• Kidney Research and Clinical Practice
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• 제36권2호
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• pp.145-157
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• 2017

Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin $E_2$ ($PGE_2$) receptor EP4. Methods: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS ($1{\mu}g/mL$). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. Results: The expression of cyclooxygenase-2, $PGE_2$, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB ($NF-{\kappa}B$) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 $NF-{\kappa}B$ nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and $NF-{\kappa}B$ signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

• 방사선산업학회지
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• 제5권4호
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• pp.337-345
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• 2011

In order to provide an effective preparedness for a nuclear or radiological emergency happening in the domestic or neighborhood countries and to solve the vague fear of the people for the ingestion of radioactive livestock products, the establishment of national guideline level for radionuclides in feed is urgently necessary. This is because it is important to secure the safety and to manage the crisis in the agricultural, fishery and food sector by performing the effective safety control during and after nuclear incident. This study was performed to investigate the report cases of international organizations and foreign countries to set up a domestic control standard for managing radioactive substances that may be contaminated in animal feeds due to the nuclear power plant incident. In addition, an attempt was made to provide a useful reference that can help prepare a domestic control standard, using a coefficient that can consider the transfer into livestock through the intake of radioactive contaminated animal feeds. The standard radioisotopes investigated were confined to radioactive cesium ($^{137+134}Cs$) and iodine ($^{131}I$). Guideline level for the radionuclides was calculated by using the transfer coefficient factor and the maximum daily intake of animal feed provided by IAEA. For example, the maximum daily intake of animal feed was set as $25kg\;d^{-1}$ for dairy cows, $10kg\;d^{-1}$ for beef cattle, $3.0kg\;d^{-1}$ for pigs and $0.15kg\;d^{-1}$ for chickens. The result values for radioactive cesium were calculated as $8,696Bq\;kg^{-1}$, $4,545Bq\;kg^{-1}$, $1,667Bq\;kg^{-1}$ and $2,469Bq\;kg^{-1}$, respectively. The results for radioactive iodine showed the ranges between $741Bq\;kg^{-1}$ and $76,628Bq\;kg^{-1}$. These data can be utilized as a scientific reference for the preparation of a crisis management manual for the emergency control due to nuclear power plant accident in Korea and neighboring country. These results will contribute to establish the safe feed management system at national level as manual for responding the radioactive exposure of agricultural products and animal feeds, which are currently not established.

• 생명과학회지
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• 제29권11호
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• pp.1200-1207
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• 2019

Loganin은 Corni fructus의 주요 iridoid glycoside이며 항염증, 항당뇨 그리고 뇌신경보호 효과 등이 보고되었다. 본 연구에서는 ${\alpha}-MSH$와 IBMX처리된 B16F10세포에서 loganin의 melanogenesis억제효과의 신호전달 경로를 조사하였다. Loganin의 미백 활성을 확인하기 위해 B16F10세포에서 $1{\mu}m$에서 $20{\mu}m$사이의 농도를 처리하여 세포독성 실험을 수행한 결과 최대 $20{\mu}m$농도에서 독성을 나타내지 않았다. 또한 loganin은 ${\alpha}-MSH$와 IBMX처리된 B16F10세포에서 농도-의존적으로 멜라닌 생성을 감소시키는 것을 확인하였다. 또한 loganin의 멜라닌 생성을 억제하는 신호전달 경로를 Western blotting을 실시하여 조사하였다. Western blot결과에 따르면 loganin은 ${\alpha}-MSH$와 IBMX 처리된 B16F10세포에서 증가된 CREB인산화(Ser133)와 MITF 발현 및 tyrosinase의 유전자 발현을 감소시켰고 ERK의 인산화를 증가시켜 melanin 생성을 억제하였다. 결론적으로 loganin은 ${\alpha}-MSH$와 IBMX에 의해 유도된 과도한 멜라닌 합성을 CREB인산화와 MITF 및 tyrosinase의 유전자 발현을 억제하고 ERK의 활성화를 통해 멜라닌 합성을 감소됨을 확인하였다. 따라서 loganin은 과색소 침착과 관련된 피부질환의 보호제로서 활용될 가능성을 가지는 것으로 사료된다.

• 대한임상독성학회지
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• 제17권2호
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• pp.47-57
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• 2019

Purpose: Osmolar gap (OG) has been used for decades to screen for toxic alcohol levels. However, its reliability may vary due to several reasons. We validated the estimated ethanol concentration formula for patients with suspected poisoning and who visited the emergency department. We examined discrepancies in the ethanol level and patient characteristics by applying this formula when it was used to screen for intoxication due to toxic levels of alcohol. Methods: We retrospectively reviewed 153 emergency department cases to determine the measured levels of toxic ethanol ingestion and we calculated alcohol ingestion using a formula based on serum osmolality. Those patients who were subjected to simultaneous measurements of osmolality, sodium, urea, glucose, and ethanol were included in this study. Patients with exposure to other toxic alcohols (methanol, ethylene glycol, or isopropanol) or poisons that affect osmolality were excluded. OG (the measured-calculated serum osmolality) was used to determine the calculated ethanol concentration. Results: Among the 153 included cases, 114 had normal OGs (OG≤14 mOsm/kg), and 39 cases had elevated OGs (OG>14). The mean difference between the measured and estimated (calculated ethanol using OG) ethanol concentration was -9.8 mg/dL. The 95% limits of agreement were -121.1 and 101.5 mg/dL, and the correlation coefficient R was 0.7037. For the four subgroups stratified by comorbidities and poisoning, the correlation coefficients R were 0.692, 0.588, 0.835, and 0.412, respectively, and the mean differences in measurement between the measured and calculated ethanol levels were -2.4 mg/dL, -48.8 mg/dL, 9.4 mg/dL, and -4.7 mg/dL, respectively. The equation plots had wide limits of agreement. Conclusion: We found that there were some discrepancies between OGs and the calculated ethanol concentrations. Addition of a correction factor for unmeasured osmoles to the equation of the calculated serum osmolality would help mitigate these discrepancies.

• 한국구조물진단유지관리공학회 논문집
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• 제25권5호
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• pp.68-75
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• 2021

본 연구에서는 콘크리트의 균열조건에 따른 수분 흡수 현상을 해석적으로 분석하였다. 흡수 시간의 증가에 따라 콘크리트 표면을 통해 흡수되는 수분의 양을 실험적으로 분석한 기존 연구 결과들을 바탕으로 2차원 유한요소해석 모델을 개발하였다. 고려된 균열조건은 균열 폭(0.1 mm, 0.3 mm), 균열 깊이(0 ~ 250 mm), 균열 간격(0 ~ 200 mm)이며 총 30개 모델에 대한 유한요소해석을 수행하였다. 유한요소해석을 수행한 결과, 콘크리트 균열부의 수분 흡수량 증가에 중요한 영향을 미치는 조건은 균열 폭 및 균열 깊이의 변화로 확인되었다. 또한 비균열 조건의 콘크리트에 비해 균열부에서 추가로 흡수되는 물의 양을 정량적으로 분석하기 위하여, 균열부 수분 흡수계수(S_crack) 개념을 도입하고 이를 추정하기 위한 예측 식을 제안하였다. 균열 깊이에 대한 분석 결과, 콘크리트 균열 폭과 관계없이 균열 깊이 150 mm 이하에서는 균열로 인한 수분 흡수가 활발하게 발생할 수 있음을 확인하였다. 따라서 외부에 노출된 철근콘크리트 구조물은 제설제와 같은 수용액 등의 흡수로 인하여 철근 부식이 발생할 수 있음을 고려하면, 실제 시설물의 균열 조건을 파악하기 위해서는 시설물의 점검 및 진단 시에 기존 균열 폭에 대한 조사뿐만 아니라 균열 깊이에 대한 조사도 함께 수행되어야 할 것으로 판단된다.

• 대한구강악안면병리학회지
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• 제42권5호
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• pp.111-118
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• 2018

Nicotine of tobacco component has a controversial impact in the clinical outcome of dental implants. Although numerous nicotine effects on bone healing around implants have been presented, it is rarely reported in vitro study about normal human osteoblast(NHost) from oral and maxillofacial area at the surface of implants. The purpose of the present study was to evaluate the effect of nicotine on the proliferation and differentiation response of NHost to plasmatic and salivary levels of nicotine reported in smokers at the surface of screw-type plasma-sprayed titanium implants. NHosts were seeded on the surface of titanium implants and cultured for 21 days in ${\alpha}-MEM$ supplemented with 10% FBS, 50mg/ml ascorbic acid, 5mM ${\beta}$-glycerophosphate and 100nM dexamethasone. Seeded implants were exposed to various nicotine concentration(0.05-0.5mg/ml) from 1 to 21 days, and characterized for cell morphology, proliferation, differentiation, alkaline phosphatase(ALP) activity and ionized calcium concentration(Cai) of medium. Continuous exposure to higher nicotine concentration(above 0.3mg/ml) induced a dose- and time-dependent vacuolation of the cytoplasm, and a tendency to detach from the implant surface. 0.05mg/ml(lower nicotine concentration) did not cause significant effects in the cell proliferation and ALP activity. 0.1-0.2mg/ml caused evident dose-dependent effects in increased cell proliferation, ALP activity and earlier onset of matrix mineralization at levels up to 0.2mg/ml, while a dose-dependent inhibitory effect at 0.3-0.5mg/ml. Cai concentration of control group was decreased at 14 days. Increased Cai concentration at 0.1-0.2mg/ml, decreased Cai concentration at 0.3mg/ml and no change at 0.5mg/ml during the culture period were seen. It suggested that nicotine concentration could paly an role in modulating NHost activity as a contributing factor associated with proliferation and differentiation of NHost at the surface of implants.

• BMB Reports
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• 제51권12호
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• pp.660-665
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• 2018

Human epidermal growth factor receptor 2 (HER2) inhibitors, such as trastuzumab and lapatinib are used to treat HER2-positive breast and gastric cancers. However, as with other targeted therapies, intrinsic or acquired resistance to HER2 inhibitors presents unresolved therapeutic problems for HER2-positive gastric cancer. The present study describes investigations with AUY922, a heat shock protein 90 (HSP90) inhibitor, in primary lapatinib-resistant (ESO26 and OE33) and lapatinib-sensitive gastric cancer cells (OE19, N87, and SNU-216) harboring HER2 amplification/over-expression. In order to investigate whether AUY922 could overcome intrinsic and acquired resistance to HER2 inhibitors in HER2-positive gastric cancer, we generated lapatinib-resistant gastric cancer cell lines (OE19/LR and N87/LR) by continuous exposure to lapatinib in vitro. We found that activation of HER2 and protein kinase B (AKT) were key factors in inducing intrinsic and acquired lapatinib-resistant gastric cancer cell lines, and that AUY922 effectively suppressed activation of both HER2 and AKT in acquired lapatinib-resistant gastric cancer cell lines. In conclusion, AUY922 showed a synergistic anti-cancer effect with lapatinib and sensitized gastric cancer cells with intrinsic resistance to lapatinib. Dual inhibition of the HSP90 and HER2 signaling pathways could represent a potent therapeutic strategy to treat HER2-positive gastric cancer with intrinsic and acquired resistance to lapatinib.

• 문화기술의 융합
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• 제5권3호
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• pp.345-349
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• 2019

우리나라는 산지가 70% 이상으로 도로, 철도, 산업단지 조성 등의 기반시설 구축시 원지반 일부를 깍아 부지를 형성하는 이른바 깍기 비탈면이 널리 쓰이고 있다. 최근에는 환경 훼손에 대한 규제가 더욱 엄격해져 대규모 깍기 비탈면을 지양하고 최소한의 용지사용으로 목적구조물을 건설하기 위하여 다양한 방법의 공법들이 개발되어 적용되고 있으며, 그 중 활발하게 적용되는 공법이 패널식 옹벽 공법이다. 패널식 옹벽은 지보재 보강을 통한 원지반의 전단강도 증가와 그 지보재 전면에 프리캐스트 옹벽을 체결하여 벽체를 형성시킴으로써 수평토압에 저항하는 공법이다. 지보재는 쏘일네일링, 어스볼트, 그라운드앵커 등이 사용되고 있으며, 그 중 그라운드앵커는 강선에 미리 인장하중을 도입하는 보다 적극적인 보강형태로 전면판인 패널에 큰 집중하중이 작용하게 된다. 이러한 집중하중은 콘크리트 패널에 균열을 발생시키고 옹벽 자체의 내구성을 저해시키는 요인으로 본 연구에서는 이러한 기존 패널식 옹벽의 단점을 보완하기 위하여 패널 정착부에 강관 슬리브 및 보강재를 매입함으로써 균열을 방지하고, 패널 단부에 요철 모양의 전단키를 적용하여 기존 그라우트앵커가 가지는 개별거동에 대한 취약점을 보완하여 안정성을 향상시켰으며, 옹벽 전면 콘크리트 노출 및 정착부 돌출에 의한 경관성 저하문제를 자연석 문양 연출과 정착부를 돌출시키지 않는 단면구성으로 해결하였다. 패널에 사용된 균열방지 슬리브 및 보강재의 효과를 검증하기 위하여 실내시험 및 3차원 수치해석을 수행한 결과, 강관슬리브 및 보강재의 사용으로 패널의 전반적인 강도 증가와 균열억제 효과가 입증되었다.

• Toxicological Research
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• 제35권4호
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• pp.361-369
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• 2019

1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.

• Animal Bioscience
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• 제34권6호
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• pp.993-1005
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• 2021

Objective: Zearalenone (ZEA) has estrogen-like effects. Our previous study has shown that ZEA (0.5 to 1.5 mg/kg) could induce abnormal uterine proliferation through transforming growth factor signaling pathway. To further study the other regulatory networks of uterine hypertrophy caused by ZEA, the potential mechanism of ZEA on porcine endometrial epithelial cells (PECs) was explored by the Illumina Hiseq 2000 sequencing system. Methods: The PECs were treated with ZEA at 0 (ZEA0), 5 (ZEA5), 20 (ZEA20), and 80 (ZEA80) µmol/L for 24 h. The collected cells were subjected to cell cycle, RNA-seq, real-time quantitative polymerase chain reaction, immunofluorescence, and western blot analysis. Results: The proportion of cells in the S and G2 phases decreased (p<0.05), but the proportion of cells in the G1 phase increased (p<0.05) in the ZEA80 treatment. Data analysis revealed that the expression of Wnt pathway-related genes, estrogen-related genes, and mitogen-activated protein kinase pathway-related genes increased (p<0.05), but the expression of genetic stability genes decreased (p<0.05) with increasing ZEA concentrations. The relative mRNA and protein expression of WNT1, β-catenin, glycogen synthase kinase 3β (GSK-3β) were increased (p<0.05) with ZEA increasing, while the relative mRNA and protein expression of cyclin D1 (CCND1) was decreased (p<0.05). Moreover, our immunofluorescence results indicate that β-catenin accumulated around the nucleus from the cell membrane and cytoplasm with increasing ZEA concentrations. Conclusion: In summary, ZEA can activate the Wnt/β-catenin signaling pathway by up-regulating WNT1 and β-catenin expression, to promote the proliferation and development of PECs. At the same time, the up-regulation of GSK-3β and down-regulation of CCND1, as well as the mRNA expression of other pathway related genes indicated that other potential effects of ZEA on the uterine development need further study.