• Molecules and Cells
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• v.28 no.3
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• pp.201-207
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• 2009

Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of $NF-{\kappa}B$, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit $TNF-{\alpha}$-induced osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and $TNF-{\alpha}$.

• The Journal of the Korea Contents Association
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• v.9 no.4
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• pp.114-120
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• 2009

In this study, we employed the idea that disease-related proteins tend to be work as an important factor for architecture of the disease network. We initially obtained 43 atopy-related proteins from the Online Mendelian Inheritance in Man (OMIM) and then constructed atopy-related protein interaction network. The protein network can be derived the map of the relationship between different disease proteins, denoted disease interaction network. We demonstrate that the associations between diseases are directly correlated to their underlying protein-protein interaction networks. From constructed the disease-protein bipartite network, we derived three diseasomal proteins, CCR5, CCL11, and IL/4R. Although we use the relatively small subnetwork, an atopy-related disease network, it is sufficient that the discovery of protein interaction networks assigned by diseases will provide insight into the underlying molecular mechanisms and biological processes in complex human disease system.

• BMB Reports
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• v.45 no.3
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• pp.171-176
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• 2012

Receptor activator of NF-${\kappa}B$ ligand (RANKL) triggers the differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) of hematopoietic origin into osteoclasts through the activation of mitogen-activated protein (MAP) kinases and transcription factors. Recently, reactive oxygen species (ROS) and antioxidant enzymes were shown to be closely associated with RANKL-mediated osteoclast differentiation. Although glutaredoxin2 (Glrx2) plays a role in cellular redox homeostasis, its role in RANKL-mediated osteoclastogenesis is unclear. We found that Glrx2 isoform b (Glrx2b) expression is induced during RANKLmediated osteoclastogenesis. Over-expression of Glrx2b strongly enhanced RANKL- mediated osteoclastogenesis. In addition, Glrx2b-transduced BMMs enhanced the expression of key transcription factors c-Fos and NFATc1, but pre-treatment with SB203580, a p38-specific inhibitor, completely blocked this enhancement. Conversely, down-regulation of Glrx2b decreased RANKL- mediated osteoclastogenesis and the expression of c-Fos and NFATc1 proteins. Also, Glrx2b down-regulation attenuated the RANKL-induced activation of p38. Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.11
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• pp.1662-1669
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• 2007

The high mobility group AT-hook1 (HMGA1) proteins are known to be related to the regulation of gene transcription, replication and promotion of metastatic progression in cancer cells. The loss of expression by disrupting the HMGA1 gene affects insulin signaling and causes diabetes in the mouse. Previously identified single nucleotide polymorphism (SNP) of HMGA1 was significantly associated with fat deposition traits in the pig. In this study, we identified 3,935 bp nucleotide sequences from exon 5 to exon 8 of the bovine HMGA1 gene and its mRNA expression was observed by quantitative real-time PCR. Six single nucleotide polymorphisms in the bovine HMGA1 gene were detected and the allele frequencies of these SNPs were investigated using the PCR-RFLP method in nine cattle breeds including Limousin, Simmental, Brown Swiss, Hereford, Angus, Charolais, Hanwoo, Brahman and Red Chittagong cattle. The map location showed that the bovine HMGA1 gene was also closely located with a previously identified meat quality QTL region indicating this gene is the most likely positional candidate for meat quality traits in cattle.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.7-13
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• 2001

Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4405-4409
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• 2014

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

• Journal of KIISE:Software and Applications
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• v.31 no.3
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• pp.343-352
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• 2004

Recently, the information processing of ever increasing bio-related data is becoming a very important issue. One of the main sources of these bio-data comes with the form of biopathways, which includes molecular transactions and processes that are part of biochemical systems. The information represented by biopathways includes various organic relations among its components. However, most of the current systems to represent biopathways have been initially developed without computer processing in mind, and hence suffer from inconsistencies and ambiguities. In this paper, we propose an improved notation, called UniPath, for clear and systematic representation of biopathways. The proposed system is designed to provide a unified representation of metabolic and regulatory pathways. We also designed and implemented a graphic editor for UniPath to draw biopathwavs map according to the proposed notation. The graphic editor is designed so that biopathway data can be easily transformed into XML format.

• Journal of The Korean Astronomical Society
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• v.35 no.2
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• pp.105-110
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• 2002

We present the results of VLA $NH_3$ (1,1) and (2,2) line observations of the young-stellar object (YSO) IRAS 19550+3248. The integrated intensity map of the $NH_3$ (1,1) line shows that there are two ammonia cores in this region; core A which is associated with the YSO, and core B which is diffuse and located at the northeast of core A. Core A is compact and elongated along the east-west direction (0.07 pc$\times$0.05 pc) roughly perpendicular to the molecular outflow axis. Core B is diffuse and extended (0.18 pc$\times$0.07 pc). $NH_3$ (2,2) line is detected only toward core A, which indicates that it is hotter (~ 15 K), presumably due to the heating by the YSO. The $NH_3$ (1,1) line toward core A is wide (${\Delta}v{\ge} 3 km s^{-l}$) and appears to have an anomalous intensity ratio of the inner satellite hyperfine lines. The large line width may be attributed to the embedded YSO, but the hyperfine anomaly is difficult to explain. We compare the results of $NH_3$ observations with those of previous CS observations and find that the CS emission is detected only toward core A and is much more extended than the $NH_3$ emission.

• The Bulletin of The Korean Astronomical Society
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• v.40 no.2
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• pp.53.2-53.2
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• 2015

We present preliminary results from a series of observations toward G108.8-00.8, which is one of Planck Cold Clumps and a promising candidate of massive prestellar cores. In the integrated intensity map of SCUBA 850 micron dust continuum emission, highly fragmented structures appear. These are distributed along one long filamentary structure seen in the CO 1-0 and 13CO 1-0 integrated intensity maps obtained with the PMO 13.7 m telescope. The northern part of the filament is divided into two parts, as seen in the CO 2-1, 13CO 2-1, and C18O 2-1 integrated intensity maps obtained with the CSO 10 m telescope. The observations of HCO+ 1-0, N2H+ 1-0, and HCN 1-0 with the IRAM 30 m telescope focus on the northern part of the CSO maps, which show a head-tail structure. NH3 (1,1) also shows similar distribution with IRAM maps. The depletion factors, derived by the comparison between the dust continuum and C18O 2-1 emission, varies from 1.5 to 6 over the region, suggesting different evolutionary status of each component. To study the chemical and physical environments of G108.8-00.8, more detailed analysis is in progress.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.44 no.4
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• pp.345-349
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• 1999

This study was carried out to map Bphl and bph2 gene in Mudgo and Sangju13 (Oryza sativa L.) respectively conferring resistance to brown plan-thopper (BPH) and to establish the marker-assisted selection (MAS) system. Bulked seedling (grown for 20 days) test was conducted with the 73 F4 lines derived from a cross between Nagdongbyeo and Mudgo for Bphl and with 53 BC3F5 lines derived from the Milyang95/Sangju13 cross for bph2. Bph1 was mapped between RG413 and RG901 on chromo-some 12 at a distance of 7.5 cM from RG413 and 8.4 cM from RG90l. A recessive gene bph2 was located near RZ76 on chromosome 12 at a distance of 14.4 cM. Bphl and bph2 were linked to each other with a distance of about 30 cM. An RFLP marker, RG413 linked to Bphl, was converted to an STS marker to facilitate the marker-assisted selection. BPH resistant genotypes could be selected with 92% accuracy in a population derived from a line of NM47-B-B.