• Title/Summary/Keyword: Gene modulation

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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.

The Recent Study on Pain Modulation of Acupuncture (침의 통증 조절에 관한 최근 연구 동향)

  • Kim, Jong-Yoon;Koh, Hyeong-Gyun;Nam, Sang-Soo
    • Journal of Acupuncture Research
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    • v.23 no.1
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    • pp.145-154
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    • 2006
  • Objectives : To research the recent trends of study related to pain modulation of acupuncture. Methods : We searched the resent study related to pain modulation of acupuncture. Results & Conclusion : 1) Early studies demonstrated that the analgesic effects of acupuncture are mediated by opioid peptides in the periaqueductal gray. Recent evidences show that nitric oxide plays an important role in mediating the cardiovascular responses to acupuncture stimulation through gracile nucleus-thalamic pathway. 2) Recent evidences show that acupuncture stimulate gene expression related to pain. 3) By using functional magnetic resonance and positron emission tomography, recent study suggest that acupuncture has regionally specific, quantifiable effects on pain-relevant brain structures.

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A Molecular Study of Sopungsungi-won(Shufengshunqiyuan) about Regulation of PPARs in Mouse NMu2Li Liver Cells and C2C12 Skeletal Muscle Myogenic Progenital Cells (소풍순기원(疏風順氣元)이 mouse의 NMu2Li 간세포와 C2C12 골격근세포에서 PPARs 조절의 분자기전에 미치는 영향)

  • Oh, Young-Jin;Shin, Soon-Shik;Yoon, Mi-Chung;Kim, Bo-Kyung
    • Journal of Oriental Neuropsychiatry
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    • v.20 no.1
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    • pp.147-164
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    • 2009
  • Objectives : We investigated the effects of Sopungsungi-won(Shu!engshunqiyuan) (SSEx1, SSEx2) to treat the metabolic syndrome by the molecular mechanism of regulation of PPAR and modulation of mitochondrial MCAD, VLCAD mRNA expression. Methods : Mouse NMu2Li liver cells and C2C12 skeletal muscle myogenic progenital cells were transiently transfected with expression plasmids for PPAR(PPAR${\alpha}$, PPAR${\delta}$), a luciferase reporter gene construct containing 3 copies of the PPRE from the rat acyl-CoA oxidase gene and ${\beta}$-galactosidase gene. Cells were treated with several concentrated kinds of SSEx1, SSEx2 at the initial time of culture and analyzed PPAR${\alpha}$, PPAR${\delta}$ reporter gene activity using spectrophotometer (405 nm). Total RNA was extracted from SSEx1, SSEx2 and measured mRNA levels of mitochondrial MCAD, VLCAD. Representative RT-PCR bands are shown. Results : 1. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05), SSEx2 at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05) significantly in NMu2Li liver cell lines. 2. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 1 ${\mu}$g/ml (p${\mu}$g/ml (p${\alpha}$ reporter gene activities in C2C12 skeletal muscle cells. 4. SSEx1 increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in NMu2Li liver cell lines. 5. SSEx1, SSEx2 both increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in C2C12 skeletal muscle cells. Conclusions : These results show the SSEx1, SSEx2 can be used as therapeutic agent for metabolic syndrome and it's molecular mechanisms of PPAR more contribute to the activation of PPAR${\alpha}$ then PPAR${\delta}$ reporter gene activities and it's total RNA more contribute to the modulation of mitochondrial MCAD then VLCAD mRNA expression.

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Anti-inflammatory Flavonoids: Modulators of Proinflammatory Gene Expression

  • Kim, Hyun-Pyo;Son, Kun-Ho;Chang, Hyeun-Wook;Kang, Sam-Sik
    • Natural Product Sciences
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    • v.10 no.1
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    • pp.1-10
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    • 2004
  • Plant flavonoids possess anti-inflammatory activity in vitro and in vivo. Although the action mechanisms are not fully understood, recent studies have clearly shown that certain flavonoids, especially flavone derivatives, express their anti-inflammatory activity at least in part by modulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase and various cytokines. This review summarizes the recent findings of flavonoids modulating expression of proinflammatory molecules.

The Expression of Immunomodulation-Related Cytokines and Genes of Adipose- and Bone Marrow-Derived Human Mesenchymal Stromal Cells from Early to Late Passages

  • Mun, Chin Hee;Kang, Mi-Il;Shin, Yong Dae;Kim, Yeseul;Park, Yong-Beom
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.771-779
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    • 2018
  • BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent stem cells that can differentiate into several cell types. In addition, many studies have shown that MSCs modulate the immune response. However, little information is currently available regarding the maintenance of immunomodulatory characteristics of MSCs through passages. Therefore, we investigated and compared cytokine and gene expression levels from adipose (AD) and bone marrow (BM)-derived MSCs relevant to immune modulation from early to late passages. METHODS: MSC immunophenotype, growth characteristics, cytokine expressions, and gene expressions were analyzed. RESULTS: AD-MSCs and BM-MSCs had similar cell morphologies and surface marker expressions from passage 4 to passage 10. Cytokines secreted by AD-MSCs and BM-MSCs were similar from early to late passages. AD-MSCs and BM-MSCs showed similar immunomodulatory properties in terms of cytokine secretion levels. However, the gene expressions of tumor necrosis factor-stimulated gene (TSG)-6 and human leukocyte antigen (HLA)-G were decreased and gene expressions of galectin-1 and -3 were increased in both AD- and BM-MSCs with repeated passages. CONCLUSION: Our study showed that the immunophenotype and expression of immunomodulation-related cytokines of AD-MSCs and BM-MSCs immunomodulation through the passages were not significantly different, even though the gene expressions of both MSCs were different.

Applications of Genetically Modified Tools to Safety Assessment in Drug Development

  • Kay, Hee-Yeon;Wu, Hong-Min;Lee, Seo-In;Kim, Sang-Geon
    • Toxicological Research
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    • v.26 no.1
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    • pp.1-8
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    • 2010
  • The process of new drug development consists of several stages; after identifying potential candidate compounds, preclinical studies using animal models link the laboratory and human clinical trials. Among many steps in preclinical studies, toxicology and safety assessments contribute to identify potential adverse events and provide rationale for setting the initial doses in clinical trials. Gene modulation is one of the important tools of modern biology, and is commonly employed to examine the function of genes of interest. Advances in new drug development have been achieved by exploding information on target selection and validation using genetically modified animal models as well as those of cells. In this review, a recent trend of genetically modified methods is discussed with reference to safety assessments, and the exemplary applications of gene-modulating tools to the tests in new drug development were summarized.

Evaluation of Anti-Inflammatory Effects of Yukmijihwangtang and Individual Drug Substances Based on the Extraction Methods (추출 방법에 따른 육미지황탕의 항염증 작용 평가)

  • Lee, Gui-Hee;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.2
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    • pp.89-107
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    • 2012
  • Objectives: This study was performed to develop therapeutic prescription that is more significant than existing ones through extraction method and formulation changes. Methods: Yukmijihwangtang(YMJHT) was extracted in 80% ethanol, and their relative anti-oxidant activities as well as anti-inflammatory effects through immune modulation were measured. Results: Both water and ethanol extracted YMJHT showed does-dependent DPPH elimination activities. ROS inhibition activity was greater in water extracted YMJHT except for Moutan Cortex. NO inhibition assay results indicated that all groups showed higher NO inhibition activities in RAW 264.7 cells in dose dependent manner. Water extracted group showed higher NO inhibition activity than that of ethanol extracted group. TNF-${\alpha}$ secretion inhibition assay using RAW 264.7 cells, water extracted YMJHT showed higher activity than ethanol extracts. Growth rate of spleen cells was greater in all tested groups, with higher rate in YMJHT-EtOH than YMJHT-DW. Suppression of gene expression of IFN-r in spleen cells stimulated by Con A was higher in YMJHT-EtOH than YMJHT-DW. Suppression of gene expression of IL-10 in spleen cells stimulated by Con A was highest in YMJHT-DW with 40%. Suppression of gene expression of IL-4 in spleen cells stimulated by Con A were significant with 90% or higher in all groups and that of IL-12p35 were also higher than 90% in all cases. Conclusions: From the results, it shows that YMJHT has anti-inflammatory effects through immune modulation. However, the difference between YMJHT-EtOH and YMJHT-DW was not that significant. Further studies are needed to find out effective extraction methods of herbal medicine.