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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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    • v.54 no.2
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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.

Physicochemical properties of deposited particles on surface of pine leaves as biomarker for air pollution (솔잎가지 표면에 침착된 입자상 물질의 물리화학적 특성 및 대기오염 지표로서의 가능성 고찰)

  • Chung, David;Choi, Jeong-Heui;Lee, Jang-Ho;Lee, Soo-Yong;Lee, Ha-Eun;Park, Ki-Wan;Shim, Kyu-Young;Lee, Jong-Chun
    • Analytical Science and Technology
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    • v.31 no.6
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    • pp.247-258
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    • 2018
  • The purpose of the present study was to investigate whether the degree of air pollution can be evaluated via examination of local plants. Selected sites included two parks in an industrial area, as well as two parks in an urban area. Selected plant samples comprised one-year-old pine shoot leaves. Leaves growing over 2 m from the ground were collected from over 10 pine trees. Leaf surface was analyzed for deposition of 14 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs), including particle size and mass, surface imaging, precipitation-mediated particle removal rate, and concentration. Particle size ranged from 0.4 to $200{\mu}m$, and the volume percentage of particles ${\leq}10$ was 20 %. Deposited particle mass ranged from 0.450-0.825 mg, and precipitation-mediated removal rate ranged from 10.0-27.6 %. Trace element concentration, as measured by ICP/MS after microwave acid digestion, was 18.8-26.3 mg/kg As, 0.08-0.13 mg/kg Be, 0.06-0.08 mg/kg Cd, 4.91-17.8 mg/kg Cr, 5.26-405 mg/kg Cu, 1,930-2,670 mg/kg Fe, 3.03-28.1 mg/kg Pb, 26.9-42.8 mg/kg Mn, 2.66-10.4 mg/kg Ni, 4,560-8,730 mg/kg Al, 2,500-6,120 mg/kg Ba, 5.27-17.8 mg/kg Rb, 40.9-95.3 mg/kg Sr, and 4,030-8,260 mg/kg Zn. Concentration of PAHs, as analyzed by GC/MS/MS after liquid-liquid extraction and purification of deposited particles, ranged from 1.17 to 12.378 mg/kg for ${\Sigma}PAH_{16}$ and from 1.17 to 12.378 mg/kg for ${\Sigma}PAH_7$.

Geochemical Origin, Behavior and Enrichment of Environmental Toxic Elements in Coaly Metapelite from the Deokpyeong Area, Korea (덕평지역의 탄질 변성니질암에 관한 환경적 독성원소의 지구화학적 기원, 거동 및 부화)

  • Lee, Hyun Koo;Lee, Chan Hee
    • Economic and Environmental Geology
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    • v.30 no.6
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    • pp.553-566
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    • 1997
  • Origin, behavior and enrichment of environmental toxic elements from the Deokpyeong area were investigated on the basis of major, trace and rare earth element geochemistry. Coaly metapelites of the Deokpyeong area are subdivided into grey phyllite, dark grey phyllite, coaly slate and black slate, which are interbedded along the Ogcheon Supergroup. The coaly slate had been mined for coal, but mining is closed. The coaly and black slates are lower contents of $SiO_2$ and $Al_2O_3$, and higher contents of LOI, CaO, $Na_2O$ and BaO as compared with the phyllitic rocks. Rare earth elements are highly enriched in the coaly and black slate. Average compositions (ppm) of minor and/or environmental toxic elements in the coaly and black slate are revealed as As=127, Ba=30,163, Cd=18, Cr=740, Cu=84, Mo=378, Pb=43, Sb=12, Se=44, U=144, V=8,147 and Zn=292, which are extremely high concentrations than those in the NASC compositions. Major elements (average enrichment index; 5.34) in the coaly metapelites are mostly depleted, excepting $P_2O_5$ and BaO, normalized by NASC. Rare earth elements (average enrichment index; 1.48) are enriched in the coaly slate. On the basis of NASC, minor and/or environmental toxic elements in the coaly metapelites were strongly enriched of all the elements with the exception of Co, Cs, Ni and Sr. Average enrichment index of trace elements in coaly metapelite is 31.51 (coaly slate; 51.94 and black slate; 15.46). Especially, enrichment index of potentially toxic elements (As, Ba, Cr, Cu, Mo, Ni, Sb, Se, U, V and Zn) of the rock is 46.10 (grey phyllite; 7.15, dark grey phyllite; 4.77, coaly slate; 88.96 and black slate; 22.11). These coal formations were deposited in basin of boundary between terrestrial and marine environments deduced to carbon, sulfur (C/S=2.2 to 275.7), trace and rare earth elements characteristics. Irregular behavior and dispersion between major, minor and rare earth elements of those metapelites indicates a variable source materials, incomplete mixing of differential source and/or reequilibrium of diagenesis and metamorphism.

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Effects of Moxi-tar Herbal Acupuncture of LI11 on inflammatory bowel disease induced by TNBS in mice (TNBS로 유도된 대장염에서 곡지의 구진약침 효과)

  • Song, Moon-Young;Park, Sang-Yeon;Kim, Jae-Hyo;Ahn, Sung-Hun;Kim, Kyoung-Sik;Sohn, In-Chul
    • Korean Journal of Acupuncture
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    • v.25 no.3
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    • pp.147-166
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    • 2008
  • Objectives : Crohn's disease (CD) is characterized by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Methods : Mice (preventive animal model of gliotoxin) were treated with 5 % 2,4,6-trinitrobenzenesulfonic acid (TNBS) at day 1 and day 7. To investigate preventive effects of acupuncture with Gujin at $LI_{11}$, acupuncture was carried out at day -1, day 1, day 3. And, to investigate therapeutic effects, acupuncture with Gujin was carried out at day 3, day 5, day 7. For the data analysis, we checked weight and width of colon, diarrhea, edema, survival rate, changes of body weight, and myeloperoxygenase (MPO) activity. For analysing protein expression, we carried out immunohistochemical staining and Western blot and we analyzed mRNA expression by RT-PCR. Results : Colon of TNBS treated mice was erosive and shortening compared with the colon of control mice and induced damages of colon epithelial cell layer and induced infiltration of immune cells in all layer of colon. Acupuncture of gujin at $LI_{11}$ in preventive mode suppressed macorscopic damages such as erosive and shortening of colon by TNBS and damages of intestinal epithelial cells and infiltration of immune cells in the colon. The average weight of 5 cm distal colon was increased in TNBS treated mice (758${\mu}g$) compared with in control mice (112${\mu}g$) and width of distal colon was also increased in TNBS treated mice (4.9mm) compared with in control mice (1.3mm). Acupuncture with Gujin at $LI_{11}$ in preventive and therapeutic mode suppressed increase of colon weight and width by TNBS. TNBS induced edema of colon and diarrhea and Acupunctured with Gujin at $LI_{11}$ in preventive and therapeutic mode ameliorated these symptom by TNBS. In preventive and therapeutic mode, the effects of acupuncture with Gujin at $LI_{11}$ were increasing the motility, suppressing body weight decreasing, suppressing MPO activity, reducing expressing of TNF-${\alpha}$, IL-1b, and ICAM-1 in colon compared with that by TNBS Conclusions : This study demonstrates that acupuncture with Gujin at $LI_{11}$ represents a potential therapeutic method of Crohn's disease.

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A Novel Pyrazolo[3,4-d]pyrimidine Induces Heme Oxygenase-1 and Exerts Anti-Inflammatory and Neuroprotective Effects

  • Lee, Ji Ae;Kwon, Young-Won;Kim, Hye Ri;Shin, Nari;Son, Hyo Jin;Cheong, Chan Seong;Kim, Dong Jin;Hwang, Onyou
    • Molecules and Cells
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    • v.45 no.3
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    • pp.134-147
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    • 2022
  • The anti-oxidant enzyme heme oxygenase-1 (HO-1) is known to exert anti-inflammatory effects. From a library of pyrazolo[3,4-d]pyrimidines, we identified a novel compound KKC080096 that upregulated HO-1 at the mRNA and protein levels in microglial BV-2 cells. KKC080096 exhibited anti-inflammatory effects via suppressing nitric oxide, interleukin1β (IL-1β), and iNOS production in lipopolysaccharide (LPS)-challenged cells. It inhibited the phosphorylation of IKK and MAP kinases (p38, JNK, ERK), which trigger inflammatory signaling, and whose activities are inhibited by HO-1. Further, KKC080096 upregulated anti-inflammatory marker (Arg1, YM1, CD206, IL-10, transforming growth factor-β [TGF-β]) expression. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated mice, KKC080096 lowered microglial activation, protected the nigral dopaminergic neurons, and nigral damage-associated motor deficits. Next, we elucidated the mechanisms by which KKC080096 upregulated HO-1. KKC080096 induced the phosphorylation of AMPK and its known upstream kinases LKB1 and CaMKKbeta, and pharmacological inhibition of AMPK activity reduced the effects of KKC080096 on HO-1 expression and LPS-induced NO generation, suggesting that KKC080096-induced HO-1 upregulation involves LKB1/AMPK and CaMKKbeta/AMPK pathway activation. Further, KKC080096 caused an increase in cellular Nrf2 level, bound to Keap1 (Nrf2 inhibitor protein) with high affinity, and blocked Keap1-Nrf2 interaction. This Nrf2 activation resulted in concurrent induction of HO-1 and other Nrf2-targeted antioxidant enzymes in BV-2 and in dopaminergic CATH.a cells. These results indicate that KKC080096 is a potential therapeutic for oxidative stress-and inflammation-related neurodegenerative disorders such as Parkinson's disease.

Growth, Body shape and Carcass cutting yield traits of Duroc and Crossbred(Duroc×Pietrain×Pietrain)pigs (두록과 교잡돈(두록×피어트레인×피어트레인)의 성장, 체형형질 및 도체 부분육 생산량 비교)

  • Kim, Young Sin;Kim, JeongA;Jeong, Yong Dae;Choi, Yo Han;Cho, Eun Seok;Chung, Hak Jae;Sa, Soo Jin;Beak, Sun Young;Hong, Joon Ki
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.7
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    • pp.255-261
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    • 2020
  • This study was undertaken to evaluate the growth, body shape and carcass cutting yield traits of Duroc (D) and crossbred (Duroc×Pietrain×Pietrain; DPP) pigs. A total of 147 D and 101 DPP pigs were used for analyzing the growth trait, whereas 16 D and 16 DPP pigs were evaluated for carcass yields. Backfat thickness (BF) and average daily feed intake (ADFI) were significantly higher in D (14.07±0.24 mm, 2,101 g) than in DPP (12.69±3.25 mm, 1,909 g) (p <0.001). Moreover, D exhibited significantly higher body shape traits including body height (BH), chest depth (CD) and chest width (CW), as compared to DPP pigs (p <0.001). No differences were observed for body length (BL) between the two strains. Analysis of the carcass cutting yield traits determined for D and DPP were in the order: ham (HM; 31.17% and 33.43%), belly (BY; 23.40% and 19.55%), and picnic shoulder (PS; 16.54% and 16.87%), respectively. Then, HM showed a difference of 2.26% P with D(31.17%) and DPP(33.43%), while BY showed a difference of 3.85% P with D(23.40%) and DPP(19.55%). Taken together, our results indicate that DPP has a better feed efficiency than D, and therefore has the potential to increase the production of low-fat pork, targeting consumers having a high preference who have opted for a healthy lifestyle. These results can be used as basic data for developing an ideal pig breed.

The Monitoring on Plasticizers and Heavy Metals in Teabags (침출용 티백 포장재의 안전성에 관한 연구)

  • Eom, Mi-Ok;Kwak, In-Shin;Kang, Kil-Jin;Jeon, Dae-Hoon;Kim, Hyung-Il;Sung, Jun-Hyun;Choi, Hee-Jung;Lee, Young-Ja
    • Journal of Food Hygiene and Safety
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    • v.21 no.4
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    • pp.231-237
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    • 2006
  • Nowadays the teabag is worldwide used for various products including green tea, tea, coffee, etc. since it is convenient for use. In case of outer packaging printed, however, there is a possibility that the plasticizers which is used for improvement in adhesiveness of printing ink may shift to inner tea bag. In this study, in order to monitor residual levels of plasticizers in teabags, we have established the simultaneous analysis method of 9 phthalates and 7 adipates plasticizers using gas chromatography (GC). These compounds were also confirmed using gas chromatography-mass spectrometry (GC-MSD). The recoveries of plasticizers analyzed by GC ranged from 82.7% to 104.6% with coefficient of variation of $0.6\sim2.7%$ and the correlation coefficients of each plasticizer was $0.9991\sim0.9999$. Therefore this simultaneous analysis method was showed excellent reproducibility and linearity. And limit of detection (LOD) and limit of quantitation (LOQ) on individual plasticizer were $0.1\sim3.5\;ppm\;and\;0.3\sim11.5\;ppm$ respectively. When 143 commercial products of teabag were monitored, no plasticizers analysed were detected in filter of teabag products. The migration into $95^{\circ}C$ water as food was also examined and the 16 plasticizers are not detected. In addition we carried out analysis of heavy metals, lead (Pb), cadmium (Cd), arsenic (As) and aluminum (Al) in teabag filters using ICP/AES. $Trace\sim23{\mu}g$ Pb per teabag and $0.6\sim1718{\mu}g$ Al per teabag were detected in materials of samples and Cd and As are detected less than LOQ (0.05 ppm). The migration levels of Pb and Al from teabag filter to $95^{\circ}C$ water were upto $11.5{\mu}g\;and\;20.8{\mu}g$ per teabag, respectively and Cd and As were not detected in exudate water of all samples. Collectively, these results suggest that there is no safety concern from using teabag filter.

Geochemistry and Water Quality in the Tidal Flat of Saemangum Area, West Sea of Korea in Summer (하계 새만금 갯벌의 수질 분포 및 지화학적 특성에 관한 연구)

  • Park, Gyung Soo;Park, Soung Yun;Lee, Sam Geun;Lee, Yoon
    • Journal of Wetlands Research
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    • v.6 no.1
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    • pp.133-147
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    • 2004
  • Environmental quality(water and sediment) was analyzed in the tidal flat of Saemangum of Jeonbuk Province, the west coast of Korea, using the 101 sediment samples and 69 water samples collected in September 4~13, 2001. Major water quality parameters with the means of 69 surface water samples are as follows; $25.51{\pm}0.68^{\circ}C$ for water temperature, $29.88{\pm}5.01$ for salinity, $1.40{\pm}0.78mg/L$ for COD, $0.352{\pm}0.417mg/L$ for DIN, and $0.027{\pm}0.023mg/L$ for phosphate, respectively. Higher values were found at the subestuary of Dongjin and Mangyung River, and lower values at the Saemangum embayment and Gomso Bay. There was a significant negative correlation between salinity and the other water quality parameters(p<0.0001) such as COD, nutrients, SS and N/P. This correlation suggested that the major pollution sources be from terrestrial inputs through tributaries in this area. Principal component analysis clearly revealed a spatial variation of water quality; stations with higher values of nutrients and COD located subestuary of tributaries. 14 sediment quality parameters including 8 trace metals were measured using the 101 surface sediment samples. Average values for the parameters are as follows; Al $2.28{\pm}0.92%$, Cd $0.61{\pm}0.27ppm$, Cu $8.95{\pm}4.06ppm$, Fe $1.19{\pm}0.37%$, Mn $182.31{\pm}77.45ppm$, Ni $10.83{\pm}4.97ppm$, Pb $15.20{\pm}4.35ppm$, Zn $41.34{\pm}34.62ppm$, COD $2.68{\pm}1.85mg/g\;dry$, AVS $0.04{\pm}0.08mg/g\;dry$, IL $1.29{\pm}1.08%$, water content $24.11{\pm}4.49%$, TN $0.02{\pm}0.02%$, TC $0.22{\pm}0.30%$. Spatial variations of sediment quality were not clear as water quality. Some higher values were found at the subestuary of Gum River and lower values at the other area. There was a significant positive correlation between the heavy metal concentrations and organic materials within the sediment(p<0.05). Enrichment factors showed the ranges of 1~2 for most of the metals in the sediment except zinc(1~6), indicating no serious exogenous input of heavy metals in the study area. Also, the heavy metal concentrations in the sediment were within the ranges found at the natural marine environments.

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