• Title/Summary/Keyword: Cd tolerance

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Targeted Immunotherapy for Autoimmune Disease

  • Seung Min Jung;Wan-Uk Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.9.1-9.23
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    • 2022
  • In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

Studies on the Cellular Immune Response in Animal Model of Arthritis after the Induction of Oral Tolerance (콜라겐으로 경구 관용을 유도한 관절염 동물 모델의 세포 특이적 면역 반응 조사)

  • Min, So-Youn;Hwang, Sue-Yun;Lee, Jae-sun;Kim, Ju-Young;Lee, Kang-Eun;Kim, Kyung-Wun;Kim, Young-Hun;Do, Ju-Ho;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.136-144
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    • 2003
  • Oral administration of antigen has long been considered as a promising alternative for the treatment of chronic autoimmune diseases including rheumatoid arthritis (RA), and oral application of type II collagen (CII) has been proven to improve pathogenic symptoms in RA patients without problematic side effects. To further current understandings about the immune suppression mechanisms mediated by orally administered antigens, we examined the changes in IgG subtypes, T-cell proliferative response, and proportion of interleukin (IL)-10 producing Th subsets in a time course study of collagen induced arthritis (CIA) animal models. We found that joint inflammation in CIA mouse peaked at 5 weeks after first immunization with CII, which was significantly subdued in mice pre-treated by repeated oral administration of CII. Orally tolerized mice also showed increase in their serum level of IgG1, while the level of IgG2a was decreased. T-cell proliferation upon CII stimulation was also suppressed in lymph nodes of mice given oral administration of CII compared to non-tolerized controls. When cultured in vitro in the presence of CII, T-cells isolated from orally tolerized mice presented higher proportion of $CD4^+IL-10^+$ subsets compared to non-tolerized controls. Interestingly, such increase in IL-10 producing cells were obvious first in Peyer's patch, then by 5 weeks after immunization, in mesenteric lymph node and spleen instead. This result indicates that a particular subset of T-cells with immune suppressive functions might have migrated from the original contact site with CII to inflamed joints via peripheral blood after 5 weeks post immunization.

Trace Metal Contents in Cultured and Wild fishes from the Coastal Area of Tongyeoung, Korea and their Safely Evaluations (통영연근해역 양식산 및 자연산 어류 중의 미량금속 함량 및 안전성 평가)

  • Choi Jong-Duck;Jeoung In-geon
    • Journal of Food Hygiene and Safety
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    • v.20 no.4
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    • pp.205-210
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    • 2005
  • The content of the trace metals in the cultured and wild fishes were determined. The tested fishes were genuin porgy (Pagrus major) and black porgy (Acanthopogrus schlegeli). The samples of the cultured and wild fishes were collected from slices of raw fish in shops, during 2003 to 2004. The samples were digested with acids, then analyzed by ICP (inductively Coupled plasma Spectrometer) and AAS (Automic Absorption Spectrometer) for the content of lead (Pb), cadmium (Cd), arsenic (As), copper (Cu), manganese (Mn) and zinc (Zn). The content of mercury (Hg) was determined using mercury analyzer. The mean contents of trace metals in cultured and wild fish was 0.031,0.047mg/kg far total-mercury,0.321,0.407 for Pb, 0.048,0.063 for Cd, 1.006, 1.132 for As, 0.467,0.806 for Cu, 0.233, 0.293 for Cr, 9.69, 12.20 for Zn,0.798, 0.624 mg/kg far Mn, respectively. The content of all the trace metals except manganese in wild fish was more than that in cultured fish. The highest level of total-mercury, lead, cadmium, zinc, chromium and arsenic in the samples analyzed were all below the quarantine limit of Korean regulation and guideline established by the U.S. Food and Drug Administration f3r human consumption. The level of the trace metals in the samples was negligible, which could be endogenous. Our data obtained in this study showed that the average weekly intakes of lead, cadmium and mercury from cultured and wild fishes takes about $6\∼13\%$ of Un(Provisional Tolerance Weekley Intakes) that FAO/WHO Joint Food Additive and Contaminants Committee has set to evaluate their safeties.

A Study of Entomopathogenic Nematode at Heavy Metal Contents in the Polluted Soil of Kyungsangbuk-do Area (경상북도지역의 오염된 토양에서의 중금속 함량에 관한 곤충병원성 선충에 관한 연구)

  • 한상미;황경숙;백하주;김무식;한명세
    • Korean Journal of Environmental Biology
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    • v.20 no.4
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    • pp.360-365
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    • 2002
  • The variety and density of entomopathogenic nematodes from the polluted soils of heavy metals were examined. In order to investigate the pollution of heavy metals in soil, 300 sites in kyungsangbuk-do were collected from March to October in 2001. We measured the contents of seven heavy metal elements (Cd, Cu, As, Hg, Pb, Cr^{6+}$, CN) and than cheesed soil of 25 sites with high concentration of heavy metals. The seven strains of nematodes were isolated from seven samples by silkworm host (Bombyx mori mori) and white trap. Isolated nematodes are composed of two families, one order. The members of Rhabditida were isolated in the soil with mean Cd content of 0.870 ppm. And they were isolated in the soil samples with As content less than 0.745 ppm. However they were isolated regardless of concentration of Cu and Pb. The members of Cylindrocorpidae were isolated in the soil samples with Cr^{6+}$ content less than 0.05 ppm. Any entomopathogenic nematode was not detected in the CN polluted soil. Isolated nematodes successfully cultured on the silkworm host and were confirmed the pathogenicity, multiplicity, and tolerance against various condition of preservation. Which proved its potential usefulness as biological agent.

Generation of single stranded DNA with selective affinity to bovine spermatozoa

  • Vinod, Sivadasan Pathiyil;Vignesh, Rajamani;Priyanka, Mani;Tirumurugaan, Krishnaswamy Gopalan;Sivaselvam, Salem Nagalingam;Raj, Gopal Dhinakar
    • Animal Bioscience
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    • v.34 no.10
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    • pp.1579-1589
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    • 2021
  • Objective: This study was conducted to generate single stranded DNA oligonucleotides with selective affinity to bovine spermatozoa, assess its binding potential and explore its potential utility in trapping spermatozoa from suspensions. Methods: A combinatorial library of 94 mer long oligonucleotide was used for systematic evolution of ligands by exponential enrichment (SELEX) with bovine spermatozoa. The amplicons from sixth and seventh rounds of SELEX were sequenced, and the reads were clustered employing cluster database at high identity with tolerance (CD-HIT) and FASTAptamer. The enriched nucleotides were predicted for secondary structures by Mfold, motifs by Multiple Em for Motif Elicitation and 5' labelled with biotin/6-FAM to determine the binding potential and binding pattern. Results: We generated 14.1 and 17.7 million reads from sixth and seventh rounds of SELEX respectively to bovine spermatozoa. The CD-HIT clustered 78,098 and 21,196 reads in the top ten clusters and FASTAptamer identified 2,195 and 4,405 unique sequences in the top three clusters from the sixth and seventh rounds, respectively. The identified oligonucleotides formed secondary structures with delta G values between -1.17 to -26.18 kcal/mol indicating varied stability. Confocal imaging with the oligonucleotides from the seventh round revealed different patterns of binding to bovine spermatozoa (fluorescence of the whole head, spot of fluorescence in head and mid- piece and tail). Use of a 5'-biotin tagged oligonucleotide from the sixth round at 100 pmol with 4×106 spermatozoa could trap almost 80% from the suspension. Conclusion: The binding patterns and ability of the identified oligonucleotides confirms successful optimization of the SELEX process and generation of aptamers to bovine spermatozoa. These oligonucleotides provide a quick approach for selective capture of spermatozoa from complex samples. Future SELEX rounds with X- or Y- enriched sperm suspension will be used to generate oligonucleotides that bind to spermatozoa of a specific sex type.

Pesticides, heavy metals, radioactive substances, and ash of Poria cocos distributed in Korea (국내 유통 복령(Poria cocos)의 농약, 중금속, 방사선물질 및 회분 함량 조사 연구)

  • Jang, Eun-Kyoung;Jang, Hye-Mi;Wi, Chang-Heun;Ban, Seung-Eon
    • Journal of Mushroom
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    • v.19 no.4
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    • pp.294-299
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    • 2021
  • The purpose of this study is to provide basic data on the safety of Poria cocos, a major Korean herbal medicine, and to establish tolerance levels for hazardous substances. Residual pesticides (321 types), heavy metals (7 types), radioactivity (3 types), and ash content were analyzed in 10 Poria cocos products distributed in Korea (5 domestic and 5 in China). Of the residual pesticides, cypermethrin was detected at 0.03 mg/kg in one domestic sample and was below the standard value. Of the heavy metals, the levels of Zn, Pb, Ni, Cu, Hg, and Cr were below the standard values in all samples. Hg was not detected in any sample. Cd was detected at 0.011 mg/kg in one Chinese sample. The radioactivity concentration was also below the MDA value in all P. cocos samples. The ash content was less than the standard value of 1.0% in all P. cocos samples. The findings indicate that P. cocos distributed in Korea is safe. However, because P. cocos is always exposed to harmful substances because of the nature of its cultivation in the soil, it seems necessary to establish systematic management standards for the entire production stage, such as cultivation, storage, and distribution.

Load-balanced Topology Maintenance with Partial Topology Reconstruction (부분 토폴로지 재구성 기법을 적용한 부하 균형 토폴로지 유지)

  • Hong, Youn-Sik;Lim, Hwa-Seok
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.35 no.12A
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    • pp.1188-1197
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    • 2010
  • A most important thing in a connected dominating set(CDS)-based routing in a wireless ad-hoc network is to select a minimum number of dominating nodes and then build a backbone network which is made of them. Node failure in a CDS is an event of non-negligible probability. For applications where fault tolerance is critical, a traditional dominating-set based routing may not be a desirable form of clustering. It is necessary to minimize the frequency of reconstruction of a CDS to reduce message overhead due to message flooding. The idea is that by finding alternative nodes within a restricted range and locally reconstructing a CDS to include them, instead of totally reconstructing a new CDS. With the proposed algorithm, the resulting number of dominating nodes after partial reconstruction of CDS is not changed and also its execution time is faster than well-known algorithm of construction of CDS by 20~40%. In the case of high mobility situation, the proposed algorithm gives better results for the performance metrics, packet receive ratio and energy consumption.

Functional analysis of the rice BRI1 receptor kinase (벼 Brassinosteroid Insensitive 1 Receptor Kinase의 기능에 관한 연구)

  • Yeon, Jinouk;Kim, Hoy-Taek;Nou, Ill-Sup;Oh, Man-Ho
    • Journal of Plant Biotechnology
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    • v.43 no.1
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    • pp.30-36
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    • 2016
  • Brassinosteroids (BRs) are essential plant steroid hormones required for cell elongation, plant growth, development and abiotic and biotic stress tolerance. BRs are recognized by BRI1 receptor kinase that is localized in the plasma membrane, and the BRI1 protein will eventually autophosphorylate in the intracellular domain and transphosphorylate BAK1, which is a co-receptor in Arabidopsis thaliana. However, little is known of the role OsBRI1 receptor kinase plays in Oryza sativa, monocotyledonous plants, compared to that in Arabidopsis thaliana, dicotyledonous plants. As such, we have studied OsBRI1 receptor kinase in vitro and in vivo with recombinant protein and transgenic plants, whose phenotypes were also investigated. A OsBRI1 cytoplasmic domain (CD) recombinant protein was induced in BL21 (DE3) E.coli cells with IPTG, and purified to obtain OsBRI1 recombinant protein. Based on Western blot analysis with phospho-specific pTyr and pThr antibodies, OsBRI1 recombinant protein and OsBRI1-Flag protein were phosphorylated on Threonine residue(s), however, not on Tyrosine residue(s), both in vitro and in vivo. This is particularly intriguing as AtBRI1 protein was phosphorylated on both Ser/Thr and Tyr residues. Also, the OsBRI1 full-length gene was expressed in, and rescued, bri1-5 mutants, such as is seen in normal wild-type plants where AtBRI1-Flag rescues bri1-5 mutant plants. Root growth in seedlings decreased in Ws2, AtBRI1, and 3 independent OsBRI1 transgenic seedlings and had an almost complete lack of response to brassinolide in the bri1-5 mutant. In conclusion, OsBRI1, an orthologous gene of AtBRI1, can mediate normal BR signaling for plant growth and development in Arabidopsis thaliana.

Phytoremediation of Heavy Metal Contaminated Soils Using Transgenic Plants (중금속 오염토양의 식물정화 기술과 형질전환 식물의 이용에 관한 최근 연구동향)

  • Ok, Yong-Sik;Kim, Jeong-Gyu;Yang, Jae E.;Kim, Hee-Joung;Yoo, Kyung-Yoal;Park, Chang-Jin;Jeong, Deok-Yeong
    • Korean Journal of Soil Science and Fertilizer
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    • v.37 no.6
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    • pp.396-406
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    • 2004
  • Current physical and chemical methodologies, conventionally used to clean up metal contaminated soils, are generally too expensive to apply in large hazardous waste sites including agricultural lands adjacent to closed or abandoned metal mines. Phytoremediation using plants to extract, sequester and detoxify environmental pollutants is one of the cost-effective and aesthetically-pleasing alternatives, compared with environmentally destructive remedial methods currently being practiced. But, phytoremediation has some limitations such as time consuming and low performance: in general, it is seasonally dependent and slower in removing metals than other methods, and metal accumulating plants are slow growers. Improvement of plants for metal tolerance, accumulation, and translocation using genetic engineering techniques recently opened up new possibilities for phytoremediation. In this paper, we have discussed about recent developments in conventional and genetically engineered phytoremediation. For the conventional phytoremediation, focuses are on the natural hyperaccumulator and the chemically assisted phytoremediation. Some pros and cons on the phytoremediation using transgenic plants, coupled with focusing on the mechanistic view points, are also discussed. It might be concluded that the transgenic plants will be effective tools in the practical application of phytoremediation especially for the highly contaminated soils but mechanisms involved should be deeply understood in advance.

Distribution of hazardous heavy metals in commercial herbal medicines classified by plant parts used in seoul (서울지역 유통한약재의 약용부위에 따른 유해중금속 분포)

  • Kim, Donggyu;Kim, Bogsoon;Han, Eunjung;Han, Changho;Kim, Oukhee;Choi, Byunghyun;Hwang, Insook;Chae, Youngzoo;Kim, Minyoung;Park, Seungkook
    • Analytical Science and Technology
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    • v.22 no.6
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    • pp.504-513
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    • 2009
  • In this study, the safety of commercial herbal medicines was evaluated by determining concentration of hazardous heavy metals. 3,152 samples (244 types) purchased by individual packing unit from market in Seoul, were analyzed using ICP-MS and mercury analyzer. As a result, the content (mg $kg^{-1}$) of Pb was higher in the above-ground part (0.92) than underground part (0.43). But in case of As and Cd contents, there is slightly higher in the underground-parts (0.26, 0.13) than the above-ground parts (0.18, 0.08). There were many herbal medicines exceeding regulatory limits of Cd comparing with other metals. The levels of Hg seemed to be different between above-ground part(0.009) and underground part (0.008) but there was no sample exceeding tolerance limits. In the comparison of imported samples with domestic herbal medicines, it was shown that Pb, As, and Hg were measured highly in the imported ones, Cd was not significantly different (t-test, p<0.05). The significant correlation was observed between Pb and As (r=0.386, p<0.01) but there was no difference in other parts. The heavy metal contamination of herbal medicines measured in total amount of respective heavy metals (mg $kg^{-1}$) was high in Flos (6.241) and Caulis (2.238), and decreased in the order of Cortex (1.634), Herba (1.154), Perithecium (0.861), Rhizoma (0.828), Radix (0.825), Fructus (0.475), and was low in Semen (0.422) (ANOVA-test, p<0.05).