• Journal of Life Science
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• v.17 no.6 s.86
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• pp.748-755
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• 2007

The in vitro activity of ST1571, an inhibitor of the Abl group of protein-tyrosine kinases, alone or in combination with camptothecin (CPT), a specific topoisomerase I inhibitor, was evaluated against human cancer cells with different metastatic capacity and drug resistance potency. These cell lines showed different sensitivity to ST157 on growth inhibition, and the expression of DNA-dependent protein kinase (DNA-PK), which interacts constitutively with c-Abl, was significantly decreased in drug sensitive CEM and MCF-7 cells and poorly metastatic PC3 and KMl2 cells as compared with that of multidrug resistant CEM/MDR and MCF-7/MDR cells and highly metastatic PC3-MM2 and KM/L4a cells, respectively. These results suggest differential modulation of DNA-PK by ST1571 treatment in drug resistance and metastatic degree dependent manner. We showed that CPT as well as ST1571 significantly inhibits the expression of DNA-PK. The combined treatment with ST15fl and CPT revealed synergistic effect, and the effect was accompanied by inhibition of cell proliferation due to significant reduced expression of DNA-PK components, which resulted in CPT sensitizes human cancer cells resistant to ST1571. Therefore, the results of our study suggested that the suppression of DNA-PK using combination of ST1571 and CPT could be a novel molecular target for against drugresistant and metastatic cancer cells.

• Journal of Life Science
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• v.22 no.12
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• pp.1600-1607
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• 2012

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

• Polymer(Korea)
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• v.26 no.5
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• pp.691-700
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• 2002

Interstitial therapy using biodegradable polymeric device loaded with anticancer agent can deliver the drug to the tumor site at high concentration, resulting in an increase of therapeutic efficacy. 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) is most commonly used as chemotherapeutic agent for brain tumors. The design of implantable device is regarded as an important factor lot the efficient delivery of antitumor agent to targeting site. In order to control the release profile of drug, the release pattern of BCNU with the changes of various dimension and additives was investigated. The PLGA wafers containing 3.85, 10, 20 and 30% of BCNU were prepared in various shape (diameter of 3, 5 and 10 mm, thickness of 0.5, 1 and 2 mm) by direct compression method. In vitro drug release profile of BCNU-loaded PLGA wafers could be controlled by changing the dimension of wafers such as initial drug content, weight, diameter, thickness, volume and surface area of wafers, as well as PLGA molecular weight and additives. Drug release from BCNU-loaded PLGA wafers was facilitated with an increase of BCNU-loading amount or presence of poly(N-vinylpyrrolidone)(PVP) or sodium chloride (NaCl). The effects of various geometric factors and additives on the BCNU release pattern were confirmed by the investigation of mass loss and morphology of BCNU-loaded PLGA wafers.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.133-140
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• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

• Journal of Nutrition and Health
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• v.54 no.5
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• pp.448-458
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• 2021

Purpose: Mulberry (Morus alba L.) fruit is widely grown in Asia and consumed as fresh fruit, jam, and juices. The fruit has beneficial health effects, including anti-diabetic, anti-tumor, and anti-obesity properties. However, the mechanisms by which mulberry fruit juice powder (MJ) regulates inflammatory microRNAs (miRs) are not yet known. This study investigated the effect of mulberry fruit juice powder on the regulation of inflammation and miR-132/143 during 3T3-L1 adipocyte differentiation. Methods: The 3T3-L1 cells were induced to differentiate for 2 days and then treated with various concentrations of MJ for 7 days. Cytotoxicity was determined by evaluating cell viability using a water-soluble tetrazolium salt-8 assay kit. Intracellular lipid accumulation was evaluated by oil-red O staining. The levels of the expression of genes involved in adipogenesis and inflammation, and miR-132/143 were measured by quantitative real-time polymerase chain reactions. Results: MJ showed no cytotoxic effect on 3T3-L1 adipocytes at concentrations below 100 ng/mL. Intracellular lipid accumulation was reduced by MJ treatment at concentrations of 100 ng/mL. The messenger RNA (mRNA) levels of proliferator-activated receptor-γ, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer-binding protein-α, and adipocyte protein 2, which are involved in adipogenesis, were suppressed by MJ. A reduction was also seen in mRNA levels of genes related to the inflammatory response, such as tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The expression of the inflammatory miR-132 and miR-143 was also decreased by MJ. Conclusion: These results suggest that MJ may suppress adipogenesis and inflammation through the regulation of miR-132/143 expression in 3T3-L1 adipocytes. Thus, MJ may be useful as a food agent that prevents obesity-associated inflammation.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• Journal of the Korean Society of Radiology
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• v.16 no.2
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• pp.103-113
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• 2022

In this paper, a combined ¹⁸F-FDG(fluorodeoxyglucose) and MNP(magnetic nanoparticles) contrast agent was synthesized using N-(p-maleimidophenyl) isocyanate as the crosslinker for use in simultaneous PET-MRI scans. PET-MRI images were acquired and evaluated before and after injection of the combined contrast imaging agent (¹⁸F-FDG labeled MNP) from a glioma stem cell mouse model. After setting the region of interest (ROI) on each acquired image, the area of the lesion was calculated by segmentation. As a result, the PET image was larger than the MRI. In particular, the simultaneous PET-MRI images showed accurate lesions along with the surrounding soft tissue. The mean and standard deviation values were higher in the MRI images alone than in the PET images or the simultaneous PET-MRI images, regardless of whether the contrast agent was injected. In addition, the simultaneous PET-MRI image values were higher than for the PET images. For PSNR experiments, the original image was PET Image using 18F-FDG, MRI using MNPs, and MRI without contrast medium, and the target image was simultaneous PET-MRI image using 18F-FDG labeled MNPs contrast medium. As a result, all of them appeared significantly, suggesting that the 18F-FDG labeled MNPs contrast medium is useful. Future research is needed to develop an agent that can simultaneously diagnose and treat through SPECT-MRI imaging research that can use various nuclides.

• Journal of Life Science
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• v.32 no.9
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• pp.712-720
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• 2022

The purpose of this study was to investigate the efficacy of rat corneal-derived epithelial cells as an in vitro model to evaluate the harmfulness of the cornea caused by particulate matter 2.5 (PM_2.5). To establish an experimental model for the effect of PM_2.5 on corneal epithelial cells, it was confirmed that primary cultured cells isolated from rat eyes were corneal epithelial cells through pan-cytokeratin staining. Our results showed that PM_2.5 treatment reduced cell viability of primary rat corneal epithelial (RCE) cells, which was associated with the induction of apoptosis. PM_2.5 treatment also increased the generation of reactive oxygen species due to mitochondrial dysfunction. In addition, the production of nitric oxide and inflammatory cytokines was increased in PM_2.5-treated RCE cells. Furthermore, through heatmap analysis showing various expression profiling between PM_2.5-exposed and unexposed RCE cells, we proposed five genes, including BLNK, IL-1RA, Itga2b, ABCb1a and Ptgs2, as potential targets for clinical treatment of PM-related ocular diseases. These findings indicate that the primary RCE cell line is a useful in vitro model system for the study of PM_2.5-mediated pathological mechanisms and that PM2.5-induced oxidative and inflammatory responses are key factors in PM2.5-induced ocular surface disorders.

• Journal of Life Science
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• v.33 no.6
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• pp.455-462
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• 2023

During pregnancy, maternal immune activation (MIA) from infection increases the risk of neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. MIA induced by polyinosinic-polycytidylic acid (poly (I:C)) and lipopolysaccharide (LPS) in animal experiments has led to offspring with abnormal behaviors and brain development. In addition, it has recently been reported that microglia, which reside in the brain and function as immune cells, play an important role in behavioral abnormalities and brain development in MIA-induced offspring. However, the underlying mechanism remains unclear. In this study, we investigated whether microglia-specific inhibition of GPR56, a member of the G protein-coupled receptor (GPCR) family, causes behavioral abnormalities in brain development. First, MIA induction did not affect the microglia population, but when examining the expression of microglial GRP56 in MIA-induced fetuses, GPR56 expression was inhibited between embryonic days 14.5 (E14.5) and E18.5 regardless of sex. Furthermore, microglial GPR56-suppressed mice showed abnormal behaviors in the MIA-induced offspring, including sociability deficits, repetitive behavioral patterns, and increased anxiety levels. Although abnormal cortical development such as that in the MIA-induced offspring were not observed in the microglial GPR56-suppressed mice, their brain activity was observed through c-fos staining. These results suggest that microglia-specific GPR56 deficiency may cause abnormal behaviors and could be used as a biomarker for the diagnosis and/or as a therapeutic target of behavioral deficits in MIA offspring.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.2
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• pp.105-112
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• 2023

Leucine-rich repeat kinase 2 (LRRK2) is known to play a crucial role in the pathophysiology of neurodegenerative disorders such as Parkinson's disease. LRRK2 is predominantly expressed in the lung as well as the brain. However, it is unclear whether LRRK2 expression correlates with the pathogenesis of lung squamous cell carcinoma (LUSC). This study analyzes the prognostic significance of LRRK2 in LUSC using the Kaplan-Meier plotter tool. High expression of LRRK2 is known to be associated with a bad prognosis in patients with LUSC. Patients with high LRRK2 expression, tumor mutational burden, high neoantigen load, and even gender correlation reportedly have the worse survival rates. In the gene expression profiling interactive analysis (GEPIA) database, the severity of pathogenesis in LUSC with high LRRK2 expression positively corresponds to a high expression of anti-inflammatory cytokines but not inflammatory cytokines. Similarly, the increased expression of interleukin (IL)10-related genes was shown to be significantly linked in LRRK2-high LUSC patients having a poor prognosis. Moreover, the tumor immune estimation resource (TIMER) database suggests that macrophages are one of the cellular sources of IL10 in LRRK2-high LUSC patients. Collectively, our results demonstrate that the postulated LRRK2-IL10 axis is a potential therapeutic target and prognostic biomarker for LUSC.