• Title/Summary/Keyword: Cd tolerance

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Insights into the Role of Follicular Helper T Cells in Autoimmunity

  • Park, Hong-Jai;Kim, Do-Hyun;Lim, Sang-Ho;Kim, Won-Ju;Youn, Jeehee;Choi, Youn-Soo;Choi, Je-Min
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.21-29
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    • 2014
  • Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

Chemical Composition of Cultured and Wild Codonopsis lanceolata Roots of Different Age Groups -I. Proximate Composition, Minerals and Protein Fractions- (더덕(沙蔘)의 년근별(年根別) 화학성분(化學成分)에 관(關)한 연구(硏究) -제1보(第1報) : 일반성분(一般成分), 무기질(無機質) 및 단백질(蛋白質) 분획(分劃)-)

  • Park, Boo-Duck;Park, Yong-Gone;Choi, Kwang-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.14 no.3
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    • pp.274-279
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    • 1985
  • Proximate compositions, minerals and protein fractions of the roots of cultured and wild Codonopsis lanceolata of different age groups were examined as the basic research for the study of their source of processed foods. The most abundant proximate composition of the roots of C. lanceolata was observed to be total sugars and next come crude protein, crude fiber, crude fat and ash in descending order irrespective of cultured and wild ones. The richest mineral contained in the roots was noticed to be K and followed by Mg and Ca. Generally increased tendency of crude protein, fat, ash, K, Mg, Ca, Mn, Zn, Cu and P contents were observed with older roots, however, decreased total sugars and Fe content. Lead and cadmium content was far bellow the authorized tolerance limits. The quantitative fractionation of the protein of the roots ranked albumin the highest content, followed by globuin, prolamin and glutelin. Decreased albumin content was observed with the older age roots, while increased globulin, prolamin and glutelin content. The minimum solubility of the soluble protein of the roots was found to be at pH 4.0 and maximum, at pH 10.0. Disc gel electrophoresis of the soluble protein of C. lanceolata roots showed almost similar patterns and numbers of bands. The molecular weight for main band protein was estimated to be about 90,000.

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Preclinical Study of DA-5018, a Non-narcotic Analgesic Agent

  • Kim, Soon-Hoe
    • Proceedings of the PSK Conference
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    • 2000.04a
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    • pp.70-81
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    • 2000
  • DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

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Risk Assessment of As, Cd, Cu and Pb in Different Rice Varieties Grown on the Contaminated Paddy Soil (중금속 오염 논토양에서 재배된 벼 품종간 위해성평가 비교)

  • Kim, Won-Il;Kim, Jin-Kyoung;Yoo, Ji-Hyock;Paik, Min-Kyoung;Park, Sang-Won;Kwon, Oh-Kyung;Hong, Moo-Ki;Yang, Jay-E;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.42 no.1
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    • pp.53-57
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    • 2009
  • Heavy metal pollution may be one of the most serious challenges confront crop production and human health. Therefore, the selection of heavy metal tolerance cultivars which adapted to the contaminated fields will introduced a suitable solution for management this critical environmental risk. The objectives of this research is to assess human health risk using geochemical analyses and exposure assessment of heavy metals in rice cultivars. Risk for inhabitants in the closed mine area was comparatively assessed for As, Cd, Cu and Pb in 10 rice varieties as a major exposure pathway. The average daily dose (ADD) of each heavy metal was estimated by analyzing the exposure pathways to rice and soil. For the non-carcinogenic risk characterization, Hazard Quotient (HQ) and Hazard Index (HI) were calculated using toxicity indices provided by US-EPA IRIS. The different rice varieties revealed a wide range of HI values from 23.6 to 34.3, indicating that all rice varieties have a high potential toxic risk. The DA rice variety showed the lowest HI value while the TB rice variety the highest. The probabilities of cancer risk for As via rice consumption were varied with rice varieties ranging from 2.0E-03 to 3.5E-03 which exceeded the regulatory acceptable risk of 1 in 10,000 set by US-EPA. The DA rice variety also showed the lowest value while the TB rice variety gave the highest value. Our results indicate that risk assessment can be contribute to screen the pollution safe rice cultivars in paddy fields affected by the mining activity.