• Title/Summary/Keyword: Stat1

Search Result 391, Processing Time 0.025 seconds

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
    • /
    • v.27 no.3
    • /
    • pp.151-160
    • /
    • 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.

Ginsenosides: potential therapeutic source for fibrosis-associated human diseases

  • Li, Xiaobing;Mo, Nan;Li, Zhenzhen
    • Journal of Ginseng Research
    • /
    • v.44 no.3
    • /
    • pp.386-398
    • /
    • 2020
  • Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

Calcium/Calmodulin-Dependent Protein Kinase is Involved in the Release of High Mobility Group Box 1 Via the Interferon-${\beta}$ Signaling Pathway

  • Ma, Lijuan;Kim, Seon-Ju;Oh, Kwon-Ik
    • IMMUNE NETWORK
    • /
    • v.12 no.4
    • /
    • pp.148-154
    • /
    • 2012
  • Previously, we have reported that high mobility group box 1 (HMGB1), a proinflammatory mediator in sepsis, is released via the IFN-${\beta}$-mediated JAK/STAT pathway. However, detailed mechanisms are still unclear. In this study, we dissected upstream signaling pathways of HMGB1 release using various molecular biology methods. Here, we found that calcium/calmodulin-dependent protein kinase (CaM kinase, CaMK) is involved in HMGB1 release by regulating IFN-${\beta}$ production. CaMK inhibitor, STO609, treatment inhibits LPS-induced IFN-${\beta}$ production, which is correlated with the phosphorylation of interferon regulatory factor 3 (IRF3). Additionally, we show that CaMK-I plays a major role in IFN-${\beta}$ production although other CaMK members also seem to contribute to this event. Furthermore, the CaMK inhibitor treatment reduced IFN-${\beta}$ production in a murine endotoxemia. Our results suggest CaMKs contribute to HMGB1 release by enhancing IFN-${\beta}$ production in sepsis.

Improvement of Leptin Resistance (렙틴 저항성의 개선)

  • Kim, Yong Woon
    • Journal of Yeungnam Medical Science
    • /
    • v.30 no.1
    • /
    • pp.4-9
    • /
    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

Construction and validation of a synthetic phage-displayed nanobody library

  • Minju Kim;Xuelian Bai;Hyewon Im;Jisoo Yang;Youngju Kim;Minjoo MJ Kim;Yeonji Oh;Yuna Jeon;Hayoung Kwon;Seunghyun Lee;Chang-Han Lee
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.28 no.5
    • /
    • pp.457-467
    • /
    • 2024
  • Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phage-displayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

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
    • /
    • v.24 no.2
    • /
    • pp.133-140
    • /
    • 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.

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
    • /
    • v.18 no.2
    • /
    • pp.101-108
    • /
    • 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.

  • PDF

EGFR Antisense Oligonucleotides Encapsulated with Nanoparticles Decrease EGFR, MAPK1 and STAT5 Expression in a Human Colon Cancer Cell Line

  • Najar, Ahmad Gholamhoseinian;Pashaei-Asl, Roghiyeh;Omidi, Yadollah;Farajnia, Safar;Nourazarian, Ali Reza
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.1
    • /
    • pp.495-498
    • /
    • 2013
  • Epidermal growth factor receptor (EGFR) is over-expressed in several human cancers. This would suggest that inhibition of EGFR is a reasonable approach for cancer treatment. In this study we investigated EGFR blocking and its effects on the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was investigated by fluorescence microscopy and flow cytometry analysis. The effect of EGFR antisense on the expression of EGFR in HT29 cells was examined by real time PCR and Western blots, which showed that antisense encapsulated with PAMAM decreased the level of EGFR mRNA and protein. In addition, real time PCR results confirmed that EGFR inhibition had an effective role in the reduction of EGFR dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM nanoparticles down regulated EGFR and EGFR-mediated genes.

YAC tripeptide of epidermal growth factor promotes the proliferation of HaCaT keratinocytes through activation of EGFR

  • Yoo, Yeon Ho;Kim, Yu Ri;Kim, Min Seo;Lee, Kyoung-Jin;Park, Kyeong Han;Hahn, Jang-Hee
    • BMB Reports
    • /
    • v.47 no.10
    • /
    • pp.581-586
    • /
    • 2014
  • Epidermal growth factor (EGF) is known to play key roles in skin regeneration and wound-healing. Here, we demonstrate that Pep2-YAC, a tripeptide covering residues 29-31 in the B loop of EGF, promotes the proliferation of HaCaT keratinocytes with activity comparable to EGF. The treatment of HaCaT cells with Pep2-YAC induced phosphorylation, internalization, and degradation of EGFR and organization of signaling complexes, which consist of Grb2, Gab1, SHP2, and PI3K. In addition, it stimulated the phosphorylation of ERK1/2 at Thr 202/Tyr 204 and of Akt1 at Ser 473 and the nuclear translocation of EGFR, STAT3, c-Jun, and c-Fos. These results suggest that Pep2-YAC may be useful as a therapeutic agent for skin regeneration and wound-healing as an EGFR agonist.

The Evaluation of Major Macroeconomic Indicators in Russia and the Leading Countries-partners

  • Vyborova, Elena Nikolaevna
    • East Asian Journal of Business Economics (EAJBE)
    • /
    • v.5 no.3
    • /
    • pp.1-32
    • /
    • 2017
  • Purpose - This study is to analyze the main macroeconomic indicators in Russia and the leading countries- partners and to research GDP, the debt, the foreign trade and other indicators. This main indicator is using in regulation in the economic stability of country, of stability of trade with countries-partners. Research design, data, and methodology - This paper used the amount of data to be analyzed at the present stage, from the 2010 to 2015 in Russia. In order to assess trends of development, the array of data on the indicators used for the 1995-2017. The data analyzed using the methods of multivariate statistics and application of the software package Stat graphics. Results - Hypothesis 1. In the recent years GDP has tended to increase in the most countries of the world. In Russia and its structure of branch of economics is uneven. Hypothesis 2. The foreign trade turnover also has tended to grow. The foreign trade balance in Russia and in the leading countries-partners has a positive balance, dominated by the export of goods. Conclusions - This paper finds that the foreign trade turnover also has tends to grow. The foreign trade balance in Russia and in the leading countries-partners has a positive balance, dominated by the export of goods.