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Glucosylsphingosine Activates Serotonin Receptor 2a and 2b: Implication of a Novel Itch Signaling Pathway

  • Afzal, Ramsha;Shim, Won-Sik
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.497-503
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    • 2017
  • Recent reports claimed that glucosylsphingosine (GS) is highly accumulated and specifically evoking itch-scratch responses in the skins of atopic dermatitis (AD) patients. However, it was unclear how GS can trigger itch-scratch responses, since there were no known molecular singling pathways revealed yet. In the present study, it was verified for the first time that GS can activate mouse serotonin receptor 2a (mHtr2a) and 2b (mHtr2b), but not 2c (mHtr2c) that are expressed in HEK293T cells. Specifically, effects of GS on all mouse serotonin receptor 2 subfamily were evaluated by calcium imaging techniques. The GS-induced intracellular calcium increase was dose-dependent, and antagonists such as ketanserin (Htr2a antagonist) and RS-127445 (Htr2b antagonist) significantly blocked the GS-induced responses. Moreover, the proposed GS-induced responses appear to be mediated by phospholipase C (PLC), since pretreatment of a PLC inhibitor U-73122 abolished the GS-induced responses. Additionally, the GS-induced calcium influx is probably mediated by endogenous TRPC ion channels in HEK293T cells, since pretreatment of SKF-96365, an inhibitor for TRPC, significantly suppressed GS-induced response. In conclusion, the present study revealed for the first time that GS can stimulate mHtr2a and mHtr2b to induce calcium influx, by utilizing PLC-dependent pathway afterwards. Considering that GS is regarded as a pruritogen in AD, the present study implicates a novel GS-induced itch signaling pathway.

Synthesis of Methyl 2, 6-Dimethyl-5-(1', 2'-Dioxo-2'-Ethoxyethyl)-4-(3'-Nitrophenyl)-1, 4 Dihydropyridine -3-Carboxylate

  • Suh, Jung-Jin;Hong, You-Hwa
    • Archives of Pharmacal Research
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    • v.13 no.3
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    • pp.257-260
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    • 1990
  • Hantzch's type reaction of methyl acetopyruvate (2a), methyl 3-aminocrotonate (3) and 3-nitrobenzaldehyde (4) led to dimethyl 3-acetyl-6-methyl-4-(3'-nitrophenyl)-2, 5-dicarboxylate (5a) and methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'-methoxyethyl)-4-(3' nitrophenyl)- 2, 5-dicarboxylate (5a) and methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'methoxyethyl_4-(3' nitrophenyl)1, 4-dihydropyridine-3-carboxylate (6a) in 26.7 and 9.2% yield, respectively. On the other hand, methyl 2, 60dimethyl-4-(3'-nitrophenyl)-1, 4-dihydropyridine 3-carboxylate (9) was acylated by ethyl oxaly chloride to give methyl 2, 6-dimethyl-5-(1', 2'-dioxo-2'-ethoxyethyl)-4-(3'-nitrophenyl)-a, 4-dihydropyridine-3-carboxylate (6b) in 76.8% yield.

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한국인으로부터 분리한 비피더스균의 특성과 Bifidobacterium longum A-2의 임상실험에 관한 연구

  • Kim, Yeong-Chan
    • Proceedings of the Korean Society for Food Science of Animal Resources Conference
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    • 1998.10a
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    • pp.83-106
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    • 1998
  • This study was conducted to investigate the probiotics(acid and bile resistance, fermentation properties, viability, cholesterol assimilation, antimicrobial activity, antimutagenicity, and immunoactivation) of the strains of bifidobacteria isolated from healthy Koreans and to investigate the effects of oral administration of Bifidobacterium longum A-2 on the fecal microflora, ${\beta}-glucuronidase$ activity, pH values, Ammonia concentration. The experimental results are summarized as follows: The probiotics were tested for 23 strains including three commer챠al strains as controls. Compared to other strains, strains of A-2 and A-9 showed more acid resistance whereas A-2, A-5, A-13, A-14, A-18 and A-22 showed excellent bile resistances. The properties of bifidobacteria during fermentation were tested. Strains of A-1, A-2, A-3, A-4, A-6, and A-23 resulted in less than pH 4.5 and titratable acidity over 0.90 after 24 hr of fermentation. When the strains of A-2 was grown with glucose, maltose, and fructooligosaccharide, the acetic acid production were higher than with sorbitol and mannitol. The storage stability of the strains of A-2 and A-22 were tesed, indicating the strain A-2 was more stable over 10 days of storage at both $4^{\circ}C$ and $20^{\circ}C$ than A-22. The strains of A-8, A-10, A-11, A-12 and A-20 assimilated more than 30% of cholesterol included in the media. The strains of A-1 and A-2 showed antimicrobial activity against Sta. aureus. The antimutagenicity of the strains were also tested, showing that the mutation was suppressed more by three strains(A-2, A-12, and A-23). In addition, strain A-5 improved immunological activity(phagocytosis, $TNF-{\alpha}$, IL-6) more than other strains. In the effects of oral administration of Bif. longum A-2, the number of fecal bifidobacteria was siginificantly increased(p<0.01) and the level of fecal ${\beta}-glucuronidase$ also was siginificantly reduced(p<0.05). However there were no siginificant differences in the level of Lαctobacilli, Enterobacteriaceae, Clostridium perfringens, pH and ammonia by the administration. The results suggested that Bif. longum A-2 may be met the criteria for probiotics culture.

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Inhibition of Cytochrome P450 by Propolis in Human Liver Microsomes

  • Ryu, Chang Seon;Oh, Soo Jin;Oh, Jung Min;Lee, Ji-Yoon;Lee, Sang Yoon;Chae, Jung-woo;Kwon, Kwang-il;Kim, Sang Kyum
    • Toxicological Research
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    • v.32 no.3
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    • pp.207-213
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    • 2016
  • Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an $IC_{50}$ value of 6.9, 16.8, and $43.1{\mu}g/mL$, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.

Synthesis and Sintering Behavior of Zr2WP2O12 Ceramics (Zr2WP2O12 세라믹스의 합성과 소결거동 연구)

  • Kim, Yong-Hyeon;Kim, Nam-Ok;Lee, Sang-Jin
    • Journal of the Korean Ceramic Society
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    • v.49 no.6
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    • pp.586-591
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    • 2012
  • $Zr_2WP_2O_{12}$ powder, which has a negative thermal expansion coefficient, was synthesized by a solid-state reaction with $ZrO_2$, $WO_3$ and $NH_4H_2PO_4$ as the starting materials. The synthesis behavior was dependent on the solvent media used in the wet mixing process. The $Zr_2WP_2O_{12}$ powder prepared with a solvent consisting of D. I. water was fully crystallized at $1200^{\circ}C$, showing a sub-micron particle size. According to the results obtained from a thermal analysis, a $ZrP_2O_7$ was synthesized at a low temperature of $310^{\circ}C$, after which it was reacted with $WO_3$ at $1200^{\circ}C$. A new sintering additive, $Al(OH)_3$, was applied for the densification of the $Zr_2WP_2O_{12}$ powders. The cold isostatically pressed samples were densified with 1 wt% $Al(OH)_3$ additive or more at $1200^{\circ}C$ for 4 h. The main densification mechanism was liquid-phase sintering due to the liquid which resulted from the reaction with amorphous or unstable $Al_2O_3$ and $WO_3$. The densified $Zr_2WP_2O_{12}$ ceramics showed a relative density of 90% and a negative thermal expansion coefficient of $-3.4{\times}10^{-6}/^{\circ}C$. When using ${\alpha}-Al_2O_3$ as the sintering agent, densification was not observed at $1200^{\circ}C$.

Annexin A2 gene interacting with viral matrix protein to promote bovine ephemeral fever virus release

  • Chen, Lihui;Li, Xingyu;Wang, Hongmei;Hou, Peili;He, Hongbin
    • Journal of Veterinary Science
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    • v.21 no.2
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    • pp.33.1-33.15
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    • 2020
  • Bovine ephemeral fever virus (BEFV) causes bovine ephemeral fever, which can produce considerable economic damage to the cattle industry. However, there is limited experimental evidence regarding the underlying mechanisms of BEFV. Annexin A2 (AnxA2) is a calcium and lipid-conjugated protein that binds phospholipids and the cytoskeleton in a Ca2+-dependent manner, and it participates in various cellular functions, including vesicular trafficking, organization of membrane domains, and virus proliferation. The role of the AnxA2 gene during virus infection has not yet been reported. In this study, we observed that AnxA2 gene expression was up-regulated in BHK-21 cells infected with the virus. Additionally, overexpression of the AnxA2 gene promoted the release of mature virus particles, whereas BEFV replication was remarkably inhibited after reducing AnxA2 gene expression by using the small interfering RNA (siRNA). For viral proteins, overexpression of the Matrix (M) gene promotes the release of mature virus particles. Moreover, the AnxA2 protein interaction with the M protein of BEFV was confirmed by GST pull-down and co-immunoprecipitation assays. Experimental results indicate that the C-terminal domain (268-334 aa) of AxnA2 contributes to this interaction. An additional mechanistic study showed that AnxA2 protein interacts with M protein and mediates the localization of the M protein at the plasma membrane. Furthermore, the absence of the AnxA2-V domain could attenuate the effect of AnxA2 on BEFV replication. These findings can contribute to elucidating the regulation of BEFV replication and may have implications for antiviral strategy development.

Effect of Packaging Material and Oxygen Absorbant on Quality Properties of Yukwa (포장재질 및 탈산소재가 유과의 품질특성에 미치는 영향)

  • Lee, Yong-Hwan;Kum, Jun-Seok;Ahn, Yong-Sik;Kim, Woo-Jung
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.728-736
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    • 2001
  • Effects of packaging material and oxygen absorbant on physical and chemical properties of Yukwu were studied during storage to develop packaging conditions. The packaging materials used were PET/EVOH $(16\;{\mu}m)/PL$ : P1 and PET/EVOH $(24\;{\mu}m)/PL$ : P2 with or without oxygen absorbent (E1A : P1 and E2A : P2 for w/ $O_2$, absorbent, E1EA : P1 and E2EA : P2 for w/o $O_2$, absorbent). Color values for Yukwu indicated that L values of E1A, E1EA, E2A and E2EA were decreased during storage while those b values were increased. Hardness and chewiness of Yukwa were generally decreased, however those of E1A and E1EA were rather increased after 6 weeks of storage. Acid value of E2A had maintained less than 2.0 during 12 weeks of storage. E1A, E2A had the below of 20 in peroxide during 12 weeks. Aroma data by using electronic nose showed that there was no difference after 6 week storage time in different packaging materials. Sensory evaluation (Yukwa odor and rancid odor) showed very similar results with electronic nose one. E2A had the highest value of overall acceptability for sensory evaluation. Hardness and cheweness in physical measurement results had the highest correlation with hardness, crispness, overall-acceptability in sensory evaluation results.

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Photodegradation of Pyrene, Chrysene and Benzo[a]pyrene in Water (II) (수중의 Pyrene, Chrysene 및 Benzo[a]pyrene의 광분해(II))

  • 감상규;김지용;주창식;이민규
    • Journal of Environmental Science International
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    • v.12 no.7
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    • pp.775-782
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    • 2003
  • The photodegradations of pyrene, chrysene and benzo[a]pyrene that were similar in structure among polycyclic aromatic hydrocarbons (PAHs) were investigated with a low-pressure mercury lamp(the wavelength of 253.7 nm and UV output of 1.35${\times}$10$\^$-3/J/s). The optimum concentrations of TiO$_2$ and H$_2$O$_2$ on the photodegradation of pyrene, chrysene and benzo[a]pyrene were 1 g/L and 1.5${\times}$10$\^$-3/ M, respectively. By these optimum concentrations, their rates increased with increasing the concentration of TiO$_2$ and H$_2$O$_2$ because the amounts of OH radical formed increased, but for the higher concentrations than the optimum, their rates decreased with increasing those concentrations because the white turbidity phenomena occurs in case of TiO$_2$ and H$_2$O$_2$ acts as an OH radical inhibitor. The photodegradation rates among the photodegradation processes such as UV, UV/TiO$_2$, UV/H$_2$O$_2$, and UV/H$_2$O$_2$/TiO$_2$ decreased in the following sequences.: UV/H$_2$O$_2$/TiO$_2$> UV/H$_2$O$_2$> UV/TiO$_2$> UV.

Sequential adsorption - photocatalytic oxidation process for wastewater treatment using a composite material TiO2/activated carbon

  • Andriantsiferana, Caroline;Mohamed, Elham Farouk;Delmas, Henri
    • Environmental Engineering Research
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    • v.20 no.2
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    • pp.181-189
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    • 2015
  • A composite material was tested to eliminate phenol in aqueous solution combining adsorption on activated carbon and photocatalysis with $TiO_2$ in two different ways. A first implementation involved a sequential process with a loop reactor. The aim was to reuse this material as adsorbent several times with in situ photocatalytic regeneration. This process alternated a step of adsorption in the dark and a step of photocatalytic oxidation under UV irradiation with or without $H_2O_2$. Without $H_2O_2$, the composite material was poorly regenerated due to the accumulation of phenol and intermediates in the solution and on $TiO_2$ particles. In presence of $H_2O_2$, the regeneration of the composite material was clearly enhanced. After five consecutive adsorption runs, the amount of eliminated phenol was twice the maximum adsorption capacity. The phenol degradation could be described by a pseudo first-order kinetic model where constants were much higher with $H_2O_2$ (about tenfold) due to additional ${\bullet}OH$ radicals. The second implementation was in a continuous process as with a fixed bed reactor where adsorption and photocatalysis occurred simultaneously. The results were promising as a steady state was reached indicating stabilized behavior for both adsorption and photocatalysis.

HILBERT-SCHMIDT INTERPOLATION ON AX=Y IN A TRIDIAGONAL ALGEBRA ALG${\pounds}$

  • Kang, Joo-Ho
    • The Pure and Applied Mathematics
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    • v.15 no.4
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    • pp.401-406
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    • 2008
  • Given operators X and Y acting on a separable complex Hilbert space H, an interpolating operator is a bounded operator A such that AX=Y. In this article, we investigate Hilbert-Schmidt interpolation problems for operators in a tridiagonal algebra and we get the following: Let ${\pounds}$ be a subspace lattice acting on a separable complex Hilbert space H and let X=$(x_{ij})$ and Y=$(y_{ij})$ be operators acting on H. Then the following are equivalent: (1) There exists a Hilbert-Schmidt operator $A=(a_{ij})$ in Alg${\pounds}$ such that AX=Y. (2) There is a bounded sequence $\{{\alpha}_n\}$ in $\mathbb{C}$ such that ${\sum}_{n=1}^{\infty}|{\alpha}_n|^2<{\infty}$ and $$y1_i={\alpha}_1x_{1i}+{\alpha}_2x_{2i}$$ $$y2k_i={\alpha}_{4k-1}x_2k_i$$ $$y{2k+1}_i={\alpha}_{4k}x_{2k}_i+{\alpha}_{4k+1}x_{2k+1}_i+{\alpha}_{4k+2}x_{2k+2}_i\;for\;all\;i,\;k\;\mathbb{N}$$.

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