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Finasteride Increases the Expression of Hemoxygenase-1 (HO-1) and NF-E2-Related Factor-2 (Nrf2) Proteins in PC-3 Cells: Implication of Finasteride-Mediated High-Grade Prostate Tumor Occurrence

  • Yun, Do-Kyung;Lee, June;Keum, Young-Sam
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.49-53
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    • 2013
  • A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic $5{\alpha}$-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.

The Effect of Estrogen on the Transcription of the Insulin-like Growth Factor-I Gene in the Uterus (자궁 내 insulin-like growth factor-I 유전자 발현에 미치는 에스트로겐의 영향)

  • Kwak, In-Seok
    • Journal of Life Science
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    • v.19 no.5
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    • pp.593-597
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    • 2009
  • The uterus plays a critical role in pregnancy and steroid hormones, and both estrogen (E2) and progesterone (P4) especially play important roles in the cross-talk between embryos and uterus to support the pregnancy. E2 stimulates uterine growth during early pregnancy to prepare for implantation of embryos. This cross-talk during the implantation period involves hormones (E2 and P4) and growth factors, including insulin-like growth factor-I (IGF-I). In the uterus of a pregnant pig, the action of E2 is mediated by estrogen receptor-${\beta}$ (ER-${\beta}$). The expression of ER-a was much higher in early pregnancy than in mid- and late- pregnancy, suggesting E2 secretion from embryos enhances transcription of ER-a during early pregnancy. In order to prove whether IGF-I is an E2 target gene, quantitative real-time PCR was performed on ovariectomized murine uterus with E2 and/or P4 treatment(s). Increased IGF-I mRNA expression was observed with E2 treatment, however, it was not significantly induced by P4 treatment, which clearly demonstrates that, in mice, E2 depends on the activation of uterine IGF-I gene expression. The expression of IGF-I in the uterus of pigs was much higher in early pregnancy than in mid- and late- pregnancy and these data exhibited the same expression pattern with the ER-${\beta}$ gene expression in the uterus. It suggests that a positive co-relationship between IGF-I and ER-${\beta}$ expression exists in the uterus, and that both gene expressions of IGF-I and ER-${\beta}$ are regulated by E2. It further suggests that uterine the IGF-I gene expression might be initiated by E2 secreted from embryos to increase ER-${\beta}$ gene expression, and that this increased ER-${\beta}$ further stimulates the expression of IGF-I in the uterus during early pregnancy.

Phylogenetic Groups and Virulence Factors of Escherichia coli Causing Urinary Tract Infection in Children (소아 요로감염의 원인 Escherichia coli 균의 계통 분류와 독성인자 분석)

  • Kim, Ji Mok;Cho, Eun Young;Lee, Jae Ho
    • Pediatric Infection and Vaccine
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    • v.22 no.3
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    • pp.194-200
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    • 2015
  • Purpose: Urinary tract infection (UTI) is a common bacterial infection in children and Escherichia coli is a predominant pathogen. The purpose of this study is to evaluate phylogenetic groups and virulence factors of E. coli causing UTI in children in Korea. Methods: From October 2010 to April 2013, urinary E. coli strains were isolated from the 33 pediatric patients of UTI. Multiplex polymerase chain reactions were performed to evaluate the phylogenetic groups and 5 virulence factor genes (fimH, sfa, papA, hylA, and cnf1) of E. coli. Distribution of molecular characteristics of E. coli was analyzed by clinical diagnosis and accompanying vesicoureteral reflux (VUR). Results: Most (84.8%) uropathogenic E. coli were belonged to phylogenetics group B2 and the others (15.2%) were belonged to group D. The virulence factors were distributed as: fimH (100%), sfa (100%), hylA (63.6%), cnfI (63.6%), and papA (36.4%). According to clinical diagnosis, phylogenetic distribution of E. coli strain was 92.3% of B2 and 7.7% of D in acute pyelonephritis and 57.1% of B2 and 42.9% of D in cystitis. Distribution of virulence factors was similar in both groups. In patients with acute pyelonephritis, phylogenetic distribution was similar in VUR and non-VUR group, but proportion of papA genes were lower in VUR group than that of non-VUR group (43.8% vs. 20.0%, P=0.399). Conclusions: This study provides current epidemiologic molecular data of E. coli causing pediatric UTI in Korea and will be a fundamental for understanding the pathogenesis of pediatric UTI.

Virulence Factor Profiles of Escherichia coli Isolated from Pork and Chicken Meats Obtained from Retail Markets (소매시장에서 판매하는 돼지고기와 닭고기에서 분리된 Escherichia coli의 병원성 인자)

  • Choi, Sun-Keum;Lee, Min-Hwa;Lee, Bog-Hieu;Jung, Ji-Youn;Choi, Chang-Sun
    • Food Science of Animal Resources
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    • v.30 no.1
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    • pp.148-153
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    • 2010
  • The aim of this study was to investigate the virulence factor profiles of Escherichia coli strains isolated from pork and chicken meats purchased from retail markets in Korea. From 943 pork and 142 chicken meats, 217 isolates of E. coli were cultured. The presence of 11 virulence factors (elt, estI, estII, astA, stx, cdt, cnf, agg, inve, eae, afa) were detected by polymerase chain reaction. Forty one (18.9%) of 217 E. coli isolates carried at least one virulence factor. Among 175 E. coli isolates from pork, the detection rate of astA, elt, eae, estII, estI, afa, and cnf were 6.9%, 4.6%, 4.6%, 4.0%, 2.3%, 1.1%, and 0.6%, respectively. However, stx, agg, and cdt were not detected in our isolates. Therefore, we conclude that astA is the most prevalent virulence factor in E. coli isolates contaminated in pork and chicken meats in Korea.

Exploratory Factor Analysis of SME Internationalization: Factor Differences between AEO and Non-AEO Authorized Companies

  • Son, Sung-Kyun;Kim, Tae-Joong;Kim, So-Hyung
    • Journal of Distribution Science
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    • v.12 no.7
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    • pp.5-12
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    • 2014
  • Purpose - This study identified internationalization factors forKorean SMEs and explored factor differences between AEO and non-AEO authorized companies. Research design, data, and methodology - The study was designed to assess internationalization factors for AEO authorization in Korea through a questionnaire survey and an empirical analysis. The questionnaires were conducted for AEO and Non-AEO authorized companies that were undergoing AEO authorization. The study was conducted through e-mail and AEO manager education classes. Ninety-five questionnaires were collected. We employed the exploratory factor analysis methodology to derive internationalization factors for KoreanSMEs, and explored the factor differences between AEO and Non-AEO authorized companies. Results - AEO authorized companies outperformed Non-AEO authorized companies in R&D and technology. This indicated that AEO authorized companies were recognized as reliable and safe companies by the Korea Customs Service and other Customs services in trade facilitation and customs clearance processes. Conclusions - This study has some implications for AEO authorization and internationalization processes, and involved the empirical analysis of SMEs and the exploratory factor analysis in the internationalization process.

Four active monomers from Moutan Cortex exert inhibitory effects against oxidative stress by activating Nrf2/Keap1 signaling pathway

  • Zhang, Baoshun;Yu, Deqing;Luo, Nanxuan;Yang, Changqing;Zhu, Yurong
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.373-384
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    • 2020
  • Paeonol, quercetin, β-sitosterol, and gallic acid extracted from Moutan Cortex had been reported to possess anti-oxidative, anti-inflammatory, and anti-tumor activities. This work aimed to illustrate the potential anti-oxidative mechanism of monomers in human liver hepatocellular carcinoma (HepG2) cells-induced by hydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect of monomers was independence or synergy in mice stimulated by carbon tetrachloride (CCl4). Monomers protected against oxidative stress in HepG2 cells in a dose-response manner by inhibiting the generation of reactive oxygen species, increasing total antioxidant capacity, catalase and superoxide dismutase (SOD) activities, and activating the antioxidative pathway of nuclear factor E2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that the in vitro antioxidant capacities of paeonol and quercetin were better than those of β-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levels of alanine transaminase and aspartate aminotransferase, augmented the contents of glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1 proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, β-sitosterol, and gallic acid play a defensive role against H2O2-induced oxidative stress through activating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidative properties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotective effects, which is independent rather than synergy.

Cloning and Characterization of cDNA for Korean Rockfish (Sebastes schlegeli ) Insulin-like Growth Factor-I

  • Kwon, Mi-Jin;Jo, Jae-Yoon;Nam, Taek-Jeong
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.119-125
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    • 2006
  • To understand the comprehensive mechanisms of biological function for insulin-like growth factor-I (IGF-I) in vertebrates, we have investigated the cDNA sequence of this gene in the korean rockfish (Sebastes schlegeli). The mature form of korean rockfish IGF-I was found to be comprised of 67 amino acid residues, showing about a 7 kDa molecular weight. In this study, we used the polymerase chain reaction (PCR) to obtain a korean rockfish IGF-I (KR IGF-I) cDNA fragment, and methods of rapid amplification of cDNA ends (RACE) to obtain a full length of the KR IGF-I sequence. The KR IGF-I encoded for a predicted amino acid sequence showed identities of 93.6 %, 90.7 %, and 85.4 % in comparison with flounder, chinook salmon, and human IGF-I, respectively. To obtain recombinant biologically active polypeptides, korean rockfish B-C-A-D domains were amplified using the PCR, then the isolated cDNA was expressed in the E. coli BL21(DE3). The recombinant KR IGF-I protein biological function was measured by stimulation of [$^3H$] thymidine incorporation, suggesting the cDNA codes for the korean rockfish proIGF-I.

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Kinematic Analysis According to the Intentional Curve Ball at Golf Driver Swing (골프 드라이버 스윙 시 의도적인 구질 변화에 따른 운동학적 분석)

  • Hong, Soo-Young;So, Jae-Moo;Kim, Yong-Seok
    • Korean Journal of Applied Biomechanics
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    • v.22 no.3
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    • pp.269-276
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    • 2012
  • The purpose of This study's aim is to examine the difference in the changes of body segment movement, variables for ball quality, and carry at golf driver swing according to the ball quality using comparative analysis. Regarding the impact variables according to the ball quality using the track man and carry, club speed was the fastest at draw shot, ball speed was the fastest at straight shot, and smash factor was the lowest at draw shot. About the vertical launch angle, the fade shot showed the highest launch angle while the max height of the ground and ball was the highest at fade shot. And carry was the longest at draw shot. For the flight time, it was the longest at draw shot. The landing angle was the largest at fade shot. About the club head position change and trajectory, at the overall event point, the fade shot drew a more outer trajectory at the point of the follow through(E6) than the straight or draw shot. Regarding the angular speed of shoulder rotation, at the overall event point, the fade shot showed the greatest angular speed change in the follow through(E6). Also, about the angular speed of pelvic rotation, at the overall event point, the draw shot showed the greatest angular speed change at the point of down swing(E4). Concerning the stance angle change, both straight and fade shots were open as the concept of open stance whereas the draw shot was close as that of close stance. Regarding the previous study, the most important factor of deciding Ball Quality is the club face angle's open and close state at Impact. In short, the Ball Quality and carry were decided by this factor.

Consumption of Jeju Ground Water Containing Vanadium Components Enhances Hepatic Antioxidant Defense Systems in ob/ob Mice (비만 마우스 간의 항산화시스템에 대한 바나듐 함유 제주지하수의 증강효과)

  • Kim, A-Reum-Da-Seul;You, Ho-Jin;Hyun, Jin-Won
    • Journal of Life Science
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    • v.22 no.1
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    • pp.1-6
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    • 2012
  • The present study examined the effects of consumption of Jeju ground water containing vanadium components on oxidative stress in obese (ob/ob) mice. Intake of Jeju ground water decreased the generation of oxidative stress induced-lipid peroxidation in the liver of ob/ob mice It also enhanced the enzymatic antioxidant defense system by increasing the protein expression and activity of superoxide dismutase, catalase, and glutathione peroxidase in liver tissues. Jeju ground water intake also upregulated the intracellular content of reduced glutathione. The induction of antioxidant enzyme expression by consumption of Jeju ground water was mediated by the erythroid transcription factor NF-E2 (Nrf2). Increased nuclear expression of phospho Nrf2 was observed in ob/ob mouse liver cells following ntake of Jeju ground water. These results suggest that consumption of Jeju ground water stimulated the antioxidant defense system in the livers of ob/ob mice via induction of Nrf2.

Study on Correlation between Acoustic Profiles and Fatigue (노권상과 음성 지표간의 상관성에 관한 연구)

  • Cho, Shin-Woong;Park, Young-Bae;Park, Young-Jae
    • The Journal of the Society of Korean Medicine Diagnostics
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    • v.14 no.1
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    • pp.15-35
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    • 2010
  • Objectives : The purpose of this study is to find out the correlation between the Vocal indicators and the 'Buzhongyiqi-Tang questionnaire' and the 'Chalder fatigue scale.' Methods : This study examined the mean value of each factor in the 'Buzhongyiqi-Tang Questionnaire,' 'Chalder fatigue scale' and the different voice indicators conducted on 81 healthy adult participants in relation to the results of the /a/ /e/ /i/ /o/ /u/ pronunciation test. Results : There was significant correlation between the pronunciation of /a/ /e/ /i/ /o/ /u/ vowels' F0 indexes and 'the Deficiency symptoms of Buzhongyiqi-Tang'. The results of the regression analysis showed the following significant findings for each pronouncing vowels: /i/ as a factor for 'the Deficiency symptoms of Buzhongyiqi-Tang'.; /a/ for 'the Consumptive fever of Buzhongyiqi-Tang'.; /i/ for 'the Vocal inflammation of Buzhongyiqi-Tang.; and /e/ as a factor of 'the Chadler physical fatigue'. Conclusions : The study showed a negative correlation between the Fundamental Frequency and the mean value of the questionnaire, which could be understood as higher the fatigue level, increased level of vocal vibration and higher pitch tone compared to the less fatigued group. We expect future studies to conduct research on methods to diagnose other illnesses using the vocal indicators based on the correlation between the vocal index and illnesses prescribed under traditional oriental medicine.