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Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

  • Pandurangan, Ashok Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2201-2205
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    • 2013
  • Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature ${\beta}$-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

Mammalian Target of Rapamycin Signaling Pathways and Depression (Mammalian Target of Rapamycin 신호전달체계와 우울증)

  • Lee, Jung Goo;Seo, Mi Kyong;Park, Sung Woo;Kim, Young Hoon
    • Korean Journal of Biological Psychiatry
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    • v.23 no.1
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    • pp.18-23
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    • 2016
  • Depression is a complicated psychiatric illness with severe consequences. Despite recent advanced achievements of molecular neurobiology, pathophysiology of depression has not been well elucidated. Among new findings of pathophysiology of depression, the possible fast antidepressant effect by N-methyl-D-asparate receptor antagonist, such as ketamine, is regarded as a promising treatment target of depression. Ketamine stimulates the mammalian target of rapamycin (mTOR) signaling pathway and activation of mTOR signaling pathway may be a key mechanism of the antidepressant effect of ketamine. Thus, this review describes the role of mTOR signaling in the pathophysiology of depression and developing a new treatment target of depression.

Dielectric properties of $BiNbO_4$ dielectric ceramics for multilayer microwave device (적층형 마이크로파 소자용 $BiNbO_4$ 유전체 세라믹스의 유전특성)

  • 박정흠;장낙원;윤광희;최형욱;박창엽
    • Electrical & Electronic Materials
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    • v.9 no.9
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    • pp.900-905
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    • 1996
  • We have investigated dielectric properties of low fired ceramics BiNbO$_{4}$ containing 0.05[wt%] V$_{2}$O$_{5}$ and x[wt%l Cr$_{2}$O$_{3}$ (x=0, 0.2, 0.4, 0.8, 1.2). By substituting Cr for Bi, dielectric constant .epsilon.$_{r}$ and quality factor Q.f increased and temperature coefficient of resonant frecquency .tau.$_{f}$ changed to positive value. In the composition of BiNbO$_{4}$+0.05 [Wt%] V$_{2}$O$_{5}$+0.8[wt%]Cr$_{2}$O$_{3}$ sintered at 960[.deg. C], we could obtain microwave dielectric properties of .epsilon.$_{r}$=49, Q.f.simeq.3000[GHz](at 4.8[GHz]), .tau.$_{f}$.simeq.0[ppm/.deg. C]. As the above ceramics can be sintered near 960[.deg. C], it is applicable to multilayer microwave device with Ag conductor.tor.tor.tor.

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Analysis of the Axial Thrust Force of a Centrifugal Impeller with a Thrust Labyrinth Seal at its Backside (스러스트 래버린스 실을 배면에 갖는 원심형 임펠러의 축력 해석)

  • Park, Jun Hyuk;Kim, Tae Ho
    • Tribology and Lubricants
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    • v.37 no.1
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    • pp.31-40
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    • 2021
  • This study describes the effects of a thrust labyrinth seal applied to the backside of a centrifugal impeller on the axial thrust force for high speed turbomachinery. The bulk flow model using Neumann's equation calculates the seal cavity pressures and leakage flow rate of the thrust labyrinth seal based on three configurations: teeth-on-rotor (TOR), teeth-on-stator (TOS), and interlocking labyrinth seal (ILS). Prediction results show that the ILS is superior to the TOR and TOS in terms of leakage flow rate. A mathematical model of a centrifugal impeller with a thrust labyrinth seal on its backside calculates the force components corresponding to the impeller inlet, shroud, impeller backside outer, backside seal, and backside inner pressures. A summation of the force components renders the total axial thrust force acting on the centrifugal impeller. The Newton-Raphson numerical scheme iteratively calculates the pressures and leakage flow rate through the impeller wall gap. The prediction results reveal that the leakage flow rate and total axial thrust force increase with rotor speed, and the ILS significantly decreases the leakage flow rate, whereas it slightly increases the axial thrust force when compared to TOR and TOS. Increasing the seal clearance causes an increase in the leakage flow rate and a slight decrease in the axial thrust force with the ILS.

Enhancement of body performance and growth performance of juvenile mahseer (Tor soro) using differently colored containers

  • Teuku Fadlon Haser;Eddy Supriyono;Kukuh Nirmala;Widanarni;Tri Heru Prihadi;Tatag Budiardi;Reza Syamsudin;Muh Saleh Nurdin
    • Fisheries and Aquatic Sciences
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    • v.27 no.5
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    • pp.283-293
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    • 2024
  • Mahseer (Tor soro) growth performance tends to be slow, necessitating further development and intensification of cultivation. One way to develop aquaculture intensification is to manipulate cultivation containers to create optimal environmental conditions for the mahseer to grow. This study aimed to examine the body performance and growth performance of mahseer reared in different colored containers. Experimental research with completely randomized design was employed, with four colored container treatments namely treatment A (transparent), B (green), C (blue), and D (black), with four replications in each treatment. Findings indicate that different rearing media colors had significant effect on absolute length (4.68 ± 0.24 cm), absolute weight (1.58 ± 0.35 g), specific growth rate (2.17 ± 0.38%), feed conversion ratio (2.87 ± 0.04), survival rate (100 ± 0.00%), gross energy (3,816 ± 65.05 cal/g), and body proximate. Physiologically, mahseer fish bred using blue and black containers tend to be more resistant to stress.The best body performance and growth performance were observed in the blue and black colored containers.

Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation

  • Eun-Hyeon Shim;Sae-Hae Kim;Doo-Jin Kim;Yong-Suk Jang
    • IMMUNE NETWORK
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    • v.24 no.4
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    • pp.24.1-24.8
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    • 2024
  • Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Melittin inhibits cell migration and invasion via blocking of the epithelial-mesenchymal transition (EMT) in lung cancer cells (EMT 억제를 통한 멜리틴의 폐암세포 이동 및 침투 억제 효과)

  • Cho, Hyun-Ji;Jeong, Yun-Jeong;Kim, Mun-Hyeon;Chung, Il-Kyung;Kang, Dong Wook;Chang, Young-Chae
    • Korean Journal of Food Science and Technology
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    • v.50 no.1
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    • pp.105-110
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    • 2018
  • Melittin is the main component of apitoxin (bee venom) that has been reported to have anti-inflammatory and anti-cancer effects. Herein, we demonstrated that inhibition of epithelial-mesenchymal transition (EMT) by melittin causes suppression of cancer cell migration and invasion. Melittin significantly suppressed the epidermal growth factor (EGF)-induced cell migration and invasion in lung cancer cells. Moreover, melittin up-regulated the expression of epithelial marker protein, E-cadherin, and down-regulated the expression of EMT related proteins, vimentin and fibronectin. Mechanistic studies revealed that melittin markedly suppressed the expression of EMT mediated transcription factors, ZEB2, Slug, and Snail. The EGF-induced phosphorylation of AKT, mTOR, P70S6K, and 4EBP1 was also inhibited by melittin, but not that of ERK and JNK. Therefore, the inhibitory effect of melittin on migration and invasion of lung cancer cells may be associated with the inhibition of EMT via blocking of the AKT-mTOR-P70S6K-4EBP1 pathway.

Involvement of Multiple Signaling Molecules in Peptidoglycan-induced Expression of Interleukin-1α in THP-1 Monocytes/Macrophages (THP-1 단핵구의 펩티도글리칸 유래 인터루킨-1 알파 발현에서 TLR2, PI3K/Akt/mTOR, MAPKs의 역할)

  • Heo, Weon;Son, Yonghae;Cho, Hyok-rae;Kim, Koanhoi
    • Journal of Life Science
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    • v.32 no.6
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    • pp.421-429
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    • 2022
  • The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.