• Title/Summary/Keyword: Pi-b

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Improvement of Leptin Resistance (렙틴 저항성의 개선)

  • Kim, Yong Woon
    • Journal of Yeungnam Medical Science
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    • v.30 no.1
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    • pp.4-9
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    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

Metformin Down-regulates Endometrial Carcinoma Cell Secretion of IGF-1 and Expression of IGF-1R

  • Zhang, Yu;Li, Meng-Xiong;Wang, Huan;Zeng, Zheng;Li, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.221-225
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    • 2015
  • As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

  • Pandurangan, Ashok Kumar;Esa, Norhaizan Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.551-560
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    • 2014
  • Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-${\kappa}B$, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, $Wnt/{\beta}$-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

A scalar MSDD with multiple antenna reception of Differential Space-Time π/2-Shifted BPSK Modulation

  • Kim Jae-Hyung;Hwang Seung-Wook;Kim Jung-Keun;Kim Yong-Jae
    • Journal of Navigation and Port Research
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    • v.30 no.2
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    • pp.167-172
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    • 2006
  • In this paper, the issue of blind detection of Alamouti-type differential space-time (ST) ${\pi}/2$-shifted BPSK modulation in static Rayleigh fading channels is considered. We introduce a novel transformation to the received signal from each receiver antenna such that this binary ST modulation, which has a second-order transmit-diversity, is equivalent to QPSK modulation with second-order receive-diversity. The pre-detection combining of the result of transformation allows us to apply a low complexity detection technique specifically designed for receive-diversity, namely, scalar multiple-symbol differential detection (MSDD). With receiver complexity proportional to the observation window length, our receiver can achieve the performance 1.5dB better than that of conventional differential detection ST and 0.5dB worse than that qf a coherent maximum ratio combining receiver (with differential decoding) approximately.

Synthesis and Properties of Oligomers Containing 3-Triethylsilyl-1-silacyclopent-3-ene and Borane Derivatives via Polyaddition Reaction

  • Lee, Jung-Hwan;Park, Young-Tae
    • Bulletin of the Korean Chemical Society
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    • v.25 no.6
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    • pp.889-894
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    • 2004
  • Polyaddition reactions of 1,1-diethynyl-3-triethylsilyl-1-silacyclopent-3-ene with several organoborane derivatives have afforded the oligomeric materials containing organosilacyclic group and organoboron moiety along the oligomer main chains. All of these materials are soluble in THF as well as chloroform, and their molecular weights are in the range of 1,990/1,190-21,950/7,050 ($M_w/M_n$) with the polydispersity indexes of 1.67-3.43. The prepared oligomers are characterized by several spectroscopic methods such as $^1H,\;^{13}C, \;^{29}Si,\;^{11}B$ NMR and FTIR spectra along with elemental analysis. FTIR spectra of all the oligomers show that the new strong C=C stretching frequencies appear at 1599-1712 $cm^{-1}$, in particular. The UV-vis absorption spectra of the materials in THF solution exhibit the strong absorption bands at the ${\lambda}_{max}$ of 268-275 nm. The oligomeric materials show that the strong excitation peaks appear at the ${\lambda}_{max}$ of 255-279 nm and the strong fluorescence emission bands at the ${\lambda}_{max}$ of 306-370 nm. All the spectroscopic data suggest that the obtained materials contain both the organoboron ${\pi}$-conjugation moiety of C=C-B-C=C and the organosilacyclic group of 3-triethylsilyl-1-silacyclopent-3-ene along the oligomer main chains. The oligomers are thermally stable up to 162-200 $^{\circ}C$ under nitrogen.

Numerical Simulation of Self-excited Combustion Oscillation in a Dump Combustor with Bluff-body (둔체를 갖는 연소기에서 자려 연소 진동에 관한 수치해석)

  • Kim, Hyeon-Jun;Hong, Jung-Goo;Kim, Dae-Hee;Shin, Hyun-Dong
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.32 no.9
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    • pp.659-668
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    • 2008
  • Combustion instability has been considered as very important issue for developing gas turbine and rocket engine. There is a need for fundamental understanding of combustion instability. In this study, combustion instability was numerically and experimentally investigated in a dump combustor with bluff body. The fuel and air mixture had overall equivalence ratio of 0.9 and was injected toward dump combustor. The pressure oscillation with approximately 256Hz was experimentally obtained. For numerical simulation, the standard k-$\varepsilon$ model was used for turbulence and the hybrid combustion model (eddy dissipation model and kinetically controlled model) was applied. After calculating steady solution, unsteady calculation was performed with forcing small perturbation on initial that solution. Pressure amplitude and frequency measured by pressure sensor is nearly the same as those predicted by numerical simulation. Furthermore, it is clear that a combustion instability involving vortex shedding is affected by acoustic-vortex-combustion interaction. The phase difference between the pressure and velocity is $\pi$/2, and that between the pressure and heat release rate is in excitation range described by Rayleigh, which is obvious that combustion instability for the bluff body combustor meets thermoacoustic instability criterion.

Attractive Sulfur...π Interaction between Fluorinated Dimethyl Sulfur (FDMS) and Benzene

  • Yan, Shihai;Lee, Sang-Joo;Kang, Sun-Woo;Choi, Kwang-Hyun;Rhee, Soon-Ki;Lee, Jin-Yong
    • Bulletin of the Korean Chemical Society
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    • v.28 no.6
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    • pp.959-964
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    • 2007
  • The benzene complexes with dimethyl sulfur (DMS) and fluorinated DMS (FDMS) have been investigated using ab initio calculations. The natural bond orbital (NBO) charge population on S atom varies remarkably for different conformations of DMS and FDMS, which determines the possible binding modes for their benzene complexes. The electronegative substituent at the methyl group of DMS causes a significant change in the molecular electrostatic potential around the sulfur atom and changes the interaction mode with aromatic ring. It was found that the sulfur…π interaction mode does not occur in the DMS-benzene complex, while it does in the FDMS-benzene complex. Both B3LYP and MP2 methods provide reliable structures, while the interaction energy obtained by B3LYP is unreliable.

High Frequency Properties of Patterned Fe-Al-O Thin Films

  • N.D. Ha;Park, B.C.;B.K. Min;Kim, C.G.;Kim, C.O.
    • Proceedings of the Korean Magnestics Society Conference
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    • 2003.06a
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    • pp.194-194
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    • 2003
  • As a result of the recent miniaturization an enhancement in the performance of thin film inductors and thin film transformers, there are increased demands for the thin films with high magnetic permeability in the high frequency range, high saturation magnetization, in high electrical resistivity, and low coercive force. In order to improve high frequency properties, we will investigate anisotropy field by shape and size of pattern. The Fe-Al-O thin films of 16mm and 1 $\mu\textrm{m}$ thickness were deposited on Si wafer, using RF magnetron reactive sputtering technique with the mixture of argon and oxygen gases. The fabricating conditions are obtained in the working partial pressure of 2mTorr, O$_2$ partial pressure of 5%, input power of 400W, and Al pellets on an Fe disk with purity of 99,9%. Magnetic properties of the continuous films as followed: the 4$\pi$M$\_$s/ of 19.4kG, H$\_$c/ of 0.6Oe, H$\_$k/ of 6.0Oe and effective permeability of 2500 up to 100㎒ were obtained. In this work, we expect to enhance effect of magnetic anisotropy on patterned of Fe-Al-O thin films.

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DH332, a Synthetic β-Carboline Alkaloid, Inhibits B Cell Lymphoma Growth by Activation of the Caspase Family

  • Gao, Pan;Tao, Ning;Ma, Qin;Fan, Wen-Xi;Ni, Chen;Wang, Hui;Qin, Zhi-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.9
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    • pp.3901-3906
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    • 2014
  • Aim: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new ${\beta}$-carboline alkaloids derivatives in vitro and in vivo. Materials and Methods: The effects of DH332 on human (RAMOS RA.1) and mouse (J558) B lymphoma cell lines were detected using a CCK-8 kit (Cell Counting Kit-8), and apoptosis was detected by flow cytometry with PI/annexinV staining. Western blotting was used to detected caspase-3 and caspase-8. Neurotoxic and anti-tumor effects were evaluated in animal experiments. Results: DH332 exerts a lower neurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphoma cell lines with low $IC_{50s}$. Moreover, DH332 could inhibit the proliferation and induce the apoptosis of RAMOS RA.1 and J558 cell lines in a dose-dependent manner. Our results suggest that DH332 triggers apoptosis by mainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed that DH332 significantly inhibited growth of J558 xenograft tumors. Conclusions: DH332 exerts effective antitumor activity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.

Sensitization of Cervical Carcinoma Cells to Paclitaxel by an IPP5 Active Mutant

  • Zeng, Qi-Yan;Huang, Yu;Zeng, Lin-Jie;Huang, Min;Huang, Yong-Qi;Zhu, Qi-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8337-8343
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    • 2014
  • Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of $8-60hIPP5^m$ with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that $8-60hIPP5^m$ enhances paclitaxel-induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to downregulation of NF-${\kappa}B$ activation and serine/threonine kinase Akt pathways. We noted that $8-60hIPP5^m$ downregulated the paclitaxel-induced NF-${\kappa}B$ activation, $I{\kappa}B{\alpha}$ degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-${\kappa}B$. Together, our observations indicate that paclitaxel in combination with $8-60hIPP5^m$ may provide a therapeutic advantage for the treatment of human cervical carcinoma.