• Title/Summary/Keyword: $ER{\alpha},$

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A Case of a Patient with Stuporous Mentality and Hypotension after Amitraz Ingestion (Amitraz 중독 후 혼수 상태를 보인 환자 1례)

  • Jung, Si-Young;Jung, Jin-Hee;Eo, Eun-Kyung
    • Journal of The Korean Society of Clinical Toxicology
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    • v.5 no.2
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    • pp.123-125
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    • 2007
  • Amitraz is a formamidine-derived insecticide and acaricide which is commonly used throughout the world. Amitraz intoxication is mediated through ${\alpha}_2$ adrenergic receptor agonist effects, similar to those of the ${\alpha}_2$ agonist clonidine. We report a case of a patient who experienced coma and hypotension after amitraz ingestion. A 37-year-old woman visited the ER with symptoms of vomiting and altered mental state. She had ingested a mouthful of liquid amitraz concentrate (12.5%), which rapidly led to vomiting, hypotension, bradycardia, hyperglycemia, and mental stupor. Supportive treatment, including mechanical ventilation and administration of inotropics, resulted in full recovery within four days.

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Effects of Curcuma longa L. on MDA-MB-231 Human Breast Cancer Cells and DMBA-induced Breast Cancer in Rats (울금이 MDA-MB-231 세포 및 DMBA로 유발된 흰쥐의 유방암에 미치는 영향)

  • Yang, Dong-Seon;Yang, Seung-Jeong
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.3
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    • pp.44-58
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    • 2013
  • Objectives: Breast cancer is the most common cancer among women and has rapidly increasing rate annually. At present, western cancer therapies by surgery, radiation, and anticancer drug have not been fully effective. So many interests are given to herbal medicine on cancer treatment recently. This study was designed to investigate the effects of Curcuma longa L. (CL) on MDA-MB-231 human breast cancer cells and DMBA-induced breast cancer in rats. Methods: In this experiment, MDA-MB-231 cells were cultured in cell culture plates. 0.0625, 0.125, 0.25, 0.5, 1.0 mg/ml of CL extract were tested for their anti-proliferative effects on MDA-MB-231 cells by MMT assay. And we induced breast cancer in rats. The changes in tumor's weight, and the effects on proliferations of splenocyte and thymocyte were investigated. Results: CL showed anti-proliferative effects on MDA-MB-231 cells in proportion to concentration of the CL. DMBA-induced breast cancer in rats, tumor's weight of the rat was not statistically significant, but showed a tendency to be reduced in the groups treated with CL. Proliferation rate of the rat's splenocyte and thymocyte increased in proportion to CL. In breast cancer tissue, expression of ER-${\alpha}$ was weakened proportionately to the concentration of the CL. Conclusions: These data suggest that CL can prevent the proliferation of breast cancer, then CL is useful to treat patient with breast cancer.

Effects of Sagunjatang-Gami on Uterine and Ovarian Function in the Ovariectomized Rat Postmenopause Model (사군자탕가미방(四君子湯加味方)이 난소적출 폐경 병태 모델의 자궁 및 난소 기능에 미치는 영향)

  • Maeng, Yu-Sook;Choi, Min-Sun;Ahn, In-Suk;Kim, Dong-Il
    • The Journal of Korean Obstetrics and Gynecology
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    • v.25 no.4
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    • pp.12-26
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    • 2012
  • Objectives: The purpose of this study is to examine the effects of Sagunjatang-Gami(SGJT) on uterine and ovarian function in the ovariectomized rat postmenopause model. Methods: SGJT was administered in ovariectomized Wister albino female rats for three month. After that, uterine weight, uterine index, serum estradiol-$17{\beta}$ levels and phosphorylation of ERK or AKT, and histological analysis of uterus were measured to assess the impact on uterine and ovarian function in ovariectomized rats. In addition, phosphorylation of $ER{\alpha}$, ERK, AKT by SGJT in MDA-MB-231 cells were measured. To identify safety of SGJT, the cell cytoxicity in MDA-MB-231 cells and serum GOT, GPT levels were measured in ovariectomized rats. Results: The results were as follows. 1. SGJT decreased the viability of MDA-MB-231 cells in a dose-dependent manner. 2. The level of serum GOT, GPT in SGJT-treated group showed significant decrease in comparison with control group. 3. Phosphorylation of $ER{\alpha}$, ERK, AKT by SGJT in MDA-MB-231 cells were increased. 4. Uterus index in SGJT-treated group showed significant increase in comparison with control group. The level of serum estradiol-$17{\beta}$ in SGJT-treated group showed significant increase in comparison with control group. Phosphorylation of ERK or AKT by SGJT in the uterus of ovariectomized rats was increased significantly. 5. Uterus index and the level of serum estradiol-$17{\beta}$ in SGJT-treated group increased at higher rates in comparison with estrogen-treated group. Conclusions: Taken together, we suggest that SGJT has been shown to be effective in preventing postmenopausal uterine and ovarian degeneration and curing postmenopausal low estrogen related symptoms.

Pregnancy Recognition Signaling for Establishment and Maintenance of Pregnancy

  • Bazer, Fuller W.
    • Korean Journal of Animal Reproduction
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    • v.23 no.4
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    • pp.365-369
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    • 1999
  • Interferon tau (IFN$\tau$), the pregnancy recognition signal in ruminants, suppresses transcription of the estrogen receptor (ER) gene in the endometrial luminal (LE) and superficial glandular epithelium (sGE) to prevent oxytocin receptor (OTR) expression and pulsatile release of luteolytic prostaglandin $F_{2{\alpha}}$ (PGF), Interferon regulatory factors one (IRF-l) and two (IRF-2) are transcription factors induced by IFN$\tau$ that activate and silence gene expression, respectively. Available results suggest that IFN$\tau$ acts directly on LE and sGE during pregnancy to induce sequentially IRF-l and then IRF-2 gene expression to silence transcription of ER and OTR genes, block the luteolytic mechanism to maintenance a functional corpus luteum (CL) and, signal maternal recognition of pregnancy. The theory for maternal recognition of pregnancy in pigs is that the uterine endometrium of cyclic gilts secretes PGF in an endocrine direction, toward the uterine vasculature for transport to the CL to exert its luteolytic effect. However, in pregnant pigs, estrogens secreted by the conceptuses are responsible, perhaps in concert with effects of prolactin and calcium, for exocrine secretion of PGF into the uterine lumen where it is sequestered to exert biological effects and / or be metabolized to prevent luteolysis.

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Effect of Sintering Temperature on Electrical Stability against Surge Stress of Zn-Pr-Co-Cr-Er Oxides-based Varistors (Zn-Pr-Co-Cr-Er 산화물계 바리스터의 써지 스트레스에 대한 전기적 안정성에 미치는 소결온도의 영향)

  • Nahm, Choon-Woo;Park, Jong-Ah;Yoo, Dea-Hoon
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.17 no.11
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    • pp.1167-1173
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    • 2004
  • This paper reports the variations of varistor voltage, nonlinear exponent, leakage current, and dissipation factor against surge stress of ZnO-P $r_{6}$ $O_{11}$-CoO-C $r_2$ $O_3$-E $r_2$ $O_3$(ZPCCE)-based varistors manufactured with the variations of sintering temperature. It was found that the variations of electrical parameters against surge stressing current of 100 A/$\textrm{cm}^2$(8x20 ${\mu}\textrm{s}$) is not so large under the surge stress of 700 times. Among varistors, specially the varistor sintered at 134$0^{\circ}C$ exhibited the smallest variations, with %$\Delta$ $V_{lmA}$=+0.23%, %$\Delta$$\alpha$=+0.23%, %$\Delta$ $I_{L}$=0%, %$\Delta$tan$\delta$=-6.94%. The clamping voltage ratio( $V_{c}$/ $V_{lmA}$) of all varistors was less than 2.2.2.2.2.2.2.

Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways

  • Han, Xia;Kang, Kyoung Ah;Piao, Mei Jing;Zhen, Ao Xuan;Hyun, Yu Jae;Kim, Hyun Min;Ryu, Yea Seong;Hyun, Jin Won
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.41-47
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    • 2019
  • The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated $IC_{50}$ value of $3{\mu}M$ after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G_1$ phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the $PERK/elF2{\alpha}/CHOP$ apoptotic pathway, and mitochondrial $Ca^{2+}$ accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER- and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

Improvement of the Biosensor for Detection of Endocrine Disruptors by Combination of Human Estrogen Receptorα and Co-Activator (Human Estrogen Receptor α와 Co-activator로 구성된 바이오센서를 이용한 내분비계장애물질의 검출)

  • Lee, Haeng-Seog
    • Journal of Korean Society of Water and Wastewater
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    • v.20 no.6
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    • pp.893-904
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    • 2006
  • To improve sensitivity of biosensor as yeast two-hybrid detection system for estrogenic activity of suspected chemicals, we tested effects of several combinations of the bait and fish components in the two-hybrid system on Saccharomyces cerevisiae inducted a chromosome-integrated lacZ reporter gene that was under the control of CYC1 promoter and the upstream Gal4p-binding element $UAS_{GAL}$. The bait components that were fused with the Gal4p DNA binding domain are full-length human estrogen receptor ${\alpha}$ and its ligand-binding domain. The fish components that were fused with the Gal4p transcriptional activation domain were nuclear receptor-binding domains of co-activators SRC1 and TIF2. We found that the combination of the full-length human estrogen receptor ${\alpha}$ with the nuclear receptor-binding domain of co-activator SRC1 was most effective for the estrogen-dependent induction of reporter activity among the two-hybrid systems so far reported. The relative strength of transcriptional activation by representative natural and xenobiotic chemicals was well correlated with their estrogenic potency that had been reported with other assay systems.

The Effects of Dietary Supplementation of Vitamin C or E on the Expressions of Endoplasmic Reticulum Stress, Lipid and Glucose Metabolism Associated Genes in Broiler Chickens (비타민 C 및 E의 첨가 급여가 육계의 소포체 스트레스와 지방 및 포도당 대사 연관 유전자의 발현에 미치는 영향)

  • Park, Jeong Geun;An, Young Sook;Sohn, Sea Hwan;Jang, In Surk;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.40 no.2
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    • pp.147-155
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    • 2013
  • This study was conducted to evaluate the effects of dietary supplementation of vitamin C or E on the expressions of endoplasmic reticulum (ER) stress, lipid and glucose metabolism associated genes in broiler chickens. A total of 216 one-day-old male broilers was randomly alloted to 4 treatments with 6 replicate pens per treatment and 9 broilers per pen for 35 days. The dietary treatments were control, vitamin C (control diet + ascorbic acid 200 mg/kg diet), vitamin E (control diet + ${\alpha}$-tocopherol 100 mg/kg diet), vitamin C + E (control diet + vitamin C 200 mg/kg + vitamin E 100 mg/kg), respectively. To evaluate gene expressions by quantitative real-time polymerase chain reaction, total RNA was extracted from the liver of the chicken at 35 days of age. Dietary supplementation of vitamins was significantly down-regulated the expression of stress marker genes including HSP70, HSP90, and HMGCR, as compared to the control (p<0.05). The expressions of ER stress associated genes also inhibited by supplementation of vitamins as well (p<0.05). Vitamin C supplementation suppressed the expression of lipid associated genes such as FASN, FATP1 and ACSL1. Vitamin supplementation did not affect the glucose transporters, GLUT2 and GLUT8, in the liver. The results of the present study indicated that dietary supplementation of vitamin C or E could be beneficial for the alleviating physiological stress in broiler chickens.

Kimchi attenuates fatty streak formation in the aorta of low-density lipoprotein receptor knockout mice via inhibition of endoplasmic reticulum stress and apoptosis

  • Woo, Minji;Kim, Mijeong;Noh, Jeong Sook;Park, Chan Hum;Song, Yeong Ok
    • Nutrition Research and Practice
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    • v.11 no.6
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    • pp.445-451
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    • 2017
  • BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress is positively associated with atherosclerosis via elevating macrophage cell death and plaque formation, in which oxidative stress plays a pivotal role. Antioxidative, lipid-lowering, and anti-atherogenic effects of kimchi, a Korean fermented vegetable, have been established, wherein capsaicin, ascorbic acid, quercetin, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid, and lactic acids were identified. In this study, mechanisms of action of kimchi methanol extracts (KME) on fatty streak formation via suppression of ER stress and apoptosis in aorta were examined in low-density lipoprotein receptor knockout mice. MATERIALS AND METHODS: Mice fed a high cholesterol diet with an oral administration of KME (KME group, $200 mg{\cdot}kg-bw^{-1}{\cdot}day^{-1}$) or distilled water (control group) for 8 weeks (n = 20 for group). Plasma lipid and oxidative stress levels were evaluated. Protein expression was measured by western blot assay. Fatty streak lesion size and the degree of apoptosis were examined in the aorta. RESULTS: Compared to the control group, in the KME group, plasma lipids levels were decreased and oxidative stress was alleviated (P < 0.05). Protein expression levels of nuclear factor (erythroid-derived 2)-like 2-mediated antioxidants in aorta were increased whereas those for ER stress markers, glucose regulated protein 78, phospho-protein kinase RNA-like ER kinase, phospho-eukaryotic initiation factor 2 subunit ${\alpha}$, X-box binding protein 1, and C/EBP homologous protein were decreased in the KME group (P < 0.05). Moreover, apoptosis was suppressed via downregulation of phospho-c-Jun N-terminal kinase, bcl-2-associated X protein, caspases-9, and -3 with a concomitant upregulation of anti-apoptotic protein, B-cell lymphoma 2 (P < 0.05). Fatty streak lesion size was reduced and the degree of apoptosis was less severe in the KME group (P < 0.05). CONCLUSIONS: In conclusion, antioxidant activity of KME might prevent fatty streak formation through, in part, inhibition of ER stress and apoptosis in aortic sinus where macrophages are harbored.

Non-Benzoquinone Geldanamycin Analog, WK-88-1, Induces Apoptosis in Human Breast Cancer Cell Lines

  • Zhao, Yu-Ru;Li, Hong-Mei;Zhu, Meilin;Li, Jing;Ma, Tao;Huo, Qiang;Hong, Young-Soo;Wu, Cheng-Zhu
    • Journal of Microbiology and Biotechnology
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    • v.28 no.4
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    • pp.542-550
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    • 2018
  • Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to $G_2/M$ cell cycle arrest. Further studies also showed that WK-88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and $ER-{\alpha}$ in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.