• Title/Summary/Keyword: mode of death

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High-concentration Epigallocatechin Gallate Treatment Causes Endoplasmic Reticulum Stress-mediated Cell Death in HepG2 Cells

  • Ahn, Joon-Ik;Jeong, Kyoung-Ji;Ko, Moon-Jeong;Shin, Hee-Jung;Chung, Hye-Joo;Jeong, Ho-Sang
    • Genomics & Informatics
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    • v.7 no.2
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    • pp.97-106
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    • 2009
  • Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

The Study on Aging (노화(老化)에 대한 연구(硏究) (황제내경(黃帝內經)을 중심으로))

  • Baek, Sang-Ryong
    • Journal of Korean Medical classics
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    • v.12 no.2
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    • pp.176-183
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    • 1999
  • Each life has its own properties that distinguish one another. With this property, Oriental medicine suggests original diagnosis and treament. Our process of aging shows typical outline of cycle, i. e. from one's birth to death. Understanding the life cycle of men gives us very good hint to predict one's state of health, possible diseases, characteristics of disease in each term of his/her life cycle. It's because body and mode of diseases change according to age. Aging starts when $\breve{U}$m Essence(陰精)-the essence one receive from parents-dries up or when Deficient Fire(虛火) soars. Parts that compose our body-bones, muscles, flesh, etc.-gradually weaken and worn out as they no longer get support from Yang-Ki(陽氣), In "Yellow Emperor's Classic", aging starts around one's forties when $\breve{U}$m Essence(陰精) is reduced to less than half. However, what is usually accepted is that women start aging from 49 and men 64, regarding significant geriatric disease. As it is mentioned, aging starts with exhaustion of $\breve{U}$m Essence(陰精) which results in soaring Deficient Fire. Main symptoms are weak mental state due to Sin(神) disorder, and weak physical state due to Spleen and Stomacn(脾胃) disorder. Main principle in treating and preventing diseases related to aging is preserving $\breve{U}$m Essence(陰精), as well as fortifying Ki and Blood(氣血). To do this, Lung(肺)-which collects $\breve{U}$m Essence(陰精), and Kidney(腎) stores-which stores $\breve{U}$m Essence(陰精).

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A Study for Influence of Biorhythm in Scholarly Record

  • Yi, Geun Heui
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.10 no.16
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    • pp.7-18
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    • 1987
  • From birth to death, every man is under the control of the three biorhythm curves that initiate from inner body. Those are called physical rhythm emotional rhythm and intellectual rhythm. These biorhythms have influence each other in human behaviour like physical endurance, creativity, record of examination. The result of investigation indicates that the students' records in low level period are lower than those of in high. Therefore, it is verified statistically whether the biorhythem has effects on human ability in scholarly record or not And also, this research calculates the average mixed biorhythm which is representable for a group by using mode mixed-biorhythm.

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A case study on the fire victim in the vehicle by GC/MS through derivatization of cyanide with pentafluorobenzyl bromide (PFBBr) (시안화이온의 pentafluorobenzyl bromide (PFBBr)에 의한 유도체화 후 GC/MS 분석에 의한 차량화재 변사체 사인규명에 관한 사례연구)

  • Lee, Joon-Bae;Shon, Sung Kun;Woo, Sang Hee;Park, Se Yeon;Hwang, Jung Ho;Kwon, O-Seong;Kim, Nam Yi;Paeng, Ki Jung
    • Analytical Science and Technology
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    • v.29 no.2
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    • pp.73-78
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    • 2016
  • Hydrogen cyanide (HCN) is an extremely toxic gas frequently produced during the incineration of plastics, such as acrylonitrile-butadiene-styrene (ABS). A victim of a fire who has inhaled smoke could have cyanide in the blood. Therefore, cyanide could be a good marker for a post-mortem examination of a fire as well as carboxyhemoglobine (COHb) test of blood samples. For a particular fire case, a burned body with a suicide note was found inside a burned vehicle. Even though the COHb value is conclusive evidence, measuring the COHb for denatured blood might be difficult due to severe thermal denaturation or the formation of methemoglobin (MetHb). To overcome this difficulty, cyanide could be used as an indicator when investigating the death of a fire victim. In this study, gas chromatography/mass spectrometry (GC/MS) was adopted to measure the levels of cyanide in the blood through derivatization with pentafluorobenzyl bromide (PFBBr) under cation surfactant by scan and SIM mode. The concentration of cyanide in the blood of heart blood and brain of the victim was found to be 0.36 µg/mL and 1.20 µg/mL respectively, which was higher than the average value (0.041 µg/mL) found in the blood of 14 people who smoked.

Snail Switches 5-FU-induced Apoptosis to Necrosis through Akt/PKB Activation and p53 Down-regulation (Snail의 Akt/PKB의 활성화와 p53의 downregulation를 통한 5-FU-induced apoptosis의 necrosis로의 전환)

  • Lee, Su-Yeon;Jeon, Hyun-Min;Ju, Min-Kyung;Kim, Cho-Hee;Jeong, Eui-Kyong;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.22 no.8
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    • pp.1018-1023
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    • 2012
  • Snail is a zinc finger transcription factor that induces epithelial-to-mesenchymal transition (EMT), which promotes tumor invasion and metastasis by repressing E-cadherin expression. In addition, Snail restricts the cellular apoptotic response to apoptotic stimuli or survival factor withdrawal; however, its molecular mechanism remains largely unknown. In this study, we have investigated the mechanism underlying Snail-mediated chemoresistance to 5-fluorouracil (5-FU), one of the most widely used anti-cancer drugs. When Snail was overexpressed by doxycycline (DOX) in MCF-7 #5 cells, it inhibited 5-FU-induced apoptotic cell death and switched the cell death mode to necrosis. Snail expression, either by DOX treatment in MCF-7 #5 cells or by the transfection of Snail expression vectors pCR3.1-Snail-Flg, phosphorylation-resistant pCR3.1-S104, and 107A Snail-Flg in MCF-7 cells specifically induced PTEN down-regulation/inactivation and Akt/PKB activation, without affecting ERK1/2 activity. In addition, Snail prominently suppressed 5-FU-induced increases in p53 levels. These findings demonstrate that Snail switches 5-FU-induced apoptosis to necrosis through the activation of Akt/PKB and the down-regulation of p53 levels.

Physiological Effects of TOPE, a Photo - independent Diphenylether, on Higher Plants (비광요구형 디페닐에테르계 TOPE 의 생리적 작용에 관한 연구)

  • Kim, J.S.;Cho, K.Y.;Pyon, J.Y.
    • Korean Journal of Weed Science
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    • v.16 no.2
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    • pp.160-170
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    • 1996
  • Several physiological responses were investigated in plants treated with TOPE as a preliminary step to know its action site. Unlike photo-dependent diphenylethers, herbicidal activity of TOPE appeared slowly and its typical symptoms were both burning of leaf blades and abnormal division of meristem in grasses, Similarly, both leakage of cell electrolytes and the curling of cotyledon margin were also shown in cucumber(Cucumis sativus L.). Biosynthesis of chlorophyll in etiolated cucumber cotyledon was not inhibited directly by treatment of TOPE at low light intensity(5.5${\mu}$ mol $m^{-2}s^{-1}$ PAR) and protoporphyrin IX was not also accumulated. The contents of phytoene, phytofluene and ${\beta}$-carotene were abnormaly increased. Photosynthesis was inhibited only at high concentration. Mitochondrial respiration was inhibited at high concentration but rather increased significantly at 10${\mu}$M of TOPE. However, respiration inhibitors did not alleviate the two symptoms of TOPE in cucumber cotyledon. In the same experiments, using inhibitors of protein or nucleic acid biosynthesis, only one of the two symptoms was alleviated by chloramphenicol and cycloheximide. In contrast, both symptoms were alleviated by actinomycin-D and hydroxyurea, suggesting that nucleic acid metabolism might be preferentially related to the mode of action of TOPE. DNA, RNA and protein contents were accumulated in both cucumber cotyledon and rice (Oryza sativa L.) routs treated with TOPE, and the DNA of them was increased at first. Thus, it is conjectured that TOPE increase nucleic acid metabolism directly or indirectly, and then disturb various metabolic pathways causing abnormal physiological and morphological effects followed by final death.

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Induction of Apoptosis and Cell Cycle Arrest by Dorema Glabrum Root Extracts in a Gastric Adenocarcinoma (AGS) Cell Line

  • Jafari, Naser;Zargar, Seyed Jalal;Yassa, Narguess;Delnavazi, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5189-5193
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    • 2016
  • Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

In Vitro Antitumor Properties of an Isolate from Leaves of Cassia alata L

  • Olarte, Elizabeth Iglesias;Herrera, Annabelle Aliga;Villasenor, Irene Manese;Jacinto, Sonia Donaldo
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3191-3196
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    • 2013
  • Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

Wordsworth's Re-Formation of Individuality: "Spots of Time," the Fragment and the Autobiography

  • Park, Mikyung
    • Journal of English Language & Literature
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    • v.56 no.6
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    • pp.1361-1378
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    • 2010
  • This paper argues that it is possible to construct an analogy of the literary fragment to an organic individual on the basis of an autonomous system of organic unity by reading William Wordsworth's ways of self-writing in The Prelude. The organicity of a fragment is borrowed from Friedrich Schlegel's theoretic and literary approach to the Romantic fragment. Focusing primarily on the two "spots of time" in Book Twelfth, I attempt to formulate a reciprocal relationship between a work of art and a literary autobiographer in terms of the self-generativity of the fragment. To be precise, both the fragment and the autobiographical project presuppose and at the same time depend on the engendering force of an organic unity and its resistance to discontinuity, which ironically affirms the persistent threat of disruption and death. Rewriting traumatic childhood experiences as rites of passage into adulthood, the two specified "spots of time" show the dominant mode of memory operative in the poem. Asserting the prominence of the individual as the very vehicle of realizing universal humanity, Wordsworth tries to re-form his individuality grounded in his childhood memories in a literary fashion. Under the premise that the poet is remembered by his posterity, The Prelude is constituted and reconstituted in conjunction with different versions of each memory. The poem also marks the poet's unachieved project of writing a philosophical poem, namely, The Recluse; for this very reason, The Prelude, which is complete in itself, points to an eternal work in progress, turning the truth of every fragment complete in its incompletion. As a trope of fragmentation, an autobiographical individuality is reformed in the poet's process of writing and re-visioning while simultaneously being dispersed once again between words, sentences, and pages.

Homeopathic mother tincture of Conium initiates reactive oxygen species mediated DNA damage and makes HeLa cells prone to apoptosis

  • Bishayee, Kausik;Mukherjee, Avinaba;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
    • CELLMED
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    • v.2 no.3
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    • pp.26.1-26.5
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    • 2012
  • Adverse side-effects and lack of scientific validation of some chemotherapeutic agents prevent the use of many traditional medicines claimed to have anti-cancer effects. Ethanolic extract of Conium maculatum has long been used in traditional and alternative systems of medicine including homeopathy for the treatment of glandular enlargements, cancerous tumours or hard lumps of testicles, prostate, ovaries, breasts and/ or uterus, particularly in the breast. However, if and how it acts still remains scientifically unknown. This study aims to test if Conium extract (CE), used as mother tincture of Conium in homeopathy, has demonstrable anti-cancer potentials without having much cytotoxicity in normal cells. Cytotoxicity of the drug was tested by conducting MTT assay on both normal (peripheral blood mononuclear cells) and HeLa cells. We also evaluated DNA fragmentation and DNA damage by DAPI and diphenylamine assay. The LDH activity assay was done to evaluate the percentages of apoptosis and necrosis. ROS accumulation also was evaluated to pin-point the actual events of apoptosis. Administration of drug clearly demonstrated its anti-cancer potentials as evidenced by the DNA damage analysis. The ROS activity also increased in case of the CE treated cells. LDH data revealed that the mode of cell death was mainly apoptotic and not necrotic. CE appears to induce apoptosis of cancer cells through ROS mediated pathway, and has negligible cytotoxicity against normal cells.