• Title/Summary/Keyword: STAT1/STAT6

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Effect of Inhibition Macrophage Migration Inhibitory Factor Activation by Hominis Placenta Herbal Acupuncture on Rheumatic Arthritis (자하차약침(紫河車藥鍼)의 MIF 활성 억제를 통한 LPS 유발 류마티스성 관절염의 치료 효과)

  • Hwang, Ji-Hye;Cho, Hyun-Seok;Lee, Hyun-Jin;Lee, Dong-Gun;Jeong, Won-Je;Jung, Chan-Yung;Kim, Kyung-Ho
    • Journal of Acupuncture Research
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    • v.25 no.3
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    • pp.41-51
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    • 2008
  • Objectives : This study is to evaluate Effect of Inhibition Macrophage Migration Inhibitory Factor(MIF) activation by Hominis Placenta Herbal Acupuncture(HPA) on Rheumatic Arthritis(RA). Hominis Placenta is the placenta of healthy human, which is vital-strengthening medical stuff. In recent years, Hominis Placenta applied to chronic diseases because it makes us more resistance to diseases. Therefore it is supposed that HPA is effective on RA, a kind of autoimmune disease. When RA is induced, MIF is activated, too. MIF affects the process of inflammatory disease including RA. Methods : In order to investigate the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP(Matrix Metallo Proteinase)-9 mRNA expression by means of Reverse Transcriptase- Polymerase Chain Reaction(RT-PCR). In this study, we investigated the effect of Hominis Placenta extraction on MIF(early RA inducing cytokine) and MMP-9 mRNA expression by means of RT-PCR. Besides we investigated changing of MIF in synovial membrane and, Interleukin-6 receptor(IL-6R)-$\alpha$(pro-inflammatory cytokine), Signal transducers and activators of transcription(STAT)-3, MMP-9 after treating mouse, which is artificially attacked with RA, with HPA on its $ST_{35}$, LE201 in vivo. Results : 1. As a result of treating Lipopolysaccharide(LPS)-stimulated Raw246.7cell with HPA, MIF(RA related cytokine) and MMP-9 mRNA expression is reduced in vitro. And this reaction is concentration-dependatant. 2. In synovial membrane of the mice treated with HPA, inhibition of MIF, IL-6R-$\alpha$, STAT3 & MMP-9 activation is observed in vivo. Conclusions : From the above results, it might be suggested that HPA mitigate tissue damage originated from RA, because it intercepts the early process of by inhibition MIF activity.

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Astragaloside IV Prevents Obesity-Associated Hypertension by Improving Pro-Inflammatory Reaction and Leptin Resistance

  • Jiang, Ping;Ma, Dufang;Wang, Xue;Wang, Yongcheng;Bi, Yuxin;Yang, Jinlong;Wang, Xuebing;Li, Xiao
    • Molecules and Cells
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    • v.41 no.3
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    • pp.244-255
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    • 2018
  • Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

SPECTROSCOPIC OBSERVATIONS OF GEO-STAT10NARY SATELLITES OVER THE KOREAN PENINSULA (한반도 주변상공의 정지궤도 인공위성 분광관측1)

  • 이동규;김상준;한원용;박준성;민상웅
    • Journal of Astronomy and Space Sciences
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    • v.18 no.2
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    • pp.101-108
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    • 2001
  • Low resolution spectroscopic observations of leo-stationary satellites over the Korean peninsula have been carried out at the KyungHee Optical Satellite Observing Facility (KOSOF) with a 40cm telescope. We have observed 9 telecommunication satellites and 1 weather satellite of 6 countries. The obtained spectral data showed that satellites could be classified and grouped with similar basic spectral feature. We divided the 10 satellites into 4 groups based on spectral slop and reflectance. It is suggested that the material types of the satellites can be determined through spectral comparisons with the ground laboratory data. We will continuously observe additional geo-stationary satellites for the accurate classification of spectral features.

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The Effect of Deer Antler Herbal Acupuncture Control to Hyper-inflammatory Responses on Synovial Membrane by LPS-induced Arthritis (약용약침(藥茸藥鍼)이 LPS 유발(誘發) 관절염(關節炎)의 윤활관절막내(潤滑關節膜內) 과다염증반응(過多炎症反應) 조절(調節)에 미치는 영향(影響))

  • Chung, Yong-Re;Lee, Seung-Deok;Byun, Hyuk;Park, In-Shik;Jung, Chan-Yung;Lee, Chang-Hwan;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.24 no.4
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    • pp.167-181
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    • 2007
  • Objectives: To evaluate expression of MIF mRNA, MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT-3, $NF-{\kappa}B$ p65, COX-2 and iNOS, MMP-9mRNA after injecting deer antler herbal acupuncture solution in a LPS rat model. Methods: The experiment was divided in category of the control group, RA group, and NA group. RA was induced in the mice via injecting 300ug/kg LPS. The deer antler herbal acupuncture solution 50ug/kg was applied on $ST_{35}$(犢鼻) and EX-LE201(內膝眼) for 19days from $3^{rd}$ day of RA inducement. Results: 1. In the deer antler herbal acupuncture solution treated RAW 264.7cell, the mRNA expression of cytokines, RA related inflammation factors, such as the MIF, COX- 2, iNOS, and MMP-g reduced concentration dependently. 2. In the deer antler herbal acupuncture treated mice's synovial membrane, decrease in the cell replication of synovial joint cells, regeneration of blood vessel, fibrosis and fibroblastic cells expansion were observed. 3. Positive reaction of RA-related cytokines MIF, $TNF-{\alpha}$, $IL-6R-{\alpha}$, STAT3, COX-2, iNOS, $NF-\;{\kappa}B$ p65, MMP-9 was reduced. Conclusion : On the basis of the results, it was concluded that deer antler herbal acupuncture extract has significant protecting ability against acute progressive RA by inhibiting the production of MIF, as a top in cytokines related to inflammation.

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Viscum album and its Constituents Downregulate MMP-13 Expression in Chondrocytes and Protect Cartilage Degradation

  • Lee, Ju Hee;Kwon, Yong Soo;Jung, Da Young;Kim, Na Young;Lim, Hyun;Kim, Hyun Pyo
    • Natural Product Sciences
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    • v.27 no.3
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    • pp.151-160
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    • 2021
  • Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs) including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanol extract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yielded five constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2), syringin (3), homoflavoyadorinin B (4), and 4,4'-dihydroxy-3,6'-dimethoxychalcone-2'-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 - 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

Isolation of Microorganism with HIgh Productivity and Cultivation Optimization for Lactic Acid Production (고생산성 젖산생성균 분리 및 배양 최적화)

  • Cho, Kyu-Hong;Cho, Yun-Kyung;Hong, Seung-Suh;Lee, Hyun-Soo
    • Microbiology and Biotechnology Letters
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    • v.23 no.1
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    • pp.6-11
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    • 1995
  • In order to screen microorganism producing lactic acid with high productivity from nature, we used a medium containing 100 g/l glucose and selected several microorganisms producing more than 80 g/l L-lactic acid. We investigated their physiological characteristics and compared them. The best microorganism was identified as Lactobacillus casei subsp. rhamnosus. The optimum pH for growth and production of lactic acid was 6.0 and this strain showed the highest growth rate at around 30$\circ$C , but the optimum temperature for lactic acid production was 45$\circ$C . The growth was inhibited proportionally from 50 g/l to 300 g/l of glucose and the maximal cell mass increased according to increasing the concentration of corn steep liquor (CSL) protein up to 30 g/l. In batch fermentation for lactic acid production, we produced 128 g/l L-lactic acid with 20 g/l CSL protein and 150 g/l glucose in 35 hours. In pH-stat fed-batch fermentation, we were able to produce 183 g/l L-lactic acid.

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Voluntary Motor Control Change after Gait Training in Patients with Spinal Cord Injury (척수신경손상 환자의 보행훈련 전.후의 능동적 근육제어의 변화)

  • 임현균;이동철;이영신;셔우드아더
    • Journal of Biomedical Engineering Research
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    • v.24 no.2
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    • pp.133-140
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    • 2003
  • In this study, muscle activity was measured using surface EMG (sEMG) during a voluntary maneuver (ankle dorsiflexion) in the supine position was compared pre and post gait training. Nine patients with incomplete spinal cord injury participated in a supported treadmill ambulation training (STAT), twenty minutes a day, five days a week for three months. Two tests, a gait speed test and a voluntary maneuver test, were made the same day, or at least the same week, pre and post gait training. Ten healthy subjects' data recorded using the same voluntary maneuvers were used for the reference. sEMG measured from ten lower limb muscles was used to observe the two features of amplitude and motor control distribution pattern, named response vector. The result showed that the average gait speed of patients increased significantly (p〈0.1) from 0.47$\pm$0.35 m/s to 0.68$\pm$0.52 m/s. In sEMG analysis, six out of nine patients showed a tendency to increase the right tibialis anterior activity during right ankle dorsiflexion from 109.7$\pm$148.5 $mutextrm{V}$ to 145.9$\pm$180.7 $mutextrm{V}$ but it was not significant (p〈0.055). In addition, only two patients showed increase of correlation coefficient and total muscle activity in the left fide during left dorsiflexion. Patients' muscle activity changes after gait training varied individually and generally depended on their muscle control abilities of the pre-STAT status. Response vector being introduced for quantitative analysis showed good Possibility to anticipate. evaluate, and/or guide patients with SCI, before and after gait training.

Role of Interleukin(IL)-6 in NK Activity to Hypoxic-Induced Highly Invasive Hepatocellular Carcinoma(HCC) Cells

  • Hwan Hee Lee;Hyojung Kang;Hyosun Cho
    • Journal of Microbiology and Biotechnology
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    • v.33 no.7
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    • pp.864-874
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    • 2023
  • Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

Self-renewal and circulating capacities of metastatic hepatocarcinoma cells required for collaboration between TM4SF5 and CD44

  • Lee, Doohyung;Lee, Jung Weon
    • BMB Reports
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    • v.48 no.3
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    • pp.127-128
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    • 2015
  • Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

Optimization of Culture Media for Enhanced Chitinase Production from a Novel Strain of Stenotrophomonas maltophilia Using Response Surface Methodology

  • Khan, Minhaj Ahmad;Hamid, Rifat;Ahmad, Mahboob;Abdin, M.Z.;Javed, Saleem
    • Journal of Microbiology and Biotechnology
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    • v.20 no.11
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    • pp.1597-1602
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    • 2010
  • Chitinase is one of the most important mycolytic enzymes with industrial significance. This enzyme is produced by a number of organisms including bacteria. In this study, we describe the optimization of media components with increased production of chitinase for the selected bacteria, Stenotrophomonas maltophilia, isolated from soil. Different components of the defined media responsible for influencing chitinase secretion by the bacterial isolate were screened using Plackett-Burman experimental design and were further optimized by Box-Behnken factorial design of response surface methodology in liquid culture. Maximum chitinase production was predicted in medium containing 4.94 g/l chitin, 5.56 g/l maltose, 0.62 g/l yeast extract, 1.33 g/l $KH_2PO_4$, and 0.65 g/l $MgSO_4{\cdot}7H_2O$ using response surface plots and the point prediction tool of the DESIGN EXPERT 7.1.6 (Stat-Ease, USA) software.