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Meta-analysis of Association Studies of CYP1A1 Genetic Polymorphisms with Digestive Tract Cancers Susceptibility in Chinese

  • Liu, Chang;Jiang, Zheng;Deng, Qian-xi;Zhao, Ya-nan
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권11호
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    • pp.4689-4695
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    • 2014
  • Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

1-(Benzotriazol-1-yl)alkyl Aryl Sulfone의 합성 (Synthesis of 1-(Benzotriazol-1-yl)alkyl Aryl Sulfones)

  • 홍영석;김현묵;이정근;박용태;김호식
    • 대한화학회지
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    • 제40권9호
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    • pp.615-622
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    • 1996
  • 1-(Benzotriazol-1-yl)-1-benzenesulfonylmethane 1a에 LDA 및 methyl iodide를 작용시켜 1-(Benzotriazol-1-yl)-1-benzenesulfonylmethane 2a와 2-(Benzotriazol-1-yl)-2-benzenesulfonylpropane 2b를 각각 얻었다. 같은 방법으로 1-(Benzotriazol-1-yl)-1-benzenesulfonylmethane 1b로부터 1-(Benzotriazol-1-yl)-1-benzenesulfonylpropane 3a와 3-(Benzotriazol-1-yl)-3-benzenesulfonylpentane 3b를 얻었다. 한편, 1, 1-di(benzotriazol-1-yl)-1-arylmethane 4를 butyl lithiym과 diphenyl disulfide로 처리하여 1, 1-di(benzotriazol-1-yl)-1-aryl-1-thiophenoxymethane 5를 합성하였다. 1, 1-di(benzotriazol-1-yl)methane 8을 butyl lithiym과 diphenyl disulfide로 처리하여 1, 1-di(benzotriazol-1-yl)-1-thiophenoxymethane 9a와 1, 1-di(benzotriazol-1-yl)-1, 1-dithiophenoxymethane 9b를 각각 얻었다. 화합물 9a를 m-CPBA로 산화시켜 1, 1-di(benzotriazol-1-yl)-1-benzenesulfoxymethane 10a와 1, 1-di(benzotriazol-1-yl)-1-benzenesulfonylmethane 10b를 얻었다. 한편, 화합물 3b를 170.deg.C 에서 열분해시켜 3-toluenesulfonyl-2-pentene 11ㅇ르 얻었으며, 150.deg.C의 강철봄베속에서 3b를 과량의 물로 가수분해 시켰더니 sulfone의 C-N 및 C-S 결합 모두가 절단된 diethyl ketone 13a가 생성됨을 확인하였다.

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Metagonimus yokogawai 세르카리아의 감각유두에 관한 연구 (Study on Sensory Papillae of Metagonimus yokogawai Cercaria)

  • 김재진;민득영소진탁
    • Parasites, Hosts and Diseases
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    • 제22권1호
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    • pp.11-20
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    • 1984
  • A number of studies on the papillae of cercariae of trematodes reported that the papillar patterns (or chaetotaxy) of cercariae might be an excellent method to attain better understanding of the digenetic trematodes (Richard, 1971 ; Short and Cartrett, 1973; Bayssade-Dufour, 1979) . The present study was aimed to determine the number, distribution pattern and structure of the sensory papillae of Metagonimus yokogawai cercariae, and to elucidate the chaetotaxy of this digenetic trematode. M. yokogawai cercariae were pipetted from a vial in which infected snails (Semisulcospira libertina) had been kept for 3 hours. The snails were collected from an endemic area of M. yokogawai, Boseong river in west-southern part of Korea. Observations of papillae were based on light microscopy of those stained with silver nitrate, and on scanning electron microscopy The results are summarized as follows: 1, All papillae observed were uniciliated. 2. Cilia in anterior tip were shorter than the others in other portions. 3. The body papillae were arranged in essentially symmetrical patterns, Total number of the papillae was 126(63 pairs) in average; anterior tip 40(20 pairs), ventral 20(10 pairs), lateral 42(21 pairs), and caudal 8(4 pairs). 4. The chaetotany of M. yokogawai cercaria was: Ci cycle ($3+3C_{I}V,{\;}2+2C_{I}L,{\;}2+3C_{I}D),{\;}C_{II}{\;}cycle(2C_{II}V,{\;}1C_{II}L,{\;}2C_{II}D),{\;}C_{lll}{\;}cycle{\;}(1+lC_{III}V,{\;}1C_{IlI}L),{\;}C_{IV}{\;}cycle{\;}(1C_{IV}V,{\;}IC_{lV}L){\;}in{\;}cephalic{\;}region:{\;}A_I(1A_{IV}V,{\;}1+2A_{I}L,{\;}1A_{I}D),{\;}A_{II}(1A_{II}V,{\;}1+3A_{II}L,{\;}1A_{II}D),{\;}A_{III}(1A_{III}V,{\;}1+1A_{III}L,{\;}1A_{III}D){\;}and{\;}A_{IV}(1A_{IV}V,{\;}2A_{IV}L)$ in antacetabular region: $1M_{I}V{\;}and{\;}2M_{I}L$ in median: $1+1P_{I}L,{\;}1P_{II}L,{\;}1P_{II}D,{\;}1P_{III}L,{\;}1P_{IV}L{\;}and{\;}1P_{IV}D$ in postacetabular region: 2-2-2-2 in caudal region.

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Direct Block of Cloned $K^+$ Channels, Kv1.5 and Kv1.3, by Cyclosporin A, Independent of Calcineurin Inhibition

  • Choi, Bok-Hee;Hahn, Sang-June
    • The Korean Journal of Physiology and Pharmacology
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    • 제9권6호
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    • pp.353-361
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    • 2005
  • The interaction of cyclosporine A (CsA), an immunosuppressant, with rat brain Kv1.5 (Kv1.5) channels, which were stably expressed in Chinese hamster ovary cells, was investigated using the whole-cell patch-clamp technique. CsA reversibly blocked Kv1.5 currents at +50 mV in a reversible concentrationdependent manner with an apparent $IC_{50}$ of 1.0μM. Other calcineurin inhibitors (cypermethrin, autoinhibitory peptide) had no effect on Kv1.5 and did not prevent the inhibitory effect of CsA. Fast application of CsA led to a rapid and reversible block of Kv1.5, and the onset time constants of the CsA-induced block were decreased in a concentration-dependent manner. The CsA-induced block of Kv1.5 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the block exhibited voltage independence over the voltage range in which channels were fully activated. The rate constants for association and dissociation of CsA were $7.0{\mu}M{-1}s^{-1}$ and $8.1s^{-1}$, respectively. CsA slowed the deactivation time course, resulting in a tail crossover phenomenon. Block of Kv1.5 by CsA was use-dependent. CsA also blocked Kv1.3 currents at +50 mV in a reversible concentration-dependent manner with an apparent $IC_{50}$ of $1.1{\mu}M$. The same effects of CsA on Kv1.3 were also observed in excised inside-out patches when applied to the internal surface of the membrane. The present results suggest that CsA acts directly on Kv1.5 currents as an open-channel blocker, independently of the effects of CsA on calcineurin activity.

Hypoxic repression of CYP7A1 through a HIF-1α- and SHP-independent mechanism

  • Moon, Yunwon;Park, Bongju;Park, Hyunsung
    • BMB Reports
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    • 제49권3호
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    • pp.173-178
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    • 2016
  • Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1.

Entire Functions and Their Derivatives Share Two Finite Sets

  • Meng, Chao;Hu, Pei-Chu
    • Kyungpook Mathematical Journal
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    • 제49권3호
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    • pp.473-481
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    • 2009
  • In this paper, we study the uniqueness of entire functions and prove the following theorem. Let n(${\geq}$ 5), k be positive integers, and let $S_1$ = {z : $z^n$ = 1}, $S_2$ = {$a_1$, $a_2$, ${\cdots}$, $a_m$}, where $a_1$, $a_2$, ${\cdots}$, $a_m$ are distinct nonzero constants. If two non-constant entire functions f and g satisfy $E_f(S_1,2)$ = $E_g(S_1,2)$ and $E_{f^{(k)}}(S_2,{\infty})$ = $E_{g^{(k)}}(S_2,{\infty})$, then one of the following cases must occur: (1) f = tg, {$a_1$, $a_2$, ${\cdots}$, $a_m$} = t{$a_1$, $a_2$, ${\cdots}$, $a_m$}, where t is a constant satisfying $t^n$ = 1; (2) f(z) = $de^{cz}$, g(z) = $\frac{t}{d}e^{-cz}$, {$a_1$, $a_2$, ${\cdots}$, $a_m$} = $(-1)^kc^{2k}t\{\frac{1}{a_1},{\cdots},\frac{1}{a_m}\}$, where t, c, d are nonzero constants and $t^n$ = 1. The results in this paper improve the result given by Fang (M.L. Fang, Entire functions and their derivatives share two finite sets, Bull. Malaysian Math. Sc. Soc. 24(2001), 7-16).

Associated Factors of Depression and Suicidal Behaviors among Korean Adolescents: Web-based Survey of the Korea Youth Risk Behavior in 2015~2017

  • Choi, Hyun-A;Yang, Hyejin
    • 지역사회간호학회지
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    • 제32권3호
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    • pp.292-302
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    • 2021
  • Purpose: Suicide among adolescents is a serious problem worldwide, and especially, the suicide rate of teenagers is increasing rapidly in South Korea. This study was conducted to investigate the factors affecting the respective suicidal behavior in terms of home-environment characteristics, health behavior characteristics, and psychological health characteristics in Korean adolescents. Methods: The data of the Web-based Survey of the Youth Risk Behavior from 2015 to 2017 collected by the Korea Centers for Disease Control and Prevention (KCDC) was analyzed using multivariable logistic regression analysis. Results: The influential factors by depression and suicidal behavior (suicidal ideation (SI), suicidal plan (SP), and suicidal attempt (SA)) were female(adjusted odds ratios [aOR], 1.45, 1.69, 1.30, 2.19), age (aOR 1.03, 0.98, 0.97, 0.90), no family members (aOR 1.21, 1.36, 2.11, 2.32), living with only the father (aOR 1.05, 1.06, 1.07, 1.11), high economic status (aOR 1.15, 1.22, 1.34, 1.46), residence in relatives' home (aOR 1.6, 1.36, 2.34, 1.97), drinking experience (aOR 1.35, 1.47, 1.57, 1.76), smoking experience (aOR 1.28, 1.30, 1.31, 1.94), hospital treatment experience due to violence (aOR 2.18, 3.33, 6.24, 8.40), bad health status (aOR 1.23, 1.48, 2.00, 2.15), unhappiness (aOR 2.49, 6.14, 6.72, 8.89), and a lot of stress (aOR 6.05, 10.40, 4.86, 5.52). Conclusion: The suicidal behavior risk screening and prevention program for adolescents should be developed considering the subjective happiness and hospital treatment experience status due to violence that affects suicidal behavior.

LOCAL PERMUTATION POLYNOMIALS OVER FINITE FIELDS

  • Lee, Jung-Bok;Ko, Hyoung-June
    • 대한수학회논문집
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    • 제9권3호
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    • pp.539-545
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    • 1994
  • Let $q = p^r$, where p is a prime. A polynomial $f(x) \in GF(q)[x]$ is called a permutation polynomial (PP) over GF(q) if the numbers f(a) where $a \in GF(Q)$ are a permutation of the a's. In other words, the equation f(x) = a has a unique solution in GF(q) for each $a \in GF(q)$. More generally, $f(x_1, \cdots, x_n)$ is a PP in n variables if $f(x_1,\cdots,x_n) = \alpha$ has exactly $q^{n-1}$ solutions in $GF(q)^n$ for each $\alpha \in GF(q)$. Mullen ([3], [4], [5]) has studied the concepts of local permutation polynomials (LPP's) over finite fields. A polynomial $f(x_i, x_2, \cdots, x_n) \in GF(q)[x_i, \codts,x_n]$ is called a LPP if for each i = 1,\cdots, n, f(a_i,\cdots,x_n]$ is a PP in $x_i$ for all $a_j \in GF(q), j \neq 1$.Mullen ([3],[4]) found a set of necessary and three variables over GF(q) in order that f be a LPP. As examples, there are 12 LPP's over GF(3) in two indeterminates ; $f(x_1, x_2) = a_{10}x_1 + a_{10}x_2 + a_{00}$ where $a_{10} = 1$ or 2, $a_{01} = 1$ or x, $a_{00} = 0,1$, or 2. There are 24 LPP's over GF(3) of three indeterminates ; $F(x_1, x_2, x_3) = ax_1 + bx_2 +cx_3 +d$ where a,b and c = 1 or 2, d = 0,1, or 2.

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대장균에서 발현된 인간 Cytochrome P450 1A1과 Rat NADPH-P450 Reductase와의 Fusion Protein의 효소 특성 연구 (Enzymatic Properties of a Fusion Protein between Human Cytochrome P450 1A1 and Rat NADPH-P450 Reductase Expressed in Escherichia Coli)

  • 천영진;정태천;이현걸;한상섭;노정구
    • Toxicological Research
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    • 제12권2호
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    • pp.155-161
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    • 1996
  • The enzymatic properties for NADPH-P450 reductase domain of a fusion protein between human cytochrome P450 1A1 and rat NADPH-P450 reductase expressed in Escherichia coli were investigated. The fusion plasmid pCW/1A1OR-expressed E. coli membrane showed high NADPH-cytochrome c reductase activity ($830.1\pm 85.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$), while pCW control vector and P 450 1A1 expression vector pCW/1A1 showed relatively quite low activity ($4.35\pm 0.49, 3.27\pm 0.50 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively). The kinetic curves for NADPH-cytochrome c reductase followed typical Michaelis-Menten kinetics. The $K_{max}$ and $V_{max}$ for NADPH-dependent reductase activity were $8.24\pm 2.61\mu $and $817.9\pm 60.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively, whereas those for cytochrome c-dependent reductase activity were $19.97\pm 2.86\mu M$ and $1303.5\pm 67.1 nmol\cdot min^{-1}\cdot mg protein^{-1}$. The reductase activities were also compared with those of rat, porcine and human liver microsomes. The activity of pCW/ 1A1OR-expressed E. coli membrane was 15.2-fold higher than that of rat liver microsome. Treatment with benzo(a)pyrene, 7-ethoxyresorufin and $\alpha$-naphthofiavone which are known as specific substrates or inhibitor for human P450 1A1 increased NADPH-cytochrome c reductase activity of fusion protein in E. coli membrane dose-dependently. These results demonstrate that the membrane topology of fused enzyme may be important for activity of its NADPH-P450 reductase domain.

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Proline-Rich Acidic Protein 1 (PRAP1) is a Target of ARID1A and PGR in the Murine Uterus

  • Kim, Tae Hoon;Jeong, Jae-Wook
    • 한국발생생물학회지:발생과생식
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    • 제23권3호
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    • pp.277-284
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    • 2019
  • ARID1A and PGR plays an important role in embryo implantation and decidualization during early pregnancy. Uterine specific Arid1a knockout ($Pgr^{cre/+}Arid1a^{f/f}$) mice exhibit in non-receptive endometrium at day 3.5 of gestation (GD 3.5). In previous studies, using transcriptomic analysis in the uterus of $Pgr^{cre/+}Arid1a^{f/f}$ mice, we identified proline-rich acidic protein 1 (PRAP1) as one of the down-regulated genes by ARID1A in the uterus. In the present study, we performed RT-qPCR and immunohistochemistry analysis to investigate the regulation of PRAP1 by ARID1A and determine expression patterns of PRAP1 in the uterus during early pregnancy. During early pregnancy, PRAP1 expression was strong at day 0.5 of gestation (GD 0.5) and then decreased at GD 3.5 in the epithelium and stroma. After implantation, PRAP1 expression was remarkably reduced in the uterus. However, the expression of PRAP1 at GD 3.5 was remarkably increased in the $Pgr^{cre/+}Arid1a^{f/f}$ mice. To determine the ovarian steroid hormone regulation of PRAP1, we examined the expression of PRAP1 in ovariectomized control, $Pgr^{cre/+}Arid1a^{f/f}$, and progesterone receptor knock-out (PRKO) mice treated with progesterone. While PRAP1 proteins were strongly expressed in the luminal and glandular epithelium of control mice treated with vehicle, progesterone treatment suppressed the expression of PRAP1. However, PRAP1 was not suppressed in both the $Pgr^{cre/+}Arid1a^{f/f}$ and PRKO mice compared to controls. Our results identified PRAP1 as a novel target of ARID1A and PGR in the murine uterus.