Expression of acetaldehyde dehydrogenase 2 in endometrial carcinoma and its correlation with clinical characteristics of patients / 中国医师杂志

Objective:To detect the expression of acetaldehyde dehydrogenase (ALDH) 2 and microRNA (miR)-135b-3p in endometrial cancer (EC) tissues, and to explore their correlation with clinical characteristics.Methods:94 endometrial cancer tissue specimens (EC group) and 60 normal endometrial specimens (control group) were selected from Northwest Women′s and Children′s Hospital from February 2019 to February 2022. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression changes of ALDH2 mRNA and miR-135b-3p in endometrial tissue of two groups, and immunohistochemistry was used to detect the positive expression rate of ALDH2 protein. The relationship between the expression levels of ALDH2 and miR-135b-3p and the clinicopathological characteristics was analyzed.Results:The expression of ALDH2 mRNA in the EC group (0.67±0.15) was lower than that in the control group (1.05±0.12), and the expression level of miR-135b-3p (1.52±0.26) was higher than that in the control group (1.01±0.06). The positive expression rate of ALDH2 in cancer tissue of EC group was 30.85%(29/94), which was lower than 51.67%(31/60) in normal endometrial tissue of the control group ( P<0.05). The expression levels of ALDH2 mRNA and miR-135b-3p in EC patients were related to International Federation of Obstetrics and Gynecology (FIGO) stage, lymph node metastasis, differentiation and myometrium invasion (all P<0.05), but not to age, pathological type, menopause, HPV infection, menarche age, parity, tumor length and BMI (all P>0.05). Conclusions:In EC tissues, the expression of ALDH2 is down-regulated and the expression of miR-135b-3p is up-regulated, which may be involved in the occurrence and development of EC.

Control strategy for the limit of aldehydes in polysorbates based on genotoxicity and influence on the aggregation of monoclonal antibody / 中国药科大学学报

@#An HPLC pre-column derivatization detection method was established to detect and analyze the formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 from different manufacturers.The effects of aldehyde and acetaldehyde on the aggregation of adalimumab under different conditions were monitored.Based on the control of genotoxic impurities and the influence on the stability of monoclonal antibody preparations, the control limits of the two chemicals were preliminarily obtained.2, 4-dinitrophenylhydrazine (2, 4-DNPH) was applied as the derivatization reagent in HPLC pre-column derivatization; acetonitrile and water were used as mobile phase to perform a gradient elution on a C8 (4.6 mm × 150 mm, 5 μm) chromatographic column.The detection wavelength was 360 nm, and the external standard method was used for quantification.Verification results showed that the method was suitable for the quantitative analysis of trace formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 . The detection and analysis of formaldehyde or acetaldehyde in different batches of polysorbate 80 and polysorbate 20 from different manufacturers showed that the content of formaldehyde and acetaldehyde were quite different. The content of formaldehyde and acetaldehyde in polysorbate 80 were significantly higher than those of polysorbate 20. After monitoring the changes of adalimumab aggregates treated by formaldehyde and acetaldehyde by size exclusion chromatography (SEC), it was found that the effect of formaldehyde on adalimumab aggregation was significantly higher than that of acetaldehyde.According to the requirements of ICH M7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk), the impurity limits of formaldehyde and acetaldehyde in polysorbate 80 and polysorbate 20 for monoclonal antibody preparations were calculated from the perspective of risk assessment.Combined with the influence on the aggregation stability of monoclonal antibodies, the preliminary limis for acetaldehyde and acetaldehyde were recommended to be ≤ 7 μg/g and ≤ 765 μg/g, respectively.

The relationship between Candida albicans infection and oral cancer / 口腔疾病防治

@#Oral cancer is one of the most common cancers that occur in the head and neck and can seriously affect the life span and living standard of oral cancer patients. Candida albicans （C. albicans） is the most common opportunistic pathogenic fungus in the oral cavity, shows pathogenicity and easily causes Candida infection when the host′s immune function is low. Recent studies have shown that C. albicans infection is closely related to oral cancer. This paper reviews the epidemiology of C. albicans infection in oral cancer patients, the influence of C. albicans infection on the occurrence and development of oral cancer and research on its mechanism. Existing studies have shown an increased risk of C. albicans infection in oral cancer patients, while C. albicans infection may promote the occurrence and development of oral cancer through mechanisms such as damaging the oral epithelium; producing carcinogens, including nitrosamine and acetaldehyde; and inducing a chronic inflammatory response and T helper cell 17 immune response. However, these mechanisms are still relatively superficial and lack sufficient direct evidence. In the future, additional in-depth studies are still needed to further clarify the cancer-promoting mechanisms of C. albicans and provide new ideas for the prevention and treatment of oral cancer.

Research progress of Candida albicans on malignant transformation of oral mucosal diseases / 华西口腔医学杂志

Oral cancer is the most common malignant tumor in the head and neck, and is one of the world's top ten malignancies. Microbial infection is an important risk factor of oral cancer. Candida albicans is the most popular opportunistic fungal pathogen. Epidemiological studies have shown that Candida albicans is closely tied to oral malignancy. Animal experimentation have also proven that infection of Candida albicans can promote the development of oral epithelial carcinogenesis. The current studies have revealed several mechanisms involved in this process, including destroying the epithelial barrier, producing carcinogenic substances (nitrosamines, acetaldehyde), inducing chronic inflammation, activating immune response, etc. However, current researches on mechanisms are still inadequate, and some hypotheses remain controversial. Here, we review the findings related to Candida albicans' effect on the malignant transformation of oral mucosa, hoping to provide reference for deep research and controlling oral cancer clinically.

Improvement of detection method for acetaldehyde, butyraldehyde and isobutyraldehyde in workplace air / 中国职业医学

OBJECTIVE: To improve the standard detection method for acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace. METHODS: Acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace were collected using silica gel tube, desorbed with 45.0% ethanol, separated by a capillary column and detected by a flame ionization detector. RESULTS: The linear range of this method for detecting acetaldehyde, butyraldehyde and isobutyraldehyde were 1.57-1 568.00, 1.60-1 600.00 and 1.59-1 588.00 mg/L, respectively. All the correlation coefficients were greater than 0.999. The detection limits were 0.52, 0.46 and 0.54 mg/L, respectively. The desorption efficiency was 91.0%-103.0%. The within-run relative standard deviation(RSD) was 0.7%-1.7%.The between-run RSD was 2.0%-3.7%. The samples could be stored for at least 10 days at room temperature. CONCLUSION: This method can be used for simultaneous detection of acetaldehyde, butyraldehyde and isobutyraldehyde in the air of workplace.

Hangover relieving and antioxidant effects of Gynostemma pentaphyllum (Thunb.) Makino and/or Hovenia dulcis Thunb. extracts

The present study attempts to study alcohol metabolizing and antioxidant properties of Gynostemma pentaphyllum(Thunb.) Makino distillate (GPD) and combination effects with Hovenia dulcis Thunb. extract (HDE) on these activities.The alcohol-metabolizing activity of GPD with/without HDE was determined by assessing alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase (ALDH) activities. To define the effect of GPD with/without HDE on alcoholmetabolism, antioxidant activities and total phenolic content of GPD with/without HD extract were evaluated using2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous chelating assays, and the Folin–Ciocalteu method.Cytotoxicity against human normal liver CHANG cells was also evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. GPD treatment alone or in combination with HDE significantly increased ADHand ALDH activities; combined treatment was most effective. Total phenolic and flavonoid contents were greater incombination than the level found in GPD alone. GPD revealed a synergistic antioxidant effect when combined withHDE. GPD and/or HDE had no antiproliferative activity against the normal liver cell line. These results suggest thatGPD-HDE combination is the possible natural resource for the management of alcohol-induced liver injury.

Relationship between Blood Acetaldehyde Concentration and Psychomotor Function of Individuals with Different ALDH2 Genotypes after Alcohol Consumption / 法医学杂志

Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.

Relationship between acetaldehyde concentration in mouth air and characteristics of microbiota of tongue dorsum in Japanese healthy adults: a cross-sectional study

Abstract Acetaldehyde, associated with consumption of alcoholic beverages, is known to be a carcinogen and to be related to the tongue dorsum. Objective The aim of this study was to investigate the relationship between acetaldehyde concentration in mouth air and bacterial characteristics on the tongue dorsum. Methodology Thirty-nine healthy volunteers participated in the study. Acetaldehyde concentrations in mouth air were evaluated by a high-sensitivity semiconductor gas sensor. A 16S rRNA gene sequencing technique was used to compare microbiomes between two groups, focusing on the six samples with the highest acetaldehyde concentrations (HG) and the six samples with lowest acetaldehyde concentrations (LG). Results Acetaldehyde concentration increased in correlation with the increase in bacterial count (p=0.048). The number of species observed in the oral microbiome of the HG was higher than that in the oral microbiome of the LG (p=0.011). The relative abundances of Gemella sanguinis, Veillonella parvula and Neisseria flavescens in the oral microbiome of the HG were higher than those in the oral microbiome of the LG (p<0.05). Conclusion Acetaldehyde concentration in mouth air was associated with bacterial count, diversity of microbiome, and relative abundance of G. sanguinis, V. parvula, and N. flavescens.

Carbonyl compounds in wine: factors related to presence and toxic effects / Compostos carbonílicos em vinho: fatores relacionados a presença e efeitos tóxicos

ABSTRACT: The objective of this study was to review technological and toxicological factors related to presence of carbonyl compounds found in wines, including acetaldehyde, formaldehyde, acrolein, ethyl carbamate (EC) and furfural. Acetaldehyde and formaldehyde may be formed through the ethanol and methanol oxidation, respectively. Acrolein may arise as a thermal degradation product of glycerol, amino acids, carbohydrates and triglycerides or by metabolic activity of microorganisms. In addition, acrolein and furfural are formed during wood combustion; therefore, these aldehydes may be present in raw materials due to the environmental contamination. Furfural is also a product of the Maillard reaction formed from sugars and amino acids, while ethyl carbamate occurs through the reaction between urea and ethanol. These compounds may react with SO2 and phenolic compounds to form non-volatile adducts, which positively modulates color stability, astringency and aroma in wine. However, when ingested through wine, electrophilic carbonyl compounds may form adducts with nucleophilic targets, such as DNA, resulting in genotoxicity along the gastrointestinal tract. Furthermore, carbonyl compounds induce the increase of reactive oxygen species and can trigger apoptosis, in addition to hepatocellular adenoma and carcinoma as a consequence of chronic hepatotoxicity. Neurodegenerative diseases may be related to the exposure to carbonyl compounds. Therefore, strategies to reduce the levels of these compounds should be studied in order to get the most out of the beneficial functional properties of wine consumption.

RESUMO: O objetivo deste estudo foi revisar os fatores tecnológicos e toxicológicos relacionados à presença de compostos carbonílicos encontrados em vinhos, incluindo acetaldeído, formaldeído, acroleína, carbamato de etila (CE) e furfural. O acetaldeído e o formaldeído podem ser formados através da oxidação do etanol e do metanol, respectivamente. A acroleína pode surgir como um produto de degradação térmica de glicerol, aminoácidos, carboidratos e triglicerídeos ou pela atividade metabólica de microorganismos. Além disso, a acroleína e o furfural são formados durante a combustão da madeira. Portanto, esses aldeídos podem estar presentes nas matérias-primas devido à contaminação ambiental. O furfural é também um produto da reação de Maillard formado a partir de açúcares e aminoácidos, enquanto o carbamato de etila ocorre através da reação entre uréia e etanol. Estes compostos podem reagir com SO2 e compostos fenólicos para formar adutos não voláteis, que modulam positivamente a estabilidade da cor, adstringência e aroma no vinho. No entanto, quando ingeridos através do vinho, os compostos carbonílicos que são eletrofílicos podem formar adutos com alvos nucleofílicos, como o DNA, resultando em genotoxicidade ao longo do trato gastrintestinal. Além disso, os compostos carbonílicos também induzem o aumento de espécies reativas de oxigênio e podem desencadear a apoptose, além de adenoma e carcinoma hepatocelular como consequência da hepatotoxicidade crônica. Doenças neurodegenerativas podem estar relacionadas à exposição aos compostos carbonílicos. Com isso, estratégias para reduzir os níveis desses compostos devem ser estudadas para obter o máximo das propriedades funcionais benéficas do consumo de vinho.

Molecular Pathways for Nasopharyngeal Carcinoma focused on Acetaldehyde, Nitrosamines and Nicotine Exposures

@#Recently, one of the head and neck tumours located at the nasopharynx epithelium known as nasopharyngeal carcinoma (NPC) have been associated with few cancer-promoting compounds that derived from alcohol, salt preserved foods consumptions and tobacco smoking such as acetaldehyde, nitrosamine, nicotine. These cancer-promoting compounds present the ability to damage the genome and disrupt cellular metabolic processes. This review will discuss further on the molecular mechanism of acetaldehyde, nitrosamine, nicotine and NPC risk. Acetaldehyde can exert influence as carcinogen macromolecular adducts to cellular proteins and DNAs whilst nitrosamines that commonly found in preserved salted foods/diets can contribute as a powerful carcinogen via endogenous nitrosation and reactives molecules by CYP2E1. Nicotine present in tobacco could reacts with nitrosamine to form NNN and NNK known as carcinogenic agent. NNK mediates unstable reactive oxygen species that can induce DNA lesion (α -hydroxylation of NNN at positions 2’and 5’) and microenvironment alteration for tumorigenesis. In conclusion, this study suggests acetaldehydes, nitrosamine and nicotine may contribute to NPC tumourigenesis.

Effects of mitochondrial aldehyde dehydrogenase 2 on autophagy-associated proteins in neonatal rat myocardial fibroblasts cultured in high glucose / 南方医科大学学报

OBJECTIVE@#To investigate whether autophagy mediates the effects of aldehyde dehydrogenase 2 (ALDH2) on the proliferation of neonatal rat cardiac fibroblasts cultured in high glucose.@*METHODS@#Cardiac fibroblasts were isolated from neonatal (within 3 days) SD rats and subcultured. The fibroblasts of the third passage, after identification with immunofluorescence staining for vimentin, were treated with 5.5 mmol/L glucose (control group), 30 mmol/L glucose (high glucose group), or 30 mmol/L glucose in the presence of Alda-1 (an ALDH2 agonist), daidzin (an ALDH2 2 inhibitor), or both. Western blotting was employed to detect ALDH2, microtubule-associated protein 1 light chain 3B subunit (LC3B) and Beclin-1 in the cells, and a hydroxyproline detection kit was used for determining hydroxyproline content in cell culture medium; CCK- 8 kit was used for assessing the proliferation ability of the cardiac fibroblasts after the treatments.@*RESULTS@#Compared with the control cells, the cells exposed to high glucose exhibited obviously decreased expressions of ALDH2, Beclin-1 and LC3B and increased cell number and hydroxyproline content in the culture medium. Treatment of the high glucose-exposed cells with Alda-1 significantly increased Beclin-1, LC3B, and ALDH2 protein expressions and lowered the cell number and intracellular hydroxyproline content, whereas the application of daidzin resulted in reverse changes in the expressions of ALDH2, Beclin-1 and LC3B, viable cell number and intracellular hydroxyproline content in high glucose-exposed cells.@*CONCLUSIONS@#Mitochondrial ALDH2 inhibits the proliferation of neonatal rat cardiac fibroblasts induced by high glucose, and the effect is possibly mediated by the up-regulation of autophagy-related proteins Beclin-1 and LC3B.

Pilot Study of a Brief WeChat Intervention in China to Increase Students' Willingness to Assist a Flushing Student to Reduce Alcohol Use / 예방의학회지

OBJECTIVES: This pilot study tested the effectiveness of a brief alcohol-related intervention delivered by the social media app WeChat to teach about ethanol-induced facial flushing and increase the willingness of students who see another student flushing to suggest that he or she should reduce or stop drinking. In the context of Chinese drinking culture, it is sometimes socially difficult to refuse a drink, even when experiencing physical discomfort, such as flushing. METHODS: Classrooms of students in a medical university in China were randomly assigned to the intervention or control group. Students in the intervention group were invited to view 3 alcohol education lessons on WeChat during a 2-week period. A pretest and posttest before and after the 2-week period assessed changes in students’ willingness to intervene if they saw someone flush while drinking. Data were collected about students’ alcohol use and their ratings of the lessons. RESULTS: Mixed-design analysis of variance yielded a significant time-by-treatment interaction effect on the variable of willingness to suggest that a flushing person stop or slow down their drinking, and the change was significant between the intervention and control groups. One-way analysis of covariance yielded a significant treatment effect at the posttest, after controlling for the pretest score. Students rated the lessons above the midpoint of the scale for being informative, interesting, and useful. CONCLUSIONS: The pilot study showed that a brief alcohol-related intervention delivered by WeChat could produce a measurable positive change in the willingness of university students to suggest that a student who flushes should stop drinking. This pilot study also suggested improvements for future lessons and evaluation design.

Pre-column Derivation HPLC Method for Detemination of Aldehydes and Research on the Correlation between Aldehydes and Peroxide Value in Polysorbates / 中国药学杂志

OBJECTIVE: To develop a quantitative determination method of formaldehyde and acetaldehyde and study the correlation between aldehydes and peroxide value in polysorbate 20, 40, 60 and 80.METHODS: Formaldehyde and acetaldehyde in polysorbates reacted with 2,4-dinitrophenylhydrazine(DNPH) for 60 min at room temperature and stable phenylhydrazone compounds,formaldehyde-DNPH and acetaldehyde-DNPH, were obtained, respectively.The two phenylhydrazone compounds were simultaneously detected by HPLC to calculate the contents of formaldehyde and acetaldehyde in polysorates. The peroxide value of polysorbates was also determined according to chapter of Chinese Pharmacopoeia 2015. RESULTS: The HPLC method for quantitative determination of aldehydes in polysorates had good specificity. The resolutions of formaldehyde-DNPH and acetaldehyde-DNPH were 2.0 and 2.9, respectively. There was good linearity in the range of 0.1-35.0 μg•mL-1 for formaldehyde(r=0.999 8) and 0.2-50.0 μg•mL-1 for acetaldehyde(r=0.999 6). The average spiked recoveries were in the range of 88.6%-103.5% and their relative standard deviations(RSDs) were in the range of 1.2%-2.6%.The RSDs of intra-day and inter-day precision were not more than 6.0%.The limits of detection and quantitation were 0.03 and 0.1 μg•mL-1 for formaldehyde and 0.06 and 0.2 μg•mL-1 for acetaldehyde, respectively. The contents of aldehydes in polysorbates from different manufacturers were 0-593.1 μg•g-1 for formaldehyde and 0-740.5 μg•g-1 for acetaldehyde, however, the peroxide values of most polysorbate products were less than 10. CONCLUSION: The pre-column derivation HPLC method is suitable for assay of trace aldehydes in polysorbates. Moreover, the weak correlation between aldehydes and peroxide value indicated that the latter testing item is not enough to control the risk of aldehydes in polysorbates. Therefore, aldehydes as well as quantitative determination method are suggested to be included in the monographs of polysorbates to improve their quality standard.

Molecular mechanism of alcohol-associated gastric cancer / 中国药理学通报

Gastric cancer is the second most common cancer in China. Alcohol consumption is related to gastric cancer as a sig-nificant risk factor. Some key enzymes is expected to influence the alcohol-associated metabolism. There are many molecular mechanisms of alcohol-related gastric cancer, such as generation of acetaldehyde by microbiome, inflammation, up-regulation of Pol Ⅲ genes, carcinogen-DNA adduct formation and genetic polymorphisms of alcohol metabolizing enzymes. Different types and concentrations of alcohol have different effects on the devel-opment of gastric cancer. This review presents a systematic ex-position on the molecular mechanism of alcohol-associated gastric cancer.

Correlation analysis of Aldehyde dehydrogenase 2 genetic Glu504Lys polymorphism and hypertension in chongqing area / 国际检验医学杂志

Objective To study the acetaldehyde dehydrogenase 2(ALDH2)Glu504Lys polymorphism and the correlation of hypertension in Chongqing area.Methods The ALDH2 genotype of 144 patients hyperten-sion group and 193 healthy people controls group were detected by gene chip.Results Three types of ALDH2 genotypes were detected,which were ALDH2*1/*1(wild type),ALDH2*1/*2 and ALDH2*2/*2(mu-tant).The wild type and mutant type in hypertension group and control group were 112(77.78%),32 (22.22%)and 114(59.07%),79(40.93%)respectively,distribution accorded with Hardy-Weinberg equilibrium.The wild type ratio of hypertension group was higher than that of the control group,and the difference was statistically significant(P<0.05).Logistic regression analysis showed that ALDH 2 gene poly-morphism was an independent risk factor for hypertension.Conclusion The ALDH2 wild type in chongqing is closely related to hypertension.

Correlation of Genetic Polymorphism, Alcoholic Beverage Type and Ethanol Metabolism / 法医学杂志

Objective To explore the effects of A DH1B and A LDH2 gene polymorphism and type of al-coholic beverage on ethanol metabolism, to provide data support for cases involving the interpretation of ethanol metabolism or back calculation of blood ethanol concentration in forensic practice. Methods A total of 81 volunteers were selected. The genotypes of A DH1B, A DH1C and A LDH2 were obtained by a multiplex SNaPshot genotyping method. Each subject was administered with 1.0 g/kg of alcohol. About 1 mL venous blood was collected before and after the alcohol consumption at 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h and 8 h, respectively. The concentrations of ethanol and acetaldehyde in blood were determined by headspace gas chromatography. The peak times of blood ethanol concentration (Tmax), the peak mass concentrations of ethanol (Cmax), the area under curve (AUC) of ethanol (AUCethanol), AUCacetaldehyde and ethanol elimination rates (β) were calculated. In order to eliminate the influence of A DH1C, the A DH1C*1/*1 carriers were grouped based on the genotype of A DH1B and A LDH2. The data of each group were evaluated by one-way analysis of variance and pairwise comparison tests were performed by least significant difference method. The gene interactions were evaluated by two-way analysis of variance. Each parameter of three kinds of alcoholic beverage (white wine, red wine and beer) among groups was analysed by variance analysis with randomized block design. Results There were no differences in the value of Tmax and Cmax between the groups with different A DH1B and A LDH2 genotype. The differences in the values of AUCethanol, β and AUCacetaldehyde among some groups carrying different A DH1B and A LDH2 geno-type had statistical significance, while no significant difference was observed in these parameters when one individual taking same dose of different alcoholic beverage type. Conclusion The ethanol metabolism is associated with the related gene polymorphism, which is barely affected by alcoholic beverage type.

Expression of Acetaldehyde Dehydrogenase in Gefitinib-resistant Human Lung Adenocarcinoma HCC-827/GR Cells / 中国肺癌杂志

BACKGROUND@#Tumor recurrence and drug resistance are the main causes of death in tumor patients. The family of acetaldehyde dehydrogenase (ALDH) is closely related to the proliferation, migration, invasion and resistance of tumor cells, and different ALDH subtypes are expressed in different tumor cells. The aim of this study is to elucidate the ALDH subtype in human lung adenocarcinoma HCC-827/GR cells, which resistant to the gefitinib.@*METHODS@#The human lung adenocarcinoma HCC-827 cells were used to generate the gefitinib-resistant HCC-827/GR cells; the expression of ALDH subtype in either HCC-827 or HCC-827/GR was detected by flow cytometry; The proliferative capacity and sensitivity to gefitinib of hcc-827/GR cells were analyzed by MTT assay before and after treatment with 100 μmol/L diethyllaminaldehyde (DEAB); Real-time quantitative PCR was used to detect the expression of ALDH subtypes at mRNA levels in hcc-827 cells and hcc-827/GR cells.@*RESULTS@#Compared with HCC-827 cells, the positive rate of ALDH in HCC-827/GR cells increased. The proliferation ability of HCC-827/GR cells decreased after treatment with 100 μmol/L DEAB. Compared with HCC-827 cells, the expression of ALDH1A1 and ALDH1L1 mRNA was increased in hcc-827/GR cells, but the ALDH3B2 expression was decreased.@*CONCLUSIONS@#ALDH might be used as a molecular biomarker to test the gefitinib-resistant to lung adenocarcinoma cancer cells, and the ALDH1A1 may play a role in gefitinib resistance in lung cancer.

Mitochondrial aldehyde dehydrogenase 2 protects against high glucose-induced injury in neonatal rat cardiomyocytes by regulating CaN-NFAT3 signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate whether CaN-NFAT3 pathway mediates the protective effects of aldehyde dehydrogenase (ALDH) 2 in high glucose-treated neonatal rat ventricular myocytes.@*METHODS@#The ventricular myocytes were isolated from the heart of neonatal (within 3 days) SD rats by enzyme digestion and cultured in the presence of 5-Brdu. After reaching confluence, the cultured ventricular myocytes were identified using immunofluorescence assay for -SA protein. The cells were then cultured in either normal (5 mmol/L) or high glucose (30 mmol/L) medium in the presence of ALDH2 agonist Alda-1, ALDH 2 inhibitor Daidzin, or Alda-1 and NFAT3 inhibitor (11R-VIVIT). Fluorescent probe and ELISA were used to detect intracellular Ca concentration and CaN content, respectively; ALDH2, CaN and NFAT3 protein expressions in the cells were detected using Western blotting.@*RESULTS@#Compared with cells cultured in normal glucose, the cells exposed to high glucose showed a significantly decreased expression of ALDH2 protein ( < 0.05) and increased expressions of CaN ( < 0.05) and NFAT3 proteins with also increased intracellular CaN and Ca concentrations ( < 0.01). Alda-1 treatment significantly lowered Ca concentration ( < 0.05), intracellular CaN content ( < 0.01), and CaN and NFAT3 protein expressions ( < 0.05), and increased ALDH2 protein expression ( < 0.05) in high glucose- exposed cells; Daidzin treatment significantly increased Ca concentration ( < 0.01) and intracellular CaN content ( < 0.05) in the exposed cells. Compared with Alda-1 alone, treatment of the high glucose-exposed cells with both Alda-1 and 11R-VIVIT did not produce significant changes in the expression of ALDH2 protein (>0.05) but significantly reduced the expression of NFAT3 protein ( < 0.05).@*CONCLUSIONS@#Mitochondrial ALDH2 protects neonatal rat cardiomyocytes against high glucose-induced injury possibly by negatively regulating Ca-CaN-NFAT3 signaling pathway.

Activation of aldehyde dehydrogenase 2 alleviates H O -induced injury in cardiomyocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of aldehyde dehydrogenase 2 (ALDH2) expression in H O inducedcardiomyocytes oxidative stress injury.</p><p><b>METHODS</b>Cultured H9C2 cardiomyocytes were exposed to H O -inducedoxidative stress and the effects of the ALDH2 agonist Alda-1 and ALDH2 inhibitor Daidzin were tested on the stress level ofthe exposed cells. MTT colorimetric assay was used to assess the cell viability after the treatments. The oxidative stress level inthe myocardial cells was detected using DHE fluorescence staining, and the activity and protein level of ALDH2 were detectedwith spectrophotometry and Western blotting.</p><p><b>RESULTS</b>Compared with normal control cells, Alda-1 treatment did notsignificantly affect the cell viability, oxidative stress level, or ALDH2 activity and protein level. H O exposure significantlylowered the cell activity and ALDH2 activity and protein expression and increased the oxidative stress level; Alda-1 treatmentobvious antagonized the effects of H O . Blocking ALDH2 with Daidzin produced similar effects to H O exposure on theviability, oxidative stress level, and ALDH2 activity and expression in the myocardial cells.</p><p><b>CONCLUSIONS</b>H O exposure lowersthe activity and reduces the protein expression of ALDH2 in cardiomyocyte H9C2 cells, and activation of ALDH2 can alleviateH O -induced oxidative stress in the cells.</p>

Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats / 한국실험동물학회지

Hangover is characterized by a number of unpleasant physical and mental symptoms that occur after heavy alcohol drinking. In addition, consistently excessive alcohol intake is considered as a major reason causes liver disease. The present study investigated the in vivo effects of DA-5513 (Morning care® Kang Hwang) on biological parameters relevant to hangover relief and alcoholic fatty liver. Blood alcohol and acetaldehyde concentrations were determined in rats administered a single dose of alcohol and treated with DA-5513 or commercially available hangover relief beverages (Yeomyung® and Ukon®). The effects of DA-5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and alanine aminotransferase activities) and serum/liver lipid levels were assessed. Blood alcohol and acetaldehyde concentrations were lower in the groups treated with DA-5513 or Yeomyung®, as compared with control rats. However, Ukon® did not produce any significant effects on these parameters. Treatment with DA-5513 significantly reduced serum aspartate and alanine aminotransferase activities and markedly reduced serum cholesterol and triglyceride levels, as compared with control rats. Histological observations using Oil Red O staining found that DA-5513 delayed the development of alcoholic fatty liver by reversing hepatic fat accumulation. These findings suggest that DA-5513 could have a beneficial effect on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty liver.