• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.139-147
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• 2013

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

• Korean Journal of Materials Research
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• v.29 no.12
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• pp.790-797
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• 2019

To improve photocatalytic performance, CdS nanoparticle deposited TiO₂ nanotubular photocatalysts are synthesized. The TiO₂ nanotube is fabricated by electrochemical anodization at a constant voltage of 60 V, and annealed at 500 for crystallization. The CdS nanoparticles on TiO₂ nanotubes are synthesized by successive ionic layer adsorption and reaction method. The surface characteristics and photocurrent responses of TNT/CdS photocatalysts are investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-Vis spectrometer and LED light source installed potentiostat. The bandgaps of the CdS deposited TiO₂ photocatalysts are gradually narrowed with increasing of amounts of deposited CdS nanoparticles, which enhances visible light absorption ability of composite photocatalysts. Enhanced photoelectrochemical performance is observed in the nanocomposite TiO₂ photocatalyst. However, the maximum photocurrent response and dye degradation efficiency are observed for TNT/CdS30 photocatalyst. The excellent photocatalytic performance of TNT/CdS30 catalyst can be ascribed to the synergistic effects of its better absorption ability of visible light region and efficient charge transport process.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.16-22
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• 2003

BBP (Butyl benzyl phthalate), a widely used plasticizer. can enter the food and environment as consequence of its manufacture, use, and disposal. BBP was found to be developmental and teratogenic or endocrine disrupting chemical in rats. The effects of BBP were investigated in female rats (P) and second generation (F1) via lactations. Sprague-Dawley were given BBP by oral administration at 0, 5, 10, 100, 1000 mg/kg on day 0 to 21 of lactation period. The results were as follows : At maternal findings, there were some significant changes (p<0.05) in relative organ weight, especially liver and uterus weight by BBP administration. In estrous cycle, high treated group was inclined to be proestrus or estrus compared to control group. BBP indues estrous cycle earlier than the control group. At fetal findings, there were some significant changes in relative liver and spleen weight, especially 100, 1000 mg/kg administered groups. The relative weight of ventral prostate was decreased, so it was represent to dose-response tendency. Parent rats (P) were detected monobenzyl phthalate (MBeP) 3.21~5.81 $\mu\textrm{g}$/ml in 100, 1000 mg/kg dose groups. MBeP of male and female fetuses (F1) were detected at the level of 1.21~2.63 $\mu\textrm{g}$/ml of serum. Male serum concentration oi MBeP was higher than the females'. Estrogen receptor $\alpha$ expression by BBP and bisphenol A in uterus and testis of F1 were studied. The ER$\alpha$ expression were increased in F1 male testis and female uterus. F1 male showed distint ER$\alpha$ expression, especially in the combined exposrue. Synergistic ER$\alpha$ expression was found by combined treatment group of BBP and bisphenol A. From the above results, it could be concluded that the effects of dams and F1 by BBP administration during lactation period were estrogenic, and BBP can transfer to F1 via lactation, and make estrogenic at F1 reproductive organs.

• BMB Reports
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• v.38 no.5
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• pp.602-608
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• 2005

As a crucial transcription factor family, heat-shock factors were mainly analyzed and characterized in tomato and Arabidopsis. In this study, we isolated two putative heat shock factors OsHSF6 and OsHSF12 that interact specifically with heat-shock element (HSE) from Oryza sativa L by yeast one-hybrid method. The full-length cDNA of OsHSF6 and OsHSF12 have 1074bp and 920bp open reading frame (ORF), respectively. Analysis of the deduced amino acid sequences revealed that OsHSF6 was a class A heat shock factor (HSF) with all the conserved sequence elements characteristic of heat stress transcription factor, while OsHSF12 was a class B HSF with C-terminal domain (CTD) lacking of AHA motif. Bioinformatic analysis showed that the sequences and structures of two HSFs' DNA binding domain (DBD) had a high similarity with LpHSF24. The results of RT-PCR indicated OsHSF6 gene was expressed immediately after rice plants exposure to heat stress, and the transcription of OsHSF6 gene accumulated primarily in immature seeds, roots and leaves. However, we did not find the transcription of OsHSF12 gene in different organs and growth periods. Our results implied that OsHSF6 might be function as a HSF regulating early expression of stress genes in response to heat shock, and OsHSF12 might be act as a synergistic factor to regulate the expression of down-stream genes.

• Toxicological Research
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• v.16 no.3
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• pp.195-200
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• 2000

Antidotal efficacy of physostigmine plus procyclidine, the combinational prophylactics for organophosphate poisoning, was evaluated in rats and guinea pigs. To assess the dose-response relation-ship in rats, various doses (0.3-6.0mg/kg) of procyclidine in combination with a fixed dose (0.1mg/kg) of physostigmine were pretreated subcutaneously 30 min prior to subcutaneous exposure to nerve-agents. Physostigmine alone exerted protection ratios of 2.44, 1.20, 1.50, 1.50 and 2.20 folds for tabun, sarin, soman, cyclosarin and V-agent, respectively. Interestingly, coadmnistration of procyclidine with physostigmine exhibited remarkable synergistic effects in a dose-dependent manner, leading to 4.00~8.00 folds for tabun, 2.15-8.50 folds for sarin, 1.92~507 folds for so man, 2.15~2.90 folds for cyclosarin, and 2.71~10.50 folds for V-agent. On the contrary, a low effect (l.65 fold) was achieved with the traditional antidotes atropine (17.4 mg/kg) plus 2-pralidoxime (30 mg/kg) treated immediately after soman poisoning. Noteworthy, the combinational prophylactics markedly potentiated the effect of atropine plus 2-pralidoxime to 6.13 and 12.27 folds with 1.0 and 3.0 mg/kg of procyclidine, respectively, against soman poisoning. In guinea pigs, the physostigmine plus procyclidine prophylactics exerted protective effects of 3.00~4.70 folds against soman intoxcation, which were much higher at low doses (0.3~1.0 mg/kg) of procyclidine than those in rats. Taken together, it is proposed that the combinational prophylactics composed oj physostigmine and procyclidine could be a promising antidote regimen for the poisoning with organophosphates possessing diverse properties.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1979-1985
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• 2016

Background: Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. Aim of the study: To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Materials and Methods: Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of $CCL_4$ administration until the end of the study. Animals were killed after 8 weeks of $CCL_4$-induced hepatotoxicity. Results: Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to $CCL_4$-treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the $CCL_4$-intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-${\beta}$. Conclusions: We suggest that addition of JAT as a supportive r egimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.6
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• pp.733-741
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• 2010

Dietary karaya saponin and Rhodobacter capsulatus (R. capsulatus) are known to have hypocholesterolemic actions, as reported in our previous studies. This study examined possible synergistic hypocholesterolemic effects of karaya saponin and R. capsulatus in broilers. A total of 150 broilers were allocated into 10 treatments: control, saponin 25 mg, saponin 50 mg, saponin 75 mg, saponin 25 mg+R. capsulatus 0.2 g, saponin 25 mg+R. capsulatus 0.4 g, saponin 50 mg+R. capsulatus 0.2 g, saponin 50 mg+R. capsulatus 0.4 g, saponin 75 mg+R. capsulatus 0.2 g and saponin 75 mg+R. capsulatus 0.4 g. Feed intake and feed efficiency were improved when karaya saponin and R. capsulatus were synergistically supplemented in the diet. Combinations of karaya saponin, especially supplementation of karaya saponin 50 mg+R. capsulatus 0.4 g were shown to have potential hypolipidemic actions in breast and thigh muscle cholesterol and triglycerides, serum cholesterol, low density lipoprotein-cholesterol and triglycerides, as well as improved high density lipoprotein (HDL)-cholesterol (p<0.05). Compared to the control, almost all the treatments significantly increased serum, liver and fecal concentrations of bile acids (p<0.05). Supplementation of both karaya saponin (75 mg) and saponin 50 mg+R. capsulatus 0.4 g reduced palmitic acid (C16:0) and stearic acid (C18:0) in a similar fashion (p<0.05). The ratios of PUFA:SFA or PUFA+MUFA:SFA in the thigh and breast muscle of broilers were greater in karaya saponin and R. capsulatus supplemented groups than in the control group. Thus, our study concluded that supplementation of karaya saponin synergistically with R. capsulatus in the diet of broilers is an effective way to obtain low-cholesterol, low-triglyceride and high HDL-cholesterol enriched poultry meat with a unique fatty acid balance.

• YAKHAK HOEJI
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• v.47 no.3
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• pp.159-166
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• 2003

In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8％ respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1％ therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95％ in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.197-201
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• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.