• Journal of the Korean Chemical Society
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• v.5 no.1
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• pp.33-37
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• 1961

We have shown that carboxy-peptidase destroys the biological activity of angiotensin octa-and deca-peptides. Since Proline occurs as the seventh amino acid from the amino end of the chain and since carboxypeptidase does not cleave proline from a peptid chain, it is evident that the heptapeptid H.asp-arg-val-tyr-ileu-his-pro.OH is formed by this hydrolysis. This peptide must then be biologically inactive. In order to determine whether the phenyl group of the C-terminal amino acid was the necessary requirement for biological activity of the octapeptide, $ala^8$ angiotensin octapeptide(amino acids of peptides numbered from amino end) was synthesized. For this synthesis the four dipeptides were prepared: carbobenzoxy-L-prolyl-L-alanine-P-nitrobenzyl-ester, m.p. $134-135^{\circ}C,$ carbobenzoxy-L-isoleucyl-imidazole benzyl-L-histidine methyl ester, m.p. $114-116^{\circ}C,$ carbobenzoxy-L-valyl-L-tyrosine hydrazide and carbobenzoxy B-benzyl-L-aspartyl-nitro-L-arginine. The first three dipeptides were obtained as crystalline compounds. Imidazole-benzyl-L-histidine was used in the hope that it would block the histidine imidazole against side reactions in steps subsequent to the formation of the C-terminal tetrapeptide. Also, it was through that the imidazole benzylated peptides would be easier to crystallize. This, however, was not the case. The tetrapeptide, carbobenzoxy-L-isoleucyl-L-im, benzyl-histidyl, L-prolyl-L-alanine-nitrobenzyl ester was not obtained in a crystalline form. Neither could the mono-or dihydrobromide of the tetrapeptide free base be induced to crystallize. Carbobenzoxy-L-valyl-L-tyrosine azide was condensed with the tetrapeptide free base to yield the protected hexapeptide; carbobenzoxy-L-valyl-L-tyrosyl-L-isoleucyl-L-im, benzyl, histidyl-L-Prolyl-L-alanine-nitrobenzyl ester. Upon removal of the carbobenzoxy group with hydrogen bromide in acetic acid an amorphous free base hexapeptide ester was obtained. This compound gave the correct C, H, N analysis and contained the six amino acids in the correct ratio. The octapeptide was obtained by condensing this hexapeptide with carbobenzoxy-B-benzyl-L-aspartyl-nitro, L-arginine using the mixed anhydride method of condensation. This amorphous product was proven to be homogenous by chromatography in two solvent systems and upon hydrolysis yielded the eight amino acids in correct ratio. The five protecting groups were removed from the octapeptide by hydrogenolysis over palladium black catalyst. Biological assay of the free peptide indicated that it possessed less than 0.1 per cent of both pressor and oxytocic activity of the phenylalanine8 angiotensin. This suggests that the phenyl group is a point of attachment between angiotensin and its biological receptor site.

• Journal of Korean Neurosurgical Society
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• v.67 no.4
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• pp.418-430
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• 2024

Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

• Journal of the Korean Society of Marine Environment & Safety
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• v.30 no.5
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• pp.387-395
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• 2024

In 2011, the Fukushima nuclear power plant accident in Japan resulted in more than 1.3 million tons of radioactive contaminated water, and the Japanese government has been releasing large amounts of contaminated water into the ocean since 2023. This accident has raised concerns about marine pollution and seafood consumption, as well as the effects on highly radiosensitive children and fetuses. Radiation protection materials are being researched to better prepare for various radiation accidents, including marine radioactive contamination incidents. Natural radioprotectors have fewer side effects and are more easily commercialized than chemical radioprotectors. This study aimed to confirm the function of a mixture of folic acid and α-tocopherol, natural antioxidants, in protecting living organisms from radiation. In the experiment, Spraque-Dawley rats (SD rats) were used to induce pregnancy to target fetuses with high radiation sensitivity, and the second generation's skeletal system, blood analysis, body weight, spleen, brain, and small intestine were examined after birth. After administering a mixture of folic acid and α-tocopherol, the irradiated group showed significant recovery (p<0.05) in blood analysis, small intestinal villus length, and cerebral cortex thickness measurements compared to the comparison group (irradiated group), suggesting that the mixture of folic acid and α-tocopherol is effective for in vivo radioprotection in a radioactive contaminated environment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Korean Journal of Environmental Biology
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• v.33 no.4
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• pp.450-458
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• 2015

The heat shock proteins (Hsps), one of the most highly conserved groups of proteins, play crucial roles in protecting cells against environmental stressors, such as temperature, salinity, heavy metals and pathogenic bacteria. The glutathione S-transferases (GST) have important role in detoxification of oxidative damage, environmental chemicals and environmental stress. The purpose of this study is to investigate the gene expression of Hsp70 and GST on change of temperature and salinity in Mytilus coruscus. The M. coruscus was cultured in incubator of separate temperature and salinity (8, 20, $30^{\circ}C{\times}20$‰, 25‰, 30‰) for 28 days. Ten individuals in each group were selected after each 14 and 28 days exposure. Results that the expression of Hsp70 mRNA was no significant changed in M. coruscus exposed to temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$) and salinity (20‰, 25‰, 30‰) for 14 days. Whereas the expression of Hsp70 mRNA was increased in exposure to temperature $30^{\circ}C$ and salinity (20‰, 25‰, 30‰) for 28 days. The expression of GST mRNA was increased in exposure to temperature $30^{\circ}C$, salinity (25‰, 30‰) for 14 days and temperature ($8^{\circ}C$, $20^{\circ}C$, $30^{\circ}C$), salinity (20‰, 25‰, 30‰) for 28 days. These results suggest that Hsp70 and GST were played roles in biomarker gene on the thermal and salinity stress.

• Journal of Chest Surgery
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• v.46 no.6
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• pp.413-425
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• 2013

Background: Graft vessel preservation solution in coronary artery bypass surgery is used to maintain the graft conduit in optimal condition during the perioperative period. Nafamostat mesilate (NM) has anticoagulation and anti-inflammatory properties. Therefore, we investigated NM as a conduit preservative agent and compared it to papaverine. Methods: Sprague-Dawley (SD) rat thoracic aortas were examined for their contraction-relaxation ability using phenylephrine (PE) and acetylcholine (ACh) following preincubation with papaverine and NM in standard classical organ baths. Human umbilical vein endothelial cells (HUVECs) were cultured to check for the endothelial cell viability. Histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were performed on the thoracic aortas of SD rats. Results: The anti-contraction effects of papaverine were superior to those of NM at PE (p<0.05). The relaxation effect of NM on ACh-induced vasodilatation was not statistically different from that of papaverine. Viability assays using HUVECs showed endothelial cell survival rates of >90% in various concentrations of both NM and papaverine. A histopathological study showed a protective effect against necrosis and apoptosis (p<0.05) in the NM group. Conclusion: NM exhibited good vascular relaxation and a reasonable anti-vasocontraction effect with a better cell protecting effect than papaverine; therefore, we concluded that NM is a good potential conduit preserving agent.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.109-115
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• 2001

Background: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. Methods: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon ${\alpha}$ ($IFN{\alpha}$). Results: In the absence of $IFN{\alpha}$, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of $IFN{\alpha}$-mediated protection against VSV infection. The $IFN{\alpha}$-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great. On the contrary, the viral titers in the $IFN{\alpha}$-treated DBD clones increased at 24 h then decreased by 48 h. Conclusion: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the $IFN{\alpha}$- mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.3017-3021
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• 2011

Two chiral stationary phases (CSPs) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 bonded covalently to silica gel were applied for the first time to the resolution of racemic vigabatrin and its analogue ${\gamma}$-amino acids and the resolution results were compared to those on the commercially available Crownpak CR(+) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 coated dynamically onto octadecylsilica gel. While vigabatrin was not resolved at all on Crownpak CR(+), it was resolved quite well on the two CSPs. Among four vigabatrin analogue ${\gamma}$-amino acids, only two were resolved on Crownpak CR(+), but three were resolved on the CSP (CSP 1) containing residual silanol groups and all of four were resolved on the CSP (CSP 2) containing residual silanol group-protecting n-octyl groups. The improved lipophilicity in CSP 2 was proposed to be responsible for its superiority to CSP 1 for the resolution of vigabatrin and analogue ${\gamma}$-amino acids. In addition, the composition of aqueous mobile phase was found to affect the chiral recognition behaviors for the resolution of vigabatrin and analogue ${\gamma}$-amino acids on CSP 2.

• BMB Reports
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• v.32 no.4
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• pp.370-378
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• 1999

The effects of carnosine and related compounds (CRC) including anserine, homocarnosine, histidine, and ${\beta}$-alanine, found in most mammalian tissues, were investigated on in vitro glucose oxidation and glycation of human serum albumin (HSA). Carnosin and anserine were more reactive with D-glucose than with L-lysine. In the presence of $10\;{\mu}M$ Cu (II), although carnosine and anserine at low concentrations effectively inhibited formation of ${\alpha}$-ketoaldehyde from D-glucose, they increased generation of $H_2O_2$ in a dose-dependent manner. Carnosine, homocarnosine, anserine, and histidine effectively inhibited hydroxylation of salicylate and deoxyribose degradation in the presence of glucose and $10\;{\mu}M$ Cu (II). In the presence of 25 mM D-glucose, copper and ascorbic acid stimulated carbonyl formation from HSA. Except for ${\beta}$-alanine, CRC effectively inhibited the copper-catalyzed carbonyl formation from HSA. The addition of 25 mM D-glucose and/or $10\;{\mu}M$ Cu (II) to low density lipoprotein (LDL) increased formation of conjugated dienes. CRC effectively inhibited the glucose and/or copper-catalyzed LDL oxidation. CRC also inhibited glycation of HSA as determined by hydroxymethyl furfural and lysine with free ${\varepsilon}$-amino group. These results suggest that CRC may play an important role in protecting against diabetic complications by reacting with sugars, chelating copper, and scavenging free radicals.

• Strategy21
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• s.32
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• pp.97-122
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• 2013

The basic stance of the Republic of Korea Ministry of Foreign Affairs was 'quiet diplomacy'. However, there had been demands for specific plans for practical protection of Dokdo. In 2011, Prime Minister Kim Hwang Sik mentioned that they are reviewing measures of stationing marines on Dokdo, while on August 10th, 2012, former president Lee Myung Bak visited Dokdo. The visit itself was meaningful as he was the first supreme commander to visit Dokdo. This paper studies on the necessity of naval power on Dokdo to maintain its effective control. The effective control must be done by a national organization in a peaceful and unimpaired method. If so, can stationing naval power, whether directly or indirectly, on Dokdo be considered a violation of 'peaceful' method? A 'peaceful' effective of control meas the right of sovereignty over a territory without other country's protest. In such terms, protecting a territory falls under practicing the right of sovereignty, and therefore does not violate 'peaceful'. In addition, looking at international cases such as Ligitan/Sipadan Case and Pedra Blanca Case, evidences such as 'navy activity', 'flyng ensign', and 'military communication facility installation' was used. In ter case of Yemen-Eritrea dispute over Hanish, methods on effective control over island and sea was also ruled by the installation of military posts and military surveillance activities. Thus, stationing naval power on Dokdo can be a way of maintaining effective control per international law. To station naval poer on Dokdo, Presidential Instruction 24 integrated Defense Guideline Enforcement Ordinance, which is domestic law, must be revised. Reason being, the Enforcement Ordinance states that the navy area of responsibility excluded Ullundo, where Dokdo is under jurisdiction of Ullungdim thus excluding navy control. In addition, considering the diplomatic situation, it is more fut to install navy radar site on Dokdo rather than 'stationing marines'. In other words, enforcing surveillance in the vicinity of Dokdo and installing radar site instead of stationing direct combatants is one way of practicing effective control without stimulating diplomatic disputes.