• Title/Summary/Keyword: Potential barrier

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Arg-Leu-Tyr-Glu Suppresses Retinal Endothelial Permeability and Choroidal Neovascularization by Inhibiting the VEGF Receptor 2 Signaling Pathway

  • Park, Wonjin;Baek, Yi-Yong;Kim, Joohwan;Jo, Dong Hyun;Choi, Seunghwan;Kim, Jin Hyoung;Kim, Taesam;Kim, Suji;Park, Minsik;Kim, Ji Yoon;Won, Moo-Ho;Ha, Kwon-Soo;Kim, Jeong Hun;Kwon, Young-Guen;Kim, Young-Myeong
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.474-483
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    • 2019
  • Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

A Study on National Response Strategies of Large-scale Marine Disaster (대규모 해양재난의 국가적 대응전략에 관한 연구)

  • Lee, Choonjae
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.25 no.5
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    • pp.550-559
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    • 2019
  • The sinking of the M/V SEWOL in April 2014 was not a mere marine accident, but a marine catastrophe. This grim case developed into a social tragedy that impinged the national sentiment and communal integrity. It is imperative that thorough provisions and measures be outlined at the national level with regard to massive marine accidents, oil pollution, and natural disasters that might critically affect government affairs. Pivoting on "The Black Swan Theory," a concept of improperly rationalizing a national crisis based on uncertainties, this research assesses a variety of response strategies that minimize the national economic and social damage caused by a large-scale marine disaster. Along with the effort of minimizing any potential defects in each protective barrier, the "Black Swan Detection System of the Marine Disaster" needs to be incorporated to prevent cases wherein such defects lead to an actual crisis. Maritime safety must be systematically unified under a supervisory organization, and a structure for maritime crisis on-scene command and cooperation must likewise be established in order that every force on the scene of a marine disaster may act effectively and consistently under the direction of an on-scene commander.

Gintonin facilitates brain delivery of donepezil, a therapeutic drug for Alzheimer disease, through lysophosphatidic acid 1/3 and vascular endothelial growth factor receptors

  • Choi, Sun-Hye;Lee, Na-Eun;Cho, Hee-Jung;Lee, Ra Mi;Rhim, Hyewhon;Kim, Hyoung-Chun;Han, Mun;Lee, Eun-Hee;Park, Juyoung;Kim, Jeong Nam;Kim, Byung Joo;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.264-272
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    • 2021
  • Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.

Skin Moisturizing Properties and Anti-Inflammatory effects of extracts from Coptis chinensis in HaCaT cells (HaCaT cell에서 황련 추출물(Coptis chinensis)의 피부보습과 항염증 효과)

  • Kim, Eun-Hee;Moon, Young-Lan;Jang, Young-Ah
    • Journal of the Korean Applied Science and Technology
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    • v.38 no.3
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    • pp.870-882
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    • 2021
  • Coptis chinensis has been used in the treatment of various diseases such as soothing, anti-inflammation, antimicrobial and antipyretic in oriental traditional medicine. In this study, we investigated the effect of hot water extract of Coptis chinensis(CCW) on skin barrier and inflammation-related factors in UVB and TNF-α/IFN-γ-induced HaCaT cells and evaluated its potential as a moisturizing and anti-inflammatory material. Based on result, the amount of HA (Hyaluronic acid) production and protein and mRNA expression of filaggrin were measured. In TNF-α/IFN-γ-induced HaCaT cells, CCW increased the amount of HA production in a concentration-dependent manner. In the measurement of protein and mRNA expression of filaggrin, the expression rate increased as the concentration of CCW increased. In UVB-induced HaCaT cells, CCW decreased the production of ROS and showed significant results with EGCG ((-)-epigallocatechin-3-gallate), a positive control. In addition, CCW inhibited the expression of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8 in TNF-α/IFN-γ-induced HaCaT cells. It was confirmed that the protein and mRNA expression of COX-2, a major factor in skin inflammation, was decreased in a concentration-dependent manner. These results suggest that hot water extract from Coptis chinensis can be used as a cosmetic material having a moisturizing and anti-inflammatory effect.

Assessing Conservation Priority of Private Land in Unexecuted Urban Parks in Seoul Using Betweenness Centrality Analysis (매개중심성 분석을 활용한 서울시 미집행공원 내 사유지 보전 우선순위 평가)

  • Hwang, Byungmook;Ko, Dongwook W.;Kang, Wanmo
    • Journal of Korean Society of Forest Science
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    • v.110 no.1
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    • pp.22-34
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    • 2021
  • The implementation of the sunset provision of unexecuted urban parks in Seoul has been postponed; however, the mentioned parks still remain vulnerable since they can be subject to development under certain circumstances. Local governments may purchase the parks to prevent their loss but are constrained due to limited resources. The purpose of this study is to prioritize the purchase of unexecuted urban parks in Seoul based on landscape connectivity, which represents the important role of allowing the movement of wildlife and providing biodiversity in urban environments. In this study, we used four potential scenarios (PB100, PB1, PA100, PA1), which reflects the degree of land cover change resulting from the implementation of the sunset provision, and the role of Han River as a conduit or barrier for wildlife movement. Landscape connectivity was evaluated by calculating current flow betweenness centrality (CFBC). This was used to rank the importance of the unexecuted urban parks in Seoul. The results demonstrated that the implementation of the sunset provision will greatly decrease the connectivity of all parks in Seoul and particularly more so for parks in the southern part of the city. In addition, the results suggested that the low connectivity of Han river will diminish the connectivity around Bukhansan Mountain in the northern part of Seoul. Our study can be used for the prioritization of purchase, since it has the ability to evaluate the anticipated vulnerability of each park's connectivity after the sunset provision.

A Study on the Design of Stearic Acid-Based Solid Lipid Nanoparticles for the Improvement of Artificial Skin Tissue Transmittance of Serine (Serine 의 인공피부조직 투과 개선을 위한 Stearic Acid 기반 고형지질나노입자의 설계 연구)

  • Yeo, Sooho
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.2
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    • pp.179-184
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    • 2021
  • Stratum corneum known as a skin barrier, which maintains water in skin, is the outer layer of the skin. Natural moisturizing factors (NMF) are one of the constituents in stratum corneum and amino acids are the highest components among NMF. In this study, we designed stearic acid-based solid lipid nanoparticles (SLNs) for improved skin penetration of serine (Ser). Ser-capsulated SLN was manufactured by double-melting emulsification method. The mean particle size and zeta potential of SLNs were 256.30 ~ 416.93 nm and -17.60 ~ -35.27 mV, respectively. The higher the degree of hydrophobicity or hydrophilicity of emulsifiers, the smaller the particle size and the higher the stability and capsulation rate. In addition, skin penetration was conducted using SkinEthicTM RHE which is one of the reconstructed human epidermis models. The results of Ser penetration demonstrated that all SLNs enhanced than serine solution. The amount of enhanced Ser penetration from SLNs were approximately 4.1 ~ 6.2 times higher than that from Ser solution. Therefore, Ser-loaded SLN might be a promising drug delivery system for moisturizing formulation in cosmeceutical.

Fabrication of edible gelatin-based films by heat pressing (열 압착을 이용한 가식성 젤라틴 필름 제조)

  • Kim, Eui Hyun;Song, Ah Young;Min, Sea Cheol
    • Korean Journal of Food Science and Technology
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    • v.54 no.2
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    • pp.179-184
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    • 2022
  • In this study, edible films made of fish and mammalian gelatins were produced using heat pressing, and their physical properties were investigated. Transparent and smooth films were formed continuously and uniformly using a mixture of fish skin gelatin (FG) or mammalian gelatin (MG), glycerol, and water under the process of heat pressing at 90℃ and 20 MPa for 5 min. Heat-pressed FG films possessed lower light transmittance and tensile strength than heat-pressed MG films; however, their appearance, surface morphology, water vapor permeability, lightness, and redness were not different from those of heat-pressed MG films. Although heat-pressed FG films had lower tensile strength, they had a flatter and more uniform surfaces and demonstrated higher transparency and moisture barrier properties compared to the casted FG films. These results demonstrate the potential utility of heat pressing for the large-scale production of edible films using both FG and MG.

Anticancer Effect of Novel Peptide from Abalone (Haliotis discus hannai) based on Next Generation Sequencing Data (차세대염기서열분석 데이터 기반으로 선별한 전복(Haliotis discus hannai) 유래 신규 펩타이드의 항암 효과)

  • Moon, Hyunhye;Hwang-bo, Jeon;Veerappan, Karpagam;Natarajan, Sathishkumar;Chung, Hoyong;Park, Junhyung
    • Journal of Marine Life Science
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    • v.7 no.1
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    • pp.15-20
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    • 2022
  • Glioblastoma is one of the highly aggressive central nervous system tumors and it is difficult to treat owing its anatomical location. Peptides are novel class of drugs which has the potential to cross the blood brain barrier and exerts its anti-tumor activity. Here, we discovered a novel peptide from abalone (Haliotis discus hannai) next generation sequencing (NGS) data and tested its anticancer effect on glioblastoma cell line SNU-489. The anticancer activity was measured using a cytotoxicity assay in a time and dose-dependent manner. A concentration and time dependent increase in the cytotoxicity was seen in cells treated with the novel peptide. The highest cytotoxicity rate of about 67% was observed in SNU-489 cells treated with 200 µM peptide for 48 hrs. However, the cytotoxic effect was not or less observed in a normal skin cell line HaCaT at similar concentration, thus, evident of peptide's cell specific anticancer activity. In addition, the gene expression level of necroptosis-related genes was analyzed by qRT-PCR to elucidate the anticancer mechanism of the novel peptide. RIPK3 expression was significantly increased by 9.6-fold in 200 µM of novel peptide treatment group, and MLKL expression level was significantly elevated by 2-fold in 100 µM treated group compared to the control group. Therefore, this study confirmed that the novel abalone-derived peptide has anticancer potency, and it causes cancer cell death through the necroptosis mechanism. Collectively, these results suggest that the novel peptide could be candidate anticancer agent for the treatment of glioblastoma in the future.

The Rationalization of PDM in Pusan Port for the Period of Round Pacific Area (환태평양 시대의 부산항 물류산업 합리화)

  • Park, S. Y.;Park, C. S.
    • Journal of Korean Port Research
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    • v.6 no.1
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    • pp.93-110
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    • 1992
  • The most change in this century is supposed to be declination of ideology, and block of world economy. Addition to down full of cold war atmosphere around Northeast Asia, not only economic and social mood in this region is dramatically changed, but also it gave birth to the block of Northeast economy that accerlated new hub of world economy. According to dramatic change of economic surroundings the dynamic potential of growth in this region will be guided to enlarge inter-regional trade and increase volume of trade, thus suggests to grow steadily transportation. cargos in this region will have to arrange the system of delivery and inner transportation, accessary facilities, inter-regional harbors if North America and EC has connected easily. As have accerlated GATT and UR represented multilateralism and regionalism, it has regulated to increase trades of region due to relief of the trade barrier through specific areas has agreed with separately. The flow of regionalism of world economy has appeared to realize EC and NAFTA centered U.S.A, and also has presented to free trade region or one-size market agreement in Asia as APEC, EAEG in Malaysia, and etc. In defense to this block and internationalism of world economy, Pusan has to come forward to the hub of Northeast others has proposed a project to dominate the Northeast, Economy Association Agreement as Far East comprehensive development project in USSR, Hunchun development project in NK, and East Sea development project in PRC, Niigate regional development in Japan, Duman River development project in NK, and East Sea development project in Korea. As this exercise has proceed, Pusan also have arranged development strategy definitely and prepared provisions systematically. Engaging to participate center of delivery system is meant to be completed complex functions, namely the transfer storage processing & assembly function of international commodity. Pusan has ability to be terminal point of TSR. it had been connected to EC as the biggest economy block and TKR as complex transportation root to Far East, it would be the center of inground and seabase delivery terminal to Rotterdom as the biggest container pier and major piers to North-East and South East Asia. In order to provide a Role of 21 century's internationalization, Pusan has appealed to participate in management information research and development connected to Pohang-Ulsan-Changwon-Masan, and has utilized efficiently the resources such as man, material, money and information.

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Sustained release of alginate hydrogel containing antimicrobial peptide Chol-37(F34-R) in vitro and its effect on wound healing in murine model of Pseudomonas aeruginosa infection

  • Shuaibing Shi;Hefan Dong;Xiaoyou Chen;Siqi Xu;Yue Song;Meiting Li;Zhiling Yan ;Xiaoli Wang ;Mingfu Niu ;Min Zhang;Chengshui Liao
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.44.1-44.17
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    • 2023
  • Background: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions: Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.