• Title/Summary/Keyword: stress dependent

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Hypertonicity Down-regulates the $1{\alpha},25(OH)_2$ Vitamin $D_3$-induced Osteoclastogenesis Via the Modulation of RANKL Expression in Osteoblast

  • Jeong, Hyun-Joo;Yushun, Tian;Kim, Bo-Hye;Nam, Mi-Young;Lee, Hyun-A;Yoo, Yun-Jung;Seo, Jeong-Taeg;Shin, Dong-Min;Ohk, Seung-Ho;Lee, Syng-Ill
    • International Journal of Oral Biology
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    • v.30 no.1
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    • pp.23-30
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    • 2005
  • Bone remodeling is a process controlled by the action of two major bone cells; the bone forming osteoblast and the bone resorbing osteoclast. In the process of osteoclastogenesis, stromal cells and osteoblast produce RANKL, OPG, and M-CSF, which in turn regulate the osteoclastogenesis. During the bone resorption by activated osteoclasts, extracellular $Ca^{2+}/{PO_4}^{2-}$ concentration and degraded organic materials goes up, providing the hypertonic microenvironment. In this study, we tested the effects of hypertonicity due to the degraded organic materials on osteoclastogenesis in co-culture system. It was examined the cellular response of osteoblastic cell in terms of osteoclastogenesis by applying the sucrose, and mannitol, as a substitute of degraded organic materials to co-culture system. Apart from the sucrose, mannitol, and NaCl was tested to be compared to the effect of organic osmotic particles. The addition of sucrose and mannitol (25, 50, 100, 150, or 200 mM) to co-culture medium inhibited the number of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells induced by 10 nM $1{\alpha},25(OH)_2vitaminD_3$ ($1{\alpha},25(OH)_2D_3$). However, NaCl did exert harmful effect upon the cells in this co-culture system, which is attributed to DNA damage in high concentration of NaCl. To further investigate the mechanism by which hypertonicity inhibits $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis, the mRNA expressions of receptor activator of nuclear factor (NF)-kB ligand (RANKL) and osteoprotegerin (OPG) were monitored by RT-PCR. In the presence of sucrose (50 mM), RANKL mRNA expression was decreased in a dose-dependent manner, while the change in OPG and M-CSF mRNA were not occurred in significantly. The RANKL mRNA expression was inhibited for 48 hours in the presence of sucrose (50 mM), but such a decrement recovered after 72 hours. However, there were no considerable changes in the expression of OPG and M-CSF mRNA. Conclusively, these findings strongly suggest that hypertonic stress down-regulates $1{\alpha},25(OH)_2D_3$-induced osteoclastogenesis via RANKL signal pathway in osteoblastic cell, and may playa pivotal role as a regulator that modulates osteoclastogenesis.

Condition Evaluation of the Pavement Foundations Using Multi-load Level FWD Deflections (다단계 하중 FWD를 사용한 도로기초 상태평가 연구)

  • Park, Hee-Mun;Kim, Richard Y.;Park, Seong-Wan
    • Journal of the Korean Geotechnical Society
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    • v.19 no.6
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    • pp.261-271
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    • 2003
  • A condition evaluation procedure for the pavement foundations using multi-load level Falling Weight Deflectometer(FWD) deflections is presented in this paper. A dynamic finite element program incorporating a stress-dependent material model, was used to generate the synthetic deflection database. Based on this synthetic database, the relationships between surface deflections and critical responses, such as stresses and strains in base and subgrade layers, have been established. FWD deflection data, Dynamic Cone Penetrometer(UP) data, and repeated load resilient modulus testing results used in developing this procedure were collected from the Long Term Pavement Performance (LTPP) and North Carolina Department of Transportation (NCDOT) database. Research effort focused on investigation of the effect of the FWD load level on the condition evaluation procedures. The results indicate that the proposed procedure can estimate the pavement foundation conditions. It is also found that structurally adjusted Base Damage Index (BDI) and Base Curvature Index (BCI) are good indicators for the prediction of stiffness characteristics of aggregate base and subgrade respectively. A FWD test with a load of 66.7 kN or less does not improve the accuracy of this procedure. Results from the study for the nonlinear behavior of a pavement foundations indicate that the deflection ratio obtained from multi-load level deflections can predict the type and quality of the pavement foundation materials.

습사료에 첨가한 유용미생물 및 한약재 혼합제(한방천ㆍ어력천) 특성과 혼합 첨가제가 넙치간의 활성에 미치는 효과

  • Yeo, In-Kyu;Rho, Sum
    • Journal of Aquaculture
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    • v.17 no.2
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    • pp.109-114
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    • 2004
  • The effects of different concentrations (0, 0.3, 0.6 and 0.9%) of fish feed additives (Hanbangchun and Olyukchun) utilizing effective microorganisms and herb medicine on activity of liver function were examined in olive flounder, Paralichthys olivaceus, Moreover, we investigated the characteristics of the additives. Total number of microorganisms (Lactic acid bacteria, Bacillus subtilis, Saccharomyces cerevisiae, Photosynthetic bacteria and Azotobactor) in the additives was 5.6${\times}$10$^{8}$ CFU/g in the Hanbangchun and 3.0${\times}$10$^{8}$ CFU/g in the Olyukchun. Levels of three typical pathological microorgamisms (Edwardsiella tarda, Vibrio anguillarum and Streptococcus sp.) in moist pellets (MP) were significantly decreased by the additives in a concentration-dependent way. Hepatosomatic index of fish in the 0.3% group was significantly increased. Total serum protein was increased in all the groups containing additives, but the protein content in liver was higher in the control group. Higher activities of catalase and superoxide dismutase which are involved in physiological defense mechanisms were found in the dietary groups containing 0.3% and 0.6%, respectively. These results suggest that the additives, Hanbangchun and Olyukchun, can increase tolerance of olive flounder against stress and hypoxic conditions by increasing activities of body antioxidant enzymes.

Autophagy Inhibition with Monensin Enhances Cell Cycle Arrest and Apoptosis Induced by mTOR or Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cells

  • Choi, Hyeong Sim;Jeong, Eun-Hui;Lee, Tae-Gul;Kim, Seo Yun;Kim, Hye-Ryoun;Kim, Cheol Hyeon
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.1
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    • pp.9-17
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    • 2013
  • Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

The Structural and Functional Role of p53 as a Cancer Therapeutic Target (암 치료 표적으로서 p53의 구조적 및 기능적 역할)

  • Han, Chang Woo;Park, So Young;Jeong, Mi Suk;Jang, Se Bok
    • Journal of Life Science
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    • v.28 no.4
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    • pp.488-495
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    • 2018
  • The p53 gene plays a critical role in the transcriptional regulation of cellular response to stress, DNA damage, hypoxia, and tumor development. Keeping in mind the recently discovered manifold physiological functions of p53, its involvement in the regulation of cancer is not surprising. In about 50% of all human cancers, inactivation of p53's protein function occurs either through mutations in the gene itself or defects in the mechanisms that activate it. This disorder plays a crucial role in tumor evolution by allowing the evasion of a p53-dependent response. Many recent studies have focused on directly targeting p53 mutants by identifying selective, small molecular compounds to deplete them or to restore their tumor-suppressive function. These small molecules should effectively regulate various interactions while maintaining good drug-like properties. Among them, the discovery of the key p53-negative regulator, MDM2, has led to the design of new small molecule inhibitors that block the interaction between p53 and MDM2. Some of these small molecule compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, more personalized anti-carcinogenic medicines. Here, we review the structural and functional consequences of wild type and mutant p53 as well as the development of therapeutic agents that directly target this gene, and compounds that inhibit the interaction between it and MDM2.

Fortified Antioxidative Potential by Chrysoeriol through the Regulation of the Nrf2/MAPK-mediated HO-1 Signaling Pathway in RAW 264.7 Cells (생쥐 대식세포에서 HO-1 발현 유도를 통한 chrysoeriol의 항산화 효과)

  • Park, Chung Mu
    • Journal of Life Science
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    • v.28 no.1
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    • pp.43-49
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    • 2018
  • Chrysoeriol is a widespread flavone, and it is usually found in alfalfa, which has been used as a traditional medicine to treat dyspepsia, asthma, and urinary system disorders. Recently, analysis has been conducted on the anti-inflammatory activity of chrysoeriol, but information on its antioxidative capacity is limited. In this study, the antioxidative potential of chrysoeriol against oxidative damage and its molecular mechanisms were evaluated by analysis of the cell viability, reactive oxygen species (ROS) formation, and Western blots in the RAW 264.7 cell line. Chrysoeriol significantly scavenged lipopolysaccharide (LPS)-induced intracellular ROS formation in a dose-dependent manner, without any cytotoxicity. Heme oxygenase-1 (HO-1), a phase II enzyme that exerts antioxidative activity, was also potently induced by chrysoeriol treatment, which corresponded to the translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) into the nucleus. Moreover, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) were analyzed due to their important role in maintaining cellular redox homeostasis against oxidative stress. As a result, chrysoeriol-induced HO-1 upregulation was mediated by extracellular signal - regulated kinase (ERK), c-Jun $NH_2$-terminal kinase (JNK), and p38 phosphorylation. To identify the antioxidative potential exerted by HO-1, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was applied and mitigated by chrysoeriol treatment, which was confirmed by the HO-1 selective inhibitor and inducer, respectively. Consequently, chrysoeriol strongly strengthened the HO-1-mediated antioxidative potential through the regulation of the Nrf2/MAPK signaling pathways.

Molecular Cloning and Function Analysis of an Anthocyanidin Synthase Gene from Ginkgo biloba, and Its Expression in Abiotic Stress Responses

  • Xu, Feng;Cheng, Hua;Cai, Rong;Li, Lin Ling;Chang, Jie;Zhu, Jun;Zhang, Feng Xia;Chen, Liu Ji;Wang, Yan;Cheng, Shu Han;Cheng, Shui Yuan
    • Molecules and Cells
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    • v.26 no.6
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    • pp.536-547
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    • 2008
  • Anthocyanidin synthase (ANS, leucoanthocyanidin oxygenase), a 2-oxoglutarate iron-dependent oxygenase, catalyzed the penultimate step in the biosynthesis of the anthocyanin class of flavonoids, from the colorless leucoanthocyanidins to the colored anthocyanidins. The full-length cDNA and genomic DNA sequences of ANS gene (designated as GbANS) were isolated from Ginkgo biloba for the first time. The full-length cDNA of GbANS contained a 1062-bp open reading frame (ORF) encoding a 354-amino-acid protein. The genomic DNA analysis showed that GbANS gene had three exons and two introns. The deduced GbANS protein showed high identities to other plant ANSs. The conserved amino acids (H-X-D) ligating ferrous iron and residues (R-X-S) participating in 2-oxoglutarate binding were found in GbANS at the similar positions like other ANSs. Southern blot analysis indicated that GbANS belonged to a multi-gene family. The expression analysis by real-time PCR showed that GbANS expressed in a tissue-specific manner in G. biloba. GbANS was also found to be up-regulated by all of the six tested abiotic stresses, UV-B, abscisic acid, sucrose, salicylic acid, cold and ethylene, consistent with the promoter region analysis of GbANS. The recombinant protein was successfully expressed in E. coli strain with pET-28a vector. The in vitro enzyme activity assay by HPLC indicated that recombinant GbANS protein could catalyze the formation the cyanidin from leucocyanidin and conversion of dihydroquercetin to quercetin, suggesting GbANS is a bifunctional enzyme within the anthocyanidin and flavonol biosynthetic pathway.

Linkage Between Brown Planthopper Resistance Gene and Salt Tolerance in Rice (벼멸구 저항성 유전자와 내염성과의 연관)

  • Yang Dae Hwa;Kim Jin-Hong;Wi Seung Gon;Baek Myung-Hwa;Lim Sang Yong;Lee In Sok;Lee Kyu-Seong;Lee Myung Chul;Lim Yong-Pyo;Chung Byung Yeoup;Kim Jae-Sung
    • Journal of Life Science
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    • v.15 no.1 s.68
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    • pp.61-65
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    • 2005
  • Using two japonica rice cultivars (Ilpumbyeo and Sanghaehyanghyella), which are distinguishable by the brown planthopper (BHP) resistance maker (R208), a relationship between the BPH resistance gene (Os-Bil) and salt-tolerance was investigated. To do this, changes in the expression level of Os-Bil by the salt stress were quantified by the real-time PCR in the two cultivars, and compared with those in other two indica rice cultivars (Pokkali and IR29). In Ilpumbyeo, the expression level of Os-Bil decreased by the treatments of 50 and 200 mM NaCl in a concentration-dependent manner, and in Sanghaehyanghyella it rather increased slightly at 50 mM but decreased drastically at 200 mM. Comparably, IR29, a salt-sensitive cultivar, showed a reduction of the Os-Bil gene expression after the treatment of 100 mM NaCl, but Pokkali, a salt-tolerance cultivar, rather increased about two times in the level of Os-Bil transcripts. These results suggest that the BPH resistance gene may involve in the difference in the salt-tolerance at least between the two indica rice cultivars.

Antihypertensive Effects of Novel Isoflavone-Free Black Soy Peptide Mixture as HO-1 Inducer (Heme 산화효소 발현 유도체로서 Isoflavone-Free 검은콩 펩타이드의 항고혈압 활성)

  • Shin, Mi-Kyung;Kwon, Yong-Hyun;Ahn, Chang-Won;Shin, Dong-Seok;Park, Soo-Hyun;Choi, Bo-Hwa;Hong, Soon-Sun;Kang, Ju-Hee;Park, Chang-Shin
    • YAKHAK HOEJI
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    • v.56 no.3
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    • pp.191-197
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    • 2012
  • We previously reported that the novel isoflavone-free peptide mixture (black soybean peptide, BSP) had several beneficial effects like antiobesity and hypotriglyceridemic effect. However, there are no reports for BSP on anti-hypertensive activity. BSP induced heme oxygenase-1 (HO-1) in HUVECs, thus investigated the HO-1-induced activity in HUVECs and the anti-hypertensive effects in SHR animal model. BSP significantly induced HO-1 expression both at transcriptional and protein levels in a time- and dose-dependent manner as measured by RT-PCR and Western blot analysis, respectively. These inductions were abolished by pretreatment of N-acetyl-cystein (NAC, 1~10 mM), but not by employing Tempol, a superoxide dismutase (SOD) mimetic (1~5 mM). As expected, enzymatic activity (~2 fold) determined by bilirubin formation assay and cGMP concentration (~6 fold) were significantly increased in BSP-treated cells. Based on the numerous evidences on the beneficial effects of HO-1 and our results, we investigated in vivo effects of BSP on the antihypertensive activity. The administration of BSP (1% in drinking water) significantly decreased mean blood pressure (BP) (from $218.6{\pm}6.99$ to $190.0{\pm}3.42$ mm Hg, p<0.01). This result indicates that BSP is strong inducer of HO-1 expression, which may be triggered by oxidative stress, and has anti-hypertensive activity.

Use of Electroencephalogram to Supplement Sensory Assessment for the Evaluation of Body Odor (인체 체취 평가시 감성평가를 위한 뇌파측정기의 적용)

  • Seo, Young Kyoung;Baek, Ji Hwoon;Boo, Yong Chool;Koh, Jae Sook
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.3
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    • pp.265-272
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    • 2020
  • The body odor as well as the skin changes has become an important issue. Humans leave respective specific odors dependent on sex and age; The odor has been known to affect social relationship of human. In this study, we wanted to confirm the possibility as parameters to evaluate body odor into existing odor evaluation methods by experts. The 15 subjects, aged from 50 to 61 years wore cotton t-shirts for 72 hours and collected body odor. The cotton t-shirts containing body odor were used for sensory evaluation and EEG measurement by the odor experts. In order to evaluate body odors of each subject, an odor sensory evaluation and electroencephalogram (EEG) were conducted by odor exports and the correlation in between two assessments was analyzed. Pearson correlation analysis shows negative correlation of the sensory evaluation versus 'Excitement' in EEG parameter (r = - 0.649, p = 0.009) and positive correlation of the sensory evaluation versus 'Stress' in EEG parameter (r = 0.704, p = 0.003). In conclusion, it is considered that the evaluation of body odor through EEG measurement can be used as a method to complement the odor evaluation by experts.