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Effects of Lactobacillus reuteri MG5346 on Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL)-Induced Osteoclastogenesis and Ligature-Induced Experimental Periodontitis Rats

  • Yu-Jin Jeong;Jae-In Jung;YongGyeong Kim;Chang-Ho Kang;Jee-Young Imm
    • Food Science of Animal Resources
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    • v.43 no.1
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    • pp.157-169
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    • 2023
  • Effects of culture supernatants of Lactobacillus reuteri MG5346 (CS-MG5346) on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis were examined. CS-MG5346 treatment up to 400 ㎍/mL significantly reduced tartrate-resistant acid-phosphatase (TRAP) activity, the phenotype biomarker of osteoclast, without affecting cell viability. CS-MG5346 inhibited the expression of osteoclast specific transcriptional factors (c-fos and nuclear factor-activated T cells c1) and their target genes (TRAP, cathepsin, and matrix metallo-proteinase-9) in a dose-dependent manner (p<0.05). The administration of L. reuteri MG5346 (2×108 CFU/day) for 8 wks significantly improved furcation involvement, but no difference was observed in alveolar bone loss in ligature-induced experimental periodontitis rats. The elevated RANKL/osteoprotegerin ratio, the biomarker of periodontitis, was significantly lowered in the gingival tissue by administration of L. reuteri MG5346 (p<0.05). L. reuteri MG5346 showed excellent stability in simulated stomach and intestinal fluids and did not have antibiotic resistance. Based on the results, L. reuteri MG5346 has the potential to be a promising probiotic strain for oral health.

Signal Transduction Events Elicited by Natural Products: Role of MAPK and Caspase Pathways in Homeostatic Response and Induction of Apoptosis

  • Kong, Ah-Ng Tony;Yu, Rong;Chen, Chi;Mandlekar, Sandhya;Primiano, Thomas
    • Archives of Pharmacal Research
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    • v.23 no.1
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    • pp.1-16
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    • 2000
  • Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many man become important therapeuitc drugs of the future.

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Deep Brain Photoreceptors and Photoperiodism in Vertebrates

  • Oishi, Tadashi;Haida, Yuka;Okano, Keiko;Yoshikawa, Tomoko;Kawano, Emi;Nagai, Kiyoko;Fukada, Yoshitaka;Tsutsui, Kazuyoshi;Tamotsu, Satoshi
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.5-8
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    • 2002
  • Photoperiodism is an important adaptive phenomenon in various physiological parameters including reproduction to cope with seasonal changes. Involvement of extraretinal photoreceptors in the photoperiodism in non-mammalian vertebrates has been well established. In addition, circadian clock system is known to be involved in the photoperiodic time measurement. The pathway consists of light-input system, time measurement system (circadian clock), gonadotropin releasing hormone (GnRH) production in the hypothalamus, luteinizing hormone (LH) and follicle stimulating hormone (FSH) production in the pituitary, and final gonadal development. Recently, several laboratories reported photopigments newly cloned in the pineal, eyes and deep brain in addition to already known visual pigments in the retina. These are pinopsin, parapinopsin, VA-opsin, melanopsin, etc. All these photopigments belong to the opsin family having retinal as the chromophore. However, the function of these photopigments remains unknown. I reviewed the studies on the location of the photopigments by immunocytochemistry. I also discussed the results on the action spectra for induction of gonadal development in relation with the location of the photoreceptors. Various physiologically active substances distribute in the vertebrate brain. Such substances are GnRH, GnIH, neuropeptide Y, vasoactive intestinal peptide, c-Fos, galanin, neurosteroids, etc. I summarized the immunhistochemical studies on the distribution and the photoperiodic changes of these substances and discussed the route from the deep brain photoreceptor to GnRH cells.

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The Anti-Cancer Effect of Apamin in Bee-Venom on Melanoma cell line SK-MEL-2 and Inhibitory Effect on the MAP-Kinase Signal Pathway (약침용(藥鍼用) 봉독성분(蜂毒成分) 중(中) Apamin의 항암효과(抗癌效果)와 MAP-Kinase 신호전달체계에 관한 연구(硏究))

  • Kim, Youn-Mi;Lee, Jae-Dong;Park, Dong-Seok
    • Journal of Acupuncture Research
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    • v.18 no.4
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    • pp.101-115
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    • 2001
  • Objective : To characterize the antitumorigenic potential of Apamin, one of the major components of bee venom, its effects on cell proliferation and the mitogen-activated protein kinase (MAPK) signal transduction pathway were characterized using the human melanoma cell line SK-MEL-2. Methods & Results : Cell counting analysis for cell death demonstrated that consistent with a previous results, SK-MEL-2 cells treated with $0.5-2.0{\mu}g/ml$ of Apamin showed no recognizable cytotoxic effect whereas detectable induction of cell death was identified at concentrations over $5.0{\mu}g/ml$. [3H]thymidine incorporation assay for cell proliferation demonstrated that DNA replication of SK-MEL-2 cells is inhibited by Apamin in a dose- and time-dependent manner. To explore whether Apamin-induced growth suppression is associated with the MAPK signaling pathway, phosphorylation of Erk, a function mediator of MAPK growth-stimulating signal, was examined Western blot assay using a phospho-specific Erkl/2 antibody. A significant increase of Erkl/2 phosphorylation level was observed in Apamin-treated cells compared with untreated control cells. Qantitative RT-PCR analysis revealed that Apamin inhibit expression of MAPK downstream genes such as c-Jun, c-Fos, and cyclin D1 but not expression of MAPK pathway component genes including Ha-Ras, c-Raf-1, MEK1, and Erk. Conclusion : It is strongly suggested that the antitumorigenic activity of Apamin might result in part from its inhibitory effect on the MAPK signaling pathway in human melanoma cells SK-MEL-2.

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Characteristics of Thermal Coefficient of Fiber Bragg Grating for Temperature Measurement (온도 측정을 위한 광섬유 브래그 격자 센서의 온도 계수 특성 평가)

  • Kim, Heon-Young;Kang, Donghoon;Lee, Jin-Hyuk;Kim, Dae-Hyun
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.37 no.8
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    • pp.999-1005
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    • 2013
  • A fiber Bragg grating sensor is considered a smart sensor that shows outstanding performance in the field of structural health monitoring (SHM). It has a powerful advantage, especially that of multiplexing, which enables several parameters to be sensed at multiple points by using a single optical fiber line. Among several parameters, the thermal expansion coefficient and thermo-optic coefficient are required to measure temperature. In previous studies, these were considered constant variables. This study shows that two parameters vary with temperature and newly proposes a temperature function for these two parameters. Specifically, these two parameters were defined as a single variable, and then, it was experimentally verified that this variable is a function of temperature. Finally, it was shown that temperature from RT to $100^{\circ}C$ was precisely measured by using the temperature function that was defined through the experiment.

On the Japanese New Alternative Dispute Resolution System in the Financial Sector (일본의 금융분야 ADR 에 관한 검토)

  • Kim, Sun-Jeong
    • Journal of Arbitration Studies
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    • v.20 no.3
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    • pp.121-145
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    • 2010
  • In the past, ADR has not been used as frequently in Japan as it has in other parts of the industrialized world. However, though litigation is still the most utilized vehicle of dispute resolution by Japanese financial institutions, this will be changing. The New Financial ADR system, which was created by a June 2009 amendment to the Financial Instruments and Exchange Act, is meant to deal with every stage of financial-related disputes and, as such, strives to resolve disputes before they become significant and acts to ameliorate any post-ADR issues that may remain, thereby completing the FIEA's purpose to protect investors. Since the foundation of the New Financial ADR system applies to all related industries, new provisions were set out in 16 business related acts, such as the Banking Act, the Insurance Business Act, and FIEA itself. October 2010 will mark the formal introduction of a new system of financial ADR in Japan. New Financial ADR in Japan will be modeled on the Financial Ombudsman Service in the United Kingdom, but will not feature one comprehensive dispute resolution system in which one dispute resolution institution covers all disputes in the financial field. The New Financial ADR system is merely one step towards a foundation of comprehensive financial ADR such as FOS. It must be noted, however, that this all important first step was over seven years in the making, involving a great deal of discussion, debate, and compromise amongst many parts of Japanese government, business, and society. The New Financial ADR system grants participating parties the ability to stop the clock on any statute of limitations which may correspond to any future possible court cases related to the dispute,13 and further grants the ability to suspend related court proceedings while the parties are utilizing the New Financial ADR system. In addition, where financial institutions have not accepted dispute resolution proceedings or have not accepted a special conciliation proposal, the Ministry of Finance may issue an order compelling compliance if it is found that certain actions are necessary to ensure the appropriate operations of a financial institution's business. In Japan, as best practices have not yet been created.

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Effect Analysis of Residual Frequency Offsets for Asynchronous MC-CDMA Uplink Systems (비동기 MC-CDMA 상향 링크 시스템에서의 잔류 주파수 옵셋 영향 분석)

  • Ko, Kyun-Byoung;Woo, Choong-Chae
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.47 no.8
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    • pp.9-15
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    • 2010
  • This paper presents an analysis of asynchronous multicarrier-code division multiple access (MC-CDMA) uplink systems over frequency-selective multipath fading channels when the frequency offsets (FOs) of all users are random variables and the frequency offset for the desired user is compensated. The effect of a residual frequency offset(RFO) on the average bit error rate (BER) is evaluated by the semi-analytical method, then the approximated BER performance is obtained as a closed-form expression. Moreover, the signal to noise ratio (SNR) loss caused by RFO is evaluated. Derived results show that the performance degradation due to RFO is negligible if the estimation error of RFO for the desired user is less than the normalized value of 0.1.

Suppressive Effects of Hesperidin on Th2-associated Cytokines Expression in RBL-2H3 Cells (RBL-2H3 세포에서 Hesperidin의 Th2 사이토카인 발현 억제 효과)

  • Jeong, Hwa-Hyun;Kim, Soon-Rye;Pyo, Myoung-Yun
    • Korean Journal of Pharmacognosy
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    • v.44 no.2
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    • pp.104-109
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    • 2013
  • Hesperidin (HES), a flavonone glycoside isolated from the citrus fruits such as lemons and oranges, has been reported to have many biological properties including antiinflammatory, antioxidant, and antiallergy activities. In this study, we focused on the action of HES modulating Th2-associated cytokines such as IL-4 and IL-13 expression in PMA/ionomycin (PI)-stimulated rat basophilic leukemia (RBL-2H3) cells. The production of IL-4 and IL-13 was quantified by ELISA and the mRNA expression was detected by using RT-PCR assay. In addition, western blot analysis was performed to determine the transcription factors involved in the cytokine expression. We found that HES significantly decreased PI-induced IL-4 and IL-13 productions and also decreased the level of mRNA in a dose-dependent manner. Furthermore, western blot analysis of the transcription factors implied that HES down-regulated the protein level of c-Jun and c-Fos, which are the activating protein 1 (AP-1) family and nuclear factor-kappaB (NF-${\kappa}B$) characterized as a transcription factors related to the Th2-associated cytokine expression. Taken together, our data showed that the action of HES responsible for antiallergy activities is based on suppression of Th2-associated cytokines through inhibition of AP-1 and NF-${\kappa}B$ transcription factors.

Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats

  • Lee, Min Ju;Yoon, Tae Gyoon;Kang, Moonkyu;Kim, Hyun Jeong;Kang, Kyung Sun
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.153-160
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    • 2017
  • In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

Metabolism of Soyasaponin I by Human Intestinal Microflora and Its Estrogenic and Cytotoxic Effects

  • Chang, Seo-Young;Han, Myung-Joo;Han, Sang-Jun;Kim, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.430-437
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    • 2009
  • Metabolites of Soyasaponin I, a major constituent of soybean, by human intestinal microflora were investigated by LC-MS/MS analysis. We found four peaks, one parental constituent and three metabolites: m/z 941 [M-H]$^-$, m/z 795 [M-rha-H]$^-$, m/z 441 [aglycone-$H_2O$+H]$^+$, and m/z 633 [M-rha-gal-H]$^-$, which was an unknown metabolite, soyasapogenol B 3-$\beta$-D-glucuronide. When soyasaponin I was incubated with the human fecal microbial fraction from ten individuals for 48 h, soyasaponin I was metabolized to soyasapogenol B via soyasaponin III and soyasapogenol B 3-$\beta$-D-glucuronide or via soyasaponin III alone. Both soyasaponin I and its metabolite soyasapgenol B exhibited estrogenic activity. Soyasaponin I increased the proliferation, mRNA expression of c-fos and pS2, in MCF7 cells more potently than soyasapogenol B. However, soyasapogenol B showed potent cytotoxicity against A549, MCF7, HeLa and HepG2 cells, while soyasaponin I did not. The cytotoxicity of soyasapogenol B may prevent its estrogenic effect from increasing dose-dependently. These findings suggest that orally administered soyasaponin I may be metabolized to soyasapogenol B by intestinal microflora and that soyasapogenol B may express a cytotoxic effect rather than an estrogenic effect.