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Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

  • Jalin, Angela M.A. Anthony;Lee, Jae-Chul;Cho, Geum-Sil;Kim, Chunsook;Ju, Chung;Pahk, Kisoo;Song, Hwa Young;Kim, Won-Ki
    • Biomolecules & Therapeutics
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    • v.23 no.6
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    • pp.531-538
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    • 2015
  • Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

Modulatory Effects of 21 kinds of Medicinal Herbs Including Herba Pogostemi (Agastache rugosa) on Nitric Oxide Production in Macrophage Cell line RAW 264.7 cells (곽향(Agastache rugosa)을 포함한 21종의 한약재가 대식세포주 RAW 264.7 세포의 nitric oxide(NO) 생산 조절에 미치는 효과)

  • Kim, Seung-Hyun;Kang, Mi-Young;Nam, Seok-Hyun
    • Applied Biological Chemistry
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    • v.48 no.4
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    • pp.411-417
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    • 2005
  • Aqueous extracts were prepared from 21 medicinal herbs including Herba Pogostemi (Agastache rugosa) to examine their modulatory effects on NO production in mouse macrophage cell line RAW264.7 cells. While almost all medicinal herb extracts failed to show marked scavenging activities to NO produced by LPS stimulation, only Herba Pogostemi showed a rather strong induction of NO production in RAW264.7 cells without stimulation with LPS. When we treated the cell with $200{\mu}M\;of\;N^G-monomethyl-L-arginine\;(N^GMMA)$, a NOS2 inhibitor, a significant reduction in NO production could be observed. Moreover, a treatment of $100{\mu}M$ pyrrolidine dithiocarbamate (PDTC) led to about a 79% reduction of NO production. These results demonstrated that the aqueous extract of Herba Pogostemi might provide a second signal for the expression of NOS2 in RAW264.7 cells, and suggested that Herba Pogostemi induces NO production through L-argininedependent pathway.

Metabolism of Ginsenoside Rg5, a Main Constituent Isolated from Red Ginseng, by Human Intestinal Microflora and Their Antiallergic Effect

  • Shin, Yong-Wook;Bae, Eun-Ah;Han, Myung-Joo;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.11
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    • pp.1791-1798
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    • 2006
  • When ginsenoside Rg5, a main component isolated from red ginseng, was incubated with three human fecal microflora for 24 h, all specimens showed hydrolyzing activity: all specimens produced ginsenoside Rh3 as a main metabolite, but a minor metabolite $3{\beta},12{\beta}$-dihydroxydammar-21(22),24-diene (DD) was observed in two specimens. To evaluate the antiallergic effect of ginsenoside Rg5 and its metabolites, the inhibitory effect of ginsenoside Rg5 and its metabolite ginsenoside Rh3 against RBL-2H3 cell degranulation, mouse passive cutaneous anaphylaxis (PCA) reaction induced by the IgE-antigen complex, and mouse ear skin dermatitis induced by 12-O-tetradecanoilphorbol-13-acetate (TPA) were measured. Ginsenosides Rg5 and Rh3 potently inhibited degranulation of RBL-2H3 cells. These ginsenosides also inhibited mRNA expression of proinflammatory cytokines IL-6 and $TNF-{\alpha}$ in RBL-2H3 cells stimulated by IgE-antigen. Orally and intraperitoneally administered ginsenoside Rg3 and orally administered ginsenoside Rg5 to mice potently inhibited the PCA reaction induced by IgE-antigen complex. However, intraperitoneally administered ginsenoside Rg5 nearly did not inhibit the PCA reaction. These ginsenosides not only suppressed the swelling of mouse ears induced by TPA, but also inhibited mRNA expression of cyclooxygenase-2, $TNF-{\alpha}$, and IL-4 and activation of transcription factor NF-kB. These inhibitions of ginsenoside Rh3 were more potent than those of ginsenoside Rg5. These findings suggest that ginsenoside Rg5 may be metabolized in vivo to ginsenoside Rh3 by human intestinal microflora, and ginsenoside Rh3 may improve antiallergic diseases, such as rhinitis and dermatitis.

Antiallergic Effects of Fermented Ixeris sonchifolia and Its Constituents in Mice

  • Trinh, Hien-Trung;Bae, Eun-Ah;Hyun, Yang-Jin;Jang, Yoon-Ah;Yun, Hyung-Kwon;Hong, Seong-Sig;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.20 no.1
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    • pp.217-223
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    • 2010
  • To evaluate the antiallergic effect of fermented Ixeris sonchifolia (IS, family Compositae), we prepared IS kimchi, isolated lactic acid bacteria (LAB) from it, fermented IS with these LAB, and investigated their antiallergic effects. IS kimchi inhibited the passive cutaneous anaphylaxis (PCA) reaction induced by an IgE-antigen complex as well as the scratching behavior induced by compound 48/80 or histamine more potently than IS. When IS was fermented with LAB isolated from IS kimchi, its antiallergic effects was also increased. Of LAB used for fermentation, Lactobacillus brevis more potently increased the antiallergic effects. Its main constituents, chlorogenic acid and luteolin, potently inhibited the PCA reaction induced by the IgE-antigen complex as well as the pruritis induced by compound 48/80 or histamine. These constituents inhibited the expression of pro inflammatory and allergic cytokines, TNF-$\alpha$. and IL-4, and transcription factor NF-${\kappa}B$ activation induced by the IgE-antigen complex in RBL-2H3 cells, as well as the degranulation of RBL-2H3 cells induced by the IgE-antigen complex. Luteolin more potently inhibited these allergic reactions than chlorogenic acid. These findings suggest that the antiallergic effect of IS can be increased by LAB fermentation, and the fermented IS might improve allergic reactions such as pruritus, anaphylaxis, and inflammation.

The Aqueous Extract of Radio-Resistant Deinococcus actinosclerus BM2T Suppresses Lipopolysaccharide-Mediated Inflammation in RAW264.7 Cells

  • Kim, Myung Kyum;Jang, Seon-A;Namkoong, Seung;Lee, Jin Woo;Park, Yuna;Kim, Sung Hyeok;Lee, Sung Ryul;Sohn, Eun-Hwa
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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    • pp.583-590
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    • 2020
  • Deinococcus actinosclerus BM2T (GenBank: KT448814) is a radio-resistant bacterium that is newly isolated from the soil of a rocky hillside in Seoul. As an extremophile, D. actinosclerus BM2T may possess anti-inflammatory properties that may be beneficial to human health. In this study, we evaluated the anti-inflammatory effects of BM2U, an aqueous extract of D. actinosclerus BM2T, on lipopolysaccharide (LPS)-mediated inflammatory responses in RAW264.7 macrophage cells. BM2U showed antioxidant capacity, as determined by the DPPH radical scavenging (IC50 = 349.3 ㎍/ml) and ORAC (IC50 = 50.24 ㎍/ml) assays. At 20 ㎍/ml, BM2U induced a significant increase in heme oxygenase-1 (HO-1) expression (p < 0.05). BM2U treatment (0.2-20 ㎍/ml) significantly suppressed LPS-induced increase in the mRNA expression of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 (p < 0.05). BM2U treatment also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which are involved in the production of inflammatory mediators. BM2U treatment also inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs): JNK, ERK, and p-38 (p < 0.05). Collectively, BM2U exhibited anti-inflammatory potential that can be exploited in attenuating inflammatory responses.

Association of Toll-Like Receptor 5 Gene Polymorphism with Susceptibility to Ossification of the Posterior Longitudinal Ligament of the Spine in Korean Population

  • Chung, Won-Suk;Nam, Dong-Hyun;Jo, Dae-Jean;Lee, Jun-Hwan
    • Journal of Korean Neurosurgical Society
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    • v.49 no.1
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    • pp.8-12
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    • 2011
  • Objective: Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may playa role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-${\kappa}B$). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population. Methods: A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR). Results: None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p> 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models. Conclusion: These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.

Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis

  • Lee, Jin;Cho, Joon-Yong;Kim, Won-Kyu
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.284-291
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    • 2014
  • BACKGROUND/OBJECTIVES: The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis. MATERIALS/METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS: The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-, ${\alpha}$, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION: These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS.

Response of Soil Microbial Communities to Applications of Green Manures in Paddy at an Early Rice-Growing Stage (녹비 시용이 초기 논 토양 미생물군집에 미치는 영향)

  • Kim, Eun-Seok;Lee, Young-Han
    • Korean Journal of Soil Science and Fertilizer
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    • v.44 no.2
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    • pp.221-227
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    • 2011
  • Applications of green manures generally improve the soil quality in rice paddy in part through restructuring of soil microbial communities. To determine how different green manures affect soil microbial communities during the early stages of rice growth, fatty acid methyl ester (FAME) profiles were used to the effects of different management practices: 1) conventional farming (CF), 2) no-treatment (NT), 3) Chinese milk vetch (CMV), 4) green barley (GB), and 5) triticale in paddy field. With applications of green manures, soil organic matter was significantly higher than CF, while soil Na concentration was significantly lower compared with CF (p<0.05). Total soil microbial biomass of CMV was higher (p<0.05) than NF by approximately 31%. The highest ratio of monounsaturated fatty acid to saturated fatty acid was found in the GB plot, followed by CMV and triticale compared with CF (p<0.05), possibly indicating that microbial stress was less in GB and CMV plots. Populations of Gram-negative bacteria and arbuscular mycorrhizal fungi also were significantly higher green manures than CF (p<0.05). Our findings suggest that GB should be considered as optimum green manure for enhancing soil microbial community at an early growing stage in paddy field.

Characterization and Numerical Taxonomy of Heterotrophic Bacterial Community in Naktong Estuarine Ecosystem (낙동강 하구 생태계의 종속영양세균의 군집구조 분석 및 수리학적 분류)

  • 귄오섭;조경제
    • Korean Journal of Microbiology
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    • v.30 no.6
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    • pp.444-449
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    • 1992
  • A total of 858 heterotrohic bacteria were isolated and analyzed hy numerical method to investigate the heterotrophic hacterial community structure in Naktong Estuary. Although the values of H' (Shannon's diversity index). ranged between 1.54 and 3.49. were similar with those of the data hefore the construction of Naktong River barrage, however J' (evenness index. 0.31-0.80) was reduced. Physiological tolerance index for water temperature ($P_{s}$) was high at St.l and 2 whose depthes arc shallower than the other stations. and indices for pH ($P_{h}$) and salinity ($P_{s}$) were high at St. 2. 3. 4 where freshwater and seawater arc mixed. The predominant clusters were identified as Aeromonas. Vihrio. Pseudomonas. Acinelobacter-Morexella. Alcaligenes. Flavobacterium. Micrococcaccae. and Enterohacteriaceae. The kinds nf the isolates were similar with the previous result. hut the dominant genus was changed. These results suggest that the environmental changes in Naktong Estuary affect the hacterial physiological adaptation rather than the composition of heterotrophic hactcrial community.

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The Design and implementation of a Low Noise Amplifier for DSRC using GaAs MESFET (GaAs MESFET을 이용한 DSRC용 LNA MMIC 설계 및 구현)

  • Moon, Tae-Jung;Hwang, Sung-Bum;Kim, Byoung-Kook;Ha, Young-Chul;Hur, Hyuk;Song, Chung-Kun;Hong, Chang-Hee
    • Proceedings of the IEEK Conference
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    • 2002.06b
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    • pp.61-64
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    • 2002
  • We have optimally designed and implemented by a monolithic microwave integrated circuit(MMIC) the low noise amplifier(LNA) of 5.8GHz band composed of receiver front-end(RFE) in a on-board equipment system for dedicated short range communication using a depletion-mode GaAs MESFET. The LNA is provided with two active devices, matching circuits, and two drain bias circuits. Operating at a single supply of 3V and a consumption current of 18㎃, The gain at center frequency 5.8GHz is 13.4dB, Noise figure(NF) is 1.94dB, Input 3rd order intercept point(lIPS) is 3dBm, and Input return loss(5$_{11}$) and Output return loss(S$_{22}$) is -l8dB and -13.3dB, respectively. The circuit size is 1.2$\times$O.7$\textrm{mm}^2$.EX>.>.

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