• Journal of Life Science
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• v.29 no.2
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• pp.173-180
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• 2019

Amyloid ${\beta}$-protein ($A{\beta}$) is the principal component of senile plaques characteristic of Alzheimer's disease (AD) and elicits a toxic effect on neurons in vitro and in vivo. Many environmental factors, including antioxidants and proteoglycans, modify $A{\beta}$ toxicity. It is worthwhile to isolate novel natural compounds that could prove therapeutic for patients with AD without causing detrimental side effects. In this study, we investigated the in vitro neuroprotective effects of the ethyl acetate fraction of methanol extract of Ophiophogon japonicas (OJEA fraction). We used an MTT reduction assay to detect protective effects of the OJEA fraction on $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells. We also used a cell-based ${\beta}$-secretase assay system to investigate the inhibitory effect of the OJEA fraction on ${\beta}$-secretase activity. In addition, we performed an in vitro lipid peroxidation assay to evaluate the protective effect of the OJEA fraction against oxidative stress induced by $A{\beta}_{25-35}$ in PC12 cells. The OJEA fraction had strong protective effects against $A{\beta}_{25-35}$-induced cytotoxicity to PC12 cells and was strongly inhibitory to ${\beta}$-secretase activity, which resulted in the attenuation of $A{\beta}$ generation. In addition, the OJEA fraction significantly decreased malondialdehyde (MDA) content, which is induced by the exposure of PC12 cells to $A{\beta}_{25-35}$. Our results suggested that the OJEA fraction contained active compounds exhibiting a neuroprotective effect on $A{\beta}$ toxicity.

• Journal of Life Science
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• v.31 no.8
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• pp.710-718
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• 2021

Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.

• Journal of Life Science
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• v.32 no.1
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• pp.1-10
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• 2022

Natural products have gained increasing attention due to their advantage of long-term safety and low toxicity for a very long time. Torreya nucifera is widespread in southern Korea and Jeju Island and its seeds are commonly used as edible food. Oriental ingredients have often been reported for their insecticidal, antioxidant and antibacterial properties, but there have not yet been any studies on their antidiabetic effect. In this study, we investigated several biological activities of T. nucifera pericarp (TNP) and seeds (TNS) extracts and proceeded to characterize the antidiabetic compounds of TNS. The initial results suggested that TNS extract at 15 and 10 ㎍/ml concentration has inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B, that is 14.5 and 4.35 times higher than TNP, respectively. Thus, the stronger antidiabetic TNS was selected for the subsequent experiments to characterize its active compounds. Ultrafiltration was used to determine the apparent molecular weight of the active compounds, showing 300 kDa or more. Finally the mixture was then partially purified using Diaion HP-20 column chromatography by eluting with 50~100% methanol. Therefore we concluded that the active compounds of TNS have potential as therapeutic agents in functional food or supplemental treatment to improve diabetic diseases.

• Journal of Life Science
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• v.32 no.2
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• pp.108-118
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• 2022

The subventricular zone (SVZ) in the brain contains neural stem cells (NSCs) that generate new neurons throughout one's lifetime. Many extracellular and intracellular factors that affect cell proliferation and neuronal differentiation of NSCs are already well-known. Recently, L-type calcium channels have been reported to regulate neural development and are present in NSCs, differentiating neuroblasts, and mature neurons in the SVZ. Nifedipine, a blocker of L-type calcium channels, has been long used as a therapeutic drug for hypertension. However, studies on the use of nifedipine to inhibit L-type calcium channels of NSCs are lacking. Herein, we treated NSCs cultured from mouse postnatal SVZ with nifedipine during neuronal differentiation. Nifedipine increased the number of Tuj1-positive neurons but did not significantly change the number of Olig2-positive oligodendrocytes. Nifedipine increased cell division during early differentiation, which was detected using the 5-ethynyl-2'-deoxyuridine incorporation assay and immunocytochemistry assessment by staining the cells with phosphorylated histone H3, a mitosis marker. Nifedipine increased the transcription of Dlx2, a neurogenic transcription factor, and the level of Mash1, a marker for early neurogenesis. In addition to nifedipine, verapamil, which is also an L-type calcium channel blocker, showed a slight increase in neurogenesis, but its statistical significance was very low. In contrast, pimozide, a T-type calcium channel blocker, did not affect neurogenesis, although T-type calcium channel genes Cav3.1, Cav3.2, and Cav3.3 were expressed. In summary, nifedipine might promote the neuronal fate of NSCs during early differentiation and calcium signaling through L-type calcium channels might be involved in neuronal differentiation, especially during the early stages of differentiation.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.106-112
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• 1999

The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.9-16
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• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Journal of Korea Entertainment Industry Association
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• v.13 no.7
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• pp.539-548
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• 2019

This study was designed to examine the effects of complex breathing exercise and neuromuscular electrical stimulation of Quadriceps Femoris muscle on pulmonary function and cerebral cortex activity in patients with severe chronic obstructive pulmonary disease. After collecting samples from 20 patients with severe chronic obstructive pulmonary disease aged 60 to 80, 10 patients each were randomly placed in an experimental group and a control group. The experimental group conducted complex breathing exercise and neuromuscular electrical stimulation of Quadriceps Femoris muscle, and the control group only conducted complex breathing exercise. As a pretest, pulmonary function and cerebral cortex activity were measured. The intervention program was applied to each group for 30 minutes, once a day, for 4 days a week, for 6 weeks, and the posttest was carried out the same way as the pretest. As a result, both groups showed significant differences in FEV1.0(Forced Expiratory Volume in One Second)(p<.001)(p<.05), and there were significant differences between the groups as well(p<.05). When comparing alpha waves in each domain of cerebral cortex, both of the experimental and control groups showed significant differences in Fp1, Fp2, F3 and F4 domains (p<.01)(p<.05). During the 6-week experiment, complex breathing exercise and neuromuscular electrical stimulation of Quadriceps Femoris muscle improved pulmonary function of patients with severe chronic obstructive pulmonary disease, and in relation to cerebral cortex activity, a positive breathing change was found due to the increase of alpha waves in the forehead domain. Therefore, it is considered that applying neuromuscular electrical stimulation of Quadriceps Femoris muscle to patients with severe chronic obstructive pulmonary disease additionally along with complex breathing exercise will bring a better therapeutic effect.

• Korean Journal of Culture and Social Issue
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• v.23 no.2
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• pp.131-157
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• 2017

Loving-kindness & compassion meditation (LCM) is one of the popular intervention on clinical setting to cultivate loving-kindness & compassion for self and other. Shame is known for unconscious and implicit emotion including negative self-concept. Some researchers suggest that people with high shame have difficulty in cultivating loving-kindness & compassion toward oneself because of shame including the negative self-critic. In this research, it is explored the influence of shame for the object of LCM. There are 2 experiments to find out the answer to this question. In experiment 1, participants (N = 108) are randomly assigned to two conditions. The one condition is loving-kindness meditation for self, and the other is loving-kindness meditation for positive others. Dislike and engagement from participants about loving-kindness meditation instruction are measured after meditation for 8 minutes. From the experiment 2, loving-kindness meditation is replaced with compassion meditation from the design of experiment 1. This experiment is conducted because of psychological differences between loving-kindness and compassion. Participants (N = 116) are randomly assigned to two conditions, compassion meditation for self and positive others, respectively. The results of experiment 1 show that dislike of loving-kindness meditation for self seems to high when people have high shame, but shame does not have an influence on engagement. For loving-kindness meditation for positive others, shame seems to not affect on dislike and engagement about loving-kindness meditation instruction. The results of experiment 2 show that dislike is higher for self than for positive others about compassion meditation for people with high shame, but shame does not affect on engagement. For discussion, it is suggested that shame has special features of emotion. For the future, we discuss the therapeutic strategy for people with negative self-concept.

• Therapeutic Science for Rehabilitation
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• v.12 no.4
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• pp.81-96
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• 2023

Objective : This study aimed to examine the association between the structural and functional aspects of social networks and health-promoting behaviors in community-dwelling older adults. Methods : Social networks based on structural and functional aspects and health-promoting behaviors by lifestyle were measured in 226 community-dwelling adults aged 65 years and over. To analyze the collected data, an independent t-test, one-way ANOVA, Pearson's correlation analysis, and hierarchical regression were performed. Results : The network size was the highest in the friend network, and the frequency of contact and social support was the highest in the non-living family network. Health-promoting behaviors were highest for activities of daily living and lowest for productive and social activities. All subfactors of social networks showed significant positive correlations with health-promoting behaviors. Hierarchical regression showed social support from neighbors as the variable with a significant effect on health-promoting behaviors; gender and depression were also influencing factors, and this model showed 37% explanatory power. Conclusion : To promote healthy behaviors of older adultsin the community, the development of health promotion programs and related policies considering social networks centering on social support from neighbors is required.

• Journal of Life Science
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• v.33 no.10
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• pp.783-790
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• 2023

Modern people have an increased incidence of metabolic diseases due to changed eating habits, and diabetes is considered the most significant metabolic disease. Given that existing diabetes treatments are accompanied by side effects, the aim of this study was to identify traditional natural products that have anti-diabetic activity. The potential anti-diabetic and antioxidant activities of natural products were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, α-glucosidase assay, and protein tyrosine phosphatase 1B (PTP1B) inhibition assay. Methanol extracts of Ulmus davidiana var. japonica, Acer tegmentosum branches, Nelumbo nucifera seeds, and Carthamus tinctorius seeds were found to have high anti-diabetic activity and further fractionated with solvents using ethyl acetate and butanol. Consequently, the ethyl acetate fraction of C. tinctorius seeds (MG-11-E) with high α-glucosidase and PTP1B inhibitory activity was selected. MG-11-E was subjected to preparative thin layer chromatography, and fraction #6 showed high α-glucosidase and PTP1B inhibitory activity. Fraction #6 was analyzed and fractionated via high performance liquid chromatography with 50% methanol as the mobile phase, and anti-diabetic activity was observed in the sample that eluted after 4 min as a single peak. The α-glucosidase inhibitory activity exhibited by this sample seemed to be greater than the PTP1B inhibitory activity; thus, it was concluded that a greater anti-diabetic therapeutic effect may be achieved by combining this agent with natural products that inhibit PTP1B activity.