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Nature Communications Jun 2023Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic...
Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.
Topics: Male; Animals; Mice; Non-alcoholic Fatty Liver Disease; Klebsiella pneumoniae; Bacteriophages; Ethanol; Liver; Microbiota; Anti-Bacterial Agents
PubMed: 37270557
DOI: 10.1038/s41467-023-39028-w -
EBioMedicine Jul 2023Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with alcohol use disorder (AUD). However,...
BACKGROUND
Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with alcohol use disorder (AUD). However, the probability of low semaglutide doses, an agonist with higher potency and affinity for GLP-1R, to attenuate alcohol-related responses in rodents and the underlying neuronal mechanisms is unknown.
METHODS
In the intermittent access model, we examined the ability of semaglutide to decrease alcohol intake and block relapse-like drinking, as well as imaging the binding of fluorescently marked semaglutide to nucleus accumbens (NAc) in both male and female rats. The suppressive effect of semaglutide on alcohol-induced locomotor stimulation and in vivo dopamine release in NAc was tested in male mice. We evaluated effect of semaglutide on the in vivo release of dopamine metabolites (DOPAC and HVA) and gene expression of enzymes metabolising dopamine (MAOA and COMT) in male mice.
FINDINGS
In male and female rats, acute and repeated semaglutide administration reduced alcohol intake and prevented relapse-like drinking. Moreover, fluorescently labelled semaglutide was detected in NAc of alcohol-drinking male and female rats. Further, semaglutide attenuated the ability of alcohol to cause hyperlocomotion and to elevate dopamine in NAc in male mice. As further shown in male mice, semaglutide enhanced DOPAC and HVA in NAc when alcohol was onboard and increased the gene expression of COMT and MAOA.
INTERPRETATION
Altogether, this indicates that semaglutide reduces alcohol drinking behaviours, possibly via a reduction in alcohol-induced reward and NAc dependent mechanisms. As semaglutide also decreased body weight of alcohol-drinking rats of both sexes, upcoming clinical studies should test the plausibility that semaglutide reduces alcohol intake and body weight in overweight AUD patients.
FUNDING
Swedish Research Council (2019-01676), LUA/ALF (723941) from the Sahlgrenska University Hospital and the Swedish brain foundation.
Topics: Female; Rats; Mice; Male; Animals; Exenatide; Dopamine; 3,4-Dihydroxyphenylacetic Acid; Overweight; Ethanol; Alcoholism; Alcohol Drinking; Recurrence
PubMed: 37295046
DOI: 10.1016/j.ebiom.2023.104642 -
Ugeskrift For Laeger Jun 202371% of the Danish municipal alcohol treatment centres use NADA acupuncture. This status report based on recent reviews of the effect and risks of using auricular...
71% of the Danish municipal alcohol treatment centres use NADA acupuncture. This status report based on recent reviews of the effect and risks of using auricular acupuncture in alcohol treatment shows that the available studies do not have sufficient strength and methodological quality to draw conclusions about effectiveness on craving, alcohol-related outcome measures or withdrawal symptoms. The results warrant a reassessment of the use of NADA in publicly funded alcohol treatment.
Topics: Humans; Acupuncture, Ear; Ethanol; Acupuncture Therapy; Substance Withdrawal Syndrome; Outcome Assessment, Health Care
PubMed: 37325981
DOI: No ID Found -
Annual Review of Pharmacology and... Jan 2024Alcohol use disorder (AUD) afflicts over 29 million individuals and causes more than 140,000 deaths annually in the United States. A heuristic framework for AUD includes... (Review)
Review
Alcohol use disorder (AUD) afflicts over 29 million individuals and causes more than 140,000 deaths annually in the United States. A heuristic framework for AUD includes a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that provides a starting point for exploring the heterogeneity of AUD with regard to treatment. Effective behavioral health treatments and US Food and Drug Administration-approved medications are available but greatly underutilized, creating a major treatment gap. This review outlines challenges that face the alcohol field in closing this treatment gap and offers solutions, including broadening end points for the approval of medications for the treatment of AUD; increasing the uptake of screening, brief intervention, and referral to treatment; addressing stigma; implementing a heuristic definition of recovery; engaging early treatment; and educating health-care professionals and the public about challenges that are associated with alcohol misuse. Additionally, this review focuses on broadening potential targets for the development of medications for AUD by utilizing the three-stage heuristic model of addiction that outlines domains of dysfunction in AUD and the mediating neurobiology of AUD.
Topics: United States; Humans; Alcoholism; Behavior, Addictive; Ethanol; Biological Transport; United States Food and Drug Administration
PubMed: 38261428
DOI: 10.1146/annurev-pharmtox-031323-115847 -
Cold Spring Harbor Protocols Oct 2023is a powerful genetic model for investigating the mechanisms underlying ethanol-induced behaviors, metabolism, and preference. Ethanol-induced locomotor activity is...
is a powerful genetic model for investigating the mechanisms underlying ethanol-induced behaviors, metabolism, and preference. Ethanol-induced locomotor activity is especially useful for understanding the mechanisms by which ethanol acutely affects the brain and behavior. Ethanol-induced locomotor activity is characterized by hyperlocomotion and subsequent sedation with increased exposure duration or concentration. Locomotor activity is an efficient, easy, robust, and reproducible behavioral screening tool for identifying underlying genes and neuronal circuits as well as investigating genetic and molecular pathways. We introduce a detailed protocol for performing experiments investigating how volatilized ethanol affects locomotor activity using the fly Group Activity Monitor (flyGrAM). We introduce installation, implementation, data collection, and subsequent data-analysis methods for investigating how volatilized stimuli affect activity. We also introduce a procedure for how to optogenetically probe neuronal activity to identify the neural mechanisms underlying locomotor activity.
Topics: Animals; Ethanol; Drosophila; Drosophila melanogaster; Behavior, Animal; Neurons
PubMed: 37019606
DOI: 10.1101/pdb.top107887 -
Biological Research Nov 2023Prenatal ethanol exposure (PEE) (mainly through maternal alcohol consumption) has become widespread. However, studies suggest that it can cause intrauterine growth... (Review)
Review
Prenatal ethanol exposure (PEE) (mainly through maternal alcohol consumption) has become widespread. However, studies suggest that it can cause intrauterine growth retardation (IUGR) and multi-organ developmental toxicity in offspring, and susceptibility to various chronic diseases (such as neuropsychiatric diseases, metabolic syndrome, and related diseases) in adults. Through ethanol's direct effects and its indirect effects mediated by maternal-derived glucocorticoids, PEE alters epigenetic modifications and organ developmental programming during fetal development, which damages the offspring health and increases susceptibility to various chronic diseases after birth. Ethanol directly leads to the developmental toxicity of multiple tissues and organs in many ways. Regarding maternal-derived glucocorticoid-mediated IUGR, developmental programming, and susceptibility to multiple conditions after birth, ethanol induces programmed changes in the neuroendocrine axes of offspring, such as the hypothalamus-pituitary-adrenal (HPA) and glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axes. In addition, the differences in ethanol metabolic enzymes, placental glucocorticoid barrier function, and the sensitivity to glucocorticoids in various tissues and organs mediate the severity and sex differences in the developmental toxicity of ethanol exposure during pregnancy. Offspring exposed to ethanol during pregnancy have a "thrifty phenotype" in the fetal period, and show "catch-up growth" in the case of abundant nutrition after birth; when encountering adverse environments, these offspring are more likely to develop diseases. Here, we review the developmental toxicity, functional alterations in multiple organs, and neuroendocrine metabolic programming mechanisms induced by PEE based on our research and that of other investigators. This should provide new perspectives for the effective prevention and treatment of ethanol developmental toxicity and the early prevention of related fetal-originated diseases.
Topics: Rats; Animals; Adult; Female; Pregnancy; Humans; Male; Glucocorticoids; Prenatal Exposure Delayed Effects; Rats, Wistar; Placenta; Fetal Development; Ethanol; Chronic Disease
PubMed: 37978540
DOI: 10.1186/s40659-023-00473-y -
Molecular Psychiatry Jul 2023Concurrent cocaine and alcohol use is among the most frequent drug combination, and among the most dangerous in terms of deleterious outcomes. Cocaine increases...
Concurrent cocaine and alcohol use is among the most frequent drug combination, and among the most dangerous in terms of deleterious outcomes. Cocaine increases extracellular monoamines by blocking dopamine (DA), norepinephrine (NE) and serotonin (5-HT) transporters (DAT, NET and SERT, respectively). Likewise, ethanol also increases extracellular monoamines, however evidence suggests that ethanol does so independently of DAT, NET and SERT. Organic cation transporter 3 (OCT3) is an emergent key player in the regulation of monoamine signaling. Using a battery of in vitro, in vivo electrochemical, and behavioral approaches, as well as wild-type and constitutive OCT3 knockout mice, we show that ethanol's actions to inhibit monoamine uptake are dependent on OCT3. These findings provide a novel mechanistic basis whereby ethanol enhances the neurochemical and behavioral effects of cocaine and encourage further research into OCT3 as a target for therapeutic intervention in the treatment of ethanol and ethanol/cocaine use disorders.
Topics: Mice; Animals; Dopamine; Ethanol; Carrier Proteins; Cocaine-Related Disorders; Cocaine; Serotonin; Mice, Knockout; Cations; Dopamine Plasma Membrane Transport Proteins; Serotonin Plasma Membrane Transport Proteins
PubMed: 37308680
DOI: 10.1038/s41380-023-02064-5 -
Alcohol Research : Current Reviews 2023Alcohol-related myopathy is one of the earliest alcohol-associated pathological tissue changes that is progressively exacerbated by cumulative long-term alcohol misuse.... (Review)
Review
PURPOSE
Alcohol-related myopathy is one of the earliest alcohol-associated pathological tissue changes that is progressively exacerbated by cumulative long-term alcohol misuse. Acute and chronic alcohol use leads to changes in skeletal muscle mass and function. As discussed in this evidence-based review, alcohol-mediated mechanisms are multifactorial with effects on anabolic and catabolic signaling, mitochondrial bioenergetics, extracellular matrix remodeling, and epigenomic alterations. However, systematic studies are limited, especially regarding the acute effects of alcohol on skeletal muscle.
SEARCH METHODS
This review focuses on peer-reviewed manuscripts published between January 2012 and November 2022 using the search terms "alcohol" or "ethanol" and "skeletal muscle" in MEDLINE, PubMed, and Web of Science using EndNote reference management software.
SEARCH RESULTS
Eligible manuscripts included full-length research papers that discussed acute and chronic effects of alcohol on skeletal muscle mass and function in both clinical and preclinical studies. The review also includes alcohol-mediated skeletal muscle effects in the context of comorbidities. The three databases together yielded 708 manuscripts. Of these, the authors excluded from this review 548 papers that did not have "alcohol" or "muscle" in the title and 64 papers that were duplicates or did not discuss skeletal muscle. Thus, of all the manuscripts considered for this review, 96 are included and 612 are excluded. Additionally, relevant papers published earlier than 2012 are included to provide context to the review.
DISCUSSION AND CONCLUSIONS
Both acute and chronic alcohol use decrease protein synthesis and increase protein degradation. Alcohol also impairs mitochondrial function and extracellular matrix remodeling. However, there is a gap in the literature on the known alcohol-mediated mechanisms, including senescence, role of immune activation, and interorgan communication, on the development of alcohol-related myopathy. With increased life expectancy, changing alcohol use patterns, and increasing frequency of alcohol use among females, current observational studies are needed on the prevalence of alcohol-related myopathy. Additionally, the compounding effects of acute and chronic alcohol use on skeletal muscle with aging or exercise, in response to injury or disuse, and in the context of comorbidities including diabetes and human immunodeficiency virus (HIV), call for further investigation. Though evidence suggests that abstinence or reducing alcohol use can improve muscle mass and function, they are not restored to normal levels. Hence, understanding the pathophysiological mechanisms can help in the design of therapeutic strategies to improve skeletal muscle health.
Topics: Female; Humans; Ethanol; Muscle, Skeletal; Muscular Diseases; Alcohol Drinking; Signal Transduction
PubMed: 37937295
DOI: 10.35946/arcr.v43.1.04 -
Health Technology Assessment... Dec 2023A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
OBJECTIVE
To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
REVIEW METHODS
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
RESULTS
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified ( ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included ( = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
LIMITATIONS
Many studies were small and of poor quality. No comparative studies were found for some therapies.
CONCLUSIONS
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
STUDY REGISTRATION
PROSPERO CRD42020221357.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in ; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Carcinoma, Hepatocellular; Ethanol; Liver Neoplasms; Network Meta-Analysis; Prospective Studies; Randomized Controlled Trials as Topic; Ablation Techniques
PubMed: 38149643
DOI: 10.3310/GK5221 -
Molecules (Basel, Switzerland) Aug 2023Propolis is a natural bee-produced substance with antimicrobial, anti-inflammatory, and wound-healing properties, containing some components from the leaves, buds and... (Review)
Review
Propolis is a natural bee-produced substance with antimicrobial, anti-inflammatory, and wound-healing properties, containing some components from the leaves, buds and resins of plants. It has been used for centuries for various health benefits. In this manuscript, our group reviewed the radioprotective effect of propolis using PubMed and Embase, and our review was conducted according to the PRISMA statement. Finally, 27 articles were included in this review, which includes the radioprotective effect of propolis from cell-based studies ( = 8), animal models ( = 14), and human trials ( = 5). Results reflected that the dosage forms of propolis extracted in the scientific literature were ethanolic extracts of propolis, a water-soluble derivate of propolis, or capsules. The efficacy of the radioprotective properties from propolis is extracted from the bibliography, as several compounds of this resinous mixture individually or synergistically are possible candidates that have the radioprotective effect. In fact, studies prior to 2011 lacked a comprehensive characterization of propolis due to the variability in active compounds among different batches of propolis and were limited to analytical techniques. Furthermore, in this manuscript, we have selected studies to include primarily propolis types from Brazil, Croatia, Egypt, European countries, and those commercialized in Spain. They all contained ethanolic extract of propolis (EEP) and were influenced by different dosage forms. EEP showed a significant presence of lipophilic bioactive compounds like flavones, flavonols, and flavanones.
Topics: Humans; Animals; Propolis; Anti-Infective Agents; Flavanones; Ethanol; Water
PubMed: 37570811
DOI: 10.3390/molecules28155842