• IMMUNE NETWORK
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• v.22 no.4
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• pp.33.1-33.17
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• 2022

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

• Molecules and Cells
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• v.40 no.7
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• pp.503-514
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• 2017

Nicotinamide (NAM) plays essential roles in physiology through facilitating $NAD^+$ redox homeostasis. Importantly, at high doses, it protects cells under oxidative stresses, and has shown therapeutic effectiveness in a variety of disease conditions. In our previous studies, NAM lowered reactive oxygen species (ROS) levels and extended cellular life span in primary human cells. In the treated cells, levels of $NAD^+/NADH$ and SIRT1 activity increased, while mitochondrial content decreased through autophagy activation. The remaining mitochondria were marked with low superoxide levels and high membrane potentials (${\Delta}_{{\Psi}m}$); we posited that the treatment of NAM induced an activation of mitophagy that is selective for depolarized mitochondria, which produce high levels of ROS. However, evidence for the selective mitophagy that is mediated by SIRT1 has never been provided. This study sought to explain the mechanisms by which NAM lowers ROS levels and increases ${\Delta}_{{\Psi}m}$. Our results showed that NAM and SIRT1 activation exert quite different effects on mitochondrial physiology. Furthermore, the changes in ROS and ${\Delta}_{{\Psi}m}$ were not found to be mediated through autophagy or SIRT activation. Rather, NAM suppressed superoxide generation via a direct reduction of electron transport, and increased ${\Delta}_{{\Psi}m}$ via suppression of mitochondrial permeability transition pore formation. Our results dissected the effects of cellular $NAD^+$ redox modulation, and emphasized the importance of the $NAD^+/NADH$ ratio in the mitochondria as well as the cytosol in maintaining mitochondrial quality.

• Journal of the korean society of oceanography
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• v.34 no.1
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• pp.1-21
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• 1999

A two-layer quasi-geostrophic numerical model is used to investigate the temporal variability of the East Korea Warm Current (EKWC), especially the separation from the Korean coast and the generation of warm eddies. An attention is given on the active role of the nonlinear boundary layer process. For this, an idealized flat bottom model of the East Sea is forced with the annual mean wind curl and with the inflow-outflow specified at the Korea (Tsushima) and Tsugaru Straits. Two types of separation mechanisms are identified. The first one is influenced by the westward movement of the recirculating leg of the EKWC (externally driven separation),the second one is solely driven by the boundary layer dynamics (internally driven separation). However, these two processes are not independent, and usually coexist. It is hypothesized that 'internally driven separation' arises as the result of relative vorticity production at the wall, its subsequent advection via the EKWC, and its accumulation up to a critical level characterized by the separation of the boundary flow from the coast. It is found that the sharp southeastern corner of the Korean peninsula provides a favorable condition for the accumulation of relative vorticity. The separation of the EKWC usually accompanies the generation of a warm eddy with a diameter of about 120 km. The warm eddy has a typical layer-averaged velocity of 0.3 m/s and its lifespan is up to a year. In general, the characteristics of the simulated warm eddy are compatible with observations. A conclusion is therefore drawn that the variability of the EKWC is at least partially self-excited, not being influenced by any sources of perturbation in the forcing field, and that the likely source of the variability is the barotropic instability although the extent of contribution from the baroclinic instability remains unknown. The effects of the seasonal wind curl and inflow-outflow strength are also investigated.

• Proceedings of the KSR Conference
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• 2007.05a
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• pp.1097-1106
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• 2007

Rail provides running tract for train and broadly and widely conveys the weight of the train exerted from the train wheels that the rail directly supports onto the cross tie and roadbed, and supports the cross-sectional pressure exerted by centrifugal force at curvatures. That is, stationary rail provides surface on which dynamic train runs and guarantees cross-sectional resistance to enable the vertical snake motion of the train wheels as well as to maintain lateral force at curvatures. Rail provides running surface on which train wheels can run smoothly, and secures vertical and lateral force. However, it undergoes continuous destructive reactions (wearing and damages) and abrasion of the cladding by the train wheels. It is obvious that wearing will result when two metal parts act against each other. However, occurrence of abnormal wearing such as rapid wearing of the rail side due to complex generation of various mechanisms at the contact surface between the rail and train wheel flange. It is not easy to simply examine the causes of occurrence of abnormal wearing of rail and train wheel flange. Although countless number of academicians and specialists are conducting researches on abnormal wearing of rail and vertical wearing of train wheels, I believe it is too early to argue on pros and cons due to insufficiency of officially verified information on the issue. This review will be focusing on the examples of repairs that reduced the generation of abnormal wearing of rail by reviewing and improving characteristics of wearing and slack, speed of the train and cant as well as status of lubricator by choosing the compound curves present in the section between the $Anguk{\sim}Jongno3-ga$ Stations of the Route No. 3 among the compound curve tracks of the Seoul Metro Routes No. 3 & 4 at which abnormal wearing is generated continuously.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1594-1598
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• 2005

Scopoletin (6-methoxy-7-hydrorycournarin) is a phenolic coumarin and a member of the phytoalexins. In this study we investigated whether scopoletin causes apoptosis in human hepatoma HepG2 cells and, if so, by what mechanisms. We report that scopoletin induced apoptosis as confirmed by a chromatin condensation. The signal cascade acivated by scopoletin included the activation of caspase-3 as evidenced by increased pretense activity. Activation of caspase-3 resulted in the cleavage of 116 kDa poly(ADP-ribose) polymerase (PARP) to 85 kDa cleavage product in a dose-dependent fashion. Also, scopoletin-induced apoptotic mechanism of HepG2 cells involved the generation of hydrogen peroxide. Taken together, these results suggest that scopgletin induces hydrogen peroxide generation, which, in turn, causes activation of caspase-3, degradation of PARP, and eventually leads to apoptotic cell death in HepG2 cells.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.499-507
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• 2024

Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiationinduced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP⁺/NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP⁺ production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.

• Nuclear Engineering and Technology
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• v.54 no.7
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• pp.2395-2407
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• 2022

The sodium-cooled fast reactor is among the innovative nuclear technologies selected in the framework of the development of Generation IV concepts, allowing the irradiation of uranium-plutonium mixed oxide fuels (MOX). A fundamental step for the safety assessment of MOX-fuelled pins for fast reactor applications is the evaluation, by means of fuel performance codes, of the integral thermal-mechanical behaviour under irradiation, involving the fission gas behaviour and release in the fuel-cladding gap. This work is dedicated to the performance analysis of an inner-core fuel pin representative of the ASTRID sodium-cooled concept design, selected as case study for the benchmark between the GERMINAL and TRANSURANUS fuel performance codes. The focus is on fission gas-related mechanisms and integral outcomes as predicted by means of the SCIANTIX module (allowing the physics-based treatment of inert gas behaviour and release) coupled to both fuel performance codes. The benchmark activity involves the application of both GERMINAL and TRANSURANUS in their "pre-INSPYRE" versions, i.e., adopting the state-of-the-art recommended correlations available in the codes, compared with the "post-INSPYRE" code results, obtained by implementing novel models for MOX fuel properties and phenomena (SCIANTIX included) developed in the framework of the INSPYRE H2020 Project. The SCIANTIX modelling includes the consideration of burst releases of the fission gas stored at the grain boundaries occurring during power transients of shutdown and start-up, whose effect on a fast reactor fuel concept is analysed. A clear need to further extend and validate the SCIANTIX module for application to fast reactor MOX emerges from this work; nevertheless, the GERMINAL-TRANSURANUS benchmark on the ASTRID case study highlights the achieved code capabilities for fast reactor conditions and paves the way towards the proper application of fuel performance codes to safety evaluations on Generation IV reactor concepts.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.9
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• pp.1353-1362
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• 2016

Hanwoo, a Korean native cattle (Bos taurus coreana), has great economic value due to high meat quality. Also, the breed has genetic variations that are associated with production traits such as health, disease resistance, reproduction, growth as well as carcass quality. In this study, next generation sequencing technologies and the availability of an appropriate reference genome were applied to discover a large amount of single nucleotide polymorphisms (SNPs) in ten Hanwoo bulls. Analysis of whole-genome resequencing generated a total of 26.5 Gb data, of which 594,716,859 and 592,990,750 reads covered 98.73% and 93.79% of the bovine reference genomes of UMD 3.1 and Btau 4.6.1, respectively. In total, 2,473,884 and 2,402,997 putative SNPs were discovered, of which 1,095,922 (44.3%) and 982,674 (40.9%) novel SNPs were discovered against UMD3.1 and Btau 4.6.1, respectively. Among the SNPs, the 46,301 (UMD 3.1) and 28,613 SNPs (Btau 4.6.1) that were identified as Hanwoo-specific SNPs were included in the functional genes that may be involved in the mechanisms of milk production, tenderness, juiciness, marbling of Hanwoo beef and yellow hair. Most of the Hanwoo-specific SNPs were identified in the promoter region, suggesting that the SNPs influence differential expression of the regulated genes relative to the relevant traits. In particular, the non-synonymous (ns) SNPs found in CORIN, which is a negative regulator of Agouti, might be a causal variant to determine yellow hair of Hanwoo. Our results will provide abundant genetic sources of variation to characterize Hanwoo genetics and for subsequent breeding.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.136-145
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• 2024

People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-β-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4⁺T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-β-dependent manner and induces CD4⁺T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-β and inhibit CD4⁺T cell proliferation, directly regulated Treg differentiation from CD4⁺T cells. These results indicate that the IF regimen enhances the TGF-β-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.

• Journal of Life Science
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• v.24 no.8
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• pp.903-909
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• 2014

Plants are an invaluable source of potential new anti-cancer drugs. Sasa quelpaertensis Nakai (Korean name, Jeju-Joritdae) is one of these plants with medical value, which is a bamboo grass widely distributed in Mt. Halla on Jeju Island, Korea. Here, we investigated the apoptotic effects of S. quelpaertensis leaf extracts in six human cancer cell lines (A549, MCF-7, HepG-2, Hela, HCT116 and A375). MTT assay signified the antiproliferative nature of S. quelpaertensis extracts against all tested cancer cells: S. quelpaertensis displayed slight cytotoxicity against A549, MCF-7 and HepG-2 cells, whereas it was exclusively cytotoxic to Hela, HCT116 and A375 cells. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). PI staining indicated increasing accumulation of Hela, HCT116 and A375 cells at sub-G1 phase. Further events like generation of nitric oxide ($NO^{\bullet}$) were accompanied in the S. quelpaertensis Nakai-induced apoptosis. Augmented $NO^{\bullet}$ generation resulted in the DNA fragmentation of Hela, HCT116 and A375 cells by treatment with S. quelpaertensis leaf extracts. These results suggest that S. quelpaertensis may be a potential natural resource for treating cancer cell. To identify the exact mechanisms of molecular mechanism of S. quelpaertensis induced apoptosis awaits further investigation.