• YAKHAK HOEJI
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• v.49 no.4
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• pp.347-354
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• 2005

Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.

• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.22-29
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• 2015

Objective : Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children. Methods : A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9. Results : The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss. Conclusion : Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.195-200
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• 2009

Zinc released from excited glutamatergic neurons accelerates amyloid ${\beta}$ (A ${\beta}$) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A ${\beta}$ concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A ${\beta}$ production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A ${\beta}$ 40 and A ${\beta}$ 42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both ${\beta}$-and ${\alpha}$-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A ${\beta}$ 40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A ${\beta}$ secretion.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.3063-3073
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• 2011

The synthesis and biological evaluation of 1-heteroarylmethyl 1,4-diazepane derivatives as potential T-type calcium channel blockers is described. In this study, we have identified the compound 21i exhibiting the most potent T-type calcium channel blocking activity with $IC_{50}$ value of 0.20 ${\mu}M$, which is superior to that of mibefradil.

• IMMUNE NETWORK
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• v.23 no.5
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• pp.42.1-42.21
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• 2023

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wildtype (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

• Bulletin of the Korean Chemical Society
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• v.30 no.6
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• pp.1357-1359
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• 2009

Many researchers studied cell culturing on surfaces with chemical functional groups. Previously, we reported surface properties of plasma polymerized ethylenediamine (PPEDA) films deposited by plasma enhanced chemical vapor deposition with various plasma conditions. Surface properties of PPEDA films can be controlled by plasma power during deposition. In this work, to analyze correlation of cell adherence/proliferation with surface property, we cultured rat intestinal epithelial cells-18 on the PPEDA films deposited with various plasma powers. It was shown that as plasma power was decreased, density of cells cultured on the PPEDA film surface was increased. Our findings indicate that plasma power changed the amine density of the PPEDA film surface, resulting in density change of cells cultured on the PPEDA film surface.

• Journal of Plant Biotechnology
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• v.43 no.1
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• pp.104-109
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• 2016

Rosa rugosa is a medicinal, ornamental, and edible plant native to Eastern Asian countries, including Korea, Japan, and China. The aim of this study was to establish a system for biomass production and secondary metabolite accumulation during in vitro culture and acclimatization of Rosa rugosa. The highest rate of multiple shoot proliferation was achieved with $8.8{\mu}M$ benzyladenine (BA) (83.3%). However, the number of shoots (14.4 per explant) at $4.4{\mu}M$ BA was higher than that at $8.8{\mu}M$ BA. Compared to BA, a combination of thidiazuron (TDZ) and indole butyric acid (IBA) exhibited significantly lower shoot induction, with only 50.0~79.2% and 4.2~16.7% relative shoot formation, respectively. During acclimatization, shoots were sampled every week and their total phenolic contents were analyzed. Among various growth factors, fresh weight showed the most dramatic increase from the 3rd week (88.0 mg/plant) to 4th week (132.7 mg/plant). Total phenolics and flavonoids contents were the highest at $1^{st}$ week of acclimatization. Depending on developmental stages, total phenolics and flavonoids contents were higher in 1-yr-old shoots grown ex vitro than in those of older field-grown or in vitro-grown plants. Amongst different ages of field grown plants, 6-year-old plants, the oldest in this study, showed the lowest content in total phenolics.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.85-91
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• 2021

Selective amino acid conjugation of bulky antibodies is a valuable asset for real-time diagnosis and therapy. However, selective conjugation incorporating a chelate-bearing radioactive atom into an antibody without affecting its immunoreactivity is a challenging task. A bifunctional chelator (BFC), a selective amino acid-targeting probe, and a linker have been developed to overcome this problem. Here, we report the synthesis of a novel propylene cross-bridged chelator (PCB)-1,8-N,N'-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane (TE2A)-luminol BFC via a click reaction and radiolabel it with a ⁶⁴Cu ion for tyrosine-selective conjugation of trastuzumab. In the initial optimization study, we tried different oxidative addition conditions such as electro-oxidation, hemin, horseradish peroxidase, iodogen tube, chloramine-T, and iodo beads. In this study, up to 82% of ⁶⁴Cu-PCB-TE2A-luminol was conjugated with the antibody in an iodo bead-catalyzed oxidative addition reaction with an isolated yield of 24.4%.

• Molecules and Cells
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• v.45 no.2
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• pp.53-64
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• 2022

Three-dimensional cultures of human neural tissue/organlike structures in vitro can be achieved by mimicking the developmental processes occurring in vivo. Rapid progress in the field of neural organoids has fueled the hope (and hype) for improved understanding of brain development and functions, modeling of neural diseases, discovery of new drugs, and supply of surrogate sources of transplantation. In this short review, we summarize the state-of-the-art applications of this fascinating tool in various research fields and discuss the reality of the technique hoping that the current limitations will soon be overcome by the efforts of ingenious researchers.

• BMB Reports
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• v.48 no.3
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• pp.139-146
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• 2015

Adaptive brain function and synaptic plasticity rely on dynamic regulation of local proteome. One way for the neuron to introduce new proteins to the axon terminal is to transport those from the cell body, which had long been thought as the only source of axonal proteins. Another way, which is the topic of this review, is synthesizing proteins on site by local mRNA translation. Recent evidence indicates that the axon stores a reservoir of translationally silent mRNAs and regulates their expression solely by translational control. Different stimuli to axons, such as guidance cues, growth factors, and nerve injury, promote translation of selective mRNAs, a process required for the axon's ability to respond to these cues. One of the critical questions in the field of axonal protein synthesis is how mRNA-specific local translation is regulated by extracellular cues. Here, we review current experimental techniques that can be used to answer this question. Furthermore, we discuss how new technologies can help us understand what biological processes are regulated by axonal protein synthesis in vivo.