• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.449-456
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• 2023

N-methyl-D-aspartate (NMDA) receptors are ionic glutamine receptors involved in brain development and functions such as learning and memory formation. NMDA receptor inhibition is associated with autophagy activation. In this study, we investigated whether the NMDA receptor antagonists, memantine and ifenprodil, induce autophagy in human retinal pigment epithelial cells (ARPE-19) to remove N-retinylidene-N-retinylethanolamine (A2E), an intracellular lipofuscin component. Fluorometric analysis using labeled A2E (A2E-BDP) and confocal microscopic examination revealed that low concentrations of NMDA receptor antagonists, which did not induce cytotoxicity, significantly reduced A2E accumulation in ARPE-19 cells. In addition, memantine and ifenprodil activated autophagy in ARPE-19 cells as measured by microtubule-associated protein 1A/1B-light chain3-II formation and phosphorylated p62 protein levels. Further, to understand the correlation between memantine- and ifenprodil-mediated A2E degradation and autophagy, autophagy-related 5 (ATG5) was depleted using RNA interference. Memantine and ifenprodil failed to degrade A2E in ARPE-19 cells lacking ATG5. Taken together, our study indicates that the NMDA receptor antagonists, memantine and ifenprodil, can remove A2E accumulated in cells via autophagy activation in ARPE-19 cells.

• Genomics & Informatics
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• v.19 no.4
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• pp.48.1-48.10
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• 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes small envelope protein (E) that plays a major role in viral assembly, release, pathogenesis, and host inflammation. Previous studies demonstrated that pyrazine ring containing amiloride analogs inhibit this protein in different types of coronavirus including SARS-CoV-1 small envelope protein E (SARS-CoV-1 E). SARS-CoV-1 E has 93.42% sequence identity with SARS-CoV-2 E and shared a conserved domain NS3/small envelope protein (NS3_envE). Amiloride analog hexamethylene amiloride (HMA) can inhibit SARS-CoV-1 E. Therefore, we performed molecular docking and dynamics simulations to explore whether amiloride analogs are effective in inhibiting SARS-CoV-2 E. To do so, SARS-CoV-1 E and SARS-CoV-2 E proteins were taken as receptors while HMA and 3-amino-5-(azepan-1-yl)-N-(diaminomethylidene)-6-pyrimidin-5-ylpyrazine-2-carboxamide (3A5NP2C) were selected as ligands. Molecular docking simulation showed higher binding affinity scores of HMA and 3A5NP2C for SARS-CoV-2 E than SARS-CoV-1 E. Moreover, HMA and 3A5NP2C engaged more amino acids in SARS-CoV-2 E. Molecular dynamics simulation for 1 ㎲ (1,000 ns) revealed that these ligands could alter the native structure of the proteins and their flexibility. Our study suggests that suitable amiloride analogs might yield a prospective drug against coronavirus disease 2019.

• Journal of the Korean Magnetics Society
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• v.11 no.2
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• pp.58-62
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• 2001

The L $i_{0.5}$F $e_{2.5-x}$A $l_{x}$ $O_4$ systems (x=0, 0.3, 0.6, 0.9, 1.2, 1.5) were investigated by X-ray diffraction and Mossbauer spectroscopy. The structure of all the samples is cubic spinel type and lattice constant decrease with increasing Al content x. The Moissbauer spectra reveal two sextet for 0$\leq$x$\leq$0.6, two sextet and a doublet for 0.9$\leq$x$\leq$1.2, and a doublet for x=1.5. The cation distribution of the samples is (L $i_{1-a}$$^{+}$F $e_{a}$ $^{3+}$)$^{A}$[L $i_{a-0.5}$$^{+}$A $l_{2.5-a-x}$$^{+}$F $e_{2.5-a-x}$$^{3+}$]$^{B}$ $O_4$$^{2-}$ and substituted $Al^{3+}$ ions decrease the covalency of F $e^{3+}$- $O^{2-}$ bond in B-sites and A-B super-exchange interactions.tions.s.tions.ons.s.

• YAKHAK HOEJI
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• v.45 no.4
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• pp.339-346
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• 2001

A new oxygenated monoterpene (4) was isolated from the methanol extract of the aerial part of Erechtites hieracifolia together with six known components, a dimethylheptane (1), three ionone derivatives (2, 3 and 7) and two phenylpropanoids (5 and 6). Their structures were identified by means of physico-chemical and spectral data to be (2E, 5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal (1), 3(R)-hydroxy-5,6-epoxy-$\beta$-ionone (2), 3(R)-hydroxy-5,6-epoxy-7-ionol (3), (3E, 6E)-3,7-dimethylocta-3,5-dien-1,2,7-triol(4), 2-hydroxy-4-(2-propenyl)phenyl-$\beta$-D-glucopyranoside (5), 2-methoxy-4-(2-propenyl)phenyl -$\beta$-D-glucopyra-noside (6) and (6R, 9R)-3-oxo-$\beta$-ionol-$\alpha$-D -glucopyranoside (7).

• Microbiology and Biotechnology Letters
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• v.16 no.2
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• pp.111-118
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• 1988

The growth inhibition of enteropathogenic Escheriohia coli $A_2$and Escherichia coli G$_7$, causing the diarrhea in piglets, by the organic acid producing bacteria was studied in vitro. The metabolites of the organic acid bacteria, such as lactic acid, acetic acid inhibited the growth of E. coli $A_2$and E. coli G$_7$ in BL medium. The more the organic acid producing bacteria have ability to produce the organic acids, the higher these bacteria excelled the inhibitory efficacy against enteropathogenic E. coli. Among the strains examined, Lactobacillus casei Y and Streptococcus faecium C showed relatively strong growth inhibition against enteropathogenic E. coli.. When the organic acid producing bacteria and the enteropathogenic E. coli were incubated simultaneously in BL medium, bacteriostasis of E. coli was observed when the pH of BL culture was lowered to 5.0, and bacteriocidal effect was observed when the pH became Bess than 4.5, E. coli. $A_2$was more resistant to the organic acid bacteria than E. coli G$_7$.

• Restorative Dentistry and Endodontics
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• v.48 no.3
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• pp.29.1-29.8
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• 2023

Objectives: This study tested the hypothesis that cryotherapy duration influences lipopolysaccharide (LPS)-induced inflammation in a rat model. Materials and Methods: Six Wistar rats (Rattus norvegicus albinus) were used. Five sites were selected per animal and divided into 5 groups: a negative control group (NC), 2 positive control groups (PC1 and PC2), and 2 experimental groups (E1 and E2). Cryotherapy was applied for 1 minute (E1) or 5 minutes (E2). An acute inflammatory response was induced in the PC and E groups via subcutaneous administration of 0.5 mL/kg. In the PC2 group, a catheter was inserted without additional treatment. For the E1 and E2 groups, 2.5℃ saline solution was administered through the implanted catheters for 1 and 5 minutes, respectively. The rats were sacrificed, and samples were obtained and processed for histological analysis, specifically examining the presence of polymorphonuclear neutrophils and hemorrhage. The χ² test was used to compare the presence of acute inflammation across groups. Dependent variables were compared using the linear-by-linear association test. Results: Inflammation and hemorrhage varied significantly among the groups (p = 0.001). A significantly higher degree of acute inflammation was detected (p = 0.0002) in the PC and E1 samples than in the E2 group, in which cryotherapy was administered for 5 minutes. The PC and E1 groups also exhibited significantly greater numbers of neutrophils (p = 0.007), which were essentially absent in both the NC and E2 groups. Conclusions: Cryotherapy administration for 5 minutes reduced the acute inflammation associated with LPS and catheter implantation.

• Journal of Aquaculture
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• v.11 no.2
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• pp.241-248
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• 1998

Effects of A23187 on estradiol$-17^{\beta}$-induced vitellogenin (VTG) induction were electrophore-tically examined in primary hepatocyte cultures in rainbow trout. hepatocytes were predultured for 2 days and then estradiol-$17^{\beta}$(E2, $2{\times}10^{-6}$M) and calcium ionophore (A23187, $10^{-7)$~$10^{-5}$ M) were added to the incubation medium. The hepatocytes were cultured for 7 more days. In addition, effects of A23187 on $E_2$-primed VTG production were investigated for 7 days. The addition of A23187 ($10^{-7)$~$10^{-5}$M) to the incubation medium specifically reduced VTG production by hepatocytes in a concentration-dependent way. The addition of A23187 significantly reduced the rate of $E_2$-primed VTG production to 18% of the control (E2 only) on Day 7. However, $E_2$-primed VTG production was reduced to 47% of the control by withdrawal of $E_2$ from the incubation medium. Therefore, these results suggest that intracellualr sequestered calcium could regulate VTG synthesis at the translational and/or post-translational stage.

• Archives of Pharmacal Research
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• v.11 no.1
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• pp.33-40
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• 1988

Two new nitro analogs of tranylcypromine, (E)-2-(p-nitrophenyl)cyclopropylamine ((E)-p-NTCP) and (E)-2-(m-nitrophenyl)cyclopropylamine ((E)-m-NTCP) were synthesized in order to examine the effect of aromatic nitro substitution on the MAO-inhibitory activity of 2-phenylcyclopropylamines. The compounds were obtained by treating t-butyl (E)-2-(p-nitrophenyl) cyclopropanecarbamate and t-butyl (E)-2-(m-nitrophenyl)cyclopropanecarbamate with p-toluenesulfonic acid in $CH_3$CN. Inhibitions of rat brain mitochondrial MAO-A and B by the compounds were examined using serotonin and benzylamine as the substrate at both in vitro and ex vivo levels. It was found from in vitro measurements that (E)-p-NTCP at $6.0{\times}10^{-5}M$ elicited merely 22.5% inhibition against MAO-B without any effect on MAO-A. In contrast, (E)-m-NTCP showed fair degrees of inhibitions of MAO-A and B with $IC_{50}$ values, $2.5{\times}10^{-7}M\;and\;1.4{\times}10^{-6}M$, respectively. It was also noted from (E)-m-NTCP that m-nitro substitution caused a shift of selectivity of the inhibition toward MAO-A. According to ex vivo measurements at 1.5, 3, 6, and 12 hr following the administration of a dose of 0.015 mmol/kg, i.p. to the rats, the inhibition percents of MAO-A by (E)-m-NTCP were 58.6, 63.7 63.6, and 46.6%, slightly lower than those observed by tranylcypromine. Whereas, (E)-m-NTCP at the same dose level did not show significant inhibitions against both MAO-A and MAO-B. Possible reasons for the difference in potencies between (E)-m-NTCP and (E)-p-NTCP were sought in relation to differing electron withdrawing effects of m- and p-substituents which will influence electron density of the side chain amino functions and the partitions.

• Molecules and Cells
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• v.25 no.2
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• pp.172-177
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• 2008

Eukaryotic translation initiation factor 5B (eIF5B) plays a role in recognition of the AUG codon in conjunction with translation factor eIF2, and promotes joining of the 60S ribosomal subunit. To see whether the eIF5B proteins of other organisms function in Saccharomyces cerevisiae, we cloned the corresponding genes from Oryza sativa, Arabidopsis thaliana, Aspergillus nidulans and Candida albican and expressed them under the control of the galactose-inducible GAL promoter in the $fun12{\Delta}$ strain of Saccharomyces cerevisiae. Expression of Candida albicans eIF5B complemented the slow-growth phenotype of the $fun12{\Delta}$ strain, but that of Aspergillus nidulance did not, despite the fact that its protein was expressed better than that of Candida albicans. The Arabidopsis thaliana protein was also not functional in Saccharomyces. These results reveal that the eIF5B in Candida albicans has a close functional relationship with that of Sacharomyces cerevisiae, as also shown by a phylogenetic analysis based on the amino acid sequences of the eIF5Bs.

• Preventive Nutrition and Food Science
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• v.5 no.4
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• pp.213-218
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• 2000

The purpose of the study was to investigate the effects of dietary green tea catechin and vitamin E on the phospholipse {TEX}$A_{2}${/TEX} activity and th antioxidative defense system in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats weighing 100$\pm$10 gm were randomly assigned to one normal and five STZ-induced diabetic groups. The diabetic groups were assigned either a catechin-free diet (DM group), 0.5% catechin diet (DM-0.5C group), 1% catechin diet (DM-1C group), vitamin E-free diet (DM-0E group), and 400 mg vitamin E per kg diet (DM-400E group) according to the levels of dietary catechin or vitamin E supplementation. The vitamin E levels of the normal, DM, DM-0.5C, and DM-1C groups were 40 mg per kg diet. Diabetes was experimentally induced by an intravenous injection of streptozotocin after 4 weeks of feeding the five experimental diets. The animals were sacrificed on the 6th day of he diabetic state. The body weight gains were lower in all five diabetic groups after the STZ injection. The platelet phospholipase {TEX}$A_{2}${/TEX}({TEX}$PLA_{2}${/TEX}) activity in the diabetic groups was higher than that in the normal group. However, the enzyme activity in the DM-0.5C, DM-1C, and DM-400E groups was lower than that in the DM and DM-0E groups. The cytochrome {TEX}$P_{450}${/TEX} and cytochrome {TEX}$b_{5}${/TEX} content and NADPH-cytochrome {TEX}$P_{450}${/TEX} reductase activity were about 50~110% higher in the DM and DM-0E groups than in the normal group, yet significantly reduced by either catechin or vitamin E supplementation. The superoxide dismutase (SOD) content in the liver did not differ significantly in any of the groups. However, the glutathione peroxidase (GSHpx) activity was generally lower in the diabetic groups, compared with the normal group, whereas that of the DM-0.5C, DM-1C, and DM-400E groups was significantly higher compared with that of the DM and DM-0E groups. The levels of thiobarbituric acid reactive substances (TBARS) in the liver tissue were 148% and 201% higher in the DM and DM-0E groups, respectively, compared with the normal group, however, these levels were reduced by either catechin or vitamin E supplementation (DM-0.5, DM-1C and DM-400E). Accordingly, the present results indicate that STZ-induced diabetic rats exhibited an imbalance between free radical generation and scavenger systems in the liver which led to the acceleration of lipid peroxidation. However, these abnormalities were reduced and the antioxidative defense system was restored by either dietary catechin or vitamin E supplementation. In conclusion, the effects of dietary catechin or vitamin E in streptozotocin-induced diabetic rats would appear to inhibit lipid peroxidation as an anti-oxidant by regulating the activity of {TEX}$PLA_{2}${/TEX}.