• Title/Summary/Keyword: hER

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Cholic Acid Attenuates ER Stress-Induced Cell Death in Coxsackievirus-B3 Infection

  • Han, Jae-Young;Jeong, Hae In;Park, Cheol-Woo;Yoon, Jisoo;Ko, Jaeyoung;Nam, Sang-Jip;Lim, Byung-Kwan
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.109-114
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    • 2018
  • Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the Picornaviridae and causes various diseases such as myocarditis and hand-foot-mouth disease. However, an effective antiviral drug is still not developed. In this study, we looked for potential inhibitors of CVB3 replication by examining the survival of CVB3-infected HeLa cells. We detected an antiviral effect by cholic acid and identified it as a candidate inhibitor of CVB3 replication. Cholic acid circulates in the liver and intestines, and it helps the digestion and absorption of lipids in the small intestine. HeLa cells were cultured in 12-well plates and treated with cholic acid (1 and $10{\mu}g/ml$) and $10^6PFU/ml$ of CVB3. After 16 h post-infection, the cells were lysed and subjected to western blot analysis and RT-PCR. The production of the viral capsid protein VP1 was dramatically decreased, and translation initiation factor eIF4G1 cleavage was significantly inhibited by treatment with $10{\mu}g/ml$ cholic acid. Moreover, cholic acid inhibited ERK signaling in CVB3-infected HeLa cells. RT-PCR showed that the amounts of the CVB3 RNA genome and mRNA for the ER stress-related transcription factor ATF4 were significantly reduced. These results showed that cholic acid strongly reduced ER stress and CVB3 proliferation. This compound can be developed as a safe natural therapeutic agent for enterovirus infections.

New HDAC inhibitor, IN2001 induces apoptosis/cell cycle arrest in human breast cancer cells

  • Joung, Ki-Eun;Min, Kyung-Nan;Cho, Min-Jung;An, Jin-Young;Kim, Dae-Ki;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.90-90
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    • 2003
  • The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47D and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

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Implications of Sex Hormone Receptor Gene Expression in the Predominance of Hepatocellular Carcinoma in Males: Role of Natural Products

  • Ahmed, Hanaa H;Shousha, Wafaa Gh;Shalby, Aziza B;El-Mezayen, Hatem A;Ismaiel, Nora N;Mahmoud, Nadia S
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4949-4954
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    • 2015
  • The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

New HDAC inhibitor, IN2001 induces apoptosis/cell cycle arrest in human breast cancer cells

  • Euno, Joung-Ki;Nan, Min-Kyung;Jung, Cho-Min;Young, An-Jin;Kim, -Dae-Ki;Yhong, Sheen-Yhun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.180-180
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    • 2003
  • The acetylation of histone is one of the mechanisms involved in the regulation of gene expression and is tightly controlled by two core enzymes, histone acetyltransferase (HAT) and deacetylase (HDAC). There are several reports that imbalance of HAT and HDAC activity is associated with abnormal behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, an increasing number of structurally diverse HDAC inhibitors have been identified that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in vivo and in vitro. In this study, we have investigated the effects of novel HDAC inhibitors, IN2001 on ER positive and ER negative human breast cancer cell lines. The growth inhibition, cell cycle arrest and apoptosis of cells by HDAC inhibitors were determined using SRB assay, DNA fragmentation, and flow cytometry. We found that IN 2001 as well as Trichostatin A inhibited cell growth dose-dependently in both ER Positive and ER negative human breast cancer cell lines. The growth inhibition with HDAC inhibitors was associated with profound morphological change. The result of cell cycle analysis after 24 h exposure of IN2001 showed G2-M cell cycle arrest in MCF-7 cell and apoptosis in T47B and MDA-MB-231 cell. In summary, IN2001 has antiproliferative effect on human breast cancer cells regardless of the expression of estrogen receptor. These findings heights the possibility of developing HDAC inhibitors as potential anticancer therapeutic agents for the treatment of breast cancer.

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St. John's Wort (Hypericum perforatum) stimulates human osteoblastic MG-63 cell proliferation and attenuates trabecular bone loss induced by ovariectomy

  • You, Mi-kyoung;Kim, Du-Woon;Jeong, Kyu-Shik;Bang, Mi-Ae;Kim, Hwan-Seon;Rhuy, Jin;Kim, Hyeon-A
    • Nutrition Research and Practice
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    • v.9 no.5
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    • pp.459-465
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    • 2015
  • BACKGROUND/OBJECFTIVES: The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS: Proliferation, expression of estrogen receptor (ER) ${\alpha}$ and ER ${\beta}$, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, ${\beta}$-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS: SJW increased MG-63 cell proliferation and expression of ER ${\alpha}$ and ER ${\beta}$, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. CONCLUSION: The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement.

Comparison between Korean Triage and Acuity Scale and Injury Severity Scoring System in Emergency Trauma Patients (외상환자의 한국형 중증도 분류와 손상중증도 점수체계의 비교)

  • Choi, YoonHee;Kim, BoHwa;Shin, JiEun;Jang, MyungJin;Lee, EunJa
    • Journal of East-West Nursing Research
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    • v.28 no.1
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    • pp.10-20
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    • 2022
  • Purpose: We compared the Korean Triage and Acuity Scale (KTAS), Injury Severity Score (ISS), and Revised Trauma Score (RTS) determined the validity of KTAS for classifying trauma patients. Methods: A retrospective chart review of 10,865 trauma patients (aged ≥15 years) who visited a single regional trauma and emergency medical center from January 1, 2016, to December 31, 2020, was conducted. Data were collected from the Korean Trauma Data Bank. Based on KTAS classification, the rates of intensive care unit admission, surgery and intervention, transfusion, emergency room (ER) and hospital mortality, and ER stay time were investigated. Data were analyzed using Chi-square test, Pearson's correlation coefficient, receiver operating characteristic curve, and area under the ROC curve. Results: In the KTAS, severe trauma patients (ISS ≥16) were classified as Level 1 (79.6%), 2 (44.8%), 3 (15.5%), 4 (4.0%) and 5 (7.6%). The following were the predictive powers of KTAS, ISS, and RTS for different parameters: surgery and intervention rate, KTAS (.71), ISS (.70), and RTS (.63); transfusion rate within 4h, KTAS (.82), ISS (.82), and RTS (.74); ER stay time within 90 min, KTAS (.72), ISS (.62), and RTS (.56); and ER mortality, KTAS (.84), ISS (.72), and RTS (.88). These findings were statistically significant (p<.001). The sensitivity and specificity of KTAS for trauma patients were .88 (.87~.90), and .38 (.37~.39), respectively. Conclusion: KTAS is a useful classification system that can predict the clinical outcomes of patients with trauma, and effectively triage acutely ill trauma patients, thus provide appropriate treatment.