• Title/Summary/Keyword: ${\alpha}$-LA

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Altered Protein Expression in Ovarian and Cervical Cancer Cells by the Treatment of Extracts from Euonymus alatus Sieb, Oldenlandia diffusa (Willd.) Roxburgh, and Orostachys japonicus A. Berger (귀전우, 백화사설초, 와송 추출물을 처치한 난소암과 자궁경부암 세포에서의 단백질 발현 변화)

  • Kim, Kyung-Soon;Yea, Sung-Chul;Yoo, Byong-Chul;Cho, Chong-Kwan;Lee, Yeon-Weol;Yoo, Hwa-Seung
    • The Journal of Internal Korean Medicine
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    • v.32 no.1
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    • pp.33-42
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    • 2011
  • Background : Despite recent advances in cancer management, prognosis of ovarian cancer is poor. Anticancer effects of herbal medicine, such as Euonymus alatus Sieb, Oldenlandia diffusa (Willd.) Roxburgh, and Orostachys japonicus A. Berger, have been reported in treatment of ovarian and cervical cancers, but the systematic approaches to explain their molecular mechanism(s) have not yet been established. Objectives : To establish a basis of understanding for anti-cancer mechanisms of herbal medicine, we profiled protein expression in human ovarian and cervical cancer cells treated with the extracts from Euonymus alatus Sieb, Oldenlandia diffusa (Willd.) Roxburgh and Orostachys japonicus A. Berger. Methods : Human ovarian cancer cell line NIH:OVCAR-3, and human cervical cancer cell line HeLa were employed in the present study. Whole protein was obtained from the cells harvested at 48 hours after the treatment with herbal water-extract, and analyzed by 2DE-based proteomic approach. Results : Various changes of protein expression induced by the herbal treatment were monitored : down-regulation of molecular chaperone (calreticulin variant), glycolytic enzymes (D-3-phosphoglycerate dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase and alpha-enolase), RNA processing molecules (hnRNP A2/B1), and antioxidant protein (peroxiredoxin 1). Conclusions : Repression of glycolysis has been accepted as the mechanism to increase anticancer reagent's effect. Thus, down-regulation of glycolytic enzymes by the herbal extracts suggested a possible synergistic effect of herbs in the presence of platinum-based therapeutics. In further study, as well as the synergistic effect of the herbs, it has to be further validated whether artificial regulation of hnRNP A2/B1 in ovarian cancer cells affects various cancer survival factors, since RNA processing can be interrupted by deranged expression of hnRNP subtypes, and it results in an inhibition of cancer cell growth.

Biological Activities of the Vaporized Liquid of Water-boiled Pine Needle (솔잎 열수 증류액의 생리활성 효과)

  • Lee Hyo-Jin;Cui Cheng-Bi;Choi Hyung-Taek;Kim Soo-Hyun;Ham Young-An;Lee Deuk-Sik;Ham Seung-Shi
    • Food Science and Preservation
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    • v.12 no.2
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    • pp.179-183
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    • 2005
  • This study was performed to determine the antioxidative, antimutagenic, and anticancer effects of vaporized liquid of water-boiled pine needle(VLP) using DPPH free radical donating method, Ames test, and cytotoxicity. VLP showed the highest electron donating activities $(18.4\;{\mu}L)$. The inhibition rate of VLP $(200\;{\mu}L/plate)$ in the Salmonella. typhimurium TA100 strain showed $45.9\%$ inhibition against the mutagenesis induced by MNNG. In addition, the suppression of with same concentration of VLP in the S. typhimurium TA100 strains showed $85.5\%$ inhibition against 4NQO, respectively. The suppressions under the same condition against Trp-P-1 in the TA98 and TA100 strains were $91.0\%$ and $62.1\%$, respectively. The cytotoxic effects of VLP against the cell lines with human lung carcinoma (A549), human hepatocellular carcinoma (HepG2) , human gastric carcinoma (AGS), human breast adenocarcinoma (MCF-7) and human cervical adenocarcinoma (HeLa) were inhibited with increase of the VLP concentration. The treatment of $50\;{\mu}L/well$ VLP showed strong cytotoxicities of $78.7\%,\;90.3\%,\;90.8\%,\;62.3\%$ and $93.7\%$ against A549, HepG2, AGS, MCF-7 and HeLa, respectively.

Ginsengenin derivatives synthesized from 20(R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway

  • Guo, Hong-Yan;Xing, Yue;Sun, Yu-Qiao;Liu, Can;Xu, Qian;Shang, Fan-Fan;Zhang, Run-Hui;Jin, Xue-Jun;Chen, Fener;Lee, Jung Joon;Kang, Dongzhou;Shen, Qing-Kun;Quan, Zhe-Shan
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.738-749
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    • 2022
  • Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1H-NMR, 13C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC50 < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC50 > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

Evaluation of the Oxygen Transfer Parameters (α and F) of a Coarse Bubble Aeration System by Off-gas Column Test (Off-gas Column Test를 이용한 하수처리장 심층포기시스템의 산소전달 매개변수(α와 F)의 산정)

  • Kim, Chul Woong;Lee, Se Ho;Shin, Dong Rok;Lee, Ji Yong;Park, Jae Han;Ahn, Yoon Hee;Ko, Kwang Baik
    • Journal of Korean Society on Water Environment
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    • v.22 no.6
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    • pp.1119-1122
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    • 2006
  • Aeration by using diffusers usually requires approximately 50~90% of the total electricity needed to operate WWTP (WasteWater Treatment Plant)s. Accurate evaluation of the oxygen transfer efficiency for an aeration system, and recommendation of a better alternative may help saving WWTP operational costs. Appropriate techniques and methods to achieve this purpose have not been introduced in Korea. In this study, in-process analysis was performed for a coarse bubble aeration system by the off-gas method to evaluate its applicability in Korea. To accomplish this analysis, an off-gas test, unsteady-state clean water test and steady-state off-gas column test was conducted and comparisons to other aeration systems were made. The ${\alpha}$ and the F estimated from the results of the unsteady-state clean water test and the steady-state off-gas column test were 0.61 and 0.90 respectively in a coarse bubble aeration system. The comparison of P.E tube diffusers laid out single spiral roll and ceramic dome diffusers laid out full floor coverage showed that the oxygen transfer efficiency of the coarse bubble aeration system was less than or similar to other aeration systems. But, airflow rates per unit area were 4~5 times greater than other aeration systems. In regards to the oxygen transfer efficiency for airflow rates per unit area, a retrofit to higher efficiency diffusers was urgently needed. This study showed proved that off-gas methods can apply to evaluate diffuser performances to estimate operating factors and to compare other aeration systems in Korea.

Chemical Characteristics in Fermented Cordycepin-enriched Cordyceps militaris (발효 동충하초의 이화학적 특성)

  • Ahn, Hee-Young;Park, Kyu-Rim;Kim, Yu-Ra;Cha, Jae-Young;Cho, Young-Su
    • Journal of Life Science
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    • v.23 no.8
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    • pp.1032-1040
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    • 2013
  • The comparative effects of fibrinolytic, antioxidative activity and electrophoretical protein patterns with Cordyceps militaris powder (CM) and cordycepin-enriched Cordyceps militaris JLM0636 powder (CCM) and fermented cordycepin-enriched Cordyceps militaris JLM0636 powder by several microscopic organisms were investigated. In addition, nutritional materials such as mineral, protein, and fatty acids were also measured. The protein concentration was higher in CCM than that in CM. The protein concentration in fermented CCM was the highest in CCM treated by Aspergillus kawachii among the various samples. When total protein patterns of CM, CCM, and both fermented CCMs were analyzed by native- and SDS-PAGE, there were slightly varietal differences in electrophoretical protein patterns. Major minerals were K, Ca, Mg, and Zn. Major fatty acids were palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. Fibrinolytic activity was the highest in the fermented CCM by Bs treatment among the various samples. The ${\alpha},{\alpha}^{\prime}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical scavenging activity was slightly stronger in the CCM treated with Aspergillus kawachii among the various samples; however, these samples all exhibited relatively low levels of activity compared with the butylated hydroxytoluene (BHT). These results may provide the basic data necessary to understand the biological activities and chemical characteristics of Cordyceps militaris JLM0636 powder fermented by several microscopic organisms to develop functional foods.

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

  • Botanas, Chrislean Jun;Yoon, Seong Shoon;de la Pena, June Bryan;dela Pena, Irene Joy;Kim, Mikyung;Woo, Taeseon;Seo, Joung-Wook;Jang, Choon-Gon;Park, Kyung-Tae;Lee, Young Hun;Lee, Yong Sup;Kim, Hee Jin;Cheong, Jae Hoon
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.122-129
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    • 2017
  • A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) ${\alpha}-piperidinopropiophenone$ (PIPP) and (2) ${\alpha}-piperidinopentiothiophenone$ (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.

Physicochemical and Microbiological Properties of Ginseng-Whey Beverages (인삼 유청음료의 이화학적 및 미생물학적 특성)

  • 기해진;홍윤호
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.2
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    • pp.208-214
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    • 1993
  • Ginseng-whey beverages were prepared with rennet whey, ginseng, sweetener, honey and Japanese apricot, inoculated with different strains of lactic acid bacteria or unfermented partly. The samples were stored at 4$^{\circ}C$ or 30$\pm$1$0^{\circ}C$ and then physicochemical and microbiological properties were investigated. The yield of whey was 78.8%. The pH-values reduced and acidities increased during the storage period. The contents of solid-substances, ash and lipid in ginseng-whey beverages were 7.90~8.20%, 0.62~0.66% and 0.16%, respectively. The protein contents of ginseng-whey beverages were 0.42~0.56% and the contents were not changed during the storage period. The lactose contents of fermented beverages were higher than those of unfermented beverages. During the storage period (1~5 weeks), the ranges of D(-) - and L(+)- lactic acid contents in fermented ginseng-whey beverages (17.3~156.1 mg/100g, 347.3~1894.2mg/100g) were higher than those of unfermented ginseng-whey beverages (6.2~82.8mg/100g, 7.1~885.5mg/100g). The contents of total saponin in unfermented sample and fermented sample (Lac. casei sub-sp. casei+Str. salivarius sub-sp. thermophilus) were increased during the storage period. But, those of the fermented sample(Lac. acidophilus+Lac. delbrueckii sub-sp. bulgaricus) were reduced. In the electrophoretic results of ginseng-whey beverages, an $\alpha$-lactalbumin and a $\beta$-lactoglobulin bands were shown apparently and there were no changes observed during the storage period. During the storage period (1~3 week) the coliform was not detected and total plate counts and psychrotrophs were increased according to the storage period.

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The Role of Transglutaminase in Double-stranded DNA-Triggered Antiviral Innate Immune Response

  • Yoo, Jae-Wook;Hong, Sun-Woo;Bose, Shambhunath;Kim, Ho-Jun;Kim, Soo-Youl;Kim, So-Youn;Lee, Dong-Ki
    • Bulletin of the Korean Chemical Society
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    • v.32 no.11
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    • pp.3893-3898
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    • 2011
  • Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

Interactions between secreted GRA proteins and host cell proteins across the parasitophorous vacuolar membrane in the parasitism of Toxoplasma gondii

  • Ahn, Hye-Jin;Kim, Sehra;Kim, Hee-Eun;Nam, Ho-Woo
    • Parasites, Hosts and Diseases
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    • v.44 no.4 s.140
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    • pp.303-312
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    • 2006
  • Interactions between GRA proteins of dense granules in Toxoplasma gondii and host cell proteins were analyzed by yeast two-hybrid technique. The cMyc-GRA fusion proteins expressed from pGBKT7 plasmid in Y187 yeast were bound to host cell proteins from pGADT7-Rec-HeLa cDNA library transformed to AH109 yeast by mating method. By the selection procedures, a total of 939 colonies of the SD/-AHLT culture, 348 colonies of the $X-\alpha-gal$ positive and PCR, 157 colonies of the $X-\beta-gal$ assay were chosen for sequencing the cDNA and finally 90 colonies containing ORF were selected to analyze the interactions. GRA proteins interacted with a variety of host cell proteins such as enzymes, structural and functional proteins of organellar proteins of broad spectrum. Several specific bindings of each GRA protein to host proteins were discussed presumptively the role of GRA proteins after secreting into the parasitophorous vacuoles (PV) and the PV membrane in the parasitism of this parasite.

Exercise training and selenium or a combined treatment ameliorates aberrant expression of glucose and lactate metabolic proteins in skeletal muscle in a rodent model of diabetes

  • Kim, Seung-Suk;Koo, Jung-Hoon;Kwon, In-Su;Oh, Yoo-Sung;Lee, Sun-Jang;Kim, Eung-Joon;Kim, Won-Kyu;Lee, Jin;Cho, Joon-Yong
    • Nutrition Research and Practice
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    • v.5 no.3
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    • pp.205-213
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    • 2011
  • Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC- $1{\alpha}$, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, ($5\;{\mu}mol{\cdot}kg$ body $wt^{-1}{\cdot}day^{-1}$) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-la, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.