• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1604-1613
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• 2018

Lactobacillus rhamnosus GG (LGG) is a probiotic commonly used in fermented dairy products. In this study, RNA-sequencing was performed to unravel the effects of acid stress on LGG. The transcriptomic data revealed that the exposure of LGG to acid at pH 4.5 (resembling the final pH of fermented dairy products) for 1 h or 24 h provoked a stringent-type transcriptomic response wherein stress response- and glycolysis-related genes were upregulated, whereas genes involved in gluconeogenesis, amino acid metabolism, and nucleotide metabolism were suppressed. Notably, the pilus-specific adhesion genes, spaC, and spaF were significantly upregulated upon exposure to acid-stress. The transcriptomic results were further confirmed via quantitative polymerase chain reaction analysis. Moreover, acid-stressed LGG demonstrated an enhanced mucin-binding ability in vitro, with 1 log more LGG cells (p < 0.05) bound to a mucin layer in a 96-well culture plate as compared to the control. The enhanced intestinal binding ability of acid-stressed LGG was confirmed in an animal study, wherein significantly more viable LGG cells (${\geq}2log\;CFU/g$) were observed in the ileum, caecum, and colon of acid-stressed LGG-treated mice as compared with a non-acid-stressed LGG-treated control group. To our knowledge, this is the first report showing that acid stress enhanced the intestine-binding ability of LGG through the induction of pili-related genes.

• 대한예방한의학회지
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• 제10권1호
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• pp.75-93
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• 2006

Rhus verniciflua Stokes(RVS) has been widely used as a food and traditional herbal medicine in Korea. RVS has been reported that the extract from its wood and fruit has strong antioxidant activity and anticancer effect but there is little information on Lacca Sinica Exsiccata(LSE), the resin of RVS, as a medicinal use. The aim of this study was to evaluate the antidiabetic effect of ethanol-eluted extract of LSE on streptozotocin(STZ) - induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats with STZ injection. Oral administration of LSE extract(50mg or 100mg/kg of body weight/day) was given to diabetic group. During 4 weeks of experiment, diabetic rats showed significant weight loss and decreasing feed efficiency ratios(FER) compared with normal rats, while the diabetic group orally fed with LSE extract showed a trend of decreasing weight loss and a significant increase of FER(p<0.05). In 4 weeks after induction of diabetes, diabetic rats showed an increase in weight of liver, kidney and heart, whereas the diabetic rats administered with LSE extract showed a reduction in the weight of heart. Blood glucose level was decreased in diabetic rats treated with LSE extract, but it was not statistically significant. Glutamic oxaloacetic transaminase, Glutamic pyruvate transaminase and total cholesterol levels were lower in the diabetic group treated with LSE extract than in untreated diabetic group, but not significant. These results present that LSE may partly have antidiabetic effect and may protect against the development of diabetic heart complications resulting from impaired glucose metabolism.

• 한국식생활문화학회지
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• 제20권2호
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• pp.194-203
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• 2005

This study was peformed to investigate effect of feeding experimental mixture containing chitosan, hibiscus extract and L-carnitine on body weight and lipid metabolism in rats. Forty-eight male rats(Charles River CD) of eight weeks old and weighing $336.5{\pm}2.3g$ were raised for five weeks with high fat diet(40% fat as calorie) to induce obesity. After induction of obesity, rats weighing $560.4{\pm}5.6g$ were blocked into four groups according to body weight and raised for eight weeks with diet containing either 0.09%(+1D group), 0.9%(+10D group) or 4.5%(+50D group) of experimental mixture. Aspartate aminotransferase(AST) and alanine aminotransferase(ALT), total protein and albumin were normal levels in plasma. Body weight gain and epididymal fat pad weight were lower in experimental mixture groups than control group However, weights of perirenal fat pad and brown adipose tissue were not significantly different among all groups. There was no significant difference in plasma and hepatic lipid levels among all groups. Liver citrate lyase and camitine acyltransferase activities were not significantly different among all groups, however, citrate lyase activity was tended to be decreased with increasing experimental mixture level in diet. Fecal total lipid and total cholesterol excretions were highest in +50D group, and triglyceride excretion was highest in +1D group. in conclusion, intake of experimental mixture containing chitosan, hibiscus extract and L-camitine was effective in reducing body weight and body fat, and its inhibitory effects might lead to obesity improvement.

• 생명과학회지
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• 제24권7호
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• pp.762-768
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• 2014

Starvation에 의해서 down-regulation 되는 유전자 10개를 얻었다(Comt, RGN, Scd1, Temt, Idi1, Fabp5, Car3, Cyp2c70, Pinx1, Poldip3). 이들은 starvation에 의한 대사변화의 대부분은 liver와 관련된 것으로 볼 수 있다. Starvation중에 물 공급은 암수 동일하게 apoptosis, autophage, endoplasmic reticulum quality control (ERQC)유도에 영향을 미치지 않았다. 이 같이 starvation에 의해서 down-regulation되는 유전자발현조절이 liver에 국한된 것이라기보다는 개체의 항상성유지에 관련 많은 pathway가 관련되어있는 것으로 판단된다. 장기간의 간혈 starvation은 glucose소비가 많은 brain과 면역기능조절에 중요한 thymus의 정상기능에 영향을 미칠 수 있는 것으로 보인다. 유전자 Scd1의 경우는 ♀보다가 ♂이 민감한 반응을 보이는 것으로 보아 ♀/♂의 성 특이적인 대사에 starvation과 NaCl이 밀접한 관계가 있는 것으로 보인다. Starvation시 물 공급도 중요하지만 개체의 항상성유지에 NaCl공급이 중요하다는 결과를 얻었다.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.890-897
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• 2006

In inflammatory responses, induction of cytokines and other immune regulator genes in macrophages by pathogen-associated signal such as lipopolysaccharide (LPS) plays a crucial role. In this study, the gene expression profile changes by LPS treatment in the macrophage/monocyte lineage cell line RAW264.7 was investigated. A 60-mer oligonucleotide microarray of which probes target 32381 mouse genes was used. A reverse transcription-in vitro translation labeling protocol and a chemileuminescence detection system were employed. The mRNA expression levels in RAW264.7 cells treated for 6 h with LPS and the control vehicle were compared. 747 genes were up-regulated and 523 genes were down-regulated by more than 2 folds. 320 genes showing more than 4-fold change by LPS treatment were further classified for the biological process, molecular function, and signaling pathway. The biological process categories that showed high number of increased genes include the immunity and defense, the nucleic acid metabolism, the protein metabolism and modification, and the signal transduction process. The chemokine-cytokine signaling, interleukin signaling, Toll receptor signaling, and apoptosis signaling pathways involved high number of genes differentially expressed in response to LPS. These expression profile data provide more comprehensive information on LPS-target genes in RAW264.7 cells, which will be useful in comparing gene expression changes induced by extracts and compounds from anti-inflammatory medicinal herbs.

• 한국식품영양과학회지
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• 제22권6호
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• pp.702-708
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• 1993

Bromobenzene투여시 GE-132의 해독기전을 추구할 목적으로 epoxide생성계와 해독계 효소 및 glutathione 관련 효소계의 활성에 GE-132가 어떤 영향을 주는가를 검토하여 다음과 같은 실험 결과를 얻었다. GE-132(100mg/kg)의 전처리로 cytochrome P-450, amino=pyrine demethylase 및 aniline hydroxylase와 해독계 효소인 epoxide hydrolase활성에는 영향을 미치지 않았으나, glutathions S-transferase활성은 증가 하였다. Bromobenzene(460mg/kg)을 주사하였을때 glutathione S-transferase의 활성이 현저히 감소되던 것이 GE-132의 투여로 대조군 수준으로 증가되었다. 조직내 glutathione의 함량변동도 bromobenzene 투여로 감소되던 것이 GE-132의 전처리로 bromobenzene단독 투여군보다 증가되었으며 ${\gamma}-glutamylcystein$ synthtase의 활성은 각 실험군에서 별다른 영향이 없는데 비해 glutathione reductase의 활성은 bromobenzene투여로 억제 되던 것이 GE-132의 전처리로 대조군 수준으로 활성을 유지하고 있었다.

• Journal of Nutrition and Health
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• 제39권2호
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• pp.100-108
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• 2006

This study was conducted to investigate whether dietary factors, normal fat and genistein leads to beneficial improvement of lipid metabolism and oxidative stress in adult hyperlipidemic male rats. Seven wk-old male SD rats were fed high fat diet (15% fat, 1% cholesterol) for 4 wks for induction of hyperlipidemic model rat. Weight-matched rats were then assigned to four groups according to dietary fat level (7% or 15% fat) and genistein contents (0 or 320 mg/kg diet). Food intake was significantly decreased by both high fat intake and genistein supplementation compared with normal fat intake and genistein no supplementaion. But weight gain was significantly decreased by genistein supplementation in normal fat intake compared with the other groups. Total lipid, total cholesterol and triglyceride in serum and liver were significantly decreased by normal fat intake compared with high fat intake. But total cholesterol in liver was significantly increased by genistein supplementation in both high fat and normal fat intake. TBARS in serum and liver was less produced by normal fat intake compared with high fat intake but TBARS in liver was significantly increased by genistein supplementation compared with genistein no supplementation in normal fat intake. Glutathione reductase activity in erythrocytes was significantly reduced by genistein supplementation in normal fat intake compared with the other groups. Glutathione peroxidase and glutathione reductase activities in liver were significantly inhibited by normal fat intake compared with high fat intake. Catalase activity in liver was significantly increased by genistein supplementation compared with genistein no supplementation in high fat intake. Nitrite was significantly decreased by normal fat intake compared with high fat intake. These results suggest that normal fat intake has the treatment effect against risk factors related with cardiovascular disease by reducing lipid profiles, lipid peroxidation. And genistein shows action as a antioxidant replacing antioxidant enzymes but also may act as prooxidant causing the production of TBARS.

• BMB Reports
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• 제55권11호
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• pp.547-552
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• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• 대한본초학회지
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• 제29권4호
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• pp.77-82
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• 2014

Objectives : The effects of ethanol extract of Plantago asiatica L. were investgated on adipocyte differentiation, lipopogenesis, lipolysis and apoptosis using differnentiated 3T3-L1 adipocytes. Methods : Plantago asiatica L. was extracted with ethanol (CCE). We carried on MTT assay for cell proliferation, Oil Red O staining for determination of cell differentiation and intracelluar adipogenesis. TUNEL staining assay for cell apoptosis, and Western blot analysis for measurement of pAMPK and pACC, $C/EBP{\alpha}$, $PPAR{\gamma}$ protein expressions were performed. Results : The addition of CCE up to 0.2 mg/ml into cell culture media showed no cytotoxicity. Treatment of 0.2 mg/ml CCE significantly inhibited differentiation in 3T3-L1 preadipocytes. Lipid accumulation of the CCE treated cells was decreased compared with that of control. Induction of cell apoptosis was increased in CCE treated cells compared with that of control. AMPK and ACC levels of the cells with 0.2 mg/ml CCE were led to phosphorylation and also expressions of $C/EBP{\alpha}$ and $PPAR{\gamma}$, as adipogenic transcription factors, were suppressed compared with those of control. Conclusions : Taken together, these results provide evidence that CCE has a regulatory role in lipid metabolism that is related to differentiation into adipocytes, adipogenesis and apoptosis.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.97-97
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• 2003

Embryonic stem (ES) cells, derived from preimplantation embryos, are able to differentiate into various types of cells consisting the whole body, or pluripotency. In addition to the plasticity, ES cells are expected to be different from terminally differentiated cells in very many ways, such as patterns of gene expressions, ability and response of the cells in confronting environmental stimulations, metabolism, and growth rate. As a model system to differentiate these two types of cells, human ES (hES, MB03) cells and terminally differentiated cells (HeLa), we examined the ability of these two types of cells in confronting a severe oxidative insult, that is $H_2 O_2$. Ratio of dying cells as determined by the relative amount of dye neutral red entrapped within the cells after the exposures. Cell death rates were not significantly different when either MB03 or HeLa were exposed up to 0.4 mM $H_2 O_2$. However, relative amount of dye entrapped within the cells sharply decreased down to 0.12% in HeLa cells when the cells were exposed to 0.8 mM $H_2 O_2$, while it was approximately 54% in MB03. Pretreatment of cells with BSO (GSH chelator) and measurement of GSH content results suggest that cellular GSH is the major defensive mechanism of hES cells. Induction of apoptosis in hES cell was confirmed by DNA laddering, induction of Bax, and chromatin condensation. In summary, hES cells 1) are extremely resistant to oxidative stress, 2) utilize GSH as a major defensive mechanism. and 3) experience apoptosis upon exposure to oxidative stress.