• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.115-120
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• 2004

Molecular imaging is a rapidly growing field due to the advances in molecular biology and imaging technologies. With the introduction of imaging reporter genes into the cell, diverse cellular processes can be monitored, quantified and imaged non-invasively in vivo. These precesses include the gene expression, protein-protein interactions, signal transduction pathways, and monitoring of cells such as cancer cells, immune cells, and stem cells. In the near future, molecular imaging analysis will allow us to observe the incipience and progression of the disease. These will make us easier to give a diagnosis in the early stage of intractable diseases such as canter, neuro-degenerative disease, and immunological disorders. Additionally, molecular imaging method will be a valuable tool for the real-time evaluation of cells in molecular biology and the basic biological studies. As newer and more powerful molecular imaging tools become available, it will be necessary to corporate clinicians, molecular biologists and biochemists for the planning, interpretation, and application of these techniques to their fullest potential. in order for such a multidisciplinary team to be effective, it is essential that a common understanding of basic biochemical and molecular biologic techniques is achieved. Basic molecular techniques for molecular imaging methods are presented in this paper.

• Molecules and Cells
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• v.45 no.3
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• pp.134-147
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• 2022

The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

• Bulletin of the Korean Chemical Society
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• v.29 no.9
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• pp.1742-1746
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• 2008

Catechol and caffeine were simultaneously analyzed with a bismuth-immobilized carbon nanotube paste electrode (BPE) using square wave (SW) stripping voltammetry. Optimum analytical conditions were determined. Simultaneous working ranges of 100-1,500 $mgL^{-1}$ for caffeine and 5-75 $mgL^{-1}$ for catechol were obtained. In the separated cell systems, a working range of 0.1-2.1 $mgL^{-1}$ catechol with a correlation coefficient of 0.9935, and a working range of 10-210 $mgL^{-1}$ caffeine with a correlation coefficient of 0.9921 were obtained. A detection limit (S/N) of 0.15 $mgL^{-1}$ (7.7 ${\times}$ $10^{-7}$ M) and a detection limit of 0.02 $mgL^{-1}$ (1.82 ${\times}$ $10^{-7}$ M), respectively, manifested for catechol and caffeine. It was found that three macro-type electrode systems could be implanted in fish and rat neuro cells. For both ions, the ion currents were observed. The physiological impulse conditions and the neuronal thinking current were also obtained.

• Biomedical Science Letters
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• v.25 no.1
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Genomics & Informatics
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• v.7 no.2
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• pp.85-96
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• 2009

The differentiation of neural precursor cells (NPCs) into neurons and astrocytes is a process that is tightly controlled by complicated and ill-defined gene networks. To extend our knowledge to gene networks, we performed a temporal analysis of gene expression during the differentiation (2, 4, and 8 days) of spinal cord-derived NPCs using oligonucleotide microarray technology. Out of 32,996 genes analyzed, 1878 exhibited significant changes in expression level (fold change>2, p<0.05) at least once throughout the differentiation process. These 1878 genes were classified into 12 groups by k-means clustering, based on their expression patterns. K-means clustering analysis revealed that the genes involved in astrogenesis were categorized into the clusters containing constantly upregulated genes, whereas the genes involved in neurogenesis were grouped to the cluster showing a sudden decrease in gene expression on Day 8. Functional analysis of the differentially expressed genes indicated the enrichment of genes for Pax6- NeuroD signaling.TGFb-SMAD and BMP-SMAD.which suggest the implication of these genes in the differentiation of NPCs and, in particular, key roles for Nova1 and TGFBR1 in the neurogenesis/astrogenesis of mouse spinal cord.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.1
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• pp.15-30
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• 2009

Purpose: In this rapidly aging society, the research and development of traditional oriental medicine treatment is one of the critical factors to protect the increasing neuro-degenerative disorders. In this study, we wanted to verify the effect of Yukul-tang (YUT) on neuro-degenerative disease model by assessing the antioxidant and anti-inflammation effects. Methods: To assess the antioxidant effects of YUT, we carried out DPPH radical and ABTS radical scavenging assays and determined the total polyphenolic contents in YUT. To evaluate the neuro-protective effects of YUT, we performed the MTT and ROS assays and TH immunohistochemistry, NO and TNF-${\alpha}$ assays in SH-SY5Y or mesencephalic dopaminergic neurons damaged by 6-OHDA. Results: The treatment of YUT showed eliminating effects on DPPH radical and ABTS radical. it showed deterring effects on ROS, NO and TNF-${\alpha}$ and protecting effects on TH-positive cell in SH-SY5Y cells or mesencephalic dopaminergic neurons. Especially in the case of the treatment of YUT with 0.2ug/mL + 6-OHDA 10uM, the protective effect on dopaminergic neurons was most outstanding. Conclusion: In this study, we have demonstrated that YUT has an antioxidant effect and a neuro-protective effect on neuro-degenerative disease model caused by neurotoxin such as 6-OHDA. The results of our present study suggest that YUT can be useful agent to prevent and to treat neuro-degenerative diseases.

• The Korean Journal of Food And Nutrition
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• v.33 no.2
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• pp.215-221
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• 2020

The purpose of this study was to investigate the protective effect on oxidative stress induced PC12 cells, and volatile flavor composition of essential oils derived from medicinal plant seeds- Gossypium hirsutum L. (G. hirsutum), Coix lachryma-jobi (C. lachryma-jobi) and Oenothera biennis (O. biennis). The essential oils were obtained by the solvent (hexane) extraction method from the seeds. The essential oils of the seeds were analyzed by the solid-phase micro-extraction gas chromatography mass spectrometry (SPME-GC/MS). The major compounds of G. hirsutum, C. lachryma-jobi and O. biennis were cyclonexanol (16.65%), β-asarone (14.29%) and ylangene (50.01%). The DPPH radical scavenging activity (IC₅₀) was the highest value of 8.52 mg/mL in the O. biennis. Additionally, IC₅₀ values of G. hirsutum and C. lachryma-jobi were 26.76 mg/mL and 36.81 mg/mL. For the oxidative stress on PC12 cells, we treated with hydrogen peroxide (H₂O₂). The pretreatment of oxidative stress induced PC12 cells with all the essential oils preserved or increased their cell viability and G. hirsutum and O. biennis attenuated the ROS generation (by 68.75% and 56.25% vs. H₂O₂ control). The results of this study suggest that the essential oils derived from medicinal plant seeds could be used as valuable back data as a natural essential oil material to prevent neurodegenerative diseases by protecting neuro-cells.

• Korean journal of applied entomology
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• v.45 no.1 s.142
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• pp.31-36
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• 2006

Inflammation in the brain has known to be associated with the development of a various neurologiacal diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide(NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease. In the study, we examined whether Harmonia axyridis extracts inhibit the NO production by a direct method using Griess reagent, western blotting and by RT-PCR(Reverse Transcription-Polymerase Chain Reactionin) the gene expression of inducible nitric oxide synthase(iNOS). Distilled water$(H_2O)$ and methanol(MeOH) extracts of H. axyridis inhibited the protein expression of TNF-a(Tumor Necrosis Factor) and IL-6(Interleukin) in LPS (Lipopolysaccharide) stimulated BV-2 cells at the concentration of 100 ng/ml. Incubation of BV-2 cells with the extracts of $H_2O$ of MeOH inhibited the LPS induced NO and iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. These data suggested that H. axyridis extracts may play a crucial role in inhibiting the NO production.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.60-65
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• 2013

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-${\alpha}$, and IL-$1{\beta}$. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.

• Korean Journal of Pharmacognosy
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• v.52 no.1
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• pp.19-25
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• 2021

We previously reported that lonicerin isolated from Lonicera japonica methanolic extract had potent neuro-protective activities in neuronal cell death injured by excessive glutamate. In this study, we tried to confirm the neuroprotective activities of L. japonica extract and lonicerin in glutamate injured HT22 cells and establish mechanisms of neuroprotective action of lonicerin. We used HT22 cell death injured by glutamate as a bioassay system. The compound decreased reactive oxygen species increased by excessive glutamate treatment in HT22 cells. Also, Ca2+ concentration was decreased by lonicerin treatment. This compound made mitochondrial membrane potential maintain to normal condition. Lonicerin also increased not only glutathione reductase but also peroxidase to the control level. And this compound increased amount of glutathione, an endogenous antioxidant. These results indicated that lonicerin isolated from L. japonica showed potent neuroprotective activity through the anti-oxidative pathway.