• 제목/요약/키워드: hDPP4

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Generation of a transgenic pig expressing human dipeptidylpeptidase-4 (DPP-4) (Human dipeptidylpeptidase-4(DPP-4) 발현 형질전환 돼지의 생산)

  • Chung, Hak Jae;Sa, Soo Jin;Baek, Sun Young;Cho, Eun Suek;Kim, Young Shin;Hong, Jun Ki;Cho, Kyu Ho;Kim, Ji Youn;Park, Mi Ryung;Kim, Kyung Woon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.9
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    • pp.306-314
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    • 2019
  • As dipeptidyl peptidase-4(DPP-4) inhibitors are used widely as a secondary treatment for type 2 diabetes because they tend to be well tolerated with minimal side effects, the human DPP-4(hDPP-4) gene was injected into a pig zygote through micro-injection, and 1-cell stage fertilized embryos were then transplanted surgically into the oviduct. Three pigs were fertilized with hDPP-4 genes and produced sixteen piglets, in which one male piglet was identified to be transgenic. Finally, transgenic pigs showing hDPP-4 gene expression in the tail were produced. Western blot and RT-PCR analysis confirmed that the hDPP-4 is expressed strongly in the membrane cells of the transgenic pig, and that the hDPP-4 gene appears in various tissues and tails. This suggests that the expression vector is normally expressed in transgenic pigs. These results are anticipated to be a model animal to check the endocrine function for insulin resistance that occurs in a hDPP-4 transgenic pig and to increase its value for use as a material in newly developed medicines.

Middle East Respiratory Syndrome-Coronavirus Infection into Established hDPP4-Transgenic Mice Accelerates Lung Damage Via Activation of the Pro-Inflammatory Response and Pulmonary Fibrosis

  • Kim, Ju;Yang, Ye Lin;Jeong, Yongsu;Jang, Yong-Suk
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.427-438
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    • 2020
  • Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells

  • Yoon, Hyunyee;Sung, Ji Hyun;Song, Moon Jung
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.154-165
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    • 2021
  • This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

Functional analysis of Bombyx mori Decapentaplegic gene for bone differentiation in a mammalian cell

  • Park, Seung-Won;Goo, Tae-Won;Choi, Gwang-Ho;Kang, Seok-Woo;Kim, Sung-Wan;Kim, Seong-Ryul
    • International Journal of Industrial Entomology and Biomaterials
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    • v.27 no.1
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    • pp.159-165
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    • 2013
  • Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF-${\beta}$) superfamily and are involved in osteoblastic differentiation. The largest TGF-${\beta}$ superfamily subgroup shares genetic homology with human BMPs (hBMPs) and silkworm decapentaplegic (dpp). In addition, hBMPs are functionally interchangeable with Drosophila dpp. Bombyx mori dpp may induce bone formation in mammalian cells. To test this hypothesis, we synthesized the 1,285-base pairs cDNA of full-length B. mori dpp using total RNAs obtained from the fat body of 3-day-old of the $5^{th}$ instar larvae and cloned the cDNA into the pCEP4 mammalian expression vector. Next, B. mori dpp was expressed in C3H10T1/2 cells. The target cells transfected with the pCEP4-Bm dpp plasmid showed biological functions similar to those of osteogenic differentiation induction growth factors such as hBMPs. We determined the relative mRNA expression rates of Runt-related transcription factor 2 (RUNX2), osterix, osteocalcin, and alkaline phosphatase (ALP) to validate the osteoblast-specific differentiation effects of B. mori dpp by performing quantitative real-time RT-PCR. Interestingly, mRNA expression levels of the 3 marker genes except RUNX2, in cells expressing B. mori dpp were much higher than those in control cells and C3H10T1/2 cells transfected with pCEP4. These results suggested that B. mori dpp signaling regulates osterix expression during osteogenic differentiation via RUNX2-independent mechanisms.

Development of a pH/dissolved- oxygen Monitoring System Using HPTS and Rudpp (HPTS, Rudpp를 활용한 pH 및 용존산소 모니터링 시스템 연구)

  • Dong Hyuk Jeong;Daewoong Jung
    • Journal of Sensor Science and Technology
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    • v.32 no.2
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    • pp.82-87
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    • 2023
  • This study proposes a pH-dissolved-oxygen monitoring system using 8-HydroxyPyrene-1,3,6-trisulfonic acid Trisodium Salt (HPTS) and tris(4,7-diphenyl-1,10-phenanthroline)Ruthenium(II) chloride (Rudpp). Commercial water-quality sensors are electrochemical devices that require frequent calibration and cleaning, are subject to high maintenance costs, and have difficulties conducting measurements in real-time. The proposed pH-dissolved-oxygen monitoring system selects a thin-film sensing layer to measure the change in fluorescence intensity. This change in fluorescence intensity is based on reactions with hydrogen ions in an aqueous solution at a given pH and specific amount of dissolved oxygen. The change in fluorescence intensity is then measured using light-emitting diodes and photodiodes in response to HPTS and Rudpp. This method enables the development of a relatively small, inexpensive, and real-time measureable water-quality measurement system.

Electrochemical Behavior and Differential Pulse Polarographic Determination of Piperacillin Sodium

  • Hahn, Young-hee;Son, Ean-ji
    • Archives of Pharmacal Research
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    • v.23 no.3
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    • pp.197-201
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    • 2000
  • In an aqueous piperacillin sodium solution, a well-defined single wave or single peak was observed by direct current(DC) polarography or differential pulse polarography(DPP). The peak potential change per pH unit was -54 mV in the phosphate buffer at $18^{\circ}C$, which indicated that protons were involved in the electrochemical reduction of the 2,3-dioxopiperazine moiety of piperacillin sodium with a $H^{+}e^{-}$ ratio of one. Using a phosphate buffer of pH 4.3, the $1.0{times}10^{-7}$ M piperacillin sodium single peak could be determined by DPP with relative standard deviation of 1.6 %(n=3). Piperacillin sodium could be analyzed with-out interference from penicillin G-potassium, which enabled the employment of DPP as a fast and simple technique for monitoring the synthetic process of the antibiotic.

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Application of Antimicrobial Peptide LL-37 as an Adjuvant for Middle East Respiratory Syndrome-Coronavirus Antigen Induces an Efficient Protective Immune Response Against Viral Infection After Intranasal Immunization

  • Ju Kim;Ye Lin Yang;Yongsu Jeong;Yong-Suk Jang
    • IMMUNE NETWORK
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    • v.22 no.5
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    • pp.41.1-41.16
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    • 2022
  • The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

Differential Power Processing System for the Capacitor Voltage Balancing of Cost-effective Photovoltaic Multi-level Inverters

  • Jeon, Young-Tae;Kim, Kyoung-Tak;Park, Joung-Hu
    • Journal of Power Electronics
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    • v.17 no.4
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    • pp.1037-1047
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    • 2017
  • The Differential Power Processing (DPP) converter is a promising multi-module photovoltaic inverter architecture recently proposed for photovoltaic systems. In this paper, a DPP converter architecture, in which each PV-panel has its own DPP converter in shunt, performs distributed maximum power point tracking (DMPPT) control. It maintains a high energy conversion efficiency, even under partial shading conditions. The system architecture only deals with the power differences among the PV panels, which reduces the power capacity of the converters. Therefore, the DPP systems can easily overcome the conventional disadvantages of PCS such as centralized, string, and module integrated converter (MIC) topologies. Among the various types of the DPP systems, the feed-forward method has been selected for both its voltage balancing and power transfer to a modified H-bridge inverter that needs charge balancing of the input capacitors. The modified H-bridge multi-level inverter had some advantages such as a low part count and cost competitiveness when compared to conventional multi-level inverters. Therefore, it is frequently used in photovoltaic (PV) power conditioning system (PCS). However, its simplified switching network draws input current asymmetrically. Therefore, input capacitors in series suffer from a problem due to a charge imbalance. This paper validates the operating principle and feasibility of the proposed topology through the simulation and experimental results. They show that the input-capacitor voltages maintain the voltage balance with the PV MPPT control operating with a 140-W hardware prototype.

Electrochemical Behavior and Differential Pulse Polarographic Determination of Rifampicin in the Pharmaceutical Preparations

  • Hahn, Young-Hee;Shin, Sun-Mi
    • Archives of Pharmacal Research
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    • v.24 no.2
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    • pp.100-104
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    • 2001
  • Differential pulse polarographic(DPP) analytical procedure for the rifampicin antibiotic, which can be applied to monitor its synthetic process from the starting antibiotic of rifamycin B or rifamycin SV has been developed based on the electrochemical reduction of an azomethine group. Rifampicin exhibited a cathodic peak due to the azomethine group in the side chain of 3-[(4-methyl-1-piperazinyl)imino]methyl moiety and another cathodic peak due to the carbonyl group in rifamycin SV by DPP. The experimental peak potential shift of an azomethine reduction was -73 mV/pH in the pH range between 3.0 and 7.5, agreeing with involvement of 4 e-and 5 $H^5$ in its reduction. By the cyclic voltammetric(CV) studies, the azomethine and the carbonyl reductions in rifampicin were processed irreversibly on the mercury electrode. The plot of peak currents vs. concentrations of rifampicin ranging $1.0{\times}10^{-7} M~$1.0{\times}10^{-5} M yielded a straight line with a correlation coefficient of 0.9996. The detection limit was $1.0{\times}10^{-8} M with a modulation amplitude of 50 mV DPP has been successfully applied for the determination of rifampicin in the pharmaceutical preparations.

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