RESUMO
Chardonnay is one of the most popular white grape wine varieties in the world, but this wine lacks typical aroma, considered a sensory defect. Our research group identified a Chardonnay bud sport with typical muscat characteristics. The goal of this work was to discover the key candidate genes related to muscat characteristics in this Chardonnay bud sport to reveal the mechanism of muscat formation and guide molecular design breeding. To this end, HS-SPME-GC-MS and RNA-Seq were used to analyze volatile organic compounds and the differentially expressed genes in Chardonnay and its aromatic bud sport. Forty-nine volatiles were identified as potential biomarkers, which included mainly aldehydes and terpenes. Geraniol, linalool, and phenylacetaldehyde were identified as the main aroma components of the mutant. The GO, KEGG, GSEA, and correlation analysis revealed HMGR, TPS1, TPS2, TPS5, novel.939, and CYP450 as key genes for terpene synthesis. MAO1 and MAO2 were significantly downregulated, but there was an increased content of phenylacetaldehyde. These key candidate genes provide a reference for the development of functional markers for muscat varieties and also provide insight into the formation mechanism of muscat aroma.
Assuntos
Metaboloma , Odorantes , Transcriptoma , Compostos Orgânicos Voláteis , Odorantes/análise , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Vitis/genética , Vitis/química , Vitis/metabolismo , Vinho/análise , Terpenos/metabolismo , Perfilação da Expressão Gênica , Monoterpenos Acíclicos/metabolismo , Regulação da Expressão Gênica de Plantas , Cromatografia Gasosa-Espectrometria de Massas , Acetaldeído/análogos & derivados , Acetaldeído/metabolismo , Monoaminoxidase/genética , Monoaminoxidase/metabolismoRESUMO
Activated hepatic stellate cells differentiate into myofibroblasts, which synthesize and secrete extracellular matrix (ECM) leading to liver fibrosis. It was previously demonstrated that bulleyaconitine A (BLA), an alkaloid from Aconitum bulleyanum, inhibits proliferation and promotes apoptosis of human hepatic Lieming Xu-2 (LX-2) cells. In this study, we analyzed the effect of BLA on the production of ECM and related proteins by LX-2 cells activated with acetaldehyde (AA). The cells were randomized into the control group, AA group (cells activated with 400 µM AA), and BLA+AA group (cells cultured in the presence of 400 µM AA and 18.75 µg/ml BLA). In the BLA+AA group, the contents of collagens I and III and the expression of α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1) were statistically significantly higher than in the control, but lower than in the AA group. Expression of MMP-1 in the BLA+AA group was also significantly higher than in the AA group, but lower than in the control. Expression of TIMP-1 in the BLA+AA group was significantly higher than in the control, but lower than in the AA group. Thus, BLA suppressed activation and proliferation of LX-2 cells by inhibiting TGF-ß1 signaling pathway and decreasing the content of collagens I and III by reducing the MMP-1/TIMP-1 ratio.
Assuntos
Acetaldeído , Aconitina , Actinas , Colágeno Tipo I , Matriz Extracelular , Células Estreladas do Fígado , Inibidor Tecidual de Metaloproteinase-1 , Fator de Crescimento Transformador beta1 , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Acetaldeído/farmacologia , Acetaldeído/análogos & derivados , Aconitina/farmacologia , Aconitina/análogos & derivados , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Actinas/metabolismo , Actinas/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/genética , Linhagem Celular , Colágeno Tipo III/metabolismo , Colágeno Tipo III/genética , Proliferação de Células/efeitos dos fármacos , Aconitum/química , Cirrose Hepática/metabolismo , Cirrose Hepática/patologiaRESUMO
We studied the effects of rheumatoid arthritis (RA) autoantibodies that target malondialdehyde-acetaldehyde protein adducts (anti-MAA) on inflammation and macrophage functions. We detected a profound reprogramming of gene expressions and the production of chemokines, such as CCL22 and CCL24, in anti-MAA exposed macrophages. Moreover, anti-MAA pretreatment promoted a more inflammatory cytokine profile upon TLR activation. Although anti-MAA are typically multi-reactive, we observed a prominent clonal diversity in inducing macrophage activation. Anti-MAA antibodies were not arthritogenic in mice, but altered a set of cytokine and growth factor encoding genes in the joints. In individuals at risk of RA anti-MAA IgG levels correlated with circulating inflammatory mediators prior to and at arthritis onset. Certain IgG anti-MAA clones may thus contribute to an inflammatory priming of the joint prior to the onset of systemic inflammation via inducing FcγR-mediated macrophage pre-activation and setting the stage for augmented responses to subsequent inflammatory stimuli.
Assuntos
Acetaldeído , Artrite Reumatoide , Autoanticorpos , Ativação de Macrófagos , Macrófagos , Malondialdeído , Artrite Reumatoide/imunologia , Animais , Ativação de Macrófagos/imunologia , Camundongos , Humanos , Autoanticorpos/imunologia , Macrófagos/imunologia , Acetaldeído/imunologia , Malondialdeído/imunologia , Inflamação/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Masculino , Feminino , Imunoglobulina G/imunologia , Pessoa de Meia-IdadeRESUMO
Nano zero-valent iron (NZVI) has been shown to effectively enhance the chain elongation (CE) process, addressing the issue of limited yield of medium-chain carboxylic acids (MCCA) from organic wastewater. However, the specific impact of NZVI on the metabolism of CE bacteria (CEB) is not well understood. In this study, it was aimed to investigate the mechanism by which an optimal concentration of NZVI influences CE metabolism, particularly in relation to ethanol oxidation, electron transfer, and MCCA synthesis. This was achieved through single-factor influence experiments and metagenomic analysis. The results showed that the addition of 1 g/gVSS NZVI achieved the highest MCCA yield (n-caproic acid + n-octanoic acid) at 2.02 g COD/L, which was 4.9 times higher than the control. This improvement in MCCA production induced by NZVI was attributed to several factors. Firstly, NZVI facilitated the oxidation of acetaldehyde, leading to its reduced accumulation in the system (from 18.4 % to 5.8 %), due to the optimized chemical environment created by NZVI corrosion, including near-neutral pH and a more reductive oxidation-reduction potential (ORP). Additionally, the inherent conductivity property of NZVI and the additional Fe ions released during corrosion improved the electron transfer efficiency between CEB. Lastly, both the composition of microbial communities and the abundance of unique enzyme genes confirmed the selective stimulation of NZVI on the reverse ß-oxidation (RBO) pathway. These findings provide valuable insights into the role of NZVI in CEB metabolism and its potential application for enhancing MCCA production in CE bioreactors.
Assuntos
Acetaldeído , Ácidos Carboxílicos , Ferro , Oxirredução , Ferro/química , Ferro/metabolismo , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Acetaldeído/química , Transporte de ElétronsRESUMO
Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.
Assuntos
Hepatócitos , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Desinfecção , Fígado/metabolismo , Fígado/efeitos dos fármacos , Acetaldeído/toxicidade , Linhagem CelularRESUMO
BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) is critical for alcohol metabolism by converting acetaldehyde to acetic acid. In East Asian descendants, an inactive genetic variant in ALDH2, rs671, triggers an alcohol flushing response due to acetaldehyde accumulation. As alcohol flushing is not exclusive to those of East Asian descent, we questioned whether additional ALDH2 genetic variants can drive facial flushing and inefficient acetaldehyde metabolism using human testing and biochemical assays. METHODS: After IRB approval, human subjects were given an alcohol challenge (0.25 g/kg) while quantifying acetaldehyde levels and the physiological response (heart rate and skin temperature) to alcohol. Further, by employing biochemical techniques including human purified ALDH2 proteins and transiently transfected NIH 3T3 cells, we characterized two newly identified ALDH2 variants for ALDH2 enzymatic activity, ALDH2 dimer/tetramer formation, and reactive oxygen species production after alcohol treatment. RESULTS: Humans heterozygous for rs747096195 (R101G) or rs190764869 (R114W) had facial flushing and a 2-fold increase in acetaldehyde levels, while rs671 (E504K) had facial flushing and a 6-fold increase in acetaldehyde levels relative to wild type ALDH2 carriers. In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2. The effect is caused by a lack of functional dimer/tetramer formation for R101G and decreased Vmax for both R101G and R114W. Transiently transfected NIH-3T3 cells with R101G and R114W also had a reduced enzymatic activity by ~ 50% relative to transfected wild-type ALDH2 and when subjected to alcohol, the R101G and R114W variants had a 2-3-fold increase in reactive oxygen species formation with respect to wild type ALDH2. CONCLUSIONS: We identified two additional ALDH2 variants in humans causing facial flushing and acetaldehyde accumulation after alcohol consumption. As alcohol use is associated with a several-fold higher risk for esophageal cancer for the E504K variant, the methodology developed here to characterize ALDH2 genetic variant response to alcohol can lead the way precision medicine strategies to further understand the interplay of alcohol consumption, ALDH2 genetics, and cancer.
Assuntos
Acetaldeído , Aldeído-Desidrogenase Mitocondrial , Etanol , Variação Genética , Acetaldeído/metabolismo , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Camundongos , Etanol/metabolismo , Células NIH 3T3 , Espécies Reativas de Oxigênio/metabolismo , Masculino , Adulto , Feminino , Rubor/metabolismo , Rubor/genéticaRESUMO
Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic and transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that, in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-coenzyme A (CoA) synthetase 2 (ACSS2) in the nucleus to couple high glucose metabolic flux with acetyl-histone H3 modification of neural crest (NC) lineage and glucose metabolism genes. Importantly, we show that acetaldehyde is a metabolite source for acetyl-histone H3 modification in an ALDH1A3-dependent manner, providing a physiologic function for this highly volatile and toxic metabolite. In a zebrafish melanoma residual disease model, an ALDH1-high subpopulation emerges following BRAF inhibitor treatment, and targeting these with an ALDH1 suicide inhibitor, nifuroxazide, delays or prevents BRAF inhibitor drug-resistant relapse. Our work reveals that the ALDH1A3-ACSS2 couple directly coordinates nuclear acetaldehyde-acetyl-CoA metabolism with specific chromatin-based gene regulation and represents a potential therapeutic vulnerability in melanoma.
Assuntos
Acetaldeído , Melanoma , Peixe-Zebra , Melanoma/metabolismo , Melanoma/genética , Melanoma/patologia , Melanoma/tratamento farmacológico , Acetaldeído/metabolismo , Acetaldeído/farmacologia , Animais , Humanos , Linhagem Celular Tumoral , Aldeído Oxirredutases/metabolismo , Aldeído Oxirredutases/genética , Histonas/metabolismo , Coenzima A Ligases/metabolismo , Coenzima A Ligases/genética , Transcrição Gênica/efeitos dos fármacos , Crista Neural/metabolismo , Crista Neural/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Golden apple snail (Pomacea canaliculata), a major alien invasive organism in China, affects food production and poses a threat to human health. Metaldehyde is a highly effective, commonly used snail killer with low toxicity. Virulence determination, tissue section, iTRAQ and RNA interference were used to systematically study the toxicity of metaldehyde on P. canaliculata. The molluscicidal activity tests showed that metaldehyde exhibits strong toxicity against P. canaliculata. Physiological and biochemical data indicate that metaldehyde can cause damage to the gills, liver, pancreas, and kidneys of snails, also reduce the oxygen consumption rate and ammonia excretion rate of golden apple snails, and cause neurological diseases. The proteome of the gill region of the golden apple snail after exposure to metaldehyde was analyzed by using iTRAQ technology. A total of 360 differential proteins were identified, and four target proteins were screened, namely, alpha-protein kinase 1 (ALPK1), cubilin (CUBN), sodium- and chloride-dependent GABA transporter 2 (GAT2), and acetylcholinesterase (AChE). RNAi was used to target the four proteins. After the ALPK1 and CUBN protein genes were interfered with by metaldehyde treatment, it was found that the mortality rate of the golden apple snail significantly increased. However, interference of GAT2 and AChE protein genes by metaldehyde led to no significant change in the mortality rates of the snails. The histopathological observation of the gill showed that the rate of cilia shedding in the gill decreased after the interference of ALPK1 and CUBN protein genes.
Assuntos
Moluscocidas , Caramujos , Animais , Caramujos/genética , Caramujos/metabolismo , Moluscocidas/metabolismo , Acetaldeído/análogos & derivados , Acetaldeído/metabolismo , Acetaldeído/toxicidade , Brânquias/metabolismo , Brânquias/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Acetilcolinesterase/genética , ChinaRESUMO
Microdialysis is an important technique for in vivo sampling of tissue's biochemical composition. Understanding the factors that affect the performance of the microdialysis probes and developing methods for sample analysis are crucial for obtaining reliable results. In this work, we used experimental and numerical procedures to study the performance of microdialysis probes having different configurations, membrane materials and dimensions. For alcohol research, it is important to understand the dynamics of ethanol metabolism, particularly in the brain and in other organs, and to simultaneously measure the concentrations of ethanol and its metabolites - acetaldehyde and acetate. Our work provides a comprehensive characterization of three microdialysis probes, in terms of recovery rates and backpressure, allowing for interpretation and optimization of experimental procedures. In vivo experiments were performed to measure the time course concentration of ethanol, acetaldehyde, and acetate in the rat brain dialysate. Additionally, the combination of in vitro experimental results with numerical simulations enabled us to calculate diffusion coefficients of molecules in the microdialysis membranes and study the extent of the depletion effect caused by continuous microdialysis sampling, thus providing additional insights for probe selection and data interpretation.
Assuntos
Encéfalo , Etanol , Microdiálise , Microdiálise/métodos , Etanol/metabolismo , Etanol/análise , Etanol/farmacocinética , Animais , Ratos , Encéfalo/metabolismo , Acetaldeído/análise , Acetaldeído/metabolismo , Masculino , Acetatos/metabolismo , Acetatos/farmacocinéticaRESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial , Etanol , Fígado , Fígado/metabolismo , Animais , Etanol/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Camundongos , Consumo de Bebidas Alcoólicas/metabolismo , Acetaldeído/metabolismo , Inativação Metabólica , Trato Gastrointestinal/metabolismo , Alcoolismo/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Microbioma Gastrointestinal , Bile/metabolismoRESUMO
Copper (II), a vital fungicide in organic viticulture, also acts as a wine oxidation catalyst. However, limited data are currently available on the impact that maximum allowed copper (II) ion doses in wine grapes at harvest can have on aged wine quality. This was the focus of the present study. We investigated the copper (II) effects by producing both white and red wines from musts containing three initial metal concentrations according to the limits set for organic farming. In detail, the influence of copper (II) on fermentation evolution, chromatic characteristics, and phenolic compounds was evaluated. Interestingly, the white wine obtained with the highest permitted copper (II) dose initially exceeded the concentration of 1.0 mg/L at fermentation completion. However, after one year of storage, the copper (II) content fell below 0.2 ± 0.01 mg/L. Conversely, red wines showed copper (II) levels below 1.0 mg/L at the end of fermentation, but the initial copper (II) level in musts significantly affected total native anthocyanins, color intensity, hue, and acetaldehyde concentration. After 12-month aging, significant differences were observed in polymeric pigments, thus suggesting a potential long-term effect of copper (II) on red wine color stability.
Assuntos
Acetaldeído , Cobre , Fermentação , Fenóis , Vitis , Vinho , Vinho/análise , Cobre/análise , Acetaldeído/análise , Fenóis/análise , Fenóis/química , Vitis/química , Cor , Antocianinas/análise , Antocianinas/químicaRESUMO
All pests can be eliminated with the help of pesticides, which can be either natural or synthetic. Because of the excessive use of pesticides, it is harmful to both ecology and people's health. Pesticides are categorised according to several criteria: their chemical composition, method of action, effects, timing of use, source of manufacture, and formulations. Many aquatic animals, birds, and critters live in danger owing to hazardous pesticides. Metaldehyde is available in various forms and causes significant impact even when small amounts are ingested. Metaldehyde can harm wildlife, including dogs, cats, and birds. This review discusses pesticides, their types and potential environmental issues, and metaldehyde's long-term effects. In addition, it examines ways to eliminate metaldehyde from the aquatic ecosystem before concluding by anticipating how pesticides may affect society. The metal-organic framework and other biosorbents have been appropriately synthesized and subsequently represent the amazing removal of pesticides from effluent as an enhanced adsorbent, such as magnetic nano adsorbents. A revision of the risk assessment for metaldehyde residuals in aqueous sources is also attempted.
Assuntos
Acetaldeído , Praguicidas , Poluentes Químicos da Água , Acetaldeído/análogos & derivados , Animais , Medição de Risco , Humanos , Adsorção , Estruturas Metalorgânicas/químicaRESUMO
We investigated the applicability of proton transfer reaction-time-of-flight mass spectrometry (PTR-TOF-MS) for quantitative analysis of mixtures comprising glycerin, acetol, glycidol, acetaldehyde, acetone, and propylene glycol. While PTR-TOF-MS offers real-time simultaneous determination, the method selectivity is limited when analyzing compounds with identical elemental compositions or when labile compounds present in the mixture produce fragments that generate overlapping ions with other matrix components. In this study, we observed significant fragmentation of glycerin, acetol, glycidol, and propylene glycol during protonation via hydronium ions (H3O+). Nevertheless, specific ions generated by glycerin (m/z 93.055) and propylene glycol (m/z 77.060) enabled their selective detection. To thoroughly investigate the selectivity of the method, various mixtures containing both isotope-labeled and unlabeled compounds were utilized. The experimental findings demonstrated that when samples contained high levels of glycerin, it was not feasible to perform time-resolved analysis in H3O+ mode for acetaldehyde, acetol, and glycidol. To overcome the observed selectivity limitations associated with the H3O+ reagent ions, alternative ionization modes were investigated. The ammonium ion mode proved appropriate for analyzing propylene glycol (m/z 94.086) and acetone (m/z 76.076) mixtures. Concerning the nitric oxide mode, specific m/z were identified for acetaldehyde (m/z 43.018), acetone (m/z 88.039), glycidol (m/z 73.028), and propylene glycol (m/z 75.044). It was concluded that considering the presence of multiple product ions and the potential influence of other compounds, it is crucial to conduct a thorough selectivity assessment when employing PTR-TOF-MS as the sole method for analyzing compounds in complex matrices of unknown composition.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Espectrometria de Massas , Nicotiana , Compostos Orgânicos Voláteis , Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Nicotiana/química , Propilenoglicol/análise , Propilenoglicol/química , Acetaldeído/análise , Acetaldeído/química , Acetona/análise , Acetona/química , Acetona/análogos & derivados , Glicerol/análise , Glicerol/química , Temperatura Alta , Compostos de Epóxi/química , Compostos de Epóxi/análise , Propanóis/química , Propanóis/análiseRESUMO
Ribose is the defining sugar in ribonucleic acid (RNA), which is often proposed to have carried the genetic information and catalyzed the biological reactions of the first life on Earth. Thus, abiological processes that yield ribose under prebiotic conditions have been studied for decades. However, aqueous environments required for the formation of ribose from materials available in quantity under geologically reasonable models, where the ribose formed is not immediately destroyed, remain unclear. This is due in large part to the challenge of analysis of carbohydrates formed under a wide range of aqueous conditions. Thus, the formation of ribose on prebiotic Earth has sometimes been questioned. We investigated the quantitative effects of pH, temperature, cation, and the concentrations of formaldehyde and glycolaldehyde on the synthesis of diverse sugars, including ribose. The results suggest a range of conditions that produce ribose and that ribose could have formed in constrained aquifers on prebiotic Earth.
Assuntos
Formaldeído , Ribose , Temperatura , Água , Ribose/química , Concentração de Íons de Hidrogênio , Água/química , Formaldeído/química , Acetaldeído/química , Acetaldeído/análogos & derivados , Planeta Terra , Origem da VidaAssuntos
Acetaldeído , Odorantes , Perfumes , Humanos , Perfumes/toxicidade , Perfumes/química , Animais , Medição de Risco , Acetaldeído/toxicidade , Acetaldeído/química , Acetaldeído/análogos & derivados , Acetais/toxicidade , Acetais/química , Determinação de Ponto Final , Qualidade de Produtos para o Consumidor , Testes de Toxicidade , Nível de Efeito Adverso não Observado , Bases de Dados de Compostos QuímicosRESUMO
Mirabegron (MRB) is a ß3-adrenoceptor agonist used for managing overactive bladder syndrome. A cost-effective, environmentally friendly, and highly sensitive spectrofluorimetric method was suggested to serve the purpose of quantifying MRB in its pure state, pharmaceutical tablets, spiked human plasma and urine, and testing content uniformity. In the present study, ninhydrin and phenylacetaldehyde react with the amino group moiety of MRB in Teorell-Stenhagen buffer (pH 7.5) to generate a strongly fluorescent diaryl pyrrolone compound that emits fluorescence at a wavelength of 477 nm upon excitation at 385 nm. The obtained calibration curve showed a linear relationship with a high correlation coefficient (r = 0.9997) in the concentration range of 0.25 to 5.0 µg mL-1. Limits of detection (LOD) and quantitation (LOQ) were 0.082 and 0.248 µg mL-1 respectively. The procedure was verified in accordance with the ICH guidelines. The suggested approach could be utilized for the selective analysis of MRB in its pharmaceuticals, either containing a single drug or co-formulated with solifenacin succinate. The greenness of the suggested method was confirmed using different green analytical metrics.
Assuntos
Acetanilidas , Limite de Detecção , Ninidrina , Espectrometria de Fluorescência , Tiazóis , Humanos , Ninidrina/química , Espectrometria de Fluorescência/métodos , Acetanilidas/urina , Acetanilidas/sangue , Acetanilidas/química , Tiazóis/química , Tiazóis/urina , Tiazóis/sangue , Pirróis/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Comprimidos , Acetaldeído/análogos & derivadosRESUMO
ß-Hydroxy-α-amino acids (ßHAAs) are an essential class of building blocks of therapeutically important compounds and complex natural products. They contain two chiral centers at Cα and Cß positions, resulting in four possible diastereoisomers. Many innovative asymmetric syntheses have been developed to access structurally diverse ßHAAs. The main challenge, however, is the control of the relative and absolute stereochemistry of the asymmetric carbons in a sustainable way. In this respect, there has been considerable attention focused on the chemoenzymatic synthesis of ßHAAs via a one-step process. Nature has evolved different enzymatic routes to produce these valuable ßHAAs. Among these naturally occurring transformations, L-threonine transaldolases present potential biocatalysts to generate ßHAAs in situ. 4-Fluorothreonine transaldolase from Streptomyces sp. MA37 (FTaseMA) catalyzes the cross-over transaldolation reaction between L-Thr and fluoroacetaldehyde to give 4-fluorothreonine and acetaldehyde (Ad). It has been demonstrated that FTaseMA displays considerable substrate plasticity toward structurally diverse aldehyde acceptors, leading to the production of various ßHAAs. In this chapter, we describe methods for the preparation of FTaseMA, and the chemoenzymatic synthesis of ßHAAs from various aldehydes and L-Thr using FTaseMA.
Assuntos
Streptomyces , Transaldolase , Streptomyces/enzimologia , Transaldolase/metabolismo , Transaldolase/química , Transaldolase/genética , Treonina/análogos & derivados , Treonina/química , Treonina/metabolismo , Biocatálise , Aminoácidos/química , Aminoácidos/metabolismo , Especificidade por Substrato , Acetaldeído/análogos & derivados , Acetaldeído/metabolismo , Acetaldeído/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Ensaios Enzimáticos/métodos , EstereoisomerismoRESUMO
Sulfite addition is a common tool for ensuring wines' oxidative stability via the activity of its free and weakly bound molecular fraction. As a nucleophile, bisulfite forms covalent adducts with wine's most relevant electrophiles, such as carbonyls, polyphenols, and thiols. The equilibrium in these reactions is often represented as dissociation rather than formation. Recent studies from our laboratory demonstrate, first, the acetaldehyde sulfonate dissociation, and second, the chemical stability of cysteine and epicatechin sulfonates under wine aging conditions. Thus, the objective of this study was to monitor by 1H NMR the binding specificity of known carbonyl-derived SO2 binders (acetaldehyde and pyruvic acid) in the presence of S-containing compounds (cysteine and glutathione). We report that during simulated wine aging, the sulfur dioxide that is rapidly bound to carbonyl compounds will be released and will bind to cysteine and glutathione, demonstrating the long-term sulfur dioxide binding potential of S-containing compounds. These results are meant to serve as a complement to existing literature reviews focused on molecular markers related to wines' oxidative stability and emphasize once more the importance of S-containing compounds in wine aging chemical mechanisms.
Assuntos
Compostos de Sulfidrila , Vinho , Vinho/análise , Cinética , Compostos de Sulfidrila/química , Oxirredução , Dióxido de Enxofre/química , Cisteína/química , Cisteína/metabolismo , Acetaldeído/química , Sulfitos/química , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Glutationa/química , Glutationa/metabolismoRESUMO
Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4â +â T cells, CD8â +â T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.
Assuntos
Acetaldeído , Aldeído-Desidrogenase Mitocondrial , Neoplasias , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/imunologia , Aldeído-Desidrogenase Mitocondrial/metabolismo , Algoritmos , Biomarcadores , Neoplasias/genética , Prognóstico , Microambiente Tumoral/imunologiaRESUMO
In the context of the increasing global use of ethanol biofuel, this work investigates the concentrations of ethanol, methanol, and acetaldehyde, in both the gaseous phase and rainwater, across six diverse urban regions and biomes in Brazil, a country where ethanol accounts for nearly half the light-duty vehicular fuel consumption. Atmospheric ethanol median concentrations in São Paulo (SP) (12.3 ± 12.1 ppbv) and Ribeirão Preto (RP) (12.1 ± 10.9 ppbv) were remarkably close, despite the SP vehicular fleet being â¼13 times larger. Likewise, the rainwater VWM ethanol concentration in SP (4.64 ± 0.38 µmol L-1) was only 26 % higher than in RP (3.42 ± 0.13 µmol L-1). This work demonstrated the importance of evaporative emissions, together with biomass burning, as sources of the compounds studied. The importance of biogenic emissions of methanol during forest flooding was identified in campaigns in the Amazon and Atlantic forests. Marine air masses arriving at a coastal site led to the lowest concentrations of ethanol measured in this work. Besides vehicular and biomass burning emissions, secondary formation of acetaldehyde by photochemical reactions may be relevant in urban and non-urban regions. The combined deposition flux of ethanol and methanol was 6.2 kg ha-1 year-1, avoiding oxidation to the corresponding and more toxic aldehydes. Considering the species determined here, the ozone formation potential (OFP) in RP was around two-fold higher than in SP, further evidencing the importance of emissions from regional distilleries and biomass burning, in addition to vehicles. At the forest and coastal sites, the OFP was approximately 5 times lower than at the urban sites. Our work evidenced that transition from gasoline to ethanol or ethanol blends brings the associated risk of increasing the concentrations of highly toxic aldehydes and ozone, potentially impacting the atmosphere and threatening air quality and human health in urban areas.