• Title/Summary/Keyword: Signal transducer

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Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis

  • Shibuya, Masabumi
    • BMB Reports
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    • v.39 no.5
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    • pp.469-478
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    • 2006
  • Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis, binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). These receptors regulate physiological as well as pathological angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the major signals for angiogenesis. However, unlike other representative tyrosine kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase-$C{\gamma}$-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2 is a direct signal transducer for pathological angiogenesis including cancer and diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical targets for the suppression of these diseases. VEGFR1 plays dual role, a negative role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not only in endothelial cells but also in macrophage-lineage cells, and promotes tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1 was found to be present at abnormally high levels in the serum of preeclampsia patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is also an important target in the treatment of human diseases. Recently, the VEGFR2-specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly, the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic response in mice with minor side effects such as inflammation compared with VEGF-A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

  • Li, Donghua;Yan, Yurong;Yu, Lingzhi;Duan, Yong
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.489-494
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    • 2016
  • Neuropathic pain (NPP) is the main culprit among chronic pains affecting the normal life of patients. Procaine is a frequently-used local anesthesia with multiple efficacies in various diseases. However, its role in modulating NPP has not been reported yet. This study aims at uncovering the role of procaine in NPP. Rats were pretreated with procaine by intrathecal injection. Then NPP rat model was induced by sciatic nerve chronic compression injury (CCI) and behavior tests were performed to analyze the pain behaviors upon mechanical, thermal and cold stimulations. Spinal expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR and western blot. JAK2 was also overexpressed in procaine treated model rats for behavior tests. Results showed that procaine pretreatment improved the pain behaviors of model rats upon mechanical, thermal and cold stimulations, with the best effect occurring on the $15^{th}$ day post model construction (p<0.05). Procaine also inhibited JAK2 and STAT3 expression in both mRNA (p<0.05) and protein levels. Overexpression of JAK2 increased STAT3 level and reversed the improvement effects of procaine in pain behaviors (p<0.01). These findings indicate that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

  • Kim, Young Eun;Choi, Hyung Chul;Lee, In-Chul;Yuk, Dong Yeon;Lee, Hyosung;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.572-580
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    • 2016
  • 3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

Paw Edema was Reduced in Carrageenan Induced Acute Inflammation in Stat4 Deficient Mice

  • Zheng, Long-Tai;Baik, Haing-Woon;Lee, Seong-Kyu;Cho, Jeong-Je;Park, Cheung-Seog;Hong, Mee-Suk;Chung, Joo-Ho;Yim, Sung-Vin
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.257-261
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    • 2006
  • Signal transducer and activator of transcription 4 (STAT4) is one of the important mediators in generating inflammation and immune responses. To address the role of Stat4 in carrageenan induced acute inflammation, we performed paw edema measurement and 7.4 k mouse cDNA microarray analysis in carrageenan induced acute inflammation in Stat4 knockout (-/-) mice. Male BALB/c (n=8) and Stat4 -/- (n=5) were used and paw edema was induced with injection of $30\;{\mu}L$ of 1% carrageenan into plantar surface of right hind paw. Next, we isolated the mRNA in mouse whole brain and analyzed cDNA microarray profiles for the changes of the brain expression in Stat4 -/- mice. Interestingly, the increase in paw volume of Stat4 -/- mice was reduced by about 30% as compared to that of wild type. The cDNA microarray analysis revealed the altered expressions of several cytokines (Tnf, Il6, and Il4) and pain-associated proteins (Ptgs2, Gabra6, and Gabbr1) in Stat4 -/- mice. Our results suggest that Stat4 may be related to the inhibitory responses on carrageenan induced acute inflammation.

Development and Application of an Ultrasonic Gas Flowmeter (초음파 가스 유량계 개발과 활용)

  • Hwang, Won-Ho;Park, Sang-Gug;Jeong, Hee-Don;Jhang, Kyung-Young
    • Journal of the Korean Society for Nondestructive Testing
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    • v.22 no.3
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    • pp.246-253
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    • 2002
  • This paper describes the development and the field application of the ultrasonic gas flowmeter for accurate measurement of the volumetric flow rate of gases in a harsh environmental conditions in iron & steel making company. This ultrasonic flowmeter is especially suited for measuring LDG, COG, BFG gases produced in iron & steel making process. This is a transit time type ultrasonic flowmeter. We have developed the transmitting & receiving algorithm of ultrasonic wave and the ultrasonic signal processing algorithm to develope a transit time type ultrasonic flowmeter. We have evaluated the performance of ultrasonic flowmeter by the calibration system with Venturi type standard flowmeter. We has confirmed its reliability by extensive field tests for a year in POSCO, iron & steel making company. Now we have developed the commercial model of ultrasonic flowmeter and applied to the POSCO gas line.

Design of SONAR Array for Detection of Bottoming Cylindrical Objects (착저 원통형 물체 탐지를 위한 소나 어레이 설계)

  • Kim, Sunho;Jung, Jangwon;On, Baeksan;Im, Sungbin;Seo, Iksoo
    • Journal of the Institute of Electronics and Information Engineers
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    • v.54 no.3
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    • pp.15-21
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    • 2017
  • In the active SONAR system, various studies have been carried out to enhance the resolution of a received signal. In order to obtain higher resolution for detecting a bottoming cylindrical object, the design of a planar array for SONAR is investigated in this paper. It is necessary to employ planar structures for SONAR array to obtain narrower beam pattern which gives high resolution. In this study, the transmit frequency of each acoustic transducer, which consists of an array is 13 kHz. For efficient detection of a target of an asymmetric size, the concept of areal angle is applied, which considers resolution according to both azimuth and elevation angles in array design. In the design, the areal angle is first investigated to satisfy the resolution requirements, and then based on the value of areal angles, the azimuth angle and the elevation angle are calculated respectively to design an array.

The Silicon Type Load Cell with SUS630 Diaphragm (SUS630 다이아프램을 이용한 반도체식 로드셀)

  • Moon, Young-Soon;Lee, Seon-Gil;Ryu, Sang-Hyuk;Choi, Sie-Young
    • Journal of Sensor Science and Technology
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    • v.20 no.3
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    • pp.213-218
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    • 2011
  • The load cell is a force sensor and a transducer that is used to convert a physical force into a electrical signal for weighing equipment. Most conventional load cells are widely used a metal foil strain gauge for sensing element when force being applied spring element in order to converts the deformation to electrical signals. The sensitivity of a load cell is limited by its low gauge factor, hysteresis and creep. But silicon-based sensors perform with higher reliability. This paper presents the basic design and development of the silicon type load cell with an SUS630 diaphragm. The load cell consists of two parts the silicon strain gauge and the SUS630 structure with diaphragm. Structure analysis of load cell was researched by theory to optimize the load cell diaphragm design and to determine the position of peizoresistors on a silicon strain gauge. The piezo-resistors are integrated in the four points of silicon strain gauge processed by ion implantation. The thickness of the silicon strain gauge was polished by CMP under 100 ${\mu}M$. The 10 mm diameter SUS630 diaphragm was designed for loads up to 10 kg with 300 ${\mu}M$ of diaphragm thickness. The load cell was successfully tested, the variation of ${\Delta}$R(%) of four points on the silicon strain gauge is good linearity properties and sensitivity.

Development of an Ultrasonic Inspection Technique for LP Turbine Rotor Disc (초음파를 이용한 저압 터빈 로타 디스크 검사 기술 개발)

  • Chang, H.K.;Cho, K.S.;Won, S.H.;Chung, M.H.;Cho, Y.S.;Hur, K.B.
    • Journal of the Korean Society for Nondestructive Testing
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    • v.17 no.3
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    • pp.174-183
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    • 1997
  • Turbine rotor disc consists of disc, bore, keyway, hub, and rim in which the typical defects are located. And these part of disc has very complicated geometry, therefore proper transducer selection, wedge design, fabrication, classification and evaluation of the signal identification are required. In this research, test block with the artificial flaws at keyway and boresurface parts have been used in order to establish the ultrasonic inspection technique for flaw detectability on disc. The analysis of the signals from the test blocks was performed. The wedges were designed according to the curvature from the discs. All the ultrasonic signals were collected and identified for evaluation. The ultrasonic inspection technique for the flaw-detection was established from this research. And it is proved that the result of this research can be applicable in the field inspection.

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Automatic Noncontact Ultrasonic Inspection Technique (비접촉식 초음파탐상방법 자동화 기술)

  • Kim, Y.G.;Ahn, B.Y.;Lee, S.S.
    • Journal of the Korean Society for Nondestructive Testing
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    • v.13 no.4
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    • pp.25-31
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    • 1994
  • A system for EMAT, which generates ultrasound by electro-magnectic forces and performs nondestructive testing in noncontact, was established. By linking it with a 3 axis scanning system and a data acquisition and processing system the automation of EMAT testing was attempted. A EMAT sensor was fabricated and the directivity pattern of it was measured. To be suitable automation, it has a transmitter and a receiver in one case and the main beam direction of it can be controlled by the frequency of driving signal. A program which controls the EMAT system, the 3 axis scanner and the data acquisition and processing system was developed. It also processes acquired data and displays the processing results. IBM-PC/AT compatible PC was used as main controller and the stratage of the program is emulation of real devices on the PC monitor. To provide the performance of the established EMAT system, two aluminium blocks containing artificial flaws and a welded aluminium block were tested. The result of the tests were satisfactory.

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Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells

  • Lee, Mee-Hyun;Kundu, Joydeb Kumar;Keum, Young-Sam;Cho, Yong-Yeon;Surh, Young-Joon;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.22 no.5
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    • pp.426-430
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    • 2014
  • Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.