• Title/Summary/Keyword: Signaling network

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CD11b Deficiency Exacerbates Methicillin-Resistant Staphylococcus aureus-Induced Sepsis by Upregulating Inflammatory Responses of Macrophages

  • Hyunsub Sim;Daecheol Jeong;Hye-In Kim;Seongwon Pak;Bikash Thapa;Hyung-Joo Kwon;Keunwook Lee
    • IMMUNE NETWORK
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    • v.21 no.2
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    • pp.13.1-13.19
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    • 2021
  • Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

Pathophysiological Role of TLR4 in Chronic Relapsing Itch Induced by Subcutaneous Capsaicin Injection in Neonatal Rats

  • Hee Joo Kim;Eun-Hui Lee;Yoon Hee Lim;Dongil Jeong;Heung Sik Na;YunJae Jung
    • IMMUNE NETWORK
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    • v.22 no.2
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    • pp.20.1-20.9
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    • 2022
  • Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.

Systems Pharmacological Analysis of Dichroae Radix in Anti-Tumor Metastasis Activity (시스템 약리학적 분석에 의한 상산의 암전이 억제 효과)

  • Jee Ye Lee;Ah Yeon Shin;Hak Koon Kim;Won Gun An
    • Herbal Formula Science
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    • v.31 no.4
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    • pp.295-313
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    • 2023
  • Objectives : While treatments for cancer are advancing, the development of effective treatments for cancer metastasis, the main cause of cancer patient death, remains insufficient. Recent studies on Dichroae Radix have revealed that its active ingredients have the potential to inhibit cancer metastasis. This study aimed to investigate the cancer metastasis inhibitory effect of Dichroae Radix using network pharmacological analysis. Methods : The active compounds of Dichroae Radix have been identified using Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The UniProt database was used to collect each of information of all target proteins associated with the active compounds. To find the bio-metabolic processes associated with each target, the DAVID6.8 Gene Functional classifier tool was used. Compound-Target and Target-Pathway networks were analyzed via Cytoscape 3.40. Results : In total, 25 active compounds and their 62 non-redundant targets were selected through the TCMSP database and analysis platform. The target genes underwent gene ontology and pathway enrichment analysis. The gene list applied to the gene ontology analysis revealed associations with various biological processes, including signal transduction, chemical synaptic transmission, G-protein-coupled receptor signaling pathways, response to xenobiotic stimulus, and response to drugs, among others. A total of eleven genes, including HSP90AB1, CALM1, F2, AR, PAKACA, PTGS2, NOS2, RXRA, ESR1, ESR2, and NCOA1, were found to be associated with biological pathways related to cancer metastasis. Furthermore, nineteen of the active compounds from Dichroae Radix were confirmed to interact with these genes. Conclusions : The results provide valuable insights into the mechanism of action and molecular targets of Dichroae Radix. Notably, Berberine, the main active ingredient of Dichroae Radix, plays a significant role in degrading AR proteins in advanced prostate cancer. Further studies and validations can provide crucial data to advance cancer metastasis prevention and treatment strategies.

Study of the Operation of Actuated signal control Based on Vehicle Queue Length estimated by Deep Learning (딥러닝으로 추정한 차량대기길이 기반의 감응신호 연구)

  • Lee, Yong-Ju;Sim, Min-Gyeong;Kim, Yong-Man;Lee, Sang-Su;Lee, Cheol-Gi
    • The Journal of The Korea Institute of Intelligent Transport Systems
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    • v.17 no.4
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    • pp.54-62
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    • 2018
  • As a part of realization of artificial intelligence signal(AI Signal), this study proposed an actuated signal algorithm based on vehicle queue length that estimates in real time by deep learning. In order to implement the algorithm, we built an API(COM Interface) to control the micro traffic simulator Vissim in the tensorflow that implements the deep learning model. In Vissim, when the link travel time and the traffic volume collected by signal cycle are transferred to the tensorflow, the vehicle queue length is estimated by the deep learning model. The signal time is calculated based on the vehicle queue length, and the simulation is performed by adjusting the signaling inside Vissim. The algorithm developed in this study is analyzed that the vehicle delay is reduced by about 5% compared to the current TOD mode. It is applied to only one intersection in the network and its effect is limited. Future study is proposed to expand the space such as corridor control or network control using this algorithm.

P2P-based Mobility Management Protocol for Global Seamless Handover in Heterogeneous Wireless Network (이기종망에서 글로벌 끊김 없는 핸드오버를 위한 P2P 기반 이동성 관리 프로토콜)

  • Chun, Seung-Man;Lee, Seung-Mu;Park, Jong-Tae
    • Journal of the Institute of Electronics and Information Engineers
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    • v.49 no.12
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    • pp.73-80
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    • 2012
  • In this article, we propose a P2P-based mobility management protocol for global seamless handover in heterogeneous wireless networks. Unlike previous mobility management protocols such as IETF MIPv4/6 and its variants, the proposed protocol can support global seamless handover without changing the existing network infrastructure. The idea of the proposed protocol is that the location management function for mobility management is separately supported from packet forwarding function, and bidirectional IP tunnels for packet transmission are dynamically constructed between two end-to-end mobile hosts. In addition, early handover techniques have been developed to avoid large handover delays and packet losses using the IEEE 802.21 Media Independent Handover functions. The architecture and signaling procedure of the proposed protocol have been designed in detail, and the mathematical analysis and simulation have been done for performance evaluation. The performance results show that the proposed protocol outperforms the existing MIPv6 and HMIPv6 in terms of handover latency and packet loss.

A Scalable Dynamic QoS Support Protocol (확장성 있는 동적 QoS 지원 프로토콜)

  • 문새롬;이미정
    • Journal of KIISE:Information Networking
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    • v.29 no.6
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    • pp.722-737
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    • 2002
  • As the number of multimedia applications increases, various protocols and architectures have been proposed to provide QoS(Quality of Service) guarantees in the Internet. Most of these techniques, though, bear inherent contradiction between the scalability and the capability of providing QoS guarantees. In this paper, we propose a protocol, named DQSP(Dynamic QoS Support Protocol), which provides the dynamic resource allocation and admission control for QoS guarantees in a scalable way. In DQSP, the core routers only maintain the per source-edge router resource allocation state information. Each of the source-edge routers maintains the usage information for the resources allocated to itself on each of the network links. Based on this information, the source edge routers perform admission control for the incoming flows. For the resource reservation and admission control, DQSP does not incur per flow signaling at the core network, and the amount of state information at the core routers depends on the scale of the topology instead of the number of user flows. Simulation results show that DQSP achieves efficient resource utilization without incurring the number of user flow related scalability problems as with IntServ, which is one of the representative architectures providing end-to-end QoS guarantees.

Application model research on visualizing anti-inflammation effects by using the virtual cell (가상세포를 활용한 항염증 효능 응용모델 연구)

  • Kim, Chul;Yea, Sang-Jun;Kim, Jin-Hyun;Kim, Sang-Kyun;Jang, Hyun-Chul;Kim, An-Na;Nam, Ky-Youb;Song, Mi-Young
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.227-239
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    • 2010
  • Objective : The purpose of this study was to develop the simulator which can analyze the anti-inflammatory effects of herbs based on e-cell, or the virtual cell. Method : We have ensured the medical herbs and its active compounds by investigating the oriental medicine records and NBCI(Biomedicine database). Also we have developed the web-based search system for confirming database related to anti-inflammation. We have researched the cell signal pathway related with inflammatory response control and established the mathematical model of herb interaction on selected signal pathway in e-cell. Finally we have developed the prototype which can confirm the result of this model visibly. Results : We constructed the database of 62 cases of anti-inflammatory active compounds in 61 cases of medical herbs which have been known anti-inflammation effects in the paper, 16 cases of inflammatory factors, 10 cases of signal pathways related with inflammatory response and 6,834 cases of URL(Uniform Resource Locator) of referenced papers. And we embodied the web-based research system, which can research this database. User can search basic and detailed information of medical plants related with anti-inflammatory by using information system. And user can acquire information on an active compounds, a signal pathway and a link URL of related paper. Among investigated ten pathways, we selected NF-${\kappa}B$, which plays important role in activation of immune system, and we searched the mechanisms of actions of proteins which could be components of this pathway. We reduced total network into IKK-$I{\kappa}B$ - NF-${\kappa}B$, and completed mathematic modeling by using ordinary differential equations and response variables of $I{\kappa}B-NF-{\kappa}B$ signaling model network which is suggested by Baltimore Group. We designed OED(Ordinary Differential Equation) for response of IKK, $I{\kappa}B$, $NF-{\kappa}B$ in e-cell's cytoplasm and nucleus, and measured whether an active compound of medicinal plants which is inputted by an user would have a anti-inflammation effects in obedience to change in concentration over time. The proposed model was verified by using experimental results of the papers which are listed on NCBI.

Carbon Metabolism and Its Global Regulation in Corynebacterium glutamicum (Corynebacterium glutamicum의 탄소대사 및 총체적 탄소대사 조절)

  • Lee, Jung-Kee
    • Microbiology and Biotechnology Letters
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    • v.38 no.4
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    • pp.349-361
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    • 2010
  • In this review, the current knowledge of the carbon metabolism and global carbon regulation in Corynebacterium glutamicum are summarized. C. gluamicum has phosphotransferase system (PTS) for the utilization of sucrose, glucose, and fructose. C. glutamicum does not show any preference for glucose when various sugars or organic acids are present with glucose, and thus cometabolizes glucose with other sugars or organic acids. The molecular mechanism of global carbon regulation such as carbon catabolite repression (CCR) in C. glutamicum is quite different to that in Gram-negative or low-GC Gram-positive bacteria. GlxR (glyoxylate bypass regulator) in C. glutamicum is the cyclic AMP receptor protein (CRP) homologue of E. coli. GlxR has been reported to regulate genes involved in not only glyoxylate bypass, but also central carbon metabolism and CCR including glycolysis, gluconeogenesis, and tricarboxylic acid (TCA) cycle. Therefore, GlxR has been suggested as a global transcriptional regulator for the regulation of diverse physiological processes as well as carbon metabolism. Adenylate cyclase of C. glutamicum is a membrane protein belonging to class III adenylate cyclases, thus it could possibly be a sensor for some external signal, thereby modulating cAMP level in response to environmental stimuli. In addition to GlxR, three additional transcriptional regulators like RamB, RamA, and SugR are also involved in regulating the expression of many genes of carbon metabolism. Finally, recent approaches for constructing new pathways for the utilization of new carbon sources, and strategies for enhancing amino acid production through genetic modification of carbon metabolism or regulatory network are described.

Security Analysis and Implementation of Fast Inter-LMA domain Handover Scheme in Proxy Mobile IPv6 Networks (프록시 모바일 IPv6 네트워크에서 LMA도메인 간 핸드오버 기법의 보안성 분석 및 구현)

  • Chai, Hyun-Suk;Jeong, Jong-Pil
    • The KIPS Transactions:PartC
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    • v.19C no.2
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    • pp.99-118
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    • 2012
  • In PMIPv6-based network, mobile nodes can be made smaller and lighter because the network nodes perform the mobility management-related functions on behalf of the mobile nodes. The one of the protocols, Fast Handovers for Proxy Mobile IPv6(FPMIPv6)[1] has studied by the Internet Engineering Task Force(IETF). Since FPMIPv6 adopts the entities and the concepts of Fast Handovers for Mobile IPv6(FMIPv6) in Proxy Mobile IPv6(PMIPv6), it reduces the packet loss. Conventional scheme has proposed that it cooperated with an Authentication, Authorization and Accounting(AAA) infrastructure for authentication of a mobile node in PMIPv6, Despite the best efficiency, without begin secured of signaling messages, PMIPv6 is vulnerable to various security threats such as the DoS or redirect attAcks and it can not support global mobility between PMIPv. In this paper, we analyze Kang-Park & ESS-FH scheme, and then propose an Enhanced Security scheme for FPMIPv6(ESS-FP). Based on the CGA method and the pubilc key Cryptography, ESS-FP provides the strong key exchange and the key independence in addition to improving the weaknesses for FPMIPv6. The proposed scheme is formally verified based on Ban-logic, and its handover latency is analyzed and compared with that of Kang-Park scheme[3] & ESS-FH and this paper propose inter-domain fast handover sheme for PMIPv6 using proxy-based FMIPv6(FPMIPv6).

A Traffic Management Scheme for the Scalability of IP QoS (IP QoS의 확장성을 위한 트래픽 관리 방안)

  • Min, An-Gi;Suk, Jung-Bong
    • Journal of KIISE:Information Networking
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    • v.29 no.4
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    • pp.375-385
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    • 2002
  • The IETF has defined the Intserv model and the RSVP signaling protocol to improve QoS capability for a set of newly emerging services including voice and video streams that require high transmission bandwidth and low delay. However, since the current Intserv model requires each router to maintain the states of each service flow, the complexity and the overhead for processing packets in each rioter drastically increase as the size of the network increases, giving rise to the scalability problem. This motivates our work; namely, we investigate and devise new control schemes to enhance the scalability of the Intesev model. To do this, we basically resort to the SCORE network model, extend it to fairly well adapt to the three services presented in the Intserv model, and devise schemes of the QoS scheduling, the admission control, and the edge and core node architectures. We also carry out the computer simulation by using ns-2 simulator to examine the performance of the proposed scheme in respects of the bandwidth allocation capability, the packet delay, and the packet delay variation. The results show that the proposed scheme meets the QoS requirements of the respective three services of Intserv model, thus we conclude that the proposed scheme enhances the scalability, while keeping the efficiency of the current Intserv model.