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Critical Reviews in Microbiology Jun 2024stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of , alcohol dehydrogenase 1... (Review)
Review
stands as the foremost prevalent human commensal pathogen and a significant contributor to nosocomial fungal infections. In the metabolism of , alcohol dehydrogenase 1 (Adh1) is one of the important enzymes that converts acetaldehyde produced by pyruvate decarboxylation into ethanol at the end of glycolysis. Leveraging the foundational processes of alcoholic fermentation, Adh1 plays an active role in multiple biological phenomena, including biofilm formation, interactions between different species, the development of drug resistance, and the potential initiation of gastrointestinal cancer. Additionally, Adh1 within has demonstrated associations with regulating the cell cycle, stress responses, and various intracellular states. Furthermore, Adh1 is extracellularly localized on the cell wall surface, where it plays roles in processes such as tissue invasion and host immune responses. Drawing from an analysis of gene structure, expression patterns, and fundamental functions, this review elucidates the intricate connections between Adh1 and various biological processes within , underscoring its potential implications for the prevention, diagnosis, and treatment of candidiasis.
PubMed: 38916139
DOI: 10.1080/1040841X.2024.2371510 -
Nature Metabolism Jun 2024Alcohol use disorder (AUD) affects millions of people worldwide, causing extensive morbidity and mortality with limited pharmacological treatments. The liver is...
Alcohol use disorder (AUD) affects millions of people worldwide, causing extensive morbidity and mortality with limited pharmacological treatments. The liver is considered as the principal site for the detoxification of ethanol metabolite, acetaldehyde (AcH), by aldehyde dehydrogenase 2 (ALDH2) and as a target for AUD treatment, however, our recent data indicate that the liver only plays a partial role in clearing systemic AcH. Here we show that a liver-gut axis, rather than liver alone, synergistically drives systemic AcH clearance and voluntary alcohol drinking. Mechanistically, we find that after ethanol intake, a substantial proportion of AcH generated in the liver is excreted via the bile into the gastrointestinal tract where AcH is further metabolized by gut ALDH2. Modulating bile flow significantly affects serum AcH level and drinking behaviour. Thus, combined targeting of liver and gut ALDH2, and manipulation of bile flow and secretion are potential therapeutic strategies to treat AUD.
PubMed: 38902331
DOI: 10.1038/s42255-024-01063-2 -
Journal of Agricultural and Food... Jun 2024Monolignols and their derivatives exhibit various pharmaceutical and physiological characteristics, such as antioxidant and anti-inflammatory properties. However, they...
Monolignols and their derivatives exhibit various pharmaceutical and physiological characteristics, such as antioxidant and anti-inflammatory properties. However, they remain difficult to synthesize. In this study, we engineered several whole-cell bioconversion systems with carboxylate reductase (CAR)-mediated pathways for efficient synthesis of -coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine in BL21 (DE3). By overexpressing the l-tyrosine ammonia lyase from (FjTAL), carboxylate reductase from (SruCAR), alcohol dehydrogenase YqhD and hydroxylase HpaBC from , and caffeate 3-O-methyltransferase (COMT) from , three enzyme cascades FjTAL-SruCAR-YqhD, FjTAL-SruCAR-YqhD-HpaBC, and FjTAL-SruCAR-YqhD-HpaBC-COMT were constructed to produce 1028.5 mg/L -coumaryl alcohol, 1015.3 mg/L caffeyl alcohol, and 411.4 mg/L coniferyl alcohol from 1500, 1500, and 1000 mg/L l-tyrosine, with productivities of 257.1, 203.1, and 82.3 mg/L/h, respectively. This work provides an efficient strategy for the biosynthesis of -coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine.
PubMed: 38899526
DOI: 10.1021/acs.jafc.4c02611 -
Graphic Medicine Review 2024Nearly 540 million people world-wide have facial flushing and an increased heart rate after consuming alcohol. Known as the alcohol flushing response, this reaction to...
Nearly 540 million people world-wide have facial flushing and an increased heart rate after consuming alcohol. Known as the alcohol flushing response, this reaction to alcohol is a result of a genetic variant in an enzyme aldehyde dehydrogenase 2 (ALDH2), known as ALDH2*2. Mainly carried by those of East Asian descent, the genetic variant is likely the most common genetic variant carried in the world. Carrying this ALDH2*2 genetic variant has important health implications with respect cancer risk which is increased when carriers of the ALDH2*2 genetic variant frequently use of alcohol or tobacco products. This comic explains the alcohol flush response and the health risks associated with alcohol and tobacco use for those who carry an ALDH2*2 variant.
PubMed: 38895023
DOI: 10.7191/gmr.807 -
Cells May 2024Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to...
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to alcohol-induced tissue damage. However, the underlying mechanisms behind ALDH2-related gut-associated brain damage remain unclear. Age-matched young female -KO and C57BL/6J wild-type (WT) mice were gavaged with binge alcohol (4 g/kg/dose, three doses) or dextrose (control) at 12 h intervals. Tissues and sera were collected 1 h after the last ethanol dose and evaluated by histological and biochemical analyses of the gut and hippocampus and their extracts. For the mechanistic study, mouse neuroblast Neuro2A cells were exposed to ethanol with or without an Aldh2 inhibitor (Daidzin). Binge alcohol decreased intestinal tight/adherens junction proteins but increased oxidative stress-mediated post-translational modifications (PTMs) and enterocyte apoptosis, leading to elevated gut leakiness and endotoxemia in -KO mice compared to corresponding WT mice. Alcohol-exposed -KO mice also showed higher levels of hippocampal brain injury, oxidative stress-related PTMs, and neuronal apoptosis than the WT mice. Additionally, alcohol exposure reduced Neuro2A cell viability with elevated oxidative stress-related PTMs and apoptosis, all of which were exacerbated by Aldh2 inhibition. Our results show for the first time that ALDH2 plays a protective role in binge alcohol-induced brain injury partly through the gut-brain axis, suggesting that ALDH2 is a potential target for attenuating alcohol-induced tissue injury.
Topics: Animals; Aldehyde Dehydrogenase, Mitochondrial; Mice, Knockout; Mice; Mice, Inbred C57BL; Binge Drinking; Brain Injuries; Ethanol; Female; Apoptosis; Oxidative Stress; Hippocampus; Mitochondria
PubMed: 38891060
DOI: 10.3390/cells13110927 -
BMC Genomics Jun 2024Understanding the mechanisms underlying alcohol metabolism and its regulation, including the effect of polymorphisms in alcohol-metabolizing enzymes, is crucial for...
Understanding the mechanisms underlying alcohol metabolism and its regulation, including the effect of polymorphisms in alcohol-metabolizing enzymes, is crucial for research on Fetal Alcohol Spectrum Disorders. The aim of this study was to identify specific single nucleotide polymorphisms in key alcohol-metabolizing enzymes in a cohort of 71 children, including children with fetal alcohol syndrome, children prenatally exposed to ethanol but without fetal alcohol spectrum disorder, and controls. We hypothesized that certain genetic variants related to alcohol metabolism may be fixed in these populations, giving them a particular alcohol metabolism profile. In addition, the difference in certain isoforms of these enzymes determines their affinity for alcohol, which also affects the metabolism of retinoic acid, which is key to the proper development of the central nervous system. Our results showed that children prenatally exposed to ethanol without fetal alcohol spectrum disorder traits had a higher frequency of the ADH1B*3 and ADH1C*1 alleles, which are associated with increased alcohol metabolism and therefore a protective factor against circulating alcohol in the fetus after maternal drinking, compared to FAS children who had an allele with a lower affinity for alcohol. This study also revealed the presence of an ADH4 variant in the FAS population that binds weakly to the teratogen, allowing increased circulation of the toxic agent and direct induction of developmental abnormalities in the fetus. However, both groups showed dysregulation in the expression of genes related to the retinoic acid pathway, such as retinoic acid receptor and retinoid X receptor, which are involved in the development, regeneration, and maintenance of the nervous system. These findings highlight the importance of understanding the interplay between alcohol metabolism, the retinoic acid pathway and genetic factors in the development of fetal alcohol syndrome.
Topics: Humans; Fetal Alcohol Spectrum Disorders; Case-Control Studies; Female; Polymorphism, Single Nucleotide; Alcohol Dehydrogenase; Male; Receptors, Retinoic Acid; Child; Ethanol; Pregnancy; Child, Preschool; Alleles
PubMed: 38886650
DOI: 10.1186/s12864-024-10516-7 -
Journal of Comparative Physiology. B,... Jun 2024Honey bees (Apis mellifera) are one of the most crucial pollinators, providing vital ecosystem services. Their development and functioning depend on essential nutrients...
Honey bees (Apis mellifera) are one of the most crucial pollinators, providing vital ecosystem services. Their development and functioning depend on essential nutrients and substances found in the environment. While collecting nectar as a vital carbohydrate source, bees routinely encounter low doses of ethanol from yeast fermentation. Yet, the effects of repeated ethanol exposure on bees' survival and physiology remain poorly understood. Here, we investigate the impacts of constant and occasional consumption of food spiked with 1% ethanol on honey bee mortality and alcohol dehydrogenase (ADH) activity. This ethanol concentration might be tentatively judged close to that in natural conditions. We conducted an experiment in which bees were exposed to three types of long-term diets: constant sugar solution (control group that simulated conditions of no access to ethanol), sugar solution spiked with ethanol every third day (that simulated occasional, infrequent exposure to ethanol) and daily ethanol consumption (simulating constant, routine exposure to ethanol). The results revealed that both constant and occasional ethanol consumption increased the mortality of bees, but only after several days. These mortality rates rose with the frequency of ethanol intake. The ADH activity remained similar in bees from all groups. Our findings indicate that exposure of bees to ethanol carries harmful effects that accumulate over time. Further research is needed to pinpoint the exact ethanol doses ingested with food and exposure frequency in bees in natural conditions.
PubMed: 38880794
DOI: 10.1007/s00360-024-01571-3 -
Clinical Nutrition ESPEN Jun 2024Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver...
Effects of Silybum marianum, Pueraria lobate, combined with Salvia miltiorrhiza tablets on non-alcoholic fatty liver disease in adults: A triple-blind, randomized, placebo-controlled clinical trial.
BACKGROUND & AIMS
Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults.
METHODS
In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism.
RESULTS
A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058).
CONCLUSION
SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.
PubMed: 38879879
DOI: 10.1016/j.clnesp.2024.06.003 -
Food Research International (Ottawa,... Aug 2024Previous studies have demonstrated that Staphylococcus cohnii WX_M8 and S. saprophyticus MY_A10 significantly enhanced the flavor of Chinese bacon in a mixed... (Comparative Study)
Comparative Study
New insights into the dominance of mixed fermentation of Staphylococcus cohnii and Staphylococcus saprophyticus in Chinese bacon: Complete genomic and comparative genomic perspectives.
Previous studies have demonstrated that Staphylococcus cohnii WX_M8 and S. saprophyticus MY_A10 significantly enhanced the flavor of Chinese bacon in a mixed fermentation. However, due to the complexity of the processing, the contribution of the bacteria is deceptive when investigating only the phenotypic changes at the time of fermentation. In order to clarify the metabolic mechanisms of mixed fermentation, a technological characterization, whole genome and comparative genomics analysis, and metabolites were approached in this study. Results showed that differences in tolerance characteristics existed between WX_M8 and MY_A10. And the genomes of both the two strains consisted of one chromosome and four circular plasmids. Their genome sizes were 2.74 Mp and 2.62 Mp, the GC contents were 32.45% and 33.18%, and the predicted coding genes (CDS) were 2564 and 2541, respectively. Based on the annotation of gene functions and assessment of metabolic pathways in the KEGG database, WX_M8 and MY_A10 strains were found to harbor complete protein degradation and amino acid metabolic pathways, pyruvate and butanol metabolic pathways, and isoleucine metabolic pathways, and their diverse enzyme-encoding genes superimposed the metabolic functions, whereas the alcohol dehydrogenase genes, adh and frmA, achieved complementary functions in the production of esters. Comparative genomics analysis revealed a diversity of encoding genes of aminotransferases and a greater metabolism for sulfur-containing amino acids, aromatic amino acids, and branched-chain amino acids in the mixed fermentation of strains WX_M8 and MY_A10. Metabolites analysis showed that MY_A10 focused on the production of soluble peptides and free amino acids (FAAs), while WX_M8 focused on volatile organic compounds (VOCs), resulting in a significant enhancement of the flavor of Chinese bacon when the two were mixed fermented. This result may provide direction for strains WX_M8 and MY_A10 to be used as starter cultures and targeted to regulate flavor.
Topics: Fermentation; Genomics; Genome, Bacterial; Staphylococcus; Food Microbiology; Staphylococcus saprophyticus; Metabolic Networks and Pathways; Meat Products
PubMed: 38876605
DOI: 10.1016/j.foodres.2024.114544 -
International Journal For Parasitology.... Jun 2024Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals....
Lower micromolar activity of the antifungal imidazoles on the bacterial-type bifunctional aldehyde/alcohol dehydrogenase (AdhE) in Cryptosporidium parvum and in vitro efficacy against the zoonotic parasite.
Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals. However, fully effective treatments are unavailable for medical and veterinary uses. There is a need to explore new drug targets for potential development of new therapeutics. Because C. parvum relies on anaerobic metabolism to produce ATP, fermentative enzymes in this parasite are attractive targets for exploration. In this study, we investigated the ethanol-fermentation in the parasite and characterized the basic biochemical features of a bacterial-type bifunctional aldehyde/alcohol dehydrogenase, namely CpAdhE. We also screened 3892 chemical entries from three libraries and identified 14 compounds showing >50% inhibition on the enzyme activity of CpAdhE. Intriguingly, antifungal imidazoles and unsaturated fatty acids are the two major chemical groups among the top hits. We further characterized the inhibitory kinetics of selected imidazoles and unsaturated fatty acids on CpAdhE. These compounds displayed lower micromolar activities on CpAdhE (i.e., IC values ranging from 0.88 to 11.02 μM for imidazoles and 8.93 to 35.33 μM for unsaturated fatty acids). Finally, we evaluated the in vitro anti-cryptosporidial efficacies and cytotoxicity of three imidazoles (i.e., tioconazole, miconazole and isoconazole). The three antifungal imidazoles exhibited lower micromolar efficacies against the growth of C. parvum in vitro (EC values ranging from 4.85 to 10.41 μM and selectivity indices ranging from 5.19 to 10.95). The results provide a proof-of-concept data to support that imidazoles are worth being further investigated for potential development of anti-cryptosporidial therapeutics.
PubMed: 38875756
DOI: 10.1016/j.ijpddr.2024.100551