• Journal of the Korean Magnetic Resonance Society
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• v.18 no.1
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• pp.1-4
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• 2014

It is generally understood that protein-protein interactions proceed via transient encounter complexes that rapidly evolve into the functional stereospecific complex. Direct detection and characterization of the encounter complexes, however, been difficult due to their low population and short lifetimes. Recent application of NMR paramagnetic relaxation enhancement first visualized the structures of the encounter complex ensemble, and allowed the characterization of their physicochemical properties. Further, rational protein mutations that perturbed the encounter complex formation provided a clue to the target search pathway during protein-protein association. Understanding the structure and dynamics of encounter complexes will provide useful information on the mechanism of protein association.

• Journal of Microbiology and Biotechnology
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• v.23 no.6
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• pp.779-784
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• 2013

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an anti-leptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

• BMB Reports
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• v.35 no.6
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• pp.623-628
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• 2002

The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

• Korean Journal of Oriental Medicine
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• v.17 no.3
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• pp.77-85
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• 2011

Objectives : The purpose of this study was to develop a simulator which can analyze the anti-inflammatory effects of medical herbs based on e-cell concerning p38 MAPK signal pathway. Methods : We collected data concerning medical herbs with anti-inflammatory effects and the active compounds to provide as a fundamental databse and to validate the newly developed algorithm. At this time, we used the target database as pubmed and gathered the data by data mining tool, pathway studio. Also we have developed the web-based search system for confirming database related to anti-inflammation. We researched the mechanism of actions of proteins in p38 MAPK signal pathway when active compound has been inserted into the network. We reduced total network into TAK-MKK3-p38 and made the two types of mathematical model about active compounds' interaction. Results & Conclusion : We constructed the database which have 69 cases of medical herbs, 71 cases of active compounds, about 8,000 cases of URL(Uniform Resource Locator) related to papers and reports. We designed the ordinary differential equations for response of TAK, MKK3, p38 in e-cell's cytosol and nucleus. We used this formular as measure whether an active compound of medicinal plants which is inputted by an user would have an anti-inflammation effects. We developed the visualization program which could show the change of concentration over time.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2789-2800
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• 2013

Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.35 no.3
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• pp.15-24
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• 2022

Objectives : The purpose of this study is to investigate the potential mechanism of Artemisia capillaris Thunb. for psoriasis vulgaris. Methods : We conducted the network pharmacological analysis. It contains the process that search the compounds of the herb, the target proteins of the compounds, related genes of psoariasis vulgaris and the pathway/terms of the common protein lists between psoriasis vulgaris and Artemisia capillaris Thunb.. Results : 13 compounds and 30 protein targets of Artemisia Capillaris Herba were searched. And 997 psoriasis-related genes were searched. The common proteins were 11, and the core genes were 3; AKT1, CASP3, MAPK8. The related pathway/terms of 11 proteins were analyzed. ω-hydroxylase P450 pathway(60%), nitric oxide(NO) biosynthetic process(20%) were resulted. Also, 19 proteins of Artemisia Capillaris Herba were analyzed, and sterol homeostasis(78.95%), sterol biosynthetic process(15.79%), Type 2 diabetes mellitus(5.26%) were resulted. Conclusion : The Artemisia Capillaris Herba can potentially act through the ω-hydroxylase P450 pathway and nitric oxide(NO) biosynthetic process for psoriasis. Also, the metabolism of sterol biosynthesis and homeostasis can be involved in a roundabout way for psoriasis.

• Journal of Korean Neurosurgical Society
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• v.65 no.5
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• pp.697-709
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• 2022

Objective : The present study aimed to identify the function of ischemic stroke (IS) patients' peripheral blood and its role in IS, explore the pathogenesis, and provide direction for clinical research progress by comprehensive bioinformatics analysis. Methods : Two datasets, including GSE58294 and GSE22255, were downloaded from Gene Expression Omnibus database. GEO2R was utilized to obtain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the database annotation, visualization and integrated discovery database. The protein-protein interaction (PPI) network of DEGs was constructed by search tool of searching interactive gene and visualized by Cytoscape software, and then the Hub gene was identified by degree analysis. The microRNA (miRNA) and miRNA target genes closely related to the onset of stroke were obtained through the miRNA gene regulatory network. Results : In total, 36 DEGs, containing 27 up-regulated and nine down-regulated DEGs, were identified. GO functional analysis showed that these DEGs were involved in regulation of apoptotic process, cytoplasm, protein binding and other biological processes. KEGG enrichment analysis showed that these DEGs mediated signaling pathways, including human T-cell lymphotropic virus (HTLV)-I infection and microRNAs in cancer. The results of PPI network and cytohubba showed that there was a relationship between DEGs, and five hub genes related to stroke were obtained : SOCS3, KRAS, PTGS2, EGR1, and DUSP1. Combined with the visualization of DEG-miRNAs, hsa-mir-16-5p, hsa-mir-181a-5p and hsa-mir-124-3p were predicted to be the key miRNAs in stroke, and three miRNAs were related to hub gene. Conclusion : Thirty-six DEGs, five Hub genes, and three miRNA were obtained from bioinformatics analysis of IS microarray data, which might provide potential targets for diagnosis and treatment of IS.