• 제목/요약/키워드: CpG

검색결과 928건 처리시간 0.036초

Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling

  • Ham, Won-Kook;Lee, Eun-Jung;Jeon, Myung Shin;Kim, Hae-Young;Agrahari, Gaurav;An, Eun-Joo;Bang, Chul Hwan;Kim, Doo-Sik;Kim, Tae-Yoon
    • BMB Reports
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    • 제54권2호
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    • pp.142-147
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    • 2021
  • Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)-induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.

The Effect of Level of Crude Protein and Available Lysine on Finishing Pig Performance, Nitrogen Balance and Nutrient Digestibility

  • Ball, M.E.E.;Magowan, E.;McCracken, K.J.;Beattie, V.E.;Bradford, R.;Gordon, F.J.;Robinson, M.J.;Smyth, S.;Henry, W.
    • Asian-Australasian Journal of Animal Sciences
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    • 제26권4호
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    • pp.564-572
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    • 2013
  • Two trials were conducted to investigate the effect of decreasing the crude protein (CP) content of diets for finishing pigs containing two levels of available lysine on nutrient digestibility, nitrogen (N) balance and production performance. Ten finishing diets containing five levels of CP (on average 144, 155, 168, 182 and 193 g/kg fresh basis) and two levels of available lysine (6.9 and 8.2 g/kg fresh basis) were formulated. The diets were offered to pigs on a performance trial (n = 800 Large White (LW)${\times}$Landrace (LR) pigs) from 10 wk of age until finish at 21 wks+5 d of age. Average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) were calculated. In addition, a digestibility/N balance trial was conducted using pigs (n = 80 $LW{\times}LR$) housed in metabolism crates. Digestibility of dry matter (DM), CP, oil, fibre and energy was determined. N balance values were determined through analysis of N content of urine and faeces ('as determined'). N balance values were also calculated using ADG values and assuming that 16% of growth is protein deposition ("as calculated"). Pig performance was poor between 10 and 13 wk of age which indicated that the dietary treatments were nutritionally inadequate for pigs less than 40 kg. There was a significant (p<0.01) quadratic effect of increasing CP level on feed intake, ADG and FCR from 10 to 13 wk which indicated that the lower CP levels did not supply adequate levels of essential or non-essential amino acids. There was no effect of increasing available lysine level throughout the early period, which in conjunction with the response in older pigs, suggested that both 8.2 and 6.9 g/kg available lysine were insufficient to drive optimum growth. There was a positive response (p<0.05) to increasing available lysine level from 13 wk to finish which indicated that 6.9 g/kg available lysine was not adequate for finishing pigs. Energy digestibility decreased with decreasing CP level of diets containing 6.9 g/kg available lysine which may be attributed to the higher fibre content of the lower CP diets. Nitrogen excretion (g/d) was lowered when dietary CP was reduced regardless of whether the values were determined through balance or calculated using ADG. Calculated N excretion decreased linearly (p<0.001) and quadratically (p<0.001) with decreasing dietary CP content. When the N balance figures calculated in this study were compared with those quoted in the Northern Ireland and English Nitrates Directive Action Programmes, N excretion was less per pig (wean to finish) offered a 169 g/kg CP, 8.2 g/kg available lysine diet (2.39 kg vs 3.41 kg (Northern Ireland) and 2.93 kg (England)).

In vitro and in vivo Antibacterial Activities and Pharmacokinetics of 8-Fluorociprofloxacin and Ciprofloxacin (8-Fluorociprofloxacin과 Ciprofloxacin의 시험관내 및 생체내 항균효과와 약물동태의 비교)

  • 최경업;정용환;김제학
    • YAKHAK HOEJI
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    • 제37권3호
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    • pp.235-242
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    • 1993
  • 8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

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Three-step in vitro digestion model for evaluating and predicting fecal odor emission from growing pigs with different dietary protein intakes

  • Lo, Shih-Hua;Chen, Ching-Yi;Wang, Han-Tsung
    • Animal Bioscience
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    • 제35권10호
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    • pp.1592-1605
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    • 2022
  • Objective: The objective of this study was to select an effective in vitro digestion-fermentation model to estimate the effect of decreasing dietary crude protein (CP) on odor emission during pig production and to suggest potential prediction markers through in vitro and in vivo experiments. Methods: In the in vitro experiment, three diet formulations with different CP contents (170 g/kg, 150 g/kg, and 130 g/kg) but containing the same standardized ileal digestible essential amino acids (SID-EAA) were assessed. Each diet was evaluated by two different in vitro gastric-intestinal phase digestion methods (flask and dialysis), combined with fresh pig feces-ferment inoculation. Eighteen growing barrows (31.9±1.6 kg) were divided into three groups: control diet (180 g CP/kg, without SID-EAA adjustment), 170 g CP/kg diet, and 150 g CP/kg diet for 4 weeks. Results: The in vitro digestion results indicated that in vitro digestibility was affected by the gastric-intestinal phase digestion method and dietary CP level. According to the gas kinetic and digestibility results, the dialysis method showed greater distinguishability for dietary CP level adjustment. Nitrogen-related odor compounds (NH3-N, indole, p-cresol, and skatole) were highly correlated with urease and protease activity. The feeding study indicated that both EAA-adjusted diets resulted in a lower odor emission especially in p-cresol and skatole. Both protease and urease activity in feces were also closely related to odor emissions from nitrogen metabolism compounds. Conclusion: Dialysis digestion in the gastric-intestinal phase followed by fresh fecal inoculation fermentation is suitable for in vitro diet evaluation. The enzyme activity in the fermentation and the fecal samples might provide a simple and effective estimation tool for nitrogen-related odor emission prediction in both in vitro and in vivo experiments.

Silencing of Disabled-2 Gene by CpG Methylation in Human Breast Cancer Cell Line, MDA MB-231 Cells (사람의 유방암 세포주인 MDA MB-231 세포에서 CpG 메칠화에 의한 Disabled-2유전자의 발현억제)

  • Ko Myung Hyun;Oh Yu Mi;Park Jun Ho;Jeon Byung Hoon;Han Dong Min;Kim Won Sin
    • Journal of Life Science
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    • 제15권5호
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    • pp.802-808
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    • 2005
  • Human Disabled-2 (Dab2) is a candidate tumor suppressor gone that regulates cell growth by c-Fos suppression in normal cells. In many cancer cells, Dab2 expression is lost or greatly diminished in $\∼85\%$ of the breast and ovarian cancers. In this study, we have examined the methylation status of CpG island on Dab2 gene promoter using bisulfite-assisted genomic sequencing and methylation specific PCR (MSP) method in human breast cancer cell line, MDA MB-231 cells. In normal human uterus endometrial cells, Dab2 was completely unmethylated. In contrast, Dab2 was methylated on CpG dinucleotides near the TATA_ box in MDA MB-231 cells. following MDA MB-231 cells by treatment with 5-azacytidine, Dab2 gene were demethylated and reexpressed. Result of this study suggested that silencing of Dab2 gene is correlated to CpG island methylation in human breast cancer cell line, MBA MD-231 cells.

Effect of Choice Feeding on the Nutrient Intake and Performance of Broiler Ducks

  • Men, Bui Xuan;Ogle, Brian;Lindberg, Jan Erik
    • Asian-Australasian Journal of Animal Sciences
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    • 제14권12호
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    • pp.1728-1733
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    • 2001
  • An experiment was conducted at the experimental duck farm of Cantho University in the Mekong Delta of Vietnam to evaluate the effects of offering pairwise feeds with different crude protein (CP) levels to Cherry Valley broiler ducks from 28-63 days of age on feed intake and performance. Five diets consisting of mixtures of soya bean meal, fish meal, maize meal and fine rice bran, were formulated to give isocaloric diets with 30, 24, 18, 16 and 12% CP. These were offered separately as pellets to growing ducklings in the following combinations: 30+18, 30+12, 24+16 and 18+12. A diet with 20% CP (CP20) was used as control. All the diets were offered ad libitum. Daily feed intakes (g dry matter, DM) were 161, 168, 150, 101 and 143 g for the 30+18, 30+12, 24+16, 18+12 and CP20 treatments, respectively. CP intakes were 29.6, 27.0, 24.8, 17.1 and 22.9% of total DM intake, and the ratio of methionine+cystine to lysine was 0.76, 0.75, 0.75, 0.76 and 0.75 for the 30+18, 30+12, 24+16, 18+12 and CP20 treatments, respectively. Live weights at 63 days of age were 2,937, 3,054, 2,898, 2,200, and 2,811 g (p<0.001), and daily live weight gains 57.8, 61.7, 57.0, 38.5 and 55.7 g (p<0.001) for the 30+18, 30+12, 24+16, 18+12 and CP20 treatments, respectively. The weights and yields of the carcass, breast and thigh muscles, and heart decreased in the order 30+18, 30+12, 24+16, CP20 and 18+12 (p<0.001). The present study suggests that growing broiler offered a combination of high and low protein feeds pairwise will eat excessive amounts of the high protein feed, thus resulting in protein intakes above requirements.

Study on the Determination of Crude Protein Requirement for Maintenance of fattening Black Goat(Capra hircus coreanae) (비육기 흑염소의 유지를 위한 조단백질 요구량 결정에 관한 연구)

  • Yun, Yeong Sik;Jang, Se Young;Seong, Hye Jin;Tang, Yu Jiao;Ding, Yu Ling;Park, Jae Hyun;Moon, Sang Ho
    • Journal of The Korean Society of Grassland and Forage Science
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    • 제37권2호
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    • pp.176-182
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    • 2017
  • This study was conducted to evaluate the protein requirement for maintenance of fattening Korean black goat (Capra hircus coreanae). Six male goats with average initial body weight (BW) of $31.78{\pm}4.54kg$ and an average age of 8 months were used in this study. The experiment had a replicated duplicated $3{\times}3$ Latin square design for balancing carryover effects. In the course of the experiment, each of Black goats were fed three diets that were formulated to contain T1 (13%), T2 (16%) and T3 (19%) levels of crude protein (CP). A 14-day diet adjustment period was followed by a 5-day collection period. Dry matter intake (DMI) of groups fed diets with T2 was 966.67g/d which was higher than group fed diets with T1 and T3 were 925.14g/d and 936.08g/d each. Average daily gains (ADG) of black goats were the highest in T2(167.13g/d) But, there was no significant difference. Dietary protein levels affected the apparent digestibility of CP (p<0.05). A significant difference was found in CP intake among treatments and goats receiving T3, T2, and T1 recorded 181.23, 154.57, and 128.78g CP/d, respectively. This was excepted because CP intake is proportional to CP content of diet, which from highest to lowest was as follows: T3 (19%) > T2 (16%) > T1 (13%). Intercept of the regression equation between CP intake and CP balance indicated that maintenance CP requirement was 1.63g/BW0.75.

Adjuvant effect of liposome-encapsulated natural phosphodiester CpG-DNA

  • Kim, Dong-Bum;Kwon, Sang-Hoon;Ahn, Chi-Seok;Lee, Young-Hee;Choi, Soo-Young;Park, Jin-Seu;Kwon, Hyeok-Yil;Kwon, Hyung-Joo
    • BMB Reports
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    • 제44권11호
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    • pp.758-763
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    • 2011
  • Immunostimulatory CpG-DNA targeting TLR9 is one of the most extensively evaluated vaccine adjuvants. Previously, we found that a particular form of natural phosphodiester bond CpG-DNA (PO-ODN) encapsulated in a phosphatidyl-${\beta}$-oleoyl-${\gamma}$-palmitoyl ethanolamine (DOPE) : cholesterol hemisuccinate (CHEMS) (1 : 1 ratio) complex (Lipoplex(O)) is a potent adjuvant. Complexes containing peptide and Lipoplex(O) are extremely useful for B cell epitope screening and antibody production without carriers. Here, we showed that IL-12 production was increased in bone marrow derived dendritic cells in a CpG sequence-dependent manner when PO-ODN was encapsulated in Lipoplex(O), DOTAP or lipofectamine. However, the effects of Lipoplex(O) surpassed those of PO-ODN encapsulated in DOTAP or lipofectamine and also other various forms of liposome-encapsulated CpG-DNA in terms of potency for protein antigen-specific IgG production and Th1- associated IgG2a production. Therefore, Lipoplex(O) may have a unique potent immunoadjuvant activity which can be useful for various applications involving protein antigens as well as peptides.

Effects of Antibrowning agents on browning of apple slices during cold storage (냉장저장 중 사과 슬라이스의 갈변에 미치는 갈변저해제의 효과)

  • Ahn Sun-Choung;Lee Gui-Chu
    • Korean journal of food and cookery science
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    • 제21권1호
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    • pp.24-32
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    • 2005
  • Changes in apple slices during cold storage were investigated by evaluating the physical properties such as degree of browning and compression force. Chemical properties such as PPO activity and total phenol contents were also determined and sensory evaluation was carried out. The correlation analysis between browning parameters was conducted. Degree of browning was increased in the order of fresh apple slice, water-dipped apple slice, $0.5\%$ ascorbic acid solution-dipped apple slice and CP(caramelization product) from sucrose-dipped apple slice. PPO activity was increased in the order of fresh apple slice, water-dipped apple slice, $0.5\%$ ascorbic acid solution-dipped apple slice and CP(caramelization product) from sucrose-dipped apple slice. Amongst several treatments, CP from sucrose-dipped apple slice showed the lowest degree of browning and PPO activity. Total phenol contents were decreased from 60 to 56.2 mg and from 59.6 to 56.0 mg in fresh apple slice and water-dipped apple slice, respectively, but CP from sucrose-dipped apple slice and $0.5\%$ ascorbic acid solution-dipped apple slice were increased from 51.9 to 52.8 mg and from 54.1 to 54.4 mg, respectively, showing the smallest changes when compared with fresh apple slice and water-dipped apple slice. Compression forces of apple slices during cold storage were decreased in the order of fresh apple slice, water-dipped apple slice, $0.5\%$ ascorbic acid solution-dipped apple slice and CP from sucrose-dipped apple slice. In sensory evaluation of apple slices during cold storage, CP from sucrose-dipped apple slice had higher score than the other treatments. In addition, a significant correlation was observed among degree of browning, PPO activity and phenol content. Therefore, CP from sucrose-dipped apple slice seems to be effective in controlling of enzymatic browning during cold storage. In addition, CP from sucrose-dipped apple slice seems to be effective on other several factors. These results suggest that CP from sucrose should be a potential source for controlling enzymatic browning during storage of vegetables and fruits.

Crude Protein Requirements for Maintenance of Hanwoo Steers by Protein Balance Trial (단백질 균형시험에 의한 한우 거세우의 유지 조단백질 요구량)

  • 김경훈;오영균;이상철;신기준;강수원;문여황;송만강
    • Journal of Animal Science and Technology
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    • 제48권4호
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    • pp.533-540
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    • 2006
  • This experiment was conducted to determine crude protein requirements for maintenance (CPm) of growing Hanwoo steers. Eighteen Hanwoo steers (173.7kg) were allocated randomly to diets with three levels of crude protein in the concentrate by replacing ground corn with corn gluten meal: 0% (LCP), 7.2% (MCP) and 14.2% (HCP), respectively. Hanwoo steers in each treatment were fed diets containing rice straw (20%) and concentrates (80%). CP intake was 5.5, 7.8 and 10.7g/BW0.75 for LCP, MCP and HCP, respectively. Protein balance was -0.05, 2.36 and 4.07g/BW0.75 for LCP, MCP and HCP, respectively. Intercept of the regression equation between CP intake and retained CP indicated that CPm was 5.56g/BW0.75. The estimate of CPm adopted by Korean Feeding Standard (2002) was almost 20% higher than that adopted by Japanese Feeding Standard for Beef Cattle (2000); this would need to be verified with more feeding trial data set including protein requirements for growth.