• Title/Summary/Keyword: ER${\alpha}$

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Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response

  • Zheng Yi;Gao Bo;Ye Li;Kong Lingbao;Jing Wei;Yang Xiaojun;Wu Zhenghui;Ye Linbai
    • Journal of Microbiology
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    • v.43 no.6
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    • pp.529-536
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    • 2005
  • Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

Evaluation of the bond strength between aged composite cores and luting agent

  • Polat, Serdar;Cebe, Fatma;Tuncdemir, Aliriza;Ozturk, Caner;Usumez, Aslihan
    • The Journal of Advanced Prosthodontics
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    • v.7 no.2
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    • pp.108-114
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    • 2015
  • PURPOSE. The aim of this study was to evaluate effect of different surface treatment methods on the bond strength between aged composite-resin core and luting agent. MATERIALS AND METHODS. Seventy-five resin composites and also seventy-five zirconia ceramic discs were prepared. 60 composite samples were exposed to thermal aging (10,000 cycles, 5 to $55^{\circ}C$) and different surface treatment. All specimens were separated into 5 groups (n=15): 1) Intact specimens 2) Thermal aging-air polishing 3) Thermal aging- Er:YAG laser irradiation 4) Thermal aging- acid etching 5) Thermal-aging. All specimens were bonded to the zirconia discs with resin cement and fixed to universal testing machine and bond strength testing loaded to failure with a crosshead speed of 0.5 mm/min. The fractured surface was classified as adhesive failure, cohesive failure and adhesive-cohesive failure. The bond strength data was statistically compared by the Kruskal-Wallis method complemented by the Bonferroni correction Mann-Whitney U test. The probability level for statistical significance was set at ${\alpha}$=.05. RESULTS. Thermal aging and different surface treatment methods have significant effect on the bond strength between composite-resin cores and luting-agent (P<.05). The mean baseline bond strength values ranged between $7.07{\pm}2.11$ and $26.05{\pm}6.53$ N. The highest bond strength of $26.05{\pm}6.53$ N was obtained with Group 3. Group 5 showed the lowest value of bond strength. CONCLUSION. Appropriate surface treatment method should be applied to aged composite resin cores or aged-composites restorations should be replaced for the optimal bond strength and the clinical success.

Expression Pattern of Progesterone Receptor, Integrin, Cyclooxygenase (COX) in Human Endometrium of Patients with Endometriosis (자궁내막증 환자의 자궁내막내 성호르몬 수용체, Integrins, Cyclooxygenase의 발현과 변이 양상)

  • Kim, Mi-Ran;Park, Dong-Wook;Kwon, Hyuek-Chan;Hwang, Kyoung-Joo;Joo, Hee-Jae;Cho, Dong-Jae;Kim, Sei-Kwaug;Oh, Kie-Suk
    • Clinical and Experimental Reproductive Medicine
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    • v.27 no.2
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    • pp.117-131
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    • 2000
  • Objectives: To develop a new immunohistochemical marker system for supplementation of the Noyes histological classification of the endometrium in women of child bearing age with regular menstrual cycles, and to employ this system to evaluate pathologic factors involved in endometriosis, and thus to ascertain if it is useful in diagnosis. Materials and Methods: Endometrial biopsies were sampled from the posterior fundus of 41 (24 proliferative phases, 17 secretory phases) women with regular menstrual cycles (28-32 days), and each sample was immunohistochemically stained according to Noyes et al (1975) for determination of expression for estrogen receptor (ER), progesterone receptor (PR), integrin ${\alpha}_1$, ${\alpha}_4$, ${\beta}_3$, COX-1 and COX-2. Then, the PR, integrin ${\beta}_3$ and COX-2 which were clearly expressed in the luteal phase was with endometrial samples were obtained from 20 cases of normal patients (group 1) and 25 cases with endometriosis (group 2) after confirming the day of ovulation by sex steroid level measurements 7-8 days after ovulation Results: In the regular menstruation group the expression of ER showed a tendency to be increased in the proliferative phase and decreased in the secretory phase, and was the highest in the proliferative phase. However, PR in the stromal cells showed no change in the entire menstrual cycle while in the epithelial cells, PR reached a peak in the late proliferative phase and was almost absent in the secretory phase. Integrin (${\alpha}_1$, ${\alpha}_4$, and ${\beta}_3$ expression in the epithelial cells was absent in the proliferative phase but ${\alpha}_1$ was strongly expressed starting from the early secretory phase into the entire secretory phase. ${\alpha}_4$ was expressed strongly in the early and mid secretory phases and disappeared in the late proliferative phase, while ${\beta}_3$ appeared after the mid secretory phase and continued to be expressed until the late secretory phase. Expression in the stromal cells was weak overall and did not show any cyclic pattern. COX-1 expression was shown as a cyclic pattern in the stromal and epithelial cells and was particularly strongly expressed in the mid secretory phase of epithelial cells, and in the mid secretory and menstruation phase of stromal cells. In the endometrial epithelial cells there was strong expression during the entire cycle with stronger expression in the secretory phase compared to the prolferative phase. COX-2 was clearly expressed in the late proliferative, early and mid secretory phases in the stromal cells. No expression was observed in the proliferative phase of the epithelial cells, but which began to appear in the early secretory phase reaching a significant pattern from the mid secretory phase onwards. There was almost no expression in the stromal cells. In the cases with endometriosis showing normal endometrial maturation according to the Noyes classification, PR expression was increased while Integrin-${\beta}_3$의 expression was significantly decreased compared to the normal group. Also, COX-2 expression was slightly decreased in the stromal cells of patients with endometriosis while it was significantly increased in the stromal cells. Conclusion: Immunohistochemical markers can supplement the original Noyes classification of histological endometrial dating and therefore ascertain existing pathologic conditions. Particularly for patients with endometriosis with normally mature endometrial cells, changes in COX-2 and integrin expression patterns may assist in elucidating pathophysiologic mechanisms and therefore aid in the diagnosis of abnormal implantation conditions, and consequently determine a treatment modality.

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Effects of High Stocking Density on the Expression of Metabolic Related Genes in Two Strains of Chickens (닭의 고밀도사양 스트레스가 품종 간 체내대사 유전자 발현에 미치는 영향)

  • Sohn, Sea Hwan;Jang, In Surk;An, Young Sook;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.42 no.1
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    • pp.51-59
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    • 2015
  • Chickens are exposed to the external and internal stressors such as low and high temperature, high stocking density, feed restriction and disease. There have been a few studies on gene expressions through the investigation of chickens under direct exposure to the stress of high stocking density. The objective of the present study was to determine the expressions of genes associated with stress, endoplasmic reticulum (ER)-stress, lipid and glucose metabolism in two strains of chickens, Korean Native Chicken (KNC) and White Leghorn (WL), raised in high stocking density. A total of 164 chickens aged 40 weeks were randomly allotted to a $540cm^2/bird$ stocking density (control), whereas the chickens in a high density group were assigned in a $311cm^2/bird$ stocking density with feeding ad libitum for 10 weeks. Total RNA was extracted from the live for qRT-PCR. The expression levels of hsp70 and $hsp90{\alpha}$ were higher in WL subjected to stress with high stocking density compared with those genes in control (P<0.05), while the expressions of genes were not affected in KNC. ER stress marker gene XBP1 was also highly expressed in WL with stress (P<0.05), but the stress of high stocking density did not influence to ER stress marker genes in KNC. Lipid metabolism associated genes including FABP4, FATP1 and ACSL1 were highly expressed in WL compared with KNC when subjected to high stocking density stress (P<0.05). The expression of glucose transport gene GLUT2 and GLUT8 were increased in chickens exposured to the stress of high stocking density (P<0.05). The data indicate that WL is more sensitive to the stress of high stocking density compared with KNC and the stress may influence the modulation of lipid and glucose metabolism in the liver of chickens.

Effects of Lycii Fructus and Lycii Folium Extracts on Osteoporosis in Ovariectomized Rats (구기자와 구기엽 추출물이 난소적출 흰쥐의 골다공증에 미치는 영향)

  • Kim, Jin-Ho;Kim, Jeong-Sang
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.1
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    • pp.24-29
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    • 2014
  • The effects of Lycii fructus and Lycii folium on osteoporosis and serum cholesterol levels were tested in ovariectomized (OVX) rats. Twenty-four female Sprague-Dawley rats were divided into four groups: Sham group (sham-operated), Control group (OVX, ovariectomized model), LCF group (Ovx+Lycii fructus extract), and LCL group (OVX+Lycium folium extract). After 8 weeks, the OVX ($330{\pm}5.39$ g), LCF ($315{\pm}2.99$ g), and LCL ($318{\pm}2.06$ g) groups showed increased body weight compared with sham group ($281{\pm}1.71$ g). The levels of serum osteocalcin (OC) also increased in the LCF ($444.6{\pm}26.9$ ng/mL) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($107{\pm}3.52$ ng/mL). The activities of serum alkaline phosphatase (ALP) increased in the LCF ($108{\pm}2.7$ U/L) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($95{\pm}2.9$ U/L). Stereomicroscopy found that the low bone density that developed in the OVX group was significantly reversed in the LCF and LCL groups after 8 weeks. We also obtained molecular-based in vivo evidence that supports a mechanism of action involving novel estrogen receptor ($ER{\alpha}$) modulator in the uterus. We found that expression of ER${\alpha}$ mRNA in the OVX rat uterus was elevated by Lycium chinense. These results suggest that Lycii fructus and Lycii folium administered to rats during 8 weeks after oophorectomy may partially recover postmenopausal osteoporosis or delay the progression of osteoporotic changes.

The Influence of Estrogen on the Immunologic Function of T Lymphocytes (에스트로겐이 T 림프구 면역기능에 미치는 영향)

  • Chun, Sung-Wook;Chun, Kyung-Chun;Ku, Seung-Yup
    • Clinical and Experimental Reproductive Medicine
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    • v.36 no.2
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    • pp.89-100
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    • 2009
  • SLE 등의 자가면역질환 병인론에 있어서 $CD4^+$ T 조력 림프구 (T helper cell)의 기능과 항상성 조절의 이상이 중요하다는 것은 알려진 사실이지만 $CD4^+$ T 조력 림프구 (T helper cell)의 발달과 기능에 대한 성호르몬의 정확한 역할에 대하여는 아직 확립되어 있지 않은 실정이다. 에스트로겐의 $CD4^+$ T 림프구에 대한 여러 방면의 작용에 대한 결과는 에스트로겐 매개 신호가 전달되는 정황에 매우 의존적이라고 할 수 있으며, 또한 에스트로겐이 B 림프구와 항원발현세포들 같이 T 림프구 기능을 변화시킬 수 있는 다른 분획 세포들의 기능에 대해서도 영향을 미칠 수 있다는 사실을 고려한다면, 에스트로겐이 $CD4^+$ T 림프구매개반응에 미치는 작용은 매우 복잡하다고 할 수 있다. 현재로선 이런 과정들과 관련된 에스트로겐의 정확한 기전에 대한 연구 성과는 현재로선 아직걸음마 단계에 지나지 않는다고 볼 수 있다. 일부 분자학적 표적들의 발견에도 불구하고 ER-$\alpha$와 ER-$\beta$, 또는 이런 표적들의 조절에 대한 유전자적 또는 비유전자적 경로의 상대적 역할에 대해서는 현재로선 알려진 바가 많지 않은 것 또한 사실이며, T 림프구 자체의 미세 환경과 ER 매개 전사반응에 영향을 미칠 수 있는 방법 역시 아직까진 알려진 바가 없다. 따라서 에스트로겐의 $CD4^+$ T 림프구에 대한 다각적 영향을 규명하는 데 있어 이런 경로들에 대한 보다 체계적이고 상세한 연구가 반드시 필요하다. 최근 골다공증의 병인에 있어 에스트로겐에 의한 TNF 및 RANK-RANKL계 억제에 대해 연구가 심도 있게 진행됨으로써 결과적으로 다른 시토카인과 면역세포들에 대한 영향이 간접적으로 규명되고 있는 점은 매우 고무적인 현상이라고 여겨진다. 이러한 연구들은 추후 에스트로겐의 면역 및 염증체계에 대한 특징적 작용을 규명하는데 있어서 밑거름이 될 수 있을 것이다. 나아가 호르몬 자체, 또는 SERM 같은 준호르몬제제들이 면역계에 미치는 영향을 분자학적으로 규명함으로써 향후 이러한 지식들이 또한 류마티스성 자가면역질환이나 만성염증성질환, 또는 전신성 감염질환에 있어 면역글로불린이나 기타 다른 기존 치료 약제들을 대체 보완할 수 있는 호르몬 치료로 이어질 수 있는 결정적인 단서를 제공할 수 있을 것이라 기대할 수 있을 것이다.

Electronic state calculation of ceramics by $DV-X\;{\alpha}$ cluster method

  • Adachi, Hirohiko
    • Proceedings of the Materials Research Society of Korea Conference
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    • 1994.11a
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    • pp.1-1
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    • 1994
  • ;The electronic state calculations for various types of ceramic materials have beell performed by the use of $DV-X\;{\alpha}$ cluster method. The molecular orbital levels and wave functions for model clusters have been computed to study the electronic properties ami chemical bonding of the ceramics. For ${\beta}-sialon(Si_{6-z}Al_zO_zN_{8-z})$ which is a high temperature structural material based on ${\beta}-Si_3N_4$, we have made model cluster calculations to estimate the strength of chemical bonding between atoms by the Mulliken population analysis. It is found that the covalent bonding between Si and N atoms is very strong in pure ${\beta}-Si_3N_4$, but the covalency around solute atom is considerably weakened when Si atom is substituted by AI. This tendency is enhanced by an additional substitution of oxygen atom for N. The result calculated can well explain the experimental data of changes in mechanical properties such as the reductions of Young's modulus and Vickers hardness with increment of z-value in ${\beta}-sialon$. Various model clusters for transition metal oxides which show many interesting physical and chemical properties have also been calculated. High-valent perovskite-type iron oxides EMFe0_3E(M=Ca and Sr) possess very interesting magnetic and chemical properties. In these oxides, iron exists as $Fe^{4+}$ state, but the experimental measurement of Mossba~er effect suggests that disproportionation $2Fe^{4+}=Fe^{3+}+Fe^{5+}$ takes place for $CaFe0_3$ at low temperatures. The model cluster calculations for these compounds indicated the existence of considerably strong covalent bonding of Fe-O. The calculations of hyperfine interaction at iron neucleus show very good agreement with the experimental Mossbauer measurements. The result calculated also implies that the disproportionation reaction is strongly possible by assuming the quenching of breathing phonon mode at low temperatures.tures.

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Branched-chain Amino Acids Reverse the Growth of Intrauterine Growth Retardation Rats in a Malnutrition Model

  • Zheng, Chuan;Huang, Chengfei;Cao, Yunhe;Wang, Junjun;Dong, Bing
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.11
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    • pp.1495-1503
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    • 2009
  • This experiment was conducted to determine the effect of dietary supplementation with BCAA (branched-chain amino acids: leucine, isoleucine and valine) on improving the growth of rats in a malnutritional IUGR (Intrauterine Growth Retardation) model, which was established by feeding restriction. In the experimental treatment, rats were fed purified diets supplemented with BCAA (mixed) during the whole gestation period, while arginine and alanine supplementation were set as the positive and negative control group, respectively. The results showed that, compared to the effect of alanine, BCAA reversed IUGR by increasing the fetus weights by 18.4% and placental weights by 18.0% while fetal numbers were statistically increased. Analysis of gene and protein expression revealed that BCAA treatment increased embryonic liver IGF-I expression; the uterus expressed higher levels of estrogen receptor-$\alpha$ (ER-$\alpha$) and progesterone receptor (PR), and the placenta expressed higher levels of IGF-II. Amino acid analysis of dam plasma revealed that BCAA supplementation effectively enhanced the plasma BCAA levels caused by the feed restriction. BCAA also enhanced the embryonic liver gluconeogenesis by augmenting the expression of two key enzymes, namely fructose-1,6-biphosphatase (FBP) and phosphoenolpyruvate carboxykinase (PEPCK). In conclusion, supplementation of BCAA increased litter size, embryonic weight and litter embryonic weight by improving the dam uterus and placental functions as well as increasing gluconeogenesis in the embryonic liver, which further provided energy to enhance the embryonic growth.

Effect of Reinforcement of Glass fiber on Auto and Heat polymerized denture base resin (유리 섬유의 첨가에 따른 자가중합 및 열중합 의치상용 레진의 강화효과)

  • Yu, Sang-Hui;Kim, Yeoun-Soo;Choi, Un-Jae;Jun, Jong-Nam
    • Journal of Technologic Dentistry
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    • v.31 no.4
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    • pp.37-43
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    • 2009
  • This study evaluated the effect of concentration of glass fiber reinforcement on the flexural properties of auto and heat polymerized denture base resin. The test specimens($64{\times}10{\times}3.3mm$) were made of auto and heat polymerized resin(Vertex, Dentimax, Netherlands). Glass fiber(ER 270FW, Hankuk Fiber Glass, Korea) were used to reinforce the denture base resin. The 2.6%, 5.3% and 7.9% volume pre-impregnated fiber were located at the bottom of specimen. The test specimens(n=7) of each group were stored in distilled water at $37^{\circ}C$ for 50 hours before test. The flexural strength and modulus were measured by an universal testing machine(Z020, Zwick, Germany) at a crosshead speed of 5 mm/min in a three-point bending mode. The data was analyzed by one-way ANOVA and the Duncan's multiple range test(${\alpha}$=0.05). The difference of auto polymerized resin groups and heat polymerized resin groups were statistically analyzed by t-test(${\alpha}$=0.05). Glass fiber showed significant reinforcing effects on auto and heat polymerized resin. For flexural strength and modulus, auto polymerized resin was the highest in 7.9% volume, while heat polymerized resin was the highest in 5.3% volume. In this study, glass fiber at 7.9% volume ratio showed most effective reinforcing effect on auto polymerized resin and glass fiber at 5.3% volume ratio showed most effective reinforcing effect on heat polymerized resin in terms of flexural strength and flexural modulus.

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Genetic Polymorphisms and Cancer Susceptibility of Breast Cancer in Korean Women

  • Kang, Dae-Hee
    • BMB Reports
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    • v.36 no.1
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    • pp.28-34
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    • 2003
  • Breast cancer is the most prevalent cancer among women in Western countries, and its prevalence is also increasing in Asia. The major risk factor for breast cancer can be traced to reproductive events that influence the lifetime levels of hormones. However, a large percentage of breast cancer cases cannot, be explained by these risk factors. The identification of susceptibility factors that predispose individuals to breast cancer (for instance, if they are exposed to particular environmental agents) could possibly give further insight into the etiology of this malignancy and provide targets for the future development of therapeutics. The most interesting candidate genes include those that mediate a range of functions. These include carcinogen metabolism, DNA repair, steroid hormone metabolism, signal transduction, and cell cycle control. We conducted a hospital-based case-control study in South Korea to evaluate the potential modifying role of the genetic polymorphisms of selected low penetrance genes that are involved in carcinogen metabolisms (i.e., CYP1A1, CYP2E1, GSTM1/T1/P1, NAT1/2, etc.), estrogen synthesis and metabolism (i.e., CYP19, CYP17, CYP1B1, COMT, ER-$\alpha$, etc.), DNA repair (i.e., XRCC1/3, ERCC2/4, ATM, AGT, etc.), and signal transduction as well as others (i.e., TGF-$\beta$, IGF-1, TNF-$\beta$, IL-1B, IL-1RN, etc.). We also took into account the potential interaction between these and the known risk factors of breast cancer. The results of selected genes will be presented in this mini-review.