• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.17-17
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• 2023

Chrysanthemum zawadskii (C. zawadskii) is used in traditional East Asian medicine for the treatment of various diseases, including inflammatory disease. However, it has remained unclear whether extracts of C. zawadskii inhibit inflammasome activation in macrophages. The present study assessed the inhibitory effect of an ethanol extract of C. zawadskii (CZE) on the activation of the inflammasome in macrophages and the underlying mechanism. Bone marrow[-derived macrophages (BMDMs) were obtained from wild-type C57BL/6 mice. The release of IL-1β and lactate dehydrogenase in response to nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activators, such as ATP, nigericin and monosodium urate (MSU) crystals, was significantly decreased by CZE in lipopolysaccharide(LPS)-primed BMDMs. Western blotting revealed that CZE inhibited ATP-induced caspase-1 cleavage and IL-1β maturation. To investigate whether CZE inhibits the priming step of the NLRP3 inflammasome, we confirmed the role of CZE at the gene level using RT-qPCR. CZE also downregulated the gene expression of NLRP3 and pro-IL-1β as well as NF-κB activation in BMDMs in response to LPS. Apoptosis associated speck-like protein containing a caspase-recruitment domain (CARD) oligomerization and speck formation by NLRP3 inflammasome activators were suppressed by CZE. By contrast, CZE did not affect NLR family CARD domain containing protein 4 (NLRC4) or absent in melanoma 2 (AIM2) inflammasome activation in response to Salmonella typhimurium and poly(dA:dT) in LPS-primed BMDMs, respectively. The results revealed that three key components of CZE, namely linarin, 3,5-dicaffeoylquinic acid and chlorogenic acid, decreased IL-1β secretion in response to ATP, nigericin and MSU. These findings suggest that CZE effectively inhibited activation of the NLRP3 inflammasome.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.147-152
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• 1993

Background: There is evidence that platelet is activated in chronic obstructive pulmonary disease and activated platelet with injured endothelium contribute to the pathogenesis of pulmonary hypertension, prognostic factor of chronic obstructive pulmonary disease. So, we have investigated platelet function further in chronic obstructive pulmonary disease and effect of platelet activation on pulmonary hypertension. Method: We studied platelet aggregation ratio and alpha-granule products such as platelet factor 4(PF4) and beta-thromboglobulin (${\beta}$-TG) in control subjects and COPD without and with pulmonary hypertension subjects. Result: 1) The platelet aggregation ratio (PAR) was $0.99{\pm}0.04$ in control subjects, $0.98{\pm}0.05$ in COPD without pulmonary hypertension subjects and $0.89{\pm}0.08$ in COPD with pulmonary hypertension subjects. The platelet aggregation ratio of COPD subjects was tend to decrease than that of control subjects and the ratio of COPD with pulmonary hypertension subjects was significantly lower than that of control subjects. 2) The platelet factor 4 (PF4, IU/ml) was $4.7{\pm}1.2$ in control subjects, $18.6{\pm}4.9$ in COPD without pulmonary hypertension subjects and $57.2{\pm}12.7$ in COPD with pulmonary hypertension subjects. The level of COPD subjects was significantly higher than that of control subjects and the level of COPD with pulmonary hypertension subjects was significantly higher than that of COPD without pulmonary hypertension subjects. 3) The beta-thromboglobulin (${\beta}$-TG, IU/ml) was $34.4{\pm}5.8$ in control subjects, $80.4{\pm}18.1$ in COPD without pulmonary hypertension subjects and $93.0{\pm}14.0$ in COPD with pulmonary hypertension subjects. The level of COPD subjects was significantly higher than that of conrtrol subjects and the level of COPD with pulmonary hypertension subjects was tend to increase than that of COPD without pulmonary hypertension subjects. 4) There was no correlation between the clinical parameters and PAR, PF4 and ${\beta}$-TG but there was significant correlation among PAR, PF4 and ${\beta}$-TG. Conclusion: The platelet is activated in chronic obstructive pulmonary disease and the platelet of COPD with pulmonary hypertension is tend to be activated more than that of COPD without pulmonary hypertension. So, activated platelet may involve in the pathogenesis and maintenance of pulmonary hypertension in COPD subjects and modulation of platelet activity that might reduce pulmonary hypertension needs to be determined.

• Journal of IKEEE
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• v.12 no.3
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• pp.176-183
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• 2008

The high efficiency power management IC(PMIC) with DTMOS(Dynamic Threshold voltage MOSFET) switching device is proposed in this paper. PMIC is controlled with PWM control method in order to have high power efficiency at high current level. DTMOS with low on-resistance is designed to decrease conduction loss. The control parts in Buck converter, that is, PWM control circuits consist of a saw-tooth generator, a band-gap reference circuit, an error amplifier and a comparator circuit as a block. The Saw-tooth generator is made to have 1.2 MHz oscillation frequency and full range of output swing from ground to supply voltage(VDD:3.3V). The comparator is designed with two stage OP amplifier. And the error amplifier has 70dB DC gain and $64^{\circ}$ phase margin. DC-DC converter, based on Voltage-mode PWM control circuits and low on-resistance switching device, achieved the high efficiency near 95% at 100mA output current. And DC-DC converter is designed with LDO in stand-by mode which fewer than 1mA for high efficiency.

• Journal of Radiation Protection and Research
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• v.39 no.3
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• pp.134-141
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• 2014

Along with the wide use of radiotherapy in cancer treatment, there is growing interest in beneficial effect of low-dose irradiation (LDI) in cancer therapy. Therefore, we investigate how LDI affects immune responses in mice model. Total body irradiation (TBI) on C57BL/6 mice was given at low-dose rate of $1mGy{\cdot}min^{-1}$ using $^{137}Cs$ source at three times for consecutive three days. Hematological examination, total cell numbers of spleen, populations and characteristics of splenocytes were determined. Total numbers of RBC or platelet in irradiated mice showed no significant changes. WBC counts were decreased in a dose-dependent manner 2 days after TBI, however, these differences are gradually waned until 28 days. Dose-dependent decrease in the number of splenocytes of TBI mice at day 2 was also improved as time progressed. While the level of Foxp3 mRNA was decreased, the frequency of $CD4^+$ T cells and $CD69^+$ cells in spleen was increased at day 2 and 14. Fractionated low-dose TBI on mice exhibited normal body weight with no distinguishable behavior during whole experimental periods. These results suggest that some parameters of immune system could be altered and evaluated by fractionated low-dose TBI and be used to broaden boundary of low dose radiation research.

• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1693-1706
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• 2019

Atopic dermatitis (AD) is a chronic inflammatory skin disease of mainly infants and children. Currently, the development of safe and effective treatments for AD is urgently required. The present study was conducted to investigate the immunomodulatory effects of yeast-extracted β-1,3/1,6-glucan and/or Lactobacillus plantarum (L. plantarum) LM1004 against AD-like symptoms. To purpose, β-1,3/1,6-glucan and/or L. plantarum LM1004 were orally administered to AD-induced animal models of rat (histamine-induced vasodilation) and mouse (pruritus and contact dermatitis) exhibiting different symptoms of AD. We then investigated the treatment effects on AD-like symptoms, gene expression of immune-related factors, and gut microbiomes. Oral administration of β-1,3/1,6-glucan (0.01 g/kg initial body weight) and/or 2 × 10¹² cells/g L. plantarum LM1004 (0.01 g/kg initial body weight) to AD-induced animal models showed significantly reduced vasodilation in the rat model, and pruritus, edema, and serum histamine in the mouse models (p < 0.05). Interestingly, β-1,3/1,6-glucan and/or L. plantarum LM1004 significantly decreased the mRNA levels of Th2 and Th17 cell transcription factors, while the transcription factors of Th1 and Treg cells, galactin-9, filaggrin increased, which are indicative of enhanced immunomodulation (p < 0.05). Moreover, in rats with no AD induction, the same treatments significantly increased the relative abundance of phylum Bacteroidetes and the genus Bacteroides. Furthermore, bacterial taxa associated with butyrate production such as, Lachnospiraceae and Ruminococcaceae at family, and Roseburia at genus level were increased in the treated groups. These findings suggest that the dietary supplementation of β-1,3/1,6-glucan and/or L. plantarum LM1004 has a great potential for treatment of AD as well as obesity in humans through mechanisms that might involve modulation of host immune systems and gut microbiota.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.780-803
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• 2003

Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB ($\textrm{NF}_{-{\kappa}}\textrm{B}$) activators [e.g. tumor necrosis factor-$\alpha$, interleukin-1, lipopolysaccharides, and ultraviolet light] leads to phosphorylation and degradation of the inhibitory protein, $\textrm{I}_{{\kappa}}\textrm{B}$. Liberated $\textrm{NF}_{-{\kappa}}\textrm{B}$ is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. In order to demonstrate the possible role of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of $\textrm{NF}_{-{\kappa}}\textrm{B}$ induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with $\textrm{pNF}_{-{\kappa}}\textrm{B}$-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the $\textrm{NF}_{-{\kappa}}\textrm{B}$ activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation was measured with the SEAP reporter gene assay using a fluorescence detection method. Of the Mis tested, kojic acid ($IC_{50}$/ = 60 $\mu$M) was found to be the most potent inhibitor of UVB-upregulating $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in transfectant HaCaT cells, which is followed by niacinamide ($IC_{50}$/= 540 $\mu$M). Pretreatment of the transfectant HaCaT cells with the Mis, especially kojic acid and niacinamide, effectively lowered $\textrm{NF}_{-{\kappa}}\textrm{B}$ binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. These observations suggest that Mis working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

• Nutrition Research and Practice
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• v.4 no.2
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.129-135
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• 2008

Berberine is an isoquinoline alkaloid used in traditional Chinese medicine and has been isolated from a variety of plants, such as Coptis chinensis and Phellodendron amurense. It has a wide spectrum of clinical applications such as in anti-tumor, anti-microbial, and anti-inflammatory activities. However, it is still unknown that berberine related with reactive oxygen species (ROS)-mediated apoptosis pathway in human hepatoma HepG2 cells. In the present study, we are examined the molecular mechanism of ROS- and p38 MAP kinase-mediated apoptosis by berberine in HepG2 cells. Berberine increased cytotoxicity effects by time- and does-dependent manner. $LD_{50}$ was detected 50 ${\mu}M$ at 48h of exposure to berberine. Nuclei cleavage and apoptotic DNA fragmentation were observed in cells treated with 50 ${\mu}M$ of berberine for 48h. Moreover, berberine induced the activating of caspase-3, p53, p38 and Bax expression, whereas the expression of anti-apoptotic signaling pathways, Bcl-2, was decreased. Additionally, berberine-treated cells had an increased level of generation of ROS and nitric oxide (NO). These results indicated that berberine induces apoptosis of HepG2 cells may be mediated oxidative injury acts as an early and upstream change, triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, p38 and p53 activation, caspase-3 activation, and consequent leading to apoptosis.

• JSTS:Journal of Semiconductor Technology and Science
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• v.16 no.1
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• pp.126-142
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• 2016

This paper presents a wide-frequency-range, low-power transceiver with an automatic impedance-matching calibration for TV-white-space (TVWS) application. The wide-range automatic impedance matching calibration (AIMC) is proposed for the Drive Amplifier (DA) and LNA. The optimal $S_{22}$ and $S_{11}$ matching capacitances are selected in the DA and LNA, respectively. Also, the Single Pole Double Throw (SPDT) switch is integrated to share the antenna and matching network between the transmitter and receiver, thereby minimizing the systemic cost. An N-path filter is proposed to reject the large interferers in the TVWS frequency band. The current-driven mixer with a 25% duty LO generator is designed to achieve the high-gain and low-noise figures; also, the frequency synthesizer is designed to generate the wide-range LO signals, and it is used to implement the FSK modulation with a programmable loop bandwidth for multi-rate communication. The TVWS transceiver is implemented in $0.13{\mu}m$, 1-poly, 6-metal CMOS technology. The die area of the transceiver is $4mm{\times}3mm$. The power consumption levels of the transmitter and receiver are 64.35 mW and 39.8 mW, respectively, when the output-power level of the transmitter is +10 dBm at a supply voltage of 3.3 V. The phase noise of the PLL output at Band 2 is -128.3 dBc/Hz with a 1 MHz offset.

• Korean Journal of Food Science and Technology
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• v.43 no.4
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• pp.483-489
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• 2011

Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound frequently found in green tea, and its physiological actions have been extensively investigated. In the present study, changes in chemical stability and cytotoxic properties of EGCG in the presence of different types of antioxidants were investigated. The antioxidants used modulated the chemical stability of EGCG. Superoxide dismutase (SOD) significantly increased EGCG stability; EGCG was less stable in the presence of catalase. Ascorbic acid, N-acetylcysteine (NAC), and glutathione (GSH) stabilized EGCG concentration dependently. The $H_2O_2$ level generated from EGCG was decreased by catalase, SOD, and NAC but not by GSH. The cytotoxic effects of EGCG also decreased in the presence of NAC, catalase, and SOD. GSH, however, showed a complicated modulatory pattern according to the EGCG and GSH concentrations, and ascorbic acid rather enhanced EGCG toxicity. The results suggest that certain antioxidants could modulate the cytotoxic properties of EGCG in a cell culture system not only by removing reactive oxygen species but by modulating chemical stability and other factors, which should be considered carefully when studying reactive oxygen species-dependent mechanisms of EGCG.