• Title/Summary/Keyword: IRF-1,7

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Clinical Significance of Immature Reticulocyte as an Early Recovery Indicator after Bone Marrow Transplantation (골수이식 후 미성숙 망상적혈구의 유용성 평가)

  • Seo, Suk Won;Kim, Chun Hee;Chi, Hyun Sook
    • Korean Journal of Clinical Laboratory Science
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    • v.36 no.1
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    • pp.27-32
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    • 2004
  • Bone marrow transplantation(BMT) is widely used as curative means of various malignant and nonmalignant hematologic disorders, and early and accurate determination of engraftment is very important for critical management decisions. Reticulocyte counts performed by automated flow cytometric methods is a good indicator of erythropoietic activity and its evaluation has been proposed as an early predictor of bone marrow regeneration. Some reports highlighted the usefulness of the percentage of highly fluorescent reticulocytes and the sum of highly and medium fluorescent reticulocytes(immature reticulocyte fraction, IRF). In Asan Medical Center, the criteria for engraftment following BMT or PBSCT was defined as the first day of a 3-day trend of absolute neutrophil count(ANC)${\geq}500/uL$ and platelet count${\geq}30{\times}10^3/uL$. In 1999, Grotto et al proposed an indidator of bone marrow recovery as the first day on which the IRF was twice the minimum value after bone marrow transplantation. To compare the both criterias, we got consecutive datas of immature reticulocyte fraction, absolute neutrophil count(ANC), WBC count, platelet count and reticulocyte count by XE-2100 automated hematology analyzer(Sysmex Co. Japan) from 33 patients daily after BMT. When compared to standard neutrophil engraftment(10-30 days, $16.2{\pm}4.6days$), IRF engraftment (5-21 days, $11.0{\pm}3.9days$) occured significantly earlier in 87.9% of patients(P<0.05). The mean engraftment day for WBC count(11-29 days, $16.4{\pm}4.3days$) was similar to ANC, but platelet count and reticulocyte count revealed more delayed data (10-49 days, $19.1{\pm}7.4days$ vs 17-64 days, $31.4{\pm}14.1days$). In conclusion, our results confirm that an increase in the immature reticulocyte population is the earliest sign of the hematopoietic recovery after BMT and that automated reticulocyte quantification including immature fraction may be integrated into clinical protocols to evaluate bone marrow reconstitution.

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In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components

  • Baek, Kwang-Soo;Yi, Young-Su;Son, Young-Jin;Yoo, Sulgi;Sung, Nak Yoon;Kim, Yong;Hong, Sungyoul;Aravinthan, Adithan;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.437-444
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    • 2016
  • Background: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. Methods: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. Results: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 mg/mL significantly suppressed NO production at $100{\mu}g/mL$, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interferon-${\beta}$ at $200{\mu}g/mL$, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. Conclusion: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

Anti-inflammatory Effects of Omisodokeum (오미소독음(五味消毒飮)의 항염효과(抗炎效果) 및 기전(機轉)에 관(關)한 실험적연구(實驗的硏究))

  • Seo, Yun-Jung;Kim, Song-Baeg;Cho, Han-Baek;Choe, Chang-Min;Lee, Soon-Yee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.1
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    • pp.39-54
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    • 2008
  • Purpose: The purpose of this study was to investigate the anti-inflammatory effects of the water extract of Omisodokeum (OMSDE) on peritoneal macrophages, Methods: To verify the anti-inflammatory mechanism of OMSDE, the activation of nuclear $factor-{\kappa}B$ $(NF-{\kappa}B)$ and the phosphorylation of MAPK were examined. Results: The extract of OMSDE suppressed the production of LPS-induced nitric oxide (NO), tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and IL-12 in the macrophages. OMSDE inhibited the degradation of inhibitory ${\kappa}B-{\alpha}$ $(I{\kappa}B-{\alpha})$ and it suppressed the activation of extracellular signal-regulated kinase (ERK 1/2) but didn't inhibit c-Jun N-terminal kinase (JNK) and p38, indicating that OMSDE may inhibit the pro-inflammatory cytokine production process by inhibiting the activation of $NF-{\kappa}B$ and ERK 1/2. Furthermore, OMSDE inhibited the production of interferon $(IFN)-{\beta}$ but didn't inhibit of $IFN-{\alpha}$ in the LPS-stimulated macrophages through the down-regulation of interferon regulatory factor (IRF)-1 and IRF-7. The Oral administration of OMSDE inhibited LPS-induced endotoxin shock and the production of $TNF-{\alpha}$ in serum but didn't inhibit of $IL-1{\beta}$ and IL-6. Conclusion: These results suggest that OMSDE may be effective in the prevention and treatment of inflammatory diseases.

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Genetic Features of Lung Adenocarcinoma with Ground-Glass Opacity: What Causes the Invasiveness of Lung Adenocarcinoma?

  • Kim, Dohun;Lee, Jong-Young;Yoo, Jin Young;Cho, Jun Yeun
    • Journal of Chest Surgery
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    • v.53 no.5
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    • pp.250-257
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    • 2020
  • Background: Lung adenocarcinoma (LUAD) with ground-glass opacity (GGO) can become aggravated, but the reasons for this aggravation are not fully understood. The goal of this study was to analyze the genetic features and causes of progression of GGO LUAD. Methods: LUAD tumor samples and normal tissues were analyzed using an Illumina HiSeq 4000 system. After the tumor mutational burden (TMB) was calculated, the identified mutations were classified as those found only in GGO LUAD, those present only in nonGGO LUAD, and those common to both tissue types. Ten high-frequency genes were selected from each domain, after which protein interaction network analysis was conducted. Results: Overall, 227 mutations in GGO LUAD, 212 in non-GGO LUAD, and 48 that were common to both tumor types were found. The TMB was 8.8 in GGO and 7.8 in non-GGO samples. In GGO LUAD, mutations of FCGBP and SFTPA1 were identified. FOXQ1, IRF5, and MAGEC1 mutations were common to both types, and CDC27 and NOTCH4 mutations were identified in the non-GGO LUAD. Protein interaction network analysis indicated that IRF5 (common to both tissue types) and CDC27 (found in the non-GGO LUAD) had significant biological functions related to the cell cycle and proliferation. Conclusion: In conclusion, GGO LUAD exhibited a higher TMB than non-GGO LUAD. No clinically meaningful mutations were found to be specific to GGO LUAD, but mutations involved in the epithelial-mesenchymal transition or cell cycle were found in both tumor types and in non-GGO tissue alone. These findings could explain the non-invasiveness of GGO-type LUAD.

CKD-712, (S)-1-(${\alpha}$-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-${\kappa}B$ Activation and Augments Akt Activation during TLR4 Signaling

  • Lee, Jeong-Gi;Yang, Eun-Jeong;Shin, Jeon-Soo;Kim, Dal-Hyun;Lee, Sung-Sook;Choi, In-Hong
    • IMMUNE NETWORK
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    • v.11 no.6
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    • pp.420-423
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    • 2011
  • Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-${\kappa}B$ was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-${\kappa}B$ signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-${\kappa}B$ activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.

TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells

  • Zahra Zandieh;Azam Govahi;Azin Aghamajidi;Ehsan Raoufi;Fatemehsadat Amjadi;Samaneh Aghajanpour;Masoomeh Golestan;Reza Aflatoonian
    • Clinical and Experimental Reproductive Medicine
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    • v.50 no.1
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    • pp.44-52
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    • 2023
  • Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Design and Structural Safety Evaluation of 1MW Class Tidal Current Turbine Blade applied Composite Materials (복합재료를 적용한 1MW급 조류 발전 터빈 블레이드의 설계와 구조 안전성 평가)

  • Haechang Jeong;Min-seon Choi;Changjo Yang
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.28 no.7
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    • pp.1222-1230
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    • 2022
  • The rotor blade is an important component of a tidal stream turbine and is affected by a large thrust force and load due to the high density of seawater. Therefore, the performance must be secured through the geometrical and structural design of the blade and the blade structural safety to which the composite material is applied. In this study, a 1 MW class large turbine blade was designed using the blade element momentum (BEM) theory. GFRP is a fiber-reinforced plastic used for turbine blade materials. A sandwich structure was applied with CFRP to lay-up the blade cross-section. In addition, to evaluate structural safety according to flow variations, static load analysis within the linear elasticity range was performed using the fluid-structure interactive (FSI) method. Structural safety was evaluated by analyzing tip deflection, strain, and failure index of the blade due to bending moment. As a result, Model-B was able to reduce blade tip deflection and weight. In addition, safety could be secured by indicating that the failure index, inverse reserve factor (IRF), was 1 or less in all load ranges excluding 3.0*Vr of Model-A. In the future, structural safety will be evaluated by applying various failure theories and redesigning the laminated pattern as well as the change of blade material.

The Impact of COVID-19 on Individual Industry Sectors: Evidence from Vietnam Stock Exchange

  • TU, Thi Hoang Lan;HOANG, Tri M.
    • The Journal of Asian Finance, Economics and Business
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    • v.8 no.7
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    • pp.91-101
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    • 2021
  • The paper examines the impact of the COVID-19 pandemic on the stock market prices. The vector autoregression model (VAR) has been used in this analysis to survey 341 stocks on the Ho Chi Minh City Stock Exchange (HOSE) for the period from January 23, 2020 to December 31, 2020. The empirical results obtained from the analysis of 11 economic sectors suggest that there is a statistically significant impact relationship between COVID-19 and the healthcare and utility industries. Additional findings show a statistically significant negative impact of COVID-19 on the utility share price at lag 1. Analysis of impulse response function (IRF) and forecast error variance decomposition (FEVD) show an inverse reaction of utility stock prices to the impact of COVID-19 and a gradual disappearing shock after two steps. Major findings show that there is a clear negative effect of the COVID-19 pandemic on share prices, and the daily increase in the number of confirmed cases, indicate that, in future disease outbreaks, early containment measures and positive responses are necessary conditions for governments and nations to protect stock markets from excessive depreciation. Utility stocks are among the most severely impacted shares on financial exchanges during a pandemic due to the high risk of immediate or irreversible closure of manufacturing lines and poor demand for basic amenities.

The Effect of Image Rejection Filter on Flatness of Microwave Terrestrial Receiver

  • Han, Sok-Kyun;Park, Byung-Ha
    • Journal of electromagnetic engineering and science
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    • v.3 no.2
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    • pp.86-90
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    • 2003
  • A flat conversion loss in microwave mixer is hard to achieve if integrating with an image rejection filter(IRF). This is due to the change of termination condition with respect to the LO and IF frequency at RF port where the filter has 50 ohm termination property only in the RF band. This paper describes a flatness maintenance in the down mixer concerning a diode matching condition as well as an electrical length of embedding line at RF port. The implemented single balance diode mixer is suitable for a 23 ㎓ European Terrestrial Radio. RF, LO and fixed IF frequency chosen in this paper are 21.2∼22.4 ㎓, 22.4∼23.6 ㎓ and 1.2 ㎓, respectively. The measured results show a conversion loss of 8.5 ㏈, flatness of 1.2 ㏈ p-p, input P1㏈ of 7㏈m, IIP3 of 15.42 ㏈m with nominal LO power level of 10㏈m. The return loss of RF and LO port are less than - 15 ㏈ and - 12 ㏈, respectively and IF port is less than - 6 ㏈. LO/RF and LO/IF isolation are 18 ㏈ and 50 ㏈, respectively. This approach would be a helpful reference for designing up/down converter possessing a filtering element.

Induction of IFN-β through TLR-3- and RIG-I-Mediated Signaling Pathways in Canine Respiratory Epithelial Cells Infected with H3N2 Canine Influenza Virus

  • Park, Woo-Jung;Han, Sang-Hoon;Kim, Dong-Hwi;Song, Young-Jo;Lee, Joong-Bok;Park, Seung-Yong;Song, Chang-Seon;Lee, Sang-Won;Choi, In-Soo
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.942-948
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    • 2021
  • Canine influenza virus (CIV) induces acute respiratory disease in dogs. In this study, we aimed to determine the signaling pathways leading to the induction of IFN-β in a canine respiratory epithelial cell line (KU-CBE) infected with the H3N2 subtype of CIV. Small interfering RNAs (siRNAs) specific to pattern recognition receptors (PRRs) and transcription factors were used to block the IFN-β induction signals in H3N2 CIV-infected KU-CBE cells. Among the PRRs, only the TLR3 and RIG-I expression levels significantly (p < 0.001) increased in CIV-infected cells. Following transfection with siRNA specific to TLR3 (siTLR3) or RIG-I (siRIG-I), the mRNA expression levels of IFN-β significantly (p < 0.001) decreased, and the protein expression of IFN-β also decreased in infected cells. In addition, co-transfection with both siTLR3 and siRIG-I significantly reduced IRF3 (p < 0.001) and IFN-β (p < 0.001) mRNA levels. Moreover, the protein concentration of IFN-β was significantly (p < 0.01) lower in cells co-transfected with both siTLR3 and siRIG-I than in cells transfected with either siTLR3 or siRIG-I alone. Also, the antiviral protein MX1 was only expressed in KU-CBE cells infected with CIV or treated with IFN-β or IFN-α. Thus, we speculate that IFN-β further induces MX1 expression, which might suppress CIV replication. Taken together, these data indicate that TLR3 and RIG-I synergistically induce IFN-β expression via the activation of IRF3, and the produced IFN-β further induces the production of MX1, which would suppress CIV replication in CIV-infected cells.