• Title/Summary/Keyword: PI Resistance

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Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway

  • Choi, Eun-Ok;Cho, Eun-Ju;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Hwang, Hye-Jin;Moon, Sung-Kwon;Son, Chang Gue;Kim, Wun-Jae;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.213-221
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    • 2017
  • Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1-/- Mice Mediated by miR-33

  • Tang, Chen-Yi;Man, Xiao-Fei;Guo, Yue;Tang, Hao-Neng;Tang, Jun;Zhou, Ci-La;Tan, Shu-Wen;Wang, Min;Zhou, Hou-De
    • Molecules and Cells
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    • v.40 no.2
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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.

Diverse Mechanisms of Relaxin's Action in the Regulation of Smooth Muscles and Extracellular Matrix of Vasculature and Fibrosis (혈관과 섬유증의 평활근 및 세포외기질 조절에 대한 릴랙신의 다양한 작용기전)

  • Min, Gyesik
    • Journal of Life Science
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    • v.32 no.2
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    • pp.175-188
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    • 2022
  • Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IKCa channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI2. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

Reliability of Cu Interconnect under Compressive Fatigue Deformation Varying Interfacial Adhesion Treatment (유연소자용 기판과의 접착 특성에 따른 구리 배선의 압축 피로 거동 및 신뢰성)

  • Min Ju Kim;Jeong A Heo;Jun Hyeok Hyun;So-Yeon Lee
    • Journal of the Microelectronics and Packaging Society
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    • v.30 no.4
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    • pp.105-111
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    • 2023
  • Electronic devices have been evolved to be mechanically flexible that can be endured repetitive deformation. This evolution emphasizes the importance of long-term reliability in metal wiring connecting electronic components, especially under bending fatigue in compressed environments. This study investigated methods to enhance adhesion between copper (Cu) and polyimide (PI) substrates, aiming to improve the reliability of copper wiring under such conditions. We applied oxygen plasma treatment and introduced a chromium (Cr) adhesion layer to the polyimide substrate. Our findings revealed that these adhesion enhancement methods significantly affect compression fatigue behavior. Notably, the chromium adhesion layer, while showing weaker fatigue characteristics at 1.5% strain, demonstrated superior performance at 2.0% strain with no delamination, outperforming other methods. These results offer valuable insights for improving the reliability of flexible electronic devices, including reducing crack occurrence and enhancing fatigue resistance in their typical usage environments.

cDNA Microarray Analysis of Phytophthora Resistance Related Genes Isolated from Pepper

  • Kim, Hyounjoung;Lee, Mi-Yeon;Kim, Ukjo;Lee, Sanghyeob;Park, Soon-Ho;Her, Nam-Han;Lee, Jing-Ha;Yang, Seung-Gyun;Harn, Chee-Hark
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.67.1-67
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    • 2003
  • Phytophthora blight is a devastating disease of pepper and occurs almost anywhere peppers are grown. Phytophthora blight is caused by Phytophthora capsici and this pathogen can infect every part of the plant by moving inoculum in the soil, by infecting water on surface, by aerial dispersal to sporulating lesions. Management of Phytophthora blight currently relies on cultural practices, crop rotation, and use of selective fungicides. Since these treatments are a short-term management, a classical breeding for development of resistant pepper against the Phytophthora is an alternative. So far some of the resistant cultivars have been on the market, but those are limited regionally and commercially. Therefore, ultimately an elite line resistant against this disease should be developed, if possible, by biotechnology. We have set out a series of work recently in order to develop Phytophthora resistant pepper cultivar. For the first time, the cDNA microarray analysis was peformed using an EST chip that holds around 5000 pepper EST clones to identify genes responsive to Phytophthora infection. Total RNA samples were obtained from Capsicum annuum PI201234 after inoculating P. capsici to roots and soil and exposed to the chip. .Around 900 EST clones were up-regulated and down-regulated depending on the two RNA sample tissues, leaf and root. From those, we have found 55 transcription factors that may be involved in gene regulation of the disease defense mechanism. Further and in detail information will be provided in the poster.

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Development of Small-scale Organic Rankine Cycle System and Study on its Operating Characteristics (소형 유기랭킨사이클 시스템 개발 및 작동특성에 관한 연구)

  • Yun, Eunkoo;Kim, Hyun Dong;Yoon, Sang Youl;Kim, Kyung Chun
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.37 no.10
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    • pp.919-926
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    • 2013
  • Experiments were conducted to determine the operating characteristics of a small-scale ORC (organic Rankine cycle) system for various low-temperature heat sources. A small-scale ORC power generation system adopting R-245fa as a working fluid was designed and manufactured. Hot water was used as the heat source, and the temperature was controlled using 110-kW electric resistance heaters that provided temperatures of up to $150^{\circ}C$. An open-drive oil-free scroll expander directly connected to a synchronous generator was installed in the ORC unit. Experiments were conducted by varying the rotational speed of the expander under the same heat source temperature conditions. The factors that influence the performance of the small-scale ORC system were analyzed and discussed.

Myocardial Function and Metabolic Energetics in Low Flow Ischemia and with $\beta$-Adrenergic Stimulation in Spontaneously Hypertensive Rat Hearts

  • Kang, Young-Hee;Kang, Jung-Sook;Park, Han-Yoon
    • Preventive Nutrition and Food Science
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    • v.6 no.1
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    • pp.43-50
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    • 2001
  • The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.

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Development of SNP marker set for discriminating among Korean rice varieties and imported rice in Korea

  • Park, Seul-Gi;Lee, Hyo-Jeong;Lee, Keon-Mi;Baek, Man-Kee;Park, Hyun-Su;Shin, Woon-Chul;Nam, Jeong-Kwon;Kim, Choon-Song;Kim, Bo-Kyeong;Cho, Young-Chan
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.154-154
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    • 2017
  • In accordance with the opening of the Korean rice market, this study was focused on establishment of database for discriminating the Korean rice varieties and imported brand rices using DNA markers. In this study, the SNP markers were developed using single nucleotide polymorphisms between the reference sequences of japonica and them of 40 brand rices which collected in Australia, China, Thailand, United States and Vietnam. The developed SNP markers were screened to a total of 360 rices including 320 Korean rice varieties and 40 imported brand rices. We selected polymorphic markers among Korean bred rive varieties and imported brand rices. The selected markers were classified into 3 grades. The markers of A grade produced DNA band in 360 rices of 30~40%, B grades produced in 40~60%, and C grades produced bands over 60% rices. First, we tried to set-up the discriminating system using the minimum SNP markers of A grade. Especially, a set of sixteen SNP markers could identify among Korean bred rice varieties and imported brand rices. Additionally, some SNP markers like NSb for Pib gene, JJ80-T for Pi5 and YL155/YL87 for Pita which linked to resistance genes to blast were used to fingerprinting system. These markers were set-up as multiplex set for enhancing the identification efficiency among rice varieties. Finally, the selected SNP markers would be used to the fluidigm assay to construct the database for elaborate discrimination of rice varieties.

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A Study on DC Traction Power Supply System Using PWM Converter (PWM컨버터를 적용한 경전철 전력공급시스템에 관한 연구)

  • Kim, Joorak;Park, Chang-Reung;Park, Kijun;Kim, Joo-Uk
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.29 no.4
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    • pp.250-254
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    • 2016
  • Currently, power conversion system which converts AC to DC Power is applied in domestic urban railway. The diode rectifier is used in most of them. However the diode rectifier can not control the output voltage and can not regenerate power as well. On the other hand, PWM (pulse width modulation) converter using IGBT (isolated gate bipolar transistor) can control output voltage, allowing it to reduce the output voltage drop. Moreover the Bi-directional conduction regenerates power which does not require additional device for power regeneration control. This paper compared the simulation results for the DC power supply system on both the diode rectifier and the PWM converter. Under the same load condition, simulation circuit for each power supply system was constructed with the PSIM (performance simulation and modeling tool) software. The load condition was set according to the resistance value of the currently operating impedance of light rail line, and the line impedance was set according to the distance of each substations. The train was set using a passive resistor. PI (proportional integral) controller was applied to regulate the output voltage. PSIM simulation was conducted to verify that the PWM Converter was more efficient than the diode rectifier in DC Traction power supply system.

Differential Expressions of Apoptosis-related Genes in Lung Cancer Cell Lines Determine the Responsiveness to Ionizing Radiation

  • Lee, Su-Yeon;Choi, Moon-Kyung;Lim, Jung-Min;Wu, Hong-Gyun;Kim, Ju-Han;Park, Woong-Yang
    • Genomics & Informatics
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    • v.6 no.1
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    • pp.36-43
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    • 2008
  • Radiotherapy would be the choice of treatment for human cancers, because of high cost-effectiveness. However, a certain population of patients shows a resistance to radiotherapy and recurrence. In an effort to increase the efficacy of radiotherapy, many efforts were driven to find the genes causing the unresponsiveness to ionizing radiation. In this paper, we compared the gene expression profiles of two lung cancer cell lines, H460 and H1299, which showed differential responses to ionizing radiations. Each cell were irradiated at 2 Gy, and harvested after 0, 2, 4, 8, 12 and 24 hours to examine the expressions. Two-way ANOVA analysis on time-series experiments of two cells could select 2863 genes differentially expressed upon ionizing radiation among 32,321 genes in microarray (p<0.05). We classified these genes into 21 clusters by SOM clustering according to the interaction between cell types and time. Two SOM clusters were enriched with apoptosis-related genes in pathway analysis. One cluster contained higher levels of phosphatidyl inositol 3-phosphate kinase (PI3K) subunits in H1299, radio-resistant cells than H460, radiosensitive cells. TRAIL receptors were expressed in H460 cells while the decoy receptor for TRAIL was expressed in H1299 cells. From these results, we could characterize the differential responsiveness to ionizing radiation according to their differential expressions of apoptosis-related genes, which might be the candidates to increase the power of radiotherapy.