• BMB Reports
• /
• 제35권6호
• /
• pp.583-589
• /
• 2002

The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

• Molecular & Cellular Toxicology
• /
• 제5권3호
• /
• pp.187-192
• /
• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• 대한임상검사과학회지
• /
• 제36권1호
• /
• pp.27-32
• /
• 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.

• Nutritional Sciences
• /
• 제8권1호
• /
• pp.23-27
• /
• 2005

The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

• IMMUNE NETWORK
• /
• 제11권6호
• /
• pp.420-423
• /
• 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.

• 대한한방부인과학회지
• /
• 제21권1호
• /
• pp.39-54
• /
• 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.

• 한국인터넷방송통신학회논문지
• /
• 제20권3호
• /
• pp.9-14
• /
• 2020

본 논문에서는 SAR 탑재체에 적용할 수 있는 X-band 주파수합성기 인증모델(QM)을 설계 및 제작하고, 우주환경모의 시험을 통해 그 성능을 검증하였다. 제작된 주파수합성기는 상하향변환에 필요한 13.XXGHz 의 저잡음 국부신호를 생성하는 역할을 수행하며, 10Hz에서 1MHz 까지 측정된 적분 위상잡음은 -37.91 dBc 이다. 측정된 위상잡음을 통해 SAR 성능지표인 IRF성능 영향분석을 수행하였으며, 0.2 ps 의 지터로 PSLR과 ISLR에 영향 없이 SAR 시스템에 적용 가능함을 확인하였다. 또한, 열분석, 구조분석을 수행하여 안정성을 확인하였으며, 열진공, 열주기, 진동, 충격 시험을 통해 우주환경 내성을 확인하였다. 제작된 QM 급 주파수합성기는 L-band, C-band, Ku-band 주파수를 출력하며, 6U모듈 2개로 설계를 하였다. 본 연구를 통해 국내 위성용 RF 모듈의 국산화 기술 확보와 SAR 위성용 주파수합성기 기술 개발에 활용이 가능하다.

• 한국항행학회논문지
• /
• 제21권3호
• /
• pp.220-229
• /
• 2017

본 연구는 다양한 DC 전원을 활용할 수 있는 승압형 DC-DC 컨버터로 설계사양을 통한 인덕터 L과 커패시터 C의 값을 산출하여 PSPICE를 통한 최적의 값을 추정하였다. 승압형 DC-DC 컨버터는 스위치 소자로 IRF840을 사용하였으며 역회복 시간(reverse recovery time)이 뛰어난 쇼트키 다이오드(schottky rectifiers)인 D10SC6M을 사용하여 정전류 제어 (constant current controller)가 가능하도록 구성하였으며 열저항을 고려한 파워 LED 모듈 (power LED module)을 제작하여 구동하였다. 컨버터의 스위칭 주파수는 50 kHz로 최초 듀티비는 10 %에서 출력전압의 검출 값에 따라 점차적으로 증가시키도록 하였다. 그 결과로 승압형 파워 LED 구동기를 시뮬레이션 한 특성은 설계사양과 비교하여 5 %이하의 오차로 근사적으로 나타났고, 입력전압 15 V를 인가하여 안정된 24 V의 안정된 출력전압을 얻었으며 디밍제어 (dimming control)를 통한 밝기 조절 및 소비전류의 조정이 가능하였다.

• Nuclear Engineering and Technology
• /
• 제54권6호
• /
• pp.2023-2030
• /
• 2022

A novel pulse fitting analysis (PFA) method is presented for the acquisition of nuclear spectra. The charging process of the feedback capacitor in the resistive feedback charge-sensitive preamplifier is equivalent to the impulsive pulse, and its impulse response function (IRF) can be obtained by non-linear fitting of the falling edge of the nuclear pulse. The integral of the IRF excluding the baseline represents the energy deposition of the particles in the detector. In addition, since the non-linear fitting process in PFA method is difficult to achieve in the conventional architecture of spectroscopy system, a new multi-channel analyzer (MCA) based on Zynq SoC is proposed, which transmits all the data of nuclear pulses from the programmable logic (PL) to the processing system (PS) by high-speed AXI-Stream in order to implement PFA method with precision. The linearity of new MCA has been tested. The spectrum of ¹³⁷Cs was obtained using LaBr₃(Ce) scintillator detector, and was compared with commercial MCA by ORTEC. The results of tests indicate that the MCA based on PFA method has the same performance as the commercial MCA based on pulse height analysis (PHA) method and excellent linearity for γ-rays with different energies, which infers that PFA method is an effective and promising method for the acquisition of spectra. Furthermore, it provides a new solution for nuclear pulse processing algorithms involving regression and iterative processes.

• Clinical and Experimental Reproductive Medicine
• /
• 제50권1호
• /
• pp.44-52
• /
• 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.