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Bi-flavonoids are Superior to Mono-flavonoid in Inhibiting Amyloid-${\beta}$ Toxicity and Fibrillogenesis through Accumulating Nontoxic Oligomer-like Structures

  • Merlin Jayalal, L.P.
    • Journal of Integrative Natural Science
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    • v.5 no.2
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    • pp.107-119
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    • 2012
  • Polymerization of monomeric amyloid-${\beta}$ peptides ($A{\beta}$) into soluble oligomers and insoluble fibrils is one of the major pathways triggering the pathogenesis of Alzheimer's disease (AD). Using small molecules to prevent the polymerization of $A{\beta}$ peptides can, therefore, be an effective therapeutic strategy for AD. In this study, we investigated the effects of mono- and bi-flavonoids on $A{\beta}42$ toxicity and fibrillogenesis and found that the bi-flavonoid, taiwaniaflavone (TF) effectively and specifically inhibits $A{\beta}$ toxicity and fibrillogenesis. Compared to TF, the mono-flavonoid apigenin (AP) is less effective and less specific. Our data showed that differential effects of the mono- and bi-flavonoids on $A{\beta}$ fibrillogenesis correlate with their varying cytoprotective efficacies. We also found that other bi-flavonoids, namely 2',8"-biapigenin, amentoflavone, and sumaflavone, can also effectively inhibit $A{\beta}$ toxicity and fibrillogenesis, implying that the participation of two mono-flavonoids in a single bi-flavonoid molecule enhanced their activity. Bi-flavonoids, while strongly inhibited $A{\beta}$ fibrillogenesis, accumulated nontoxic $A{\beta}$ oligomeric structures, suggesting that these are off-pathway-oligomers. Moreover, TF abrogated the toxicity of preformed $A{\beta}$ oligomers and fibrils, indicating that TF and other bi-flavonoids may also reduce the toxicity of toxic $A{\beta}$ species. Altogether, our data clearly show that bi-flavonoids, possibly due to the possession of two $A{\beta}$ binders separated by an appropriate size linker, are likely to be promising therapeutics to suppress $A{\beta}$ toxicity.

Beta-Catenin Downregulation Contributes to Epidermal Growth Factor-induced Migration and Invasion of MDAMB231 Cells

  • Kwon, Arang;Park, Hyun-Jung;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.43 no.3
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    • pp.161-169
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    • 2018
  • We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.

Kinetics and Mechanism of the Hydrolysis of ${\alpha}$-Cyano-${\beta}$-piperonylacrylic Acid (${\alpha}$-Cyano-${\beta}$-Piperonylacrylic Acid의 가수분해 메카니즘과 그의 반응속도론적 연구)

  • Tae Rin Kim;Kwang Il Lee
    • Journal of the Korean Chemical Society
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    • v.17 no.4
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    • pp.269-274
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    • 1973
  • The rate constants of the hydrolysis of ${\alpha}$-Cyano-${\beta}$-piperonylacrylic acid were determined by Ultraviolet spectrophotometry at various pH and a rate equation which can be applied over wide pH range was obtained. The reaction mechanism of hydrolysis of ${\alpha}$-Cyano-${\beta}$-piperonylic acid and especially the catalytic contribution of hydroxide ion which not studied carefully before in acidic media, can be fully explained by the rate equation obtained. The rate equation reveals that; below pH 4.0, the reaction is initiated by the addition of water molecule to ${\alpha}$-Cyano-${\beta}$-piperonyl acrylic acid. At pH $5.0{\sim}7.5$, ${\alpha}$-Cyano-${\beta}$-piperonylacrylic acid compete with ${\alpha}$-Cyano-${\beta}$-piperonyl acrylate ion in adding of water. At pH 8.0, water is the only nucleophile for ${\alpha}$-Cyano-${\beta}$-piperonylacrylate ion, however, above pH 12.0, hydroxide ion is an addendum and the accepter is ${\alpha}$-Cyano-${\beta}$-piperonylacrylate ion.

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Molecular Mechanisms through Which Peptidoglycan Induces IL-1β Expression in Monocytic Cells (펩티도글라이칸에 의한 인터루킨-1 베타 발현 기전 연구)

  • Seo, Hyun-Cheol;Kim, Sun-Mi;Lee, Sae-A;Rhim, Byung-Yong;Kim, Koanhoi
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1637-1643
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    • 2012
  • This study investigated the effects of PG on IL-$1{\beta}$ expression and determined cellular factors involved in PG-mediated IL-$1{\beta}$ up-regulation in mononuclear cells in order to understand the molecular mechanisms underlying inflammatory responses associated with bacterial pathogen-associated molecular patterns in the diseased artery. Exposure of human monocytic leukemia THP-1 cells to PG resulted in enhanced secretion of IL-$1{\beta}$ and also profound induction of the IL-$1{\beta}$ gene transcript. These effects were abrogated by OxPAPC, an inhibitor of TLR-2/4. Pharmacological inhibitors such as U0126, SP6001250, Akti IV, rapamycin, and DPI also significantly attenuated PG-mediated IL-$1{\beta}$ up-regulation. However, polymyxin B did not influence the IL-$1{\beta}$ expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-$1{\beta}$ via TLR-2, Akt, mTOR, MAPKs, and ROS.

The Effect of Hot Taste Preference on Dietary Intake and Level of Serum $\beta$-Carotene Concentration in Korean Female College Students (매운 맛 선호도가 한국 여대생의 $\beta$-Carotene 섭취와 혈청수준에 미치는 영향)

  • 백희영;이심열
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.4
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    • pp.530-536
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    • 1995
  • A study was performed to assess dietary intake and serum levels of $\beta$-carotene and the influence of preference for hot taste on $\beta$-carotene intake in Korean female college students. Daily intake of $\beta$-carotene was estimated with a questionnaire composed of food item of high $\beta$-carotene contents and the average daily intake level was 4089$\pm$2400$\mu\textrm{g}$. The major sources of $\beta$-carotene included carrot, pumpkin, spinach, tomatoes and red pepper powder. 14$\pm$10% of total dietary $\beta$-carotene intake was from foods containing red pepper powder. The average amount of red pepper powder added to bean sprout soupr were 0.32$\pm$0.34g. Subjects preferring hot taste added significantly larger amount of red pepper powder(p<0.05) than those not preferring hot taste. Subjects of the lowest quartile of $\beta$-carotene intake level showed the lowest precentage of subjects preferring hot taste. The average serum $\beta$-carotene concentration was 36.5$\mu\textrm{g}$/dl and large variation in the amount among the subject has been observed. The level of dietary $\beta$-carotene intake and serum $\beta$-carotene concentration of Korean female college students were not significantly correlated but both were higher than levels in reports from western countries. These results indicate that $\beta$-carotene intake levels of the subjects are adequate and the preference for hot taste affects $\beta$-carotene intake significantly.

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The Effect of TGF-{\beta}_1 on Cellular Activity of Periodontal Ligament Cells activated by PDGF-BB (PDGF-BB에 의한 치주인대세포활성에 대한 TGF-{\beta}의 효과)

  • Baek, Sang-Churl;Park, Jin-Woo;Suh, Jo-Young
    • Journal of Periodontal and Implant Science
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    • v.32 no.3
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    • pp.457-473
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    • 2002
  • The purposes of this study is to evaluate the combination effects of TGF-${\beta}_1$ and PDGF-BB on the periodontal ligament cells to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM/100% FBS at the $37^{\circ}C$, 5% $CO_2$ incubator. Authors measured the DNA synthesis, total protein, collagen and noncollagenous protein synthesis according to the concentration of TGF-${\beta}_1$,(1,5ng/ml) and PDGF-BB (1,10 ng/ml) in combination. To explore further this delayed effect of TGF-${\beta}_1$, we preincubated human periodontal ligament cells with TGF-${\beta}_1$ for 4 or 24 hours before PDGF-BB stimulation. The results were as follows: The DNA synthetic activity was increased dose dependently by TGF-${\beta}_1$, PDGF-BB. The combination of TGF-${\beta}_1$ and PDGF-BB consistently enhanced the DNA synthetic activity to PDGF-BB alone. The ability of TGF-${\beta}_1$ to enhance DNA synthetic activity in PDGF-BB treated periodontal ligament cells was dose dependent. The maximum mitogenic effect was at the 5ng/ml of TGF-${\beta}_1$ and l0ng/ml of PDGF-BB. Preincubation of cell with TGF-${\beta}_1$ resulted in significantly greater response to PDGF-BB at all TGF-${\beta}_1$ concentration studied, and may be useful for clinical application in periodontal regenerative procedures. The total protein, collagen and noncollagen synthesis was increased dose pendently by TGF-${\beta}_1$, PDGF-BB. The % of collagen was slightly decreased according to the concentration of TGF-${\beta}_1$, PDGF-BB. The effect of TGF-${\beta}_1$, PDGF-BB were not specific for collagen synthesis since it also increased noncollagenous protein synthesis. This study demonstrates that PDGF-BB is major mitogens for human periodontal ligament cells in vitro, and supports a role for TGF-${\beta}_1$ as a regulation of the mitogenic and total protein formation to PDGF-BB in these cells.

ON GENERALIZED (α, β)-DERIVATIONS IN BCI-ALGEBRAS

  • Al-Roqi, Abdullah M.
    • Journal of applied mathematics & informatics
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    • v.32 no.1_2
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    • pp.27-38
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    • 2014
  • The notion of generalized (regular) (${\alpha},\;{\beta}$)-derivations of a BCI-algebra is introduced, some useful examples are discussed, and related properties are investigated. The condition for a generalized (${\alpha},\;{\beta}$)-derivation to be regular is provided. The concepts of a generalized F-invariant (${\alpha},\;{\beta}$)-derivation and ${\alpha}$-ideal are introduced, and their relations are discussed. Moreover, some results on regular generalized (${\alpha},\;{\beta}$)-derivations are proved.

ON TWO-DIMENSIONAL LANDSBERG SPACE WITH A SPECIAL (${\alpha},\;{\beta}$)-METRIC

  • Lee, Il-Yong
    • The Pure and Applied Mathematics
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    • v.10 no.4
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    • pp.279-288
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    • 2003
  • In the present paper, we treat a Finsler space with a special (${\alpha},\;{\beta}$)-metric $L({\alpha},\;{\beta})\;\;C_1{\alpha}+C_2{\beta}+{\alpha}^2/{\beta}$ satisfying some conditions. We find a condition that a Finsler space with a special (${\alpha},\;{\beta}$)-metric be a Berwald space. Then it is shown that if a two-dimensional Finsler space with a special (${\alpha},\;{\beta}$)-metric is a Landsberg space, then it is a Berwald space.

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ON THE BERWALD CONNECTION OF A FINSLER SPACE WITH A SPECIAL $({\alpha},{\beta})$-METRIC

  • Park, Hong-Suh;Park, Ha-Yong;Kim, Byung-Doo
    • Communications of the Korean Mathematical Society
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    • v.12 no.2
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    • pp.355-364
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    • 1997
  • In a Finsler space, we introduce a special $(\alpha,\beta)$-metric L satisfying $L^2(\alpha,\beta) = c_1\alpha^2 + 2c_2\alpha\beta + c_3\beta^2$, which $c_i$ are constants. We investigate the Berwald connection in a Finsler space with this special $\alpha,\beta)$-metric.

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NILPOTENCY CLASSES OF RIGHT NILPOTENT CONGRUENCES

  • Jeong, Joo-Hee
    • Bulletin of the Korean Mathematical Society
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    • v.36 no.1
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    • pp.139-146
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    • 1999
  • It is known that a right nilpotent congruence $\beta$ on a finite algebra A is also left nilpotent [3]. The question on whether the left nilpotency class of $\beta$ in less than or equal to the right nilpotency class of $\beta$is still open. In this paper we find an upper limit for the left nilpotency class of $\beta$. In addition, under the assumption that 1 $\in$ typ{A}, we show that $(\beta]^k=[\beta)^k$ for all k$\geq$1. Thus the left and right nilpotency classes of $\beta$ are the same in this case.

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