• Title/Summary/Keyword: E-MDR

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Toxicity of Organophosphorus Flame Retardants (OPFRs) and Their Mixtures in Aliivibrio fischeri and Human Hepatocyte HepG2 (인체 간세포주 HepG2 및 발광박테리아를 활용한 유기인계 난연제와 그 혼합물의 독성 스크리닝)

  • Sunmi Kim;Kyounghee Kang;Jiyun Kim;Minju Na;Jiwon Choi
    • Journal of Environmental Health Sciences
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    • v.49 no.2
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    • pp.89-98
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    • 2023
  • Background: Organophosphorus flame retardants (OPFRs) are a group of chemical substances used in building materials and plastic products to suppress or mitigate the combustion of materials. Although OPFRs are generally used in mixed form, information on their mixture toxicity is quite scarce. Objectives: This study aims to elucidate the toxicity and determine the types of interaction (e.g., synergistic, additive, and antagonistic effect) of OPFRs mixtures. Methods: Nine organophosphorus flame retardants, including TEHP (tris(2-ethylhexyl) phosphate) and TDCPP (tris(1,3-dichloro-2-propyl) phosphate), were selected based on indoor dust measurement data in South Korea. Nine OPFRs were exposed to the luminescent bacteria Aliivibrio fischeri for 30 minutes and the human hepatocyte cell line HepG2 for 48 hours. Chemicals with significant toxicity were only used for mixture toxicity tests in HepG2. In addition, the observed ECx values were compared with the predicted toxicity values in the CA (concentration addition) prediction model, and the MDR (model deviation ratio) was calculated to determine the type of interaction. Results: Only four chemicals showed significant toxicity in the luminescent bacteria assays. However, EC50 values were derived for seven out of nine OPFRs in the HepG2 assays. In the HepG2 assays, the highest to lowest EC50 were in the order of the molecular weight of the target chemicals. In the further mixture tests, most binary mixtures show additive interactions except for the two combinations that have TPhP (triphenyl phosphate), i.e., TPhP and TDCPP, and TPhP and TBOEP (tris(2-butoxyethyl) phosphate). Conclusions: Our data shows OPFR mixtures usually have additivity; however, more research is needed to find out the reason for the synergistic effect of TPhP. Also, the mixture experimental dataset can be used as a training and validation set for developing the mixture toxicity prediction model as a further step.

A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-${\kappa}B$ Signaling Cascade

  • Mongre, Raj Kumar;Sodhi, Simrinder Singh;Ghosh, Mrinmoy;Kim, Jeong Hyun;Kim, Nameun;Sharma, Neelesh;Jeong, Dong Kee
    • Development and Reproduction
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    • v.18 no.4
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    • pp.197-212
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    • 2014
  • Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

Transfer of Genes for Antimicrobial Resistance and Toxin of Hemolytic Escherichia coli Isolated from Feces of Pig Suffering Diarrhea to Human Isolates (설사 증상의 돼지 분변에서 분리된 용혈성 대장균의 항생제 내성과 독소의 인체로부터 분리된 균주로의 전이)

  • Lee Kyenam;Jung Byeong Yeal;Lee Yeonhee
    • Korean Journal of Microbiology
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    • v.40 no.4
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    • pp.286-294
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    • 2004
  • Between 1997 and 1998 in Korea, 56 isolates of Escherichia coli were obtained from pig suffering diarrhea. Among those, 38 isolates that showed the hemolytic activity, antimicrobial resistance, and toxin production were studied. Among 38 isolates, thirty-six isolates $(94.7\%)$ were resistant to tetracycline, 27 isolates $(71.0\%)$ were resistant to ampicillin, 26 isolates $(68.4\%)$ were resistant to chloramphenicol, and 21 isolates $(55.2\%)$ were resistant to trimethoprim, while none was resistant to aztreonam, amikacin, and norfloxacin. Among these iso­lates, 21 isolates $(55.3\%)$ were multiple drug resistant to at least four different class antimicrobial agents. Extended spectrum $\beta-lactamase$ producing isolates were not detected in the double disk synergy test. In these hemolytic Escherichia coli, heat-stable enterotoxin $(89.5\%)$ was the most prevalent toxin, followed by vero­toxins $(47.4\%),$ and then heat-labile enterotoxin $(31.6\%).$ Except 8 isolates $(21.0\%)$ which produced ST only, 12 isolates $(31.6\%)$ produced ST and LT, 13 isolates $(34.2\%)$ produced ST, VT, and VTe, and 5 isolates $(13.2\%)$ produced VT and VTe. However, none produced all 4 types of toxin, simultaneously. The predominant serotype could not be determined by the agglutination method. Sixteen isolates $(42.1\%)$ were strongly adhered to T-24 bladder cell and 17 isolates $(44.7\%)$ were to Caco-2 intestinal cell. Especially, 11 strains $(28.9\%)$ were evaluated as strongly adhesive to both T-24 cells and Caco-2 cells. Genes for toxin and the antimicrobial resistance were transferred to clinical isolates of Escherichia coli from human urine by the filter mating method. Results suggest the possibility that antimicrobial resistance and toxin can be transferred from animals to humans by direct con­tact of resistant bacteria as well as gene transfer, although there was no correlation between toxin production, adherent activity, and antimicrobial resistance among hemolytic E. coli isolated from pig suffering diarrhea.