Protective effect of purple sweet potato leaf (Ipomoea batatas Linn Convolvulaceae) against alcohol-induced liver damage in mice

Purpose: To investigate the hepatoprotective effect of Ipomoea batatas extract against alcohol-induced liver damage in mice. Methods: Male C57BL/6 mice were randomly divided into 4 experimental groups (n = 10). Normal Group: The animals received distilled water 5 ml/kg for 7 days; Alcohol Group: The animals received alcohol 5 ml/kg of 40 % w/v alcohol for 7 days; Alcohol + Purple sweet potato leaf extract (PSPE) Group: PSPE 400 mg/kg was for 7 days. The animals received alcohol 5 ml/kg of 40 % w/v alcohol for 7 days; Alcohol + Hovenia dulcis Thunb extract (HDE) Group: HDE 400 mg/kg was for 7 days. To confirmed to the liver protection effect of PSPE, it was calculated, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC) in serum were detected. To evaluate changes of histological in alcohol-fed mice, liver tissue was determined by H&E staining. Results: Blood alcohol concentration in purple sweet potato leaf extract (PSPE) 200 mg/kg and Hovenia dulcis (H. dulcis) extract (HDE) 200 mg/kg treated group significantly decreased compared to - alcohol with water treated group (p < 0.05). Serum ALT (alanine aminotransferase) and AST (aspartate aminotransferase) were markedly reduced. Liver sections in mice stained with H&E (hematoxylin and eosin) stain to displayed the physiological changes in the liver tissue. Furthermore, the results showed that inflammatory cells increased in the alcohol group compared to the normal group, but spontaneously decreased in the PSPE or HDE-treated group. Conclusion: These results demonstrate that Ipomoea batatas may be therapeutically effective in protecting the liver from alcohol-induced hepatotoxicity and fatty liver.

Prevalence of marijuana use in pregnant women with concurrent opioid use disorder or alcohol use in pregnancy

Background A quarter of pregnant women use alcohol, 6.5/1000 deliveries are affected by opioid use disorder (OUD), and the prevalence of cannabis use in pregnant women is increasing. However, marijuana co-exposure in polysubstance-using women is not well described. Methods The well-characterized ENRICH-1 cohort (n = 251), which focused on the effects of two primary exposures of interest—opioids and alcohol, was used to (1) estimate the prevalence/frequency of marijuana use in those with OUD and/or alcohol use, and (2) examined correlates of marijuana use. Participants were classified into an OUD group (n = 125), Alcohol group (n = 69), and concurrent OUD and Alcohol (OUD + Alcohol) group (n = 57). Self-report and biomarkers ascertained substance use. Multivariable logistic regression identified correlates of marijuana use. Results The prevalence of any marijuana use in pregnancy was 43.2%, 52.6%, and 46.4% in the OUD, OUD + Alcohol, and Alcohol groups, respectively. Correspondingly, weekly or daily use was reported by 19.4%, 21.0%, and 24.6% of participants. In the OUD and OUD + Alcohol groups, the proportion of women using marijuana was significantly higher in those taking buprenorphine (45.8% and 58.3%, respectively) compared to women using methadone (37.5% and 42.9%, respectively). Mean maternal age was lower in women who used marijuana in all three groups compared to non-marijuana users. Independent correlates of marijuana use (controlling for group, race/ethnicity, education, and smoking) were maternal age (adjusted Odds Ratio (aOR) per 5-year increment 0.61; (95% CI 0.47, 0.79)), and polysubstance use (aOR 2.02; 95% CI 1.11, 3.67). There was a significant interaction between partnership status and group: among women who were not in a partnership, those in the OUD and OUD + Alcohol groups had lower odds of marijuana use relative to the Alcohol group. For women in the Alcohol group, partnered women had lower odds of marijuana use than un-partnered women (aOR 0.12; 95% CI: 0.02, 0.68). Conclusions Results indicate a relatively high prevalence and frequency of marijuana use in pregnant women being treated for OUD and/or women consuming alcohol while pregnant. These results highlight the need for ongoing risk reduction strategies addressing marijuana use for pregnant women receiving OUD treatment and those with alcohol exposure.

Meta-Analysis of Volatile Compounds from Vinegar Produced by the Slow Method and the Fast Method

Volatile compounds are one of the important characteristics of vinegar, where the content and composition of these compounds is an account for the aroma profile of vinegar. The difference in production technology used in making vinegar produces vinegar with different characteristics. There are two general methods commonly used in the production of vinegar, namely the slow method and the fast method. This meta-analysis was used to conclude several studies that examined the differences in volatile compounds in vinegar produced through the slow methods and the fast methods. From this study, it can be seen that comparison of volatile compounds characteristics in vinegar produced by the slow method and the fast method where the slow method tends to produce vinegar with a high concentration of acetate ester group and alcohol group, and the fast method tend to produced vinegar with a high concentration in a volatile acid group.

One-pot access to 2-oxazolines via a Castro-Stephens coupling and intramolecular cyclization

Aim: Here, we have reported easy one-pot access to a series of oxazolines using a modified Castro-Stephens coupling protocol. Background: 2-oxazolines have been shown to have significant biological activity and wide-ranging applications in organic chemistry. These properties make oxazolines as heterocyclic compounds of immense importance. Objective: The objective of this study is to synthesize oxazoline derivatives via an economical and one-pot protocol. Method: 2-oxazoline has been synthesized through Cu-powder mediated Castro-Stephens coupling and intramolecular cyclization route. The mechanism involves a rearrangement in which one of the oxygen from the N-acylamino alcohol group is liberated as water and then transferred to alkyne functionality to form 2-oxazoline derivatives. The oxazolines were characterized by NMR, mass, and XRD studies. Result: The protocol is economically viable and uses readily available Cu-powder along with DMF for cross-coupling and cyclization steps.

Behavioural and molecular effects of alcohol in the stress model of zebrafish

Objectives: Stress and anxiety disorders are common health problems that have been related to an increase in the likelihood of developing addictions, which have individual and social consequences. Although socially acceptable, alcohol is a substance that can generate dependence and abuse. Alcohol misuse, its relationship with stress and its consequences have been studied; however, multiple limitations are placed on clinical research in humans. In this exploratory work, we analysed the behavioural and molecular effects of joint exposure to ethanol and an unpredictable stress protocol (USP) in adult zebrafish. Materials and Methods: Adult zebrafish behaviour was studied employing unpredictable stress and behavioural tests. The tests were performed in stressed and nonstressed animals with and without exposure to known concentrations of alcohol. To evaluate the behaviour, tracking techniques were used on video recordings and parameters such as distance travelled, swimming speed and place preference as well as aggression patterns with mirror proximity tests were measured. In the control and 0.75% alcohol group, the expression of candidate stress-related genes (slc6a4a, slc6a3, comta and bdnf3) was analysed by RT-qPCR. Results: The results showed that concentrations of 0.75% alcohol reduced the locomotor activity of the fish, which can be interpreted as an increase in the anxiolytic effect of alcohol under nonstress conditions. Expression of comta, bdnf3 and slc6a3 was reduced in the stress and stress plus 0.75% ethanol groups and expression of slc6a4a was increased in the stress plus 0.75% alcohol group. Conclusion: Our exploratory work contributes novel insights about the molecular and behavioural effects of the combination of unpredicted stress and alcohol misuse. The USP and ethanol exposure increase anxiety behaviour and reduce the expression of genes involved in brain homeostasis. Future study of other pharmacological compounds and additional genes will be helpful for a deeper understanding of the molecular mechanisms involved in the response to stress and alcohol use.

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Objective. To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis as well as the alleviation of alcohol-induced kidney injury and inhibition of renal interstitial fibrosis by dapagliflozin. Methods. 48 male rats were randomly divided into 4 groups: control group, alcohol group, alcohol + dapagliflozin group, and alcohol + losartan group, each with 12 rats. Different drugs were administered by gavage for modeling and treatment. Six days later, the rats were sacrificed, blood was collected from the heart to separate the serum, and the blood creatinine (Scr) and urea nitrogen (BUN) contents were detected biochemically. After blood collection, the kidney tissue was taken and fixed in10% neutral formalin. The expression of renal tissue inflammatory factors (CRP, IL-6, and TNF-α) and renal fibrosis indexes (LN, HA, and TGF-β1) were detected; MMP-24 and TIMP-1 in the kidney tissue of rats in different treatment groups were detected, and Smad3 expression was also detected. Results. After treatment, the general condition of the alcohol + dapagliflozin group and the alcohol + losartan group improved to different degrees. The weight first decreased and then gradually increased over time. There was no statistical difference in the weight change between the two groups; Compared with the control group, the Scr level, BUN content, renal index, inflammatory factors, and renal fibrosis indexes in the alcohol group were significantly increased ( P < 0.05 ); after 6 weeks of treatment, in the alcohol + dapagliflozin group and alcohol + losartan group, Scr level, BUN content, kidney index, inflammatory factors, and renal fibrosis indexes were significantly decreased ( P < 0.05 ); the expression of MMP-24 in the kidney tissue of the control group was upregulated, and the expression of TIMP-1 and Smad3 was downregulated; MMP-24 expression was downregulated, and TIMP-1 and Smad3 expression was significantly upregulated ( P < 0.05 ) in the rats of the alcohol group. After dapagliflozin and losartan treatment, MMP-24 expression gradually increased and TIMP-1 and Smad3 expression gradually decreased ( P < 0.05 ). Conclusion. Long-term large-scale alcohol intake can cause kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be decreased. However, dapagliflozin and losartan have certain therapeutic effects on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and Smad3 and upregulating the expression of MMP-24 and other cytokines in the kidney.

Plasma Concentrations of Lysophosphatidic Acid and Autotaxin in Abstinent Patients with Alcohol Use Disorder and Comorbid Liver Disease

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid and a bioactive lipid that is synthesized by the enzyme autotaxin (ATX). The ATX–LPA axis has been associated with cognitive dysfunction and inflammatory diseases, mainly in a range of nonalcoholic liver diseases. Recently, preclinical and clinical evidence has suggested a role of LPA signaling in alcohol use disorder (AUD) and AUD-related cognitive function. However, the ATX–LPA axis has not been sufficiently investigated in alcoholic liver diseases. An exploratory study was conducted in 136 participants, 66 abstinent patients with AUD seeking treatment for alcohol (alcohol group), and 70 healthy control subjects (control group). The alcohol group was divided according to the presence of comorbid liver diseases (i.e., fatty liver/steatosis, alcoholic steatohepatitis, or cirrhosis). All participants were clinically evaluated, and plasma concentrations of total LPA and ATX were measured using enzyme-linked immunosorbent assays. Data were primarily analyzed using analysis of covariance (ANCOVA) while controlling for age, body mass index, and sex. Logistic regression models were created to assess the association of the ATX–LPA axis and AUD or liver disease. LPA and ATX were log10-transformed to fit the assumptions of parametric testing.The main results were as follows: total LPA and ATX concentrations were dysregulated in the alcohol group, and patients with AUD had significantly lower LPA (F(1,131) = 10.677, p = 0.001) and higher ATX (F(1,131) = 8.327, p = 0.005) concentrations than control subjects; patients with AUD and liver disease had significantly higher ATX concentrations (post hoc test, p < 0.05) than patients with AUD but not liver disease; significant correlations between AUD-related variables and concentrations of LPA and ATX were only found in the non-liver disease subgroup (the duration of alcohol abstinence with LPA and ATX (r = +0.33, p < 0.05); and the severity of AUD with ATX (rho = −0.33, p < 0.05)); and a logistic regression model with LPA, ATX, and AUD-related variables showed an excellent discriminative power (area under the curve (AUC) = 0.915, p < 0.001) for distinguishing patients with AUD and comorbid liver disease. In conclusion, our data show that the ATX–LPA axis is dysregulated in AUD and suggest this lipid signaling, in combination with relevant AUD-related variables, as a reliable biomarker of alcoholic liver diseases.

Unhealthy alcohol use is an independent risk factor for increased COVID-19 disease severity: observational cross-sectional study (Preprint)

BACKGROUND Unhealthy alcohol use (UAU) is known to disrupt pulmonary immune mechanisms and increase the risk of acute respiratory distress syndrome in patients with pneumonia; however, little is known about the effects of UAU on outcomes in patients with COVID-19 pneumonia. To our knowledge, this is the first observational cross-sectional study that aims to understand the effect of UAU on the severity of COVID-19 disease. OBJECTIVE We aim to determine if UAU is associated with more severe clinical presentation and worse health outcomes related to COVID-19 and if socioeconomic status, smoking, age, body mass index (BMI), race/ethnicity, and pattern of alcohol use modify the risk. METHODS In this observational cross-sectional study, we ran a digital machine learning classifier on the electronic health record of patients who tested positive via nasopharyngeal swab for SARS-CoV-2 or had two COVID-19 international classification of disease codes to identify patients with UAU. We then performed a multivariable regression to examine the relationship between UAU and COVID-19 severity as measured by hospital care level, i.e. emergency department admission, emergency department admission with ventilator, or death. We used a predefined cutoff of 0.15 (optimal sensitivity and specificity) on the digital classifier to compare disease severity in patients with versus without UAU. Models were adjusted for age, sex, race/ethnicity, BMI, smoking status, and insurance status. RESULTS Each incremental increase in the predicted probability from the digital alcohol classifier was associated with a greater odds risk for more severe COVID-19 disease(OR 1.15, 95% CI: 1.10 - 1.20). Using the predefined cut-off of 0.15 to group patients into binary unhealthy alcohol group or not, we found that the unhealthy alcohol group had a greater odds risk to develop more severe disease (OR = 1.89, 95% CI: 1.17 - 3.06), suggesting that alcohol positive classification was associated with a 89% increase in the odds of being in a higher severity category. CONCLUSIONS In patients infected with SARS-CoV-2, UAU is an independent risk factor associated with greater disease severity and/or death.

Chlorhexidine–alcohol versus povidone–iodine as preoperative skin antisepsis for prevention of surgical site infection in cesarean delivery—a pilot randomized control trial

Objectives To compare the efficacy of chlorhexidine–alcohol and povidone–iodine as preoperative antiseptic skin preparation for prevention of surgical site infection (SSI) after cesarean delivery (CD). Materials and methods A total of 311 eligible women who underwent CS were recruited in the study after fulfilling all the eligibility and exclusion criteria. Patients were randomized into two groups (153 in chlorhexidine–alcohol group and 158 in povidone–iodine group) by a computer-generated randomization table. Patients were followed for a period of 30 days in postoperative period to monitor for SSI. Results The rate of SSI in the chlorhexidine–alcohol group is 5.4% and that of the povidone–iodine group is 8.6%. E. coli, K. pneumoniae, and Acinetobacter baumannii were the most common organisms isolated. E. coli was found in 9.5% of the total SSI cases. Conclusions The study found that the patients who received chlorhexidine–alcohol as skin antiseptic had less chance of developing SSI than those who received povidone–iodine; however, it did not reach a statistical significance. Trial registration Clinical Trials Registry of India CTRI/2018/05/014294. Registered on May 31, 2018

A Putative Lignin Copper Oxidase from Trichoderma reesei

The ability of Trichoderma reesei, a fungus widely used for the commercial production of hemicellulases and cellulases, to grow and modify technical soda lignin was investigated. By quantifying fungal genomic DNA, T. reesei showed growth and sporulation in solid and liquid cultures containing lignin alone. The analysis of released soluble lignin and residual insoluble lignin was indicative of enzymatic oxidative conversion of phenolic lignin side chains and the modification of lignin structure by cleaving the β-O-4 linkages. The results also showed that polymerization reactions were taking place. A proteomic analysis conducted to investigate secreted proteins at days 3, 7, and 14 of growth revealed the presence of five auxiliary activity (AA) enzymes in the secretome: AA6, AA9, two AA3 enzymes), and the only copper radical oxidase encoded in the genome of T. reesei. This enzyme was heterologously produced and characterized, and its activity on lignin-derived molecules was investigated. Phylogenetic characterization demonstrated that this enzyme belonged to the AA5_1 family, which includes characterized glyoxal oxidases. However, the enzyme displayed overlapping physicochemical and catalytic properties across the AA5 family. The enzyme was remarkably stable at high pH and oxidized both, alcohols and aldehydes with preference to the alcohol group. It was also active on lignin-derived phenolic molecules as well as simple carbohydrates. HPSEC and LC-MS analyses on the reactions of the produced protein on lignin dimers (SS ββ, SS βO4 and GG β5) uncovered the polymerizing activity of this enzyme, which was accordingly named lignin copper oxidase (TrLOx). Polymers of up 10 units were formed by hydroxy group oxidation and radical formation. The activations of lignin molecules by TrLOx along with the co-secretion of this enzyme with reductases and FAD flavoproteins oxidoreductases during growth on lignin suggest a synergistic mechanism for lignin breakdown.