Effect Modification of Acetaldehyde Dehydrogenase 2 rs671 Polymorphism on the Association between Alcohol Intake and Blood Pressure: the Dong-gu Study

BACKGROUND: Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes.METHODS: This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed.RESULTS: In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91–1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15–1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women.CONCLUSION: ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers.

Estudo da expressão imunohistoquímica de SOX2 e ALDH1 como biomarcadores em pacientes portadores de carcinoma espinocelular do pênis / Immunohistochemical expression of sox2 and aldh1 as biomarkers in patients with penile squamous cell carcinoma

Introdução: O câncer de pênis pode chegar, em alguns países em desenvolvimento, até a 20% das neoplasias no homem. O tratamento padrão é a amputação do tumor primário e na linfadenectomia regional. A baixa acurácia dos métodos de estadiamento da doença linfonodal, que no momento é o fator prognóstico mais importante e a alta taxa de morbidade da linfadenectomia tem estimulado o estudo de novos fatores prognósticos preditivos de metástases em linfonodos, facilitando a seleção de pacientes a serem submetidos à linfadenectomia. Foram escolhidos SOX2 e ALDH1 por terem sido bons resultados preditivos em outros CEC, mas sem estudos em tecido peniano Objetivos: O presente estudo visa estudar a expressão imunoistoquímica de SOX 2 e ALDH1 no carcinoma peniano, além de identificar o valor prognóstico dessa expressão correlacionando-a com o tumor primário no risco de metástase linfonodal e a relação destes com as variáveis clinicas, demográficas e anatomopatológicas, bem como sua relação com sobrevida livre de doença e global. População e Métodos: Foram avaliados retrospectivamente 203 pacientes com diagnóstico de carcinoma epidermóide do pênis submetidos ao tratamento do tumor primário e a linfadenectomia radical ou aqueles submetidos ao tratamento do tumor primário, não linfadenectomizados, com pelo menos cinco anos de seguimento, utilizando a imunoistoquímica para analisar os marcadores. Resultados: A expressão de SOX2 esteve associada inversa e significantemente com o padrão de crescimento vertical e infiltração de corpo esponjoso e uretra, porém sem relação com sobrevida global ou câncer especifica. O biomarcador ALDH1 reagiu apenas com 2% da amostra, o que fez com que não pudéssemos avaliá-lo satisfatoriamente. Quando analisado metástase linfonodal, não houve diferença significante com a expressão nenhum dos marcadores. A infiltração perineural, metástase linfonodal, estdiamento pT foram os fatores independentes de pior sobrevida global Conclusão: SOX2, apesar de presente no carcinoma peniano, não se relacionou com metástase linfonodal ou sobrevida. ALDH1 não parece ser considerável em carcinoma peniano

Introduction: In some developing countries, up to 20% of all neoplasia in males is due to penile cancer. The standard treatment is primary tumor amputation and regional lymphadenectomy. The poor accuracy of lymph node staging methods, currently the most important prognostic factor and the high morbidity rate of lymphadenectomy, stimulated the study of new prognostic factors that predict lymph node metastases, facilitating the selection of patients for lymphadenectomy. SOX2 and ALDH1 were selected because they presented good predictive results in other squamous cell carcinomas, but studies on penile tissue were not available. Objectives: To study the immunohistochemical expression of SOX 2 and ALDH1 in penile carcinoma, as well as identify the prognostic value of this expression, correlate it with the primary tumor regarding risk of lymph node metastasis and the relationship with clinical, demographic and anatomopathological variables as well as disease-free and overall survival. Methods: 203 patients diagnosed with penile squamous cell carcinoma who underwent primary tumor treatment and radical lymphadenectomy or primary tumor treatment without lymphadenectomy with at least five years of follow-up were assessed using immunohistochemistry to analyze the markers. Results: The SOX2 expression was inversely and significantly related to the vertical growth pattern and the infiltration of the corpus spongiosum and urethra but without any relationship to overall or specific cancer survival. The biomarker ALDH1 only reacted with 2% of the samples, which meant it could not be satisfactorily evaluated. None of the markers presented a significant difference regarding lymph node metastasis. Perineural infiltration, lymph node metastasis, and staging pT were independent factors of poor overall survival. Conclusion: Although SOX2 is present in penile carcinoma, it is not related to lymph node metastasis or survival. ALDH1 does not appear to have a considerable presence in penile carcinoma

Single Nucleotide Polymorphisms Associated with Alcohol-Induced Flushing Syndrome in Korean Population / 대한법의학회지

Alcohol-induced flushing syndrome is one of the alcohol hypersensitivity reactions commonly found among Asian population. This study was designed to find markers that can predict this particular propensity among Korean population and to assess the applicability of this finding to build a prediction model as forensic DNA phenotyping tool to operate in practical forensic cases. Five hundred seventy unrelated Koreans were genotyped using microfluidic technology with 24 possible candidate single nucleotide polymorphism (SNP) markers. Of the 24 candidate SNPs, four markers, rs671, rs2074356, rs4646776, and rs10849915, on chromosome 12 showed statistically significant association with P-values ranging from 1.39×10⁻¹⁴ to 0.004988 among our subjects. All four markers show relatively high specificity values, ranging from 0.804651 to 0.972093, presenting their capabilities as differential SNPs that can distinguish a person with or without alcohol-induced flushing syndrome. Maneuvering these candidate SNPs as well as finding additional potential markers through future studies will help building an appropriate prediction model for Koreans that can be used as supplementary tool for individual identification.

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.

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.

Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice / 中国天然药物

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.

Stem cell analysis with intraductally treated mammary epithelial cells

PURPOSE: The activity of mammary stem cells (MaSCs) is essential to mammary growth, differentiation and regeneration in cycles of pregnancy, lactation, and involution. The capability to recruit the mammary gland through the cycles is attributed to stem cells. It was shown that the intraductal (i.duc) injection of pegylated liposomal doxorubicin (PLD) to multiparous FVB/N mice was associated with a significantly reduced outgrowth potential of mammary gland cells. We have explored i.duc PLD's effect on stem cell number and function in mouse mammary gland and aldehyde dehydrogenase (ALDH)'s availability as a mouse MaSC marker.METHODS: The total mammary epithelium was purified from 6 to 8-month-old FVB/N control and i.duc PLD-administered mice treated twice and analyzed by flow cytometry and limiting dilution cleared mammary fat pad transplants.RESULTS: There was no significant difference in the proportions of stem cell-enriched population (CD49(fhigh)CD24(med)) between control and i.duc PLD-treated groups. However, we found a significant reduction in the outgrowth potential of CD49(fhigh)CD24(med) and CD49(fhigh)CD24(med)ALDH(+) cells from i.duc PLD-treated mammary glands. We discovered that adding ALDH to CD49(fhigh)CD24(med) had the possibility of better marker selection for MaSC of mice.CONCLUSION: We present i.duc administration of PLD to reduce MaSC function, but not the number; and ALDH activity may add further selection of MaSCs to CD49f CD24 in mouse mammary glands. Screening of chemotherapeutic drugs or other natural products by this method of stem cell analysis may provide safe i.duc treatment in breast cancer.

Disulfiram, a Re-positioned Aldehyde Dehydrogenase Inhibitor, Enhances Radiosensitivity of Human Glioblastoma Cells In Vitro / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Glioblastoma, the most common brain tumor in adults, has poor prognosis. The purpose of this study was to determine the effect of disulfiram (DSF), an aldehyde dehydrogenase inhibitor, on in vitro radiosensitivity of glioblastoma cells with different methylation status of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter and the underlying mechanism of such effect. MATERIALS AND METHODS: Five human glioblastoma cells (U138MG, T98G, U251MG, U87MG, and U373MG) and one normal human astrocyte (NHA) cell were cultured and treated with DSF or 6MV X-rays (0, 2, 4, 6, and 8 Gy). For combined treatment, cells were treated with DSF before irradiation. Surviving fractions fit from cell survival based on colony forming ability. Apoptosis, DNA damage repair, and cell cycle distributionwere assayed bywestern blot for cleaved caspase-3, γH2AX staining, and flow cytometry, respectively. RESULTS: DSF induced radiosensitization in most of the glioblastoma cells, especially, in the cells with radioresistance as wildtype unmethylated promoter (MGMT-wt), but did not in normal NHA cell. DSF augmented or induced cleavage of caspase-3 in all cells after irradiation. DSF inhibited repair of radiation-induced DNA damage in MGMT-wt cells, but not in cells with methylated MGMT promoter. DSF abrogated radiation-induced G2/M arrest in T98G and U251MG cells. CONCLUSION: Radiosensitivity of glioblastoma cells were preferentially enhanced by pre-irradiation DSF treatment compared to normal cell, especially radioresistant cells such as MGMT-wt cells. Induction of apoptosis or inhibition of DNA damage repair may underlie DSF-induced radiosensitization. Clinical benefit of combining DSF with radiotherapy should be investigated in the future.

Epileptic Seizure Due to Disulfiram Treatment / 가정의학회지

Disulfiram has been used for the treatment of alcohol dependence for nearly 65 years and is approved by the Food and Drug Administration. It causes negative reinforcement by accumulating toxic acetaldehyde due to irreversible inhibition of aldehyde dehydrogenase. Disulfiram has very few side effects when taken without alcohol. Epileptic seizure induction is a rare side effect in therapeutic doses, and its mechanism is unknown. We present a patient with a single epileptic seizure which was thought to be due to disulfiram used in the treatment of alcohol dependence. We did not find it ethical to administer disulfiram again because the patient discontinued alcohol use and was afraid of epileptic seizures.

ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line

PURPOSE: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). METHODS: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. RESULTS: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. CONCLUSION: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

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.

Cancer Energy Metabolism: Shutting Power off Cancer Factory

In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.

Early Activation of Astrocytes does not Affect Amyloid Plaque Load in an Animal Model of Alzheimer's Disease / 神经科学通报·英文版

Astrocytes are closely associated with Alzheimer's disease (AD). However, their precise roles in AD pathogenesis remain controversial. One of the reasons behind the different results reported by different groups might be that astrocytes were targeted at different stages of disease progression. In this study, by crossing hAPP (human amyloid precursor protein)-J20 mice with a line of GFAP-TK mice, we found that astrocytes were activated specifically at an early stage of AD before the occurrence of amyloid plaques, while microglia were not affected by this crossing. Activation of astrocytes at the age of 3-5 months did not affect the proteolytic processing of hAPP and amyloid plaque loads in the brains of hAPP-J20 mice. Our data suggest that early activation of astrocytes does not affect the deposition of amyloid β in an animal model of AD.

Hangover relieving effect of Sanghwang mushroom mycelium cultured in germinated buckwheat

The present study was performed to evaluate the hangover relieving effect of germinated buckwheat (GB) and Sanghwang mushroom mycelium cultured in GB (SGB). Both GB and SGB showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and significantly increased (p < 0.001) aldehyde dehydrogenase (ALDH) activities; up to 140% increase at concentrations of 16 µL/mL. Locomotor activity test results from alcohol-SGB and alcohol-GB groups showed improved motor activities over that of the alcohol-water group at 90 min post-administration. Both alcohol-GB and alcohol-SGB groups had significantly reduced (p < 0.001) alcohol (40.02 ± 33.38 µg/mL, 66.01 ± 22.04 µg/mL, respectively) and aldehyde (5.72 ± 0.47 µg/mL, 6.72 ± 1.70 µg/mL, respectively) concentrations in blood compared to those in the alcohol-water group (199.75 ± 33.83 µg/mL, 50.43 ± 13.88 µg/mL, respectively) at 90 min post-administration. Based on cDNA microarray analysis, expressions of ALDH genes ALDH1a7 and ALDH18a1 and cytochrome P450 (CY450) gene CYP4a30b were upregulated in the alcohol-GB and alcohol-SGB groups compared to levels in the control group. Overall, the results suggest that both GB and SGB have hangover relieving effects by reducing blood acetaldehyde levels. The molecular mechanisms may involve ALDH activation and upregulated expression of alcohol metabolism-related genes such as ALDH and CYP450.

Laminin Modulates the Stem Cell Population in LM05-E Murine Breast Cancer Cells through the Activation of the MAPK/ERK Pathway / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the effects of laminin on the fraction of cells with self-renewing capacity in the estrogen-dependent, tamoxifen-sensitive LM05-E breast cancer cell line. We also determined whether laminin affected the response to tamoxifen. MATERIALS AND METHODS: The LM05-E breast cancer cell line was used as a model for all experiments. Aldehyde dehydrogenase (ALDH) activity, clonogenic and mammosphere assays were performed to measure the effects of laminin on modulation of the stem cell subpopulation. Pluripotent gene expression was analyzed by reverse transcriptase–polymerase chain reaction. The involvement of the mitogen-activated protein kinase (MAPK)/ERK pathway was determined using specific inhibitors. The effects of laminin on the response to tamoxifenwere determined and the involvement of α6 integrin was investigated. RESULTS: We found that pretreatment with laminin leads to a decrease in cells with the ability to form mammospheres that was accompanied by a decrease in ALDH activity. Moreover, exposure of mammospheres to laminin reduced the capacity to form secondary mammospheres and decreased the expression of Sox-2, Nanog, and Oct-4. We previously reported that 4-OH-tamoxifen leads to an increase in the expression of these genes in LM05-E cells. Treatment with signaling pathway inhibitors revealed that the MAPK/ERK pathway mediates the effects of laminin. Finally, laminin induced tamoxifen resistance in LM05-E cells through α6 integrin. CONCLUSION: Our results suggest that the final number of cells with self-renewing capacity in estrogen-dependent breast tumors may result from the combined effects of endocrine treatment and microenvironmental cues.

Intermittent convulsions for 1.5 years and psychomotor retardation in a girl / 中国当代儿科杂志

The study reports a girl with pyridoxine-dependent epilepsy. The girl was admitted at the age of 2 years because of intermittent convulsions for 1.5 years and psychomotor retardation. She had a history of "hypoxia" in the neonatal period. At the age of 5 months recurrent epileptic seizures occurred. The child was resistant to antiepileptic drugs, and had many more seizures when she got cold or fever. She also had a lot of convulsive status epilepticus. No discharges were found during several video-EEG monitorings. Cerebral MRI examinations showed normal results. So Dravet syndrome was clinically suspected. ALDH7N1 gene mutation analysis revealed two heterozygote mutations, and pyridoxine-dependent epilepsy was thus confirmed. Seizures were generally controlled after pyridoxine supplementation.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism. Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks. Mendelian randomization (MR) studies have demonstrated that alcohol consumption predicted by ALDH2 genotype is causally related to cardiovascular risks. Moreover, recent MR studies suggest that the ALDH2 variant has mechanistic effects on some disease outcomes or mortality through increased blood levels of acetaldehyde, showing differences therein between heterozygotes (ALDH2*2*2) and homozygotes (ALDH2*1*2) in those who consume alcohol. Accordingly, consideration of ALDH2 genotype in alcohol prevention programs is warranted. In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required.

Associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length in Korean adults

BACKGROUND/OBJECTIVES: Telomere length is a useful biomarker for determining general aging status. Some studies have reported an association between alcohol consumption and telomere length in a general population; however, it is unclear whether the alcohol flush reaction, which is an alcohol-related trait predominantly due to acetaldehyde dehydrogenase deficiency, is associated with telomere length. This cross-sectional study aimed to evaluate the associations of alcohol consumption and alcohol flush reaction with leukocyte telomere length (LTL). SUBJECTS/METHODS: The study included 1,803 Korean adults. Participants provided blood specimens for LTL measurement assay and reported their alcohol drinking status and the presence of an alcohol flush reaction via a questionnaire-based interview. Relative LTL was determined by using a quantitative polymerase chain reaction. Statistical analysis used multiple linear regression models stratified by sex and age groups, and potential confounding factors were considered. RESULTS: Age-specific analyses showed that heavy alcohol consumption (> 30 g/day) was strongly associated with a reduced LTL in participants aged ≥ 65 years (P 15 g/day of alcohol (P < 0.01). No significant alcohol consumption or alcohol flush reaction associations with LTL were observed in the sex-specific analyses. CONCLUSIONS: The results suggest that older alcohol drinkers, particularly those with the alcohol flush reaction, may have an accelerated aging process.

Partial purification and characterization of the recombinant benzaldehyde dehydrogenase from rhodococcus ruber UKMP-5M

Background: Benzaldehyde dehydrogenase [BZDH] is encoded by the xylC that catalyzes the conversion of benzaldehyde into benzoate in many pathways such as toluene degradation

Objectives: In this study, the xylC gene from Rhodococcus ruber UKMP-5M was expressed in Escherichia coli, purified, and characterized

Materials and Methods: The xylC was amplified and cloned in E. coli. The recombinant plasmid pGEMT-xylC was digested by NdeI and HindIII to construct plasmid pET28b-xylC and transformed in E. coli BL21 [DE3]. Expression of the recombinant protein was induced by 1 mM isopropyl beta-D-thiogalactoside [IPTG] at 37[degree]C. The BZDH was purified by ion exchange chromatography, in which the product was an NAD-dependent enzyme using benzaldehyde as a substrate for enzyme characterization. The end metabolite was identified via gas chromatography mass spectrometry [GC-MS]

Results: The recombinant BZDH is 27 kDa, purified by ion exchange chromatography. The activity of BZDH was 9.4 U.microL[-1] The optimum pH and temperature were 8.5 and 25[degree]C, respectively. The Michaelis constant [K[m]] and maximum velocity [V[max]] were 4.2 mM and 19.7 U.mL[-1], respectively. The metabolite of BZDH was benzene carboxylic acid as determined by GC-MS analysis

Conclusions: BZDH has the ability to degrade benzaldehyde to less toxic compounds. The BZDH is a critical enzyme for the degradation of aromatic hydrocarbons in Rhodococcus sp. The BZDH from R. ruber UKMP-5M is showed similar function with other aldehyde dehydrogenases

Aldehyde dehydrogenase is used by cancer cells for energy metabolism

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.