• Title/Summary/Keyword: IRF-1

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A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

  • Melath, Anil;Santhakumar, Gopi Krishnan;Madhavannair, Shyam Sunder;Nedumgottil, Binoy Mathews;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6803-6806
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    • 2013
  • Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.

Clinical Significance of Immature Reticulocyte Fraction and Reticulocyte Cellular Indices in Pediatric Anemia Patients (망상적혈구 지수 및 미성숙망상적혈구 분획의 소아 빈혈에서의 임상적 의의)

  • Seo, Young;Jung, Hye Lim;Shim, Jae Won;Kim, Deok Su;Shim, Jeong Yeon;Park, Moon Soo
    • Clinical and Experimental Pediatrics
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    • v.48 no.3
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    • pp.284-291
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    • 2005
  • Purpose : Flow cytometric automated reticulocyte analysis is a superior method to manual reticulocyte counting, with respect to precision and sensitivity. Furthermore, flow cytometric analysis is able to measure immature reticulocyte fraction(IRF) and reticulocyte cellular indices(RCI : cell hemoglobin content : CHr, mean cell volume : MCVr, cell hemoglobin concentration mean : CHCMr, distribytion width : RDWr, HDWr, CHDWr). In this study, we investigated the mean values and clinical significances of IRF and RCI in healthy children and pediatric anemia patients. Methods : IRF and RCI were measured with an automated blood cell analyzer, ADVIA 120(Bayer, USA) using oxazine 750 dye, in 57 healthy children and 61 children with anemia. The anemia group consisted of 27 iron deficiency anemia(IDA) patients and 34 patients with anemia associated with acute infection(AAI). We compared the mean values of IRF and RCI in the control group classified according to age, between anemia groups and the control group, and between the IDA group and the AAI group. Results : For the normal control group, the mean values of IRF, CHr, MCVr and HDWr were higher in neonates when compared to older children. The mean values of IRF and RDWr were significantly higher, and the mean values of CHr and CHCMr were significantly lower in the IDA group when compared to the control group. The mean value of IRF was significantly higher, and the mean value of CHDWr was significantly lower in the AAI group when compared to the control group. The mean values of IRF, CHr and CHCMr were significantly lower in the IDA group when compared to the AAI group. Conclusion : We could determine the normal mean values of IRF and RCI in healthy children classified according to age for understanding of hematopoietic response differences according to age. The evaluation of IRF and RCI by automated reticulocyte analyzer seemed to be accurate and clinically useful for the early diagnosis of anemia and the differentiation of IDA from AAI.

Inhibitory Effect of Mix proportion of Root of Scutellaria baicalensis and Coptis chinensis on LPS-induced type-I interferon Production in RAW264.7 Cells (LPS로 자극한 RAW267.4 세포에서 황금(黃芩), 황련(黃連) 배합 비율에 따른 TYPE-1 interferon 억제효과)

  • Kook, Yoon-Bum
    • Herbal Formula Science
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    • v.16 no.2
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    • pp.155-162
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    • 2008
  • Objectives : The present study was designed to investigate corelation between mix proportion of Scutellaria baicalensis (SB) and Coptis chinensis (CC) on lipopolysaccharide (LPS)-induced TYPE-1 interferon production. Methods : I examined TYPE-1 interferon, interferon regulating factor (IRF)-1,7 and interleukin(IL)-10 production on LPS-induced RAW264.7 cells to evaluate inhibitory effect of mix proportion of SB and CC using real time PCR. Results : Mixture of SB and CC regulated TYPE-1 interferon and IRF-1,7 mRNA expression with SB dose dependent manner, while maintained IL-10 mRNA expression on LPS-induced RAW264.7 cells. Conclusion : In mixture of SB and CC, SB plays a key role in reducing TYPE-1 interferon through inactivation IRF-1,7. Furthermore mixture of SB and CC maintained IL-10 mRNA level. Collectively, this results suggest that SB confer beneficial effects in autoimmune diseases clinically.

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The Effect of Lipopolysaccharide on Noxa Expression Is Mediated through IRF1, 3, and 7

  • Piya, Sujan;Kim, Tae-Hyoung
    • Journal of Microbiology and Biotechnology
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    • v.28 no.3
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    • pp.491-497
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    • 2018
  • Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, elicits the secretion of cytokines, such as interferons, that stimulate the host defense system. Previously, we demonstrated that interferons induce interferon regulatory factors (IRFs) 1, 3, and 7, which regulate the transcription of Noxa and alter the expression profiles of Bcl-2 family proteins in tumors. However, the immediate consequences of LPS stimulation on Noxa and BH3 expression in tumor cells remain uncharacterized. In this study, we determined that LPS induced Noxa expression in CT26 cells. Furthermore, studies in HCT116 parental and HCT116 p53-deficient cells revealed that LPS-mediated Noxa was independent of p53. Meanwhile, IRF1, 3, and 7 in CT26, HCT116 parental, and HT116 p53-deficient cells were upregulated by LPS stimulation, suggesting that LPS induces the expression of these IRFs in a p53-independent manner. The responsiveness of IRF1, 3, 4, and 7 binding to the Noxa promoter region to LPS indicated that IRF1, 3, and 7 activated Noxa expression, whereas IRF4 repressed Noxa expression. Together, these results suggest that LPS directly affects Noxa expression in tumor cells through IRFs, implicating that it may contribute to LPS-induced tumor regression.

Orostachys japonicus Hexane Fraction Attenuates Pro-inflammatory Cytokines in LPS-activated Macrophage Cells by Suppression of AP-1 and IRF3 Transcription Factors (LPS로 유도된 대식세포에 대한 와송 핵산추출물의 AP-1과 IRF3 전사인자의 억제에 의한 전염증성 사이토카인의 감소 효과)

  • Lee, Hyeong-Seon
    • Microbiology and Biotechnology Letters
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    • v.48 no.3
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    • pp.310-315
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    • 2020
  • Orostachys japonicus (O. japonicus) is known as a medicinal plant for the treatment of various symptoms. This study investigated the anti-inflammatory effect of the hexane fraction from O. japonicus (OJH) on the LPS-stimulated response in RAW 264.7 macrophage cells. This study was conducted to confirm the effect of cell cytotoxicity and production of reactive oxygen species (ROS) in OJH-treated macrophage cells. Additionally, pro-inflammatory cytokines and transcription factors were determined using RT-PCR and western blotting assay. OJH showed no change in lactate dehydrogenase (LDH) levels and exhibited reduced ROS levels in LPS-induced inflammatory cells. Moreover, OJH significantly suppressed the mRNA levels of proinflammatory cytokines, including IL-1β, IL-2, IL-6, TNF-α, and IP-10. Furthermore, OJH effectively inhibited the protein levels of AP-1 (p-c-Jun and p-c-Fos) and p-IRF3 in a dose-dependent manner. In conclusion, our results demonstrate that OJH exhibits strong anti-inflammatory activities via regulation of inflammatory factors.

A Study on the Inhibitory Effect and Mechanism of Lonicera Japonica on Type I Interferon (금은화의 type I interferon 억제효과 및 기전에 관한 연구)

  • Kang, Yong-Goo;Ryu, Ik-Han;Kim, Song-Baek;Choi, Chang-Min;Seo, Yun-Jung;Cho, Han-Baek
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.2
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    • pp.17-32
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    • 2013
  • Objectives: The purpose of this study was to investigate whether Lonicera japonica(LJ) could inhibit LPS-induced type I IFN production. Methods: To evaluate inhibitory effect of LJ on type I IFN, we examined type I IFN, IRF-1, 7 and IL-10 production on LPS-induced macrophages using real time RT-PCR. Next, we observed the interaction of type I IFN, IRF-1, 7 and IL-10 using IL-10 neutralizing antibody. Finally we examined the activation of STAT-1, 3 using western blot. Results: LJ inhibited Type I IFN expression of mRNA and increased IL-10 expression of mRNA. Also LJ inhibited the level of IRF-1, 7 mRNA and the nuclear translocation of IRF-3. Further more, LJ reduced the activation of STAT-1, 3 which are involved in continuous secretion of immune cytokines. Blockade of IL-10 action caused a significant reduction of type I IFN and IRF-1, 7 than LPS-induced LJ pretreatment. Conclusions: LJ inhibits LPS-induced production of type I IFN by IL-10. This study may provide a clinical basis for anti-inflammatory properties of LJ.

A Performance Consideration on Conversion Loss in the Integrated Single Balanced Diode Mixer

  • Han, Sok-Kyun;Kim, Kab-Ki
    • Journal of information and communication convergence engineering
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    • v.1 no.3
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    • pp.139-142
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    • 2003
  • In this paper, we consider the factors that affect a conversion loss performance in designing a single balanced diode mixer integrated with IRF(Image Reject Filter), based on the embedded electrical wavelength placed between the IRF and mixer, diode matching and LO drive amplifier. To evaluate the conversion loss performance, we suggest two types of a single balanced mixer using 90 degree branch line coupler, microstrip line and schottky diode. One is only mixer and the other is integrated with IRF and LO drive amplifier. The measured results of a single balance diode mixer integrated IRF show the conversion loss of 8.5 dB and the flatness of 1 dB p-p from 21.2 GHz to 22.6 GHz with 10 dBm LO. The measured input PI dB and IIP3 are 7 dBm and 15 dBm respectively under the nominal LO power level of 10dBm. The LO/RF and LO/IF isolation are 22 dB and 50 dB, respectively.

IRF Analysis Considering Clutter Background for SAR Image Qualification

  • Jung, Chul-H.;Oh, Tae-B.;Song, Sun-H.;Kwag, Young-K.
    • International Journal of Aeronautical and Space Sciences
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    • v.10 no.1
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    • pp.83-90
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    • 2009
  • A new IRF (Impulse Response Function) analysis technique in high resolution SAR image is presented by taking into account the real clutter environment. In order to investigate the realistic effect of clutter background on the impulse response function of SAR image, an ideally generated impulse response function is superimposed with a large number of background clutter data which are extracted from the various regions of an actual SAR image. As a performance measure, PSLR (Peak Sidelobe Ratio) of the clutter-contained IRF is presented in the various groups of clutter background, and finally the results are compared with the stochastic model.

PD-1 Expression in LPS-Induced Raw264.7 Cells Is Regulated via Co-activation of Transcription Factor NF-κB and IRF-1 (Lipopolysaccharide 유도된 Raw264.7 세포주에서 전사조절인자 NF-κB와 IRF-1의 공동작용에 의해 조절되는 PD-1 발현연구)

  • Choi, Eun-Kyoung;Lee, Soo-Woon;Lee, Soo-Woong
    • Korean Journal of Microbiology
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    • v.49 no.4
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    • pp.301-308
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    • 2013
  • Programmed Death-1 (PD-1) is one of the important immune-inhibitory molecules which was expressed in T cells, B cells, NKT cells, and macrophages activated by various immune activating factors. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is one of the crucial immunogens for PD-1 expression. However, there are only a few reports on the expression mechanisms of PD-1 in innate immune cells. In this study, we investigate the expression mechanisms of PD-1 in LPS-stimulated Raw264.7 cell lines by RT-PCR, Western Blot, flow cytometry as well as ChIP assay and co-immunoprecipitation. When Raw264.7 cells were stimulated with LPS, PD-1 expression was greatly up-regulated via PI3K and p38 signaling. Primary macrophages isolated from LPS-injected mice were also shown the increased expression of PD-1. In promoter assay, NF-${\kappa}B$ and IRF-1 binding regions in mouse PD-1 promoter are important for PD-1 expression. We also found that the co-activation of NF-${\kappa}B$ and IRF-1 is indispensable for the maximum PD-1 expression. These results indicate that the modulation of PD-1 expressed in innate immune cells could be a crucial for the disease therapy such as LPS-induced mouse sepsis model.

Review of Instant Release Fractions of Long-lived Radionuclides in CANDU and PWR Spent Nuclear Fuels Under the Geological Disposal Conditions

  • Choi, Heui Joo;Koo, Yang-Hyun;Cho, Dong-Keun
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.20 no.2
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    • pp.231-241
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    • 2022
  • Several countries, including Korea, are considering the direct disposal of spent nuclear fuels. The radiological safety assessment results published after a geological repository closure indicate that the instant release is the main radiation source rather than the congruent release. Three Safety Case reports recently published were reviewed and the IRF values of seven long-lived radionuclides, including relevant experimental results, were compared. According to the literature review, the IRF values of both the CANDU and low burnup PWR spent fuel have been experimentally measured and used reasonably. In particular, the IRF values of volatile long-lived nuclides, such as 129I and 135Cs, were estimated from the FGR value. Because experimental leaching data regarding high burnup spent nuclear fuels are extremely scarce, a mathematical modelling approach proposed by Johnson and McGinnes was successfully applied to the domestic high burnup PWR spent nuclear fuel to derive the IRF values of iodine and cesium. The best estimate of the IRF was 5.5% at a discharge burnup of 55 GWd tHM-1.