• 제목/요약/키워드: down-regulation

검색결과 1,254건 처리시간 0.025초

Experimental study on modified low liquid limit silt for abutment backfill in bridge-embankment transition section

  • Shu-jian Wang;Yong Sun;Zhen-bao Li;Kai Xiao;Wei Cui
    • Geomechanics and Engineering
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    • 제32권6호
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    • pp.601-613
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    • 2023
  • Low liquid limit silt, widely distributed in the middle and down reaches of Yellow River, has the disadvantages of poor grading, less clay content and poor colloidal activity. It is very easy to cause vehicle jumping at the bridge-embankment transition section when the low liquid limit silt used as the backfill at the abutment back. In this paper, a series of laboratory tests were carried out to study the physical and mechanical properties of the low liquid limit silt used as back filling. Ground granulated blast furnace slag (GGBFS) was excited by active MgO and hydrated lime to solidify silt as abutment backfill. The optimum ratio of firming agent and the compaction and mechanical properties of reinforced soil were revealed through compaction test and unconfined compressive strength (UCS) test. Scanning electron microscope (SEM) test was used to study the pore characteristics and hydration products of reinforced soil. 6% hydrated lime and alkali activated slag were used to solidify silt and fill the model of subgrade respectively. The pavement settlement regulation and soil internal stress-strain regulation of subgrade with different materials under uniformly distributed load were studied by model experiment. The effect of alkali activated slag curing agent on curing silt was verified. The research results can provide technical support for highway construction in silt area of the Yellow River alluvial plain.

Parthenolide inhibits osteoclast differentiation and bone resorbing activity by down-regulation of NFATc1 induction and c-Fos stability, during RANKL-mediated osteoclastogenesis

  • Kim, Ju-Young;Cheon, Yoon-Hee;Yoon, Kwon-Ha;Lee, Myeung Su;Oh, Jaemin
    • BMB Reports
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    • 제47권8호
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    • pp.451-456
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    • 2014
  • Parthenolide, a natural product derived from Feverfew, prevents septic shock and inflammation. We aimed to identify the effects of parthenolide on the RANKL (receptor activator of $NF-{\kappa}B$ ligand)-induced differentiation and bone resorbing activity of osteoclasts. In this study, parthenolide dose-dependently inhibited RANKL-mediated osteoclast differentiation in BMMs, without any evidence of cytotoxicity and the phosphorylation of p38, ERK, and $I{\kappa}B$, as well as $I{\kappa}B$ degradation by RANKL treatment. Parthenolide suppressed the expression of NFATc1, OSCAR, TRAP, DC-STAMP, and cathepsin K in RANKL-treated BMMs. Furthermore, parthenolide down-regulated the stability of c-Fos protein, but could not suppress the expression of c-Fos. Overexpression of NFATc1 and c-Fos in BMMs reversed the inhibitory effect of parthenolide on RANKL-mediated osteoclast differentiation. Parthenolide also inhibited the bone resorbing activity of mature osteoclasts. Parthenolide inhibits the differentiation and bone-resolving activity of osteoclast by RANKL, suggesting its potential therapeutic value for bone destructive disorders associated with osteoclast-mediated bone resorption.

Inhibition of the NEDD8 Conjugation Pathway by shRNA to UBA3, the Subunit of the NEDD8-Activating Enzyme, Suppresses the Growth of Melanoma Cells

  • Cheng, Fang;Chen, Hao;Zhang, Lei;Ruo-Hong, Li;Liu, Yi;Sun, Jian-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권1호
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    • pp.57-62
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    • 2012
  • Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8), a ubiquitin-like protein, mainly functions through covalent ligation to cullin proteins. Conjugation of NEDD8 with cullins can promote ubiquitination, which plays a critical role in the degradation of many proteins. UBA3 is the subunit of NEDD8-activating enzyme which is one of the keys for NEDD8 linkage to cullin proteins. Previous research showed NEDD8 conjugation to be up-regulated in highly proliferative cell lines. In the present study, up-regulated NEDD8 conjugation was observed in melanoma cell lines by Western blot analysis. After down-regulation with a RNAi to UBA3, proliferation of M14 was suppressed in vitro and in vivo. In conclusion, up-regulated NEDD8 conjugation may be involved in the development of melanoma. Interference in this pathway might offera promising method for melanoma therapy.

시·도별 주거복지 관련 자치법규에 대한 연구 (A Study of Housing Welfare Regulations of City & Province)

  • 이지숙
    • 한국주거학회논문집
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    • 제27권6호
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    • pp.77-84
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    • 2016
  • The increase rate of total population slows down and the ratio of the elderly population & single-household in our country is growing rapidly. Korean's housing penetration has already exceeded 100%. So people focus on the qualitative aspects of housing, namely housing welfare than the quantitative supply of housing The purpose of the study proposes the desirable direction for housing welfare policy based on the housing welfare regulations. The data for the analysis was collected through the regulations of 8 cities and 9 provinces. So housing welfare contents like housing welfare business, housing welfare center, etc. were extracted from 4 Housing Welfare Support Regulations, 5 Housing Basic Regulations and 8 Housing Regulations. The results were as follows: To stabilize housing and improve housing, the contents of housing welfare contained in related ordinance are still insufficient. Continue to be effective and housing welfare work, it shall be presented in detail in the regulations with respect to the financing plan. To those who need the housing welfare will have to be built an effective delivery system that can be delivered in a timely manner. For housing welfare for the elderly, housing welfare business information is detailed and broken down, it should be codified.

Toxicogenomic Study to Identify Potential New Mechanistic Markers on Direct-Acting Mutagens in Human Hepatocytes (THLE-3)

  • Kim, Youn-Jung;Song, Mi-Kyung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • 제3권4호
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    • pp.231-237
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    • 2007
  • Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

Fibroin Enhances Insulin Sensitivity and Reverses Insulin Resistance in 3T3-L1 Adipocytes

  • Hyun Chang-Kee;Frost Susan C.
    • 한국식품영양과학회:학술대회논문집
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    • 한국식품영양과학회 2004년도 Annual Meeting and International Symposium
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    • pp.185-197
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    • 2004
  • Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes (6). To explore the mechanism underlying this effect, we have used the 3T3-Ll adipocytes as a cell type which would represent the periphery, in vivo. Exposure of 3T3-Ll adipocytes to chronic insulin leads to the a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to fibroin blocked, in part, the response to chronic insulin but also increased the sensitivity of control cells to the acute action of insulin. The later effect was most robust at physiological concentrations of insulin. Fibroin did not prevent the insulin-induced down-regulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no affect on the loss in activity of the insulin-sensitive down-stream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin up-regulated GLUT1 which increased its expression at the cell surface and caused the redistribution of GLUT4 to the plasma membrane. Together, these later effects would lead to an improvement in hyperglycemia in vivo which would in turn reduce the need for insulin.

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Nebulin in Z-discs and Costameres

  • Lee, Min-A;Park, Sin-Woo;Moon, Hyung-Tae;Ko, Han-Suk;Lee, Yeong-Mi;Kim, So-Young;Joo, Young-Mi;Kim, Chong-Rak
    • 대한의생명과학회지
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    • 제9권4호
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    • pp.231-240
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    • 2003
  • Deciphering the molecular interactions of proteins forming Z-lines is pivotal for understanding the regulation of myofibril assembly, sarcomeric organization, and mechanical properties of striated muscle. The purpose of this study is to searched for potential novel ligands of the Z-line portion of nebulin. In this study interacting proteins with intra-Z-line region of nebulin were screened using a yeast two-hybrid approach. The interaction was conformed by GST pull-down assay. We identified 269 residues within villin/gelsolin homology domain of supervillin that intreacts with the serine rich region of nebulin. The specific interactions of nebulin and supervillin were confirmed in vitro by GST pull-down experiments. Our data suggest that supervillin attaches directly to the Z-line through its interaction with the serine rich domain of nebulin in skeletal muscles. This interaction may link myofibrillar Z-discs to the membrane-associated complexes, costameres.

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Biochemical Characterization of Adriamycin-Resistance in PC-14 Human Lung Adenocarcinoma Cell Line

  • Yi, Jae-Youn;Hong, Weon-Seon;Son, Young-Sook
    • BMB Reports
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    • 제34권1호
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    • pp.66-72
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    • 2001
  • To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

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ZNF217 is Overexpressed and Enhances Cell Migration and Invasion in Colorectal Carcinoma

  • Zhang, Zi-Chao;Zheng, Li-Qiang;Pan, Li-Jie;Guo, Jin-Xing;Yang, Guo-Shan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권6호
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    • pp.2459-2463
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    • 2015
  • Background: To investigate the expression and clinical significance of zinc finger protein 217 (ZNF217) in human colorectal carcinoma (CRC). Materials and Methods: The expression of ZNF217 in 60 CRC tissues and matched tumor adjacent tissues, collected between January 2013 and June 2014, was assessed immunohistochemically. The relationship between the expression of ZNF217 and clinicopathlogical features was analyzed by Pearson chi-square test. In addition, siRNA was used to down-regulate the expression of ZNF217 in CRC cells. The effects of ZNF217 for cell migration and invasion were measured by wound healing assay and transwell assay, respectively. Results: The expression level of ZNF217 was significantly higher in CRC tissues than in tumor adjacent tissues (p<0.05), positively correlating with tumor size, lymphatic metastasis and advanced TNM stage (p<0.05). Down-regulation of ZNF217 in CRC cells could significantly suppress cell migration and invasion. Conclusions: ZNF217 is overexpressed in colorectal carcinoma tissues and is associated with tumor malignant clinicopathological features. ZNF217 may promote CRC progression by inducing cell migration and invasion.

A2B Adenosine Receptor Stimulation Down-regulates M-CSF-mediated Osteoclast Proliferation

  • Oh, Yoon Taek;Lee, Na Kyung
    • 대한의생명과학회지
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    • 제23권3호
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    • pp.194-200
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    • 2017
  • Bone-resorbing osteoclasts play a major role in maintaining bone homeostasis with bone-forming osteoblasts. Although it has been reported that A2B adenosine receptor (A2BAR) regulates osteoclast differentiation, its effects on apoptosis or proliferation of osteoclasts have been less-defined. Here, we demonstrate that A2BAR stimulation regulates macrophage-colony stimulating factor (M-CSF)-mediated osteoclast proliferation. Stimulation with a specific agonist of A2BAR, BAY 60-6583, significantly reduced M-CSF-mediated osteoclast proliferation in a time- and dose-dependent manner. In addition, A2BAR stimulation induced both apoptosis of the cells and cell arrest in the G1 phase with a decrease of cell number in the G2/M phase. Stimulation with BAY 60-6583 inhibited the activation of Akt by M-CSF, whereas M-CSF-induced ERK1/2 activation was not affected. These results suggest that the inhibition of M-CSF-mediated Akt activation by A2BAR stimulation increases apoptotic response of osteoclasts and induces cell cycle arrest in the G1 phase, thus contributing to the down-regulation of osteoclast proliferation.