Ameliorative potential of ethanol extract of Calyptrochilum emarginatum leaves on scopolamine-induced amnesia in male swiss mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Calyptrochilum emarginatum (Afzel. Ex Sw.) Schltr. (Orchidaceae) is a traditional medicinal plant known for its antimicrobial properties and efficacy in managing convulsive fever and menstrual disorders and addressing conditions such as malaria, tuberculosis, and cough. AIM OF THE STUDY: The study aims to examine the memory-enhancing and neuroprotective properties of ethanol extract of Calyptrochilum emarginatum leaves (EECEL) in scopolamine-induced amnesia mice model. MATERIALS AND METHODS: Forty-two male mice were divided into six groups (n = 7). Group 1 served as control, administered distilled water (10 mL/kg, p. o), group 2 received scopolamine only (3 mg/kg, i. p.), groups 3 to 6 received pretreatments of EECEL (50, 100, and 200 mg/kg, p. o.) and donepezil (1 mg/kg, p. o.) 30 min before scopolamine (3 mg/kg), for seven days. Following treatments, behavioral (learning and memory) assessments were carried out, while biochemical (acetylcholinesterase activity, oxidative stress markers, inflammatory cytokines markers) and histological evaluations were done after euthanasia. RESULTS: Scopolamine significantly impaired spatial, long term and recognition memory. Nevertheless, administration of EECEL (50, 100, and 200 mg/kg orally) enhanced memory function in mice, as observed in the Y maze [F (5, 30) = 20.23, p < 0.0001], Morris water maze [F (10, 90) = 3.105, p = 0.0019; [F (5, 30) = 21.13, p < 0.0001]], and novel object recognition tasks [F (5, 30) = 37.22, p < 0.0001)]. Scopolamine-treated mice exhibited significant dysfunction in the cholinergic system, as evidenced by elevated AChE activity [0.099 ± 0.005 vs. 0.063 ± 0.004 mol/min/g] with an elevation in oxidative stress. On the other hand, administration of EECEL counteracted these consequences by reducing AChE activity, mitigating oxidative damage, reducing pro-inflammatory cytokines, and preventing degeneration of neurons. CONCLUSION: The results demonstrated that EECEL effectively mitigates scopolamine-induced memory impairment via an oxido-inflammatory mechanism and modulation of the central cholinergic system.

Application of electroencephalogram (EEG) in the study of the influence of different contents of alcohol and Baijiu on brain perception.

Alcoholic beverages flavour is complex and unique with different alcohol content, and the application of flavour perception could improve the objectivity of flavour evaluation. This study utilized electroencephalogram (EEG) to assess brain reactions to alcohol percentages (5 %-53 %) and Baijiu's complex flavours. The findings demonstrate the brain's proficiency in discerning between alcohol concentrations, evidenced by increasing physiological signal strength in tandem with alcohol content. When contrasted with alcohol solutions of equivalent concentrations, Baijiu prompts a more significant activation of brain signals, underscoring EEG's capability to detect subtleties due to flavour complexity. Additionally, the study reveals notable correlations, with δ and α wave intensities escalating in response to alcohol stimulation, coupled with substantial activation in the frontal, parietal, and right temporal regions. These insights verify the efficacy of EEG in charting the brain's engagement with alcoholic flavours, setting the stage for more detailed exploration into the neural encoding of these sensory experiences.

Tailored design of novel Co0-Coδ+ dual phase nanoparticles for selective CO2 hydrogenation to ethanol.

Catalytic hydrogenation of CO2 to ethanol is a promising solution to address the greenhouse gas (GHG) emissions, but many current catalysts face efficiency and cost challenges. Cobalt based catalysts are frequently examined due to their abundance, cost-efficiency, and effectiveness in the reaction, where managing the Co0 to Coδ+ ratio is essential. In this study, we adjusted support nature (Al2O3, MgO-MgAl2O4, and MgO) and reduction conditions to optimize this balance of Co0 to Coδ+ sites on the catalyst surface, enhancing ethanol production. The selectivity of ethanol reached 17.9% in a continuous flow fixed bed micro-reactor over 20 mol% Co@MgO-MgAl2O4 (CoMgAl) catalyst at 270 °C and 3.0 MPa, when reduced at 400 °C for 8 h. Characterisation results coupled with activity analysis confirmed that mild reduction condition (400 °C, 10% H2 balance N2, 8 h) with intermediate metal support interaction favoured the generation of partially reduced Co sites (Coδ+ and Co0 sites in single atom) over MgO-MgAl2O4 surface, which promoted ethanol synthesis by coupling of dissociative (CHx*)/non-dissociative (CHxO*) intermediates, as confirmed by density functional theory analysis. Additionally, the CoMgAl, affordably prepared through the coprecipitation method, offers a potential alternative for CO2 hydrogenation to yield valuable chemicals.

Oxygen alters redox cofactor dynamics and induces metabolic shifts in Saccharomyces cerevisiae during alcoholic fermentation.

Environmental conditions significantly impact the metabolism of Saccharomyces cerevisiae, a Crabtree-positive yeast that maintains a fermentative metabolism in high-sugar environments even in the presence of oxygen. Although the introduction of oxygen has been reported to induce alterations in yeast metabolism, knowledge of the mechanisms behind these metabolic adaptations in relation to redox cofactor metabolism and their implications in the context of wine fermentation remains limited. This study aimed to compare the intracellular redox cofactor levels, the cofactor ratios, and primary metabolite production in S. cerevisiae under aerobic and anaerobic conditions in synthetic grape juice. The molecular mechanisms underlying these metabolic differences were explored using a transcriptomic approach. Aerobic conditions resulted in an enhanced fermentation rate and biomass yield. Total NADP(H) levels were threefold higher during aerobiosis, while a decline in the total levels of NAD(H) was observed. However, there were stark differences in the ratio of NAD+/NADH between the treatments. Despite few changes in the differential expression of genes involved in redox cofactor metabolism, anaerobiosis resulted in an increased expression of genes involved in lipid biosynthesis pathways, while the presence of oxygen increased the expression of genes associated with thiamine, methionine, and sulfur metabolism. The production of fermentation by-products was linked with differences in the redox metabolism in each treatment. This study provides valuable insights that may help steer the production of metabolites of industrial interest during alcoholic fermentation (including winemaking) by using oxygen as a lever of redox metabolism.

Polyol-assisted ternary deep eutectic solvent protective lignocellulose pretreatment for high-efficiency xylan utilization and ethanol production.

The traditional lignocellulose pretreatment by deep eutectic solvent (DES) was usually conducted under higher acidic, alkaline and high temperature conditions, which leads to the severe degradation of xylan, decreasing the subsequent reducing sugar concentration by enzymatic hydrolysis and further ethanol fermentation. It is essential to develop an effective DES that selectively removes lignin while preventing excessive xylan degradation during lignocellulose pretreatment. An effective ethylene glycol-assisted ternary DES was designed to treat corn straw (CS) at 100 °C for 6 h. 65.51 % lignin removal was achieved, over 93.46 % cellulose and 50.22 % xylan were retained in pretreated CS with excellent enzymatic digestibility (glucan conversion of 77.05 % and xylan conversion of 71.72 %), total sugar conversion could reach 75.93 %, implying the unique capacity to selectively remove lignin while preserving carbohydrate components. Furthermore, the universality of the selective removal of lignin and effective retention of xylan by ternary DES has been successfully proven by other polyols. The enzymatic hydrolysate of ternary DES-pretreated CS fermented over our genetically engineered yeast strain SFA1OE gave a high ethanol yield of 0.488 g/g total reducing sugar, demonstrating the effectiveness of the polyol-assisted ternary DES pretreatment in achieving high-efficiency cellulosic ethanol production.

In vitro assessment of Ethanolic extracts from specific herbs on controlling aquatic leech (Tyrannobdella rex) and land leech (Philobdella sp.) infestation in Mithun (Bos frontalis).

Leech infestation poses a significant threat to Mithun (Bos frontalis) in the north-eastern region of India, leading to various health issues and potential fatality. To address this pressing concern, we conducted a comprehensive research study aimed at assessing the efficacy of herbal plant extracts against aquatic leeches, particularly Tyrannobdella rex, and land leeches of the Philobdella sp. Our investigation involved the evaluation of six distinct plant extracts, with a focus on their ability to combat leech infestation. The results of our study revealed that among the various plant extracts tested, only the ethanolic extracts of soapnut (Sapindus mukorossi) and tobacco (Nicotiana tabacum) exhibited notable effectiveness in combating aquatic leeches. At a concentration of 5%, these extracts displayed significant lethality, with soapnut extract achieving a remarkable kill time of 6.0 ± 0.40 min, while tobacco extract showed a kill time of 31.5 ± 1.32 min. In the case of land leeches, tobacco extract proved to be highly efficient, with an average kill time of 1.5 ± 0.28 min at a 5% concentration. Soapnut extract also exhibited effectiveness against land leeches, albeit with a slightly longer kill time of 14.25 ± 1.10 min at the same concentration. Additionally, Litsea grass oil (Litsea cubeba) demonstrated promising efficacy against both aquatic and land leeches, suggesting its potential as a versatile leech control agent. These compelling findings have significant implications for the management and control of leech infestation among Mithun populations. By identifying and harnessing the leech-repelling properties of soapnut, tobacco, and Litsea grass oil, this research offers practical and environmentally friendly solutions for mitigating the adverse effects of leech infestation. Furthermore, the insights gained from this study pave the way for the development of innovative strategies to safeguard the health and well-being of Mithun in the future.

Comparative study of the anthelmintic activity of ethanolic and aqueous extracts of Atriplex halimus, the anti-echinococcal plant used in Algeria.

Cystic echinococcosis (CE) remains a major human public health problem in Algeria. Surgical treatment is the gold standard. However, one of the most critical complications of surgery is a recurrence of the disease, which is attributed to the dissemination of protoscoleces during the operation. This study aimed to compare the scolicidal effect of two ethanolic and aqueous extracts of Atriplex halimus, a plant used by the Algerian population against CE. The comparison involved the assessment of the phytochemical content, making screening using GC-MS/MS, and the evaluation of the antioxidant activity using DPPH and the in vitro scolicidal effect of A. halimus extracts. The aqueous and ethanolic extracts of leaves contained 19.601 ± 0.016 and 15.406 ± 0.003 mg of gallic acid equivalent per g of extract (GAE/g extract) of total phenolic. However, the flavonoid content in ethanolic and aqueous extracts was 4.350 ± 0.023 and 1.995 ± 0.026 mg of quercetin equivalent per g (QE/g extract), respectively. Four compounds were identified by GC-MS/MS for the ethanolic extract, while twenty-three compounds were determined for the aqueous extract. The ethanolic and aqueous extracts of A. halimus demonstrated an antioxidant activity with IC50 = 0.850 ± 0.026 mg/ml and IC50 = 0.897 ± 0.060 mg/ml, respectively. The higher in vitro scolicidal effect was 100% after 90 min and 10 min at 100 and 150 mg/ml, respectively for the ethanolic extract and after 120 and 60 min at 100 and 150 mg/ml, respectively for the aqueous extract. Atriplex halimus could be used as a natural source for the production of a potential scolicidal agent for use during CE surgery and/or percutaneous interventions.

Effect of commercial Saccharomyces cerevisiae and non-Saccharomyces yeasts on the chemical composition and bioaccessibility of pineapple wine.

Alcoholic fermentation is one of man's most efficient food preservation processes, and innovations in this area are a trend in food science and nutrition. In addition to the classic Saccharomyces yeasts, various other species may have desirable characteristics for obtaining fruit wines. This study investigated the profile of non-Saccharomyces commercial yeasts compared with S. cerevisiae regarding pineapple wine's chemical composition and bioaccessibility. The fermentation profile of the yeasts Lachancea thermotolerans, Brettanomyces bruxellensis, Brettanomyces lambicus, and S. cerevisiae was evaluated for sugar and alcohol content, and the pineapple wines obtained were analyzed for amino acids, phenolics, and organic acids by HPLC and volatile profile by GC/MS. All yeast strains were able to produce ethanol and glycerol at acceptable levels. L. thermotolerans produced higher levels of lactic acid (0.95 g/L) and higher consumption of free amino acids. B. bruxellensis produced higher levels of individual phenolics and ethanol 109 g/L. The alcoholic fermentation process improved the bioaccessibility of phenolics such as catechin (237 %), epigallocatechin gallate (81 %), procyanidin B1 (61 %) and procyanidin B2 (61 %). The yeasts differed in their volatile profiles, with Brettanomyces and Lachancea producing higher levels of compounds associated with pineapple aroma, such as ester ethyl butyrate (260-270 µg/L). These results demonstrate the importance of choosing the yeast strain for the conduction of alcoholic fermentation and that the yeasts Brettanomyces and Lachancea showed technological potential in obtaining pineapple wines. This study contributes to developing processes for obtaining fruit wines by highlighting two non-Saccharomyces yeast species with technological potential for alcoholic fermentations.

Skin Penetration and Permeation Properties of Transcutol® in Complex Formulations.

Percutaneous delivery is explored as alternative pathway for addressing the drawbacks associated with the oral administration of otherwise efficacious drugs. Short of breaching the skin by physical means, the preference goes to formulation strategies that augment passive diffusion across the skin. One such strategy lies in the use of skin penetration and permeation enhancers notably of hydroxylated solvents like propylene glycol (PG), ethanol (EtOH), and diethylene glycol monoethyl ether (Transcutol®, TRC). In a previous publication, we focused on the role of Transcutol® as enhancer in neat or diluted systems. Herein, we explore its' role in complex formulation systems, including patches, emulsions, vesicles, solid lipid nanoparticles, and micro or nanoemulsions. This review discusses enhancement mechanisms associated with hydroalcoholic solvents in general and TRC in particular, as manifested in multi-component formulation settings alongside other solvents and enhancers. The principles that govern skin penetration and permeation, notably the importance of drug diffusion due to solubilization and thermodynamic activity in the vehicle (formulation), drug solubilization and partitioning in the stratum corneum (SC), and/or solvent drag across the skin into deeper tissue for systemic absorption are discussed. Emphasized also are the interplay between the drug properties, the skin barrier function and the formulation parameters that are key to successful (trans)dermal delivery.

Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species.

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.

Drinking excessive amounts of alcohol during pregnancy can cause foetal alcohol spectrum disorder and other conditions in children that affect their physical and mental development. Many countries advise women who are pregnant or trying to conceive to avoid drinking alcohol entirely. However, surveys of large groups of women in Western countries indicate that most women continue drinking low to moderate amounts of alcohol until they discover they are pregnant and then stop consuming alcohol for the rest of their pregnancy. It remains unclear how this common drinking pattern affects the foetus. The instructions needed to build and maintain a human body are stored within molecules of DNA. Some regions of DNA called genes contain the instructions to make proteins, which perform many tasks in the body. Other so-called 'non-coding' regions do not code for any proteins but instead have roles in regulating gene activity. One way cells control which genes are switched on or off is adding or removing tags known as methyl groups to certain locations on DNA. Previous studies indicate that alcohol may affect how children develop by changing the patterns of methyl tags on DNA. To investigate the effect of moderate drinking during the early stages of pregnancy, Bestry et al. exposed pregnant mice to alcohol and examined how this affected the patterns of methyl tags on DNA in their offspring. The experiments found moderate levels of alcohol were sufficient to alter the patterns of methyl tags in the brains and livers of the newborn mice. Most of the changes were observed in non-coding regions of DNA, suggesting alcohol may affect how large groups of genes are regulated. Fewer changes in the patterns of methyl tags were found in mice whose mothers had diets rich in two essential nutrients known as folate and choline. Further experiments found that some of the affected mouse genes were similar to genes linked to foetal alcohol spectrum disorder and other related conditions in humans. These findings highlight the potential risks of consuming even moderate levels of alcohol during pregnancy and suggest that a maternal diet rich in folate and choline may help mitigate some of the harmful effects on the developing foetus.

Blended nexus molecules promote CO2 to l-tyrosine conversion.

Using CO2 as the primary feedstock offers the potential for high-value utilization of CO2 while forging sustainable pathways for producing valuable natural products, such as l-tyrosine. Cascade catalysis is a promising approach but limited by stringent purity demands of nexus molecules. We developed an abiotic/biotic cascade catalysis using blended nexus molecules for l-tyrosine synthesis. Specifically, we begin by constructing a solid-state reactor to reduce CO2 electrochemically, yielding a mixture of acetic acid and ethanol, which serves as the blended nexus molecules. Subsequently, we use genetic engineering to introduce an ethanol utilization pathway and a tyrosine producing pathway to Escherichia coli to facilitate l-tyrosine production. The ethanol pathway synergistically cooperated with the acetic acid pathway, boosting l-tyrosine production rate (nearly five times higher compared to the strain without ethanol utilization pathway) and enhancing carbon efficiency. Our findings demonstrate that using blended nexus molecules could potentially offer a more favorable strategy for the cascade catalysis aimed at producing valuable natural products.

Natural killer cell effector function is critical for host defense against alcohol-associated bacterial pneumonia.

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-ß) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-ß and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia.

Integration of Animal Behavioral Assessment and Convolutional Neural Network to Study Wasabi-Alcohol Taste-Smell Interaction.

The commercial wasabi pastes commonly used for food preparation contain a homologous compound of chemosensory isothiocyanates (ITCs) that elicit an irritating sensation upon consumption. The impact of sniffing dietary alcoholic beverages on the sensation of wasabi spiciness has never been studied. While most sensory evaluation studies focus on individual food and beverages separately, there is a lack of research on the olfactory study of sniffing liquor while consuming wasabi. Here, a methodology is developed that combines the use of an animal behavioral study and a convolutional neural network to analyze the facial expressions of mice when they simultaneously sniff liquor and consume wasabi. The results demonstrate that the trained and validated deep learning model recognizes 29% of the images depicting co-treatment of wasabi and alcohol belonging to the class of the wasabi-negative liquor-positive group without the need for prior training materials filtering. Statistical analysis of mouse grimace scale scores obtained from the selected video frame images reveals a significant difference (P < 0.01) between the presence and absence of liquor. This finding suggests that dietary alcoholic beverages might have a diminishing effect on the wasabi-elicited reactions in mice. This combinatory methodology holds potential for individual ITC compound screening and sensory analyses of spirit components in the future. However, further study is required to investigate the underlying mechanism of alcohol-induced suppression of wasabi pungency.

Identification of genes associated with the high-temperature fermentation trait in the Saccharomyces cerevisiae natural isolate BCC39850.

The fermentative model yeast Saccharomyces cerevisiae has been extensively used to study the genetic basis of stress response and homeostasis. In this study, we performed quantitative trait loci (QTL) analysis of the high-temperature fermentation trait of the progeny from the mating of the S. cerevisiae natural isolate BCC39850 (haploid#17) and the laboratory strain CEN.PK2-1C. A single QTL on chromosome X was identified, encompassing six candidate genes (GEA1, PTK2, NTA1, NPA3, IRT1, and IML1). The functions of these candidates were tested by reverse genetic experiments. Deletion mutants of PTK2, NTA1, and IML1 showed growth defects at 42 °C. The PTK2 knock-out mutant also showed significantly reduced ethanol production and plasma membrane H+ ATPase activity and increased sensitivity to acetic acid, ethanol, amphotericin B (AMB), and ß-1,3-glucanase treatment. The CRISPR-Cas9 system was used to construct knock-in mutants by replacement of PTK2, NTA1, IML1, and NPA3 genes with BCC39850 alleles. The PTK2 and NTA1 knock-in mutants showed increased growth and ethanol production titers at 42 °C. These findings suggest an important role for the PTK2 serine/threonine protein kinase in regulating plasma membrane H+ ATPase activity and the NTA1 N-terminal amidase in protein degradation via the ubiquitin-proteasome system machinery, which affects tolerance to heat stress in S. cerevisiae.

Ethanol Inhalation as a Method to Denature the Spike Protein of SARS-CoV-2.

The SARS-CoV-2 virus caused the 2019 COVID pandemic by infecting almost eight hundred million people worldwide. Because it was a new viral infection, there were no vaccines or small molecule medications that could prevent or treat the disease.  This chapter provides some details for an obscure treatment for COVID-19, that has decades of anti-viral activity data both in vitro and in vivo in the literature. The medicinal molecules are compared to other small molecules that were identified as possible medications for COVID-19.  We developed a computational method that ranks small molecules and their ability to penetrate mucus in the lungs of a COVID-19 patient. Our focus is ethanol as a COVID-19 treatment. The results discussed here are based on Lipinski Rules and QSAR computational methods as well as in vitro and in vivo data. These parameters indicate that ethanol should be a strong candidate for future evaluations.

Oxytocin decreases alcohol self-administration in male baboons.

The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.

Enhanced production of bioethanol through supercritical carbon dioxide-mediated pretreatment and saccharification of dewaxed bagasse.

The pretreatment and saccharification of dewaxed bagasse (DWB) has been investigated under various reaction conditions ranging 2000 to 3200 psi, at 70 ± 1 °C in supercritical carbon dioxide (SCC). This has been in attempt to transform the DWB into fermentable sugar and bioethanol in high yields. The effect of SCC mediated pretreatment and enzymatic hydrolysis on structural and morphological alterations in DWB has been ascertained through diverse analytical methods. The sugar has been released through cellulase (40 FPU/mL) mediated enzymatic hydrolysis of pretreated DWB in sodium acetate buffer (pH 4.7) within 1 h at SCC 2800 psi, 70 ± 1 °C. The released sugar was subsequently fermented in the presence of yeast (Saccharomyces crevices, 135 CFU) at 28 ± 1 °C over 72 h to afford the bioethanol. The SCC mediated process conducted in acetic acid:water media (1:1) at 2800 psi, 70 ± 1 °C over 6 h has afforded the pretreated DWB with maximum yield towards the production of fermentable sugar and bioethanol. The production of fermentable sugar and bioethanol has been electrochemically estimated through cyclic voltammetry (CV) and square wave voltammetry (SWV) over glassy carbon electrode in KOH (0.1 M). The electrochemical methods were found selective and in close agreement for estimation of the yields (%) of fermentable sugars and bioethanol. The yield (%) of fermentable sugar estimated from CV and SWV were 80.10 ± 5.34 and 79.00 ± 5.09 respectively. Whereas the yield (%) of bioethanol estimated from CV and SWV were 81.30 ± 2.78% and 78.6 ± 1.25% respectively. Present investigation delivers a SCC mediated green and sustainable method of pretreatment of DWB to afford the enhanced saccharification, to produce bioethanol in high yields.

Impact of final rinse with saline or alcohol solution on root canal sealability.

Endodontic irrigation protocols are not only used to clean and disinfect the root canal system, but also to condition the canal wall dentine for subsequent root filling. In this study we tested whether a final irrigation step with saline solution or 80% ethanol improved root canal sealabilty by two popular sealers, an epoxy resin (AH Plus) and a hydraulic calcium silicate cement-based product (BioRoot RCS). Root canals in extracted single-rooted human teeth were instrumented and filled with a matched gutta-percha cone and sealer. During instrumentation and prior to root filling, sealer-specific irrigation protocols were applied. These involved a combined sodium hypochlorite/1-hydroxyethylidene-1,1-diphosphonic acid application, which was followed by irrigation with ethylenediaminetetraacetic acid (EDTA) for AH Plus. Protocols were followed by a 5-ml ultimate rinse with saline solution or 80% ethanol. No such final rinse was the control (N = 9). Canals were then dried with matched paper points. One week after root filling and storage of the teeth at 37°C in a humid environment, Rhodamine B was used to trace leakage. Two-way ANOVA revealed that the type of sealer had a significant (P < 0.05) impact on apical dye penetration while the final rinse did not (P > 0.05). AH Plus provided the slightly better seal (P < 0.05). Leakage occurred between the sealer and the dentin with AH Plus, and between the sealer-to-dentin as well as the sealer-to-gutta-percha interface with BioRoot RCS. In summary and under current conditions, there was no benefit from applying saline or ethanol as an ultimate rinsing solution prior to drying the canal with matched paper points.

Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.

Glioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA-seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS-treated GBM cells and the control cells. Protein-protein interactions between DEGs with fold changes less than -3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21-activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment.

Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques.

AIMS: As the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet. METHODS: Macaques were administered chronic binge alcohol (CBA; 13-14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue. RESULTS: CBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group. CONCLUSIONS: These results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation.