• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.59-72
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• 2024

To investigate the mechanism of Wenshen Xuanbi Decoction (WSXB) in treating osteoarthritis (OA) via network pharmacology, bioinformatics analysis, and experimental verification. The active components and prediction targets of WSXB were obtained from the TCMSP database and Swiss Target Prediction website, respectively. OA-related genes were retrieved from GeneCards and OMIM databases. Protein-protein interaction and functional enrichment analyses were performed, resulting in the construction of the Herb-Component-Target network. In addition, differential genes of OA were obtained from the GEO database to verify the potential mechanism of WSXB in OA treatment. Subsequently, potential active components were subjected to molecular verification with the hub targets. Finally, we selected the most crucial hub targets and pathways for experimental verification in vitro. The active components in the study included quercetin, linolenic acid, methyl linoleate, isobergapten, and beta-sitosterol. AKT1, tumor necrosis factor (TNF), interleukin (IL)-6, GAPDH, and CTNNB1 were identified as the most crucial hub targets. Molecular docking revealed that the active components and hub targets exhibited strong binding energy. Experimental verification demonstrated that the mRNA and protein expression levels of IL-6, IL-17, and TNF in the WSXB group were lower than those in the KOA group (p < 0.05). WSXB exhibits a chondroprotective effect on OA and delays disease progression. The mechanism is potentially related to the suppression of IL-17 and TNF signaling pathways and the down-regulation of IL-6.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• BMB Reports
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• v.51 no.11
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• pp.602-607
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• 2018

Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. $NF-{\kappa}B$ activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating $NF-{\kappa}B$ p65, and this may provide a novel therapeutic approach for TNBC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.179-184
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• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2018.06a
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• pp.62-62
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• 2018

Pt is still considered as one of the most active electrocatalysts for ORR in alkaline fuel cells. However, the high cost and scarcity of Pt hamper the widespread commercialization of fuel cells. As a strong candidate for the replacement of Pt catalyst, silver (Ag) has been extensively studied due to its high activity, abundance, and low cost. Ag is more stable than Pt in the pH range of 8~14 as the equilibrium potential of Ag/Ag+ being ${\approx}200mV$ higher than that of Pt/PtO. However, Ag is the overall catalytic activity of Ag for oxygen reduction reaction(ORR) is still not comparable to Pt catalyst since the surface Ag atoms are approximately 10 times less active than Pt atoms. Therefore, further enhancement in the ORR activity of Ag catalysts is necessary to be competitive with current cutting-edge Pt-based catalysts. We demonstrate the architectural design of Ag catalysts, synthesized using plasma discharge in liquid phase, for enhanced ORR kinetics in alkaline media. An attractive feature of this work is that the plasma status controlled via electric-field could form the Ag nanowires or dendrites without any chemical agents. The plasma reactor was made of a Teflon vessel with an inner diameter of 80 mm and a height of 80 mm, where a pair of tungsten(W) electrodes with a diameter of 2 mm was placed horizontally. The stock solutions were made by dissolving the 5-mM AgNO3 in DI water. For the synthesis of Agnanowires, the electricfield of 3.6kVcm-1 in a 200-ml AgNO3 aqueous solution was applied across the electrodes using a bipolar pulsed power supply(Kurita, Seisakusyo Co. Ltd). The repetition rate and pulse width were fixed at 30kHz and 2.0 us, respectively. The plasma discharge was carried out for a fixed reaction time of 60 min. In case of Ag nanodendrites, the electric field of 32kVcm-1 in a 200-ml AgNO3 aqueous solution was applied and other conditions were identical to the plasma discharge in water in terms of electrode configuration, repetition rate and discharge time. Using SEM and STEM, morphology of Ag nanowires and dendrites were investigated. With 3.6 kV/cm, Ag nanowire was obtained, while Ag dendrite was constructed with 32 kV/cm. The average diameter and legth of Ag nanowireses were 50 nm and 3.5 um, and thoes values of Ag dendrites were 40 nm and 3.0 um. As a results of XPS analysis, the surface defects in the Ag nanowires facilitated O2 incorporation into the surface region via the interaction between the oxygen and the electron cloud of the adjacent Ag atoms. The catalytic activity of Ag for oxygen reduction reaction(ORR) showed that the catalytic ORR activity of Ag nanowires are much better than Ag nanodendrites, and electron transfer number of Ag nanowires is similar to that of Pt (${\approx}4$).

• Journal of The Korean Society of Grassland and Forage Science
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• v.19 no.1
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• pp.1-10
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• 1999

To find out the way to be able to prolong the grazing years of mixed pasture under Cheju summer-hot weather, an experiment designed with split plot (main plot : 3 cutting-plant height such as 15cm, 30cm and 45cm and sub plot : 4 white clover varieties such as Regal, Tahora, Brown and SRVR) was carried out at Cheju Agricultural Experiment Station during the period from Sept. 1994 to Oct. 1996 Dry matter yield in 15cm plant height in cutting dates has shown significantly lower increase than those in 30 and 45cm(P<0.05). There was highiy significant increase in dry matter yield of Brown plot when compared with other varieties of white clover in 2nd year(P<0.01). There was no difference on botanical composition of mixed sward as affected by plant height in cuttings dates in 2nd year. The percentage of white clover tends to lower in white clover varieties Brown and SRVR when compared with Regal and Tahora. The rate of weed was not affected by plant height in cutting dates and white clover variety in mixed pasture at last cutting time of 2nd year. In 15cm plant height, concentration of ADE and NDF was the lowest one while P contents was the highest one(P<0.01). Potassium contents was the lowest one in 30cm plant cutting height(P<0.05), and nitrogen showed statistically interaction between plant cutting height and white clover variety(P<0.01). White clover variety was no effective on concentration of constituents in mixed pastures. In conclusion, white clover variety SRVR harvested at 15cm plant height is effective on nutrient value of pasture and balance of grass and white clover in botanical composition.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.3
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• pp.360-368
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• 2015

The present study evaluated the effect of controlled ryegrass-white clover herbage availability from day 128 until day 142 of pregnancy in comparison to unrestricted availability, on the performance of twin-bearing ewes of varying body condition score (BCS; 2.0, 2.5, or 3.0) and their lambs. It was hypothesised that under conditions of controlled herbage availability, the performance of lambs born to ewes with a greater BCS would be greater than those born to ewes with a lower BCS. During the period that the nutritional regimens were imposed, the pre- and post-grazing herbage masses of the Control regimen ($1,070{\pm}69$ and $801{\pm}30$ kg dry matter [DM]/ha) were lower than the ad libitum regimen ($1,784{\pm}69$ and $1,333{\pm}33kg\;DM/ha$; p<0.05). The average herbage masses during lactation were $1,410{\pm}31kg\;DM/ha$. Nutritional regimen had no effect on ewe live weight, BCS and back fat depth or on lamb live weight, indices of colostrum uptake, maximal heat production, total litter weight weaned or survival to weaning (p>0.05). The difference in ewe BCSs and back fats observed among body condition groups was maintained throughout pregnancy (p<0.05). At weaning, ewes from the BCS2.0 group had lower BCS and live weight ($2.4{\pm}0.2$, $74.3{\pm}2.6kg$) than both the BCS2.5 ($2.6{\pm}0.2$, $78.6{\pm}2.4kg$) and BCS3.0 ewes ($2.7{\pm}0.2$, $79.0{\pm}2.6kg$; p<0.05), which did not differ (p>0.05). Ewe BCS group had no effect on lamb live weight at birth or weaning or on maximal heat production (p>0.05). Serum gamma glutamyl transferase concentrations of lambs born to BCS3.0 ewes were higher within 36 hours of birth than lambs born to BCS2.0 ewes and BCS2.5 ewes ($51.8{\pm}1.9$ vs $46.5{\pm}1.9$ and $45.6{\pm}1.9IU/mL$, respectively [p<0.05]). There was, however, no effect of ewe body condition on lamb plasma glucose concentration (p>0.05). Lamb survival was the only lamb parameter that showed an interaction between ewe nutritional regimen and ewe BCS whereby survival of lambs born to BCS2.5 and BCS3.0 ewes differed but only within the Control nutritional regimen ewes (p<0.05). These results indicate farmers can provide twin-bearing ewes with pre- and post-grazing ryegrass-white clover herbage covers of approximately 1,100 and 800 kg DM/ha in late pregnancy, provided that herbage covers are 1400 in lactation, without affecting lamb performance to weaning. The present results also indicate that under these grazing conditions, there is little difference in ewe performance within the BCS range of 2.0 to 3.0 and therefore they do not need to be managed separately.

• Economic and Environmental Geology
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• v.39 no.1 s.176
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• pp.27-38
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• 2006

To understand the geologic and hydrogeochemical controls on the occurrence of high fluoride concentrations in bedrock groundwaters of South Korea, we examined a total of 367 hydrochemistry data obtained from deep groundwater wells (avg. depth=600 m) that were drilled fur exploitation of hot springs. The fluoride concentrations were generally very high (avg. 5.65mg/L) and exceeded the Drinking Water Standard (1.5 mg/L) in $72\%$ of the samples. A significant geologic control of fluoride concentrations was observed: the highest concentrations occur in the areas of granitoids and granitic gneiss, while the lowest concentrations in the areas of volcanic and sedimentary rocks. In relation to the hydrochemical facies, alkaline $Na-HCO_3$ type waters had remarkably higher F concentrations than circum-neutral to slightly alkaline $Ca-HCO_3$ type waters. The prolonged water-rock interaction occurring during the deep circulation of groundwater in the areas of granitoids and granitic gneiss is considered most important for the generation of high F concentrations. Under such condition, fluoride-rich groundwaters are likely formed through hydrogeochemical processes consisting of the removal of Ca from groundwater via calcite precipitation and/or cation exchange and the successive dissolution of plagioclase and F-bearing hydroxyl minerals (esp. biotite). Thus, groundwaters with high pH and very high Na/Ca ratio within granitoids and granitic gneiss are likely most vulnerable to the water supply problem related to enriched fluorine.

• Korean Journal of Soil Science and Fertilizer
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• v.1 no.1
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• pp.89-115
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• 1968

1. The experiment was carried out for investigating the interaction between potassium nutrition and thermoperiod (as an environment regulating factor) in relation to behaviors of several nutrients including phosphorus-32 and Potassium-42 in IPOMOEA BATAS. 2. To obtain same condition to trace the behaviors of phosphorus and potassum-42 they were simultaneously incorporated to roots. The determination of each CPM by counting twice with adequate interval and calculating true CPM of each isotope according to different half-life, was carried out with satisfactory. 3. Some specific symptoms i.e, chlorosis and withering of growing point under the condition of lower potassium level were found and was accelerated by the low night temperature. 4. A manganese shortage in growing point of the lower potassium level was found by activiation analysis and very low distribution ratio of phosphorus-32 and potassium-42 in the growing point of the lower potassium level was manifested, though the contents of nitrogen, phosphorus, potassium, sodium and magnesium were not in great difference. 5. In addition to the low water content with appearence of "hard", shorterning internode and lower ratio of roots to shoot as well as the symptoms of potassium deficiency such as brown spot in leaf blade and necrosis of leaf margin were appeared at later stage of experiment at the lower potassium level. 6. Very stimulating vegetative growth, e.g, large plant length, leaf expansion, increasing node number and fresh weight as well as high ratio of roots to shoot, high water content was resulted in the condition of higher potassium level. 7. A specific interaction between higher potassium level and thermoperiod was found, that is, the largest tuber production and the largest ratio of roots to shoot were resulted in the combined condition of higher potassium level and constant temperature while the largest plant length, fresh weight etc. i.e. the most stimulative vegetative growth was resulted in the combined condition of higher potassium level and low night temperature. 8. Comparatively low water content in the former condition of stimulative tuber production was resulted(especially at the tuber thickening stage), while high water content in the latter condition of stimulative vegetation was resulted though the higher potassium level made generally high water contents. 9. The nitrogen contents of soluble and insoluble did not make distinct difference between the lower and higher potassium level. 10. Though the phosphorus contents were not distinctly different by the potassium level, the lower potassium level made the percentage of phosphorus increased at tuber forming stage accumulating more phosphorus in roots, while the higher potassium level decreased percentage of phosphorus at that stage. 11. The higher potassium level made distinctly high potassium contents than the lower potassium level and increased contents at the tuber forming stage through both conditions. 12. The sodium contents were low in the condition of higher potassium level than the lower potassium level and decreased at tuber forming stage in both conditions, on the contary of potassium. 13. Except the noticeable deficeney of manganese in the growing point of the lower potassium level, mangense and magnesium contents in other organs did not make distinct difference according to the potassium level. 14. Generally more uptake and large absorption rate of phosphorus-32 and potassium-42 were resulted at the higher potassium level, and the most uptake, and the largest absorption rate of phosphorus and potassium-42 (especially potassium-42 at tuber forming stage) were resulted in the condition of higher potassium level and constant temperature which made the highest tuber production. 15. The higher potassium level stimulated the translocation of phoshorus-32 and potassium-42 from roots to shoots while the lower potassium level suppressed or blocked the translocation. 16. Therefore, very large distribution rate of $p^{32}$, $K^{42}$ in shoot, especially, in growing point, compared with roots was resulted in the higher potassium level. 17. The lower potassium level suppressed the translocation of phosporus-32 from roots to shoot more than that of potassium-42. 18. The uptake of potassium-42 and translocation in IPOMOEA BATATAS were more vivid than phosphorus-32. 19. A specific interaction between potassium nutrition and thermoperiod which resulted the largest tuber production etc. was discussed in relation to behaviors of minerals and potasium-42 etc. 20. Also, the specific effect of the lower and higher potassium level on the growth pattern of IPOMOEA BATATAS were discussed in relation to behaviors of minerals and isotopes. 21. An emphasize on the significance of the higher potassium level as well as the interaction with the regulating factor and problem of potassium level (gradient) for crops product ion were discussed from the point of dynamical and variable function of potassium.

• KSBB Journal
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• v.6 no.3
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• pp.309-319
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• 1991

A continuous stirred tank membrane reactor(CSTMR ) was developed and optimized for the production of cod skin gelatin hydrolyzates using endo-protease Alcalase. A experimental design methodology was used to optimize the four performance variables: enzyme concentration, substrate concentration, permeate flux and reactor volume. All four variables studied had an effect on substrate conversion, with enzyme and substrate concentrations being predominant. Conversion increased with the increase in enzyme concentration, with the decrease in substrate concentration, at high volumes and low flux. A strong interaction was observed between enzyme and substrate concentrations and smaller interactions between enzyme and flux and substrate and flux. The optimum operating conditions for the CSTMR process for an initial substrate concentration for 10% were $50^{\circ}C$, pH 8, flux 7.3ml/min, residence time 82 min, and Alcalase to substrate ratio 0.02(w/w). A gradual decay in reactor activity during 8 hrs was 2.1% conversion/hr. Enzyme leakage through the 10, 000 MWCO membrane was 16% at $50^{\circ}C$ and 12% at $35^{\circ}C$, 6hrs. However, there was no apparent correlation between enayme leakage and substrate conversion. The Km value for the CSTMR was 20 times higher than the batch reactor. The productivity(expressed as mg product/mg enzyme) of the CSTMR was more than six fold higher than the batch at $50^{\circ}C$. The hydrolyzate was non-bitter.