• Toxicological Research
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• 제18권4호
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• pp.331-339
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• 2002

Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them wing in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50 mg/kg/day, p.o.) or DCP (100 mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1 g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of $10^{-9}$ M. In 2,4-D or DCP-treated castrated rats, testosterone 6$\beta$-hydroxylase activity was not significantly modulated even when rats were co-treated with testosterone. In vitro incubation of 2,4-D and DCP with microsomes at 50 $\mu$M inhibited testosterone 6$\beta$-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disrupter by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.

• Parasites, Hosts and Diseases
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• 제35권4호
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• pp.271-276
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• 1997

메타고니무스속 흡충의 형태학적인 차이점은 잘 알려져 있으나 이러한 미세한 형태학적 차이로 종을 분류할 수 있을 지에 대해서는 의문시되어 왔다. 이 연구는 비교적 유전자 염기서열이 잘 보존되어 있 어 종간 또는 strain간의 차이를 밝힐 수 있는 리보솜리보핵산 유전자 중 ITSI 유전자와 사립체 COI 유전자를 중합효소반응으로 증폭시킨 후 제한효소로 소화시켜 나타나는 밴드의 차이를 관찰하였다 요 코가와흡충 (M. yokogawai)의 피 낭유충은 삼척산 은어에서 , 미야타흡충 (Metagonim Miyata type) 은 충주산 피라미에서, 타카하시홉충 (M. tnkqhqsrii)은 충주산 붕어에서 분리하여 사용하였다. 세 종류 충체에서 얻은 ml 유전자 증폭산물은 제한효소 Rsc I, Ak I 및 Msp I에 의해 서로 다른 크기의 밴드 로 소화되었다. 세 종류 충체의 사립체 COI 유전자 증폭산물도 Rsc I과 AIu I에 의해 서로 다른 양상으로 잘라졌다. 추정 유전자 차이 (estimated genetic divergence)는 미야타홉충과 요코가와흡충이 0.034880, 요코가와흡충과 타카하시홉충이 0.018179, 미야타흡충과 타카하시흡충이 0.028098 이었다. 이 결과로 보면 미야타흡충은 별개의 종으로 볼 수 있으며,다른 충체보다 이른 시기에 진화하였음 을 알 수 있다.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.255-260
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• 2011

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 $mg{\cdot}kg^{-1}$) with ticlopidine (3 or 9 $mg{\cdot}kg^{-1}$). The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activities were also evaluated. Ticlopidine inhibited CYP3A4 enzyme activity in a concentrationdependent manner with a 50% inhibition concentration ($IC_{50}$) of 35 ${\mu}M$. In addition, ticlopidine did not significantly enhance the cellular accumulation of rhodamine-123 in NCI/ADR-RES cells overexpressing P-gp. Compared with the control (given diltiazem alone), ticlopidine significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration ($C_{max}$) and the area under the plasma concentration-time curve (AUC) of diltiazem were significantly (9 $mg{\cdot}kg^{-1}$, p<0.05) increased in the presence of ticlopidine. The AUC of diltiazem was increased by 1.44-fold in rats in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$). Consequently, the absolute bioavailability (A.B.) of diltiazem in the presence of ticlopidine (9.3-11.5%) was signifi cantly higher (9 $mg{\cdot}kg^{-1}$, p<0.05) than that in the control group (8.0%). Although ticlopidine significantly (p<0.05) increased the AUC of desacetyldiltiazem, the metabolite-parent AUC ratio (M.R.) in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$) was significantly decreased compared to that in the control group, implying that ticlopidine could effectively inhibit the metabolism of diltiazem. In conclusion, the concomitant use of ticlopidine significantly enhanced the oral bioavailability of diltiazem in rats by inhibiting CYP3A4-mediated metabolism in the intestine and/or liver rather than by inhibiting intestinal P-gp activity or renal elimination of diltiazem.

• 한국어류학회지
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• 제28권1호
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• pp.57-64
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• 2016

전갱이과에 속하는 민전갱이 (Uraspis helvola)의 형태적 특징을 상세히 재기재하고, 국내에서 처음으로 채집된 U. uraspis와 비교 분석하였다. 민전갱이와 U. uraspis는 측선의 직선 부위 시작점 위치 (민전갱이: 등지느러미 연조 12번째~13번째, U. uraspis: 등지느러미 연조 15번째~16번째)에서 구분되며, 가슴지느러미에서 흉부 사이 무린역의 연결성 (민전갱이: 무린역이 분리, U. uraspis: 무린역이 연결)에 따라 명확하게 구분된다. 새롭게 보고되는 U. uraspis의 속명과 국명은 각각 "민전갱이속"과 "흑기민전갱이"로 제안한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.2993-2999
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• 2014

Saccharina japonica is a family member of Phaeophyceae (brown macro-alga) and extensively cultivated in China, Japan and Korea. Here, the potential anti-cancer effect of n-hexane fraction of S. japonica was evaluated in SK-Hep1 human hepatocellular carcinoma cells. The N-hexane fraction reduced cell viability and increased the numbers of apoptotic cells in a both dose- and time-dependent manner. Apoptosis was activated by both caspase-dependent and independent pathways. The caspase-dependent cell death pathway is mediated by cell surface death receptors and activated caspase-8 amplified the apoptotic signal either through direct activation of downstream caspase-3 or pro-apoptotic proteins (Bad, Bax and Bak) subsequently leading to the release of cytochrome c. On the other hand, caspase-independent apoptosis appeared mediated by disruption of mitochondrial membrane potential and translocation of AIF to the nucleus where they induced chromatin condensation and/or large-scale DNA fragmentation. In addition, the n-hexane fraction induced endoplasmic reticulum (ER)-stress and cell cycle arrest. The results suggested that potential anti-cancer effects of n-hexane extract from S. japonica on SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5201-5205
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• 2014

Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5797-5804
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• 2013

In order to enhance the bioavailability of curcumin its conjugates with piperic acid and glycine were synthesized by esterifying the 4 and 4' phenolic hydroxyls, the sites of metabolic conjugation. Antiproliferative and apoptotic efficacy of synthesized conjugates was investigated in MCF-7 and MDA-MB-231 cell lines. $IC_{50}$ values of di-O-glycinoyl (CDG) and di-O-piperoyl (CDP) esters of curcumin were found to be comparable with that of curcumin. Both conjugates induced chromatin condensation fragmentation and apoptotic body formation. CDP exposure to MCF-7 cells induced apoptosis initiating loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) followed by inhibition of translocation of transcription factor NF-${\kappa}B$ and release of Cytochrome-C. Reactive oxygen species (ROS) production was evaluated by fluorescent activated cell sorter. Change in ratio of Bcl2/Bclxl was observed, suggesting permeablization of mitochondrial membrane leading to the release of AIF, Smac and other apoptogenic molecules. DNA fragmentation as a hallmark for apoptosis was monitored by TUNEL as well as agrose gel electrophoresis. Thus, it was proven that conjugation does not affect the therapeutic potential of parent molecule in vitro, while these could work in vivo as prodrugs with enhanced pharmacokinetic profile. Pharmacokinetics of these molecules under in vivo conditions is a further scope of this study.

• Asian-Australasian Journal of Animal Sciences
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• 제25권6호
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• pp.895-902
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• 2012

The Korean native chickens (Woorimotdak$^{TM}$, KNC) and commercial broilers (Ross, CB) show obvious differences in meat flavor after cooking. To understand the contribution of protein and peptide for meat flavor, 2-dimensional (2-D) gel electrophoresis and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was performed. A total of 16 protein spots were differentially expressed in the breast and thigh meat between the two breeds. A total of seven protein spots were represented by different levels between KNC and CB for breast meat. Among them three protein spots (TU39149, TU40162 and TU39598) showed increases in their expressions in KNC while other four protein spots (BU40125, BU40119, BU40029 and BU39904) showed increases in CB. All nine protein spots that were represented by different levels between KNC and CB for thigh meat showed increases in their expression in KNC. Phosphoglucomutase 1 (PGM 1), myosin heavy chain (MyHC), heat shock protein B1 (HSP27), cytochrome c reductase (Enzyme Q), Glyoxylase 1, DNA methyltransferase 3B (DNA MTase 3) were identified as the main protein spots by MALDI-TOF mass spectrometry. These results can provide valuable basic information for understanding the molecular mechanism responsible for breed specific differences in meat quality, especially the meat flavour.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4311-4316
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• 2015

Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates. Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In this investigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cells and DTN's probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTN significantly (p<0.05) suppressed proliferation of HepG2 cells with an $IC_{50}$ value of $12.0{\mu}g/mL$, without affecting human normal liver cells, WRL-68 ($IC_{50}$ > $50{\mu}g/mL$) causing $G_0/G_1$ cell cycle arrest via apoptosis induction. Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughout the treatment period. Western blotting of treated HepG2 cells revealed inhibition of $NF-{\kappa}B$ that triggers the mitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, and down-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed further as an anticancer compound targeting human HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3345-3349
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• 2013

Background: Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. Materials and Methods: We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. Results: We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Conclusions: Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.