• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1119-1124
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• 2012

Background: The effect and possible mechanism of traditional Chinese medicine, baicalin, on the PI3K/Akt signaling pathway in drug-resistant human myeloid leukemia HL-60/ADR cells have been investigated in this current study. Methods: HL-60/ADR cells were treated by 20, 40, $80\;{\mu}mol/L$ baicalin followed by cell cycle analysis at 24h. The mRNA expression level of the apoptosis related gene, Bcl-2 and bad, were measured by RT-PCR on cells treated with $80\;{\mu}mol/L$ baicalin at 12, 24 and 48hr. Western blot was performed to detect the changes in the expression of the proteins related to HL-60/ADR cell apoptosis and the signaling pathway before and after baicalin treatment, including Bcl-2, PARP, Bad, Caspase 3, Akt, p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR. Results: Sub-G1 peak of HL-60/ADR cells appeared 24 h after $20\;{\mu}mol/L$ baicalin treatment, and the ratio increased as baicalin concentration increased. Cell cycle analysis showed 44.9% G0/G1 phase cells 24 h after baicalin treatment compared to 39.6% in the control group. Cells treated with $80\;{\mu}mol/L$ baicalin displayed a trend in decreasing of Bcl-2 mRNA expression over time. Expression level of the Bcl-2 and PARP proteins decreased significantly while that of the PARP, Caspase-3, and Bad proteins gradually increased. No significant difference in Akt expression was observed between treated and the control groups. However, the expression levels of p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR decreased significantly in a time-dependent manner. Conclusions: We conclude that baicalin may induce HL-60/ADR cell apoptosis through the PI3K/AKT signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6191-6196
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• 2012

Aims and Background: Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside $Rg_1$ ($Rg_1$), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether $Rg_1$ can induce cancer cell senescence is still unclear. Methods: In the current study, human leukemia K562 cells were subjected to $Rg_1$ exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of $Rg_1$ on cell cycle were analyzed using flow cytometry and by SA-${\beta}$-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. Results: K562 cells demonstrated a maximum proliferation inhibition rate with an $Rg_1$ concentration of $20{\mu}\;mol{\cdot}L^{-1}$ for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-${\beta}$-galactosidase (SA-${\beta}$-Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin $G_2$/M phase after $Rg_1$ interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Conclusion: Ginsenoside $Rg_1$ can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.

• Communications for Statistical Applications and Methods
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• v.18 no.5
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• pp.581-594
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• 2011

The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.

• Journal of Korean Society of Forest Science
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• v.87 no.2
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• pp.260-269
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• 1998

This study was conducted to screen the biological activity of urushiol in the sap of lac tree(Rhus verniciflua STOKES) which has been used in traditional folk remedies. Cytotoxic activity of urushiol was screened with L1210(mouse luekemia cell), PC-9(human lung adenocarcinoma cell), A427(human lung adenocarcinoma cell) and KATO III (human stomach adenocarcinoma cell) The stepwise hexane : acetone eluent fractions of the urushiol were obtained by the silica gel adsorption column chromatography and added to the culture media containing L1210, PC-9. A427, and KATO III, respectively. A hexane : acetone(90 : 10, v/v) eluent fraction of them showed the lowest 50% inhibition concentration($IC_{50}$) of $0.018{\mu}g/m{\ell}$ for the cell line of A427. Much lower level of $IC_{50}$ of the hexane : acetone(90 : 10, v/v) eluent fraction of the urushiol showed the equal inhibition effect with tetraplatin(i.e., anti-cancer drug of platinum complexes) on the cancer cell lines as follows ; 3.4 times lower for L1210, 3.9 times lower for PC-9, and 105.5 times lower for A427. However, $IC_{50}$ of the hexane : acetone(90 : 10 v/v) eluent fraction for KATO III was exceptionally 3.9 times higher than that of tetraplatin.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.135-147
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• 2008

Objectives: Oriental pear was used as traditional remedies for respiratory diseases like cough and asthma etc. The purpose of this study was to observe the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs. Methods: In order to study the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization for 10 days and 20days. And 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The experimental groups were divided 6groups(10d1P, 10d2P, 10d4P, 20d1P, 20d2P and 20d4P) by meditation quantity and period. We measured isometric contractile responses to acetylcholine(ACh) and KCl in the isolated tracheal smooth muscle(TSM), IL-4, eosinophil and lymphocyte in bronchoalveolar lavage fluid(BALF), IgE in serum, WBC, RBC and hemoglobin in blood. Results: Contractile responses of TSM to ACh, the sensitivity of TSM to Ach and the maximal contractile response of TSM to KCl were decreased by direct proportion of meditation quantity. Eosinophil and IL-4 level in BALF were more significantly decreased, and IgE level in serum was more significantly increased in 10d4P and 20d4P group than the control group. Conclusions: Based on the above results, it is assumed that oral administration of the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) can help the preventing effects of allergic asthma.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.11-19
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• 2020

Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Glycyrrhiza new varieties Wongam and Sinwongam have been developed by Korea Rural Development Administration and investigated to register on Korean Pharmacopoeia of the Ministry of Food and Drug Safety. The aim of this study is to investigate the immunomodulatory effect of Wongam and Sinwongam comparing with listed Glycyrrhiza species (Glycyrrhiza uralensis Fischer and G. glabra Linne) for evaluations about pharmacological effect of Glycyrrhiza new varieties. Methods : We studied the immunomodulatory effect of Wongam and Sinwongam compared with G. uralensis and G. glabra using THP-1 cell in vitro model. The cells were treated with phorbol 12-myristate 13-acetate (PMA) for differentiation and stimulated with lipopolysaccharides (LPS) to induce immune activation. We analyzed and compared the effects Glycyrrhiza new varieties and listed Glycyrrhiza species using nitric oxide (NO) assay, western blot, and reverse transcription-quantitative polymerase chain reaction analysis. 1) Results : Wongam and Sinwongam showed no cytotoxicity in THP-1 cells. Wongam and Sinwongam, and listed Glycyrrhiza species increased NO production, and cyclooxygenase (COX)-2 expression with or without LPS in differentiated THP-1 macrophages. Furthermore, Wongam and Sinwongam and listed Glycyrrhiza species upregulated the mRNA expressions of T helper type 1 (Th 1)-associated cytokines in LPS-stimulated THP-1 macrophages. Conclusion : These results indicated that Wongam and Sinwongam would have effect of enhancing immune response through the increase of NO and COX-2 expression, and activate Th1-associated cytokines. The findings of this study suggest the wide applicability of Glycyrrhiza new varieties.

• Korean Journal of Environmental Agriculture
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• v.31 no.2
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• pp.164-169
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• 2012

BACKGROUND: This study was conducted to monitor the residue of pesticides and to assess their risk in domestic agricultural products, such as fruit vegetables, tomatoes, oriental melons and root vegetables, garlic, potatoes and onions. METHODS AND RESULTS: 250 samples containing both general and environment-friendly certified agricultural products were collected from traditional markets and supermarkets in 6 cities. 132 pesticides except for herbicides were analysed using the multi-residue methods by GC/ECD, GC/NPD and HPLC/UVD. 17 kinds of pesticides were detected from 42 samples, which were 32 general, 1 organic, 4 pesticide-free and 5 low pesticide agricultural products. Among those, myclobutanil detected in 1 potato and procymidone detected in 10 oriental melons were unregistered pesticides for using in Korea. Fenbuconazole detected in 1 potato and phorate detected in 1 tomato were exceeded over the MRLs established by Korea Food and Drug Administration. CONCLUSION: Based on these results, a risk assesment was conducted using a percentage of acceptable daily intake(%ADI). %ADI ranged from 0.0064% to 4.6035%, and showed these values have no effect on human health.

• Analytical Science and Technology
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• v.29 no.6
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• pp.283-292
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• 2016

Conventional fingerprint powders used during crime scene investigations pose potential health hazards. Thus, multiple natural replacement powders, including squid ink powder, indigo and rice powder were used to develop (visualize) latent fingerprints on non-porous surfaces (e.g., glass, plastic and tile). Fingerprints developed using the natural powders were compared using the Automatic Fingerprint Identification System (AFIS) with those developed with traditional black powder. The peak areas of ridges were also compared using densitometric image analyses. Collectively, objective and quantitative evaluation methods were developed. The effectiveness of natural powders varied depending on the surface but, in general, squid ink powder performed well on most surfaces. Indigo powder performed well on tile surfaces, while rice powder performed well on glass surfaces. Plastic was the most difficult surface from which to develop fingerprints. Image analysis using Field Emission Scanning Electron Microscopy (SEM) demonstrated the importance of the size and shape of natural powder particles to properly adhere to the ridges. Although densitometric image analyses did not correlate the number of minutiae and ridge peak areas, an unbiased, objective evaluation method would be possible using image analyses with a reference image. Additional experimentation will yield safe and cost-effective natural powders with which adequate fingerprint development can be performed.

• The Korean Journal of Food And Nutrition
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• v.27 no.3
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• pp.532-537
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• 2014

Cortex Phellodendri (CP) is derived from the dried bark of Phellodendron amurense. It has been widely used as a drug in traditional Korea medicine for treating diarrhea, jaundice, swelling pains in the knees and feet, urinary tract infections, and infections of the body surface. Many analytical methods have been used to study oriental herbal medicines, such as thin-layer chromatography, column liquid chromatography, and high performance liquid chromatography (HPLC). In this study, preparative centrifugal partition chromatography (CPC) was successfully carried out in order to separate pure compounds from a CP methanol extract. The optimum two-phase CPC solvent system was composed of n-butanol: acetic acid: water (4:1:5 v/v/v). The flow rate of the mobile phase was 3 mL/min in ascending mode with rotation at 1,000 rpm. The CPC-separated fraction and purification procedures were carried out by preparatory HPLC. The $^1H$ NMR spectrum revealed that the resonances at ${\delta}$ 4.10 and 4.20 ppm corresponded to three protons ($-OCH_3$), whereas those at ${\delta}$ 6.10 ppm corresponded to two protons ($-OCH_2O-$). Further, two aromatic protons (H-11 and H-12) conveys a doublet-doublet pattern. The H-11 doublet and H-12 doublet appear at ${\delta}$ 7.98 and 8.11, respectively. The $^{13}C$ NMR. spectrum showed a tetrasubstituted with a methylenedioxy group at C2 and C3, and two methoxy groups at C9 and C10. The chemical structure of the berberine was identified by $^1H$, $^{13}C$-nuclear magnetic resonance and electrospray ionization-mass spectroscopy spectral data analysis.

• Korean Journal of Food Science and Technology
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• v.35 no.3
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• pp.503-509
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• 2003

For the development of the anti-obesity natural drug, the inhibitor of adipocyte differentiation was screened from Korean traditional medicinal plants. Phellodendri Cortex was selected as a candidate of adipocyte differentiation inhibitor. An inhibitory compound PC-4 was purified from the methanol (MeOH) extract of Phellodendri Cortex using silica gel and ODS RP-18 column chromatography and HPLC. PC-4 was obtained as yellow powder; UV ${\lambda}_{max}$ (MeOH): 230, 260, 340 and 430 nm. The chemical structure of PC-4 was determined as an isoquionoline alkaloid, berberine, on the basis of various NMR experiments including $^1H-\;and\;^{13}C-NMR$. The PC-4 inhibited the differentiation of preadipocyte NIH-3T3 L1 cells at a concentration of $1\;{\mu}g/mL$.