• Anatomy and Cell Biology
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• v.56 no.1
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• pp.94-108
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• 2023

Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer. Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

• Nutritional Sciences
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• v.8 no.1
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• pp.23-27
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• 2005

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

• The Journal of Engineering Geology
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• v.3 no.1
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• pp.51-61
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• 1993

Restricted maximum likelihood(RML) method was used to determine the parameters of generalized covariance, and universal krigig with RML was applied to estimate a groundwater level distribution of nonstationarv random function. Universal kriging with RML was compared to IRF-k with weighted least squares method for the comparison of their accuracies. Cross validation shows that two methods have nearly the same ability for the estimation of groundwater levels. Scattergram of estimates versus true values and contour maps of groundwater levels have nearly the same results. The reason why two methods produced the same results is thought to be the non-Gaussian distribution and the snaall number of sample data.

• Proceedings of the IEEK Conference
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• 2002.06a
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• pp.435-438
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• 2002

A design of Ku-band(11.7~12.20Hz) monolithic microwave integrated circuit(MMIC) low noise block(LNB) downconverter using self oscillating mixer (SOM) for direct broadcast satellite(DBS) application is presented The proposed LNB downconverter is composed of low noise amplifier(LNA), image reject filter(IRF), SOM , low pass filter(LPF). The conversion gain is 30dB , VSn is less than 1.7: 1 and overall noise figure is less than 1.2dB.

• Molecules and Cells
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• v.45 no.4
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• pp.257-272
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• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.1
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• pp.39-54
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• 2008

Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

• Journal of the Korean Society for Aeronautical & Space Sciences
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• v.50 no.2
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• pp.119-125
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• 2022

In this paper, we present design, implementation and test results of CTM (Chirp Transceiver Module) EM (Engineering Model) for C-Band SAR (Synthetic Aperture Radar) Payload. The CTM is designed to operate dual frequency scan method that simultaneously operate two frequencies in each 50MHz bandwidth to achieve 120Km swath with 10m resolution at about 500Km altitude. The CTM used radiation tolerant RTG4 FPGA for space environment, and implemented with the Parallel DDS (PDDS) method which uses a small memory capacity compared to the memory-map method. Test results show high purity chirp signal generation and excellent IRF performance from received chirp signal after direct digital conversion.

• The Journal of Korean Institute of Electromagnetic Engineering and Science
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• v.29 no.2
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• pp.118-127
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• 2018

In this work, we have designed and manufactured radar target simulation equipment for the performance analysis of synthetic aperture radar(SAR) systems. First, we have explained the function and performance specification of the target simulation equipment and point target scenario generation for validation of the SAR system. In addition, we have developed a simple and accurate calibration method for the time delay of the SAR system using the manufactured target simulation equipment. We have analyzed the point target impulse response function of the SAR image acquired using the SAR system and the target simulation equipment. It was observed that the measured peak to side lobe ratio(=-13.25 dB) and resolution(=0.49 m) are in good agreement with the corresponding theoretical values.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.