• Title/Summary/Keyword: 단백질 약물

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The Role of Protein Kinase C in Acute Lung Injury Induced by Endotoxin (내독소에 의한 급성폐손상에서 Protein Kinase C의 역할)

  • Kim, Yong-Hoon;Moon, Seung-Hyug;Kee, Sin-Young;Ju, Jae-Hak;Park, Tae-Eung;Im, Keon-Il;Cheong, Seung-Whan;Kim, Hyeon-Tae;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.349-359
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    • 1997
  • Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.

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A Study on Collecting and Structuring Language Resource for Named Entity Recognition and Relation Extraction from Biomedical Abstracts (생의학 분야 학술 논문에서의 개체명 인식 및 관계 추출을 위한 언어 자원 수집 및 통합적 구조화 방안 연구)

  • Kang, Seul-Ki;Choi, Yun-Soo;Choi, Sung-Pil
    • Journal of the Korean Society for Library and Information Science
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    • v.51 no.4
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    • pp.227-248
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    • 2017
  • This paper introduces an integrated model for systematically constructing a linguistic resource database that can be used by machine learning-based biomedical information extraction systems. The proposed method suggests an orderly process of collecting and constructing dictionaries and training sets for both named-entity recognition and relation extraction. Multiple heterogeneous structures for the resources which are collected from diverse sources are analyzed to derive essential items and fields for constructing the integrated database. All the collected resources are converted and refined to build an integrated linguistic resource storage. In this paper, we constructed entity dictionaries of gene, protein, disease and drug, which are considered core linguistic elements or core named entities in the biomedical domains and conducted verification tests to measure their acceptability.

Preparation and Characterization of Nano-sized Hydrogels (nanogels) Using Inverse-miniemulsion Polymerization Method for Protein Drug Delivery (단백질 약물 전달을 위한 Inverse-miniemulsion Polymerization 방법으로 제조하는 나노크기의 수화젤(나노젤)의 제조 및 특성평가)

  • Kang, Soo-Yong;Munkhjargal, Odonchimeg;Kim, Seong-Cheol;Park, Ah-Reum;Shim, Young-Key;Lee, Woo-Kyoung
    • Journal of Pharmaceutical Investigation
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    • v.40 no.2
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    • pp.73-78
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    • 2010
  • Hydrogels are thought to be a promising delivery carrier for protein drugs because of their favorable aqueous environment compared with nano/micro-particles of hydrophobic polymer such as PLGA. In this study, nano-sized hydrogels (nanogels) were fabricated using inverse-miniemulsion polymerization method. The mean size of nanogels in range of 90-160nm and affected by the preparation parameters such as sonication time and concentration of monomer. While longer sonication time and lower concentration of acrylamide monomer showed a tendency to produce smaller nanogels and to have lower lysozyme activity, variation of bis-methylene acrylamide concentration made no difference. Although both longer soncaton time and lower acrylamide concentration increased in vitro release rate, acrylamide concentration was more effectively affected to the control of protein release rate, which indicated that the release rate of protein from nanogels affected by not only their size but also internal structure. In conclusion, nanogels prepared by inverse-miniemulsion can be a useful carrier for application of protein drug, because of simple process, minimum contact of organic solvent and high protein activity.

Expression of Calponin 3 in the Striatum Following 3-Nitropropionic Acid-induced Neurotoxicity (선조체에서 3-nitropropionic acid 투여 후 calponin 3의 발현 연구)

  • Choi, Yun-Sik
    • Journal of Life Science
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    • v.23 no.1
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    • pp.125-130
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    • 2013
  • Calponin 3 is an F-actin-binding protein and plays a key role in regulating spine plasticity and synaptic activity in neurons. Unlike the other subtypes, calponin 1 and 2, which are expressed in smooth and cardiac muscle cells, calponin 3 is highly expressed in the brain. The goal of this study was to elucidate the spatiotemporal expression pattern of calponin 3 following repeated administration of 3-nitropropionic acid in mice. The repeated administration of 3-nitropropionic acid generated necrotic neuronal cell death in the striatum. Calponin 3 was up-regulated in the neuroprotective penimbral region from 1.5 days after the last injection and thereafter. Double immunofluorescence study revealed that calponin 3 was induced in GFAP-positive astrocytes. These results suggest that calponin 3 induction in the neuroprotective penumbral area following 3-nitropropionic acid intoxication may play a key role in reactive astrogliosis in the striatum.

Pharmacokinetics of a New Histone Hl Protein (p961), an Arthritis-suppressing Agent, in Rats and Rabbits (항류마치스 효과를 갖는 새로운 히스톤 H1 단백질 (p961)의 흰쥐와 토끼에 대한 약물동태)

  • 우수경;윤민혁;이재흥;권광일
    • YAKHAK HOEJI
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    • v.45 no.4
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    • pp.378-386
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    • 2001
  • A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....

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Regulatory Effect of Ginsenosides Rh1 on Monocytic U937 Cell Adhesion (홍삼유래 ginsenosides Rh1의 단핵구 U937 세포 유착조절 효과)

  • Kim, Byung-Hun;Cho, Jae-Youl
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.324-329
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    • 2009
  • Cell-cell adhesion managed by various adhesion molecules is known to be one of pathophysiological phenomena found in numerous immunological diseases such as rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)- Rh1, reported to display anti-inflammatory and anti-allergic effects, on CD29-mediated cell adhesion. G-Rh1 significantly suppressed U937 cell-cell adhesion mediated by CD29 but not CD43. It also blocked U937 cell-fibronectin adhesion, mediated by activated CD29, up to 30%. In agreement, this compound also significantly decreased the surface level of CD29 but not CD43 as well as other costimulatory molecules such as CD69, CD80, and CD86. Therefore, these results suggest that G-Rh1 may have inhibitory function on CD29-mediated cell adhesion events, probably contributing to its anti-inflammatory and anti-allergic activities.

Effect of Graft Copolymer Composition on the Compatibility of Biodegradable PCL/PCL-g-PEG Blend (PCL/PCL-g-PEG 생분해성 블렌드에서 그래프트 공중합체의 조성에 따른 상용성의 영향)

  • Cho, Kuk-Young;Lee, Ki-Seok;Park, Jung-Ki
    • Polymer(Korea)
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    • v.33 no.3
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    • pp.248-253
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    • 2009
  • Blend films based on the poly($\varepsilon$-caprolactone) (PCL) and amphiphilic biodegradable polymer, poly(ethylene glycol) grafted poly($\varepsilon$-caprolactone) (PCL-g- PEG), were prepared with different blend ratios in order to develop new biomedical material. PCL was the main component in the blend. The miscibility and characteristics of the blends were investigated. The crystallization temperature of the blend shifted to high temperatures with an increase of the graft copolymer contents when the homopolymer PCL was the main component of the blend. The PEG side chain in the blend affected the crystallization rate of the PCL crystals in the blend and alternating extinction bands were observed by optical microscopy. The protein adhesion behavior of the film was influenced by the water uptake of the film.

Animal Model for Regeneration of Olfactory Sensory Neurons (후각신경세포의 손상 및 재생 연구모델의 융합연구)

  • Jeong, Yun-Mi;Park, Jong-Su;Kim, Cheol-Hee;You, Kwan-Hee
    • Journal of the Korea Convergence Society
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    • v.7 no.2
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    • pp.61-67
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    • 2016
  • The olfactory system is an important model for the study of neuronal degeneration and regeneration, including neuronal diseases. When the olfactory sensory neurons are damaged by nerve injury or are exposed to environmental factors, they degenerate and are replaced by regenerating neurons. To monitor neuronal degeneration in living animal, we established an olfactory-specific GFP transgenic zebrafish. The effects of Triton X-100 or sodium acetate on the olfactory system were examined. A significant decrease in the number of GFP-positive olfactory sensory neurons was observed after chemical lesion. We found a recovery of GFP-positive neurons by 2 days posttreatment. From these results, we expect that further studies of olfactory degeneration and regeneration using this transgenic zebrafish will provide important advances for the study of neuronal degeneration and regeneration.

pH-Sensitive Dynamic Swelling Behavior of Glucose-containing Anionic Hydrogels (글루코스를 함유한 음이온 하이드로젤의 pH 감응성 동적 팽윤거동)

  • Kim, Bumsang
    • Korean Chemical Engineering Research
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    • v.43 no.2
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    • pp.299-304
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    • 2005
  • There have been many efforts to use anionic hydrogels as oral protein delivery carriers due to their pH-responsive swelling behavior. The dynamic swelling behavior of poly(methacrylic acid-co-methacryloxyethyl glucoside) [P(MAA-co-MEG)] hydrogels was investigated to determine the mechanism of water transport through these anionic hydrogels. The exponential relation $M_t/M_{\infty}=kt^n$ was used to calculate the exponent, n, describing the Fickian or non-Fickian behavior of swelling polymer networks. The mechanism of water transport through these gels was significantly affected by the pH of the swelling medium. The mechanism of water transport became more relaxation-controlled in the swelling medium of pH 7.0 that was higher than the $pK_a$ of the gels. Experimental results of time-dependent swelling behavior of the gels were analyzed with several mathematical models. Using ATR-FTIR spectroscopy, the effect of ionization of the carboxylic acid groups in the polymer networks on the water transport mechanism was investigated.

Electrohydrodynamic Spray Drying Using Co-axial Nozzles for Protein Encapsulation (단백질 캡슐화를 위한 동축 이중 노즐을 사용한 전기분무건조법)

  • Ho, Hwan-Ki;Park, Se-Hyun;Park, Chul-Ho;Lee, Jong-Hwi
    • Polymer(Korea)
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    • v.33 no.4
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    • pp.353-357
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    • 2009
  • Spray drying is an effective and stable process, which has been widely used to produce pharmaceutical powders. In the traditional spray drying process, it was not quite easy to control the aggregation and the size of particles. Particularly, the preparation of polymeric particles was relatively hard compared to the preparation of food and pharmaceutical ingredients, typically organic materials of small molecular weights. In this study, modification of a conventional spray dryer was tried to use electrical charge and co-axial nozzles to prepare polymeric particles. Poly(ethylene glycol) and poly (D,L-lactide-co-glycolide) were used as the inner polymeric materials, and lactose as the outer shell materials. The results showed that electrohydrodynamic spray-dried particles had a relatively uniform size and particle morphology, and the aggregation of particles could be suppressed compared to the conventional spray-dried particles. The electrohydrodynamic spray-dried powders consisted of spherical particles of $2{\sim}5{\mu}m$ diameters.