• Title/Summary/Keyword: Nuclear receptor

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CYP1A1 GENE EXPRESSION IS DOWN REGULATED BY HYPOXIC AGENTS

  • Joung, Ki-Eun;Kim, Yeo-Woon;Syrie Pang;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.187-187
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    • 2001
  • Since hypoxia-inducible factor-lalpha (HIF-lalpha) and the arylhydrocarbon receptor (AhR) shared the AhR nuclear translocator (Arnt) for hypoxia- and AhR-mediated signaling, respectively, it was possible to establish the hypothesis that hypoxia could regulate Cyp1a1 expression.(omitted)

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Oxymatrine inhibits the pyroptosis in rat insulinoma cells by affecting nuclear factor kappa B and nuclear factor (erythroid-derived 2)-like 2 protein/heme oxygenase-1 pathways

  • Gao, Jingying;Xia, Lixia;Wei, Yuanyuan
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.3
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    • pp.165-174
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    • 2022
  • As the mechanism underlying glucose metabolism regulation by oxymatrine is unclear, this study investigated the effects of oxymatrine on pyroptosis in INS-1 cells. Flow cytometry was employed to examine cell pyroptosis and reactive oxygen species (ROS) production. Cell pyroptosis was also investigated via transmission electron microscopy and lactate dehydrogenase (LDH) release. Protein levels were detected using western blotting and interleukin (IL)-1β and IL-18 secretion by enzyme-linked immunosorbent assay. The caspase-1 activity and DNA-binding activity of nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2) were also assessed. In the high glucose and high fat-treated INS-1 cells (HG + PA), the caspase-1 activity and LDH content, as well as Nod-like receptor family pyrin domain containing 3, Gsdmd-N, caspase-1, apoptosis-associated speck-like protein containing a CARD, IL-1β, and IL-18 levels were increased. Moreover, P65 protein levels increased in the nucleus but decreased in the cytoplasm. Oxymatrine attenuated these effects and suppressed high glucose and high fat-induced ROS production. The increased levels of nuclear Nrf2 and heme oxygenase-1 (HO-1) in the HG + PA cells were further elevated after oxymatrine treatment, whereas cytoplasmic Nrf2 and Keleh-like ECH-associated protein levels decreased. Additionally, the elevated transcriptional activity of p65 in HG + PA cells was reduced by oxymatrine, whereas that of Nrf2 increased. The results indicate that the inhibition of pyroptosis in INS-1 cells by oxymatrine, a key factor in its glucose metabolism regulation, involves the suppression of the NF-κB pathway and activation of the Nrf2/HO-1 pathway.

Radioactivity of biological samples of patients treated with 90Y-DOTATOC

  • Marija Z. Jeremic;Milovan D. Matovic;Nenad R. Mijatovic;Suzana B. Pantovic;Dragana Z. Krstic;Tatjana B. Miladinovic;Dragoslav R. Nikezic
    • Nuclear Engineering and Technology
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    • v.55 no.10
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    • pp.3815-3821
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    • 2023
  • Dosimetric studies in Nuclear Medicine are very important, especially with new therapeutic methods, the number of which has increased significantly with the Theranostic approach (determining diagnostic-therapeutic pairs where similar molecules are labelled with different isotopes in order to diagnose and treat malignant diseases). Peptide receptor radionuclide therapy (PRRT) has been used successfully for many years to treat neuroendocrine tumors (NET). 90Y-DOTATOC is one of the radiopharmaceuticals used frequently in this type of therapy. In this work, blood and urine samples from 13 patients treated with 90Y-DOTATOC were measured by a liquid scintillation beta counter (LSC). Calibration of the beta counter for this type of measurement was done and all results are presented in the paper. The presented paper also provides a methodology for determining the measurement uncertainty for this type of measurement. Immediately after the administration of radiopharmaceuticals, the activity in the blood was different from 6.31% to 88.9% of the applied radioactivity, while 3 h after the termination of the application, the average value of radiopharmaceuticals in the blood was only 3.84%. The activity in the excreted urine depended on the time when the patients urinated after the therapy. It was measured that as much as 58% of the applied radioactivity was excreted in the first urine after the therapy in a patient who urinated 4.5 h after the completed application of the therapy. In most patients, the highest urine activity was in the first 10 h after the application, while the activities after that time were negligibly low. The described methodology of measuring and evaluating activity in blood and excreted urine can be applied to other radiopharmaceuticals used in nuclear medicine. It could be useful for researchers for dosimetric assessments in clinical application of PRRT.

Promyelocytic Leukemia Gene Functions and Roles in Tumorigenesis

  • Imani-Saber, Zeinab;Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8019-8026
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    • 2014
  • The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha ($RAR{\alpha}$). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.

Fully automated ethanolic loop synthesis of the [11C]OMAR

  • Jang, Keun Sam;Song, Ho-Chun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.2 no.2
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    • pp.137-142
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    • 2016
  • We have successfully synthesized of 4-cyano-1-(2,4-dichlorophenyl)-5-(4-[$^{11}C$]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxzmide ([$^{11}C$]OMAR), which has been shown a progressing candidate to human brain PET study, from fully automated loop method using ethanol as the only solvent for the entire manufacturing process. The radiochemical yield of [$^{11}C$]OMAR was observed in $4.1{\pm}0.2%$ with $4990{\pm}384Ci/mmol$ of the specific activity and total synthesis time was about 45 minutes after HPLC purification (n = 3, decay corrected) from ethanolic loop system, which was exhibited to better results compared with conventional methods. Ethanolic loop chemistry is favorable and efficient method by simplifies manufacturing procedures as well as satisfied suitable for human administration.