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Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells

  • Lee, Yun-Jung;Won, Tae Joon;Hyung, Kyeong Eun;Lee, Mi Ji;Moon, Young-Hye;Lee, Ik Hee;Go, Byung Sung;Hwang, Kwang Woo
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.1
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    • pp.73-78
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    • 2014
  • Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-${\kappa}B$) translocation.

A 41dB Gain Control Range 6th-Order Band-Pass Receiver Front-End Using CMOS Switched FTI

  • Han, Seon-Ho;Nguyen, Hoai-Nam;Kim, Ki-Su;Park, Mi-Jeong;Yeo, Ik-Soo;Kim, Cheon-Soo
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.16 no.5
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    • pp.675-681
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    • 2016
  • A 41dB gain control range $6^{th}$-order band-pass receiver front-end (RFE) using CMOS switched frequency translated impedance (FTI) is presented in a 40 nm CMOS technology. The RFE consists of a frequency tunable RF band-pass filter (BPF), IQ gm cells, and IQ TIAs. The RF BPF has wide gain control range preserving constant filter Q and pass band flatness due to proposed pre-distortion scheme. Also, the RF filter using CMOS switches in FTI blocks shows low clock leakage to signal nodes, and results in low common mode noise and stable operation. The baseband IQ signals are generated by combining baseband Gm cells which receives 8-phase signal outputs down-converted at last stage of FTIs in the RF BPF. The measured results of the RFE show 36.4 dB gain and 6.3 dB NF at maximum gain mode. The pass-band IIP3 and out-band IIP3@20 MHz offset are -10 dBm and +12.6 dBm at maximum gain mode, and +14 dBm and +20.5 dBm at minimum gain mode, respectively. With a 1.2 V power supply, the current consumption of the overall RFE is 40 mA at 500 MHz carrier frequency.

Nucleotide-Binding Domain and Leucine-Rich Repeat Containing Receptor (NLR) and its Signaling Pathway

  • Park, Sangwook;Gwon, Sun-Yeong;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.19 no.3
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    • pp.173-179
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    • 2013
  • Since the identification and characterization of toll-like receptors (TLR) in Drosophila, numerous scientific studies have examined the role of TLRs in host innate immunity. Recent studies have suggested a convergence of the nuclear factor kappa B (NF-${\kappa}B$) signaling and cytokine production regulated by the cytosolic elicitor known as NLRs (nucleotide-binding domain and leucine-rich repeat containing domain receptors) as a key modulator in inflammatory diseases. Among the NLRs, NOD1 and NOD2 have been intensively investigated for its role in inflammatory bowel disease (IBD). On the other hand, NLRs such as NLRP3, NLRP1, and NLRC4 (also known as IPAF) have been identified to form the inflammasome to activate downstream signaling molecules in response to pathogenic microbes. There is evidence to suggest that substantial crosstalk exists for the TLR and NLR signaling pathway in response to pathogen associated molecular pattern (PAMP). However, the substrate and the mechanistic role of NLRs are largely unknown in innate immune response. Understanding the signaling mechanisms by which NLRs recognize PAMP and other danger signals will shed light on elucidating the pathogenesis of various human inflammatory diseases such as IBD.

Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

  • Kim, Eun Jeong;Kim, Jeeho;Lee, Min Young;Sudhanva, Muddenahalli Srinivasa;Devakumar, Sundaravinayagam;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.282-287
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    • 2014
  • We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-${\kappa}B$, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

Phospholipase D and Its Essential Role in Cancer

  • Cho, Ju Hwan;Han, Joong-Soo
    • Molecules and Cells
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    • v.40 no.11
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    • pp.805-813
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    • 2017
  • The role of phospholipase D (PLD) in cancer development and management has been a major area of interest for researchers. The purpose of this mini-review is to explore PLD and its distinct role during chemotherapy including anti-apoptotic function. PLD is an enzyme that belongs to the phospholipase super family and is found in a broad range of organisms such as viruses, yeast, bacteria, animals, and plants. The function and activity of PLD are widely dependent on and regulated by neurotransmitters, hormones, small monomeric GTPases, and lipids. A growing body of research has shown that PLD activity is significantly increased in cancer tissues and cells, indicating that it plays a critical role in signal transduction, cell proliferation, and anti-apoptotic processes. In addition, recent studies show that PLD is a downstream transcriptional target of proteins that contribute to inflammation and carcinogenesis such as Sp1, $NF{\kappa}B$, TCF4, ATF-2, NFATc2, and EWS-Fli. Thus, compounds that inhibit expression or activity of PLD in cells can be potentially useful in reducing inflammation and sensitizing resistant cancers during chemotherapy.

Effects of Gwibitang on Glutamate-induced Apoptosis in C6 Glial Cells (귀비탕이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 영향)

  • 강익현;이인;한상혁;문병순
    • The Journal of Korean Medicine
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    • v.22 no.4
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    • pp.45-57
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    • 2001
  • Objectives : The water extract of Gwibitang (GBT) has been traditionally used for treatment of psychologic disease and brain damage in Oriental Medicine, This study was designed to investigate the effect of GBT on the glutamate-induced toxicity of rat C6 glial cells. Methods : The cultured cells were pretreated with GBT and exposed to glutamate, The cell damage was assessed by using MTT assay and Hoechst, IC-l staining, Results : GBT had protective effects in glutamate-induced cytotoxicity, which was revealed as apoptosis characterized by chromatic condensation and the loss of mitochondrial membrane potential in C6 glial cells. However, GBT and glutamate had no effect in the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteasesin C6 glial ce]]s, GBT significantly recovered the depletion of GSH and inhibited the generation of $H_2O_2$ by glutamate in C6 glial cells. In addition, both GBT and antioxidants such as GSH and NAC protected the glutamate-induced cytotoxicity in C6 glial cells, indicating that GBT possibly has antioxidative effect. Moreover, GBT also inhibited the glutamate-induced degradation of $IkB{\alpha}$ in C6 glial cells, This result suggest that GBT has some inhibitory effects on the transcriptional activation of $NF-_{k}B$. Conclusions : GBT has protective effects in glutamate-induced cytotoxicity via an antioxidative mechanism.

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Anti-inflammatory effects of porcine placenta in forced swimming tested fatigue mice and RAW264.7 cells

  • Nam, Sun-Young;Kang, Sang Woo;Kim, Jongbae;Lee, Won Kyung
    • CELLMED
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    • v.7 no.4
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    • pp.20.1-20.6
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    • 2017
  • Inflammation has been linked to various diseases. Especially, fatigue is a frequent symptom in several inflammatory disorders. Therefore, blocking inflammatory process is effective in fatigue. We investigated whether Denmark porcine placenta (DPP) alleviates fatigue by inhibiting inflammatory reaction using forced swimming test (FST) animal model and RAW264.7 cells. In FST-induced fatigue animal model, the mice which received the DPP for 21 days showed decreases of interleukin $(IL)-1{\beta}$ and IL-6 serum levels. Furthermore, our data revealed that lipopolysaccharide (LPS)-induced $IL-1{\beta}$, IL-6, and tumor necrosis $factor-{\alpha}$ secretion were markedly inhibited by DPP in RAW264.7 cells without inducing cytotoxicity. LPS-enhanced nitric oxide secretion and inducible nitric oxide synthase expression were inhibited by DPP. The present study also figured out that these effects of DPP were mediated by blockade of caspase-1 and nuclear $factor-{\kappa}B$ activation. Taken together, our results indicated that DPP could be alleviating fatigue as candidate of anti-inflammatory agent.

Modeling of Plasma Etch Process using a Radial Basis Function Network (레이디얼 베이시스 함수망을 이용한 플라즈마 식각공정 모델링)

  • Park, Kyoungyoung;Kim, Byungwhan
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.18 no.1
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    • pp.1-5
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    • 2005
  • A new model of plasma etch process was constructed by using a radial basis function network (RBFN). This technique was applied to an etching of silicon carbide films in a NF$_3$ inductively coupled plasma. Experimental data to train RBFN were systematically collected by means of a 2$^4$ full factorial experiment. Appropriateness of prediction models was tested with test data consisted of 16 experiments not pertaining to the training data. Prediction performance was optimized with variations in three training factors, the number of pattern units, width of radial basis function, and initial weight distribution between the pattern and output layers. The etch responses to model were an etch rate and a surface roughness measured by atomic force microscopy. Optimized models had the root mean-squared errors of 26.1 nm/min and 0.103 nm for the etch rate and surface roughness, respectively. Compared to statistical regression models, RBFN models demonstrated an improvement of more than 20 % and 50 % for the etch rate and surface roughness, respectively. It is therefore expected that RBFN can be effectively used to construct prediction models of plasma processes.

Transcriptional Responses of Human Respiratory Epithelial Cells to Nontypeable Haemophilus influenzae Infection Analyzed by High Density cDNA Microarrays

  • Lee, Ji-Yeon;Lee, Na-Gyong
    • Journal of Microbiology and Biotechnology
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    • v.14 no.4
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    • pp.836-843
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    • 2004
  • Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

A Neurofibroma Confused with Sarcomatous Transformation on F-18 FDG PET/CT in Neurofibromatosis-1 (신경섬유종증 환자의 F-18 FDG PET/CT에서 육종전환으로 오인된 신경섬유종)

  • Park, Soon-Ah;Song, Jeong-Hoon;Yang, Chung-Yong;Kim, Hun-Soo;Park, Seung-Chol
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.4
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    • pp.361-362
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    • 2009
  • We present a patient with high $^{18}$F-fluorodeoxyglucose (FDG) uptake detected in a neurofibroma that was confused with sarcomatous transformation on a positron emission tomography/computed tomography (PET/CT) scan. A 39-year-old male patient with a 20-year history of neurofibromatosis-1 (NF-1) performed FDG PET/CT scan for the evaluation of lesions with sarcomatous transformation. The FDG PET/CT images demonstrated varying degrees of increased FDG uptake in the multiple nodules throughout whole body. The left pelvic mass with the highest FDG uptake had a maximum standardized uptake values (maxSUV) 5.0 and surgical resection was performed. Histological analysis confirmed the presence of a benign neurofibroma infiltrated with inflammatory cells.