammation is of clinical importance in the treatment of liver injury. Although many studies have hinted at the critical role of nerves in regulating inflammation, there largely remains undetermined how hepatic nerves mediate immune inflammation and how the inflammatory factors released by these nerves are involved in the process of liver injury. Therefore, the purpose of this article is to summarize previous studies in the field related to hepatic nerve and inflammation as well as future perspectives on the aforementioned questions. Our findings were presented in three aspects: types of nerve distribution in the liver, how these nerves regulate immunity, and the role of liver nerves in hepatitis and liver failure.

Attenuated Total Reflection Fourier Transform Infrared Spectroscopy for Forensic Screening of Long-Term Alcohol Consumption from Human Nails.

Fourier transform infrared (FT-IR) spectroscopy is used throughout forensic laboratories for many applications. FT-IR spectroscopy can be useful with ATR accessories in forensic analysis for several reasons. It provides excellent data quality combined with high reproducibility, with minimal user-induced variations and no sample preparation. Spectra from heterogeneous biological systems, including the integumentary system, can be associated with hundreds or thousands of biomolecules. The nail matrix of keratin possesses a complicated structure with captured circulating metabolites whose presence may vary in space and time depending on context and history. We developed a new approach by using machine-learning (ML) tools to leverage the potential and enhance the selectivity of the instrument, create classification models, and provide invaluable information saved in human nails with statistical confidence. Here, we report chemometric analysis of ATR FT-IR spectra for the classification and prediction of long-term alcohol consumption from nail clippings in 63 donors. A partial least squares discriminant analysis (PLS-DA) was used to create a classification model that was validated against an independent data set which resulted in 91% correctly classified spectra. However, when considering the prediction results at the donor level, 100% accuracy was achieved, and all donors were correctly classified. To the best of our knowledge, this proof-of-concept study demonstrates for the first time the ability of ATR FT-IR spectroscopy to discriminate donors who do not drink alcohol from those who drink alcohol on a regular basis.

Pseudoexfoliation Syndrome-Clinical Characteristics of Most Common Cause of Secondary Glaucoma.

Pseudoexfoliation syndrome (XFS) is a condition in which excess material builds up not only in the structures of the anterior chamber but also throughout the body. The frequency of the syndrome varies significantly (0.3-18%) depending on the region and the method of examination. Environmental risk factors for XFS include a large number of sunny days, proximity to the equator, dietary factors such as higher consumption of coffee and tea, long-term alcohol consumption, exposure to UV, and outdoor work. The pathognomonic sign of XFS is the presence of white material on the lens capsule and other anterior chamber components. In addition, a characteristic Sampaolesi line can be observed during gonioscopy. Systemic alterations indicative of XFS have been observed in the extracellular matrix of the eyelid skin, the heart, lungs, liver, kidneys, gallbladder, meninges, and endothelium of the blood vessels. XFS is the most common cause of secondary open-angle glaucoma, which is called pseudoexfoliative glaucoma and is more severe than primary open-angle glaucoma. It is plausible that a combination of environmental factors and genetic alterations promotes the onset of pseudoexfoliation syndrome, which requires additional research.

NEUROGENIC BLADDER INDUCED BY CHRONIC ALCOHOL ABUSE: A CASE REPORT

Long-term alcohol consumption may produce wide-ranging effects on the autonomic and peripheral nervous systems like almost all body tissues, but the pathogenesis is still under debate. We presented an extremely rare case of autonomic neurogenic bladder with bilateral hydroureteronephrosis in a male patient describing progressive abdominal distension over a year that is most significant in the last 4 months following alcohol withdrawal after a long duration of alcohol abuse. Chronic alcoholism should be considered in the differential diagnosis of a neurogenic bladder, which may be caused by autonomic dysfunction due to chronic alcohol abuse and may be precipitated by alcohol withdrawal.

A Review of the Global Microgreens’ Market by most Popular Species Grown, Farming types and Practices, end users, Revenue Generated: Opportunity Analysis, and Industry Forecast

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

Alleviation of Alcoholic Fatty Liver by Dendrobium officinale Flower Extracts due to Regulation of Gut Microbiota and Short-Chain Fatty Acids in Mice Exposed to Chronic Alcohol.

Alcoholic fatty liver disease (AFLD) is caused by long-term heavy alcohol consumption; therefore, useful and practical methods for the prevention of AFLD are urgently needed. The edible flower of Dendrobium officinale contains diverse flavonoids, and has shown antioxidant activity as well as antihypertensive and anti-inflammatory effects. In this study, an AFLD model was established, the protective effect of D. officinale flower (DOF) ethanol extract on AFLD was evaluated, and its mechanisms were investigated by analyzing gut microbiota and short-chain fatty acids (SCFAs). DOF extract (DOFE) supplementation promoted alcohol metabolism, restored hepatic antioxidant capacity, alleviated oxidative stress, reduced inflammatory factor levels, and inhibited dyslipidemia induced by alcohol intake in chronic alcohol-exposed mice, especially in the high DOFE group. Moreover, DOFE supplementation increased the diversity, structure, and composition of the gut microbiota in mice, restored some of the abnormal SCFA levels caused by AFLD, and helped restore intestinal function. DOFE supplementation significantly increased the relative abundance of Akkermansia, suggesting that Akkermansia may be a potential target of the protective effect of DOFE. Therefore, DOFE supplementation to improve the composition of the gut microbiota may be an effective therapeutic strategy for the prevention of AFLD.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

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

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