• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.456-464
• /
• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Steel and Composite Structures
• /
• v.19 no.1
• /
• pp.209-221
• /
• 2015

Results from an experimental study on the seismic response of six composite reinforced concrete column-to-steel beam interior joints are presented. The primary variable investigated is the details in the joint. For the basic specimen, the main subassemblies of the beam and column are both continuous, and the steel beam flanges extended to the joint are partly cut off. Transverse beam, steel band plates, cove plates, X shape reinforcement bars and end plates are used in the other five specimens, respectively. After the joint steel panel yielded, two failure modes were observed during the test: local failure in Specimens 1, 2 and 4, shear failure in Specimens 3, 5 and 6. Specimens 6, 3, 5 and 4 have a better strength and deformation capacity than the other two specimens for the effectiveness of their subassemblies. For Specimens 2 and 4, though the performance of strength degradation and stiffness degradation are not as good as the other four specimens, they all have excellent energy dissipation capacity comparing to the RC joint, or the Steel Reinforced Concrete (SRC) joint. Based on the test result, some suggestions are presented for the design of composite RCS joint.

• Journal of Technology Innovation
• /
• v.12 no.1
• /
• pp.161-188
• /
• 2004

The objective of this research is to evaluate the Creative Research Initiative Program (CRI), a national R＆D program funded by the Ministry of Science ＆ Technology in Korea. The evaluation of CRI covers the following research questions; 1) Have it set a unique position and characteristic distinguished from other government-funded R＆D programs\ulcorner 2) Are the achievements of the program relevant to its goal\ulcorner 3) What is its performances and how much is it achieved its goal\ulcorner The results are the followings; 1) CRI is perceived as a pure basic research, distinguished from other national basic research programs, such as the Coal Oriented Basic Research Program and the SRC and ERC. 2) CRI is a well-adapted R＆D program in confront of the environmental changes and R＆D needs, as well as follows the planned R＆D areas. 3) CRI have performed well in the raising-up world-class research leaders and the nation-wide diffusion of creative R＆D culture, while it got few performances in the overcoming the limitation of the existing technologies and the independent development of original key technologies for future industries. However, the duration of the program, 5 year, is too short to expect concrete outcome, such as creating original technologies. Many of the outcomes of CRI gets a lot of attention from top class scientists in the world, it is expected to generate various R＆D performances in the future.

• BMB Reports
• /
• v.42 no.1
• /
• pp.35-40
• /
• 2009

Protein kinase D2 (PKD2) is a member of the PKD serine/threonine protein kinase family that has been implicated in the regulation of a variety of cellular processes including proliferation, survival, protein trafficking and immune response. In the present study, we report a novel interaction between PKD2 and Lck, a member of the Src tyrosine protein kinase family that is predominantly expressed in T cells. This interaction involved the C-terminal kinase domains of both PKD2 and Lck. Moreover, co-expression of Lck enhanced the tyrosine phosphorylation of PKD2 and increased its kinase activity. Finally, we report that PKD2 enhanced T cell receptor (TCR)-induced nuclear factor of T cell (NFAT) activity in Jurkat T cells. These results suggested that Lck regulated the activity of PKD2 by tyrosine phosphorylation, which in turn may have modulated the physiological functions of PKD2 during TCR-induced T cell activation.

• International Journal of Oral Biology
• /
• v.38 no.2
• /
• pp.67-72
• /
• 2013

This study examined the anti-osteoclastogenic effects of baicalin on receptor activator of NF-${\kappa}$B ligand (RANKL)-induced RAW264.7 cells. Baicalin is a flavonoid that is produced by Scutellaria baicalensis and is known to have multiple biological properties, including antibacterial, anti-inflammatory and analgesic effects. The effects of baicalin on osteoclasts were examined by measuring 1) cell viability; 2) the formation of tartrate-resistant acid phosphatase (TRAP) (+) multinucleated cells; 3) RANK/RANKL signaling pathways and 4) mRNA levels of osteoclast-associated genes. Baicalin inhibited the formation of RANKL-stimulated TRAP (+) multinucleated cells and also suppressed the RANKL-stimulated activation of p-38, ERK, cSrc and AKT signaling. Baicalin also inhibited the RANKL-stimulated degradation of $I{\kappa}B$ in RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was found to be abrogated by this flavonoid. Baicalin was further found to decrease the mRNA expression of osteoclast-associated genes, including carbonic anhydrase II, TRAP and cathepsin K in the RAW264.7 cells. Our data thus demonstrate that baicalin inhibits osteoclastogenesis by inhibiting the RANKL-induced activation of signaling molecules and transcription factors in osteoclast precursors.

• International Journal of Industrial Entomology and Biomaterials
• /
• v.48 no.1
• /
• pp.13-18
• /
• 2024

The rice field grasshopper, Oxya chinensis sinuosa (OC), has traditionally been utilized in Korea for various purposes; however, its potential benefits in the context of osteoporosis remain unclear. The results revealed that OC ethanol extract (OCE) significantly inhibited the formation and activity of tartrate-resistant acid phosphatase (TRAP)-positive cells in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated RAW264.7 cells. Furthermore, OCE, at concentrations ranging from 100 to 400 ㎍/mL, demonstrated a dose-dependent reduction in the protein expression of osteoclast-specific markers, including nuclear factor of activated T cell cytoplasmic 1, c-Src, and TRAP, when compared to RANKL stimulation alone. Additionally, OCE significantly inhibited RANKL-induced activation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) but not the activation of extracellular signal-regulated kinase. Collectively, these results indicate that OCE suppresses osteoclastogenesis by attenuating the phosphorylation of p38 MAPK and JNK. Consequently, these findings suggest that OCE holds promise for the prevention of osteoporosis.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.5
• /
• pp.1475-1479
• /
• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• BMB Reports
• /
• v.28 no.4
• /
• pp.316-322
• /
• 1995

The GTPase activating protein (GAP) can function both as a negative regulator and an effector of $p21^{ras}$. Overexpression of GAP in NIH-3T3 cells has been shown to inhibit transformation by ms or src. To investigate the function of GAP in a differentiative system, we overexpressed this protein in the nerve growth factor (NGF)-responsive PC12 cell line. Two-fold overexpression of GAP caused a delay of several days in the onset of NGF- but not FGF-induced neuronal differentiation of PC12 cells. However, the NGF-induced activation or tyrosine phosphorylation of upstream (Trk, PLC-${\gamma}1$, SHC) and downstream (B-Raf and $p44^{mapk/erk1}$) components of $p21^{ras}$, signalling cascade was not altered by GAP overexpression. Therefore, the change of phenotype induced by GAP was probably not due to GAP functioning as a negative regulator of $p21^{ras}$. Rather, we found that NGF-induced tyrosine phosphorylation of SNT, a specific target of neurotrophin-induced tyrosine kinase activity, was inhibited by GAP overexpression. SNT is thought to function upstream or independent of $p21^{ras}$. Thus in PC12 cells, overexpressed GAP may control the rate of neuronal differentiation through a pathway involving SNT rather than the $p21^{ras}$ signalling pathway.

• BMB Reports
• /
• v.48 no.3
• /
• pp.127-128
• /
• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

• The Transactions of the Korean Institute of Power Electronics
• /
• v.20 no.1
• /
• pp.31-37
• /
• 2015

This paper proposes a 3.3-kW bi-directional EV charger with V2G and V2H functions. The bi-directional EV charger consists of a DC-DC converter and a DC-AC inverter. The proposed EV charger is suitable for wide battery voltage control due to the two-stage configuration of the DC-DC converter. By employing a fixed-frequency series loaded resonant converter as the isolated DC-DC converter, zero-current-switching can be achieved regardless of battery voltage variation, load variation, and power flow. A 3.3-kW prototype of the proposed EV charger has been built and verified with experiments, and indicates a maximum efficiency of 94.39% and rated efficiency of 94.23%.