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The standardized Korean Red Ginseng extract and its ingredient ginsenoside Rg3 inhibit manifestation of breast cancer stem cell-like properties through modulation of self-renewal signaling

  • Oh, Jisun;Yoon, Hyo-Jin;Jang, Jeong-Hoon;Kim, Do-Hee;Surh, Young-Joon
    • Journal of Ginseng Research
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    • v.43 no.3
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    • pp.421-430
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    • 2019
  • Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

AKT1-targeted proapoptotic activity of compound K in human breast cancer cells

  • Choi, Eunju;Kim, Eunji;Kim, Ji Hye;Yoon, Keejung;Kim, Sunggyu;Lee, Jongsung;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.692-698
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    • 2019
  • Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

Differential Function of EDRF in Systemic Arterial and Pulmonary Arterial System of Renal Hypertensive Rats (신성 고혈압쥐의 전신성 동맥계와 폐동맥계에 대한 EDRF 기능의 차이)

  • Lee, Byung-Ho;Shin, Hwa-Sup;Huh, In-Hoe
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.213-223
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    • 1993
  • To investigate the endothelium dependent vascular reactivity of the systemic arterial and the pulmonary arterial system in acute renal hypertensive rats of 2-kidney, 1-ligation type (RHRs), acetylcholine (ACh)-induced vasodilation and depressor effects were evaluated in isolated arteries and in vivo, respectively, in the presence and absence of functional endothelium. ACh $(10^{-5}\;M)$ relaxed the intact thoracic aortas from RHRs and normotensive rats (NRs), but the effect was significantly smaller for those from RHRs (34 and 86%, respectively, p<0.01). ACh-induced vasodilation was completely abolished after removal of endothelial cell or pretreatment with EDRF inhibitors, L-NAME and MB, indicative of its dependence on intact endothelial or EDRF function. ACh also induced vasorelaxation of the intact pulmonary arteries from RHRs and NRs; however, unlike the effects on the thorcic aorta, no significant difference in amplitude was noted between two groups. ACh $(0.1{\sim}10\;{\mu}g/kg,\;i.v.)$ reduced mean systemic arterial pressure in anesthetized RHRs and in NRs to the similar magnitude (% change: 39 and 46% at $10\;{\mu}g/kg$, respectively) and these hypotensive effects were significantly decreased after pretreatment with L-NAME (30 mg/kg, i.v.). Deprssor effects of ACh on mean pulmonary arterial pressure were similar in RHRs and NRs with and without pretreatment of L-NAME. However, in both NRs and RHRs, the depressor effects of ACh on mean pulmonary arterial pressure were significantly reduced compared with those for mean systemic arterial pressure, and the increment of mean pulmonary arterial pressure noted after L-NAME $(0.1{\mu}100\;mg/kg,\;i.v.)$ was significantly smaller than that for mean systemic arterial pressure. These results indicate that in RHRs the endothelial cell function was impaired, at least in part, in systemic arterial system, but not in pulmonary arterial system, and both ACh-evoked and basal release of EDRF was less in the pulmonary arterial system than in systemic arterial system of both NRs and RHRs.

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Development of Embedded Non-Volatile FRAMs for High Performance Smart Cards

  • Lee, Kang-Woon;Jeon, Byung-Gil;Min, Byung-Jun;Oh, Seung-Gyu;Lee, Han-Ju;Lim, Woo-Taek;Cho, Sung-Hee;Jeong, Hong-Sik;Chung, Chil-Hee;Kim, Ki-Nam
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.4 no.4
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    • pp.251-257
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    • 2004
  • Nonvolatile FRAMs with a design rule of 0.18 ${\mu}m$ were developed for the high performance smart card. A 1Mb FRAM was embedded in place of an EEPROM and a 64Kb FRAM was embedded in place of a. SRAM. It was confirmed that the FRAMs performed the roles of the EEPROM and SRAM successfully using the asynchronous write/read operation method and the one time programming (OTP) scheme. The cycle time of the FRAM was 10 MHz, which remarkably improved the write performance of the smart card in comparison with that of the conventional smart card with an EEPROM. Additionally, a simple and smart bit-line reference scheme for the future FRAM device having a 1T1C cell type was proposed.

Andro-profiler: Anti-malware system based on behavior profiling of mobile malware (행위기반의 프로파일링 기법을 활용한 모바일 악성코드 분류 기법)

  • Yun, Jae-Sung;Jang, Jae-Wook;Kim, Huy Kang
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.24 no.1
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    • pp.145-154
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    • 2014
  • In this paper, we propose a novel anti-malware system based on behavior profiling, called Andro-profiler. Andro-profiler consists of mobile devices and a remote server, and is implemented in Droidbox. Our aim is to detect and classify malware using an automatic classifier based on behavior profiling. First, we propose the representative behavior profiling for each malware family represented by system calls coupled with Droidbox system logs. This is done by executing the malicious application on an emulator and extracting integrated system logs. By comparing the behavior profiling of malicious applications with representative behavior profiling for each malware family, we can detect and classify them into malware families. Andro-profiler shows over 99% of classification accuracy in classifying malware families.

Action of atmospheric pressure non-thermal plasma on the biomolecules and bio-organism

  • Attri, Pankaj;Park, Ji Hoon;Kumar, Naresh;Ali, Anser;Kim, In Tae;Lee, Weontae;Choi, Eun Ha
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.66.1-66.1
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    • 2015
  • Plasma medicine is an upcoming research area that has attracted the scientists to explore more deeply the utility of plasma. So, apart from the treating biomaterials and tissues with plasma, we have studied the effect of plasma with different feeding gases on modification of biomolecules. Additionally, we have checked the action of nanosecond pulsed plasma on the biomolecules. We have checked the plasma action on proteins ((Hemoglobin (Hb) Myoglobin (Mb) and lysoenzyme), calf thymus DNA and amino acids. The structural changes or structural modification of proteins and DNA have been studied using circular dichroism (CD), dynamic light scattering (DLS), gel electrophoresis, protein oxidation test, UV-vis spectroscopy and 1D NMR, while Liquid Chromatograph/Capillary Electrophoresis-Mass Spectrometer(LC/CE-MS) based qualitative bio-analysis have been used to study the modification of amino acids. We have also shown the effect of NaCl and ionic liquid on the formation of OH radicals using electron spin resonance and fluorescence techinques.

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A Study on Abdominal Temperature of Male Infertility Patients (남성 불임 환자의 하복부 온도에 관한 임상적 고찰)

  • Lee, Chang-Hoon;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub;Wee, Hyo-Sun
    • Journal of Oriental Medical Thermology
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    • v.4 no.1
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    • pp.23-28
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    • 2005
  • Purpose : To examine the relation between male infertility and cold hypersensitivity on lower abdomen. Methods : From 2004, 4 to 2005, 10, a total 60(infertile male 30, normal male on semen analysis 30) patients who visited the Oriental gynecological department of Conmaul Oriental Medicine hospital was selected, and their medical records were reviewed retrospectively. We compared the temperature of 3 points(CV17, CV12, CV4) of both group by DITI(Dorex, DITI-16UTI and DITI-Spectrum 9000 MB). Results and Conclusion : The general characteristics such as age, weight, height, BMI, amount and frequency of drinking and smoking of both group were not different statistically. The mean ${\Delta}T1$ between upper and lower abdomen in infertile group was higer than in normal group but they were not different statistically. The mean ${\Delta}T2$ between chest and lower abdomen was $0.46{\pm}0.41$ in infertile group, and $0.18{\pm}0.56$ in normal group, and it shows significant difference statistically. There was no significant relationship between sperm motility and ${\Delta}T1$, ${\Delta}T2$ in infertile group. In this study, we suggest that an inclination of cold hypersensitivity of lower abdomen of infertile male, but it is expressed when it is contrasted to chest of the body rather than upper abdomen.

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Review of Domestic Research on Traditional Korean Medicine for Breast Cancer (유방암에 대한 국내 한의학 연구 동향 고찰 - 국내 한의학 논문을 중심으로 -)

  • Han, Ga-jin;Son, Ji-young;Seong, Sin;Kim, Sung-su
    • The Journal of Internal Korean Medicine
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    • v.39 no.1
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    • pp.44-68
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    • 2018
  • Objective: This study aimed to investigate the trend in the research on breast cancer using traditional Korean medicine (TKM) and establish the direction for further study. Methods: Breast cancer studies using Korean medicine were searched using the Oriental Medicine Advanced Searching Integrated System (OASIS). The search term was 'breast' and there was no restriction in year. The searched studies were analyzed according to the type of research. Results: 1. 83 studies were searched. The types and numbers of study were as follows: 42 were in vitro studies, 5 were in vivo studies, 12 were studies for review, and 27 were clinical research including case reports. 2. Various cell lines such as MCF-7, MDA-MB-231, SKBR3, and MCF-10A were used for in vitro studies. The studies reported a decrease in cell viability, induction of apoptosis, and change of expression in cancer-related genes. In vivo studies also reported induction of apoptosis, and anti-proliferative activity of herbal medicine against the cancer cells. 3. Among the clinical research, 8 were cross-sectional studies, 3 were controlled-trial, and 15 were case reports. The baseline characteristics of breast cancer patients were analyzed in the cross-sectional studies. Interventions such as pharmacopuncture, herbal medicine, massage, Qi gong, acupuncture, electroacupuncture and moxibustion were used in clinical research. 4. Research on the review of breast cancer covered various subjects as follows: herbal medicine, acupuncture, pattern identification of breast cancer in traditional Korean medicine, analysis of previous experimental studies, and clinical trials. Conclusion: We have found the applicability of TKM for treatment of breast cancer through this review. It is necessary to conduct further studies, such as well-designed clinical trials based on the results from experimental research.

Synthesis and Importance of Bulky Aromatic Cap of Novel SAHA Analogs for HDAC Inhibition and Anticancer Activity

  • Chun, Pu-Soon;Kim, Won-Hee;Kim, Jung-Su;Kang, Jin-Ah;Lee, Hye-Jin;Park, Ji-Young;Ahn, Mee-Young;Kim, Hyung-Sik;Moon, Hyung-Ryong
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.1891-1896
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    • 2011
  • On the basis of potent HDAC-inhibitory activity and anticancer activity of SAHA, novel SAHA derivatives 3a-d and 7 with a bulky cap such as p-dimethylaminophenyl, 4-phenylaminophenyl, 4-phenyloxyphenyl, 9H-fluorenyl or naphthalenyl ring were synthesized starting from the corresponding aryl amines or naphthalenyl acetic acid using an EDC-mediated amide coupling reaction in the presence of HOBt followed by a nucleophilic addition-elimination reaction with hydroxylamine. Compounds 3b, 3c and 3d showed more potent inhibitory activity on total HDACs (14~27-fold), HDAC1 (8~15-fold), HDAC2 (1.3~25-fold) and HDAC7 (1~3-fold) and more potent anticancer activity (2~22-fold) against MCF-7, MDA-MB-231, MCF-7/Dox, MCF-7/Tam, SK-OV-3, LNCaP and PC3 human cancer cell lines than SAHA.

Recombinant Expression and Characterization of Thermoanaerobacter tengcongensis Thermostable $\alpha$-Glucosidase with Regioselectivity for High-Yield Isomaltooligosaccharides Synthesis

  • Zhou, Cheng;Xue, Yanfen;Zhang, Yueling;Zeng, Yan;Ma, Yanhe
    • Journal of Microbiology and Biotechnology
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    • v.19 no.12
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    • pp.1547-1556
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    • 2009
  • A novel thermostable $\alpha$-glucosidase (TtGluA) from Thermoanaerobacter tengcongensis MB4 was successfully expressed in E. coli and characterized. The TtgluA gene contained 2,253 bp, which encodes 750 amino acids. The native TtGluA was a trimer with monomer molecular mass of 89 kDa shown by SDS-PAGE. The purified recombinant enzyme showed hydrolytic activity on maltooligosaccharides, p-nitrophenyl-$\alpha$-D-glucopyranide, and dextrin with an exotype cleavage manner. TtGluA showed preference for short-chain maltooligosaccharides and the highest specific activity for maltose of 3.26 units/mg. Maximal activity was observed at $60^{\circ}C$ and pH 5.5. The half-life was 2 h at $60^{\circ}C$. The enzyme showed good tolerance to urea and SDS but was inhibited by Tris. When maltose with the concentration over 50 mM was used as substrate, TtGluA was also capable of catalyzing transglycosylation to produce $\alpha$-1,4-linked maltotriose and $\alpha$-1,6-linked isomaltooligosaccharides. More importantly, TtGluA showed exclusive regiospecificity with high yield to produce $\alpha$-1,6-linked isomaltooligosaccharides when the reaction time extended to more than 10 h.