• Title/Summary/Keyword: 선택독성

Search Result 277, Processing Time 0.033 seconds

Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells (라이코펜이 사이토카인에 의해 유도된 베타세포 사멸에 미치는 효과 및 기전 연구)

  • Kim, Kyong;Jang, Se-Eun;Bae, Gong Deuk;Jun, Hee-Sook;Oh, Yoon Sin
    • Journal of Nutrition and Health
    • /
    • v.51 no.6
    • /
    • pp.498-506
    • /
    • 2018
  • Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

Simultaneous determination of 11-nor-Δ9-carboxy-tetrahydrocannabinol and 11-nor-Δ9-carboxy-tetrahydrocannabinol-glucuronide in urine samples by LC-MS/MS and its application to forensic science (LC-MS/MS를 이용한 소변 중 11-nor-Δ9-carboxy-tetrahydrocannabinol 및 11-nor-Δ9-carboxy-tetrahydrocannabinol-glucuronide의 동시 분석 및 법과학적 적용)

  • Park, Meejung;Kim, Sineun
    • Analytical Science and Technology
    • /
    • v.34 no.6
    • /
    • pp.259-266
    • /
    • 2021
  • Cannabis (Marijuana) is one of the most widely used drugs in the world, and its distribution has been controlled in South Korea since 1976. Identification of 11-nor-Δ9-carboxy-tetrahydrocannabinol (THCCOOH) in urine can provide important proof of cannabis use, and it is considered scientific evidence in the forensic field. In this study, we describe a simultaneous quantitative method for identifying THCCOOH and THCCOOH-glucuronide in urine, using simple liquid-liquid extraction (LLE), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). THCCOOH-D3 and THCCOOH-glucuronide-D3 were used as internal standards. Validation results of the matrix effect, as well as recovery, linearity, precision, accuracy, process efficiency, and stability were all satisfactory. No carryover, endogenous or exogenous interferences were observed. The limit of detection (LOD) of THCCOOH and THCCOOH-glucuronide were 0.3 and 0.2 ng/mL, respectively. The developed method was applied to 28 authentic human urine samples that tested positive in immunoassay screening and gas chromatography/mass spectrometry (GC/MS) tests. The ranges of concentrations of THCCOOH and THCCOOH-glucuronide in the samples were less than LOQ~266.90 ng/mL and 6.43~2133.03 ng/mL, respectively. The concentrations of THCCOOH-glucuronide were higher than those of THCCOOH in all samples. This method can be effectively and successfully applied for the confirmation of cannabinoid use in human urine samples in the forensic field.

Computational Chemistry Study on Gas Hydrate Formation Using HFC & HCFC Refrigerants (R-134a, R-227ea, R-236fa, R-141b) (수소불화탄소 및 수소염화불화탄소 냉매(R-134a, R-227ea, R-236fa, R-141b)를 이용한 가스 하이드레이트 형성에 관한 계산화학적 해석)

  • Kim, Kyung Min;An, Hye Young;Lim, Jun-Heok;Lee, Jea-Keun;Won, Yong Sun
    • Korean Chemical Engineering Research
    • /
    • v.55 no.5
    • /
    • pp.704-710
    • /
    • 2017
  • Although the desalination technique using gas hydrate formation is at a development stage compared to the commercially well-established reverse osmosis (RO), it still draws attention because of its simplicity and moderate operational conditions especially when using refrigerants for guest gases. In this study, DFT (density functional theory)-based molecular modeling was employed to explain the energetics of the gas hydrate formation using HFC (hydrofluorocarbon) and HCFC (hydrochlorofluorocarbon) refrigerants. For guest gases, R-134a, R-227ea, R-236fa, and R-141b were selected and three cavity structures ($5^{12}$, $5^{12}6^2$, and $5^{12}6^4$) composed of water molecules were constructed. The geometries of guest gas, cavity, and cavity encapsulating guest gas were optimized by molecular modeling respectively and their located energies were then used for the calculation of binding energy between the guest gas and cavity. Finally, the comparison of binding energies was used to propose which refrigerant is more favorable for the gas hydrate formation energetically. In conclusion, R-236fa was the best choice in terms of thermodynamic spontaneity, less toxicity, and low solubility in water.

Enzymatic Biodiesel Synthesis from Canola Oil in Liquid Carbon Dioxide (액체 이산화탄소 조건에서의 캐놀라 오일 유래의 효소적 바이오디젤 생산)

  • Lee, Myung-Gu;Park, Chul-Hwan;Cho, Jae-Hoon;Lee, Jun-Hak;Lee, Do-Hoon;Kim, Sang-Yong
    • KSBB Journal
    • /
    • v.25 no.4
    • /
    • pp.337-343
    • /
    • 2010
  • It has been well known that organic solvents like t-butanol and n-hexane can protect lipases from the inhibition by short-chain alcohols in the enzymatic transesterification. However, use of the organic solvents should be minimized considering their negative effects on environment and human health. Therefore, use of the greener solvents has been pursued in various are as including the enzymatic biotranformation. In this study, the liquid carbon dioxide ($LCO_2$) was employed as an alternative media for the enzymatic transesterification of canola oil. The conversion in the $LCO_2$ was comparable with those in organic solvents and the supercritical carbon dioxide, and under optimum conditions, the value reached 99.7%. It is expected that this method can provide a new type of biodiesel production process with higher energy efficiency and lower environmental impact.

Anticancer Effect of Citrus Fruit Prepared by Gamma Irradiation of Budsticks (감귤 돌연변이체의 인간 암세포 증식 억제와 자연사멸 증강효과)

  • Kim, Ji Hye;Kim, Min Young
    • Journal of Life Science
    • /
    • v.25 no.9
    • /
    • pp.1051-1058
    • /
    • 2015
  • Citrus mutant fruits were induced by irradiation of citrus budsticks with 120 Gy of cobalt (60CO) gamma irradiation. The citrus mutant inhibited the growth and induced apoptosis in various human cancer cells, including A549, HepG2, HCT116, MCF-7, and Hela. The results of a trypan blue exclusion assay showed that citrus mutant fruits exhibited excellent antiproliferation activity in various human cancer cells and low cytotoxicity in normal 16HBE140- and CHANG cells. In addition, the cell death induced by the citrus mutant fruits was associated with an increased population of cells in sub-G1 phase, and it caused DNA fragmentation in human lung adenocarcinoma A549 and hepatocellular carcinoma HepG2 cells. It also up-regulated the amount of cellular nitric oxide (NO) produced as a result of nitric oxide synthase (NOS) activation and suppressed the inhibitor of apoptosis protein (IAP) family in A549 and HepG2 cells. These findings indicate that the citrus mutant fruits activates the NO-mediated apoptotic pathway in A549 and HepG2 cells. It may merit further investigation as a potential chemotherapeutic and chemopreventive agent for the treatment of various types of cancer cells. The results provide important major new insights into the mechanisms of the anticancer activity of citrus mutant fruits.

2D-QSAR analysis for hERG ion channel inhibitors (hERG 이온채널 저해제에 대한 2D-QSAR 분석)

  • Jeon, Eul-Hye;Park, Ji-Hyeon;Jeong, Jin-Hee;Lee, Sung-Kwang
    • Analytical Science and Technology
    • /
    • v.24 no.6
    • /
    • pp.533-543
    • /
    • 2011
  • The hERG (human ether-a-go-go related gene) ion channel is a main factor for cardiac repolarization, and the blockade of this channel could induce arrhythmia and sudden death. Therefore, potential hERG ion channel inhibitors are now a primary concern in the drug discovery process, and lots of efforts are focused on the minimizing the cardiotoxic side effect. In this study, $IC_{50}$ data of 202 organic compounds in HEK (human embryonic kidney) cell from literatures were used to develop predictive 2D-QSAR model. Multiple linear regression (MLR), Support Vector Machine (SVM), and artificial neural network (ANN) were utilized to predict inhibition concentration of hERG ion channel as machine learning methods. Population based-forward selection method with cross-validation procedure was combined with each learning method and used to select best subset descriptors for each learning algorithm. The best model was ANN model based on 14 descriptors ($R^2_{CV}$=0.617, RMSECV=0.762, MAECV=0.583) and the MLR model could describe the structural characteristics of inhibitors and interaction with hERG receptors. The validation of QSAR models was evaluated through the 5-fold cross-validation and Y-scrambling test.

Study on the Illite Modification for Removal of Radioactive Cesium in Water Environment near Nuclear Facilities (원자력 시설 인근 수계에서 방사성 세슘 제거를 위한 일라이트 개질 연구)

  • Hwang, Jeonghwan;Choung, Sungwook;Shin, Woosik;Han, Weon Shik
    • Economic and Environmental Geology
    • /
    • v.51 no.2
    • /
    • pp.113-120
    • /
    • 2018
  • Radioactive cesium($^{137}Cs$) can be released into the environment through severe nuclear accidents such as the Chernobyl and Fukushima, The $^{137}Cs$ is one of major monitoring radionuclides due to its chemical toxicity, ${\gamma}$ radiation and long half-life($t_{1/2}=30.2yrs$). It has been known well that illite adsorb selectively and strongly the cesium due to frayed edge sites. The quantity of the FES in the illite could be controlled by weathering processes. Therefore, this study was modified illite samples through artificial weathering in the laboratory to increase sorption efficiency for cesium. Abundant interlayer cations(i.e., K, Ca) were eluted within 1 day, while Si and Al were gradually released from the crystal structure. In addition, broad peaks of XRD indicated the occurrence of chemical weathering. The cesium sorption distribution coefficients increased up to approximately 2 times after the weathering. These results suggested that sorption capacity of illite could be enhanced for cesium through artificial weathering under low temperature.

Immunohistochemical Study on the Suppression of Cell mediated immunity in Lymph node of mouse by Cyclosporin A -Based on the change of T lymphocytes, Il-2 receptors, and NK cells- (Cyclosporin A로 유도된 생쥐 림프절의 세포성 면역억제에 관한 면역조직화학적 연구 -T 림프구, IL-2 수용기 및 NK세포의 변화를 중심으로-)

  • Kim, Jin-Taek;Park, In-Sick;Ahn, Sang-Hyun;Choi, Nan-Hee;Kim, Dong-Hoan
    • The Journal of Dong Guk Oriental Medicine
    • /
    • v.6 no.2
    • /
    • pp.99-107
    • /
    • 1998
  • Cyclosporin A(CsA) is a selective immunosuppressive agent that has been credited with improved survival of solid organ allografts. Lymph node of BALB/C mouse administered CsA immunohistochemically observed to understand immunosuppressive effects of CsA on T lymphocytes, IL-2 receptors, and natural killer NK cells in lymph node. CsA orally administered daily for 10days at the dose 45mg/kg/day/. The lymph node were obtained at day 3, 7, and 14 after CsA administration and embedded with paraffin, and then stained by following ABC method that used monoclonal antibody including L3T4(CD4), Ly2(CD8), IL-2R(CD25), and NK-1.1(CD56). There were little changes of reactive degree and number of helper T lymphocytes, cytotoxic T lymphocytes, IL-2 receptors, and NK cells at day 3 after CsA administration, but they began to decrease at day 7. These decrease were greatest at day 14. The helper T lymphocytes. cytotoxic T lymphocytes, IL-2 receptors, and NK cells distributed in paracortex and medullary sinus. These results indicated that the secretion of IL-2 began to decrease at day 7 after CsA administration and subsequently to suppress T lymphocytes and NK cell as components of cell-mediated immunity.

  • PDF

Synthesis of pH-Sensitive Hydrogel Nanoparticles in Supercritical Carbon Dioxide (초임계 이산화탄소를 이용한 pH 감응성 하이드로젤 입자의 합성)

  • Yang, Juseung;Ryu, Won;Lee, Sangmin;Kim, Kyusik;Choi, Moonjae;Lee, Youngmoo;Kim, Bumsang
    • Korean Chemical Engineering Research
    • /
    • v.47 no.4
    • /
    • pp.453-458
    • /
    • 2009
  • Recently, new methods to synthesize and process polymers without toxic organic solvents are needed in order to solve environmental problems. The use of supercritical carbon dioxide as a solvent for the polymer synthesis is attractive since it is non-toxic, non-flammable, naturally abundant, and the product may be easily separated from the solvent. In this study, we developed the method using super critical $CO_2$ to prepare P(MAA-co-EGMA) hydrogel nanoparticles as an intelligent drug delivery carrier. The effects of concentrations of PtBuMA-PEO as a dispersion stabilizer and AIBN as an initiator on the particle synthesis were investigated. When PtBuMA-PEO concentration increased, the particle size decreased. However, there was no significant difference in the particle size according to the AIBN concentration. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-co-EGMA) hydrogel nanoparticles at a pH of around 5, which is the $pK_a$ of PMAA. At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. In release experiments using Rh-B as a model solute, the P(MAA-co-EGMA) hydrogel nanoparticles showed a pH-sensitive release behavior. At low pH(pH 4.0) a small amount of Rh-B was released while at high pH(pH 6.0) a relatively large amount of Rh-B was released from the hydrogels.

Quercetin Potentiates TRAIL-induced Apoptosis in Human Colon KM12 Cells (사람 대장암 KMl2세포에서 quercetin 의한 TRAIL이 유도하는 세포사멸의 증가)

  • Park, Jun-Ik;Kim, Hak-Bong;Kim, Mi-Ju;Lee, Jae-Won;Bae, Jae-Ho;Park, Soo-Jung;Kim, Dong-Wan;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
    • /
    • v.19 no.9
    • /
    • pp.1209-1217
    • /
    • 2009
  • Many cancer cells are sensitive to the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. However, some cancer cells show either partial or complete resistance to TRAIL. Human colon carcinoma KM12 cells have been shown to be insensitive to TRAIL-induced apoptosis. To overcome TRAIL resistance in KM12 cells, we targeted key anti-apoptotic molecules involved in the modulation of TRAIL resistance in the cells, and evaluated the effects of quercetin as a TRAIL sensitizer in the cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in KM12 cells by the down-regulation of c-FLIP and DNA-PKcs/Akt and up-regulation of death receptors (DR4/DR5), which led to the enhancement of TRAIL-mediated activation of caspases and subsequent cleavage of PARP, as well as up-regulation of Bax. These findings suggest that the DNA-PKcs/Akt signaling pathway, as well as c-FLIP, play essential roles in regulating cells in the escape from TRAIL-induced apoptosis. Based on these results, this study provides a potential application of quercetin in combination with TRAIL in the treatment of human colon cancer.