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Synthesis of Allylthiopyridazine Derivatives and Inhibition of Aflatoxin ${B_1}-Induced$ Hepatotoxicity in Rats

  • Shin, Hea-Soon;Kwon, Soon-Kyoung
    • Archives of Pharmacal Research
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    • v.26 no.5
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    • pp.351-357
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    • 2003
  • Five kinds of allylthiopyridazine derivatives were synthesized and their chemoprotective activities examined in rats exposed to aflatoxin $B_1$-toxicant. Rats were pretreated with five allylthiopyridazine derivatives at daily oral doses of 50 mg/kg for 10 consecutive days, and during this period with one or three repeated doses of the potent hepatotoxin, aflatoxin $B_1$. The hepatoprotective effects of the allylthiopyridazine derivatives against aflatoxin $B_1$ (1 mg/kg, three times at intervals of 3 days, i.p., or at 3 mg/kg, once at final days, i.p.) administration were showed the significantly normal as compared with control in body and liver weights. Aspartate aminotransferase and alanine aminotransferase levels were markedly elevated after aflatoxin $B_1$ administration, and pretreatment with allylthiopyridazine derivatives, before aflatoxin $B_1$ administration, resulted in decreased levels of these enzymes. In addition, the allylthiopyridazine derivatives, K6 (3-methoxy-), K8 (3-chloro-), K16 (3-ethoxy-) and K17 (3-n-propoxy), induced elevated hepatic GSH levels. Four kinds of allylthiopyridazine derivatives investigated were effective against aflatoxin $B_1$ -induced hepatotoxicity.

Narrow Band-pass Filter with Dual-band Using Pseudo-Combline (Pseudo-Combline을 이용한 이중대역 협대역 대역통과 여파기)

  • Yoon, Ki-Cheol;Lee, Hyun-Wook;Li, Meng;Lee, Jae-Yeong;Lee, Jong-Chul
    • The Journal of The Korea Institute of Intelligent Transport Systems
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    • v.10 no.6
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    • pp.84-90
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    • 2011
  • In this paper, a dual-band pseudo-combline narrow bandpass filter is proposed. The proposed bandpass filter adopts the open resonant stubs and the proposed bandpass filter can be used for ITS(Intelligent Transport System) and X-band satellite systems application. The proposed bandpass filter has the insertion and return losses of 1.72 dB and 15.5 dB at the bandwidth of 3.6 % and center frequency of 5.8 GHz, respectively. Also, the second operating frequency band for insertion and return losses are 1.92 dB and 16.3 dB at the bandwidth of 3% and center frequency of 8.5 GHz, respectively.

A Novel Approach to the Discovery of Non-systemic Anti-inflammatory Steroids; Antedrug

  • Lee, Henry-J.;Ko, Dong-Hoon
    • Archives of Pharmacal Research
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    • v.22 no.3
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    • pp.279-287
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    • 1999
  • Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system.. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16$\alpha$-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b 6.8; 9a, 0.7; 9b 8.6; 10a 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity form systemic adverse effects.

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Expression of Neuregulins and Their Receptors During the Differentiation of Rat Hippocampal HiB5 Cells

  • Kwon, Hyockman
    • Animal cells and systems
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    • v.5 no.3
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    • pp.247-251
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    • 2001
  • Differentiating HiB5 cells, a rat hippocampal cell line, expressed neuregulins and showed constitutive activation of a neuregulin receptor, ErbB2, suggesting development of a neuregulin autocrine loop. RT-PCR analyses indicated that HiB5 cells produced SMDF and NDF, but not GGF, during the differentiation. None of neuregulin isoforms were detected in proliferating HiB5 cells. The neuregulins in HiBS cells, at least in part, are the $\beta$-isoforms of which the most of neuronal neuregulin isoforms are. The expression of SMDF and NDF was enhanced by PDGF and bFGF that promote cell survival and differentiation, suggesting a close relationship between the synthesis of neuregulins and the differentiation process. HiB5 cells have ErbB2 and ErbB4, but not ErbB3 receptors. Constitutive tyrosine phosphorylation of ErbB2 was detected in HiB5 cells that had not been exposed to exogenous GGF.

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Evaluation of Image Quality using SE-EPI and SSH-TSE Techniques in MRDWI (자기공명확산강조영상에서 SE-EPI 와 SSH-TSE 기법을 이용한 영상의 질 평가)

  • Goo, Eun-Hoe
    • Journal of the Korean Society of Radiology
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    • v.15 no.7
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    • pp.991-998
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    • 2021
  • The purpose of this study is to investigate the image quality of the SE-EPI and SSH-TSE technique for MR DWI. Datum were analyzed for 35 PACS transmission datum(Normal part: 12 males, 13 females, Cerebral Infarction: 10(5males and 5females), and average age 68±7.32), randomly selected patients who underwent MRDWI tests. The equipment used was Ingenia CX 3.0T, SSH_TSE and SE-EPI pulse sequence and 32 Ch. head coil were used for data acquisition. Image evaluation was performed on the paired t-test and Wilcoxon tests, and was considered significant when the p value was 0.05 or less. As a result of quantitative analysis of SNR for DWI images, the mean and standard deviation values of 4 parts (WM, GM, BG, Cerebellum) in ADC (s/mm2), Diffusion b=0, 1000 images were higher in SE-EPI techniques(ADC: 120.50 ± 40, b=0: 54.50 ± 35.91, b=1000: 91.61 ± 36.63) than in SSH-TSE techniques(ADC: 99.69 ± 31.10, b=0: 43.52 ± 25.00 , b=1000: 60.74 ± 24.85)(p<0.05). The CNR values for GM-WM, BG-WM sites were also higher in SE-EPI technique (ADC: 116.08 ± 43.30, b=0:27.23 ± 09.10, b=1000: 78.50 ± 16.56) than in SSH-TSE(ADC: 101.08 ± 36.81, b=0: 23.96 ± 07.79 , b=1000: 74.30 ± 14.22). As a visual evaluation of observers, ghost artifact, magnetic susceptibility artifacts and overall image quality for SE-TSE and SSH-TSE all yielded high results from SSH-TSE techniques(ADC:3.6 ± 0.1, 2.8 ± 0.2, b=0: 4.3 ± 0.3, 3.4 ± 0.1 b=1000: 4.3 ± 0.2, 3.5 ± 0.2, p=0.000). In conclusion, the SE-EPI technique obtained an superiority in SNR and CNR measurements using SSH-TSE, SE-EPI. In the qualitative analysis, the SSH-TSE pulse sequence was obtained a high result according to the pulse sequence characteristics.

Synthesis and Structure of Benzotriazolyl Fluorenes

  • KohPark, Kwang-Hee;Jung, Hye-Mi;Lee, Tae-Woo;Kang, Sung-Kwon
    • Bulletin of the Korean Chemical Society
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    • v.31 no.4
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    • pp.984-988
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    • 2010
  • 1-(Fluoren-2-yl)-benzo[d][1,2,3]triazoles 5a-b were synthesized starting from 2-nitrofluorene. 2-Nitrofluorenes 1a-b were reduced by catalytic hydrogenation, reacted with 2,4-dinitrofluorobenzene followed by catalytic hydrogenation to afford 2-(N-2,4-diaminophenyl)aminofluorenes 4a-b. Diazotization of 4a-b with $NaNO_2/H_2SO_4$ followed by treatment with $H_3PO_2$ gave 5a-b. Sulfonation of 5a-b yielded 7-benzotriazol-1-yl-fluorene-2-sulfonic acids 6a-b. The structures of 5b and 6b were firmly identified by X-ray crystal analysis in addition to $^1H$ NMR, $^{13}C$ NMR, and elemental analysis.

Adsorption Behavior and Kinetic Characteristic of Cibacron Brilliant Red 3B-A by Granular Activated Carbon (입상활성탄에 의한 Cibacron Brilliant Red 3B-A의 흡착거동 및 동력학적 특성)

  • Lee, Jong Jib
    • Korean Chemical Engineering Research
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    • v.52 no.4
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    • pp.486-491
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    • 2014
  • In this paper, the adsorption behavior and kinetic characteristics of cibacron brilliant red 3B-A from aqueous solution using granular activated carbon were investigated. The effect of various parameters such as adsorbent dose, pH, initial concentration, contact time and temperature on the adsorption system were studied. Base on the estimated Langmuir constant ($R_L$) and Freundlich constant (1/n), This process could be employed as effective treatment method. From the Temkin constant (B) and Dubinin-Radushkevich constant (E), This adsorption process is physical adsorption. From kinetic experiments, the adsorption process followed the pseudo second order model with good correlation. Base on the Gibbs free energy and enthalpy, the adsorption of cibacron brilliant red 3B-A onto granular activated carbon was physisorption and endothermic in nature.

N-Region Addition in Immunoglobulin Kappa Light Chains in B Cell Subsets in Rheumatoid Arthritis: Evidence for Over-expression of TDT in B Lineage

  • Lee, Choong Won;Bridges, S. Louis Jr
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.89-95
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    • 2003
  • Background: Unusually high amounts of N region addition and CDR3 length diversity were found in immunoglobulin (Ig) light chain Vk and Jk joins in patients with rheumatoid arthritis (RA). We sought to determine whether this finding is due to excessive activity of the enzyme responsible for N region addition (terminal deoxynucleotidyl transferase [TdT]) in B lineage cells in bone marrow or from positive antigenic selection of B cells with long CDR3 lengths. Methods: We used FACS to isolate $IgM^+/IgD^+$ B cells (predominantly naive) and $IgM^-/IgD^-$ B cells (predominantly class-switched) B cells from peripheral blood of a patient with RA known to have enrichment for long Vk CDR3s and from that of two normal controls. RT-PCR of VkIII transcripts was performed, followed by sequencing of individual cDNA clones. We analyzed the CDR3 lengths and N region additions in 97 clones. Results: There was enrichment for long CDR3 lengths (11 or 12 amino acids) in both $IgM^+/IgD^+$ and $IgM^-/IgD^-$ B cells in RA compared to B cell subsets in the normal controls. The $IgM^+/IgD^+$ B cell subset in RA was markedly enriched for N region addition and was similar to that seen in the $IgM^-/IgD^-$ subset. Conclusion: These data suggest that enrichment for N region addition and long CDR3 lengths in RA may result from unusually high or prolonged activity of TdT in bone marrow.

MiR-374b Promotes Proliferation and Inhibits Apoptosis of Human GIST Cells by Inhibiting PTEN through Activation of the PI3K/Akt Pathway

  • Long, Zi-Wen;Wu, Jiang-Hong;Hong, Cai;Wang, Ya-Nong;Zhou, Ye
    • Molecules and Cells
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    • v.41 no.6
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    • pp.532-544
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    • 2018
  • Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.