• Title/Summary/Keyword: PTP

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Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance

  • Jiang, Ping;Ma, Dufang;Wang, Xue;Wang, Yongcheng;Bi, Yuxin;Yang, Jinlong;Wang, Xuebing;Li, Xiao
    • Molecules and Cells
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    • v.41 no.3
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    • pp.244-255
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    • 2018
  • Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

Effects of Enzymes and Emulsifiers on the Loaf Volume and Crumb Hardness of Rice Breads (효소제 및 유화제의 첨가가 쌀빵의 부피와 경도에 미치는 영향)

  • Lee, Myung-Hee;Chang, Hak-Gil;Lee, Young-Tack
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.6
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    • pp.761-766
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    • 2008
  • The effects of various enzymes and emulsifiers on the loaf volume and crumb hardness of rice breads were studied. Four different enzymes [fungal ${\alpha}$-amylase (AMYL), maltogenic bacterial ${\alpha}$-amylase (NMYL), glucose oxidases (GO), and xylanase+hemicellulases (PTP)] and four emulsifiers [sorbitan monostearate (SMS), glycerol monostearate (GMS), sodium stearoyl lactylate (SSL), and glycerol ester+propylene glycol ester+sucrose ester+sorbitan ester (SP)] were supplemented to rice dough. The addition of AMYL, GO, and GO+AMYL increased loaf volume of rice breads. The highest loaf volume was observed in rice bread supplemented with AMYL. Rice breads supplemented with enzymes firmed at lower rates during storage, and AMYL, NMYL, and GO considerably decreased crumb hardness of rice breads, exhibiting a significant antistaling effect. The addition of emulsifiers produced rice breads with better specific loaf volume and crumb texture, and continuously retarded crumb hardness of rice breads during storage. Especially, rice bread supplemented with SSL demonstrated the highest loaf volume and the lowest crumb hardness during storage.

Fire Detection Approach using Robust Moving-Region Detection and Effective Texture Features of Fire (강인한 움직임 영역 검출과 화재의 효과적인 텍스처 특징을 이용한 화재 감지 방법)

  • Nguyen, Truc Kim Thi;Kang, Myeongsu;Kim, Cheol-Hong;Kim, Jong-Myon
    • Journal of the Korea Society of Computer and Information
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    • v.18 no.6
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    • pp.21-28
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    • 2013
  • This paper proposes an effective fire detection approach that includes the following multiple heterogeneous algorithms: moving region detection using grey level histograms, color segmentation using fuzzy c-means clustering (FCM), feature extraction using a grey level co-occurrence matrix (GLCM), and fire classification using support vector machine (SVM). The proposed approach determines the optimal threshold values based on grey level histograms in order to detect moving regions, and then performs color segmentation in the CIE LAB color space by applying the FCM. These steps help to specify candidate regions of fire. We then extract features of fire using the GLCM and these features are used as inputs of SVM to classify fire or non-fire. We evaluate the proposed approach by comparing it with two state-of-the-art fire detection algorithms in terms of the fire detection rate (or percentages of true positive, PTP) and the false fire detection rate (or percentages of true negative, PTN). Experimental results indicated that the proposed approach outperformed conventional fire detection algorithms by yielding 97.94% for PTP and 4.63% for PTN, respectively.

Key Structural Features of PigCD45RO as an Essential Regulator of T-cell Antigen Receptor Signaling (T-세포 항원 수용체 매개 신호전달 조절자로서 돼지 CD45RO 구조특성)

  • Chai, Han-Ha;Lim, Dajeong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.9
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    • pp.211-226
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    • 2019
  • Pig CD45, the leukocyte common antigen, is encoded by the PTPRC gene and CD45 is a T cell-type specific tyrosine phosphatase with alternative splicing of its exons. The CD45 is a coordinated regulator of T cell antigen receptor (TCR) signal transduction achieved by dephosphorylating the phosphotyrosine of its substances, including $CD3{\zeta}$ chain of TCR, Lck, Fyn, and Zap-70 kinase. A dysregulation of CD45 is associated with a multitude of immune disease and has been a target for immuno-drug discovery. To characterize its key structural features with the effects of regulating TCR signaling, this study predicted the unknown structure of pig CD45RO (the smallest isoform) and the complex structure bound to the ITAM (REEpYDV) of $CD3{\zeta}$ chain via homology modeling and docking the peptide, based on the known human CD45 structures. These features were integrated into the structural plasticity of extracellular domains and functional KNRY and PTP signature motifs (the role of a narrow entrance into ITAM binding site) of the tyrosine phosphatase domains in a cytoplasmic region from pig CD45RO. This contributes to the selective recognition of phosphotyrosine from its substrates by adjusting the structural stability and binding affinity of the complex. The characterized features of pigCD45RO can be applied in virtual screening of the T-cell specific immunomodulator.

Caulerpa okamurae ethanol extract improves the glucose metabolism and insulin sensitivity in vitro and in vivo (옥덩굴 에탄올 추출물의 당 대사 및 인슐린 민감성 개선효과)

  • Park, Chul-Min;Thakuri, Laxmi Sen;Rhyu, Dong-Young
    • Journal of Applied Biological Chemistry
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    • v.64 no.1
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    • pp.89-96
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    • 2021
  • The aim of this study is to examine the effect of Caulerpa okamurae ethanol extract (COE) on glucose metabolism and insulin sensitivity as one of the drug targets for treatment of type2 diabetes. COE significantly inhibited protein tyrosine phosphatase (PTP1B) and dipeptidyl peptidase-IV (DPP-IV) enzyme activities in vitro assay. Also, COE significantly enhanced the glucose uptake and the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter4 (GLUT4) proteins in 3T3-L1 adipocytes or zebrafish larvae compared with control. In dexamethasone-induced resistance model of L6 myotubes, the protein expression of insulin signaling and glucose uptake was effectively increased by the treatment of COE. In contrast, the elevated phosphorylation of IRS-1 Ser307 was normally suppressed by treatment of COE. However, COE had no effect on insulin secretion in pancreatic beta cells. Thus, our results suggest that COE improves the glucose metabolism and insulin sensitivity through the regulation of insulin signaling and GLUT4 protein in insulin's target cells and zebrafish larvae.

Lupeol Improves TNF-α Induced Insulin Resistance by Downregulating the Serine Phosphorylation of Insulin Receptor Substrate 1 in 3T3-L1 Adipocytes (3T3-L1 지방세포에서 루페올의 IRS-1의 인산화 조절을 통한 TNF-α 유도 인슐린 저항성 개선 효과)

  • Hyun Ah Lee;Ji Sook Han
    • Journal of Life Science
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    • v.33 no.11
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    • pp.859-867
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    • 2023
  • Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.

Biotransformation of Diterpenoids From Aralia continentalis Roots by the Genus Fusarium (곰팡이 Fusarium 속을 이용한 독활 뿌리 추출물로부터 디테르페노이드의 생물전환)

  • Keumok Moon;Seola Lee;Eunhye Jo;Areum Lee;Jaeho Cha
    • Journal of Life Science
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    • v.34 no.4
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    • pp.215-226
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    • 2024
  • Aralia continentalis is widely distributed in Far East Asian countries such as Korea, China, and Japan. A. continentalis has traditionally been used as an herbal remedy for various conditions, including analgesia, headache, inflammation, lameness, lumbago, rheumatism, and dental diseases in Korea. Previously, epi-continentalic acid, continentalic acid, and kaurenoic acid as major active biological compounds belonging to the diterpenoid class were identified. To synthesize diterpenoid derivatives with enhanced bioavailability, Fusarium fujikuroi was employed to biotransform diterpenoids due to its known antibacterial activity. This yielded two derivatives of kaurenoic acid, namely 16α-hydroxyent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, with their chemical structures elucidated via NMR analysis. These derivatives exhibited increased polarity compared to kaur- enoic acid, as evidenced by their retention time on preparative HPLC using the ODS-A column and structural modifications. Evaluation of their antidiabetic activity targeting PTP1B, a negative regulator of the insulin signaling pathway, revealed inhibitory activities of 30.8% and 27.6%, respectively, at a concentration of 4 ㎍/ml. Additionally, both derivatives demonstrated low cytotoxicity, with an IC50 value 18 times higher than kaurenoic acid. Therefore, the augmented water solubility and reduced toxicity of 16α-hydroxy-ent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, resulting from biotransformation by F. fujikuroi, render them promising candidates for industrial applications.

Measurement of Fishing Capacity of Offshore Fisheries in Korea (우리나라 근해어업의 어획능력 측정에 관한 연구)

  • Kim Do-Hoon
    • The Journal of Fisheries Business Administration
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    • v.37 no.1 s.70
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    • pp.1-24
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    • 2006
  • Reducing fishing capacity is one of current issues in the international fisheries. This is because that increased fishing capacity has caused not only fish stocks to be depleted, but also additional fishing costs to be incurred, which resulted in reduction of economically viability of fisheries. For this reason, FAO adopted the International Plan of Action for the Management of Fishing Capacity' in 1999 and recommended member countries to estimate fishing capacity and to implement the policy to reduce fishing capacity. This study is aimed to measure fishing capacity of the Large Purse Seines Fishery that is one of offshore fisheries in Korea using both Peak - to - Peak Analysis and Data Envelopment Analysis in order to provide a policy information for preparation of domestic plan of action for the management of fishing capacity. The results of PTP Analysis were almost similar to those of DEA Analysis. The DEA results showed that the capacity utilization in 2004 was about 75%, it was obvious the capacity did not utilize enough. The sensitivity analysis on DEA results indicated that 24% of the number of ships, 26% of the tonnages, or 29% of the horse powers should be reduced if the present catch remained. In addition, if the catch remains at the MSY base level of large purse seines, the analysis suggested that the number of ships, tonnages and horse powers should be reduced by 15%, 18%, and 21% respectively.

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Design of a IEEE 1588 Based Clock Synchronization System for Femtocell Frequency Signal Generation (펨토셀 주파수 신호 생성을 위한 IEEE 1588 기반 클록 동기화 시스템의 설계)

  • Han, Jiho;Park, Yong-Jai
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.7
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    • pp.4871-4877
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    • 2015
  • This article presents a circuit and a system for IEEE 1588 based clock synchronization to generate a very accurate frequency signal required in femtocell devices. A prototype board and the experimental environment to verify the functions and to evaluate the performance are explained to verify the feasibility of the proposed synchronization system. To make low-cost femtocells without constraints on the place of installation, it is very important to study on the practical implementation of synchronization system based on IEEE 1588. The experimental result shows that the synchronization errors between -16 ns and 9 ns are guaranteed over the network of femtocell devices with the proposed synchronization circuits, thus the synchronization criteria of the 3GPP HNB are met.

2D-QSAR and HQSAR on the Inhibition Activity of Protein Tyrosine Phosphatase 1B with Oleanolic Acid Analogues

  • Chung, Young-Ho;Jang, Seok-Chan;Kim, Sang-Jin;Sung, Nack-Do
    • Journal of Applied Biological Chemistry
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    • v.50 no.2
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    • pp.52-57
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    • 2007
  • Quantitative structure-activity relationships (QSARs) on the inhibition activities by oleanolic acid analogues (1-19) as a potent inhibitor against protein tyrosine phosphatase-1B were studied quantitatively using 2D-QSAR and HQSAR methodologies. The inhibition activity was dependent on the variations of $R_{4-}$substituent, and as shown in 2D-QSAR model ($r^2=0.928$), it has a tendency to increase as the negative Randic Indice (RI) goes up. The size of the molecular fragments used in HQSAR varied from five to eight. The fragment distinctions had the best statistic value, whose predictability is $q^2=0.785$ and correlation coefficient is $r^2=0.970$, on condition of connections. From the atomic contribution maps, the factor that contributes to the inhibition activities is the $C_{15}{\sim}C_{17}$ bond in the D ring. From the analysis result of these two the models, the structural distinctions and descriptors that contribute to the inhibition activities were obtained.