• 대한본초학회지
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• 제35권4호
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• pp.9-16
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• 2020

Objective : To identify the effects of the water extract of Liriope platyphylla tuber (Liriopis tuber, LT) on the activation of astocytes, we investigated the regulatory effects of LT extract on H₂O₂-induced oxidative damage in C6 rat astrocytes. Methods : LT extract was extracted with boiling water. C6 cell line were treated with LT extract at 1, 2, and 3 mg/㎖ or without for 30 min and then stimulated with H₂O₂ at 5 ㎛ for 24 hr. The cell viability was measured by MTT assay. The expression of glial fibrillary acidic protein (GFAP), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (pSTAT3), cyclooxygenase (COX-2), Nuclear factor-κB (NF-κB), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), catalase, Akt, phospho-Akt (p-Akt) phosphoinositide 3-kinases (PI3K), and protein kinase C alpha (PKCα) proteins were determined by Western blot, respectively. GFAP expression was also observed with immunocytochemistry under a fluorescence microscope. Results : LT extract induced cell proliferation in H₂O₂-stimulated C6 cells. LT extract significantly inhibited the expression of GFAP, NF-κB and COX-2 and increased the expression of HO-1 and the phosphorylation of STAT3 in H₂O₂-stimulated C6 cells. LT extract also significantly increased the phosphorylation of Akt and decreased the expression of PKCα in a dose-dependent manner in H₂O₂-stimulated C6 cells. Conclusions : LT extract can regulate H₂O₂-induced activation of astrocytes through inhibiting the expression of NF-κB, COX-2 and regulating Akt / HO-1, STAT3 or PKCα signaling pathway.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.492-501
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• 2019

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

• 대한의생명과학회지
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• 제18권2호
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• pp.104-111
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• 2012

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.293-300
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• 2017

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.

• Journal of the Korean Data and Information Science Society
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• 제26권6호
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• pp.1249-1258
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• 2015

젖소의 유생산 형질에 가장 큰 영향을 미치는 유전자들 중 하나로 알려진 DGAT1 유전자의 효과를 국내 젖소 종축의 고밀도 유전체 정보를 이용하여 검증하기 위하여 본 연구를 수행하였다. 국내 젖소 씨수소로 구성된 353두의 고밀도 유전체 정보, 혈통, 추정 육종가 및 신뢰도 정보를 수집하였으며, 단일염기다형성 효과를 추정하기 위한 종속변량으로 가장 정확한 유전체 육종가를 예측할 수 있는 DeRegressed EBV를 산출하여 분석에 이용하였다. BovineSNP50 v2 패널을 이용하여 구명한 고밀도 유전자형 정보 중 유효성검증 과정을 통하여 41,051개 SNP을 선정하였으며, 각 단일 염기다형성의 실제적 유전체 육종가 기여도를 확인하기 위하여 유전체 선발방법 중 하나인 베이즈B (pi=0.99) 방법을 이용하여 SNP 효과를 추정하였다. 1메가 베이스페어의 구간으로 구성된 유전체 전장의 2,516개 윈도우 별 유전분산 설명력을 계산한 결과 상위 1, 3 윈도우가 DGAT1유전자 주변에서 발견되었으며, 이 두 윈도우의 유전분산 설명력은 각각 0.51% 및 0.48%인 것으로 나타났다. DGAT1유전자는 유전체 선발에 상업적으로 이용되는 50k SNP chip에 포함되어있지 않기 때문에 직접적인 유전자의 효과가 명확하게 드러나지는 않지만 DGAT1 유전자에 인접한 단일염기다형성들간의 연관불평형에 의하여 주변 윈도우에서 가장 높은 유전분산 설명력을 보이는 것으로 사료된다.

• 한국작물학회지
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• 제26권2호
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• pp.137-145
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• 1981

1979년 수원 작물시험장 포장에서 도열병에 심하게 이병된 ‘노풍’ 품종의 이병엽(짚)을 수거하여 도열병에 대한 품종 저항성을 유묘 검정하는데 접종원으로 사용하였다. 접종시외 온도 및 Water Stress 의 환경조건을 달리해 줌으로써, 공시품종의 도열병에 대한 반응에 미치는 영향을 조사하였다. 1. 이병엽(짚)을 접종원으로 사용하여 도열병에 대한 품종저항성을 검정하는 방법은 비교적 많은 품종 및 계통들을 일시에 조사할 경우 편리하게 이용될 수 있었다. 2. 고온조건(25^\circ C \sim 35^\circ C)에서보다 저온조건(15^\circ C \sim 28^\circ C)에서 공시품종들의 도열병 발병이 비교적 더 많았다. 그러나 온도에 따른 도열병 반응의 차이는 품종에 따라서 매우 상이하였다. Indica-Japonica hybrid 품종들은 대개 고온에서 발병이 더 급격하고 많았지만, Japonica 품종들은 대개 저온에서 발병이 많은 편이었다. 3. Water stress를 받지 않은 환경조건에서보다 일시적인 Water stress를 받은 환경수건에서, 공시품종들의 도열병 발병이 더 많았다. 품종의 Water stress에 따른 도열병 반응의 차이는 온도에 따른 품종간의 차이(품종과 온도의 interaction)에 비해서 적은 편이었다. 4. 저항성 품종들(Tetep, Zenith, Toride 1, 수원 288호 등)의 도열병에 대한 반응은 환경조건의 영향을 거의 받지 많았지만 중도저항성 품종들(신002, Kanto 51, 흑조, 아끼바레 등)은 환경조건의 영향을 많이 받았다. 이병성 품종들은 어떤 환경조건에서도 발병이 많았다. 5. 접종원으로 사용된 이병엽의 병원성은 Pi-\alpha 품종(‘애지욱’, ‘Ca1oro’) 및 Pi-$textsc{k}$ 품종(‘Kanto 51’), 통일계 신품종에 강한 병원성을 나타내었으나, ‘신002’, ‘Fukunishiki’, ‘진흥’ 등의 품종에 중도저항성 반응을 보였고, ‘농백’에는 병원성이 없었다. 국제판별 품종이나 일본신판별 품종으로써는 정확한 race 유별이 불가능했다. 각 환경수건에 따라 판별품종의 반응이 약관씩 다르게 나타났지만 대체로 blast nursery 성적과는 반응이 비슷하였다. 6. 정도 저항성 및 이병성으로 나타난 ‘Kanto 51’, ‘Yashiromochi’, ‘Ishikari-shiroke’ 등의 품종들에서는 접확후 병반형 및 병반수의 변이가 매우 심하였다. 급성형(이병성, PG형) 병반을 많이 형성하는 품종들(‘애지욱’, ‘Caloro’, ‘Norin 6’ 등)은 고도의 이병성이었고 저항성 품종들은 대개 병반이 없거나 저항성 병반(hypersensitivity 반응, b 혹은 bg 형)을 나타내었다.

• Molecules and Cells
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• 제40권2호
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• pp.123-132
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• 2017

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

• International Journal of Stem Cells
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• 제16권1호
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• pp.52-65
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• 2023

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

• 생명과학회지
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• 제17권10호
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• pp.1447-1451
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• 2007

해양생물 유래 항암활성을 가지는 천연물의 탐색과정에서 해면동물에서 유래된 PTX-2는 p53 결손 암세포에서 세포독성 효과가 높은 것으로 보고된 바 있다. 본 연구에서는 인체 간암세포 모델을 이용하여 PTX-2의 효능을 조사한 결과는 p53 결손 Hep3B 세포에서 p53 정상 HepG2에 비하여 항암활성이 매우 높았으며, 이는 apoptosis 유발과 연관성이 있음을 확인하였다. PTX-2에 의한 Hep3B 세포의 apoptosis 유발은 DFF family의 발현 변화, pro-apoptotic Bax 및 Bcl-xS 단백질의 발현 증가, caspases (-3, -8 및 -9)의 활성화 등이 관여함을 알 수 있었다. PTX-2는 또한 Hep3B 세포에서 AKT 및 ERK1/2의 활성화를 유도하였으며, caspase-3, AKT 및 ERK1/2의 특이적 저해제에 의하여 PTX-2에 의한 세포증식 억제 효능이 유의적으로 감소되었다. 본 연구는 PTX-2에 의한 Hep3B 세포에서의 apoptosis 유도에 AKT 및 ERK1/2 신호 전달 경로가 중요한 역할을 하고 있음을 보여주는 결과이다.

• Parasites, Hosts and Diseases
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• 제26권2호
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• pp.87-94
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• 1988

Kim et at.(1986)은 유구낭미충 낭액을 감작시켜 만든 단세포군 항체를 CNBr활성화 Sepharose 4B에 연결시켜 친화성 크로마토그래피를 실시하고 낭액에서 A-항원을 분리한 바 있다. 이 연구는 그 항원 단백질의 생화학적 성상을 관찰한 것이다. Disc-PAGE에 의해 4.5~10% 폴리아크릴아마이드 젤에서 나타내는 Rf간을 기초로 분자량을 측정한 결과 A 항원의 분자량은 150,000 dalton이었다. A-항원은 SDS-PAGE에서 15,000, 10,000, 7,000 dalton에 해당하는 polypeptide로 분획이 구별되었다. 10% 2-mcrcaptoethanol로 처리하지 않거나 $95^{\circ}C$에서 5분간 처리하지 않은 A-항원의 SDS-PAGE에서는 7,000 dalton의 polypeptide가 분리되지 않았다. A-항원의 등전점(PI)은 pH6.8이었다. 낭액항원의 각 분획에 반응하는 항체를 갖는 환자혈청으로 A-항원을 SDS-PAGE/EITB한 바 환자혈청은 15,000, 10,000, 7,000 dalton에 해당하는 부위에서만 반응하였다. 낭액 단백질의 약70%를 차지하는 A-항원은 면역학적으로 내열성을 가졌으며 포충(hydatid cyst) 낭액 항원중 Oriol et at.(1971)의 "Antigen B"와 생화학적 성상이 비슷한 단백질이었다.