• Journal of Life Science
• /
• v.25 no.7
• /
• pp.833-838
• /
• 2015

Multidrug-resistant super bacterial, fungal, viral, and parasitic infections are major health threaten pathogens. However, to overcome the present healthcare situation, among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly produced via various species in nature. AMPs, small host defense proteins, are in charge of the innate immunity for the protection of multicellular organisms such as fish, amphibian, reptile, plants and animals from infection. The number of AMPs identified per year has increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been listed into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11–50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31–70%. This report classified AMP into several categories including biological source, biological functions, peptide properties, covalent bonding pattern, and 3D structure. AMP functions not only antimicrobial activity but facilitates cell biological activity such as chemotatic activity. In addition, fibroblastic reticular cell (FRC) originated from mouse lymph node stroma induced the expression of AMP in inflammatory condition. AMP induced from FRC contained whey acidic protein (WAP) domain. It suggests that the classification of AMP will be done by protein domain.

• Journal of Life Science
• /
• v.23 no.10
• /
• pp.1223-1229
• /
• 2013

Ursolic acid (UA) a bio-active ingredient found in a variety of fruits and vegetables, and it has potent antioxidant activity. However, the role of UA in mouse embryonic stem (ES) cells is poorly understood. This study investigated the functional role of UA in regulating the development of mouse ES cells under hypoxia. Hypoxia did not exert a significant effect on the undifferentiated state of mouse ES cells. However, it induced reactive oxygen species (ROS) generation and increased the level of lactate dehydrogenase (LDH) production at 48 h of hypoxic exposure. Conversely, oxidative stress induced by hypoxia was significantly inhibited by UA ($30{\mu}M$) pretreatment. Hypoxia significantly decreased cell survival and the level of [$^3H$] thymidine incorporation, both of which recovered following pretreatment of UA. In addition, UA decreased the apoptotic effect of hypoxia by attenuating caspase-3 cleavage or by recovering cellular inhibition of the apoptotic protein (cIAP)-2 and Bcl-2 expression. We further found that UA decreased senescence-associated beta-galactosidase activity. We suggest that UA is a natural antioxidant and one of the functional modulators of hypoxia-induced survival, apoptosis, proliferation, and aging in mouse ES cells.

• Archives of Pharmacal Research
• /
• v.29 no.10
• /
• pp.866-873
• /
• 2006

When patients with cancers are treated with chemotherapeutic agents a long time, some of the cancer cells develop the multidrug resistance (MDR) phenotype. MDR cancer cells are characterized by the overexpression of multidrug resistance1 (MDR1) gene which encodes P-glycoprotein (Pgp), a surface protein of tumor cells that functions to produce an excessive efflux and thereby an insufficient intracellular concentration of chemotherapeutic agents. A variety of studies have sought potent MDR modulators to decrease MDR1 gene expression in cancer cells. Our previous study has shown that curcumin exhibits characteristics of a MDR modulator in KB-V1 multidrug-resistant cells. The aim of this study was to further investigate the effect of curcumin on MDR1 gene expression in patient leukemic cells. The leukemic cells were collected from 78 childhood leukemia patients admitted at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, in the period from July 2003 to February 2005. There were 61 cases of acute lymphoblastic leukemia (ALL), 14 cases of acute myeloblastic leukemia (AML), and 3 cases of chronic myelocytic leukemia (CML). There were 47 males and 31 females ranging from 1 to 15 years old. Bone marrows were collected. The leukemic cells were separated and cultured in the presence or absence of $10{\mu}M$ curcumin for 48 hours. MDR1 mRNA levels were determined by RT-PCR. It was found that curcumin reduced MDR1 gene expression in the cells from 33 patients (42%). Curcumin affected the MDR1 gene expression in 5 of 11 relapsed cases (45%), 10 of 26 cases of drug maintenance (38%), 7 of 18 cases of completed treatment (39%), and 11 of 23 cases of new patients (48%). The expression levels of MDR1 gene in leukemic patient cells as compared to that of KB-V1 cells were classified as low level (1-20%) in 5 of 20 cases (25%), medium level (21-60%) in 14 of 32 cases (44%), and high level (61-100%) in 14 of 20 cases (70%). In summary, curcumin decreased MDR1 mRNA level in patient leukemic cells, especially in high level of MDR1 gene groups. Thus, curcumin treatment may provide a lead for clinical treatment of leukemia patients in the future.

• Journal of the Institute of Electronics Engineers of Korea SD
• /
• v.37 no.9
• /
• pp.15-22
• /
• 2000

The effects of carrier transport and input power on the extinction ratio was theoretically analyzed in a 1.55${\mu}m$ InGaAsP/InGaAsP multiple-quantum-well(MQW) electroabsorption(EA) modulator. Poisson's equation, current continuity equations for electrons and holes, and optical field distribution were self-consistently solved by considering electric field dependent absorption coefficients. The field screening effect due to the carrier accumulation in heterointerface and the space-charge region occurred more seriously at the input side of modulator as input optical intensity increased. It was revealed that extinction ratio could be steeply degraded for modulator with the length of 200${\mu}m$ when an input power exceeds 10mW. A degradation of extinction ratio due to the field screening effect would be more significantly at high-performance devices such as a 1.55${\mu}m$DFB-LD/EA-modulator integrated source where optical coupling efficiency is almost complete or a very high-speed modulator with its length as short as a few tens ${\mu}m$.

• Tuberculosis and Respiratory Diseases
• /
• v.43 no.3
• /
• pp.359-366
• /
• 1996

Background : Eosinophilic leukocytes are prominent cellular participants in the pathogenesis of allergic disease and asthma. Chemotaxis is still a very useful method in evaluating the response of human eosinophil to novel modulators. Degranulated mast cells and activated T lymphocytes are responsible for the pathophysiology of asthma and tryptase is one of most important proteases released after activation of mast cells. The purpose of this study was to investigate the actions of trypsin and chymotrypsin on eosinophils in terms of chemotaxis and activation. Method : Eosinophils were isolated by negative immunoselection from the peripheral blood of atopic donors. Chemotaxis was studied by using micro-Boyden chambers and ECP release was assayed by fluoroimmunoassay. Results : Eosinophil showed a chemotactic response to trypsin. Maximal chemotactic response was with $1000{\mu}g/ml$ trypsin ($56.52{\pm}14.50$/HPF) which was comparable to PAP. But chymotrypsin showed no significant chemotactic response to eosinophils. Trypsin at the concentration of 10, 100, $1000{\mu}g/ml$ induced secretion of ECP, which at the concentration of $10{\mu}g/ml$ represented about 2.7 times of the spontaneous rate of release. Soybean protease inhibitor reduced trypsin induced ECP release. Conclusion : Trypsin can induce chemotactic response to eosinophils and activation of eosinophils that can induce secretion of ECP. On the contrary, chymotrypsin showed no direct effect on eosinophils. We propose a role of trypsin on the chemotaxis and activation of eosinophils.

• Proceedings of the Ginseng society Conference
• /
• 1988.08a
• /
• pp.115-121
• /
• 1988

Although Saponin A from Panax ginseng has previously been shown to inhibit carageenin induced edema. a paucity of information exists on the effects of components from ginseng on the cellular inflammatory response. specifically polymorphonuclear leukocyte (PMNL) function. The purpose of this study was 10 determine the effects of isolated neutral dammarane saponins from ginseng (i.e..glycosidic derivatives of 20(S)-protopanaxadiol [ginsenoside $Rb_1,\;Rb_2$ and Rc] and 20(S)-protopanaxatriol [ginsenosides Re and $Rg_1$]) on in vivo PMNL function and to compare their effects with those produced by a steroidal anti-inflammatory agent (dexamethasone) and commercially available saponin. Dexamethasone. the ginsenosides and saponin were all shown to he potent inhibitors of PMNL chemotaxis using the $^{51}Cr$ assay with $5{\times}10^{-8}M$ f-met-leu-phe [FMLP] as the chemoattractant. Inhibition or PMNL chemotaxis by dexamethasone. the ginsenosides and saponin were all shown to be both time-and dose-dependent and these agents did not affect cellular viability at the concentrations tested Saponin and the ginsenosides were more potent inhibitors of chemotaxis than was dexamethasone. while oxidant generation (as measured by the luminol-enhaneed chemil-uminescence of PMNL using FMNL $[10^{-6}]$ as the stimulus) was inhibited by dexamethasone. the ginsenosides $(Rb_1\;Rb_2\;Rc\;Re\;and\;Rg_1)$ and saponin at a concentration of 1 ${\mu}M$ had no significant effect on PMNL chemiluminescence. Thus. the neutral dammarane saponins are potentially important modulators or PMNL function and their inhibitory effects may he differentiated from those of the Steroidal anti-inflammatory agents.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.16 no.11
• /
• pp.7575-7581
• /
• 2015

Corticotropin-releasing factor(CRF), one of the stress driven neuropeptides, was widely proposed to influence hair loss and re-growth. For the development of receptor antagonists, the screening system based on intracellular calcium signal process was developed and optimized. The aequorin parental cells were transfected with CRF1 receptor and alpha 16 promiscuous G protein cDNA to establish HEK293a16/hCRF1, a stable cell line for the human CRF1 receptor. In HEK293a16/hCRF1 cells, the range of sauvagine dose response was 12-fold higher($EC_{50}:15.21{\pm}1.83nM$) than in the transiently expressed cells, hence essential conditions for the antagonist screening experiments such as the robust signals and high solvent tolerance were secured. The standard antagonists for the CRF1 receptor, antalarmin and CP154526, resulted $IC_{50}$ values of $414.1{\pm}5.5$ and $290.7{\pm}1.9nM$, respectively. Similar results were presented with frozen HEK293a16/hCRF1 cells. Finally, our HEK293a16/hCRF1 cells with the aequorin based cellular functional assay can be a model system for the development of functional cosmetics and modulators that can have a clinical efficacy on hair re-growth.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.5
• /
• pp.459-466
• /
• 2016

Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

• Korean Journal of Optics and Photonics
• /
• v.9 no.5
• /
• pp.277-281
• /
• 1998

One dimensional inhomogeneous aperture modulation effects on the MTF of optical system was investigated. The lens under test was a doublet made in Korea. It has 10 mm effective diameter, 87.8 mm effective focal length. The ray-fans and spot diagrams were calculated and presented on the picture for on-axis and off-axis (field of view, $1^{\circ}$ and $2^{\circ}$). Aperture modulation was carried out by positioning a aperture modulator close contacter with the lens under test. We bought two modulators from Edmud Company in U.S.A. One was linear type and the other was stepped type. The MTFs were measured on the best of focus for each modulated aperture where the MTF has the highest value for 60 line/mm and were compared with one another. For on-axis, the MTFs of some modulated apertures had higher values than the MTF of unmodulated aperture in the high frequency region. In the case of off-axis, at the field of view $1^{\circ}$, the MTF values of some modulated aperture are improved prominently and some other one are disimproved. At the field of view $2^{\circ}$ most of the MTFs of modulated apertures had lower values than the MTF of unmodulated aperture except the MTFs of linear and inverse linear type aperture in the high frequency area. But the values of MTFs in high frequency region were too low for actual use.

• Biomolecules & Therapeutics
• /
• v.25 no.3
• /
• pp.288-295
• /
• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.