• Title/Summary/Keyword: Dose indicator

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Study on the Inhibitory Effects of Diallyl Sulfide and/or Diallyl Disulfide in the Rat Hepntocarcinogenesis (Diallyl Sulfide와 Diallyl Disulfide에 의한 랫드의 간암발생 억제효과에 관한 연구)

  • 김배환;이영순
    • Biomolecules & Therapeutics
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    • v.3 no.4
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    • pp.279-287
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    • 1995
  • This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.

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Albumin-Bilirubin Score Predicts Tolerability to Adjuvant S-1 Monotherapy after Curative Gastrectomy

  • Miwa, Takashi;Kanda, Mitsuro;Tanaka, Chie;Kobayashi, Daisuke;Hayashi, Masamichi;Yamada, Suguru;Nakayama, Goro;Koike, Masahiko;Kodera, Yasuhiro
    • Journal of Gastric Cancer
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    • v.19 no.2
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    • pp.183-192
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    • 2019
  • Purpose: Due to adverse events, dose reduction or withdrawal of adjuvant chemotherapy is required for some patients. To identify the predictive factors for tolerability to postoperative adjuvant S-1 monotherapy in gastric cancer (GC) patients, we evaluated the predictive values of blood indicators. Materials and Methods: We analyzed 98 patients with pStage II/III GC who underwent postoperative adjuvant S-1 monotherapy. We retrospectively analyzed correlations between 14 parameters obtained from perioperative routine blood tests to assess their influence on the withdrawal of postoperative adjuvant S-1 monotherapy, within 6 months after discontinuation. Results: Postoperative adjuvant chemotherapy was discontinued in 21 patients (21.4%) within 6 months. Univariable analysis revealed that high preoperative albumin-bilirubin (ALBI) scores had the highest odds ratio (OR) for predicting the failure of adjuvant S-1 chemotherapy (OR, 6.47; 95% confidence interval [CI], 2.08-20.1; cutoff value, -2.696). The high ALBI group had a significantly shorter time to failure of postoperative adjuvant S-1monotherapy (hazard ratio, 3.48; 95% CI, 1.69-7.25; P=0.001). Multivariable analysis identified high preoperative ALBI score as an independent prognostic factor for tolerability (OR, 10.3; 95% CI, 2.33-45.8; P=0.002). Conclusions: Preoperative ALBI shows promise as an indicator associated with the tolerability of adjuvant S-1 monotherapy in patients with pStage II/III GC.

KAT8/MOF-Mediated Anti-Cancer Mechanism of Gemcitabine in Human Bladder Cancer Cells

  • Zhu, Huihui;Wang, Yong;Wei, Tao;Zhao, Xiaoming;Li, Fuqiang;Li, Yana;Wang, Fei;Cai, Yong;Jin, Jingji
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.184-194
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    • 2021
  • Histone acetylation is a well-characterized epigenetic modification controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalanced histone acetylation has been observed in many primary cancers. Therefore, efforts have been made to find drugs or small molecules such as HDAC inhibitors that can revert acetylation levels to normal in cancer cells. We observed dose-dependent reduction in the endogenous and exogenous protein expression levels of KAT8 (also known as human MOF), a member of the MYST family of HATs, and its corresponding histone acetylation at H4K5, H4K8, and H4K16 in chemotherapy drug gemcitabine (GEM)-exposed T24 bladder cancer (BLCA) cells. Interestingly, the reduction in MOF and histone H4 acetylation was inversely proportional to GEM-induced γH2AX, an indicator of chemotherapy drug effectiveness. Furthermore, pGL4-MOF-Luc reporter activities were significantly inhibited by GEM, thereby suggesting that GEM utilizes an MOF-mediated anti-BLCA mechanism of action. In the CCK-8, wound healing assays and Transwell® experiments, the additive effects on cell proliferation and migration were observed in the presence of exogenous MOF and GEM. In addition, the promoted cell sensitivity to GEM by exogenous MOF in BLCA cells was confirmed using an Annexin V-FITC/PI assay. Taken together, our results provide the theoretical basis for elucidating the anti-BLCA mechanism of GEM.

Improving the Viability of Freeze-dried Probiotics Using a Lysine-based Rehydration Mixture

  • Arellano, Karina;Park, Haryung;Kim, Bobae;Yeo, Subin;Jo, Hyunjoo;Kim, Jin-Hak;Ji, Yosep;Holzapfel, Wilhelm H.
    • Microbiology and Biotechnology Letters
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    • v.49 no.2
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    • pp.157-166
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    • 2021
  • The probiotic market is constantly continuing to grow, concomitantly with a widening in the range and diversity of probiotic products. Probiotics are defined as live microorganisms that provide a benefit to the host when consumed at a proper dose; the viability of a probiotic is therefore of crucial importance for its efficacy. Many products undergo lyophilization for maintaining their shelf-life. Unfortunately, this procedure may damage the integrity of the cells due to stress conditions during both the freezing and (vacuum-) drying process, thereby impacting their functionality. We propose a lysine-based mixture for rehydration of freeze-dried probiotics for improving their viability during in vitro simulated gastric and duodenum stress conditions. Measurement of the zeta potential served as an indicator of cell integrity and efficacy of this mixture, while functionality was estimated by adhesion to a human enterocyte-like Caco-2 cell-line. The freeze-dried bacteria exhibited a significantly different zeta potential compared to fresh cultures; however, this condition could be restored by rehydration with the lysine mixture. Recovery of the surface charge was found to influence adhesion ability to the Caco-2 cell-line. The optimum lysine concentration of the formulation, designated "Zeta-bio", was found to be 0.03 M for improving the viability of Lactiplantibacillus plantarum Lp-115 by up to 13.86% and a 7-strain mixture (400B) to 41.99% compared to the control rehydrated with distilled water. In addition, the lysine Zeta-bio formulation notably increased the adherence ability of lyophilized Lp-115 to the Caco-2 cell-line after subjected to the in vitro stress conditions of the simulated gastrointestinal tract passage.

Protective Effect of Glycyrrhiza glabra Extract on UV-induced Skin DNA Damage (감초추출물(Glycyrrhiza glabra Extract)의 피부에서의 DNA 손상 방지효과)

  • Shin, Jae Young;Kang, Nae Gyu
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.48 no.1
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    • pp.33-38
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    • 2022
  • Ultraviolet B (UVB) damages DNA residues in skin keratinocytes. In particular, the formation of cyclobutane pyrimidine dimers (CPD), a pyrimidine residue damage in DNA, is considered a representative indicator of skin photoaging. In this study, we confirmed defensive effect of Glycyrrhiza glabra (G. glabra) extract against UVB induced DNA damage. First of all, we confirmed UVB dependent amount of CPD formation in human keratinocyte cell line. UVB induced CPD was decreased by G. glabra extract by dose dependent manner. In addition, it was confirmed that the expression of mRNA of DNA damage recovery factors was increased by G. glabra extract. Consequently, through this study, it was possible to confirm the DNA protection effect of G. glabra extract in skin keratinocytes.

Correlation between clinical changes and viral genome copy number in rock bream infected with red sea bream iridovirus (참돔이리도바이러스 감염 돌돔에서 임상적 변화와 viral genome copy number 간의 상관관계)

  • Dong Jun Shin;Yi Seol Jeong;Min Jae Kim;Guk Hyun Kim;Kwang Il Kim
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.229-238
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    • 2023
  • In this study, the correlation between clinical changes and RSIV genome copy number was investigated to determine the quantitative criteria for the characteristics of RSIV infection. The rock bream (Oplegnathus fasciatus) was intraperitoneally injected with three different doses (1.0×101, 1.0×103 and 1.0×105 viral genome copies/fish) as low, medium, and high doses, respectively. The clinical signs (spleen enlargement, death) observation and real-time PCR were conducted at 5, 10 and 14 days post-injection. During the experiment, spleen index as a quantitative indicator for spleen enlargement was continuously increased in the medium- (up to 2.26) and high-dose (up to 4.99) challenge groups, respectively. Notably, when the spleen index was over 1.5, 2.0, 2.5 and 3.0, a positive correlation was revealed with average viral genome copy numbers of 2.51, 3.37, 4.97 and 5.43×107 viral genome copies/mg, respectively. Moreover, the threshold of spleen index over 1.5 was 1.0×106 viral genome copies/mg, while the thresholds of spleen index over 2.0 and dead was 2.51×107 viral genome copies/mg and the thresholds of spleen index over 2.5 and 3 was 3.98×107 viral genome copies/mg. These findings suggest the possibility of quantitatively analyzing the characteristics and development process of RSIV infection.

Induction of Apoptosis in Human Cancer Cells with Extracts of Taraxacum coreanum, Youngia sonchifolia and Ixeris dentate (흰민들레, 고들빼기, 씀바귀 추출물의 암세포 증식 억제 효과)

  • Shin, Seong-Ah;Lee, Hae-Nim;Choo, Gang-Sik;Kim, Hyeong-Jin;Park, Byung-Kwon;Kim, Byeong-Soo;Jung, Ji-Youn
    • Journal of Food Hygiene and Safety
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    • v.31 no.1
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    • pp.51-58
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    • 2016
  • This research examined the effects of Compositae extract on the inhibition of proliferation and apoptosis in human breast and human gastric cancer cells. Compositae extracts which is used in the experiment are Taraxacum coreanum (TC), Youngia sonchifolia (YS) and Ixeris dentata (ID). The proliferation of SK-BR-3, MDA-MB-231 and AGS cells were investigated by MTT assay. ID and YS extracts inhibited proliferation of SK-BR-3, MDA-MB-231 and AGS cells in a dose-dependent manner, but TC have barely affected. In addition, the most effective extract was ID. To assess the apoptosis of ID extract, the nuclei of human cancer cells were stained with DAPI solution respectively. Chromatin condensation, indicated apoptosis, was increased in a dose-dependent manner. We investigated change of ID extract-induced apoptosis proteins on human cancer cells by western blot analysis. The level of Bcl-2 decreased, whereas the level of Bax, cleaved-PARP increased in dose-dependent manner compared with non-treatment. Also Bax/Bcl-2 ratio, which is used in clinical indicator of apoptosis, was increased at ID extract treatment group compared with non-treatment. Moreover the Bax/Bcl-2 ratio of MDA-MB-231 cell was significantly increased as against SK-BR-3, AGS cells. These results indicated that ID extract have anti-proliferation effect better than YS or TC, and induced apoptosis in human breast cancer MDA-MB-231 cell better than human breast cancer SK-BR-3 cell, human gastric cancer. Even if further research is needed, ID can be developed as a chemopreventive or therapeutic agent of breast cancer.

Defatted Grape Seed Extracts Suppress Adipogenesis in 3T3-L1 Preadipocytes (포도씨 탈지박 추출물 처리가 3T3-L1 Preadipocyte 내 지방 생성에 미치는 영향)

  • Cho, Young-Min;Lee, Seon-Mi;Kim, Young-Hwa;Jeon, Geon-Uk;Sung, Jee-Hy;Jeong, Heon-Sang;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.6
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    • pp.927-931
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    • 2010
  • The objective of this study was to evaluate the effect of defatted grape seed extract (DGSE) on adipocyte differentiation in 3T3-L1 preadipocytes. DGSE at 100 ${\mu}g$/mL significantly suppressed lipid accumulation and glycerol-3-phosphate dehydrogenase activity in hormonally stimulated adipocytes, an indicator of adipocyte differentiation. In order to understand the anti-adipogenic effects of DGSE, the changes in the expression of several adipogenic transcription factors including peroxisome proliferator-activated receptor (PPAR) $\gamma$, CCAAT/enhancer-binding protein (C/EBP) $\alpha$ and $\beta$ were investigated using immunoblotting. DGSE suppressed the expression of PPAR$\gamma$, C/EBP$\alpha$, and C/EBP$\beta$ proteins compared with control adipocytes in a dose-dependent manner. This results indicated that DGSE may alter fat mass by directly affecting adipogensis in maturing preadipocytes and thus may have applications for the treatment of obesity.

Effects of Air Pollition on Rice Plant Growth (大氣汚染이 水稻生育에 미치는 影響)

  • 신응배;박완철;허기호
    • Journal of Korean Society for Atmospheric Environment
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    • v.2 no.1
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    • pp.11-21
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    • 1986
  • The study was performed to investigate the effects of gaseous imission of sulfur dioxide and hydrogen fluoride on the growth of rice plant under stressed field conditions. The plants were cultivated in normal paddy fields where are 88 industrial plants operating with 285 smoke stacks emitting pollutants. There has been a number of reported studies (1, 3, 11, 19, 20) which deal with rice plant damages by air pollution under a simulated exposure experimental condition. Furthermore, these experiments were conducted to examine effects of a single pollutant on the plant. Furthermore, these experiments were conducted to examine effects of a single pollutant on the plant. In korea, however, there is no study reported in literature with respect to the in-situ dose-response relationship between rice pant reduction in yields and air pollution. This study is specifically dealt with multiple effects of sulfur dioxde and hydrogen fluoride on various plant growth indicators such as leaf damage, culm height, weight of grain, panicles per hill, spikelets per panicle and percent fertility.It appears that there is a good correlation between ambient concentrations of sulfur oxides and sulfur contents found in leaves with an average correlation coefficient of 0.868 within a 1% significance level. It is interesting to note that a better multiple correlation was found between percent leaf damage and sulfur and fluoride contentd found in leaf with a significance of 1% level. The yearly correlation coefficient ranges from 0.963 to 0.987 with an average being 0.971. It is, therefore, believed that a percent leaf damage may serve as a single indicator of pollutional damages to rice plant cultivating in fields. Regarding other factors to the diminution of rice plant growth in polluted atmosphere, it appears that a significant correlation to culm length and dry weight of grain with a 1% significance level whereas T/R ratio has a good correlation with lead damage within 5% significance level. An evaluation of data observed has demonstrated that both panicles per hill and percent fertility are significantly affected by air pollutants. As expected, hydrogen fluoride has more effects than sulfur oxide. It is, however, interesting to note that spikelets per panicles has slightly been affected while no indication of effects on 1000-grain-weight has been observed. This may lead to a conclusion that a reduction in yield of rice under polluted field conditions may have more been caused by the diminution of panicles per hill and percent fertility rather than by the diminution of spikelets per panicle and grain weight.

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Studies on Endpoints of Toxicological Evaluation of Heavy Metals in Brachinella kugenumaensis (카드뮴과 구리에 노출된 풍년새우의 생태독성)

  • Park, Ki-Yun;Lee, Dong-Ju;Lee, Chang-Hoon;Won, Du-Hee;Lee, Won-Choel;Kwak, Inn-Sil
    • Environmental Analysis Health and Toxicology
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    • v.24 no.3
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    • pp.241-249
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    • 2009
  • Heavy metal contaminants on the aquatic environment are of interest because they can have severe effects on economy and public health. Recently, the studies for monitoring of heavy metals try to do on aquatic system to assess safety and health of ecosystem by heavy metals. Thus, biological responses were investigated on Korean fairy shrimp Branchinella kugenumaensis exposed to cadmium (Cd) or copper (Cu) for long-periods (30 days). The survival rate decreased significantly (p<0.05) on B. kugenumaensis exposed to Cd and Cu at all concentrations. Especially, the highest decrease was observed at the relatively high concentration of Cd and Cu (p<0.01) and the response by Cd exposure was at dose-dependent. The growth rates were also decreased significantly (p<0.05) on B. kugenumaensis exposed to Cd and Cu for at all concentrations. Then, the reproduction rate, numbering cyst, was decreased significantly (p<0.01) on B. kugenumaensis after Cd or Cu exposures. Long exposure of the relatively high concentration Cd and Cu can have severe effects on the reproduction, while exposures of Cd and Cu can not have effects on sex ratios of B. kugenumaensis. Additionally, asymmetric telson deformity was only observed after Cd exposure. Therefore, these results suggest that B. kugenumaensis is a sensitive bio-indicator of heavy metal exposure and these biological responses of B. kugenumaensis give important information for long-term monitoring on aquatic ecosystem.