• Journal of Ginseng Research
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• v.44 no.2
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Korean Journal of Food Science and Technology
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• v.35 no.2
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• pp.166-172
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• 2003

Changes in the number of microorganisms, chemical composition, and sensory quality of chungkukjang by gamma-irradiation up to 120 kGy were investigated. The total viable cell counts in chungkukjang irradiated with 10 kGy decreased from $10^9\;CFU/g$ of the control to $10^5\;CFU/g$. Proximate chemical composition and pH of chungkukjang were not much affected by irradiation. Acidity of chungkukjang decreased by irradiation with over 20 kGy. Fatty acid contents of chungkukjang irradiated under 20 kGy were the same as those of the nonirradiated ones. Polyunsaturated fatty acids content, decreased at over 40 kGy. The color and odor of chungkukjang were not significantly affected by irradiation up to 20 kGy. Unpalatable odor (p<0.01), off-flavor (p<0.001), and fish-odor (p<0.001) increased, and brown intensity (p<0.05) and acceptability (p<0.001) decreased at over 20 kGy. Results indicate 20 kGy is sufficient to decrease the microbial count of chungkukjang and prevent decrease in the content of polyunsaturated fatty acids.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1169-1173
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• 2006

Extracted fractions of the green seaweed Ulva lactuca were studied to verify the cytotoxicity and immunostimulating activity. The fractions from the ethanol extract of U. lactuca were prepared by the systematic extraction procedure with solvents such as hexane, ethyl ether, methanol, butanol and $H_2O$. The cytotoxic effects of U. lactuca fractions against human leukemia cell line U937, mouse neuroblastoma cell line (NB41A3), human hepatoma cell line (HepG2) and rat glioma cell line (C6) were investigated. Ethyl ether fraction showed the highest cytotoxicity against all four cell lines tested. In addition, $H_2O$ fraction also showed relatively high cytotoxicity. Dose dependent patterns were observed on all four cell lines. The immune-stimulating effects of U. lactuca fractions on rat macrophage cell line (RAW 264.7) were also investigated. All five fractions of U. lactuca extract stimulated NO production with concentration dependant manner. These results suggest that U. lactuca may be a useful candidate for a natural cancer preventing and immune-stimulating agents.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.4
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• pp.167-172
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• 2009

Methotrexate (MTX) in one of the antineoplastic drug and it is known to effective to management of acute lymphoblastic leukemia in children, management of choriocarcinoma and related trophoblastic tumors in women, management of carcinomas of the breast, tongue, pharynx, and tests, maintenance of remission in leukemia and treatment of serve, debilitating psoriasis. Intermediate to high-dose methotrexate administration followed by leucovorin rescue is effective in treatment of carcinoma of the lung and osteogenic sarcoma. Intrathecal administration is effective in treating meningeal leukemia or lymphoma. There are FPIA (Fluorescence polarization immunoassay) and EMIT (Enzyme multiplied immunotechique) methods that measure for MTX. We evaluated the FPIA and EMIT methods. MTX were measured by Hitachi-7600 P-module using EMIT and FPIA using TDX in the sera 60 patients. The performance characteristics evaluated were, light influence, linearity, comparison with FPIA. Also, precision evaluated were three level controls through put following CLSI evaluation protocols (EP10-A). When the MTX value of $4.16{\pm}5.78{\mu}{\mu}mol/L$ (mean, SD) by the Hitachi-7600 P-module was compared with that of $4.05{\pm}5.47{\mu}{\mu}mol/L$ by FPIA, coefficients of correlation of 0.988 was obtained. The regression equation was Y (Hitachi-7600 P-module) = 0.9408 x (FPIA) + 0.1316 (r=0.9885, n=60). CVs of MTX measured by Hitachi 7600 P-module was 6.78% at $0.33{\mu}{\mu}mol/L$, 0.96% at $1.16{\mu}{\mu}mol/L$, and 0.96% at $8.04{\mu}{\mu}mol/L$. The precision was excellent in each group. The linearity was acceptable. We evaluated that MTX is light-sensitive on prolonged exposure to direct sunlight. Comparing with the FPIA using TDX, the Hitachi-7600 P-module using EMIT showed good coefficient of correlation and precision. Therefore the Hitachi-7600 P-module can replace the FPIA for quantitative analysis of MTX.

• Journal of Preventive Medicine and Public Health
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• v.34 no.1
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• pp.80-88
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• 2001

Objectives : In an epidemiologic study on the health impact of Agent Orange exposure, the valid estimation of exposure level is the most important step. Based on recent studies, we examined the correlation between exposure levels categorized by personal exposure estimates and serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD, Dioxin), exploring the possibility of utilizing the exposure level as a surrogate for the estimate of exposure to agent orange. Methods : During the study period (Jan 1996-Feb 1996), blood specimens of 745 subjects taken randomly among 1,329 persons and kept frozen, were analyzed for 2,3,7,8-TCDO and six other dioxin congeners. The serum dioxin and congeners were measured in 1998 by CDC, adjusted for serum lipids. We categorized the total exposure scores into five groups based on Agent Orange exposure data collected by interview and military records. Pearson and Spearman's correlation coefficients & multiple regression analysis were used to identify the relationship of the exposure level categorized with serum concentration of 2,3,7,8-TCDD, and six other dioxin congeners. Results : Dioxin and the other congeners, except 1,2,4,6,7,8-HpCDD, showed significant correlations to exposure categories (p<0.005): 2,3,7,8-TCDD and OCDD showed positive correlations, whereas the other congeners did negative. The values of 2,3,7,8-TCDD differed according to exposure category and proportionally increased from the low exposure group to the high, a dose-response relationship, even after other possible confounding variables were adjusted for. In multiple regression analysis, age$(\beta=0.033)$, dioxin$(\beta=0.433)$, 1,2,3,7,8-PeCDD$(\beta=-0.998)$, 1,2,3,4,7,8-HxCDD$(\beta=-0.773)$, 1,2,3,6,7,8-HxCDD$(\beta=0.255)$, 1,2,3,7,8,9-HxCDD$(\beta=-3.468)$, 1,2,3,4,6,7,8-HpCDD$(\beta=0.109)$ we re found to be significantly related to the total exposure score(p<0.005). Conclusion : This study demonstrated that the use of such categorizations as a surrogate measure of agent orange exposure in identifying exposure degrees in a health impact study is valid.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.63-76
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• 1996

The aim of present study was to characterize phosphate uptake and to investigate the mechanism for the insulin and insulin-like growth factor(IGF) stimulation of phosphate uptake in primary cultured rabbit renal proximal tubule cells. Results were as follows : 1. The primary cultured proximal tubule cells had accumulated $6.68{\pm}0.70$ nmole phosphate/mg protein in the presence of 140 mM NaCl and $2.07{\pm}0.17$ nmole phosphate/mg protein in the presence of 140 mM KCl during a 60 minute uptake period. Raising the concentration of extracellular phosphate to 100 mM$(48.33{\pm}1.76\;pmole/mg\;protein/min)$ induced decrease in phosphate uptake compared with that in control cells maintained in 1 mM phosphate$(190.66{\pm}13.01\;pmole/mg\;protein/min)$. Optimal phosphate uptake was observed at pH 6.5 in the presence of 140 mM NaCl. Phosphate uptake at pH 7.2 and pH 7.9 decreased to $83.06{\pm}5.75%\;and\;74.61{\pm}3.29%$ of that of pH 6.5, respectively. 2. Phosphate uptake was inhibited by iodoacetic acid(IAA) or valinomycin treatment $(62.41{\pm}4.40%\;and\;12.80{\pm}1.64%\;of\;that\;of\;control,\;respectively)$. When IAA and valinomycin were added together, phosphate uptake was inhibited to $8.04{\pm}0.61%$ of that of control. Phosphate uptake by the primary proximal tubule cells was significantly reduced by ouabain treatment$(80.27{\pm}6.96%\;of\;that\;of\;control)$. Inhibition of protein and/or RNA synthesis by either cycloheximide or actinomycin D markedly attenuated phosphate uptake. 3. Extracellular CAMP and phorbol 12-myristate 13 acetate(PMA) decreased phosphate uptake in a dose-dependent manner in all experimental conditions. Treatment of cells with pertussis toxin or cholera toxin inhibited phosphate uptake. cAMP concentration between $10^{-6}\;M\;and\;10^{-4}\;M$ significantly inhibited phosphate uptake. Phosphate uptake was blocked to about 25% of that of control at 100 ng/ml PMA. 3-Isobutyl-1-methyl-xanthine(IBMX) inhibited phosphate uptake. However, in the presence of IBMX, the inhibitory effect of exogenous cAMP was not significantly potentiated. Forskolin decreased phosphate transport. Acetylsalicylic acid did not inhibit phosphate uptake. The 1,2-dioctanoyl-sn-glycorol(DAG) and 1-oleoyl-2-acetyl-sn- glycerol(OAG) showed a inhibitory effect. However, staurosporine had no effect on phosphate uptake. When PMA and staurosporine were treated together, inhibition of phosphate uptake was not observed. In conclusion, phosphate uptake is stimulated by high sodium and low phosphate and pH 6.5 in the culture medium. Membrane potential and intracellular energy levels are also an important factor fer phosphate transport. Insulin and IGF-I stimulate phosphate uptake through a mechanisms that involve do novo protein and/or RNA synthesis and decrease of intracellular cAMP level. Also protein kinase C(PKC) is may play a regulatory role in transducing the insulin and IGF-I signal for phosphate transport in primary cultured proximal tubule cells.

• Korean Journal of Medicinal Crop Science
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• v.11 no.1
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• pp.31-39
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• 2003

The antioxidative activities and biological properties in the EtOAc extracts and purified extracts of Orostachys japonicus were measured by assay of DPPH, xanthine/xanthine oxidase and mammalian cells(2-12). Scavenging of DPPH radical and inhibition of xanthine/xanthine oxidase of EtOAc extracts were showed the highest activity in the arable land and in September. The S-4 fraction showed the highest activity among the silica-gel column chromatography fractions. LH-4 fraction showed higher activity than the other fractionsins in assay of DPPH and xanthine/xanthine oxidase. Fatty acids and phenolic compounds were identified by GC/MS and main compounds were 1,2,3-benzenetriol, alpha-androsta-7,14-diene in LH-4 fraction. The activities of POD and SOD in samples havested on different habitats were high such as arable land> intermountain> seashore. That of POD and SOD in crude extracts of late stage were higher than early stage. Isozyme bands of crude extracts samplinged in all habitats and all growing stages showed two bands and the signal intensity showed strongly according to passage of growing stage. The purified extracts of LH-4 fraction showed excellent inhibition effect in proliferation of HL-60 cells and markedly suppressed colony formation in mouse fibroblast cells. Dose response between partially purified extracts(400ppm) and negative control did not produced statistically significant reduction in colony formation.

• Tuberculosis and Respiratory Diseases
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• v.70 no.1
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• pp.28-35
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• 2011

Background: The aim of the study was to describe the characteristics, treatments, and outcomes of critically ill patients with pandemic Influenza A/H1N1 2009 at a major medical center in Korea. Methods: This retrospective observational study examined critically ill adult patients with pandemic Influenza A/H1N1 2009, who were admitted to the AMC between August and December 2009. Results: 27 patients with confirmed pandemic Influenza A/H1N1 2009 were admitted to the intensive care unit (ICU) at the Asan Medical Center (AMC). The median age (IQR) was 59 years (41~67), and 66.7% of the patients were older than 51 years. A total of 81.5% of the patients had 2 or more co-morbidities. The median time (IQR) from symptom onset to presentation was 2 days (1~4), and the median time from presentation to ICU admission was 0 days (0~1.5). All patients received oseltamivir (300 mg/day) and 13 patients received triple combination therapy (oseltamivir, amantadine, ribavirin). Twelve patients required mechanical ventilation on the first day of ICU admission. A total of 6 patients (22.2%) died within 28 days of admission. The patients who died had significantly higher acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores at presentation. There were no significant differences in age, co-morbidities, or antiviral regimens between survivors and non-survivors. Conclusion: Critical illness related to pandemic Influenza A/H1N1 2009 was common in elderly patients with chronic co-morbidities. All patients were given high-dose oseltamivir or triple combination antiviral therapy. Nonetheless, patients with critical illnesses associated with pandemic Influenza A/H1N1 2009 had a death rate of 22.2%.

• Korean Journal of Food Science and Technology
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• v.46 no.4
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• pp.505-510
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• 2014

Kojongsi persimmon (Diospyros kaki L.) is the major cultivar of dried persimmon in Korea. The purpose of this study was to investigate the antioxidant and anti-inflammatory activities of water-soluble extracts from the calyx (PCE), peel (PPE) and leaf (PLE) of Kojongsi persimmon. PCE showed the highest total phenolic and flavonoid contents. In addition, the antioxidant activities (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), nitric oxide and reducing power) of PCE were higher than those of PPE and PLE. Moreover, PCE, PPE and PLE significantly suppressed the production of inflammatory mediators (nitric oxide and $prostaglandinE_2$) and pro-inflammatory cytokines (tumor necrosis factor-${\alpha}$ and interluekin-$1{\beta}$) by lipopolysaccharide-stimulated RAW 264.7 cells in a dose-dependent manner. PCE showed the highest anti-inflammatory activity. Thus, these results suggest that the calyx of Kojongsi persimmon may be highly valuable as a natural product owing to its high-quality functional components as well as its-antioxidant, ant-iinflammatory activities.

• The Korean Journal of Physiology
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• v.22 no.1
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• pp.13-29
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• 1988

In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.