• Title/Summary/Keyword: Nuclear Receptor

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Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice

  • Juhyun Lee;Ji-Won Park;Jinseon Choi;Seok Han Yun;Bong Hyo Rhee;Hyeon Jeong Jeong;Hyueyun Kim;Kihoon Lee;Kyung-Seop Ahn;Hye-Gwang Jeong;Jae-Won Lee
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.546-555
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    • 2024
  • Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

Anti-inflammatory and Antioxidative Effects of Lotus Root Extract in LPS-PG-Stimulated Human Gingival Fibroblast-1 Cells (치주염 원인균 LPS-PG로 유도된 인체 치은섬유아세포에서 연뿌리 추출물에 대한 항염증 및 항산화 효과)

  • Lee, Young-Kyung;Kim, Chul Hwan;Jeong, Dae Won;Lee, Ki Won;Oh, Young Taek;Kim, Jeong Il;Jeong, Jin-Woo
    • Korean Journal of Plant Resources
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    • v.35 no.5
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    • pp.565-573
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    • 2022
  • Gingival inflammation is one of the main causes that can be related to various periodontal diseases. Human gingival fibroblast (HGF) is the major constituent in periodontal connective tissue and secretes various inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), upon lipopolysaccharide stimulation. This study is aimed at investigating the anti-inflammatory and antioxidative activities of Lotus Root extract (LRE) in Porphyromonas gingivalis derived lipopolysaccharide (LPS-PG)-stimulated HGF-1 cells. The concentration of NO and PGE2, as well as their responsible enzymes, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), was analyzed by Griess reaction, ELISA, and western blot analysis. LPS-PG sharply elevated the production and protein expression of inflammatory mediators, which were significantly attenuated by LRE treatment in a dose-dependent manner. LRE treatment also suppressed activation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) and nuclear factor-κB (NF-κB) in LPS-PG-stimulated HGF-1 cells. In addition, one of phase II enzyme, NAD(P)H quinone dehydrogenase (NQO)-1, and its transcription factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), were significantly induced by LRE treatment. Consequently, these results suggest that LRE ameliorates LPS-PG-induced inflammatory responses by attenuating TLR4/MyD88-mediated NF-κB, and activating NQO-1/Nrf2 antioxidant response element signaling pathways in HGF-1 cells.

Inhibition of Inflammation by Popillia flavosellata Ethanol Extract in LPSinduced RAW264.7 Macrophages (LPS로 염증 유도된 RAW 264.7세포에 대한 참콩풍뎅이(Popillia flavosellata) 에탄올 추출물의 항염증 효과)

  • Yoon, Young-Il;Hwang, Jae-Sam;Kim, Mi-Ae;Ahn, Mi Young;Lee, Young-Bo;Han, Myung Sae;Goo, Tae-Won;Yun, Eun-Young
    • Journal of Life Science
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    • v.25 no.9
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    • pp.993-999
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    • 2015
  • The beetle Popillia flavosellata has been no reported its functional effects. In this study, we investigated the anti-inflammatory effect of P. flavosellata ethanol extract (PFE) on RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for the induction of inflammation. First, we examined the cytotoxicity of PFE in the RAW 264.7 cells at a concentration of 2,000 μg/ml or less. To evaluate the anti-inflammatory effects of PFE, we investigated the expression levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and proinflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether PFE inhibited the translocation of nuclear factor kappa B (NF-κB) p65 into the nucleus in the LPS-induced RAW 264.7 cells. We found that the protein levels of TNF-α and IL-6 were decreased in the LPS-induced RAW 264.7 cells after the treatment with PFE in a dose-dependent manner. In addition, we confirmed that PFE inhibited the translocation of NF-κB p65 into the nucleus, as well as the protein expression levels of iNOS and COX-2. Accordingly, we propose that PFE exerts an anti-inflammatory effect through the down-regulation of NF-κB p65, TNF-α, IL-6, iNOS, and COX-2 via the toll like receptor (TLR)-4 inflammatory signaling pathway.

Quantitative Study of Annular Single-Crystal Brain SPECT (원형단일결정을 이용한 SPECT의 정량화 연구)

  • 김희중;김한명;소수길;봉정균;이종두
    • Progress in Medical Physics
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    • v.9 no.3
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    • pp.163-173
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    • 1998
  • Nuclear medicine emission computed tomography(ECT) can be very useful to diagnose early stage of neuronal diseases and to measure theraputic results objectively, if we can quantitate energy metabolism, blood flow, biochemical processes, or dopamine receptor and transporter using ECT. However, physical factors including attenuation, scatter, partial volume effect, noise, and reconstruction algorithm make it very difficult to quantitate independent of type of SPECT. In this study, we quantitated the effects of attenuation and scatter using brain SPECT and three-dimensional brain phantom with and without applying their correction methods. Dual energy window method was applied for scatter correction. The photopeak energy window and scatter energy window were set to 140ke${\pm}$10% and 119ke${\pm}$6% and 100% of scatter window data were subtracted from the photopeak window prior to reconstruction. The projection data were reconstructed using Butterworth filter with cutoff frequency of 0.95cycles/cm and order of 10. Attenuation correction was done by Chang's method with attenuation coefficients of 0.12/cm and 0.15/cm for the reconstruction data without scatter correction and with scatter correction, respectively. For quantitation, regions of interest (ROIs) were drawn on the three slices selected at the level of the basal ganglia. Without scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.2 and 2.1, respectively. However, the ratios between basal ganglia and background were very similar for with and without attenuation correction. With scatter correction, the ratios of ROI average values between basal ganglia and background with attenuation correction and without attenuation correction were 2.69 and 2.64, respectively. These results indicate that the attenuation correction is necessary for the quantitation. When true ratios between basal ganglia and background were 6.58, 4.68, 1.86, the measured ratios with scatter and attenuation correction were 76%, 80%, 82% of their true ratios, respectively. The approximate 20% underestimation could be partially due to the effect of partial volume and reconstruction algorithm which we have not investigated in this study, and partially due to imperfect scatter and attenuation correction methods that we have applied in consideration of clinical applications.

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The Effects of Several Halophytes on Insulin Resistance in Otsuka Long-evans Tokushima Fatty Rats (OLETF 쥐에서 칠면초와 세발나물의 인슐린 저항성 개선 효과)

  • Cho, Jeong-Yong;Huang, Zhangjun;Park, Sun-Young;Park, Kyung-Hee;Pai, Tong-Kun;Kim, So-Young;Kim, Haeng-Ran;Ham, Kyung-Sik
    • Korean Journal of Food Science and Technology
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    • v.46 no.1
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    • pp.100-107
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    • 2014
  • We evaluated preventive effects of Suaeda japonica (SJ) and Spergularia marina Griseb (SMG) on the insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The 10-week old OLETF rats were fed diets containing 3% (w/w) SJ and SMG for 18 weeks. Fasting blood glucose levels in SJ and SMG groups, measured using the oral glucose tolerance test, were lower than that of the control rats. The SMG group showed significantly lower levels of insulin, glycated hemoglobin, triglyceride, and total cholesterol than the control group. In addition, these levels were relatively lower in the SJ group than those in the control rats. The SJ and SMG groups had relatively lower protein levels of nuclear factor-kappa B (NF-${\kappa}B$) p65 in adipose tissue and serine phosphorylated insulin receptor substrate 1 (IRS-1) in skeletal muscle than the control group. These results suggest that SJ and SMG prevent insulin resistance and SMG in particular reduces blood triglyceride and total cholesterol levels.

Inhibitory Effect of Conditioned Medium of Silk Fibroin-Treated Osteoblasts in Osteoclast Differentiation (실크피브로인을 처리한 MC3T3-E1 조골세포 조건배양액의 파골세포 분화억제효과)

  • Yeo, Joo-Hong;Park, Kyung-Ho;Ju, Won-Chul;Lee, Jin-Ah;Lee, Kwang-Gill;Woo, Soon-Ok;Han, Sang-Mi;Kweon, Hae-Yong;Kim, Sung-Su;Cho, Yun-Hi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.8
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    • pp.992-997
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    • 2008
  • In this study, we investigated the indirect effect of silk-fibroin on osteoclastic differentiation of RAW264.7 cells. The conditioned medium were collected from MC3T3-E1 osbeoblasts treated with $0.001\;mg/mL{\sim}0.1\;mg/mL$ silk fibroin for 6 days, mixed in 1:1 ratio with osteoclast medium, and then added into RAW264.7 cells with receptor activator of nuclear factor kappa B ligand (RANKL), a differentiation inducer for 3 days. Of osteoclastic cytokines in the conditioned medium, the protein expression of osteoprotegerin (OPG) with silk-fibroin was not significantly different. However, the protein expression of interleukin (IL)-$1{\beta}$ was specifically lower in a dose dependent manner. In RAW264.7 cells, the conditioned medium with silk-fibroin inhibited RANKL induced osteoclastic differentiation as total number of multinucleated tartrate-resistant alkaline phosphatase (TRAP)-positive osteoclasts in a dose dependent manner. Taken together, we demonstrated that the conditioned medium of silk-fibroin treated osteoblasts inhibits RANKL induced differentiation of osteoclasts with inhibiting selective expression of IL-$1{\beta}$.

Expression of Several Biologic Markers as Prognostic Markers in Non-Small Cell Lung Cancers (폐암조직에서 생물학적 지표들의 예후인자로서의 비교검토)

  • Kim, Sun-Young;Cho, Hai-Jeong;Suh, Ji-Won;Kim, Nam-Jae;Kim, Ju-Ock
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.2
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    • pp.142-148
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    • 1995
  • Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

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Inhibitory Effects of Tenebrio molitor Larvae Ethanol Extract on RANKL-Induced Osteoclast Differentiation (갈색거저리 유충 에탄올 추출물이 RANKL에 의해 유도되는 파골세포 분화에 미치는 영향)

  • Seo, Minchul;Baek, Minhee;Lee, Hwa Jeong;Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.30 no.11
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    • pp.983-989
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    • 2020
  • The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.

Effect on bone healing by the application of low intensity pulsed ultrasound after injection of adipose tissue-derived stem cells at the implantation of titanium implant in the tibia of diabetes-induced rat (당뇨유도 백서 경골에 티타늄 임플란트 매식 시 지방조직 유래 줄기세포 주입 후 저출력 초음파 적용이 골치유에 미치는 영향)

  • Jung, Tae-Young;Park, Sang-Jun;Hwang, Dae-Suk;Kim, Yong-Deok;Lee, Soo-Woon;Kim, Uk-Kyu
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.37 no.4
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    • pp.301-311
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    • 2011
  • Introduction: This study examined the effect of the application of low intensity pulsed ultrasound on bone healing after an injection of adipose tissue-derived stem cells (ADSCs) during the implantation of a titanium implant in the tibia of diabetes-induced rats. Materials and Methods: Twelve Sprague-Dawely rats were used. After inducing diabetes, the ADSCs were injected into the hole for the implant. Customized screw type implants, 2.0 mm in diameter and 3.5 mm in length, were implanted in both the tibia of the diabetes-induced rats. After implantation, LIPUS was applied with parameters of 3 MHz, 40 mW/$cm^2$, and 10 minutes for 7 days to the left tibiae (experimental group) of the diabetesinduced rats. The right tibiae in each rat were used in the control group. At 1, 2 and 4 week rats were sacrificed, and the bone tissues of both tibia were harvested. The bone tissues of the three rats in each week were used for bone-to-implant contact (BIC) and bone area (BA) analyses and the bone tissues of one rat were used to make sagittal serial sections. Results: In histomorphometric analyses, the BIC in the experimental and control group were respectively, $39.00{\pm}18.17%$ and $42.87{\pm}9.27%$ at 1 week, $43.74{\pm}6.83%$ and $32.27{\pm}6.00%$ at 2 weeks, and $32.62{\pm}11.02%$ and $47.10{\pm}9.77%$ at 4 weeks. The BA in experimental and control group were respectively, $37.28{\pm}3.68%$ and $31.90{\pm}2.84%$ at 1 week, $20.62{\pm}2.47%$ and $15.64{\pm}2.69%$ at 2 weeks, and $11.37{\pm}4.54%$ and $17.69{\pm}8.77%$ at 4 weeks. In immunohistochemistry analyses, Osteoprotegerin expression was strong at 1 and 2 weeks in the experimental group than the control group. Receptor activator of nuclear factor kB ligand expression showed similar staining at each week in the experimental and control group. Conclusion: These results suggest that the application of low intensity pulsed ultrasound after an injection of adipose tissue-derived stem cells during the implantation of titanium implants in the tibia of diabetes-induced rats provided some positive effect on bone regeneration at the early stage after implantation. On the other hand, this method is unable to increase the level of osseointegration and bone regeneration of the implant in an uncontrolled diabetic patient.

The Signal Transduction Mechanisms on the Intestinal Mucosa of Rat Following Irradiation (방사선조사후 백서소장점막에서 발생하는 신호전달체계에 관한 연구)

  • Yoo Jeong Hyun;Kim Sung Sook;Lee Kyung Ja;Rhee Chung Sik
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.79-95
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    • 1997
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

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