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Induction of Nrf2/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4/7-JNK and p38 MAPK signaling pathways in HepG2 cells

  • Bak, Min Ji;Truong, Van-Long;Ko, Se-Yeon;Nguyen, Xuan Ngan Giang;Jun, Mira;Hong, Soon-Gi;Lee, Jong-Won;Jeong, Woo-Sik
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.423-430
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    • 2016
  • Background: The induction of cellular defensive genes such as phase II detoxifying and antioxidant enzymes is a highly effective strategy for protection against carcinogenesis as well as slowing cancer development. Transcription factor Nrf2 (nuclear factor E2-related factor 2) is responsible for activation of phase II enzymes induced by natural chemopreventive compounds. Methods: Red ginseng oil (RGO) was extracted using a supercritical $CO_2$ extraction system and chemical profile of RGO was investigated by GC/MS. Effects of RGO on regulation of the Nrf2/antioxidant response element (ARE) pathway were determined by ARE-luciferase assay, western blotting, and confocal microscopy. Results: The predominant components of RGO were 9,12-octadecadienoic acid (31.48%), bicyclo[10.1.0] tridec-1-ene (22.54%), and 22,23-dihydrostigmasterol (16.90%). RGO treatment significantly increased nuclear translocation of Nrf2 as well as ARE reporter gene activity, leading to upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1. Phosphorylation of the upstream kinases such as apoptosis signal-regulating kinase (ASK)1, mitogen-activated protein kinase (MAPK) kinase (MKK)4/7, c-Jun N-terminal kinase (JNK), and p38 MAPK were enhanced by treatment with RGO. In addition, RGO-mediated Nrf2 expression and nuclear translocation was attenuated by JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190. Conclusion: RGO could be used as a potential chemopreventive agent, possibly by induction of Nrf2/ARE-mediated phase II enzymes via ASK1-MKK4/7-JNK and p38 MAPK signaling pathways.

Effects of Polyurethane Coated Urea Supplement on In vitro Ruminal Fermentation, Ammonia Release Dynamics and Lactating Performance of Holstein Dairy Cows Fed a Steam-flaked Corn-based Diet

  • Xin, H.S.;Schaefer, D.M.;Liu, Q.P.;Axe, D.E.;Meng, Q.X.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.4
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    • pp.491-500
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    • 2010
  • Three experiments were conducted to investigate the effects of polyurethane coated urea on in vitro ruminal fermentation, ammonia release dynamics and lactating performance of Holstein dairy cows fed a steam-flaked corn-based diet. In Exp. 1, a dual-flow continuous culture was run to investigate the effect of polyurethane coated urea on nutrient digestibility, rumen fermentation parameters and microbial efficiency. Three treatment diets with isonitrogenous contents (13.0% CP) were prepared: i) feedgrade urea (FGU) diet; ii) polyurethane coated urea (PCU) diet; and iii) isolated soy protein (ISP) diet. Each of the diets consisted of 40% steam-flaked corn meal, 58.5% forages and 1.5% different sources of nitrogen. PCU and FGU diets had significantly lower digestibility of NDF and ADF (p<0.01) than the ISP diet. Nitrogen source had no significant effect (p = 0.62) on CP digestibility. The microbial efficiency (expressed as grams of microbial N/kg organic matter truly digested (OMTD)) in vitro of the PCU diet (13.0 g N/kg OMTD) was significantly higher than the FGU diet (11.3 g N/kg OMTD), but comparable with the ISP diet (14.7 g N/kg OMTD). Exp. 2, an in vitro ruminal fermentation experiment, was conducted to determine the ammonia release dynamics during an 8 h ruminal fermentation. Three treatment diets were based on steam-flaked corn diets commonly fed to lactating cows in China, in which FGU, PCU or soybean meal (SBM) was added to provide 10% of total dietary N. In vitro $NH_3-N$ concentrations were lower (p<0.05) for the PCU diet than the FGU diet, but similar to that for the SBM diet at all time points. In Exp. 3, a lactation trial was performed using 24 lactating Holstein cows to compare the lactating performance and blood urea nitrogen (BUN) concentrations when cows were fed PCU, FGU and SBM diets. Cows consuming the PCU diet had approximately 12.8% more (p = 0.02) dietary dry matter intake than those consuming the FGU diet. Cows fed the PCU diet had higher milk protein content (3.16% vs. 2.94%) and lower milk urea nitrogen (MUN) concentration (13.0 mg/dl vs. 14.4 mg/dl) than those fed the FGU diet. Blood urea nitrogen (BUN) concentration was significantly lower for cows fed the PCU (16.7 mg/dl) and SBM (16.4 mg/dl) diets than the FGU (18.7 mg/dl) diet. Cows fed the PCU diet had less surplus ruminal N than those fed the FGU diet and produced a comparable lactation performance to the SBM diet, suggesting that polyurethane coated urea can partially substitute soybean meal in the dairy cow diet without impairing lactation performance.

Effect of Colored Potato Flakes Against Acetaminophen-induced Liver Damage in Rats

  • Ohba, Kiyoshi;Watanabe, Shoko;Han, Kyu-Ho;Hashimoto, Naoto;Noda, Takahiro;Shimada, Ken-Ichiro;Tanaka, Hisashi;Sekikawa, Mitsuo;Fukushima, Michihiro
    • Food Science and Biotechnology
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    • v.16 no.3
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    • pp.463-469
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    • 2007
  • We examined the hepatoprotective effects of colored potato flakes on acetaminophen (AAP)-induced liver damage in rats. F344/DuCrj (8 week-old) rats were fed a cholesterol-free diet with 54.9486 g of ${\alpha}$-corn starch/100g diet and were orally treated with 25% colored flakes of Kitamurasaki (KM: light purple), Northern Ruby (NR: red), and Shadow Queen (SQ: medium purple) potatoes co-administered with AAP (0.5 g/100 g diet) for 4 weeks. The hepatic thiobarbituric acid-reactive substances (TBARS) values in the KM, NR, and SQ groups were significantly lower (p<0.05) than those in the control groups with and without AAP. Furthermore, the hepatic catalase, Mn-superoxide dismutase (SOD), and Cu/Zn-SOD mRNA levels in the KM, NR, and SQ groups were higher than those in the control groups with and without AAP. The present findings suggest that colored potato flakes are useful as a prophylactic agent against oxidative liver damage.

Microbial Conversion of Ginsenoside from the Extract of Korean Red Ginseng (Panax ginseng) by Lactobacillus sp.

  • Cho, Hye-Jin;Jung, Eun-Young;Oh, Sung-Hoon;Yoon, Brian;Suh, Hyung-Joo;Lee, Hyun-Sun
    • Preventive Nutrition and Food Science
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    • v.15 no.2
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    • pp.105-112
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    • 2010
  • Thirty-four strains of Lactobacillus species were isolated from soil and eight of these isolates (M1-4 and P1-4) were capable of growing on red ginseng agar. The M1 and P2 strains were determined to be L. plantarum and other strains (M2, M3, M4, P1, P3 and P4) were determined to be L. brevis. Fermentation of red ginseng extract (RGE) with strains M1, M2, P2 and P4 resulted in a low level of total carbohydrate content (174.3, 170.0, 158.8 and 164.8 mg/mL, respectively). RGE fermented by M3 showed a higher level of uronic acid than the control. The polyphenol levels in RGE fermented by M1, P1 and P2 (964.9, 941.7 and $965.3\;{\mu}g/mL$, respectively) were higher than the control ($936.8\;{\mu}g/mL$). Total saponin contents in fermented RGE (except M1) were higher than the control. RGE fermented by M2 and M3 had the highest levels of total ginsenosides (31.7 and 32.7 mg/mL, respectively). The levels of the ginsenoside Rg3 increased from 2.6 mg/mL (control) to 3.0 mg/mL (M2) or 3.1 mg/mL (M3). RGE fermented by M2 and M3 also had the highest levels of Rg5+Rk1 (7.7 and 8.3 mg/mL, respectively). Metabolite contents of ginsenoside (sum of CK, Rh1, Rg5, Rk1, Rg3 and Rg2) of M2 (13.0 mg/mL) and M3 (13.9 mg/mL) were also at a high level among the fermented RGE. Protopanaxadiol and protopanaxatriol content of ginsenoside of M2 (10.9 and 5.4 mg/mL, respectively) and M3 (11.0 and 5.7 mg/mL, respectively) were at higher levels than other fermented RGE.

Cyanobacterial Bioassay (AGP test) on the Water Fertility of Treated Wastewater Effluents Discharged into Euiam and Paldang Reservoirs, Korea (의암호 및 팔당호에 유입되는 주요 하수처리 방류수의 수질 비옥도 생물검정: Algal Growth Potential(AGP) Test)

  • Seo, Wanbum;Lee, Su-Woong;Kim, Keonhee;Park, Chaehong;Choi, Bong-Geun;Sim, Yeon Bo;Hwang, Soon-Jin;Shin, Jae-Ki
    • Korean Journal of Ecology and Environment
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    • v.50 no.1
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    • pp.79-95
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    • 2017
  • Euiam and Paldang Reservoirs have often been facing water quality problems, such as eutrophication, algal blooms and off-flavors by treated wastewater effluent (TWE) in the North-Han and the Han River basins, but little is examined on the direct biological effect of TWE. This study tested algal growth potential (AGP) of four TWEs discharged into Euiam and Paldang Reservoirs to evaluate water fertility in September 2014 and March and September 2015. Test alga was used Anabaena circinalis isolated from Paldang Reservoir. Mean concentration of T-N and T-P in TWEs was $3,956.7{\mu}g\;N\;L^{-1}$ and $50.8{\mu}g\;P\;L^{-1}$, and the proportion of $NO_3-N$ and $PO_4-P$ to the total fraction was 72.1% and 40.8%, respectively. Both N and P were high in TWEs, but much higher N than P concentration indicates strong P-limitation. As a consequence, the maximum AGP was determined by $PO_4-P$ concentration (r=0.998, p<0.01). Mean AGP value was $15.4mg\;dw\;L^{-1}$ among four effluents indicating its eutrophic condition. Due to the establishment of tertiary (advanced T-P) treatment method in the studied plants recently, P concentration was significantly decreased in TWEs compared to the years prior to 2012. However, P concentration seems to be still high enough to cause eutrophication and algal blooms. Therefore, wastewater treatment to P-free level needs to be considered if effluents are directly discharged into the drinking water resources.

A Case of Citrin Deficiency Presenting with Recurrent Hypoglycemia: Diagnosed by Targeted Exome Sequencing (반복적인 저혈당으로 엑솜 시퀀싱을 통해 31개월에 진단된 Citrin 결핍증 1례)

  • Kim, Chiwoo;Hwang, Jeongyun;Yang, Aram;Kim, Jinsup;Lee, Taeheon;Jang, Ja-Hyun;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.2
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    • pp.69-76
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    • 2017
  • Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

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Protective effect of STAR of STAR series on CCl4 induced acute hepatotoxicity by regulation of reactive oxygen species (활성산소종의 조절을 통한 음료 '별의별간'의 급성간독성 보호효과)

  • Chang, Bo Yoon;Oh, Jun Seok;Han, Ji Hye;Kim, Da Eun;Hong, Jae Heoi;Kim, Sung Yeon
    • Food Science and Preservation
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    • v.23 no.2
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    • pp.275-282
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    • 2016
  • STAR of STAR (SS 01-04) is a series of drinks that consist of various extracts obtained from Coriolus versicolor, Artemisia capillaris Thunb., Hovenia dulcis, Acanthopanax sessiliflorus, Lycium chinense, Citrus reticulata, Saururus chinensis, Pueraria lobata, Pyrus pyrifolia, and Oenanthe javanica. A purpose of this study was to investigate the hepatoprotective effect of SS 01-04. Antioxidant activity of the drinks was evaluated by conducting a hydroxyl radical-scavenging assay. Cytotoxicity and hepatoprotective potential were determined using HepG2 cells in vitro, while protective effects against acute hepatotoxicity was evaluated in vivo. The antioxidant activity of the SS 01-04 at concentration of 100 and 250 mg/mL was similar to that of $50{\mu}M$ vitamin C. tert-Butyl hydroperoxide (tBHP)-induced production of reactive oxygen species (ROS) was blocked by SS 01, 03 and 04 in a dose-dependent manner. Treatment with SS 04 significantly lowered the serum levels of alanine aminotransferase and aspartate aminotransferase in an animal model of carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity (p<0.05). In addition, SS04 increased glutathione level while decreased malondialdehyde level in the liver considerably (p<0.05). It also inhibited the $CCl_4-induced$ increase in the levels of triglyceride and cholesterol in serum and the liver. These findings indicated that SS 01-04 possessed antioxidant activity and protect against ROS. In particular, SS 04 is potentially highly beneficial in treating liver damage as it scavenges reactive free radicals and boosts the endogenous antioxidant system.

Purification Characteristics and Hydraulic Conditions in an Artificial Wetland System (인공습지시스템에서 수리학적 조건과 수질정화특성)

  • Park, Byeng-Hyen;Kim, Jae-Ok;Lee, Kwng-Sik;Joo, Gea-Jae;Lee, Sang-Joon;Nam, Gui-Sook
    • Korean Journal of Ecology and Environment
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    • v.35 no.4 s.100
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    • pp.285-294
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    • 2002
  • The purpose of this study was to evaluate the relationships between purification characteristics and hydraulic conditions, and to clarify the basic and essential factors required to be considered in the construction and management of artificial wetland system for the improvement of reservoir water quality. The artificial wetland system was composed of a pumping station and six sequential plants beds with five species of macrophytes: Oenanthe javanica, Acorus calamus, Zizania latifolia, Typha angustifolia, and Phragmites australis. The system was operated on free surface-flow system, and operation conditions were $3,444-4,156\; m^3/d$ of inflow rate, 0.5-2.0 hr of HRT, 0.1-0.2 m of water depth, 6.0-9.4 m/d of hydraulic loading, and relatively low nutrients concentration (0.224-2.462 mgN/L, 0.145-0.164 mgP/L) of inflow water. The mean purification efficiencies of TN ranged from 12.1% to 14.3% by showing the highest efficiency at the Phragmites australis bed, and these of TP were 6.3-9.5% by showing the similar ranges of efficiencies among all species. The mean purification efficiencies of SS and Chl-A ranged from 17.4% to 38.5% and from 12.0% to 20.2%, respectively, and the Oenanthe javanica bed showed the highest efficiency with higher concentration of influent than others. The mean purification amount per day of each pollutant were $9.8-4.1\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in BOD, $1.299-2.343\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in TN, $0.085-1.821\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in TP, $17.9-111.6\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in SS and $0.011-0.094\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in Chl-a. The purification amount per day of TN revealed the hi링hest level at the Zizania latifolia bed, and TP showed at the Acrous calamus bed. SS and Chl-a, as particulate materials, revealed the highest purification amount per day at the Oenanthe javanica bed that was high on the whole parameters. It was estimated that the purification amount per day was increased with the high concentration of influent and shoot density of macrophytes, as was shown in the purification efficiency. Correlation coefficients between purification efficiencies and hydraulic conditions (HRT and inflow rate) were 0.016-0.731 of $R^2$ in terms of HRT, and 0.015-0.868 of $R^2$ daily inflow rate. Correlation coefficients of purification amounts per day with hydraulic conditions were 0.173-0.763 of Ra in terms of HRT, and 0.209-0.770 daily inflow rate. Among the correlation coefficients between purification efficiency and hydraulic condition, the percentages of over 0.5 range of $R^2$ were 20% in HRT and in daily inflow rate. However, the percentages of over 0.5 range of correlation coefficients ($R^2$) between purification amount per day and hydraulic conditions were 53% in HRT and 73% in daily inflow rate. The relationships between purificationamount per day and hydraulic condition were more significant than those of purifi-cation efficiency. In this study, high hydraulic conditions (HRT and inflow rate) are not likely to affect significantly the purification efficiency of nutrient. Therefore, the emphasis should be on the purification amounts per day with high hydraulicloadings (HRT and inflow rate) for the improvement of eutrophic reservoir withrelatively low nutrients concentration and large quantity to be treated.

Physicochemical characteristics and volatile flavor compounds of produced mixture wine with kiwi and permission fruits using wild yeast, Saccharomyces cerevisiae Y28 (야생 효모 Saccharomyces cerevisiae Y28을 이용하여 제조한 참다래-대봉감 혼합과실주의 이화학적 특성 및 향기성분)

  • Lee, Hee Yul;Seo, Weon Taek;Jeong, Seong Hoon;Hwang, Chung Eun;Ahn, Min Ju;Lee, Ae Ryeon;Shin, Ji Hyun;Lee, Joo Young;Jo, Hyeon Kook;Cho, Kye Man
    • Korean Journal of Microbiology
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    • v.52 no.1
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    • pp.98-109
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    • 2016
  • The study was aimed to investigate the mixing ratio of kiwi and persimmon juices for the production of good quality wine by Saccharomyces cerevisiae Y28. Firstly, the optimum condition of rapidase treatment for the kiwi and persimmon juices was established, thereafter various mixing ratio (10:0, 9:1, 8:2, 7:3, 6:4, 5:5) of kiwi and persimmon was investigated regarding physiochemical properties and flavor compounds of wine. As the result, the optimum conditions were obtained as 0.3% rapidase for 1 h in kiwi and 0.3% rapidase for 3 h in persimmon. According to higher ration of persimmon, the pH of wines increased from 3.69 to 3.77, while the acidity of wines decreased from 2.07% to 1.51% at 14 days fermentation. The ranges of brix and reducing sugar in wines were decreased which ranges around 9.6 to 8.8 and 6.07 to 6.90 g/L, respectively, after fermentation. Major organic acid in wines were identified as tartaric acid, malic acid, and citric acid. A small amount of free sugar such as sucrose and glucose were detected in wines, but fructose was completely absent. The soluble phenolic contents were decreased that ranges around 1.00 to 1.25 g/L, in contrast, browning degree were increased ranges around 0.212 to 0.412 after fermentation. The major flavor components were identified as ethyl acetate and hydrazine, and 1,1-dimethyl. Importantly, phenylethyl alcohol was detected from the all wines that have a typical rose like flavor. But sensory test results and preference of kiwi-persimmon (7:3) mixing wine was better than the other wines.

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

  • Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4983-4988
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    • 2013
  • Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.