• Annals of Surgical Treatment and Research
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• v.95 no.5
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• pp.240-248
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• 2018

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.

• Journal of Preventive Medicine and Public Health
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• v.51 no.6
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• pp.320-325
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• 2018

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.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.12
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• pp.1852-1862
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• 2018

Objective: The purpose of this study was to investigate a single step genome-wide association study (ssGWAS) for identifying genomic regions affecting reproductive traits in Landrace and Large White pigs. Methods: The traits included the number of pigs weaned per sow per year (PWSY), the number of litters per sow per year (LSY), pigs weaned per litters (PWL), born alive per litters (BAL), non-productive day (NPD) and wean to conception interval per litters (W2CL). A total of 321 animals (140 Landrace and 181 Large White pigs) were genotyped with the Illumina Porcine SNP 60k BeadChip, containing 61,177 single nucleotide polymorphisms (SNPs), while multiple traits single-step genomic BLUP method was used to calculate variances of 5 SNP windows for 11,048 Landrace and 13,985 Large White data records. Results: The outcome of ssGWAS on the reproductive traits identified twenty-five and twenty-two SNPs associated with reproductive traits in Landrace and Large White, respectively. Three known genes were identified to be candidate genes in Landrace pigs including retinol binding protein 7, and ubiquitination factor E4B genes for PWL, BAL, W2CL, and PWSY and one gene, solute carrier organic anion transporter family member 6A1, for LSY and NPD. Meanwhile, five genes were identified to be candidate genes in Large White, two of which, aldehyde dehydrogenase 1 family member A3 and leucine rich repeat kinase 1, associated with all of six reproduction traits and three genes; retrotransposon Gag like 4, transient receptor potential cation channel subfamily C member 5, and LHFPL tetraspan subfamily member 1 for five traits except W2CL. Conclusion: The genomic regions identified in this study provided a start-up point for marker assisted selection and estimating genomic breeding values for improving reproductive traits in commercial pig populations.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.421-430
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• 2019

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.367-375
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• 2022

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

• Journal of Life Science
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• v.22 no.6
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• pp.713-722
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• 2012

When proteins extracted from longissimus dorsi muscles of Landrace and Berkshire at the finishing stage were compared by 2-DE, the Landrace demonstrated a quantitative increase in proteins related to slow skeletal muscle function, such as serum albumin precursor, troponin T (slow skeletal muscle; sTnT) and myoglobin. In contrast, the Berkshire exhibited comparatively elevated enzymes involved in metabolic pathways, fast skeletal muscle function, and energy production, such as heat shock 27-kDa protein (HSP27)-1, TnT (fast skeletal muscle; fTnT), muscle creatine kinase, phosphoglucomutase 1 (PGM1), triosephosphate isomerase (Tpi1) and adenylate kinase isoenzyme 1 (AK1). When compared to growing Berkshire, finishing Berkshire showed increased levels of aldehyde dehydrogenase 1 family, member L1 (ALDHL1), and muscle creatine kinase. In contrast, the growing Berkshire muscle had elevated levels of HSP27-1, sTnT, fTnT, serum albumin precursor, PGM1, AK1, and Tpi 1 as compared to the finishing Berkshire. The Landrace longissimus dorsi muscle may be composed of slower skeletal muscle, whereas Berkshire is composed of a faster skeletal muscle. The uniquely elevated quantities of proteins involved in skeletal muscle function, energy metabolism, and cytoskeleton function in the growing Berkshire indicate that these factors support growth and maintenance during the growing stage when compared with the finishing Berkshire.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.668-672
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• 2001

To investigate the oxygen free radical and alcohol metabolizing system in liver of rats fed diets with 30% ethanol extract of Lycium chinense (LCEE), Sprague-Dawley male rats weighing 225~235g have been fed a diet supplemented with 2% or 4% LCEE for a month. The rats fed LCEE supplemented diets gained less body weight compared with the control, and had no remarkable changes of liver function. In rats fed 2% LCEE supplemented diet, hepatic cytochrome P450 contents appeared to be increased, but catalase (204.88$\pm$20.06 $H_2O$$_2$nmoles/mg protein/min), and superoxide dismutase (13.18$\pm$0.74 Unit/mg protein) activities were significantly increased compared with control 120.28$\pm$26.99 $H_2O$$_2$nmoles/mg protein/min and 10.49$\pm$0.80 Units/mg protein). There was no difference in hepatic glutathione content, glutathione peroxidase, and glutathione-S-transferase ctivities between the rats fed LCEE suplemented diets and the control diet. On the other hand, hepatic alcohol dehydrogenase activity were not changed by LCEE feeding, but hepatic aldehyde dehydrogenase activities were significantly increased in rats fed both 2 and 4% LCEE diets(5.01$\pm$0.21 and 4.47$\pm$0.06 $\mu$moles NADPH/mg protein/min) compared with control (3.28$\pm$0.21 $\mu$moles NADPH/mg protein/min) and its Vmax value was 1.9 fold increased in rats fed 2% LCEE and 1.5 fold in those fed 4% LCEE compared with control. In conclusion, it is likely that rats receiving a diet supplemented with LCEE may have the oxygen free radicals and alcohol detoxication potential.

• Journal of Life Science
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• v.18 no.8
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• pp.1173-1176
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• 2008

Individuals who regularly consume excessive quantities of alcohol are at a greater risk of developing various cancers such as esophageal, pharyngeal and lung cancers compared to normal populations if they are deficient in ALDH2 enzyme activity. We evaluated oxidative DNA damage in the liver, brain, and lung tissues of Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. The 8-hydroxydeoxyguanosine (8-OHdG) level in each tissue was evaluated as a biomarker of oxidative DNA damage. The 8-OHdG level in the liver, brain, and lung tissues was significantly increased following ethanol treatment. In addition, the level of 8-OHdG in the liver and lung tissues was affected by ALDH2 enzyme activity. This result suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated diseases, including cancer.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.706-711
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• 2009

Hepatoprotective effects of corn gluten hydrolysates (CGH) were investigated in rats orally treated with ethanol (30%(v/v), 3 g/kg body weight/day) for 4 weeks. Six-week old Sprague-Dawley male rats were divided into four dietary groups: normal diet (N), alcohol diet (E), E+CGH 1% diet (CGH-1%), and E+CGH 3% diet (CGH-3%). Body weights and liver indices were not significantly different among the four groups. However, food intakes were lower in the CGH groups than in the normal group (p<0.05). The administration of CGH significantly reduced serum alkaline phosphatase activity by 30% compared to the alcohol diet group. Among the antioxidative enzymes assessed, catalase activity was significantly decreased by 79% in the CGH diet groups compared to the alcohol diet group. In comparison to the alcohol-treated group, aldehyde dehydrogenase activity was increased by 20%, while microsomal ethanol oxidizing system activity was decreased by 20% in the CGH-treated groups. Furthermore, the area under the curve of the blood acetaldehyde concentration versus time profile after the administration of ethanol was significantly lower for the CGH rats than for the ethanol or asparaginic acid treated groups. Thus, CGH seems to offer beneficial effects by protecting against ethanol-induced hepatotoxicity by improving the acetaldehyde-related metabolizing system.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.176-188
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• 1999

Objective : The purpose of this study was to evaluate the effects of alcohol on neurocognitive function, psychomotor performance and subjective response in healthy Korean adults with different ALDH2 genotypes. Method : A total of 24 males, half with active $ALDH2^*1/2^*1$ and the other with inactive $ALDH2^*1/2^*2$, was selected through genotyping using restriction fragment length polymorphism. In a double-blind, placebo-controlled cross-over design, each subject consumed 0.5g/kg dose of alcohol, given as a mixture of 40% vodka and orange juice, and placebo(orange juice) on two separate occasions on an average of weekly intervals. The blood alcohol concentrations(BACs) were measured using a breath analyzer at baseline and at 30, 60 minutes after drinking. P300s were measured at baseline and at 30 minutes after alcohol and placebo intake. Vital signs and psychomotor performance[Critical Flicker Fusion Threshold(CFFT), Choice Reaction Time (CRT), Digit Symbol Substitution(DSS)] were measured at baseline and at 60 minutes after alcohol and placebo intake. Subjective responses were measured at the end of the study. The statistical analysis focused on whether there were any differences between groups with different ALDH2 genotypes. Results : The major results are as follows. 1) BACs in the inactive group were overall equivalent to those in the active group. Only in terms of time, BACs were significantly higher overall at 30 minutes than at 60 minutes after alcohol intake. 2) Pulse rates were significantly increased after alcohol intake compared with placebo, and the increase was greater in the inactive than in the active group. 3) P300 latencies in leads Fz(frontal), Cz(cental) and Pz(parietal) were significantly increased after alcohol intake compared to placebo, and the increase was greater in the inactive than in the active group. P300 amplitudes in leads Cz and Pz were significantly decreased overall after alcohol intake compared to placebo. 4) Compared with placebo, alcohol produced significant effect on the psychomotor performance : impairment in the inactive group, improvement in the active group. 5) Compared with placebo, alcohol significantly induced a negative or an intense effect on the subjective responses in the inactive group, but little negative and even a somewhat positive effect in the active group. Conclusions : These results suggest that ALDH isozyme variance might be an important factor to determine the effects of acute dose of alcohol on the various psychobehavioural functions and also to determine the alcohol use pattern and to predict the future development of alcohol overuse and/or abuse.