• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.285-290
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• 2018

Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

• Journal of Communications and Networks
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• v.14 no.5
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• pp.510-517
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• 2012

This paper analyzes the performance of voice-over-Internet protocol (VoIP) services in terms of the system throughput, the packet delay, and the signaling overhead in a mobile WiMAX system with a hybrid automatic repeat request (HARQ) mechanism. Furthermore, a queueing analytical model is developed with due consideration of adaptive modulation and coding, the signaling overhead, and the retransmissions of erroneous packets. The arrival process is modeled as the sum of the arrival rate at the initial transmission queue and the retransmission queue, respectively. The service rate is calculated by taking the HARQ retransmissions into consideration. This paper also evaluates the performance of VoIP services in a mobile WiMAX system with and without persistent allocation; persistent allocation is a technique used to reduce the signaling overhead for connections with a periodic traffic pattern and a relatively fixed payload. As shown in the simulation results, the HARQ mechanism increases the system throughput as well as the signaling overhead and the packet delay.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.6 no.1
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• pp.305-321
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• 2012

Since Internet Protocol (IP) is the most important protocol in Next Generation Networks (NGNs), 3rd Generation Partnership Project (3GPP) utilizes Session Initial Protocol (SIP) based on IP as the base protocol for negotiating sessions in IP Multimedia Subsystem (IMS). Different from traditional circuit-switched network, in IMS, the media traffic and signaling are delivered through IP transport. The media traffic may affect the signaling efficiency in core network, due to traffic collisions and best effort packets delivery. This paper proposes a novel path-migration mechanism for enhancing the traffic efficiency in integrated NGN-IMS. The simulation results show that the interference and traffic collision can be reduce by applying proposed path-migration mechanism and the signaling efficiency in core network can be improved with higher system capability and voice quality.

• ETRI Journal
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• v.35 no.1
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• pp.41-50
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• 2013

Network Mobility (NEMO) handles mobility of multiple nodes in an aggregate manner as a mobile network. The standard NEMO suffers from a number of limitations, such as inefficient routing and increased handoff latency. Most previous studies attempting to solve such problems have imposed an extra signaling load and/or modified the functionalities of the main entities. In this paper, we propose a more secure and lightweight route optimization (RO) mechanism based on exploiting the firewall in performing the RO services on behalf of the correspondent nodes (CNs). The proposed mechanism provides secure communications by making an authorized decision about the mobile router (MR) home of address, MR care of address, and the complete mobile network prefixes underneath the MR. In addition, it reduces the total signaling required for NEMO handoffs, especially when the number of mobile network nodes and/or CNs is increased. Moreover, our proposed mechanism can be easily deployed without modifying the mobility protocol stack of CNs. A thorough analytical model and network simulator (Ns-2) are used for evaluating the performance of the proposed mechanism compared with NEMO basic support protocol and state-of-the-art RO schemes. Numerical and simulation results demonstrate that our proposed mechanism outperforms other RO schemes in terms of handoff latency and total signaling load on wired and wireless links.

• Journal of Information Technology Services
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• v.8 no.1
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• pp.165-177
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• 2009

This paper reviews diverse IP mobility and fast handover mechanisms for seamless Internet services. Especially, fast handover mechanisms for the Proxy Mobile IPv6( PMIPv6) are categorized according to their approaches. Then, a new fast handover PMIPv6(FH-PMIPv6) mechanism is proposed using only L3 signaling message exchange. In the proposed FH-PMIPv6 mechanism, only local mobility anchor(LMA) exchanges L3 signaling messages with mobility access gateways(MAGs) for the fast handover operation. That is, inter-MAG signalling messages are not required for the fast handover operation. Therefore, unlike existing fast handover mechanisms, two relevant neighbouring MAGs need not set up the security association(SA) to protect fast handover related signaling messages and share SA related information. Moreover, the L3 triggering message is defined newly by standard ICMPv6 to trigger promptly the proposed mechanism. Analysis and comparison of the handover latency are performed for the proposed mechanism and existing mechanisms, which shows that the proposed FH-PMIPv6 mechanism has the favorable performance.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.33-33
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• 2019

The AKT signaling pathway is a highly regulated cell signaling system that forms a network with other cell signaling pathways. Hence, the AKT signaling pathway mediates several important cellular functions that include cell survival, proliferation, cell migration, and et cetera. Irregularities that led overactive AKT signaling have been linked to many diseases such as cancer and metabolic-associated diseases. Hence, modulating the overactive AKT signaling pathway via inhibitor is a tantalizing prospect for treatment of cancer and metabolic-associated diseases. Two inhibitors of the AKT signaling pathway will be presented in this symposium: 1) Bisleuconothine A (BisA), a bisindole alkaloid that inhibit autophagy and 2) Ceramicine B (CerB), a limonoid that inhibit adipogenesis. The first topic is on a bisindole alkaloid, BisA and its mechanism in inducing autophagosome formation in lung cancer cell line, A549.(1) Since most autophagy inducing agents generally induce apoptosis, we found that BisA does not induce apoptosis even in high dose. BisA up-regulation of LC3 lipidation is achieved through mTOR inactivation. The phosphorylation of PRAS40, a mTOR repressor was suppressed by BisA. This observation suggested that BisA inactivates mTOR via suppression of PRAS40 phosphorylation. Interestingly, the phosphorylation of AKT, an upstream regulator of PRAS40 phosphorylation was also down-regulated by BisA. These findings suggested that Bis-A induces autophagosomes formation by interfering with the AKT-mTOR signaling pathway. The second topic is on CerB and its mechanism in inhibiting adipogenesis in preadipocytes cell line, MC3T3-G2/PA6.(2,3) CerB inhibits the phosphorylation of protein kinase B (AKT) at the Thr308 position but not the Ser473. Consequently, the phosphorylation of FOXO3 which is located downstream of AKT is also inhibited. Considering that FOXO3 is an important regulator of PPARγ which is a key factor in adipogenesis, CerB may inhibit adipogenesis via the AKT-FOXO3 signaling pathway. Taken together, both BisA and CerB highlighted the potential of AKT signaling pathway modulation as an approach to induce autophagy and inhibit the formation of fat cells, respectively.

• Molecules and Cells
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• v.45 no.4
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• pp.169-176
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• 2022

A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.29-29
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• 2003

Compartmentation of intracellular signaling pathways serves as an important mechanism conferring the specificity of G protein-coupled receptor (GPCR) signaling. In the heart, stimulation of $\beta$$_2$-adrenoceptor ($\beta$$_2$-AR), a prototypical GPCR, activates a tightly localized protein kinase A (PKA) signaling, which regulates substrates at cell surface membranes, bypassing cytosolic target proteins (eg, phospholamban). Although a concurrent activation of $\beta$$_2$-AR-coupled $G_{i}$ proteins has been implicated in the functional compartmentation of PKA signaling, the exact mechanism underlying the restriction of the $\beta$$_2$-AR-PKA pathway remains unclear. In the present study, we demonstrate that phosphatidylinositol 3-kinase (PI3K) plays an essential role in confining the $\beta$$_2$-AR-PKA signaling. Inhibition of PI3K with LY294002 or wortmannin enables $\beta$$_2$-AR-PKA signaling to reach intracellular substrates, as manifested by a robust increase in phosphorylation of phospholamban, and markedly enhances the receptor-mediated positive contractile and relaxant responses in cardiac myocytes. These potentiating effects of PI3K inhibitors are not accompanied by an increase in $\beta$$_2$-AR-induced cAMP formation. Blocking $G_{i}$ or $G_{$\square$$\square$}$ signaling with pertussis toxin or $\beta$ARK-ct, a peptide inhibitor of $G_{$\square$$\square$}$, completely prevents the potentiating effects induced by PI3K inhibition, indicating that the pathway responsible for the functional compartmentation of $\beta$$_2$-AR-PKA siglaling sequentially involves $G_{i}$, $G_{$\square$$\square$}$, and PI3K. Thus, PI3K constitutes a key downstream event of $\beta$$_2$-AR- $G_{i}$ signaling, which confines and negates the concurrent $\beta$$_2$-AR/Gs-mediated PKA signaling.gnaling.

• Journal of KIISE:Information Networking
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• v.35 no.6
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• pp.538-548
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• 2008

In the Internet Engineering Task Force(IETF), Next Step in Signaling(NSIS) working group, proposed a mechanism to discover the Crossover Node(CRN), when the route is changed by Mobile Node(MN) handover. The CRN is divergence or convergence node on old and new path for reserving resources. Trough the CRN discovery mechanism, it possible to reduce a signaling delay and avoid the redundant reservation on the common path between old and new path. However, the QoS(Quality of Service) can be guaranteed continuously while the MN is performing handover, it is needed to pre-reserve the resource on the new path before completion of the handover. When the nodes on the new path try to make a pre-resource reservation before the handover, it is difficult to pre-reserve the resource with the existing CRN discovery mechanism. Therefore, we proposed a Passive CRN(PCRN) discovery scheme and pre-resource reservation mechanism. The PCRN which means an initial common point between the current reserved and the new paths, where the handover can take place.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.380-386
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• 2016

Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-${\kappa}B$-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ${\beta}$-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ${\beta}$-catenin protein but not mRNA. The inhibition of proteasome by MG132 and $GSK3{\beta}$ inhibition by SB216763 blocked silymarin-mediated downregulation of ${\beta}$-catenin. In addition, silymarin increased phosphorylation of ${\beta}$-catenin and a point mutation of S33Y attenuated silymarin-mediated ${\beta}$-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ${\beta}$-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.