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Mesenchymal Stem Cells Ameliorate Fibrosis by Enhancing Autophagy via Inhibiting Galectin-3/Akt/mTOR Pathway and by Alleviating the EMT via Inhibiting Galectin-3/Akt/GSK3β/Snail Pathway in NRK-52E Fibrosis

  • Yu Zhao;Chuan Guo;Lianlin Zeng;Jialing Li;Xia Liu;Yiwei Wang;Kun Zhao;Bo Chen
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.52-65
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    • 2023
  • Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

The Effectiveness of Ulmus Davidiana Planch Herbal Acupuncture to Inhibit MIF Activation on Lipopolysaccharide-induced Rheumatoid Arthritis Model (유근피(楡根皮) 약침이 lipopolysaccharide 유발 류마티스 관절염 모델에서 MIF 활성 억제에 미치는 영향)

  • Byun, Hyuk;Park, In-Shik;Cho, Hyun-Seok;Kim, Kap-Sung;Lee, Seung-Deok
    • Journal of Acupuncture Research
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    • v.23 no.6
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    • pp.117-132
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    • 2006
  • Objectives : The purpose of this study is to investigate the effect of Ulmus davidiana Planch herbal acupuncture solution in LPS-stimulated RAW 264.7 cells and mouse knee joints, perfom1ed several experimental items: those are MIF mRNA, MIF, $TNF-{\alpha}$, $NF-{\kappa}B$ p65, iNOS mRNA, iNOS, NO, synovial hyperplasia, angiogenesis and fibrosis. Methods : In order to observe mRAN expression of MIF and iNOS in LPS-stimulated RAW 264.7 cells, RT-PCR was used. NO production in LPS-stimulated RAW 264.7 cells was measured by nitrite assay. All the female BALB/c mice were bred and maintained in pathogen-free mouse colonies and were 6 weeks of age on beginning of the experiment. The experimental model of RA was induced by injection of $50{\mu}g/kg$ LPS. Ulmus davidiana Planch herbal acupuncture solution was injected into either S 35 (犢鼻) or EX-LE 202 (內膝眼) of mice in turn daily for 19 days. Immunohistochemical staining was carried out to assess $TNF-{\alpha}$, $NF-{\kappa}B$ p65 and iNOS expression in synovial membrane. Synovial hyperplasia, angiogenesis and fibrosis in synovial membrane was observed with a microscope. Results : 1. Ulmus davidiana Planch herbal acupuncture solution inhibited mRNA expression of MIF and iNOS in dependence on a density of it in LPS-stimulated RAW 264.7 cells. 2. Ulmus davidiana Planch herbal acupuncture solution decreased synovial hyperplasia, angiogenesis and fibrosis in LPS-stimulated mouse knee joints. 3. Ulmus davidiana Planch herbal acupuncture solution curtailed production of MIF, $TNF-{\alpha}$, $NF-{\kappa}B$ p65, iNOS in LPS-stimulated mouse knee joints. Conclusion : On the basis of these results, It was shown that Ulmus davidiana Planch herbal acupuncture solution is significantly able to inhibit the production of MIF as a top in cytokines related to inflammatory or irrlll1une responses. Our results may provide that Ulmus davidiana Planch herbal acupuncture solution has beneficial effect in not only RA but other inflammatory or immune deases.

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Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation

  • Lim, Ji-Young;Ryu, Da-Bin;Lee, Sung-Eun;Park, Gyeongsin;Choi, Eun Young;Min, Chang-Ki
    • Molecules and Cells
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    • v.38 no.11
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    • pp.966-974
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    • 2015
  • Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

Transmission Noise Seduction Performance of Smart Panels using Piezoelectric Shunt Damping (압전감쇠를 이용한 압전지능패널의 전달 소음저감 성능)

  • 이중근
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.3 no.1
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    • pp.49-57
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    • 2002
  • The possibility of a transmission noise reduction of piezoelectric smart panels using piezoelectric shunt damping is experimentally studied. Piezoelectric smart panel is basically a plate structure on which piezoelectric patch with shunt circuits is mounted and sound absorbing materials are bonded on the surface of the structure. Sound absorbing materials can absorb the sound transmitted at mid frequency region effectively while the use of piezoelectric shunt damping can reduce the transmission at resonance frequencies of the panel structure. To be able to reduce the sound transmission at low panel resonances, piezoelectric damping using the measured electrical impedance model is adopted. Resonant shunt circuit for piezoelectric shunt damping is composed of register and inductor in series, and they are determined by maximizing the dissipated energy throughout the circuit. The transmitted noise reduction performance of smart panels is investigated using an acoustic tunnel. The tunnel is a tube with square crosses section and a loud-speaker is mounted at one side of the tube as a sound source. Panels are mounted in the middle of the tunnel and the transmitted sound pressure across panels is measured. Noise reduction performance of a smart panels possessing absorbing material and/or air gap shows a good result at mid frequency region but little effect in the resonance frequency. By enabling the piezoelectric shunt damping, noise reduction of 10dB, 8dB is achieved at the resonance frequencise as well. Piezoelectric smart panels incorporating passive method and piezoelectric shunt damping are a promising technology for noise reduction in a broadband frequency.

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Comparative Molecular Similarity Indices Analysis (CoMSIA) on the Melanogenesis Inhibitory Activities of Alkyl-3,4-dihydroxy- benzoate and N-alkyl-3,4-dihydroxybenzamide Derivatives.

  • Kim, Sang-Jin;Sung, Nack-Do;Lee, Sang-Ho
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.733-740
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    • 2003
  • To find a new substance with superior melanogenesis inhibitory activity, the bioactivities of alkyl-3,4-dihydroxy-5-substituted benzoate (A) and N-alkyl-3,4-dihydroxy-5-substituted benzamide (B) derivatives as substrate of tyrosinase were measured in mouse melanoma cells. And the bioactivities analyzed using comparative molecular similarity indices analysis (CoMSIA). From the CoMSIA model, when cross-validation value (q$^2$) is 0.713 at four components, the pearson correlation coefficient ($r^2$) is 0.900. Unknown compounds were predicted, using QSAR analyzed results from the CoMSIA methods. Excellent agreement was obtained between the measured and the predicted bioactivities of unknown compounds. As the results of prediction from CoMSIA, we could conclude that the bioactivities were increased from pl$_{50}$=3.18-4.80 to above 5.17 by creation of 6-methylheptyl, n-pentylphenyl and 2-hydroxypentylphenyl group etc,.,.

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Anti-inflammatory Activity of 3,6,3'-Trihydroxyflavone in Mouse Macrophages, In vitro

  • Lee, Eunjung;Jeong, Ki-Woong;Shin, Areum;Kim, Yangmee
    • Bulletin of the Korean Chemical Society
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    • v.35 no.11
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    • pp.3169-3174
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    • 2014
  • Numerous studies have examined the role of flavonoids in modulating inflammatory responses in vitro. In this study, we found a novel flavonoid, 3,6,3'-trihydroxyflavone (1), with anti-inflammatory effects. Anti-inflammatory activity and mechanism of action were examined in mouse macrophages stimulated with lipopolysaccharide (LPS). Our results showed that the anti-inflammatory effects of 1 are mediated via p38 mitogen-activated protein kinase (p38 MAPK), Jun-N terminal kinase (JNK), and the extracellular-signal-regulated kinase (ERK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Binding studies revealed that 1 had a high binding affinity to JNK1 ($1.568{\times}10^8M^{-1}$) and that the 3- and 6-hydroxyl groups of the C-ring and A-ring of 1 participated in hydrogen bonding interactions with the side chains of Asn114 and Lys55, respectively. The oxygen at the 3' position of the B-ring formed a hydrogen bond with side chain of Met111. Therefore, 1 could be a potential inhibitor of JNKs, with potent anti-inflammatory activity.

Studies on The Optical and Electrical Properties of Europium Complex (Europium compound박막의 전기적 광학적 특성에 관한 연구)

  • 이명호;표상우;김영관;김정수;이한성
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 1998.06a
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    • pp.317-320
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    • 1998
  • Electroluminescent(EL) devices based on organic materials have been of great interest due to their possible applications for large-area flat-panel displays, where they are attractive because of their capability of multicolor emission, and low operation voltage. In this study, glass substrate/ITO/Eu(TTA)$_3$(Phen)/Al(A), glass substrate/ITO/TPD/Eu(TTA)$_3$(phen)/Al(B) aNd glass substrate/ITO/TPD/Eu(TTA)$_3$(Phen)/A1Q$_3$/Al (C) structures were fabricated by vacuum evaporation method, where aromatic diamine(TPD) was used as a hole transporting material, Eu(TTA)$_3$(phen) as an emitting material, and tris(8-hydroxyquinoline) Aluminum (AlQ$_3$) as an electron transporting layer. Etectroluminescent(EL) and I-V characteristics of Eu(TTA)$_3$(phen) with a various thickness were investigated. This structure shows the red EL spectrum, which is almost the same as the PL spectrum of Eu(TTA)$_3$(phen). I-V characteristics of this structure show that turn-on voltage was 9V and current density was 0.01A/㎤ at a dc operation voltage of 9V. Electrical transporting phenomena of these structures was explained using the trapped-charge-limited current model with I-V characteristics.

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Design and Implementation of a Spectrum Engineering Simulator Based on GIS (GIS를 기반으로 한 스펙트럼 엔지니어링 시뮬레이터 설계 및 개발)

  • Lee, Hyeong-Su;Jeong, Yeong-Ho;Jeong, Jin-Uk
    • The Transactions of the Korea Information Processing Society
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    • v.3 no.1
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    • pp.144-152
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    • 1996
  • Recently, as the demands for radio spectrum are growing and the number of cell sites is increasing rapidly, the spectrum engineering plays an important role in estimating frequency sharing and reuse. The radio propagation analysis is essential in the basic technology of radio network design such as deciding the service area and selecting the position of the base station. But, domestic propagation environment in which mountainous region is occupying over 70% of our terrain does not allow us to apply foreign studies which are deduced in highly different environments. Therefore, we need to have our propagation analysis system derived from our own terrain condition. In this paper, we propose the propagation prediction model which issuitable toour propagation environment, and also usinghis model, we implement thesimulator based on GIS(Geographic Information System)which can be applied to both spectrum engineering and radio propagation analysis. We showed that this simulator can well be applied to frequency assignment, propagation network design as well as other radio services. Considering the results of our analysis, we could guarantee the standard deviation of error between the measured data and predicted results as 5 to 7 dB.

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Effect of Oral Probiotics (Bifidobacterium lactis AD011 and Lactobacillus acidophilus AD031) Administration on Ovalbumin-Induced Food Allergy Mouse Model

  • Kim, Ji-Yeun;Choi, Young-Ok;Ji, Geun-Eog
    • Journal of Microbiology and Biotechnology
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    • v.18 no.8
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    • pp.1393-1400
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    • 2008
  • Recent study has demonstrated an increasing prevalence of food allergy in Korean children. Specific probiotic bacteria may promote potentially anti-allergenic processes through induction of Th1-type immunity and enhance the regulatory lymphocyte. This study investigated whether orally administrated probiotics could suppress allergic responses in an ovalbumin (OVA)-induced allergy mouse model. Thus, female C3H/HeJ mice were orally sensitized with OVA and cholera toxin for 4 weeks. Lactobacillus acidophilus AD031, Bifidobacterium lactis AD011, and L. acidophilus AD031 plus B. lactis AD011 were fed to mice from 2 weeks before the sensitization. The OVA-induced mice that were not treated with probiotics had significantly increased serum levels of OVA-specific IgE and IgG1, and OVA-specific IgA in feces. However, the mice treated with probiotics suppressed production of the OVA-specific IgE, IgG1, and IgA. The level of IL-4 was significantly lower, and the levels of INF-$\gamma$ and IL-10 were significantly higher in the mice treated with probiotics than that in the non-treated mice. The groups treated with probiotics had decreased levels of degranulated mast cells, eosinophil granules, and tail scabs. These results indicate that L. acidophilus AD031 and B. lactis AD011 might be useful for the prevention of allergy.

The Influence of the Nature of Trust on Commitment and Relational Citizenship Behavior in BtoB Exchanges Relationships (BtoB 관계에서 신뢰의 내용 및 대상 차원이 관계몰입 및 시민행동에 미치는 영향)

  • 최지호;김재욱;이성근;한계숙
    • Journal of Distribution Research
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    • v.9 no.3
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    • pp.97-118
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    • 2004
  • The primary purpose of this research is to develop and test a model that explains the process of how multidimensional trust in a supplier firm and salesperson through relational commitment influence buyer's relational citizenship behavior. The proposed framework uses a multidimensional conceptualization for the trustworthiness construct such as benevolence and credibility and incorporates two distinct facets of consumer trust, namely, organization trust, and salesperson trust. The authors test the proposed model using data from MD in buying finns.. The tests show the differential effect of trust dimensions on relational commitment and citizenship behavior. The authors discuss the implications of the findings for trust-commitment theory and practice.

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