• Title/Summary/Keyword: B-Raf

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Antimicrobial and Antifungal Activities of Lisianthus (Eustoma grandiflorum) Essential Oil (리시안셔스 유래 에센셜 오일의 항세균 및 항진균 효과)

  • Ji, Keunho;Kim, Dong Kwang;Kim, Young Tae
    • Journal of Life Science
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    • v.27 no.4
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    • pp.430-434
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    • 2017
  • Essential oils are fragrant oils extracted from the leaves, stems, peels, petals and roots of aromatic plants cultivated by natural means or using organic agricultural techniques. Essential oils have commonly been used as antibacterial and antifungal agents. In the present study, essential oil was extracted from lisianthus (Eustoma grandiflorum [Raf.] Shinn.) and tested for antifungal activities against three eumycetes (Penicillium pinophilum, Chaetomium glogosum and Aspergillus niger). Lisianthus essential oil showed high antifungal activities against three eumycetes, especially against Aspergillus niger, for which the resulting minimum inhibitory concentration (MIC) was 0.005 mg/ml. In addition, the extracted essential oil was shown to have antimicrobial activity against ten intestinal pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia, Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Pseudomonas aeruginosa, Bacillus subtilis, Enterococcus faecalis and Vibrio parahaemolyticus) according to the disc diffusion method and was also shown to exhibit strong antibacterial activity against an additional three pathogenic bacteria (Bacillus subtilis, Listeria monocytogenes and Vibrio parahaemolyticus). These results indicate that lisianthus essential oil could be used as an antibiotic against harmful bacteria that produce intestinal illnesses. From the present study, we suggest that lisianthus extracts can be utilized as potential antifungal and antibacterial agents and for the development of pharmaceutical and cosmetic products.

Prostaglandin E2 Reverses Curcumin-Induced Inhibition of Survival Signal Pathways in Human Colorectal Carcinoma (HCT-15) Cell Lines

  • Shehzad, Adeeb;Islam, Salman Ul;Lee, Jaetae;Lee, Young Sup
    • Molecules and Cells
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    • v.37 no.12
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    • pp.899-906
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    • 2014
  • Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways

  • Xu, Chang;Li, Liangchang;Wang, Chongyang;Jiang, Jingzhi;Li, Li;Zhu, Lianhua;Jin, Shan;Jin, Zhehu;Lee, Jung Joon;Li, Guanhao;Yan, Guanghai
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.550-560
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    • 2022
  • Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1β and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1β, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-κB signaling pathways.

Flora Distributed in Mt. Geumgok, Gyeongju-si, Gyeongsangbuk-do (경상북도 경주시 금곡산에 분포하는 관속식물상)

  • You, Ju Han
    • Korean Journal of Plant Resources
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    • v.26 no.2
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    • pp.248-270
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    • 2013
  • The purpose of this study is to collect the raw data for conservation of plant ecosystem by surveying and analysing the flora of Mt. Geumgok located in Gyeongju-si, Gyeongsangbuk-do, Korea. The flora were summarized as 453 taxa including 91 families, 298 genera, 397 species, 4 subspecies, 46 varieties and 6 forms. The rare plants designated by Korea Forest Service were 3 taxa such as Eranthis byunsanensis B.Y.Sun, Potentilla discolor Bunge and Iris odaesanensis Y.N.Lee. The Korean endemic plants were 6 taxa such as Carpinus laxiflora (Siebold & Zucc.) Blume, Eranthis byunsanensis B.Y.Sun, Philadelphus schrenkii Rupr., Lespedeza maritima Nakai, Vicia chosenensis Ohwi and Weigela subsessilis (Nakai) L.H.Bailey. The specific plants by floristic region were 36 taxa such as Pinus koraiensis Siebold & Zucc., Salix chaenomeloides Kimura, Anemone raddeana Regel, Chloranthus japonicus Siebold, Euphorbia pekinensis Rupr., Ilex macropoda Miq., Ajuga multiflora Bunge, Saussurea odontolepis Sch.Bip. ex Herd, Viola orientalis (Maxim.) W.Becker, Betula davurica Pall., Vitex negundo var. incisa (Lam.) C.B.Clarke and Cimicifuga heracleifolia Kom.. The naturalized plants were 36 taxa such as Fallopia dumetorum (L.) Holub, Lepidium apetalum Willd., Robinia pseudoacacia L., Trifolium repens L., Euphorbia supina Raf., Ipomoea purpurea Roth, Veronica persica Poir., Bidens pilosa L., Carduus crispus L., Xanthium canadense Mill., Bromus unioloides H.B.K. and Festuca arundinacea Schreb.. The invasive alien plants were 2 taxa such as Ambrosia artemisiifolia L. and Aster pilosus Willd.. The ratios of the urbanized index(UI), the naturalized index(NI) and the disturbed index(DI) were 11.2%, 7.9% and 18.2% each.

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.

Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses

  • Jung, Byeongjin;Kang, Hyejin;Lee, Wonhwa;Noh, Hyun Jin;Kim, You-Sun;Han, Min-Su;Baek, Moon-Chang;Kim, Jaehong;Bae, Jong-Sup
    • BMB Reports
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    • v.49 no.4
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    • pp.214-219
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    • 2016
  • A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.

BRAFV600E Mutation Analysis in Fine Needle Aspiration Biopsy Cytology and Formalin Fixed Paraffin Embedding Block of the Thyroid

  • Han, Kyung Hee;Park, Won Young;Lee, Young Nam
    • Korean Journal of Clinical Laboratory Science
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    • v.45 no.2
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    • pp.66-72
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    • 2013
  • Fine Needle Aspiration Biopsy Cytology (FNABC), which is known as the most accurate and cost-effective method for diagnosis of the thyroid nodule, may still result in indeterminate cases that are cellular paucity and show minor nuclear atypia. However, most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs which is currently helping us to differentiate malignancies from benign lesions. Cases studied included 46 histological, confirmed PTC cases. FNABC 102 cell paucity and 74 atypia benign cases were previously diagnosed as suspicious of PTC using cytologic examination. These cases were analyzed for BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme. In this study, the sensitivity and specificity were calculated and, BRAF mutation was detected by means of a histological method in 23 of 46 cases of PTC and no mutation was found in 22 cases. However, one case was not detected. In using FNABC, BRAF mutation was detected in 6 of 102 cases in cell paucity and in 11 of 74 cases in the atypia. Two cases were not detected in the atypia. The sensitivity and specificity of PCR-RFLP in FNABC were 60% and 97.4% respectively. Assessment of Formalin Fixed Paraffin Embedding (FFPE) block demonstrated similarly a 51.1% positive and 48.9% negative in PTC. Evaluation of BRAF mutation revealed high specificity and low sensitivity in using FNABC method. This study suggests that BRAF mutation analysis should be useful for the clinical diagnosis of PTC in FNABC with cytological findings suspicious for PTC.

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Cancer Chemoprevention by Tea Polyphenols Through Modulating Signal Transduction Pathways

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.561-571
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    • 2002
  • The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

Application of the Health Risk Models Estimating Skin Cancer Caused by UVB Radiation (자외선(UVB) 노출 증가에 대한 피부암 위해도 예측 모델의 적용)

  • Shin, Dong-Chun;Lee, Jong-Tae;Chung, Yong;Kang, Na-Kyung;Yang, Ji-Yeon
    • Environmental Analysis Health and Toxicology
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    • v.11 no.1_2
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    • pp.1-10
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    • 1996
  • A decrease in stratospheric ozone probably caused by chloroflurocarbons (CFCs) emissions, has been observed large parts of-the globe. It is generally accepted that if ozone levels in the stratosphere are depleted, greater amounts of shortwave ultraviolet radiationB (UVB) will reach the earth's surface, resulting in increased incidence of nonmelanoma skin cancer. In this study, we evaluated several mathematical models, such as a power and an exponential model, and a geometric model considering the surface area of a human body part and ages for the prediction of Skin cancer incidence caused by exposure to the UVB radiation. These models basically estimated the risk of skin cancer based on those measurements of the local ozone in stratosphere and UVB. Both were measured at a part of Seoul with a Dobson ozone spectrometer and Robertson-Berger UV Biometer for 1995. As a result, we calculated the point estimation applying a biological amplification factor (BAF), UVB radiation and other factors. We used a Monte-Carlo simulation technique with assumption on the distribution of each considered factor. The sensitivity analysis of model by there components conducted using Gaussian sensitivity method. The annual integral of UVB radiation was 2275 MED (minimal erythema dose)/yr. Also, an estimate of the annual amount of UVB reaching the earth's surface at a korea's latitude and altitude was 3328 MED/yr. The values of the radiation amplification factor (RAF) were ranged from 0.9 to 1.5 in Seoul. To give the effective factors required to model the prediction of skin cancer incidence caused by exposure to the UVB radiation in Korea, we studied the pros and cons of above mentioned models with the application of those parameters measured in Seoul, Korea.

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The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity

  • Sang-Yeon Lee;Jisun Lee;Hye-Lim Park;Yong-Wook Park;Hun Kim;Jae-Hwan Nam
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1576-1586
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    • 2023
  • Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.