• Title/Summary/Keyword: CYP3A11

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Association Analysis of the Essential Hypertension Susceptibility Genes in Adolescents: Kangwha Study (청소년 고혈압 관련 유전자의 연관성 분석: Kangwha Study)

  • Suh, Il;Nam, Chung-Mo;Kim, Sung-Joo;Shin, Dong-Jik;Hur, Nam-Wook;Kang, Dae-Ryong
    • Journal of Preventive Medicine and Public Health
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    • v.39 no.2
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    • pp.177-183
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    • 2006
  • Objectives : In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T47C, T1641), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. Methods : The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. Results : In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p=0.0403), AGT (M235T) (p=0.0002), and REN (G2646A) (p=0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. Conclusions : This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

Analysis of Genes Regulated by HSP90 Inhibitor Geldanamycin in Neurons

  • Yang, Young-Mo;Kim, Seung-Whan;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.15 no.1
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    • pp.97-99
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    • 2009
  • Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

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Administration of antibiotics contributes to cholestasis in pediatric patients with intestinal failure via the alteration of FXR signaling

  • Xiao, Yongtao;Zhou, Kejun;Lu, Ying;Yan, Weihui;Cai, Wei;Wang, Ying
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.14.1-14.14
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    • 2018
  • The link between antibiotic treatment and IF-associated liver disease (IFALD) is unclear. Here, we study the effect of antibiotic treatment on bile acid (BA) metabolism and investigate the involved mechanisms. The results showed that pediatric IF patients with cholestasis had a significantly lower abundance of BA-biotransforming bacteria than patients without cholestasis. In addition, the BA composition was altered in the serum, feces, and liver of pediatric IF patients with cholestasis, as reflected by the increased proportion of primary BAs. In the ileum, farnesoid X receptor (FXR) expression was reduced in patients with cholestasis. Correspondingly, the serum FGF19 levels decreased significantly in patients with cholestasis. In the liver, the expression of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), increased noticeably in IF patients with cholestasis. In mice, we showed that oral antibiotics (gentamicin, GM or vancomycin, VCM) reduced colonic microbial diversity, with a decrease in both Gram-negative bacteria (GM affected Eubacterium and Bacteroides) and Gram-positive bacteria (VCM affected Clostridium, Bifidobacterium and Lactobacillus). Concomitantly, treatment with GM or VCM decreased secondary BAs in the colonic contents, with a simultaneous increase in primary BAs in plasma. Moreover, the changes in the colonic BA profile especially that of tauro-beta-muricholic acid ($T{\beta}MCA$), were predominantly associated with the inhibition of the FXR and further altered BA synthesis and transport. In conclusion, the administration of antibiotics significantly decreased the intestinal microbiota diversity and subsequently altered the BA composition. The alterations in BA composition contributed to cholestasis in IF patients by regulating FXR signaling.

CASE REPORTS OF TREATMENT OF ERUPTION-DISTURBED MX. FIRST MOLAR BY SURGICAL EXPOSURE (맹출 장애를 가진 상악 제1대구치의 외과적 노출을 이용한 치험례)

  • Seok, Choong-Ki;Nam, Dong-Woo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.11-18
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    • 2004
  • The eruption of permanent teeth represents the movement in the alveolar bone before appearance in oral cavity, to the occlusal plane after appearance in oral cavity, and additive movement after reaching th the occlusal plane. Tooth eruption is mostly controlled by genetic signals. The eruption stage is divided to preeruptive alveolar stage, alveolar bone stage, mucosal stage according to the process of growth and development. If the disturbance is occured in any stage of eruption, tooth does not erupt. The cause of eruption disturbance are ectopic position of the tooth germ, obstruction of the eruption path and defects in the follicle or PDL. In the treatment of eruption disturbance, surgical procedures are commonly used. There are three kind of surgical procedure ; surgical exposure, surgical repositioning, surgical exposure and traction Surgical exposure is basic procedure. This involves removal of mucosa, bone, lesion that are surrounding the teeth, dental sac when necessary to maintain a patent channel between the crown and the normal eruptive path into the oral cavity. To ensure this patency, many techniques including cementation of a celluloid crown, packing with gutta-percha or zinc oxide-eugenol, or a surgical pack, are used. When surgical exposure is conducted, operators should not expose any part of cervical root cement and not injure periodontium or root of adjunct tooth. After surgical exposure, tooth should be surrounded by keratinized gingiva. There is direct relationship between the extent of development of pathophysiologic aberrations and the intensity of the manipulative injury inflicted on the tooth by surgical treatment, so operator should consider this thing. In these cases, surgical exposure is conducted on Maxillary 1st milars that have a eruption disturbance and improve the eruption disturbance effectively.

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Changes of Root Yield and Paeoniflorin Content by Cultivated Years in Paeonia lactiflora PALLS (작약(芍藥) 재배년수(栽培年數)에 따른 근수량(根收量) 및 Paeoniflorin함량변화(含量變化))

  • Kim, Ki-Jae;You, Oh-Jong;Jeong, Yeun-Seon;Park, So-Deuk;Shin, Jong-Hee;Hwang, Hyung-Baek;Choi, Boo-Sull
    • Korean Journal of Medicinal Crop Science
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    • v.4 no.1
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    • pp.68-73
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    • 1996
  • Stem length, main root length and main root diameter showed rapid increasement in two-years-old and three-years-old peony. And there after, the increasement was almost finished. Occurrence of disease was increasing every cultivated year, especially the development of leaf spot was most serious. In propagation by root dividing method, the radix yield (kg/10a) was increasing every cultivated year. However, the difference of radix yield at four and five-years-old peony were not significant. The radix yield of four-years-old peony was higher 26% than three-years-old one. As cultivated year goes by, content of paeoniflorin was increasing then the content was highest at four-years-old peony (4.06%). In 1995, the content, had no certain tendency, was highest at three-years-old peony (3.14%). At hot air drying, browing of peony radix was increasing every cultivated year. If we consider radix yield and color, three-years-old peony was proper object of harvesting.

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The Effect of Baekhogainsam-tang on Metabolism through Modulation of the Gut Microbiota and Gene Expression in High-Fat Diet Induced Metabolic Syndrome Animal Model (고지방식이로 유도된 대사증후군 모델 동물에서 백호가인삼탕(白虎加人參湯)의 장내미생물 및 유전자 발현 조절을 통한 대사 개선 효과)

  • Min-Jin Cho;Song-Yi Han;Soo Kyoung Lim;Eun-Ji Song;Young-Do Nam;Hojun Kim
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.3
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    • pp.1-15
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    • 2023
  • Objectives We aimed to find out the improvement effect of Baekhogainsam-tang (Baihu Jia Renshen-tang, BIT) on metabolic syndrome and alteration of microbiota and gene expression. Methods We used male C57BI/6 mice and randomly assigned them into three groups. Normal control group was fed 10% kcal% fat diet, high-fat diet (HFD) group was fed 45% kcal% fat diet and 10% fructose water. BIT group was fed same diet as HFD group and treated by BIT for once daily, 6 days per week, total 8 weeks. We measured their body weight and food intake every week and performed oral glucose tolerance test 1 week before the end of the study. Then we collected the blood sample to measure triglyceride, total cholesterol, high-density lipoprotein cholesterol, insulin, and hemoglobin A1c. We harvested tissue of liver, muscle, fat, and large intestine for quantitative polymerase chain reaction (qPCR) and histopathological examination. Fresh fecal samples were collected from each animal to verify alterations of gut microbiota and we used RNA from liver tissue for microarray analysis. Results The body weight and fat weight of BIT group were reduced compared to HFD group. The qPCR markers usually up-regulated in metabolic syndrome were decreased in BIT group. Bacteroides were higher in BIT group than other groups. There were also differences in gene expressions between two groups such as Cyp3a11 and Scd1. Conclusions We could find out BIT can ameliorate metabolic syndrome and suggest its effect is related to gut microbiota composition and gene expression pattern.

In Vitro Metabolism of a New Cardioprotective Agent, KR-33028 in the Human Liver Microsomes and Cryopreserved Human Hepatocytes

  • Kim Hyojin;Yoon Yune-Jung;Kim Hyunmi;Cha Eun-Young;Lee Hye Suk;Kim Jeong-Han;Yi Kyu Yang;Lee Sunkyung;Cheon Hyae Gyeong;Yoo Sung-Eun;Lee Sang-Seop;Shin Jae-Gook;Liu Kwang-Hyeon
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1287-1292
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    • 2005
  • KR-33028 (N-[4-cyano-benzo[b]thiophene-2-carbonyl]guanidine) is a new cardioprotective agent for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-33028 in human liver microsomes and to compare its metabolism with that of cryopreserved human hepatocytes. Human liver microsomal incubation of KR-33028 in the presence of NADPH and UDPGA resulted in the formation of four metabolites, M1, M2, M3, and M4. M1 and M2 were identified as 5-hydroxy-KR-33028 and 7-hydroxy-KR-33028, respectively, on the basis of LC/MS/MS analysis with the synthesized authentic standard. M3 and M4 were suggested to be dihydroxy-KR-33028 and hydroxy-KR-33028-glucuronide, respectively. Metabolism of KR-33028 in cryopreserved human hepatocytes resulted in the formation of M1, M2, and M4. These data show a good correlation between major metabolites formed in human liver microsomes and cryopreserved human hepatocytes. In addition, KR­33028 was found to inhibit moderately the metabolism of CYP1A2 substrates. Based on the results obtained metabolic pathway of KR-33028 is proposed.

Association of PAH-DNA adducts and Urinary PAH metabolites influenced by polymorphisms of xenobiotic metabolism enzymes in industrial wase incinerating workers (산업폐기물 소각장 근로자에서 요중 PAHs 대사산물과 혈중 aromatic-DNA adducts)

  • ;Masayoshi Ichiba
    • Environmental Mutagens and Carcinogens
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    • v.22 no.4
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    • pp.303-311
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    • 2002
  • This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

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Expression of Cytochrome P450 Aromatase Genes during Sex Differentiation in Korean Rockfish, Sebastes schlegeli (조피볼락, Sebastes schlegeli의 성분화 기간 중 Cytochrome P450 Aromatase 유전자의 발현)

  • Lee, Chan-Hee;Kwon, Joon-Yeong
    • Development and Reproduction
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    • v.11 no.3
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    • pp.195-203
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    • 2007
  • Sex determination and sex differentiation are influenced by genotype in many gonochoristic fish. Cytochrome P450 aromatase (CYP19) is the terminal enzyme in steridogenic pathway that converts androgens into estrogens. In this study, partial fragments of aromatase genes (ovarian aromatase, P450aromA and brain aromatase, P450aromB) were cloned and sequenced in Korean rockfish (Sebastes schlegeli), and gene specific primers were designed based on their sequences. Using these primers, aromatase gene expression during sex differentiation was investigated by RT-PCR. Expression of these aromatase genes were detected both in the head and body parts at 35 dab (days after birth). The number of fish that expressed the aromatase genes decreased at 52 dab, implying down-regulation of these genes. However, these genes were expressed at 59 dab in almost all fish studied here. The expression patterns of both genes are similar throughout the investigated period except for 45 dab where the expression of P450aromB was detected in more fish than that of P450aromA both in the head and body parts. Timing of sex differentiation in this species has been shown to be at around $50{\sim}65$ dab by histological analysis. However, the results from this study suggest that sex differentiation of rockfish may take place $1{\sim}2$ weeks earlier than the period proposed previously. The results also suggest that the mechanism of sex differentiation in viviparous fish may be similar to that in oviparous fish in terms of the importance of aromatase action during the critical period.

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Effects of Growth Regulators, Sucrose and Gelling Agents on Callus Growth and Plant Regeneration in Angelica koreana MAX. (강활(羌活)의 캘러스 증식(增殖) 및 식물체(植物體) 재분화(再分化)에 미치는 생장(生長) 조절제(調節劑), sucrose 및 배지(培地) 응고제(凝固劑)의 영향(影響))

  • Lee, Joong-Ho;Lee, Seung-Yeob;Namkoong, Seung-Bak
    • Korean Journal of Medicinal Crop Science
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    • v.4 no.1
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    • pp.78-85
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    • 1996
  • The effects of growth regulators, sucrose and gelling agents were investigated to increase the efficiency of the callus growth and plant regenerarion in tissue culture of Angelica koreana Max. The fresh weight and dry weight of subcultured callus was highest in MS medium supplemented with 1 mg/l 2,4-D. Callus growth was excellent in 2% sucrose, but it was inhibited in propotion to sucrose content. Effect of gelling agents on callus growth was highest on 1.2% agar and 0.4% Gelrite medium, respectively. The browning of callus was protected on the media supplemented with 10 mg/l ABA and 5 or 10 mg/l $AgNO_3$. In the callus induction and growth from the peduncle of immature inflorescence, 2,4-D was more effective than NAA, and the frequency of callus induction was highest as 81.7% in 2 mg/l 2,4-D. Plant was not regenerated from the callus derived from young leaf. Somatic embryos were developed from the surface of callus drived from the peduncle of immature inflorescence in the medium containing 0.5 mg/l 2,4-D, 1 mg/l kinetin, 5 mg/l ABA and 5 mg/l $AgNO_3$. Plants were developed from the matured somatic embryos in the medium supplemented with 0.2 mg/l 2,4-D and 1 mg/l kinetin.

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