• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.661-670
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• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• 한국산학기술학회논문지
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• 제18권8호
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• pp.285-293
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• 2017

본 연구의 목적은 다면적 인성검사(MMPI-2)의 임상척도와 뇌기능지수 중 자기조절지수와의 관련성을 알아보고자 하는데 있다. 연구는 상담센터에 내원한 20세 이상의 성인 남녀 중 자원한 41명을 대상으로 진행하였다. 자기보고식 검사지인 다면적 인성검사(MMPI-2)를 이용해 검사를 진행했으며, 2채널 뇌파측정기를 이용해 Fp1,과 Fp2에서 뇌파를 측정하였다. 연구결과는 다면적 인성검사(MMPI-2)의 임상척도인 척도2(D)와 자기조절지수 중 휴식 즉, 알파파와 음의 상관을 보였으며, 다면적 인성검사(MMPI-2) 척도3(Hy)은 집중력 즉, 저베타파와 양의 상관성을 보였고, 척도 7(Pt)은 휴식과 음의 상관성을 보였다. 상담현장에서 다면적 인성검사(MMPI-2)와 SQR을 상호 보완하여 사용할 수 있다는데 본 연구의 의의가 있다. 이러한 결과는 세 가지 시사점을 갖는 것으로 해석 가능하다. 첫째, 우울한 정서를 가진 사람들은 타인의 시선과 평가에 민감하여 대인관계를 맺을 시 많은 에너지를 사용하게 되어 휴식이 유지되지 못하기 때문에 피로도가 상승할 수 있다. 둘째, 지나치게 타인의 관심을 얻으려고 하고 쾌활한 모습을 지닌 사람들은 활동력이 높을 것으로 여겨진다. 셋째, 불안과 긴장 상태로 스트레스가 높아진 사람들은 쉽게 지치고 짜증과 불쾌감이 상승할 수 있다는 것을 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.255-261
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• 2014

Essential fatty acid (EFA) is known to be required for the body to function normally and healthily. However, the effect of EFA on glucose uptake in skeletal muscle has not yet been fully investigated. In this study, we examined the effect of two EFAs, linoleic acid (LA) and ${\alpha}$-linolenic acid (ALA), on glucose uptake of C2C12 skeletal muscle cells and investigated the mechanism underlying the stimulatory effect of polyunsaturated EFAs in comparison with monounsaturated oleic acid (OA). In palmitic acid (PA)-induced insulin resistant cells, the co-treatment of EFAs and OA with PA almost restored the PA-induced decrease in the basal and insulin-stimulated 2-NBDG (fluorescent D-glucose analogue) uptake, respectively. Two EFAs and OA significantly protected PA-induced suppression of insulin signaling, respectively, which was confirmed by the increased levels of Akt phosphorylation and serine/threonine kinases ($PKC{\theta}$ and JNK) dephosphorylation in the western blot analysis. In PA-untreated, control cells, the treatment of $500{\mu}M$ EFA significantly stimulated 2-NBDG uptake, whereas OA did not. Phosphorylation of AMP-activated protein kinase (AMPK) and one of its downstream molecules, acetyl-CoA carboxylase (ACC) was markedly induced by EFA, but not OA. In addition, EFA-stimulated 2-NBDG uptake was significantly inhibited by the pre-treatment of a specific AMPK inhibitor, adenine 9-${\beta}$-D-arabinofuranoside (araA). These data suggest that the restoration of suppressed insulin signaling at PA-induced insulin resistant condition and AMPK activation are involved at least in the stimulatory effect of EFA on glucose uptake in C2C12 skeletal muscle cells.

• Nutrition Research and Practice
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• 제1권2호
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• pp.105-112
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• 2007

Ascorbic acid has been reported to extend replicative life span of human embryonic fibroblast (HEF). Since the detailed molecular mechanism of this phenomenon has not been investigated, we attempted to elucidate. Continuous treatment of HEF cells with ascorbic acid at ($200{\mu}M$) from 40 population doubling (PD) increased maximum PD numbers by 18% and lowered $SA-{\beta}-gal$ positive staining, an aging marker, by 2.3 folds, indicating that ascorbic acid extends replicative life span of HEF cells. Ascorbic acid treatment lowered DCFH by about 7 folds and Rho123 by about 70%, suggesting that ascorbic acid dramatically decreased ROS formation. Ascorbic acid also increased aconitase activity, a marker of mitochondrial aging, by 41%, indicating that ascorbic acid treatment restores age-related decline of mitochondrial function. Cell cycle analysis by flow cytometry revealed that ascorbic acid treatment decreased G1 population up to 12%. Further western blot analysis showed that ascorbic acid treatment decreased levels of p53, phospho-p53 at ser 15, and p21, indicating that ascorbic acid relieved senescence-related G1 arrest. Analysis of AP (apurinic/apyrimidinic) sites showed that ascorbic acid treatment decreased AP site formation by 35%. We also tested the effect of hydrogen peroxide treatment, as an additional oxidative stress. Continuous treatment of $20{\mu}M$ of hydrogen peroxide from PD 40 of HEF cells resulted in premature senescence due to increased ROS level, and increased AP sites. Taken together, the results suggest that ascorbic acid extends replicative life span of HEF cells by reducing mitochondrial and DNA damages through lowering cellular ROS.

• 농약과학회지
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• 제9권2호
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• pp.140-145
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• 2005

정량적 구조 활성관계 모델링은 물리적인 성질과 생물학적 활성이 관계 있다는 것을 전제로 한다. 그러나, 퍼센트 활성과 같은 데이터들은 모델링에 많이 활용되지 않았다. 이것의 중요한 이유중의 하나는 이러한 값들이 정량적이 아니고 정성적인 데에 있다. 본 연구에서는 분자모델링에 퍼센트활성 데이터를 활용하기 위하여 데이터 값들을 2개의 계층으로 분류하고 CoMFA(비교분자장)를 판별함수로 활용하였다. 즉, 베타-케토아세트아닐라이드 유도체들의 토마토 역병균에 대한 항균력 시험의 퍼센트 활성 데이터를, 한 계층은 활성이 있는 것, 다른 계층은 활성이 없는 것으로 나누었다. 특히, CoMFA를 활용함으로써 화학적인 이해에 중요한 3차원적인 정보를 얻을 수 있었다. 이 모델은 주어진 데이타를 98%의 정확도로 설명하였으며, LOO 검증을 해본 결과 예측력은 약 69% 정도였다 이 결과는 활성 데이터를 근사적으로 2개의 계급으로 나누고 CoMFA를 활용하는 방식이 구조활성관계를 이해하고 화합물 유도체를 합성하는데 활용될 수 있음을 보여준다.

• IMMUNE NETWORK
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• 제3권3호
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• pp.201-210
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• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.193-202
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• 2011

Objective: We found previously that $interferon$ $regulatory$ factor ($Irf$)-1 is a germinal vesicle (GV)-selective gene that highly expressed in GV as compared to metaphase II oocytes. To our knowledge, the function of $Irf-1$ in oocytes has yet to be examined. The present study was conducted to determine the relationship between retinoic acid (RA) and RA-mediated expression of $Irf-1$ and the mouse oocyte maturation. Methods: Immature cumulus-oocyte-complexes (COCs) were collected from 17-day-old female mice and cultured $in$ $vitro$ for 16 hours in the presence of varying concentrations of RA (0-10 ${\mu}M$). Rate of oocyte maturation and activation was measured. Gene expression was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and cytokine secretion in the medium was measured by Bio-Plex analysis. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results: The rates of oocyte maturation to metaphase II and oocyte activation increased significantly with RA treatment (10 nM-1 ${\mu}M$). With 100 nM RA treatment, lowest level of $Irf-1$ mRNA and cumulus cell's apoptosis was found. Among 23 cytokines measured by Bio-Plex system, the substantial changes in secretion of tumor necrosis factor-${\alpha}$, macrophage inflammatory protein-$1{\beta}$, eotaxin and interleukin-12 (p40) from COCs in response to RA were detected. Conclusion: We concluded that the maturation of oocytes and $Irf-1$ expression are negatively correlated, and RA enhances the developmental competence of mouse immature oocytes $in$ $vitro$ by suppressing apoptosis of cumulus cells. Using a mouse model, results of the present study provide insights into improved culture conditions for $in$ $vitro$ oocyte maturation and relevant cytokine production and secretion in assisted reproductive technology.

• 한국지반공학회지:지반
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• 제14권6호
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• pp.153-166
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• 1998

본 논문은 균질 및 비균질 낙동강 사질토 지반에서 수평 및 경사하중을 받은 강관 말뚝의 수평거동에 대한 모형실험 결과들을 고찰하였다. 비균질 지반은 상부와 하부층의 2개층으로 이루졌다. 본 연구의 목적은 말뚝의 수평거동에 대한 경사하중$(Q_\beta)$, 말뚝 근입길이에 대한 하부지반의 높이비 (H/S), 그리고 상.하부지반의 지반반력계수비$(E_{h1}E_{h2})$의 영향에 관하여 실험적인 연구를 수행하고 이러한 영향들을 정량화 할 수 있는 실험결과를 얻었다. 모형실험 결과들에 의하면, 비균질 지반에서 수평거동은 다른 인자들보다 $E_{h1}E_{h2}$에 더 의존하는 것으로 나타났다. 균질지반에 대한 비균질 지반의 수평변위비$(y_{H/L}/y_{H/L=0}$)와 말뚝 근입길이에 대한 하부지반의 높이비(H/L)의 관계는 지수 함수식으로 회귀분석 되었다. 경사하중을 받는 경우의 휨 모멘트-깊이 관계는 수평하중을 받는 말뚝의 경우와 상이하게 나타났으며, 상대밀도 90%에서는 최대 휨모멘트 발생깊이는 수평하중을 받는 경우보다 약 70% 깊어졌다.

• Tuberculosis and Respiratory Diseases
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• 제55권2호
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• pp.165-174
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• 2003

연구배경 : 천식은 우리나라에서 유병률이 높은 질병 중에 하나이다. 국내에서도 천식 진료 지침이 발표되었지만 일차 진료에서 천식 진료의 실제 양상에 대해서는 연구된 바가 없다. 본 연구를 통해서 일차 진료에서 천식 진료의 실제 양상을 규명하는데 도움을 얻고자 하였다. 방 법 : 2002년 11월 서울 지역 내과 개원의 710명을 대상으로 경증 및 중증 천식 시나리오를 제시하고 천식 진료의 실제 양상에 대해서 설문 조사하였다. 1차에서는 우편조사를, 2차에서는 방문 수거조사를 실시하였으며 325명이 응답하였다 (응답률 46%). 결 과 : 응답자 중 경증 및 중증 천식시나리오에 대하여 경구 테오필린(theophylline)제를 처방하겠다고 답한 경우는 각각 71%, 81%으로 제일 많았다. 그 다음으로 많이 처방하겠다고 답한 것은 거담제(mucolytics), 경구 베타$_2$-항진제 순이었다. 하지만, 흡입 스테로이드를 처방하겠다고 답한 경우는 경증 및 중증 천식에 각각에 대하여 36%, 56%이었다. 진단적 검사로 폐기능 검사를 하겠다고 답한 경우보다 흉부 방사선 검사를 하겠다고 답한 경우가 더 많았다. 결 론 : 서울 지역 내과 개원의들은 천식 환자 치료에 흡입 스테로이드보다 경구 기관지확장제를 더 선호하였다. 일차 진료에서 천식 진료의 실제 양상과 천식 지침 사이의 차이를 줄이는데 노력을 경주해야 하겠다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권1호
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• pp.1-8
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• 2005

This study was aimed to characterize osteogenic potential of rat bone marrow stromal cells (BMSC) isolated with standard flushing method and investigate the plasticity of transdifferentiation between osteoblastic and adipocytic lineage of cultured BMSC. Unlike aspiration method in human, rat bone marrow was extracted by means of irrigation with culture media that elevates the possibility of co-extraction of committed osteoprogenitor, or preosteoblast or other progenitor cells of several types present inside bone marrow. The cultured stromal cells showed high ALP activity which is representative marker of osteoblast without any treatment. Osteogenic inducers such as Dex and BMP-2 were examined for the evaluation of their effect on osteogenic and adipocytic differentiation of stromal cells, because they function as osteoinductive agent in stromal cells, but simultaneously induce adipogenic differentiation. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity or mRNA expression of osteoblast markers such as osteopontin, bone sialoprotein, collagen type I and CbfaI, and in vitro matrix mineralization by von Kossa staining. Oil red staining method was used to detect adipocyte and adipocytic marker, aP2 and $PPAR{\gamma}2$ expression was examined using RT-PCR. It can be supposed that irrigation procedure resulted in high portion of already differentiation-committed osteoprogenitor cell showing elevated ALP activity and strong mineralization only under the supplement of $100{\mu}M$ ascorbic 2-phosphate and 10mM ${\beta}$-glycerophosphate without any treatment of osteogenic inducers such as Dex and BMP-2. Dex and BMP-2 seemed to transdifferentiate osteoprogenitor cells having high ALP activity into adipocytes temporarily, but continuous treatment redifferentiated into osteoblast and developed in vitro matrix mineralization. This property must be considered either in tissue engineering for bone regeneration, or in research of characterization of osteogenic differentiation, with rat BMSC isolated by the standard irrigation method.