• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.104-104
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• 2001

Ras는 세포의 성장과 분화 등 여러 필수적인 세포기능에 없어서는 안될 중요한 역할을 담당하며 Ras가 mutation되면 암 등의 치명적인 결과를 초래한다. Ras 발현은 유방암에서 tumor aggressiveness의 지표로 간주되고 있으며 유방세포의 침습성과 연관이 있다고 알려져 있으므로 ras가 전이과정에 미치는 영향에 관한 연구는 중요한 의미를 갖는다. 본 연구의 선행연구결과, H-ras와 N-ras 모두 transformed phenotype을 나타내지만 H-ras 만이 암전이에 있어서 중요한 침윤성을 유도하는 것을 밝혔다. 이 결과는 MCF10A 세포에서 H-ras와 N-ras에 의한 신호전달경로가 각각 다른 생물학적 전이활성을 나타냄을 시사한다. 세포의 이동성은 침습성에 있어서 결정적인 역할을 하므로, 본 연구에서 H-ras와 N-ras로 형질전환된 MCF10A세포에서 이동성을 시험한 결과, 세포의 이동성이 N-ras가 아닌 H-ras MCF10A 세포에서만 크게 증가된다는 것을 보았다. 이는 침습성을 나타내는 H-ras가 세포의 이동성을 증가시키는데 작용한다는 것을 말한다. H-ras에 의해 유도된 침습성과 이동성에 대한 분자적 기전에 관하여 연구하기 위하여 H-ras MCF10A와 N-ras MCF10A 세포에서 Ras의 downstream effector들, 특히 mitogen-activated protein kinases(MAPKinases)들인 JNK1, ERK, p38의 활성화를 살펴본 결과 p38 MAPKinase가 H-ras MCF10A 세포에서 현저하게 활성화됨을 보았다. p38 MAPKinase 저해제인 SB203580를 처리하던지 dominant negative p38 (DN p38) transfectant로 p38을 불활성화시켰을 때 세포침습성 및 이동성이 저해되는 결과를 얻었다. SB203580 처리한 H-ras MCF10A 세포에서 전이에 관여하는 효소인 MMP-2 분비가 감소되었다. H-ras에 의해 유도된 침습성과 이동성은 DN JNK1 transfectant에서는 변화가 없었으나 DN MEK transfectants에서는 유의성있게 감소되었다. 이상의 결과를 종합하면, MCF10A 세포의 침윤성과 이동성에는 p38 MAPKinase 활성이 중심적인 역할을 하며, JNK 활성은 영향을 미치지 않고, ERK-1/2 활성은 충분하지는 않으나 필요하다는 것을 알 수 있었다.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.4
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• pp.246-254
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• 2022

Current studies have revealed the capacity of mesenchymal stem cells (MSCs) in term of immunomodulatory properties, and this distinct potential is downgraded according to the disease duration of patients-derived MSCs. In order to enhance the immunomodulatory and anti-tumorigenic properties of the rheumatoid arthritis (RA) joints-derived MSCs, we aggregate synovial fluid-derived MSCs from RA joints (RA-hMSCs) into 3D-spheroids by the use of hanging drop culture method. Cells were isolated from synovial fluids of RA joints with longstanding active status over 13 years. For aggregation of RA-hMSCs into 3D-spheroids, cells were plated in hanging drops in 30 μL of advanced DMEM (ADMEM) containing 25,000-30,000 cells/drop and cultured for 48 h. To analyze the comparative immunomodulatory effects of 3D-spheroid and 2D monolayer cultured RA-hMSCs and then cells were cultured in ADMEM supplemented with 20% of synovial fluids of RA patients for 48 h and were evaluated by qRT-PCR for their expression of mRNA levels of inflammatory and anti-inflammatory markers. Cellular aggregation of RA-hMSCs was observed and cells were aggregate into a single sphere. Following treatment of RA patient's synovial fluids into the RA-hMSCs, spheroids formed RA-hMSCs showed significantly (p < 0.05) higher expression of TNFα stimulated gene/protein 6 (TSG-6) than the monolayer cultured RA-hMSCs. Therefore, the 3D-spheroid culture methods of RA-hMSCs were more effective than 2D monolayer cultures in suppressing inflammatory response treated with 20% of RA-synovial fluids by expression of TNFα (TSG-6) according to the immune response and enhanced secretion of inflammatory factors.

• Journal of Life Science
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• v.20 no.2
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• pp.202-207
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• 2010

Ras genes are responsible for up to 30% of human tumor mutations and are composed of three isoforms: H-Ras, K-Ras and N-Ras. The post-translational modification of the CAAX motif of the Ras protein is essential in Ras actions. In the present study, we studied the effects of novel farnesyl transferase inhibitors (FTIs), YH3938 and YH3945, on the actions of oncogenic mutants of H-Ras, K-Ras and N-Ras. YH3938 and YH3945 completely reverted the proliferation and morphology of oncogenic H-Ras-transformed Rat2 cells, but not of oncogenic K-Ras-transformed Rat2 cells. Oncogenic N-Ras-transformed Rat2 cells were slightly affected. Activation of SRE promoters by oncogenic H-Ras and N-Ras, but not by K-Ras, were inhibited by treatment with YH3938 and YH3945. Using bandshift analysis, YH3938 suppressed the processing of oncogenic H-Ras and N-Ras, but not that of oncogenic K-Ras protein. YH3945 only inhibited the processing of H-Ras. From these results, we conclude that YH3938 and YH3945 specifically inhibit actions of oncogenic H-Ras through inhibition of its farnesylation, that YH3938 also inhibits N-Ras activity in a dose-dependent manner, and that these drugs have no effect on oncogenic K-Ras activity.

• Journal of the Korea Society of Computer and Information
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• v.29 no.1
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• pp.1-9
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• 2024

This paper proposes an integration of the ED-H scheduling algorithm, known for optimal real-time scheduling, with the LoRaEnergySim simulator. This integration facilitates the simulation of interactions between real-time scheduling algorithms for tasks with time constraints in Class-A LoRaWAN Class-A devices using a super-capacitor-based energy harvesting system. The time and energy characteristics of LoRaWAN status and state transitions are extracted in a log format, and the task model is structured to suit the time-slot-based ED-H scheduling algorithm. The algorithm is extended to perform tasks while satisfying time constraints based on CPU executions. To evaluate the proposed approach, the ED-H scheduling algorithm is executed on a set of tasks with varying time and energy characteristics and CPU occupancy rates ranging from 10% to 90%, under the same conditions as the LoRaEnergySim simulation results for packet transmission and reception. The experimental results confirmed the applicability of co-simulation by demonstrating that tasks are prioritized based on urgency without depleting the supercapacitor's energy to satisfy time constraints, depending on the scheduling algorithm.

• Journal of the Korean Vacuum Society
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• v.8 no.1
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• pp.51-54
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• 1999

Hydrogenated amorphous silicon (a-Si:H) films are fabricated by Argon radical annealing (ArRA). The deposition rate of continuously deposited a-Si:H film is 1.9 $\AA$/s. As ArRA time are increased to 0.5 and 1 minute, the deposition rate are increased to 2.8 $\AA$/s and 3.3 $\\AA$/s. The deposition rate of a-si:H films with 2 and 3 minutes ArRA time are 3.3 $\AA$/s. As the ArRA time is increased, the optical band gap and the hydrogen contents in the a-Si:H films are increased and slightly decreased. The light-induced degradation of ArRA treated a-Si:H films are less than that of continuously deposited a-Si:H film. The dark conductivity and the conductivity activation energy ($E_a$) of continuously deposited a-Si:H film are decreased to 1/25 in room temperature and increased to 0.09eV By 1 hour light soaking, respectively. The dark conductivity and $E_a$ of ArRA treated a-Si:H film decreased to 1/3 in room temperature and increased to 0.03eV by 1 hour light soaking, respectively. We could improve the stability of a-Si:H films under the light soaking by ArRA technique and discussed the microscopic process of ArRA technique.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.208-216
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• 2002

Background: Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity. Key members of the MMR system include MutS${\alpha}$ (comprised of hMSH2 and hMSH6), which can sense and repair single base mismatches and 8-oxoguanine, and MutS${\beta}$ (comprised of hMSH2 and hMSH3), which repairs longer insertion/deletion loops. Methods: To provide further evidence of DNA damage, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells (PBC) of RA patients using specific primer sequences for 5 key microsatellites. Results: Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis (OA) tissue. Western blot analysis of the same tissues for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Western blot analysis demonstrated constitutive expression of hMSH2, 3 and 6 in RA and OA FLS. When FLS were cultured with SNAP, the RA synovial pattern of MMR expression was reproduced (high hMSH3, low hMSH6). Conclusion: Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.628-632
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• 2005

The aim of this study was to investigate the cytotoxic effect and its mechanism on Radix Aconiti(RA) extract in lung cancer cell lines. RA extract treatment decreased the cell viability in a dose-dependent fashions in lung cancer cells including A549, H460, H23 and H157 cells. Many investigators reported that A549 and H460 cells expressed wild-type p53, but H23 and H157 cells preserved mutated p53. After treatment with RA extract in A549 and H460 cells, we measured the expression of p53 protein levels using Western blot. analysis. In both cells treated with RA extracts, p53 protein expressions were increased in a dose-dependent manner. In our experiments, RA extracts also have cytotoxic effects in H23 and H157, which have mutated p53. Treatment with RA extract decreased bcl-2 protein expressions in both cells. These results suggest that RA extracts have cytotoxic effects via p53 expression increase and bcl-2 inhibitable pathways in A549, H460 cells and H23, H157 cells, respectively.

• The Journal of Traditional Korean Medicine
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• v.15 no.1
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• pp.106-112
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• 2006

The aim of this study was to investigate the cytotoxic effect and its mechanism on Radix Aconiti(RA) extract in lung cancer cell lines. RA extract treatment decreased the cell viability in a dose-dependent fashions in lung cancer cells including A549, H460, H23 and H157 cells. Many investigators reported that A549 and H460 cells expressed wild-type p53, but H23 and H157 cells preserved mutated p53. After treatment with RA extract in A549 and H460 cells, we measured the expression of p53 protein levels using Western blot. analysis. In both cells treated with RA extracts, p53 protein expressions were increased in a dose-dependent manner. In our experiments, RA extracts also have cytotoxic effects in H23 and H157, which have mutated p53. Treatment with RA extract decreased bcl-2 protein expressions in both cells. These results suggest that RA extracts have cytotoxic effects via p53 expression increase and bcl-2 inhibitable pathways in A549, H460 cells and H23, H157 cells, respectively.

• Journal of the Korean Recycled Construction Resources Institute
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• v.1 no.1
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• pp.1-7
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• 2013

This study was on leaching test(KSLT, TCLP) of the aggregate for the products(RA-1) and for the site(RA-2) to evaluate the characteristics of contaminants and the possibility of contamination arising from the aggregate. On the basis pH, conductivity and heavy metal contents in the aggregate, RA-1 indicated higher than RA-2. As a result of the leaching test, the pollutants were eluted from the aggregate increased as the particle size of the aggregate was smaller. The pH in the aggregate had a strong alkali by a pH value of 9.0~12.3, the conductivity was higher in less than 10mm RA-1 due to the leaching of dissolved inorganic ions. The heavy metals satisfied the leaching standards of KSLT and less 10% was eluted from the aggregate. As a result of evaluating water pollution possibility of the aggregate, the pH displayed in items with a very high possibility of contamination, conductivity and turbidity did in item with a low possibility of contamination and on the other hand the heavy metals did in item with a very low possibility of contamination.

• Quality Improvement in Health Care
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• v.9 no.2
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• pp.230-240
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• 2002

Background : The purpose of this study was to develop, implement and evaluate the pharmacist intervention program designed to identify and correctly adjust the dosage of $H_2$-receptor antagonists ($H_2RA$) in renally impaired patients and promote timely conversion of $H_2RA$ from IV to PO therapy. Methods : The study population consisted of renally impaired patients who received $H_2RA$ therapy from April 9 to May 8, 2001 at Hallym Medical Center. Each morning a specifically developed software program identified patients with serum creatinine (Scr) greater than 1.2 mg/dl or age greater than 65 years. The pharmacist, then screened the pharmacy profiles of the identified patients to determine if the patient was on $H_2RA$. For these patients on $H_2RA$ with renal impairement the creatinine clearance (CrCl) was calculated using Cockroft & Gault equation. The pharmacist determined the proper dosage for each identified patients based on the calculated CrCl and the oral dosage that would be appropriate for whom IV therapy was no longer indicated. Result : A total of 149 cases (101 patients) were monitored during the study period. The dosage was inappropriately prescribed for renal function in 61 of 149 cases (41%), and of those, pharmacist made recommendations for 58 cases of which 33 cases (57%) were accepted by the physicians. The administration route of H2RA was inappropriately used as IV in 22 of 53 cases (42%), and pharmacist made recommendations for those 22 cases of which 15 cases (68%) were accepted. Conclusion : Monitoring of patients with renal dysfunction by a pharmacist improved the dosing of $H_2RA$ and a dosing program of patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.