• Title/Summary/Keyword: signal molecule

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Targeted Immunotherapy for Autoimmune Disease

  • Seung Min Jung;Wan-Uk Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.9.1-9.23
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    • 2022
  • In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

Anti-Angiogenic and Anti-Cell Adhesion Effect of the Camellia japonica Flower Extract (동백꽃 추출물의 신생혈관생성 및 세포부착 억제 효과)

  • Heo, In-Do;Seo, Hyo-Jin;Kim, Jong-Deog
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1152-1156
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    • 2007
  • The Camella japonica flower(CJF) extract was studied for their anti-angiogenenic and anti-cell adhesion effect. CJF-extract inhibited the tube formation on human umbilical vein endotherial cells(HUVEC) with butanol extract by 70.2%, acetone extract by 54.2%, ethyl acetate extract by 37.0%, chloroform extract by 21.2%. Cell adhesion molecules were effectively suppressed at different concentration of CJF at 50, 100, 200 ug/well such as for intercellular adhesion molecule(ICAM) by 5.9%, 29.4% and 52.9%, for vascular cell adhesion molecule(VCAM) by 12.5%, 43.8% and 62.5%, for E-selectin by 7.1%, 21.4% and 35.7%, respectively. Signal molecules of vascular endotherial growth factor receptor 2(VEGFR2), ${/beta}$-catenin and PI3K are inhibited by different concentration of CJF at 10, 20 and 30 ${\mu}g/mL$ with western blot. Angiogenesis will be inhibited with suppressing NF-kB molecule resulted in signal molecules blocked by CJF. CJF will be useful materials for treatment of angiogenesis related diseases such as cancer, metastasis, rheumathioid arthritis and obesity.

Cinnamomum camphora Leaves Alleviate Allergic Skin Inflammatory Responses In Vitro and In Vivo

  • Kang, Na-Jin;Han, Sang-Chul;Yoon, Seok-Hyun;Sim, Jae-Yeop;Maeng, Young Hee;Kang, Hee-Kyoung;Yoo, Eun-Sook
    • Toxicological Research
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    • v.35 no.3
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    • pp.279-285
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    • 2019
  • In this study, we investigated the therapeutic potential of Cinnamomum camphora leaves on allergic skin inflammation such as atopic dermatitis. We evaluated the effects of C. camphora leaves on human adult low-calcium high-temperature keratinocytes and atopic dermatitis mice. C. camphora leaves inhibited Macrophage-derived chemokine (an inflammatory chemokine) production in $interferon-{\gamma}$ (10 ng/mL) stimulated Human adult low-calcium high-temperature keratinocytes in a dose dependent manner. C. camphora leaves suppressed the phosphorylation of janus kinase signal transducer and activator of transcription 1. C. camphora leaves also suppressed the phosphorylation of extracellular signal-regulated kinase 1/2, a central signaling molecule in the inflammation process. These results suggest that C. camphora leaves exhibits anti-inflammatory effect via the phosphorylation of signal transducer and activator of transcription 1 and extracellular signal-regulated kinase 1/2. To study the advanced effects of C. camphora leaves on atopic dermatitis, we induced experimental atopic dermatitis in mice by applying 2,4-dinitrochlorobenzene. The group treated with C. camphora leaves (100 mg/kg) showed remarkable improvement of atopic dermatitis symptoms: reduced serum immunoglobulin E levels, smaller lymph nodes with reduced thickness and length, decreased ear edema, and reduced levels of inflammatory cell infiltration in the ears. Interestingly, the effects of C. camphora leaves on atopic dermatitis symptoms were stronger than those of hydrocort cream, a positive control. Taken together, C. camphora leaves showed alleviating effects on the inflammatory chemokine production in vitro and atopic dermatitis symptoms in vivo. These results suggest that C. camphora leaves help in the treatment of allergic inflammation such as atopic dermatitis.

D99 Type I Signal Peptidase Implicated Stabilizing the Protein Structure (Type I 신호펩디드 가수분해효소에 존재하는 D99 아미노산 잔기의 구조적 역할 가능성)

  • Sung, Meesook;Eunyoung Han;Lee, Hoyoung
    • Microbiology and Biotechnology Letters
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    • v.31 no.2
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    • pp.140-144
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    • 2003
  • Type Ⅰ signal peptidase is an integral membrane protein that functions to cleave signal peptides from secreted and membrane proteins. The enzyme serves as a potential target for the development of novel antibacterial agents due to its unique physiological properties. Despite being one of the best characterized enzymes, the catalysis of Type Ⅰ signal peptidase still remains controversy over the catalytic serine/lysine dyad mechanism. It appears that the dyad proteases are generally less efficient than the prototypical serine/histidine/aspartic acid triad found in most enzymes, although Type Ⅰ signal peptidase is an exception to this rule. In this paper, we have proposed that Type Ⅰ signal peptidase may act as the serine/lysine/aspartic acid triad cataltytic mechanism. Therefore, the aspartic acid 99 residue in the E. coli signal peptidase was chosen and mutated to an alanine to see if there is any possible role of the aspartic acid in the catalytic function. Type Ⅰ signal peptidase D99A protein was inactive in vitro assay using the procoat synthesized by in vitro transcription translation. However, the mutant was active using a highly sensitive in vivo assay. Pulse-chase experiments show that the replacement of aspartic acid 99 with alanine results in a very unstable signal peptidase molecule. Therefore, we conclude that it is unlikely that the residue is directly involved in catalysis, but rather plays an important role in stabilizing the protein structure.

3',5'-Cyclic Adenosine Monophosphate (cAMP) as a Signal and a Regulatory Compound in Bacterial Cells (원핵세포에서 신호물질 및 조절인자로서의 3',5'-Cyclic Adenosine Monophosphate의 역할)

  • Chun, Se-Jin;Seok, Young-Jae;Lee, Kyu-Ho
    • Microbiology and Biotechnology Letters
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    • v.34 no.4
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    • pp.289-298
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    • 2006
  • 3',5'-cyclic adenosine monophosphate (cAMP) is an important molecule, which mediates diverse cellular processes. For example, it is involved in regulation of sugar uptake/catabolism, DNA replication, cell division, and motility in various acterial species. In addition, cAMP is one of the critical regulators for syntheses of virulence factors in many pathogenic bacteria. It is believed that cAMP acts as a signal for environmental changes as well as a regulatory factor for gene expressions. Therefore, intracellular concentration of cAMP is finely modulated by according to its rates of synthesis (by adenylate cyclase), excretion, and degradation (by cAMP phosphodiesterase). In the present review, we discuss the bacterial physiological characteristics governed by CAMP and the molecular mechanisms for gene regulation by cAMP. Furthermore, the effect of cAMP on phosphotransferase system is addressed.

Performance Evaluation of a Rapid Three Dimensional Diffusion MRI

  • Numano, Tomokazu;Homma, Kazuhiro;Nishimura, Katsuyuki
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2002.09a
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    • pp.356-358
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    • 2002
  • MRI, particularly diffusion weighted imaging (DWI), plays vital roles in detection of the acute brain infarction$\^$1-4/ and others metabolic changes of biological tissues. In general, every molecule in biological tissues may diffuse and move randomly in three-dimensional space. However, in clinical diagnosis, only 2D-DWI is used. The authors have developed a new method for rapid three-dimensional DWI (3D-DWI). In this method, by refocusing of the magnetized spin with the applied gradient field, direction of which is opposite to phase encoding field. Magnetized spin of $^1$H is kept under the SSFP (steady state free precession)$\^$5-6/. Under SSFP, in addition of FID, spin echo and stimulated echo are also generated, so the acquired signal is increased. The signal intensity is increased depending on flip angle (FA) of magnetized spin. This phenomenon is confirmed by human brain and phantom studies. The performance of this method is quantitatively analyzed by using both of conventional spin echo DWI and 3D-DWI. From experimental results, three dimensional diffusion weighted images are obtained correctly for liquid phantoms (water, acetone and oil), diffusion coefficient is enhanced in each image. Therefore, this method will provide useful information for clinical diagnosis.

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AP2/EREBP Transcription Factors in Rice

  • Kim, Yun-Ju;Jung, Eui-Whan;Hwang, Seon-Hee;Go, Seong-Joo;Hwang, Duk-Ju
    • The Plant Pathology Journal
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    • v.20 no.1
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    • pp.41-45
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    • 2004
  • Plants have the ability to defend themselves against pathogens by activating a series of defense responses. SA is known to be a signal molecule in plant defense responses. Nevertheles, SA is not the only one signal mediating defense responses. In addition to SA, ethylene and jasmonic acid have also been known to mediate plant defense responses against pathogens. The activation of a series of plant defense responses is known to be through varieties of transcription factors. Specially AP2/EREBP transcription factors are involved in ethylene mediated defense signaling. In this review, recent progress on AP2/EREBP transcription factors in arabidopsis, tomato and tobacco and a few of AP2/ EREBP transcription factors in rice related to biotic stresses will be discussed.

Isolation and Characterization of Methyl Jasmonate -Inducible Genes in Chinese Cabbage

  • Park, Yong-Soon;Cho, Tae-Ju
    • Animal cells and systems
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    • v.7 no.4
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    • pp.337-343
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    • 2003
  • Methyl jasmonate (MeJA) is a signal molecule in the activation of defense responses in plants. In this study, we isolated 15 MeJA-inducible genes by subtractive hybridization. These genes encode two myrosinase-binding proteins, five lipase-like proteins, a polygalacturonase inhibitor, a putative chlorophyll-associated protein, a terpene synthase, a dehydroascorbate reductase, an ascorbate oxidase, a cysteine protease, an O-methyltransferase, and an epithiospecifier protein. Northern analysis showed that most of the Chinese cabbage genes are barely expressed in healthy leaves, but are strongly induced by MeJA treatment. We also examined whether these MeJA-inducible genes were activated by ethethon, BTH, and Pseudomonas syringae pv. tomato (Pst), a nonhost pathogen of Chinese cabbage. The results showed that none of the MeJA-inducible genes was strongly induced by ethephon or by BTH. The genes encoding lipase-like proteins and a myrosinase-binding protein were weakly induced by Pst. Other MeJA-inducible genes were not activated at all by the pathogen.

Periplasmic Expression of a Recombinant Antibody (MabB9) in Escherichia coli

  • Chang, Hae-Choon;Kwak, Ju-Won
    • Journal of Microbiology and Biotechnology
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    • v.7 no.5
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    • pp.299-304
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    • 1997
  • Expression in the periplasm of Escherichia coli of cloned heavy and light chain cDNAs for Fab fragment of a murine monoclonal antibody MabB9 (${\gamma}2b$, K), specific for human plasma apolipoprotein B-100 of LDL, was studied. For the purpose, a vector for two-cistronic expression of the heavy chain cDNA, at the 5' terminus, and light chain cDNA, at the 3' terminus, was constructed using the signal sequences, pelB (for heavy chain) and ompA (for light chain) in a pET vector system. The constructed vector was transformed into E. coli BL21(DE3). The expressed heavy chain (25 kDa) and light chain (23 kDa) of the antibody molecule were detected in total cell extracts as well as in the periplasmic extracts of E. coli.

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Standoff Raman Spectroscopic Detection of Explosive Molecules

  • Chung, Jin Hyuk;Cho, Soo Gyeong
    • Bulletin of the Korean Chemical Society
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    • v.34 no.6
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    • pp.1668-1672
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    • 2013
  • We developed a standoff Raman detection system for explosive molecules (EMs). Our system was composed of reflective telescope with 310 mm diameter lens, 532 nm pulse laser, and Intensified Charge-Coupled Device (ICCD) camera. In order to remove huge background noise coming from ambient light, laser pulses with nanosecond time width were fired to target sample and ICCD was gated to open only during the time when the scattered Raman signal from the sample arrived at ICCD camera. We performed standoff experiments with military EMs by putting the detector at 10, 20 and 30 m away from the source. The standoff results were compared with the confocal Raman results. Based on our standoff experiments, we were able to observe the peaks in the range of 1200 and $1600cm^{-1}$, where vibrational modes of nitro groups were appeared. The wave numbers and shapes of these peaks may serve as good references in detecting and identifying various EMs.