• Title/Summary/Keyword: P-M interaction

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Quality Characteristics of Sea Tangle Single Cell Detritus (SCD) Manufactured by Vibrio sp. Isolated from Batillus cornutus (소라에서 분리한 Vibrio균으로 제조한 다시마 Single Cell Detritus(SCD)의 품질특성)

  • Bang, Sang-Jin;Shin, Il-Shik;Kim, Sang-Moo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.606-612
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    • 2006
  • Obtaining powder form of seaweed is essential for the use of seaweed as a food additive. The deterioration of seaweed caused by high temperatures during homogenization and powder processing is a serious problem and limits the use of seaweed as a food or pharmaceutical ingredient. Furthermore, many powder particles are not fluidized very well because of the interaction between particles. In order to solve this problem, sea tangle was hydrolyzed to a level of single cell detritus (SCD) by Vibrio sp., isolated from Batillus cornutus. with strong hydrolytic activity. The crude protein and amino acid contents of sea tangle SCD were higher than those of the powder, whereas the reverse was true for ash content. Sea tangle powder contained more mineral than its SCD, whereas total amino acid content was 5 times more in SCD than in power. The anticancer activities of sea tangle SCD and powder were 31.20 and 29.07%, respectively, with no significant difference (p<0.05), but about 15% higher than that of the control. The ACE inhibitory activity of the sea tangle powder, 39.31%, was higher than the 26.07% of the SCD. The antithrombin activity of the sea tangle powder, 55.3 seconds, was higher than the 34.5 seconds of the SCD. Moreover, there was no antioxidative and ischemic activities in both tile sea tangle powder and SCD.

Production of Rapamycin in Streptomyces hygroscopicus from Glycerol-Based Media Optimized by Systemic Methodology

  • Kim, Yong Hyun;Park, Bu Soo;Bhatia, Shashi Kant;Seo, Hyung-Min;Jeon, Jong-Min;Kim, Hyun-Joong;Yi, Da-Hye;Lee, Ju-Hee;Choi, Kwon-Young;Park, Hyung-Yeon;Kim, Yun-Gon;Yang, Yung-Hun
    • Journal of Microbiology and Biotechnology
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    • v.24 no.10
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    • pp.1319-1326
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    • 2014
  • Rapamycin, produced by the soil bacterium Streptomyces hygroscopicus, has the ability to suppress the immune system and is used as an antifungal, anti-inflammatory, antitumor, and immunosuppressive agent. In an attempt to increase the productivity of rapamycin, mutagenesis of wild-type Streptomyces hygroscopicus was performed using ultraviolet radiation, and the medium composition was optimized using glycerol (which is one of the cheapest starting substrates) by applying Plackett-Burman design and response surface methodology. Plackett-Burman design was used to analyze 14 medium constituents: M100 (maltodextrin), glycerol, soybean meal, soytone, yeast extract, $(NH_4)_2SO_4$, $\small{L}$-lysine, $KH_2PO_4$, $K_2HPO_4$, NaCl, $FeSO_4{cdot}7H_2O$, $CaCO_3$, 2-(N-morpholino) ethanesulfonic acid, and the initial pH level. Glycerol, soytone, yeast extract, and $CaCO_3$ were analyzed to evaluate their effect on rapamycin production. The individual and interaction effects of the four selected variables were determined by Box-Behnken design, suggesting $CaCO_3$, soytone, and yeast extract have negative effects, but glycerol was a positive factor to determine rapamycin productivity. Medium optimization using statistical design resulted in a 45% ($220.7{\pm}5.7mg/l$) increase in rapamycin production for the Streptomyces hygroscopicus mutant, compared with the unoptimized production medium ($151.9{\pm}22.6mg/l$), and nearly 588% compared with wild-type Streptomyces hygroscopicus ($37.5{\pm}2.8mg/l$). The change in pH showed that $CaCO_3$ is a critical and negative factor for rapamycin production.

Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-${\kappa}B$ DNA-binding Activity in RAW 264.7 Cells

  • Kim, Seong-Keun;Kim, Young-Mi;Yeum, Chung-Eun;Jin, Song-Hyo;Chae, Gue-Tae;Lee, Seong-Beom
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.6
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    • pp.475-482
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    • 2009
  • Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

  • Jung, Yuchae;Park, Heejoo;Zhao, Hui-Yuan;Jeon, Raok;Ryu, Jae-Ha;Kim, Woo-Young
    • Molecules and Cells
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    • v.37 no.7
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    • pp.547-553
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    • 2014
  • Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.

Improved Dissolution and Characterization of Solid Dispersed Atorvastatin Calcium (아토르바스타틴 칼슘 고체분산체의 특성화 및 용출율 개선)

  • Lee, Jun-Hee;Ku, Jeong;Park, Jung-Soo;Park, Jong-Hak;Ahn, Sik-Il;Mo, Jong-Hyun;Kim, Yun-Tae;Rhee, John-M.;Lee, Hai-Bang;Khang, Gil-Son
    • Journal of Pharmaceutical Investigation
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    • v.38 no.2
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    • pp.111-117
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    • 2008
  • To overcome the solubility of poorly water-soluble drug, the formation of solid dispersion using a spray-dryer with polymeric material, that can potentially enhance the dissolution rate extend of drug absorption was considered in this study. $Eudragit^{(R)}$ E100 as carrier for solid dispersion is acrylate copolymer that soluble in acidic buffer solutions (below pH 5.0). It was used to increase dissolution of atorvastatin calcium as a water-insoluble drug in acidic environments. In this study, a spray-dryer was used to prepare solid dispersion of atorvastatin calcium and $Eudragit^{(R)}$ E100 for purpose of improving the solubility of drug. Atorvastatin calcium and $Eudragit^{(R)}$ E100 were dissolved in ethanol and spray-dryed. DSC and XRD were used to analyze the crystallinity of the sample. It was found that atorvastatin calcium is amorphous in the $Eudragit^{(R)}$ E100 solid dispersion. FT-IR was used to analyze the salt formation by interaction between atorvastatin calcium and $Eudragit^{(R)}$ E100. Comparative dissolution study exhibited better dissolution characteristics than the commercial drug ($Lipitor^{(R)}$) as control. The dissolution rate of atorvastatin calcium was markedly increased in solid dispersion system in simulated gastric juice (pH 1.2). This study proposed that this solid dispersion system improved the bioavailability of poorly water-soluble atorvastatin calcium.

HiF-1α siRNA and Cisplatin in Combination SuppressTumor Growth in a Nude Mice Model of Esophageal Squamous Cell Carcinoma

  • Liao, Hong-Ying;Wang, Gui-Ping;Gu, Li-Jia;Huang, Shao-Hong;Chen, Xiu-Ling;Li, Yun;Cai, Song-Wang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.473-477
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    • 2012
  • Introduction: The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-$1{\alpha}$ siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice. Materials and Methods: Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-$1{\alpha}$ siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-$1{\alpha}$ mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry. Results: In our nude mice model, HIF-$1{\alpha}$ siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-$1{\alpha}$ mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-$1{\alpha}$ siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF-$1{\alpha}$ siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-$1{\alpha}$ siRNA-treated groups (P<0.05). Conclusions: Down-regulated HIF-$1{\alpha}$ expression induced by siRNA could effectively suppress the growth of transplanted ESCC $in$ $vivo$. HIF-$1{\alpha}$ siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.

THE LORENTZ FORCE IN ATMOSPHERES OF CP STARS: θ AUR

  • VALYAVIN G.;KOCHUKHOV O.;SHULYAK D.;LEE B.-C.;GALAZUTDINOV G.;KIM K.-M.;HAN I.
    • Journal of The Korean Astronomical Society
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    • v.38 no.2
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    • pp.283-287
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    • 2005
  • The slow evolution of global magnetic fields and other dynamical processes in atmospheres of CP magnetic stars lead to the development of induced electric currents in all conductive atmospheric layers. The Lorentz force, which results from the interaction between a magnetic field and the induced currents, may modify the atmospheric structure and provide insight into the formation and evolution of stellar magnetic fields. This modification of the pressure-temperature structure influences the formation of absorption spectral features producing characteristic rotational variability of some spectral lines, especially the Balmer lines (Valyavin et al., 2004 and references therein). In order to study these theoretical predictions we began systematic spectroscopic survey of Balmer line variability in spectra of brightest CP magnetic stars. Here we present the first results of the program. A0p star $\Theta$ Aur revealed significant variability of the Balmer profiles during the star's rotation. Character of this variablity corresponds to that classified by Kroll (1989) as a result of an impact of significant Lorentz force. From the obtained data we estimate that amplitudes of the variation at H$\alpha$, H$\beta$, H$\gamma$ and H$\delta$ profiles reach up to $2.4\%$during full rotation cycle of the star. Using computation of our model atmospheres (Valyavin et al., 2004) we interpret these data within the framework of the simplest model of the evolution of global magnetic fields in chemically peculiar stars. Assuming that the field is represented by a dipole, we estimate the characteristic e.m.f. induced by the field decay electric current (and the Lorentz force as the result) on the order of $E {\~} 10^{-11}$ cgs units, which may indicate very fast (< < $10^{10}$ years) evolution rate of the field. This result strongly contradicts the theoretical point of view that global stellar magnetic fields of CP stars are fossil and their the characteristic decay time of about $10^{10}$ yr. Alternatively, we briefly discuss concurring effects (like the ambipolar diffusion) which may also lead to significant atmospheric currents producing the observable Lorentz force.

KCl Mediates $K^+$ Channel-Activated Mitogen-Activated Protein Kinases Signaling in Wound Healing

  • Shim, Jung Hee;Lim, Jong Woo;Kim, Byeong Kyu;Park, Soo Jin;Kim, Suk Wha;Choi, Tae Hyun
    • Archives of Plastic Surgery
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    • v.42 no.1
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    • pp.11-19
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    • 2015
  • Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

Fermented ginseng extract, BST204, disturbs adipogenesis of mesenchymal stem cells through inhibition of S6 kinase 1 signaling

  • Yi, Sang Ah;Lee, Jieun;Park, Sun Kyu;Kim, Jeom Yong;Park, Jong Woo;Lee, Min Gyu;Nam, Ki Hong;Park, Jee Hun;Oh, Hwamok;Kim, Saetbyul;Han, Jihoon;Kim, Bo Kyung;Jo, Dong-Gyu;Han, Jeung-Whan
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.58-66
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    • 2020
  • Background: The biological and pharmacological effects of BST204, a fermented ginseng extract, have been reported in various disease conditions. However, its molecular action in metabolic disease remains poorly understood. In this study, we identified the antiadipogenic activity of BST204 resulting from its inhibition of the S6 kinase 1 (S6K1) signaling pathway. Methods: The inhibitory effects of BST204 on S6K1 signaling were investigated by immunoblot, nuclear fractionation, immunoprecipitation analyses. The antiadipogenic effect of BST204 was evaluated by measuring mRNA levels of adipogenic genes and by chromatin immunoprecipitation and quantitative real-time polymerase chain reaction analysis. Results: Treatment with BST204 inhibited activation and nuclear translocation of S6K1, further decreasing the interaction between S6K1 and histone H2B in 10T1/2 mesenchymal stem cells. Subsequently, phosphorylation of H2B at serine 36 (H2BS36p) by S6K1 was reduced by BST204, inducing an increase in the mRNA expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation and promoted myogenic and early osteogenic gene expression. Consistently, BST204 treatment during adipogenic commitment suppressed the expression of adipogenic marker genes and lipid drop formation. Conclusion: Our results indicate that BST204 blocks adipogenesis of mesenchymal stem cells through the inhibition of S6K1-mediated histone phosphorylation. This study suggests the potential therapeutic strategy using BST204 to combat obesity and musculoskeletal diseases.

Effect of cooling water and inverse lighting on short chain fatty acid and blood lipid of broiler chickens in closed poultry house during hot weather (혹서기 무창계사에서 육계의 혈액지질 및 짧은 사슬지방산에 관한 역전점등과 냉각수 효과)

  • Park, Sang-Oh;Park, Byung-Sung;Hwangbo, Jong;Choi, Hee-Chul
    • Journal of the Korean Applied Science and Technology
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    • v.31 no.1
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    • pp.31-43
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    • 2014
  • This experiment evaluated the interaction effect of extreme heat diet(EHD), inverse lighting, and cool water on the growth performance of broiler chickens under extreme heat stress. There were 4 experimental groups (T1: EHD 1, 10:00-19:00 dark, 19:00-10:00 light, cold water $9^{\circ}C$; T2: EHD 2, 10:00-19:00 dark, 19:00-10:00 light, cold water $9^{\circ}C$; T3: EHD 1, 09:00-18:00 dark, 18:00-09:00 light, cold water $14^{\circ}C$; T4: EHD 2, 09:00-18:00 dark, 18:00-09:00 light, cold water $14^{\circ}C$), each group composed of 25 broilers and the experiment was repeated 3 times. EHD 1 contained soybean oil, molasses, methionine and lysine. EHD 2 contained all nutrients of EHD 1 and vitamin C additionally. As a result, T1 and T2 displayed higher body weight increase and diet intake compared to T3 and T4 (p<0.05). The weights of their liver and gizzard were similar but the weights of the thymus and bursa F were higher for T1 and T2 compared to that of T3 and T4 (p<0.05). It was observed that T1 and T2 displayed higher concentrations of blood triglyceride, total cholesterol, HDL-C and blood sugar compared to that of T3 and T4 but LDL-C level was higher for T3 and T4 compared to that of T1 and T2 (p<0.05). T1 and T2 displayed higher levels of immunity substances such as IgG, IgA and IgM compared to T3 and T4 but the blood level of corticosterone displayed to be lower for T1 and T2 compared to T3 and T4 (p<0.05). The T1 and T2 contained a higher amount of fecal lactobacillus compared to that of T3 and T4 but the T3 and T4 contained a higher amount of fecal E. coli, total aerobic bacteria, coliform bacteria compared to that of T1 and T2 (p<0.05). T1 and T2 displayed higher concentrations of cecal acetic acid, propionic acid and total short chain fatty acids compared to T3 and T4 but T3 and T4 displayed higher concentrations of butyric acid, isobutyric acid, valeric acid and isovaleric acid compared to T1 and T2 (p<0.05). These results have been observed that broiler chickens exposed to extreme heat stress with feeding EHD, inverse lighting and cold water would improve blood lipid, and elevate the production of immunity substance, beneficial microorganisms, and short chain fatty acids. This provision would also reduce the blood sugar consumption rate as energy sources and these effects will improve the growth performance of the broilers exposed to extreme heat.