• Title/Summary/Keyword: ALDH1A1

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Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis

  • Mansoori, Abdul Anvesh;Jain, Subodh Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4803-4812
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    • 2015
  • Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

Enhanced biosynthesis of artemisinin by environmental stresses in Artemisia annua (환경스트레스 처리에 의한 개똥쑥 artemisinin 생합성 증진)

  • Kyung Woon Kim;Cheol Ho Hwang
    • Journal of Plant Biotechnology
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    • v.49 no.4
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    • pp.307-315
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    • 2022
  • Artemisinin is a secondary metabolite of Artemisia annua that shows potent anti-malarial, anti-bacterial, antiviral, and anti-tumor effects. The supply of artemisinin depends on its content in Artemisia annua, in which various environmental factors can affect the plant's biosynthetic yield. In this study, the effects of different light-emitting diode (LED)-irradiation conditions were tested to optimize the germination and growth of Artemisia annua for the enhanced production of artemisinin. Specifically, the ratio between the red and blue lights in the irradiating LED was varied for investigation as follows: [Red : Blue] = [6 : 4], [7 : 3], and [8 : 2]. Furthermore, additional stress factors like UV-B-irradiation (1,395 ㎼/cm2), low temperature (4℃), and dehydration were also explored to induce hormetic expressions of ADS, CYP, and ALDH1, which are essential genes for the biosynthesis of artemisinin. Quantitative polymerase chain reaction (qPCR) was used to analyze the expression levels of the respective genes and their correlation with the specified conditions. [8 : 2] LED-irradiation was the most optimal among the tested conditions for the cultivation of Artemisia annua in terms of both fresh and dry weights post-harvest. For the production of artemisinin, however, [7 : 3] LED-irradiation with dehydration for six hours pre-harvest was the most optimal condition by inducing around twofold enhancement in the biosynthetic yield of artemisinin. As expected, a correlation was observed between the expression levels of the genes and the contents of artemisinin accumulated.

Potentiation of Anticancer Effect of Artesunate by Combination with Nonsteroidal Anti-inflammatory Drugs on Human Cancer Cells (Artesunate와 비스테로이드소염제 NSAID의 병용 처리에 의한 항암 활성 증강)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.31 no.10
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    • pp.873-884
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    • 2021
  • The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

Inhibitory Effects of Angiotensin Converting Enzyme and α-Glucosidase, and Alcohol Metabolizing Activity of Fermented Omija (Schizandra chinensis Baillon) Beverage (오미자 발효음료의 알코올 분해능과 Angiotensin Converting Enzyme 및 α-Glucosidase 저해효과)

  • Cho, Eun-Kyung;Cho, Hea-Eun;Choi, Young-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.5
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    • pp.655-661
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    • 2010
  • The nutraceutical role of fermented omija (Schizandra chinensis) beverage (FOB) was determined through the analysis of fibrinolytic and alcohol metabolizing activities, nitrite scavenging activity, and angiotensin converting enzyme and $\alpha$-glucosidase inhibitory effects. Firstly, FOB increased fibrinolytic activity in a dose-dependent manner and indicated angiotensin converting enzyme inhibitory activity of 94.8% at 20% FOB (0.6 mg/mL). In addition, the inhibitory activities of FOB on $\alpha$-amylase and $\alpha$-glucosidase were determined to be 100% at 100% FOB (3 mg/mL) and 49% at 60% FOB (1.8 mg/mL), respectively. Nitrite scavenging activity of FOB was about 96.1%, 72.3%, and 68.3% on pH 1.2, 3.0, and 6.0 at 100% FOB, respectively. To determine influence of FOB on alcohol metabolism, the generating activities of reduced-nicotinamide adenine dinucleotide (NADH) by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were measured. Facilitating rate of ADH activity was 70.3% at 50% FOB, but ALDH activity was not affected. These results revealed that FOB has a strong alcohol metabolizing activity, and fibrinolytic and nitrite scavenging activities and exhibits the angiotensin converting enzyme, $\alpha$-amylase, and $\alpha$-glucosidase inhibitory activities.

Characteristics of Alcohol Metabolism of Hahyangju in Rats (하향주의 랫드에 대한 알코올 대사 특성)

  • Jung, Hee-Kyoung;Park, Chi-Duck;Hwang, Mi-Hyun;Park, Seung-Chun;Kim, Dae-Ik;Hong, Joo-Heon
    • Food Science and Preservation
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    • v.15 no.1
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    • pp.155-160
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    • 2008
  • This study was conducted to examine the volatile flavor compounds of Hahyangju, a traditional Korean liquor, and to evaluate the effect of the beverage on alcohol metabolism in rats. By GC/MS analysis, 17 volatile flavor compounds including iso-butyl alcohol and iso-amyl alcohol were detected in Hahyangju. The concentrations of acetaldehyde and ethylacetate in Hahyangju were decreased by filtration. Alcohol (0.035 mg/dL) and acetaldehyde (0.29 mg/dL) levels in the blood of rats given Hahyangju (HT animals) were lower than in rats given 17% (v/v) alcohol (AT rats). Also, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities in HT rats were $24.63{\pm}1.8{\mu}$moles/mg protein and $9.8{\pm}1.3{\mu}$moles/mg protein, respectively, and were higher than in AT animals. The increases in ADH and ALDH activity in HT animals resulted in decreases in alcohol and acetaldehyde concentrations in blood, compared to the levels seen in rats given 17% (v/v) alcohol. These results suggest that Hahyangju may increase alcohol metabolizing activity, and consumption of Hahyangju may result in less of a hangover than follows ingestion of beverages (such as wine) containing about 17% (v/v) alcohol.

A STUDY OF VERTICAL HARMONY OF ADULT CRANIOFACIAL SKELETON WITH NORMAL OCCLUTION (정상교합((정상교합) 성인(成人)의 악안면(顎顔面) 두개골격(두개골격)의 수직적(수직적) 조화(調和)에 관(關)한 연구(硏究))

  • Ahn, Eui-Young;Lee, Ki-Soo
    • The korean journal of orthodontics
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    • v.12 no.2
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    • pp.127-138
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    • 1982
  • The present study was performed to establish the cephalometric norms and to study characteristics of craniofacial skeleton of Korean male and female with normal occlusion. The author studied and analyzed statistically vertical cephalometric measurements of the 52 adult male ranging in age from 18 to 26 years and 43 adult female ranging in age from 16 to 30 years with normal occlusion and acceptable profile. The results were as follows; 1. Cephalometric craniofacial norms and standard deviation chart were abtained about adult Korean male and female with normal occlusion. 2. Vertical dimensions of the craniofacial skeleton were larger in male than in female. 3. Lower face was more divergent in female than in male. 4. In simple correlation coefficients between vertical linear mesurements in male and female, high correlation were shown between ATFH and ALFH, PTFH and PLFH, ALFH and ALDH, PLFH and PLDH.

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A Biochemical Study on the Ethanol Metabolism in the Animal Body (동물 체내에서의 에탄올 대사에 관한 생화학적 연구)

  • Kwak, Hahn-Shik
    • The Journal of Natural Sciences
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    • v.4
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    • pp.29-58
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    • 1991
  • Ethanol은 섭취량에 따라 간 대사에 여러가지 영향을 미치는 것으로 알려져 있다. 과량의 ethanol 섭취가 유해한 것은 ethanol 그 자체보다는 산화과정에서 생성된 acetaldehyde와 과량의 수소(NADH)에 기인한다. 과량의 NADH는 간 세포의 화학적 평형을 저해하고 대사이상을 초래한다. 본 연구에서는 in vitro 뿐만 아니라 in vivo에서 alcohol dehydrogenase(ADH), aldehyde dehydroge-nase(ALDH), microsomal ethanol oxidizing system(MEOS)에 미치는 인삼 사포닌의 영향을 조사하고, 간에서의 수소 평형, 간에서의 $[1^(-14)C]$-ethanol의 분포, ethanol의 acetaldehyde와 lipid로의 전환 등을 관찰하였다. 인삼 사포닌은 상기 효소외에도 ethanol 대상에 관련된 다른 효소들의 활성을 증가시키는 것으로 관찰되었으며 이는 동물 체내로부터 acetaldehyde와 과량의 수소를 신속히 제거하는 것으로 사료된다.

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Effects of Olanzapine on Gene Expression Changes in MK-801-induced Neurotoxicity Using a High-density DNA Microarray

  • Jo, Jae-Hoon;Kim, Seung-Jun;Yeon, Jong-Pil;Oh, Moon-Ju;Seo, Hye-Myung;Hwang, Seung-Yong;Kim, Sang-Kyum;Kim, Bong-Hee
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.282-291
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    • 2007
  • Although the etiology of schizophrenia is known to be linked with the disturbance of glutamatergic and dopaminergic neurotransmission, little is known about the relationship between gene expression and the disease process. To identify genes related to abnormalities in glutamatergic and dopaminergic function, we investigated the effects of olanzapine in the changes of mRNA levels in the animal model of schizophrenia, using a high-density DNA microarray. Olanzapine (3.0 mg/kg, i.p.) significantly reduced hyperlocomotive activities, which was induced by MK-801 (1.0 mg/kg, i.p.). We identified that the expression of 719 genes were significantly altered more than two folds in the prefrontal cortex of the rats treated with MK-801. We selected 15 genes out of them by the changes of the expression pattern in the treatment of Olanzapine and/or MK801 for the further confirmation in RT-PCR. The administration of MK-801 increased the expression of 7 genes (NOS3, Hspb1, Hspa1a, CRH, Serpine1, Igfbp6, Snf1lk) and decreased the expression of 1 gene (Aldh1a2), which was attenuated by olanzapine. One gene (Prss12) was up-regulated after olanzapine treatment although it did not show the significant changes after MK-801 treatment. These results showed that antipsychotic drug, such as olanzapine, may alter the gene expression patterns, which were accompanied by MK-801-induced psychosis. Our results also provide us high-density DNA microarray technology could be potential approaches to find the candidate molecules for the therapeutics and also for the early diagnosis of psychiatric diseases.

Collection, Identification and Hepatic Effect of Native Cordyceps militaris (새로운 번데기 동충하초의 수집, 동정 및 간기능에 미치는 효과)

  • Lee, Ki-Won;Nam, Byung-Hyouk;Jo, Wool-Soon;Oh, Su-Jung;Kang, Eun-Young;Cui, Yong;Lee, Jae-Yun;Cheon, Sang-Cheol;Jeong, Min-Ho;Lee, Jae-Dong
    • The Korean Journal of Mycology
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    • v.34 no.1
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    • pp.7-14
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    • 2006
  • Entomopathogenic fungus Cordyceps militaris is famous for its medicinal efficacies. It has been reported to have various pharmacological activities such as anti-tumour, insecticidal, antibacterial, immunomodulatory and antioxidant. In this study, we investigated the effect of the extract of C. militaris (MPUN8501), which was identified by the analysis of the nucleotide sequences of 5.8S ribosomal RNA, on the function of liver. C. militaris powder was extracted using hot water extracts method as time, volume and temperature and using method as differential polarity of organic solvent. Each fraction was tested for the improvement of hepatic enzyme alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. The BuOH extracts (CME) had highest activity which was used for the test of toxicity and efficacy of C. militaris. The enhancing effect of CME on the activity of ADH and ALDH was much more than medicine, drink, natural tea etc. Thus CME promoted the resolution of alcohol and acetaldehyde in rats, inducing recovery to normal condition rapidly. Furthermore, oral administration of CME effectively protected the carbon tetrachloride-induced acute hepatic injury as revealed by the hematological parameters (levels of sGOT and sGPT) and histological observation. CME was ascertained to be safe by regulatory toxicity studies of single dose toxicity and genotoxicity. These results suggest that CME would be useful for the maintaining normal hepatic activity as a functional health food.

Antioxidant and Alcohol Dehydrogenase Activity of Water Extracts From Abalone Containing Medicinal Plants (전복과 천연 식물류 복합물의 항산화 및 알코올대사 효소 활성)

  • Shin, Jung-Hye;Lee, Soo-Jung;Choi, Duk-Ju;Kang, Min-Jung;Sung, Nak-Ju
    • Korean journal of food and cookery science
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    • v.24 no.2
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    • pp.182-187
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    • 2008
  • This study was performed to evaluate the possible production of a functional beverage derived from abalone and with several plants (AP). Five types of AP composites were prepared having different medicinal plant compositions (AP- I : abalone, garlic, jujube, Chinese matrimony fruit, dried orange peel, licorice root, zinger, honey; AP- II: abalone, garlic, black bean, Chinese matrimony fruit, cornus fruit, licorice root, zinger, honey; AP-III : abalone, jujube, arrow root, milk vetch, dried orange peel, licorice root, zinger, honey; AP-N: abalone, black bean, arrow root, milk vetch, cornus fruit, liquorice root, zinger, honey; AP-V : abalone, garlic, Chinese matrimony fruit, milk vetch, licorice root, zinger, honey). In vitro analysis were performed to examine the antioxidant contents and alcohol dehydrogenase activities of the composites. AP- II had the highest total phenol contents ($28.55{\pm}1.56\;mg/l00\;g$), and AP- V the highest level of flavonoids ($47.61{\pm}1.58\;mg/l00\;g$). At $78.89{\pm}0.16%$, AP- V displayed the strongest electron donating ability followed by AP-II($57.99{\pm}0.21%$) and API ($37.66{\pm}0.20%$). Reducing power was also significantly higher in AP- V. The Hydroxyl radical scavenging and SOD-like activities of all composites were less than 15% and 20%, respectively. At 12.5% alcohol concentration, ADH activity ranged from $114.47{\pm}2.18{\sim}121.39{\pm}4.36%$ and ALDH activity ranged from $100.04{\pm}2.90{\sim}129.54{\pm}4.80%$; AP- I , AP- II, and AP- Vin 12.5% of alcoholic concentration. The composites of AP- I , AP- II, and AP- V, all containing garlic and Chinese matrimony fruit, were significantly stronger than AP-III and AP-N. Finally, also at 12.5% alcoholic concentration, the ALDH activity of AP- V was higher than its ADH activity.