• Title/Summary/Keyword: cascade effect

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Inhibitory Mechanism of Blood Coagulation and in vivo Anticoagulant Activities of Polysaccharides Isolated from Codium fragile (청각으로부터 분리한 다당류의 혈액응고 저해기작 및 in vivo 항응고 활성)

  • Shim, Yun-Yong;An, Jeung-Hee;Cho, Won-Dai;Chun, Hyug;Kim, Kyung-Im;Cho, Hong-You;Yang, Han-Chul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.917-923
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    • 2002
  • Inhibitory mechanism of the anticoagulant polysaccharide purified from Codium fragile was investigated. The anticoagulant compounds (Cf-30-IV-4-ii, CF-30-IV) prolonged the clotting time at both activated partial thrombo-plastin time (aPTT) and thrombin time (TT). The Inhibition factor assay of instrinsic coagulation pathway in the blood showed that the anticoagulant polysaccharide (CF-30-IV-4-ii) inhibited other factors such as Ⅷ, Ⅸ, Ⅵ and Ⅷ of the coagulation cascade, which did not affect the lupus anticoagulant AB activity. In the thrombin inhibition pattern the CF-30-IV-4-ii did not directly influence the fibrine formation mediated by thrombin but af-fected the anticoagulant activity through the activation of antithrombin III. Base on these result, the anticoaglant polysaccharide (CF-30-IV-4-ii) was considered to inhibit serine pretense involved in the blood coagulation cascade through the enhancing antithrombin III activity. The residual effects of anticoagulant activity and antithrombosis were tested with ICR mice. The anticoagulant polysaccharide (CF-30-W) kept its anticoagulant activitv for 6 hrs with 100% survival at a dose of 150 mg/kg in the antithromboisis test. The anticoagulant effect of CF-30-RF in ex vivo was proportional to the concentration of intravenously injected dose up to 100 mg/kg.

High-mobility Group Box 1 Induces the Epithelial-mesenchymal Transition, Glycolytic Switch, and Mitochondrial Repression via Snail Activation (HMGB1/Snail cascade에 의한 epithelial-mesenchymal transition 및 glycolytic switch, mitochondrial repression 유도)

  • Lee, Su Yeon;Ju, Min Kyung;Jeon, Hyun Min;Kim, Cho Hee;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1179-1191
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    • 2019
  • Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

Inhibitory Effect of Capsaicin on Interleukin-8 Production by Helicobacter pylori-Infected MKN-45 Cells

  • Lee, Kwang-Hyoung;Lee, Yong-Chan;Kim, Tae-Il;Noh, Sung-Hoon;Kim, Ji-Yeon;Paik, Hyun-Dong;Kim, Chang-Han
    • Journal of Microbiology and Biotechnology
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    • v.16 no.7
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    • pp.1078-1083
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    • 2006
  • Capsaicin is the active ingredient in chili pepper and has an inhibitory effect on Helicobacter pylori growth and $NF-{\kappa}B$ activation. The present study examined the effect of capsaicin on interleukin (IL)-8 production by H. pylori ATCC 43504-infected MKN-45 cells, a gastric epithelial cell line. The viability of the MKN-45 cells treated with capsaicin at 0, 50, 100, 250, and $500\;{\mu}M$ was 99, 98, 99, 99, and 85%, respectively. A capsaicin concentration as low as $50\;{\mu}M$ significantly inhibited the IL-8 production induced by H. pylori ATCC 43504 infection (43.2% of control) during 24 h of incubation. However, low concentrations of capsaicin $(50\;and\;100{\mu}M)$ did not significantly inhibit the IL-8 production by $TNF-{\alpha}-$ or PMA-treated MKN-45 cells. Therefore, the overall inhibitory effect of capsaicin on H. pylori ATCC 43504 was the sum of H. pylori ATCC 43504 growth inhibition, host cell survival, and $NF-{\kappa}B$ signal cascade inhibition.

The Role of Yoga Intervention in the Treatment of Allergic Rhinitis: A Narrative Review and Proposed Model

  • Chauhan, Ripudaman Singh;Rajesh, S.K
    • CELLMED
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    • v.10 no.3
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    • pp.25.1-25.7
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    • 2020
  • Allergic Rhinitis (AR) is an IgE (immunoglobin-E) mediated inflammatory condition of upper respiratory tract; main clinical features involve runny nose, sneezing, nasal obstruction, itching and watery eyes. AR is a global problem and has large variations in incidences, currently affects up to 20% - 40% of the population worldwide. It may not be a life-threatening disease per se but indisposition from the condition can be severe and has the potential to adversely affect the daily functioning of life. Classical yoga literature indicates that, components of yoga have been used to treat numerous inflammatory conditions including upper respiratory tract. A few yoga intervention studies reported improvement in lung capacity, Nasal air flow and symptoms of allergic rhinitis. This review examined various anti-inflammatory pathways mediated through Yoga that include downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. The hypothalaminic-pitutary-adrenal (HPA) axis and vagal efferent stimulation has been reported to mediate anti-inflammatory effect. A significant reduction is also reported in other inflammatory biomarkers like- TNF-alpha, nuclear factor kappa B (NF-κB), plasma CRP and Cortisol level. Neti, a yogic nasal cleansing technique, reported beneficial effect on AR by direct physical cleansing of thick mucus, allergens, and inflammatory mediator from nasal mucosa resulting in improved ciliary beat frequency. We do not find any study showing effect of yoga on neurogenic inflammation. In summary, Integrated Yoga Therapy may have beneficial effect in reducing symptoms and improving quality of life for patients with allergic rhinitis. Yoga may reduce inflammation through mediating neuro-endocrino-immunological network. Future studies are needed to explore the mechanism how yoga might modulate immune inflammation cascade and neurogenic inflammation at the cellular level in relevance to allergic rhinitis; the effects of kriyas (yogic cleansing techniques) also need to be evaluated in early and late phase of AR. So the proposed model could guide future research.

Soft corals collected from Jeju Island inhibits the α-MSH-induced melanogenesis in B16F10 cells through activation of ERK

  • Sanjeewa, K. K. Asanka;Park, Young-jin;Fernando, I. P. Shanura;Ann, Yong-Seok;Ko, Chang-Ik;Wang, Lei;Jeon, You-Jin;Lee, WonWoo
    • Fisheries and Aquatic Sciences
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    • v.21 no.9
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    • pp.21.1-21.8
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    • 2018
  • In the present study, we first evaluated the melanin inhibitory effect of four crude 70% ethanol extracts separated from soft corals abundantly growing along the seawaters of Jeju Island, South Korea, including Dendronephthya castanea (DC), Dendronephthya gigantea (DG), Dendronephthya puetteri (DP), and Dendronephthya spinulosa (DS). Among the four ethanol extracts, the ethanol extract of DP (DPE) did not possess any cytotoxic effect on B16F10 cells. However, all other three extracts showed a cytotoxic effect. Also, DPE reduced the melanin content and the cellular tyrosinase activity without cytotoxicity, compared to the ${\alpha}-MSH$-stimulated B16F10 cells. Specifically, DPE downregulated the expression levels of tyrosinase and microphthalmia-associated transcription factor by activating the ERK signaling cascade in ${\alpha}-MSH$-stimulated B16F10 cells. Interestingly, the melanin inhibitory effect of DPE was abolished by the co-treatment of PD98059, an ERK inhibitor. According to these results, we suggest that DPE has whitening capacity with the melanin inhibitory effects by activating ERK signaling and could be used as a potential natural melanin inhibitor for cosmeceutical products.

Effect of Relative Position of Vane and Blade on Heat/Mass Transfer Characteristics on Stationary Turbine Blade Surface (베인과 블레이드 사이의 상대위치 변화에 따른 터빈 블레이드 표면에서의 열/물질전달 특성)

  • Rhee, Dong-Ho;Cho, Hyung Hee
    • 유체기계공업학회:학술대회논문집
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    • 2004.12a
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    • pp.140-150
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    • 2004
  • In this study, the effect of relative position of the blade for the fixed vane has been investigated on blade surface heat transfer. The experiments were conducted in a low speed stationary annular cascade, and heat transfer of blade was examined for six positions within a pitch. Turbine test section has one stage composed of sixteen guide vanes and blades. The chord length of the tested blade is 150 mm and the mean tip clearance of the blade having flat tip is about $2.5\%$ of the blade chord. For the detailed mass transfer measurements on the blade surfaces, a naphthalene sublimation technique was used. The inlet flow Reynolds number is fixed to $1.5{\times}10^5$. Complex heat transfer characteristics are observed on the blade surface due to various flow characteristics, such as separation bubble, relaminarization, transition to turbulence and leakage vortices. The distributions of velocity and turbulence intensity change significantly with the relative position due to the blockage effect of the blade. This causes the variation of heat transfer patterns on the blade surface. The results show that the flow near the leading edge get highly disturbed and deflected toward the either side of the blade when the blade leading edge is positioned close to the trailing edge of the vane. Therefore, separation bubble disappears on the pressure side and overall heat transfer on the relaminarization region is increased. But, due to reduced tip gap flow at the upstream region, the effect of leakage flow on the upstream region of the blade surface is weakened. Thus, the heat transfer characteristics significantly change with the blade positions.

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THE EFFECT OF SODIUM FLUORIDE ON THE PHYSIOLOGICAL ROLE OF OSTEOBLASTIC CELL (불화나트륨이 조골세포의 생리적 활성에 미치는 영향)

  • Kim, Dae-Eop
    • Journal of the korean academy of Pediatric Dentistry
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    • v.25 no.3
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    • pp.635-648
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    • 1998
  • The clinical use of fluoride with a well known osteogenic action in osteoporotic patients is rational, because this condition is characterized by impaired bone formation. However, its anabolic effect has not been demonstrated well in vitro. The purpose of this study was to investigate the effects of sodium fluoride on the physiological role of osteoblastic cell. Osteoblastic cells were isolated from fetal rat calvaria. The results were as follows : 1. Mineralized nodules were shown in osteoblastic cell cultures, which had been maintained in the presence of ascorbic acid and ${\beta}-glycerophosphate$ up to 21 days. When cultures were treated with pulses of 48 hr duration before apparent mineralization was occurring, 2-fold increased in their number was detected. 2. Alkaline phosphatase activity of osteoblastic cells was inhibited by sodium fluoride in dose dependent manner. 3. The effect of sodium fluoride on the osteoblastic cell proliferation was measured by the incorporation of $[^3H]$-thymidine into DNA. As a result, sodium fluoride at $1{\sim}100{\mu}M$ increased the $[^3H]$-thymidine incorporation into DNA in a dose dependent manner. 4. The signaling mechanism activated by sodium fluoride dose-dependently enhanced the tyrosine phosphorylation of the adaptor molecule $Shc^{p66}$ and their association with Grb2, one of earlier events in a MAP kinase activation pathway cascade used by a significant subset of G protein-coupled receptors. 5. The phosphorylation of CREB(cAMP response element binding protein)was inhibited by the sodium fluoride in MC3T3E1 cells. In conclusion, the results of this study suggested that the mitogenic effect of the sodium fluoride in MC3T3E1 cell was stimulated in a dose-dependent manner and suggested "an important role for the interaction between She and Grb2" in controlling the proliferation of osteoblasts.

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Inhibitory Effect of a Phosphatidyl Ethanolamine Derivative on LPS-Induced Sepsis

  • Lee, Chunghyun;An, Hyun-Jung;Kim, Jung-In;Lee, Hayyoung;Paik, Sang-Gi
    • Molecules and Cells
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    • v.27 no.2
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    • pp.251-255
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    • 2009
  • Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopolysaccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethylenetriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 ($K_d$, $9.52{\times}10^{-8}M$). It dose dependently inhibited LPS-mediated activation of human myeloid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on $NF-{\kappa}B$ activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results suggest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14.

Granulocyte Macrophage-Colony Stimulating Factor Signaling in Development of Mouse Embryos (Granulocyte Macrophage Colony Stimulating Factor에 의한 생쥐 초기 배아 발생의 신호전달)

  • Suh, Hye-Young;Chung, Kyu-Hoi;Kang, Byung-Moon;Gye, Myung-Chan
    • Clinical and Experimental Reproductive Medicine
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    • v.30 no.1
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    • pp.5-14
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    • 2003
  • Objective: Present study was aimed to verify the effect of granulocyte macrophage-colony stimulating factor (GM-CSF) in the preimplantation development of mouse embryos and the involvement of the mitogen activated protein kiase (MAPK) in the GM-CSF signaling. Methods: Two-cell embryos were cultured for 96 h in the presence or absence of GM-CSF (0, 0.4, 2, 10 ng/ml) and PD98059, a MEK inhibitor (10 ${\mu}M$). Morphological development, cell number per blastocyst, and apoptotic nuclei, were eamined. MAPK activity of embryonic immunoprecipitate by MAPK (ERK1/2) antibody was measured by in vitro phosphorylation of myelin basic protein. Results: At post hCG 122 h the embryonic development among the experimental groups was significantly different (p=0.018). The rate of blastocyst development and cell number per embryo were the highest in 2 ng/ml GM-CSF treatment group. The percent of apoptotic cells of the GM-CSF-treated embryos was the lowest among the group. In blastocysts, GM-CSF treatment transiently increased MAPK activity. PD098059 attenuated the effect of GM-CSF on the morphological development, increase in cell number per blastocyst, down regulation of apoptosis, and upregulation of MAPK activity, suggesting that activation of MAPK cascade possibly mediated the embryotropic effect of GM-CSF. Conclusion: This result suggested that GM-CSF potentiated the development of preimplantation mouse embryos by activation of MAPK.

Gecko proteins induce the apoptosis of bladder cancer 5637 cells by inhibiting Akt and activating the intrinsic caspase cascade

  • Kim, Geun-Young;Park, Soon Yong;Jo, Ara;Kim, Mira;Leem, Sun-Hee;Jun, Woo-Jin;Shim, Sang In;Lee, Sang Chul;Chung, Jin Woong
    • BMB Reports
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    • v.48 no.9
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    • pp.531-536
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    • 2015
  • Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536]