• Title/Summary/Keyword: Barrier mechanism

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Acid sphingomyelinase-mediated blood-brain barrier disruption in aging

  • Park, Min Hee;Jin, Hee Kyung;Bae, Jae-sung
    • BMB Reports
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    • v.52 no.2
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    • pp.111-112
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    • 2019
  • Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

Contributions of HO-1-Dependent MAPK to Regulating Intestinal Barrier Disruption

  • Zhang, Zhenling;Zhang, Qiuping;Li, Fang;Xin, Yi;Duan, Zhijun
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.175-183
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    • 2021
  • The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

High Temperature Electrical Behavior of 2D Multilayered MoS2

  • Lee, Yeon-Seong;Jeong, Cheol-Seung;Baek, Jong-Yeol;Kim, Seon-Guk
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.377-377
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    • 2014
  • We demonstrate the high temperature-dependent electrical behavior at 2D multilayer MoS2 transistor. Our previous reports explain that the extracted field-effect mobility of good device was inversely proportional to the increase of temperature. Because scattering mechanism is dominated by phonon scattering at a well-designed MoS2 transistor, having, low Schottky barrier. However, mobility at an immature our $MoS_2$ transistor (${\mu}m$ < $10cm^2V^{-1}s^{-1}$) is proportional to the increase temperature. The existence of a big Schottky barrier at $MoS_2-Ti$ junction can reduce carrier transport and lead to lower transistor conductance. At high temperature (380K), the field-effect mobility of multilayer $MoS_2$ transistor increases from 8.93 to $16.9cm^2V^{-1}sec^{-1}$, which is 2 times higher than the value at room temperature. These results demonstrate that carrier transport at an immature $MoS_2$ with a high Schottky barrier is mainly affected by thermionic emission over the energy barrier at high temperature.

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A Study on the Workability and Application of Cooper Plate based on the Waterproofing and Root Penetration Resistance (옥상녹화 방수 및 방근 기술로서 동판재의 적합성 및 시공성에 관한 연구)

  • Park, Chang-Hwa;Cho, Il-Kyu;Kwon, Shi-Won;Oh, Sang-Keun
    • Proceedings of the Korean Institute of Building Construction Conference
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    • 2007.04a
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    • pp.151-154
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    • 2007
  • To build up the green roofs, it must not adverse effect to durability and structural safety. That is conducted by safety system which consist of waterproofing to form basically, root barrier to protect the waterproofing. The reason why root barrier form is to protect the penetration force of root growth and the root could penetrate concrete surface, move inward so far. It may cause shorten the life span on concrete structure. For this problem, government constantly demand the solution to form the root barrier for waterproofing and concrete structure before the building is service. However, the technical action is not fully prepared. Therefore, in this study, we would like to suggest the workability and suitability of the copper plate to solve not only the side of waterproofing but also root barrier for green roof system and exhibit the mechanism for root penetration resistance and corrosion resistance.

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Variations of Interface Potential Barrier Height and Leakage Current of (Ba, Sr)$TiO_3$ Thin Films Deposited by Sputtering Process

  • Hwang, Cheol-Seong;Lee, Byoung-Taek
    • The Korean Journal of Ceramics
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    • v.2 no.2
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    • pp.95-101
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    • 1996
  • Variations of the leakage current behaviors and interface potential barrier $({\Phi}_B)$ of rf-sputter deposited (Ba, Sr)$TiO_3$ (BST) thin films with thicknesses ranging from 20 nm to 150nm are investigated as a function of the thickness and bias voltages. The top and bottom electrodes are dc-sputter-deposited Pt films. ${\Phi}_B$ critically depends on the BST film deposition temperature, postannealing atmosphere and time after the annealing. The postannealing under $N_2$ atmosphere results in a high interface potential barrier height and low leakage current. Maintaining the BST capacitor in air for a long time reduces the ${\Phi}_B$ from about 2.4 eV to 1.6 eV due to the oxidation. ${\Phi}_B$ is not so dependent on the film thickness in this experimental range. The leakage conduction mechanism is very dependent on the BST film thickness; the 20 nm thick film shows tunneling current, 30 and 40 nm thick films show Shottky emission current.

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Gut-Brain Connection: Microbiome, Gut Barrier, and Environmental Sensors

  • Min-Gyu Gwak;Sun-Young Chang
    • IMMUNE NETWORK
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    • v.21 no.3
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    • pp.20.1-20.18
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    • 2021
  • The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

Imperatorin is Transported through Blood-Brain Barrier by Carrier-Mediated Transporters

  • Tun, Temdara;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • v.25 no.4
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    • pp.441-451
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    • 2017
  • Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [$^3H$]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

Epidermal Homeostasis and Dry Skin Management (표피항상성과 건조피부의 관리)

  • Park, Chang-Seo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.34 no.1
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    • pp.1-8
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    • 2008
  • Epidermis is one of the most dynamic organs in the human body. Multiple layers of keratinocytes in the epidermis continuously undergo proliferation, differentiation, and desquamation cycles, which is the bases of maintaining the epidermal homeostasis. Epidermal homeostasis eventually leads to establish and maintain permeability barrier homeostasis, the most important function of the epidermis. The permeability barrier is located in the stratum corneum. Tightly coordinated regulations are required for the sustained normal barrier function. Extensive studies have established that several nuclear hormone liposensors, including peroxisome proliferator-activated receptor a PPARa, PPARb/d, PPARg and LXRs are expressed in keratinocyte. Activation of PPARs and LXRs could provide a mechanism to coordinate the formation of the corneocytes and extracellular lipid membranes that constitute the stratum corneum. Topical application of PPAR/LXR ligands to murine skin results in the increased expression of keratinocyte differentiation-related proteins, such as involucrin, loricrin, profilaggrin, and trans-glutaminase 1, which would stimulate cornified envelope formation. In conclusion, topical application of ligands or activators of PPAR/LXR as an epidermotherapy would be a promising option to deal dry skin conditions such as atopy.

A Hardware Barrier Synchronization using Multi -drop Scheme in Parallel Computer Systems (병렬 컴퓨터 시스템에서의 Multi-drop 방식을 사용한 하드웨어 장벽 동기화)

  • Lee, June-Bum;Kim, Sung-Chun
    • Journal of KIISE:Computer Systems and Theory
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    • v.27 no.5
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    • pp.485-495
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    • 2000
  • The parallel computer system that uses parallel program on the application such as a large scale business or complex operation is required. One of crucial operation of parallel computer system is synchronization. A representative method of synchronization is barrier synchronization. A barrier forces all process to wait until all the process reach the barrier and then releases all of the processes. There are software schemes, hardware scheme, or combinations of these mechanism to achieve barrier synchronization which tends to use hardware scheme. Besides, barrier synchronization lets parallel computer system fast because it has fewer start-up overhead. In this paper, we propose a new switch module that can implement fast and fault-tolerant barrier synchronization in hardware scheme. A proposed barrier synchronization is operated not in full-switch-driven method but in processor-driven method. An effective barrier synchronization is executed with inexpensive hardware supports. Therefore, a new proposed hardware barrier synchronization is designed that it is operated in arbitrary network topology. In this paper, we only show comparison of barrier synchronization on Multistage Interconnection Network. This research results in 24.6-24.8% reduced average delay. Through this result, we can expect lower average delay in irregular network.

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Mechanism of Action of Various Vehicles That Enhance the Permeation of Ketoprofen (케토프로펜의 피부투과도를 증진시키는 다양한 용매의 작용기전)

  • Cho, Young-Joo;Choi, Hoo-Kyun
    • Journal of Pharmaceutical Investigation
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    • v.28 no.3
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    • pp.165-169
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    • 1998
  • The effect of various vehicles on the permeation of a model drug, ketoprofen in solution formulation was evaluated using a flow-through diffusion cell system at $37^{\circ}C$. To investigate the mechanism of permeation rate enhancement, the effects of pretreatment with various vehicles on the permeation of the drug were evaluated using 5 mg/ml solution and saturated solution. The order of permeation rate of ketoprofen across hairless mouse skin after pretreatment with various vehicles was similar to the case where the vehicles and the drug were coadministered except ethanol and oleic acid. The results indicate that the mechanism of enhancement can be direct action of the vehicles on the barrier property of the skin and/or carrier mechanism.

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