• Journal of Biomedical Engineering Research
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• v.40 no.2
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• pp.39-47
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• 2019

Ultrasound sonication along with microbubble (MB) could enhance drug delivery to promote the absorption of anticancer drugs into cancers in a noninvasive and targeted manners. In this study, we verify the acute drug delivery enhancement (within an hour) of two representative focused ultrasound driven drug delivery enhancement methods (MB and Doxorubicin-coated Nanoparticle complex (MB-NP) based). Experiments were conducted using in vivo mouse model with MDA-MB-231 breast cancer cell line. Ultrasound generated by single-element 1 MHz focused ultrasound transducer was delivered in pulsed sonication consisted of 0.125 msec bursts at a pulse repetition frequency of 2 Hz for 20 seconds without a significant increase in local temperature (less than $0.1^{\circ}C$) or hemorrhage. Doxorubicin concentrations in tumors were improved by 1.97 times in the case of MB-NP, and 1.98 times by using Doxorubicin and MB separately. These results indicate anticancer drug delivery based on MB and MB-NP can significantly improve the effect of anticancer drugs delivered to tumors in a short time period by using low-intensity focused ultrasound.

• Molecules and Cells
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• v.44 no.1
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• pp.26-37
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• 2021

Human papillomaviruses (HPVs) cause cellular hyperproliferation-associated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a well-defined tumor suppressor, and found that this intermolecular interaction plays a key role in E7-driven transformation and tumorigenesis. In this study, we carried out a molecular analysis of the interaction between CR3 of HPV18 E7 and the PTP domain of PTPN21, a PTP protein that shares high sequence homology with PTPN14 but is putatively oncogenic rather than tumor-suppressive. Through the combined use of biochemical tools, we verified that HPV18 E7 and PTPN21 form a 2:2 complex, with a dissociation constant of 5 nM and a nearly identical binding manner with the HPV18 E7 and PTPN14 complex. Nevertheless, despite the structural similarities, the biological consequences of the E7 interaction were found to differ between the two PTP proteins. Unlike PTPN14, PTPN21 did not appear to be subjected to proteasomal degradation in HPV18-positive HeLa cervical cancer cells. Moreover, knockdown of PTPN21 led to retardation of the migration/invasion of HeLa cells and HPV18 E7-expressing HaCaT keratinocytes, which reflects its protumor activity. In conclusion, the associations of the viral oncoprotein E7 with PTPN14 and PTPN21 are similar at the molecular level but play different physiological roles.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.482-489
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• 2021

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE₂ pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

• Animal Bioscience
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• v.35 no.7
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• pp.964-974
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• 2022

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry and economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for studies on HPAIV resistance. Therefore, in this study, we investigated gene expression related to the mitogen-activated protein kinase (MAPK) signaling pathway by comparing non-infected, HPAI-infected resistant, and susceptible Ri chicken lines. Methods: Resistant (Mx/A; BF2/B21) and susceptible Ri chickens (Mx/G; BF2/B13) were selected by genotyping the Mx and BF2 genes. Then, the tracheal tissues of non-infected and HPAIV H5N1 infected chickens were collected for RNA sequencing. Results: A gene set overlapping test between the analyzed differentially expressed genes (DEGs) and functionally categorized genes was performed, including biological processes of the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. A total of 1,794 DEGs were observed between control and H5N1-infected resistant Ri chickens, 432 DEGs between control and infected susceptible Ri chickens, and 1,202 DEGs between infected susceptible and infected resistant Ri chickens. The expression levels of MAPK signaling pathway-related genes (including MyD88, NF-κB, AP-1, c-fos, Jun, JunD, MAX, c-Myc), cytokines (IL-1β, IL-6, IL-8), type I interferons (IFN-α, IFN-β), and IFN-stimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-infected than in non-infected resistant Ri chickens. MyD88, Jun, JunD, MAX, cytokines, chemokines, IFNs, and IFN-stimulated expressed genes were higher in resistant-infected than in susceptible-infected Ri chickens. Conclusion: Resistant Ri chickens showed higher antiviral activity compared to susceptible Ri chickens, and H5N1-infected resistant Ri chickens had immune responses and antiviral activity (cytokines, chemokines, interferons, and IFN-stimulated genes), which may have been induced through the MAPK signaling pathway in response to H5N1 infection.

• BMB Reports
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• v.55 no.9
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• pp.465-471
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• 2022

Understanding and monitoring virus-mediated infections has gained importance since the global outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Studies of high-throughput omics-based immune profiling of COVID-19 patients can help manage the current pandemic and future virus-mediated pandemics. Although COVID-19 is being studied since past 2 years, detailed mechanisms of the initial induction of dynamic immune responses or the molecular mechanisms that characterize disease progression remains unclear. This study involved comprehensively collected biospecimens and longitudinal multi-omics data of 300 COVID-19 patients and 120 healthy controls, including whole genome sequencing (WGS), single-cell RNA sequencing combined with T cell receptor (TCR) and B cell receptor (BCR) sequencing (scRNA(+scTCR/BCR)-seq), bulk BCR and TCR sequencing (bulk TCR/BCR-seq), and cytokine profiling. Clinical data were also collected from hospitalized COVID-19 patients, and HLA typing, laboratory characteristics, and COVID-19 viral genome sequencing were performed during the initial diagnosis. The entire set of biospecimens and multi-omics data generated in this project can be accessed by researchers from the National Biobank of Korea with prior approval. This distribution of large-scale multi-omics data of COVID-19 patients can facilitate the understanding of biological crosstalk involved in COVID-19 infection and contribute to the development of potential methodologies for its diagnosis and treatment.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.216-223
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• 2022

Objectives: Oxidative stress plays a key role in chronic and acute brain disorders and neuronal damage associated with Alzheimer disease (AD) and other neurodegeneration symptoms. The neuroprotective effects of berberine and Berberis vulgaris (barberry) root extract against apoptosis induced by hydrogen peroxide (H₂O₂) in the human SH-SY5Y cell line were studied. Methods: The methanolic extraction of barberry root was performed using a maceration procedure. Oxidative stress was induced in SH-SY5Y cells by H₂O₂, and an MTT assay was applied to evaluate the neuroprotective effects of berberine and barberry root extract. The cells were pretreated with the half maximal inhibitory concentration (IC₅₀) of each compound (including berberine, barberry root extract, and H₂O₂), and the anti-apoptotic effects of all components were investigated using RT-PCR. Results: The SH-SY5Y cell viability increased in both groups exposed to 75 and 150 ppm barberry extract compared with that in the H₂O₂-treated group. The data showed that exposing SH-SY5Y cells to 30 ppm berberine significantly increased the cell viability compared with the H₂O₂-treated group; treatment with 150 and 300 ppm berberine and H₂O₂ significantly decreased the SH-SY5Y cell viability and was associated with berberine cytotoxicity. The mRNA levels of Bax decreased significantly under treatment with berberine at 30 ppm compared with the control group. A significant increase in Bcl-2 expression was observed only after treatment with the IC₅₀ of berberine. The expression level of Bcl-2 in cells exposed to both berberine and barberry extracts was also significantly higher than that in cells exposed to H₂O₂. Conclusion: The outcomes of this study suggest that treatment of SH-SY5Y cells with barberry extract and berberine could suppress apoptosis by regulating the actions of Bcl-2 family members.

• Journal of Life Science
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• v.33 no.7
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• pp.574-585
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• 2023

Sarcopenia is a leading cause of increased medical and nursing care costs among the elderly. In Korea, preventive measures for sarcopenia are mostly targeted toward the general elderly population without specific diseases. However, it is also necessary to implement measures for elderly individuals living in nursing homes and hospitals, where the prevalence of sarcopenia is high. Currently, computed tomography and/or magnetic resonance imaging are considered standard diagnostic tools. However, their complexity and time-consuming nature make them unsuitable for clinical use. The exact pathophysiological mechanisms of sarcopenia are unclear, as they involve various molecular biological pathways, including decreased exercise, protein and nutrient intake, changes in testosterone and growth hormone, and inflammation. Sarcopenia symptoms can lead to several diseases, such as osteoporosis, fractures, dementia, diabetes, and cardiovascular disease. Vitamin B deficiency is a significant factor in sarcopenia induction, with B vitamins being directly involved in energy and protein metabolism and nerve function. Vitamin B deficiency can lead to neuromuscular and neurogenic disorders, which often overlap with sarcopenia. Suboptimal intake of B vitamins, malabsorption, and anorexia are common among the elderly. This study aims to provide information on the role of water-soluble B vitamins in preventing and controlling muscle mass loss and deterioration among the elderly with sarcopenia. In addition, we discuss the potential of myokines from the B vitamin family in modulating sarcopenia.

• Korean Journal of Ecology and Environment
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• v.56 no.4
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• pp.339-347
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• 2023

Dissolved organic matter (DOM) is a key component in the biogeochemical cycling in freshwater ecosystem. However, it has been rarely explored, particularly complex river watershed dominated by natural and anthropogenic sources, such as various effluent facility and livestock. The current research developed a new analytical method for TOC/TN (Total Organic Carbon/Total Nitrogen) stable isotope ratio, and distinguish DOM source using stable isotope value (δ¹³C-DOC) and spectroscopic indices (fluorescence index [FI] and biological index [BIX]). The TOC/TN-IR/MS analytical system was optimized and precision and accuracy were secured using two international standards (IAEA-600 Caffein, IAEA-CH-6 Sucrose). As a result of controlling the instrumental conditions to enable TOC stable isotope analysis even in low-concentration environmental samples (<1 mgC L^-1), the minimum detection limit was improved. The 12 potential DOM source were collected from watershed, which includes top-soils, groundwater, plant group (fallen leaves, riparian plants, suspended algae) and effluent group (pig and cow livestock, agricultural land, urban, industry facility, swine facility and wastewater treatment facilities). As a result of comparing characteristics between 12 sources using spectroscopic indices and δ¹³C-DOC values, it were divided into four groups according to their characteristics as a respective DOM sources. The current study established the TOC/TN stable isotope analyses system for the first time in Korea, and found that spectroscopic indices and δ¹³C-DOC are very useful tool to trace the origin of organic matter in the aquatic environments through library database.

• Journal of The Korean Society of Integrative Medicine
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• v.12 no.1
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• pp.1-10
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• 2024

Purpose: Lycopene is abundantly contained in Tomatoes and is known for diverse biological activities such as antioxidant, anti-inflammatory, and anticancer effects. In this study, the antioxidative potential of lycopene was investigated through the induction of hemeoxygenase (HO)-1 by nuclear factor-erythroid 2 p45-related factor2 (Nrf2) and upstream signaling molecules, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Aktin RAW 264.7 cells. Methods: The antioxidative potential of lycopene against oxidative stress and its molecular mechanisms were determined by the cell viability assay, intracellular reactive oxygen species (ROS) formation assay, and Western blot analysis in RAW 264.7 cells. Results: Lycopene treatment significantly attenuated tert-butyl hydroperoxide (t-BHP) induced intracellular ROS formation in a dose-dependent manner without any cytotoxicity. In addition, 50 µM of lycopene for 6 h treatment induced potent HO-1 expression and its transcription factor, Nrf2. MAPK and PI3K/Aktwere also analyzed due to their critical roles in the regulation of cellular redox homeostasis against oxidative damage. As a result, phosphorylation of extracellular regulated kinase (ERK) was significantly induced by lycopene treatment while the activated status of c-Jun NH2-terminal kinase (JNK), p38, and Akt, were not given any effect. To confirm the antioxidative mechanism of HO-1 mediated by ERK activation, each selective inhibitor was employed in a protection assay, in which oxidative damage occurred by t-BHP. Lycopene, SnPP, and CoPP treatments reflected accelerated HO-1 expression could be a protective role against oxidative damage-initiated cell death. A selective inhibitor for ERK significantly inhibited the lycopene-induced cytoprotective effect but selective inhibitors for other signaling molecules did not attenuate the rate of t-BHP-induced cell death. Conclusion: In conclusion, lycopene potently scavenged intracellular ROS formation and enhanced the HO-1 mediated antioxidative potential through the modulation of Nrf2, MAPK signaling pathway in RAW 264.7 cells.

• Journal of Korean Tunnelling and Underground Space Association
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• v.26 no.3
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• pp.209-222
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• 2024

The Earth Pressure Balance (EPB) shield Tunnel Boring Machine (TBM) is widely used for underground tunnel construction for its advantages, such as eliminating the need for additional facilities compared to the slurry shield TBM, which requires Slurry Treatment Plant (STP). During EPB shield TBM excavation, a soil conditioning technique is employed to enhance the physical properties of the excavated soil by injecting additives, thus broadening the range of applicable ground conditions to EPB shield TBMs. This study explored the use of xanthan gum, a type of biopolymer, as an alternative to the commonly used polymer additive. Biopolymers, derived from biological sources, are fully biodegradable. In contrast to traditional polymers such as polyacrylic acid, which contain environmentally harmful components, xanthan gum is gaining attention as an eco-friendly material due to its minimal toxicity and environmental impact. Test conditions with similar workability were established through slump tests, and the rheological characteristics were assessed using a laboratory pressurized vane shear test apparatus. The experiments demonstrated that, despite exhibiting similar workability, the peak strength in the flow curve decreased with increasing the content of xanthan gum. Consequently, a correlation between the xanthan gum content and peak strength was established. Replacing the traditional polymers with xanthan gum could enable stable EPB shield TBM operation by reducing equipment load, in addition to offering environmental benefits.