• Title/Summary/Keyword: MEK2

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hEPO 형질전환 돼지 후대의 임신기간내 혈액조성 변화

  • 이연근;이현기;이풍연;김성우;김정호;박진기;장원경
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.38-38
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    • 2003
  • 본 연구는 사람 조혈촉진유전자(hEPO)가 도입된 형질전환돼지 Fl 수컷과 암컷간 교배로 F2 생산시, Fl 모돈에 대한 임신기간(약 114일)내 혈액조성(적혈구, 백혈구, Hemoglobin, Hematocrit value, MCV, MCH, MCHC, 혈소판) 변화를 구명하기 위하여 실시하였다. 시험에 이용된 암퇘지는 형질전환 F1 암컷 2마리와 일반돼지 1마리였고 교배와 동시에 임신기간동안(114일) 5일 간격으로 5ml의 혈액을 경정맥(jugular vein)에서 채취하였으며 혈액조성분석은 Celltac MEK 5108K(Nihon Kohden, Japan)를 이용하였는데 얻어진 결과는 다음과 같다. 임신기간중 혈액내 백혈구의 변화는 일반돼지의 경우 13.8($\pm$2.4)$\times$$10^3$/ul 로임신기간내에 일정한 변화양상을 보였으나 형질전환돼지의 경우 29.4($\pm$19.4)$\times$$10^3$와 22.5($\pm$14.1)$\times$$10^3$/ul 으로 일반돼지보다는 높게 나타났으며 임신기간내에 매우 높은 변화 양상을 나타내었다. 또한 적혈구는 일반돼지(7.2$\pm$0.7 $\times$$10^{6}$/ul)에 비하여 형질전환돼지(11.5$\pm$0.5 와 11.9$\pm$0.5 $\times$$10^{6}$ul)에서 매우 높게 나타났으며 변화양상은 일반돼지와 마찬가지로 작게 나타났다. 적혈구와 함께 Hemoglobin(Hb)과 평균혈구용적율(Hematocrit value ;, HCT) 모두 형질전환돼지가 일반돼지보다 높게 나타났으며 변화양상 또한 작게 나타남으로서 사람 조혈촉진유전자(hEPO)가 형질전환된 돼지에서는 지속적으로 발현되어 조혈촉진이 이루어지고 있으며, 조혈촉진에 의해 헤모글로빈 및 적혈구가 생성되어 혈액내 높은 혈구용적율(HCT)을 이루고 있음을 알 수 있었다. 적혈구 평균용적(Mean Corpuscular Volume ; MCV), 평균적혈구혈색소량(Mean Corpuscular Hemoglobin ; MCH), 평균적혈구혈색소농도(Mean Corpuscular Hemoglobin Concentration ; MCHC) 그리고 혈소판(Platelets) 분석결과 형질전환돼지가 일반돼지보다 약간 높은 수치를 나타냈으며 변화양상 또한 유사한 결과를 나타내었다. 이와 같은 시험분석결과를 토대로 사람 조혈촉진유전자(hEPO)가 형질전환된 돼지는 유즙으로 발현할 수 있도록 형질전환 되었음에도 불구하고 헤모글로빈 및 적혈구가 증가함으로서 형질전환돼지 개체의 혈장으로도 사람 조혈촉진인자가 분비하고 있음을 간접적으로 알 수 있었다. 정상돼지 보다 형질전환돼지가 약 30% 높은HCT 수준을 보였으며 이러한 현상은 사람에서는 적혈구증다증(erythrocytosis)으로 분류되고 있다. 이에 대한 고찰은 형질전환돼지 자체의 생리적 문제점(side effects)에 대한 해결과 더불어 기존의 인간질병에 대한 모델동물로서의 이용 가능성을 제시할 수 있는 것으로 사료된다.

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Semaphoring mAb: a New Guide in RIT in Inhibiting the Proliferation of Human Skin Carcinoma

  • Liu, Yuan;Ma, Jing-Yue;Luo, Su-Ju;Sun, Chen-Wei;Shao, Li-Li;Liu, Quan-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.941-945
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    • 2015
  • Semaphoring is a transmembrane receptor which participates in many cytokine-mediated signal pathways that are closely related to the angiogenesis, occurrence and development of carcinoma. The present study was designed to access the effect of mono-antibody (mAb) guided radioimmunotherapy (RIT) on skin carcinoma and investigate the potential mechanisms. Semaphoring mAb was acquired from mice (Balb/c), purified with rProtein A column; purity, concentration and activity were tested with SDS-PAGE and indirect ELISA; specificity and expression on the cutanuem carcinoma line and tissue were tested by Western blotting; morphology change was assessed by microscopy. MTT assay and colony inhibition tests were carried out to test the influence on the proliferation of tumor cells; Western blotting was also carried out for expression of apoptosis-associated (caspase-3, Bax, Bcl-2) and proliferation-related (PI3K, p-Akt, Akt, p-ERK1/2, ERK1/2) proteins and analyse the change in signal pathways (PI3K/Akt and MEK/ERK). The purity of purified semaphorin mAb was 96.5% and the titer is about $1{\times}10^6$. Western blotting showed semaphoring mAb to have specifically binding stripes with semaphoring b1b2 protein, B16F10, and A431 cells at 39KDa, 100KDa and 130KDa, respectively. Positive expression was detected both in cutanuem carcinoma line and tissue and it mostly located in cell membranes. MMT assay revealed dose-relate and time-relate inhibitory effect of semaphorin mAb on A431 and B16F10. Colony inhibition tests also showed dose-relate inhibitory effects. Western blotting demonstrated the expression of apoptosis and proliferation-related protein and changes in signal pathway. In conclusion, we demonstrated that semaphorin is highly expressed on the tumor cell-surfaces and RIT with semaphorin mAb has effect in i nhibiting proliferation and accelerating apoptosis of tumor cells.

User experience of MV2000-MT (SU:M2)® as a Mechanical Ventilator: A Comparative Clinical Study on Usability, Safety, and Medical Staff Satisfaction

  • Jeon, Soeun;Kim, Hae Kyu;Lee, Dowon;Kim, Hyae Jin;Park, Eun Ji
    • Journal of Biomedical Engineering Research
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    • v.40 no.6
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    • pp.260-267
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    • 2019
  • In the present study, we aimed to demonstrate that MV2000-MT(SU:M2)® (MV, MEK-ICS, Paju, Korea), a domestic ventilator, is not inferior in terms of usability, safety, and medical staff satisfaction as compared to Hamilton G5 (G5, Hamilton Medical AG, Rhäzuns, Switzerland). A total of 39 patients who applied MV (group M) or G5 (group H) were included in the study sample. Usability was evaluated by the following factors: the number of alarm errors, replacement requirement of breathing circuit, replacement requirement of a right-angle connector, and ease of ventilator weaning. For safety evaluation, the number of ventilator replacements due to malfunction of the ventilator was evaluated. Items for medical staff satisfaction survey were as follows: the number of MV and G5 uses, hardware, and software assessment. In the usability evaluation, the replacement requirement of the right-angle connector was lower in Group M than in Group H (mean ± standard deviation, Group M: 7.39 ± 6.72, Group H: 14.19 ± 10.24, p = 0.021); however, the evaluations of other parts were not significantly different between the two groups. The number of ventilator replacements due to a malfunction of the ventilator did not differ between two groups. The number of MV and G5 uses was 3.0 [3.0-4.0] and 10.0 [5.0-10.0] (median [interquartile range], p < 0.001). Overall, the mean medical staff satisfaction score of Hamilton G5 was higher than that of MV2000-MT(SU:M2)®. The usability of MV is comparable to that of G5. However, medical staff satisfaction with Hamilton G5 was higher than that with MV2000-MT(SU:M2)®, and this difference could be due to the difference in the number of uses. In order to improve the penetration rate of the domestic mechanical ventilator, it is necessary to find ways to increase familiarity of medical staff with domestic mechanical ventilators.

Panax ginseng and its ginsenosides: potential candidates for the prevention and treatment of chemotherapy-induced side effects

  • Wan, Yan;Wang, Jing;Xu, Jin-feng;Tang, Fei;Chen, Lu;Tan, Yu-zhu;Rao, Chao-long;Ao, Hui;Peng, Cheng
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.617-630
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    • 2021
  • Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of small interfering RNA

  • Yousef, Amany I;El-Masry, Omar S;Abdel Mohsen, Mohamed A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.743-748
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    • 2016
  • Background: $K^-Ras$ activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. Purpose: To evaluate the impact of cellular genetic makeup of two colon cancer cell lines with different genetic backgrounds, HCT-116 ($K^-Ras^-/p53^+$) and Caco-2 ($K^-Ras^+/p53^-$), on response to potential anti-tumour effects of EA. In addition, the influence of $K^-Ras$ silencing in HCT-116 cells was investigated. Materials and Methods: Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of $K^-Ras$ siRNA or incubated with ellagic acid following transfection. Results: The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce $K^-Ras$ protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected. Conclusions: Cellular genetic makeup ($K^-Ras^-/p53^-$) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant $K^-Ras$).

Study of Operation Condition of Biofilter Using Fibril-form Matrix for Odor Gas Removal (악취가스 제거를 위안 섬유상 담체를 적용한 바이오필터 운전조건에 관한 연구)

  • Jeong Gwi-Taek;Lee Gwang-Yeon;Byun Ki-Young;Lee Kyoung-Min;Sunwoo Chang-Shin;Lee Woo-Tae;Park Chan-Young;Kim Do-Hyeong;Cha Jin-Myoung;Jang Young-Seon;Park Don-Hee
    • KSBB Journal
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    • v.20 no.5 s.94
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    • pp.341-344
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    • 2005
  • This research was performed for developing of biological treatment process of odor gas such as MEK, $H_2S$, and toluene, which was generated from the food waste recycling process. To establish the operational conditions of odor gas removal by small-scale biofiltration equipment, it was continuously operated by using toluene as a treating odor object. When the odor treating microorganisms were adhered to fibril form biofilter, high removal efficiency over $93\%$ was obtained by biofilm formation. At 400 ppm of inlet odor gas concentration and 10 sec of retention time, the removal efficiency was $76\%$ and $93\%$ in 1 st stage reactor and End stage reactor, respectively. However, the removal efficiency remained over $97\%$ at the operational conditions above 15 sec of retention time.

Longitudinal Gradients and Seasonal Dynamics of Nutrients, Organic Matter and Conductivity Along the Main Axis of Han-River

  • Kim, Bit-Na;Lee, Sang-Jae;Seo, Jin-Won;An, Kwang-Guk
    • Korean Journal of Ecology and Environment
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    • v.41 no.4
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    • pp.457-465
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    • 2008
  • The purpose of the study was to evaluate spatial and temporal dynamics of nutrients (TN, TP), organic pollution (BOD, COD), and ionic dynamics (electrical conductivity, EC) in the North Han-River, South Han-River, and merged downriver using the dataset of $1998{\sim}2007$, obtained from the MEK (Ministry of Environment, Korea). Accord. ing to interannual nutrient analysis, TN varied slightly in the North Han-River and South Han-River, but decreased in the merged downriver along with BOD. Longitudinal analysis in the water quality showed that BOD, COD, and nutrients had linear decreasing trend along the main axis of headwater-to-downriver. Concentrations of TP and TN in the North Han-River averaged $26.97{\mu}g\;L^{-1}$, $1.696mg\;L^{-1}$, respectively, which were minimum in the three watersheds, followed by South Han-River and then the merged downriver in order. Ratios of TN:TP in the watersheds were >40 in all the sites, indicating that nitrogen may be enough for periphyton or phytoplankton growth and phosphorus may be limited partially. After the North Han-River water is merged with South Han-River, the concentrations of BOD, COD, TN, and TP were similar to the values of $S6{\sim}S7$, respectively or a little bit higher, but increased abruptly in Site M4 (Fig. 3). Thus, mean values of all the water quality parameters in the reach of $M4{\sim}M7$ sites were greater than any other sites. Seasonal data analysis indicated that BOD and EC in the downstream ($S3{\sim}S7$) was greater in the premonsoon than two seasons of the monsoon and postmonsoon, and no significant differences in BOD between the three seasons were found in the upstream ($S1{\sim}S2$). Empirical models of COD in the merged downriver was predicted ($R^2=0.87$, p>0.01, slope = 0.84, intercept = -1.28) well by EC. These results suggest that EC to be measured easily in the field may be used for estimations of nutrients and organic matter pollutions in the merged downriver and these linear models are cost-effective for the monitoring of the parameters.

Dielectric Properties of Semi-IPN Poly(phenylene oxide) Blend/$BaTiO_3$ Composites with Type of Cross-linker (가교체 종류에 따른 Semi-IPN Poly(phenylene oxide) 블렌드와 $BaTiO_3$ 복합재료의 유전특성)

  • Jang, Yong-Kyun;Lee, Ho-Il;Seong, Won-Mo;Park, Sang-Hoon;Yoon, Ho-Gyu
    • Polymer(Korea)
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    • v.33 no.3
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    • pp.224-229
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    • 2009
  • The dielectric properties of semi-IPN poly(phenylene oxide)(PPO) blend/$BaTiO_3$(BT) composites are investigated. The composites are fabricated via melt-mixing of crosslinker and peroxide in precursor PPO composite obtained by precipitating the suspension consisted of PPO, BT and toluene into methylethyl ketone, poor solvent of PPO. The permittivity of the precursor PPO composites shows higher value than that of integral-blended PPO composites by extruder and coincides with the theoretical value calculated by logarithmic rule of mixture. The blend of PPO and cross-linked triallyl isocyanurate is most effective for lowering the permittivity and loss tangent owing to the suppression of the orientation polarization of matrix. In contrast, 4,4'-(1,3-phenylene diisopropylidene) bisaniline, which has amine unit in its structure, increases the permittivity as well as loss tangent of the composite, but it has the ability to densify the matrix resin and the interfacial adhesion between the matrix and filler to improves flexural strength and modulus.

Diagnosis of Sapkyo Stream Watershed Using the Approach of Integrative Star-Plot Area (생태평가모형(Integrative Star-Plot Area)을 이용한 삽교천 수계 진단)

  • Kim, Ja-Hyun;Yeom, Dong-Hyuk;An, Kwang-Guk
    • Korean Journal of Ecology and Environment
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    • v.43 no.3
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    • pp.356-368
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    • 2010
  • In this study, we applied approach of integrative star-plot area (SPA), chemical water quality and habitat conditions (QHEI) to diagnoze ecological conditions at the eight sampling sites of Sapkyo Stream. These outcomes were compared with biological health based on the Index of Biological Integrity (IBI) using fish assemblage. And then, we evaluated the integrative ecological health condition using the star-plot method. This approach based on the sum of all the star-plot areas over these water and habitat characteristics. It was developed to reflect an integrative assessment of the ecological health in the stream. The biological health, based on the model values of IBI indicating "fair-poor" condition according to the criteria. Physical habitat health, based on the QHEI, averaged 123 indicating a "good-fair" condition. Also, chemical health, based on simply BOD values indicating "poor grade" according to the criteria of the Ministry of Environment Korea (MEK). The SPA indicating that 50% of the all was impaired condition and the most sampling sites were downstream sites influenced by the point and non-point sources. Overall our results suggest that the ecological health impact was a combined effect of eutrophication and habitat degradations in the stream. The approach of SPA can be used as a tool to evaluate the integrative health of stream environment and to identify possible causes of observed effects.

Lysophosphatidic Acid Stimulates SKOV-3 Cell Migration through the Generation of Reactive Oxygen Species via the mTORC2/Akt1/NOX Signaling Axis (리소포스타티드산은 SKOV-3 난소암세포의 mTORC2/Akt1/NOX 신호전달 기전을 통해 활성산소를 형성하고 이를 통해 세포의 이동을 촉진)

  • Eun Kyoung Kim;Seo Yeon Jin;Jung Min Ha;Sun Sik Bae
    • Journal of Life Science
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    • v.33 no.2
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    • pp.129-137
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    • 2023
  • Reactive oxygen species (ROS) play an essential role in a variety of cellular physiological phenomena. The present study assessed the signaling axis that mediates the lysophosphatidic acid (LPA)-induced migration of SKOV-3 cells. Insulin-like growth factor-1 (IGF-1) stimulated SKOV-3 cell migration in a time- and dose-dependent manner. Similarly, LPA stimulated SKOV-3 cell migration and the phosphorylation of Akt in a time- and dose-dependent manner. The pharmacological inhibition of LPA receptors (LPA1/LPA3) significantly suppressed LPA-induced SKOV-3 cell migration. However, IGF-1-induced SKOV-3 cell migration was not affected by the inhibition of LPA1 and LPA3. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) or Rho-associated kinase (ROCK) significantly suppressed LPA-induced migration, whereas the inhibition of MAPK kinase (MEK) had no effect. Inhibition of PI3K or ROCK completely suppressed LPA-induced ROS generation, and suppression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) or chelation of ROS by N-acetylcysteine (NAC) blocked LPA-induced SKOV-3 cell migration. LPA-induced ROS generation was suppressed by silencing Rictor or Akt1 but not Raptor or Akt2. Silencing Rictor or Akt1 significantly suppressed LPA-induced SKOV-3 cell migration, whereas silencing Raptor or Akt2 had no effect. Finally, the overexpression of the constitutively active form Akt1 (CA-Akt1) significantly enhanced the LPA-induced migration of SKOV-3 cells. Given these results, we suggest that LPA stimulates SKOV-3 cell migration by ROS generation, which is mediated by the mTORC2/Akt1/NOX signaling axis.