• Title/Summary/Keyword: mrp

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In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.911-920
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    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

Apoptotic Effect of Ethanol Extracts of Bojungbangamtang and Acidic Polysaccharide of Korea Red Ginseng in a MCF7/adR Multidrug-resistance Breast Cancer Cells (항암제 내성 유방암 MCF7/adR 세포주에 대한 보정방암탕과 홍삼산성다당체의 세포고사 유도효과)

  • Ahn, Gyu-In;Park, Cheol-Hwan;Lee, Eun-Ok;Lee, Hyo-Jung;Lee, Jae-Ho;Kim, Kwan-Hyun;Rhee, Yun-Hee;Jang, Yu-Sung;Kim, Sang-Tae;Kim, Sung-Hoon
    • YAKHAK HOEJI
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    • v.50 no.4
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    • pp.272-277
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    • 2006
  • This study was undertaken to determine whether the 9 herbal complex induces apoptosis in human breast cancer MCF-7 cells and adriamycin-resistant MCF7/adR cells. Ethanol extracts of Bojungbangamtang (BBTE) and acidic polysaccharide of Red Ginseng (GIN) induced cell death in both MCF-7 and MCF7/adR cells. Ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng also induced $G_2/M$ cell cycle arrest and increased TUNEL positive cells in MCF7/adR cells. In addition, flow cytometric analysis revealed the decreased expression of P-glycoprotein (P-gp) in ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng treated MCF7/adR cells. Similarly, decreased protein levels of P-glycoprotein and multidrug resistance associated proteins-1 were also determined by immunocytometry in ethanol extracts of Bojungbangamtang treated MCF7/adR cells. Taken together these data indicate that ethanol extracts of Bojungbangamtang and acidic polysaccharide of Red Ginseng inhibit the function of ABC transporters such as multi drug resistance associated proteins (MRPs) and P-glycoprotein as well as induce apoptosis in MCF7/adR cells. Thus, these data suggest that ethanol extracts of Bojungbangamtang and polysaccharide of Red Ginseng can be candidates for the treatment of multidrug-resistant MCF7/adR cells.

A Scheme of Data-driven Procurement and Inventory Management through Synchronizing Production Planning in Aircraft Manufacturing Industry (항공기 제조업에서 생산계획 동기화를 통한 데이터기반 구매조달 및 재고관리 방안 연구)

  • Yu, Kyoung Yul;Choi, Hong Suk;Jeong, Dae Yul
    • The Journal of Information Systems
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    • v.30 no.1
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    • pp.151-177
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    • 2021
  • Purpose This paper aims to improve management performance by effectively responding to production needs and reducing inventory through synchronizing production planning and procurement in the aviation industry. In this study, the differences in production planning and execution were first analyzed in terms of demand, supply, inventory, and process using the big data collected from a domestic aircraft manufacturers. This paper analyzed the problems in procurement and inventory management using legacy big data from ERP system in the company. Based on the analysis, we performed a simulation to derive an efficient procurement and inventory management plan. Through analysis and simulation of operational data, we were able to discover procurement and inventory policies to effectively respond to production needs. Design/methodology/approach This is an empirical study to analyze the cause of decrease in inventory turnover and increase in inventory cost due to dis-synchronize between production requirements and procurement. The actual operation data, a total of 21,306,611 transaction data which are 18 months data from January 2019 to June 2020, were extracted from the ERP system. All them are such as basic information on materials, material consumption and movement history, inventory/receipt/shipment status, and production orders. To perform data analysis, it went through three steps. At first, we identified the current states and problems of production process to grasp the situation of what happened, and secondly, analyzed the data to identify expected problems through cross-link analysis between transactions, and finally, defined what to do. Many analysis techniques such as correlation analysis, moving average analysis, and linear regression analysis were applied to predict the status of inventory. A simulation was performed to analyze the appropriate inventory level according to the control of fluctuations in the production planing. In the simulation, we tested four alternatives how to coordinate the synchronization between the procurement plan and the production plan. All the alternatives give us more plausible results than actual operation in the past. Findings Based on the big data extracted from the ERP system, the relationship between the level of delivery and the distribution of fluctuations was analyzed in terms of demand, supply, inventory, and process. As a result of analyzing the inventory turnover rate, the root cause of the inventory increase were identified. In addition, based on the data on delivery and receipt performance, it was possible to accurately analyze how much gap occurs between supply and demand, and to figure out how much this affects the inventory level. Moreover, we were able to obtain the more predictable and insightful results through simulation that organizational performance such as inventory cost and lead time can be improved by synchronizing the production planning and purchase procurement with supply and demand information. The results of big data analysis and simulation gave us more insights in production planning, procurement, and inventory management for smart manufacturing and performance improvement.

Effect of puffing treatment on the quality characteristics of bee pollen and its addition to wheat flour-puff yeot-gangjeong (팽화처리가 화분 및 이를 첨가한 밀엿강정의 품질특성에 미치는 영향)

  • Lee, Jiyea;Surh, Jeonghee
    • Korean Journal of Food Science and Technology
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    • v.54 no.3
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    • pp.306-312
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    • 2022
  • To test bee pollen as an ingredient for heat-processed foods, bee pollen was puffed under heat at various pressures and examined for its physicochemical properties and antioxidant activities. As the puffing intensity increased, the browning index, total reducing capacity, and DPPH radical scavenging activity of the bee pollen increased significantly (p<0.001). This was attributed to the formation of Maillard reaction products during the puffing process. The wheat flour-puff yeot-gangjeong added with puffed bee pollen showed significantly (p<0.01) higher antioxidant activities than its counterpart with raw bee pollen. In addition, the gangjeong retained the physicochemical characteristics of the puffed bee pollen such as color, soluble solids, titratable acidity, and pH. The results showed that the puffed bee pollen could potentially be used as an ingredient in thermally processed foods and retain its superior antioxidant properties.

Influence on Composting of Waste Mushroom Bed from Agaricus bisporus by using Mixed Organic Materials (혼용자재 특성이 양송이 폐상배지를 이용한 퇴비제조에 미치는 영향)

  • Kyung, Ki-Cheon;Lee, Hee-Duk;Jung, Young-Pil;Jang, Kab-Yeul;Yoon, Min-Ho
    • Korean Journal of Soil Science and Fertilizer
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    • v.43 no.3
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    • pp.335-340
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    • 2010
  • This study was conducted to select organic materials (OM) and nitrogen sources in composting of waste mushroom bed from Agaricus bisporus. We examined physio-chemical properties of the organic materials and the mixture ratio for preparing the wasted mushroom bed (M) compost. The carbon content of sawdust was higher than those of rice straw (R) as OM source and the nitrogen content was high in the order of fowl manure (F)>> pig manure (P)> cow manure (C). The compost was prepared to maintain the criteria of above 25% organic matter and then the change of their ingredients was estimated during the process of fermentation. The temperature of waste mushroom bed+pig manure+rice straw (MRP) treatment was varied fast throughout fermentation, on the other hand the temperature of waste mushroom bed+pig manure+sawdust (MSP) treatment was steadily elevated to the middle of composting. The pH of the compost was somewhat high to pH 8.5~9.0 at the early stage, but decreased to 7.5 at the end stage of composting. The content of OM after fermentation was decreased to the level of 19~21% in rice straw, but the sawdust treatment maintained 25~27% organic matter. The waste mushroom bed+fowl manure+rice straw (MRF) treatment, which contains 26.2% organic matter and 0.68% nitrogen, was the highest among them. The volume of compost was reduced to 50% by using rice straw as organic matter, but reduced to 30% by using the sawdust. The contents of heavy metal in the compost were suitable within the legal criteria. The number of microorganisms were higher in the rice straw than those in the sawdust. It was high in the order of fowl manure> pig manure> cow manure. The major groups consisted of aerobic bacteria, gram negative bacteria and Bacillus sp. and their populations after fermentation were increased to $1{\times}10^1{\sim}1{\times}10^2\;cfu\;g^{-1}$ rather than those before fermentation. Therefore we concluded that the waste mushroom bed+fowl manure+sawdust (MSF 3:9:1 v/v/v) treatment was suitable combination for high organic matter and nitrogen source, and the periods of composting were 50~60 days.

Effects of Salt and Soysauce Condiment on Lipid Oxidation in Broiled Mackerel (Scomber japonicus) (소금과 간장 양념이 고등어 구이의 지질산화 안정성에 미치는 영향)

  • Ryu, Seung-Hee;Lee, Young-Soon;Moon, Gap-Soon
    • Korean Journal of Food Science and Technology
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    • v.34 no.6
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    • pp.1030-1035
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    • 2002
  • Despite health benefits derived from fish oil, polyunsaturated fatty acids (PUFAs) contained in fish oil are susceptible to lipid oxidation. To determine the optimum condition for maintaining good quality cooked fish during storage, mackerels were broiled with salt or soysauce condiments, and the lipid oxidation during 12 days of storage at refrigerated condition was measured. Peroxide value of broiled mackerel group with salt significantly increased after immediate cooking and maintained higher value throughout the storage period compare to the soysauce-added group, but showed similar value to the control group. Conjugated diene content in the soysauce-group was lower than the control and salt-added groups. Malondialdehyde content of broiled mackerel increased twofold and showed similar values in soysauce-added and the control groups during storage, whereas increased in the salt-added group significantly. Fatty acid compositions of the three mackerel groups changed after cooking, whereas that of the control group was almost stable during storage. In comparison with raw mackerel, the ratio of PUFA and saturated fatty acids decreased significantly, and the content of n-3 family fatty acid decreased from 25.53 to 20.63% in salted broiled mackerel. Soysauce group showed no reduction of PUFA with increasing storage time and showed the highest ratio of n-3/n-6 among the three groups at 10 days storage. Results reveal soysauce condiment protects against lipid peroxidation of broiled mackerel. Maillard reaction products (MRPs) found in soysauce might be responsible for the inhibitory effect and is a good condiment for extending storage life of cooked fish containing high amount of PUFA.

Effects of Anti-thyroglobulin Antibody on the Measurement of Thyroglobulin : Differences Between Immunoradiometric Assay Kits Available (면역방사계수법을 이용한 Thyroglobulin 측정시 항 Thyroglobulin 항체의 존재가 미치는 영향: Thyroglobulin 측정 키트에 따른 차이)

  • Ahn, Byeong-Cheol;Seo, Ji-Hyeong;Bae, Jin-Ho;Jeong, Shin-Young;Yoo, Jeong-Soo;Jung, Jin-Hyang;Park, Ho-Yong;Kim, Jung-Guk;Ha, Sung-Woo;Sohn, Jin-Ho;Lee, In-Kyu;Lee, Jae-Tae;Kim, Bo-Wan
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.4
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    • pp.252-256
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    • 2005
  • Purpose: Thyroglobulin (Tg) is a valuable and sensitive tool as a marker for diagnosis and follow-up for several thyroid disorders, especially, in the follow-up of patients with differentiated thyroid cancer (DTC). Often, clinical decisions rely entirely on the serum Tg concentration. But the Tg assay is one of the most challenging laboratory measurements to perform accurately owing to antithyroglobulin antibody (Anti-Tg). In this study, we have compared the degree of Anti-Tg effects on the measurement of Tg between availale Tg measuring kits. Materials and Methods: Measurement of Tg levels for standard Tg solution was performed with two different kits commercially available (A/B kits) using immunoradiometric assay technique either with absence or presence of three different concentrations of Anti-Tg. Measurement of Tg for patient's serum was also performed with the same kits. Patient's serum samples were prepared with mixtures of a serum containing high Tg levels and a serum containg high Anti-Tg concentrations. Results: In the measurements of standard Tg solution, presence of Anti-Tg resulted in falsely lower Tg level by both A and B kits. Degree of Tg underestimation by h kit was more prominent than B kit. The degree of underestimation by B kit was trivial therefore clinically insignificant, but statistically significant. Addition of Anti-Tg to patient serum resulted in falsely lower Tg levels with only A kit. Conclusion: Tg level could be underestimated in the presence of anti-Tg. Anti-Tg effect on Tg measurement was variable according to assay kit used. Therefore, accuracy test must be performed for individual Tg-assay kit.

Effect of Verapamil on Cellular Uptake of Tc-99m MIBI and Tetrofosmin on Several Cancer Cells (수종의 암세포에서 Verapamil이 Tc-99m MIBI와 Tetrofosmin의 섭취에 미치는 영향)

  • Kim, Dae-Hyun;Yoo, Jung-Ah;Suh, Myung-Rang;Bae, Jin-Ho;Jeong, Shin-Young;Ahn, Byeong-Cheol;Lee, Kyu-Bo;Lee, Jae-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.1
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    • pp.85-98
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    • 2004
  • Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.