• Title/Summary/Keyword: H2AX

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Effect of Dendranthema indicum Extracts on Cell and DNA Damage Induced by Oxidative Stress (국화추출물이 산화적 스트레스에 의해 유발되는 세포와 DNA 손상에 미치는 영향)

  • Park, Young-Mi;Kim, Jee-In;Lee, Chang-Ho;Lim, Jae-Hwan;Seo, Eul-Won
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1698-1704
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    • 2011
  • In this study, we evaluated the protective effects of ethanol extracts from Dendranthema indicum on cell and DNA damages induced by oxidative stress. Antioxidant activities of D. indicum extracts are higher than scavenging activities of DPPH free radical and hydroxyl radical by 92.8% and 73.8%, respectively, and higher than ferrous iron chelating effects by 59.4%. D. indicum extracts showed a protective effect on oxidative cell damage by inhibiting lipid peroxidation by 90.3% in the control group, and inhibiting expression level of p21 protein by 79.6% for the control group. This means D. indicum extracts have a great protective effect against oxidative stress. DNA fragmentation inhibition in D. indicum extracts were 89.6% for the control group, which makes the movement of DNA tail reduced, and phosphorylation of H2AX was 20.2% of the radical experiment group. This means that D. indicum extracts effectively inhibit DNA fragmentation and H2AX phosphorylation. Taken together, we suggest that ethanol extract from D. indicum has a role as a useful chemopreventor against oxidative damage.

On Self-commutator Approximants

  • Duggal, Bhagwati Prashad
    • Kyungpook Mathematical Journal
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    • v.49 no.1
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    • pp.1-6
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    • 2009
  • Let B(X) denote the algebra of operators on a complex Banach space X, H(X) = {h ${\in}$ B(X) : h is hermitian}, and J(X) = {x ${\in}$ B(X) : x = $x_1$ + $ix_2$, $x_1$ and $x_2$ ${\in}$ H(X)}. Let ${\delta}_a$ ${\in}$ B(B(X)) denote the derivation ${\delta}_a$ = ax - xa. If J(X) is an algebra and ${\delta}_a^{-1}(0){\subseteq}{\delta}_{a^*}^{-1}(0)$ for some $a{\in}J(X)$, then ${\parallel}a{\parallel}{\leq}{\parallel}a-(x^*x-xx^*){\parallel}$ for all $x{\in}J(X){\cap}{\delta}_a^{-1}(0)$. The cases J(X) = B(H), the algebra of operators on a complex Hilbert space, and J(X) = $C_p$, the von Neumann-Schatten p-class, are considered.

Hsp90 Inhibitor Geldanamycin Enhances the Antitumor Efficacy of Enediyne Lidamycin in Association with Reduced DNA Damage Repair

  • Han, Fei-Fei;Li, Liang;Shang, Bo-Yang;Shao, Rong-Guang;Zhen, Yong-Su
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7043-7048
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    • 2014
  • Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced $G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage.

Ethanol Extract of Smilax glabra Induces Apoptotic Cell Death in Human YD10B Oral Squamous Cell Carcinoma Cells

  • Young Sun Hwang
    • Journal of dental hygiene science
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    • v.23 no.3
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    • pp.216-224
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    • 2023
  • Background: Smilax glabra has various pharmacological activities and is widely used as a herbal medicine. Although the incidence of oral cancer is low, the recurrence rate is high, and the 5-year survival rate is poor. It is necessary to search for anticancer drugs that increase the effect of cancer chemotherapy on heterogeneous oral tissues and reduce the side effects on normal cells. This study aimed to investigate the effects and mechanism of ethanol extract of Smilax glabra (EESG) as an anticancer drug for oral cancer. Methods: Smilax glabra root components extracted with 70% ethanol were used to analyze their effects on cancer cells. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay was performed for cytotoxicity analysis. Flow cytometry was performed to determine the cell cycle phase distribution. To observe apoptotic cells, terminal deoxynucleotidyl transferase dUTP nick end labeling and γH2AX were detected by fluorescence microscope. The protein levels of cleaved PARP and caspase were analyzed using western blotting. The activation of procaspase-3 was confirmed by measuring caspase-3 activity. Results: EESG was no cytotoxic to normal gingival fibroblast but was high in YD10B oral squamous cell carcinoma (OSCC) cells. EESG treatment increased the subdiploid DNA content of YD10B cells by assessing DNA content distribution. Chromatin condensation and DNA strand breaks increased in YD10B cells treated with EESG. EESG-treated YD10B cells had high Annexin V and low propidium iodide levels, confirming that early apoptosis was induced. In addition, increased levels of γH2AX foci, a marker of DNA damage, were observed in the nuclei of EESG-treated YD10B cells. The EESG-treated YD10B cells also exhibited decreased procaspase-3 and procaspase-9 levels, increased PARP cleavage and caspase-3 activity. Conclusion: These results indicate that EESG inhibited cancer cell proliferation by inducing apoptosis in YD10B OSCC cells.

Exploration of Beneficial Herbal Medicines to Attenuate Particulate Matter-induced Cellular Injury in Human Corneal Epithelial Cells (인간 각막상피세포에서 미세먼지로 인한 세포 손상을 완화할 수 있는 유익한 한약재의 탐색)

  • Kim, Da Hye;Kim, Min Yeong;Hwangbo, Hyun;Ji, Seon Yeong;Park, Seh-Kwang;Park, Sung-Ho;Kim, Mi-Young;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.8
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    • pp.647-658
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    • 2022
  • Particulate matter (PM) is known to be involved in the onset and progression of various diseases by promoting oxidative and inflammatory reactions as air pollutants containing various small particles that are harmful. In this study, the protective efficacy of herbal medicines was evaluated in human corneal epithelial cells (hCECs) to select natural products that can protect the eye, the primary organ directly exposed to external pollutants from PM. As a result, five candid ate herbal medicines [Cheonmundong, Asparagus Rhizome; Seokchangpo, Aciru Gramineri Rhizoma; Hwangryeon, Coptidis Rhizoma; Gamgug, Chrysanthemi Indici Flos; and Geumjanhwa (Marigold flower petals)] which showed inhibitory efficacy on PM2.5-induced cytotoxicity, were selected from among 12 candidate herbal medicines. To evaluate the antioxidant activity of these candidate substances, the reactive oxygen species (ROS) scavenging ability was investigated, and it was found that the extracts of Seokchangpo, Cheonmundong and Hwangryeon showed a significant inhibitory effect on PM2.5-induced ROS production, which was correlated with the preservation of mitochondrial activity. In addition, it was confirmed that they could block DNA damage caused by PM2.5 through analysis of 8-hydroxy-2'-deoxyguanosine generation and phosphorylated-H2A histone family member X (γ- H2AX) expression. Furthermore, the increase in inflammasome activity and inflammatory response in PM2.5-treated hCECs was also canceled in the presence of these extracts. Although additional studies are needed, the results of this study will be used as primary data to find novel natural compounds that protect hCECs from PM.

A BERBERIAN TYPE EXTENSION OF FUGLEDE-PUTNAM THEOREM FOR QUASI-CLASS A OPERATORS

  • Kim, In Hyoun;Jeon, In Ho
    • Korean Journal of Mathematics
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    • v.16 no.4
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    • pp.583-587
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    • 2008
  • Let $\mathfrak{L(H)}$ denote the algebra of bounded linear operators on a separable infinite dimensional complex Hilbert space $\mathfrak{H}$. We say that $T{\in}\mathfrak{L(H)}$ is a quasi-class A operator if $$T^*{\mid}T^2{\mid}T{{\geq}}T^*{\mid}T{\mid}^2T$$. In this paper we prove that if A and B are quasi-class A operators, and $B^*$ is invertible, then for a Hilbert-Schmidt operator X $$AX=XB\;implies\;A^*X=XB^*$$.

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Effect of Hydropsyche kozhantschikovi Extracts on Oxidative Stress (줄날도래 추출물이 산화적 스트레스에 미치는 영향)

  • Park, Young Mi;Lim, Jae Hwan;Lee, Jong Eun;Seo, Eul Won
    • Journal of Life Science
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    • v.23 no.1
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    • pp.31-37
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    • 2013
  • The present study aimed to investigate effects of ethanol extracts from Hydropsyche kozhantschikovi on cell and DNA damage caused by oxidative stress. In a radical scavenging assay, compared with ascorbic acid used as a control, the level of DPPH (1,1-diphenyl-2-picrylhydrazyl) and that of hydroxyl radicals in H. kozhantschikovi extracts were 60.0% and 43.7%, respectively. The ferrous iron chelating level was 37.5% compared to the chelating value of EDTA (ethylenediaminetetraacetic acid) as a positive control at the same concentration. To verify inhibitory effects of oxidative cell damage induced by reactive oxygen species (ROS), the relative level of lipid peroxidation and the expression level of the p21 protein were compared in extracts-treated and untreated groups. Lipid peroxidation was completely inhibited in the extracts-treated group compared with the radical-only treated group. The level of p21 protein expression was restored to 92.2% of p21 protein expression in the control sample. In addition, DNA cleavage inhibition in the H. kozhantschikovi extracts was 74.1% compared with that of the control group, suggesting that H. kozhantschikovi extracts repress DNA cleavage induced by ROS. Moreover, the phosphorylation ratio of the H2AX protein was 16.7% in the radical-treated group, indicating that the ethanol extracts inhibited 83.3% of DNA damage. Our findings suggest that ethanol extracts from H. kozhantschikovi are effective not only in repressing the oxidation of free radicals and highly toxic hydroxyl radicals, but also in decreasing cell and DNA damage caused by oxidative stress.

Dictyostelium discoideum Ax2 as an Assay System for Screening of Pharmacological Chaperones for Phenylketonuria Mutations

  • Kim, Yu-Min;Yang, Yun Gyeong;Kim, Hye-Lim;Park, Young Shik
    • Journal of Microbiology and Biotechnology
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    • v.25 no.6
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    • pp.782-787
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    • 2015
  • In this study, we developed an assay system for missense mutations in human phenylalanine hydroxylases (hPAHs). To demonstrate the reliability of the system, eight mutant proteins (F39L, K42I, L48S, I65T, R252Q, L255V, S349L, and R408W) were expressed in a mutant strain (pah-) of Dictyostelium discoideum Ax2 disrupted in the indigenous gene encoding PAH. The transformed pah - cells grown in FM minimal medium were measured for growth rate and PAH activity to reveal a positive correlation between them. The protein level of hPAH was also determined by western blotting to show the impact of each mutation on protein stability and catalytic activity. The result was highly compatible with the previous ones obtained from other expression systems, suggesting that Dictyostelium is a dependable alternative to other expression systems. Furthermore, we found that both the protein level and activity of S349L and R408W, which were impaired severely in protein stability, were rescued in HL5 nutrient medium. Although the responsible component(s) remains unidentified, this unexpected finding showed an important advantage of our expression system for studying unstable proteins. As an economic and stable cell-based expression system, our development will contribute to mass-screening of pharmacological chaperones for missense PAH mutations as well as to the in-depth characterization of individual mutations.

WEYL@S THEOREMS FOR POSINORMAL OPERATORS

  • DUGGAL BHAGWATI PRASHAD;KUBRUSLY CARLOS
    • Journal of the Korean Mathematical Society
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    • v.42 no.3
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    • pp.529-541
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    • 2005
  • An operator T belonging to the algebra B(H) of bounded linear transformations on a Hilbert H into itself is said to be posinormal if there exists a positive operator $P{\in}B(H)$ such that $TT^*\;=\;T^*PT$. A posinormal operator T is said to be conditionally totally posinormal (resp., totally posinormal), shortened to $T{\in}CTP(resp.,\;T{\in}TP)$, if to each complex number, $\lambda$ there corresponds a positive operator $P_\lambda$ such that $|(T-{\lambda}I)^{\ast}|^{2}\;=\;|P_{\lambda}^{\frac{1}{2}}(T-{\lambda}I)|^{2}$ (resp., if there exists a positive operator P such that $|(T-{\lambda}I)^{\ast}|^{2}\;=\;|P^{\frac{1}{2}}(T-{\lambda}I)|^{2}\;for\;all\;\lambda)$. This paper proves Weyl's theorem type results for TP and CTP operators. If $A\;{\in}\;TP$, if $B^*\;{\in}\;CTP$ is isoloid and if $d_{AB}\;{\in}\;B(B(H))$ denotes either of the elementary operators $\delta_{AB}(X)\;=\;AX\;-\;XB\;and\;\Delta_{AB}(X)\;=\;AXB\;-\;X$, then it is proved that $d_{AB}$ satisfies Weyl's theorem and $d^{\ast}_{AB}\;satisfies\;\alpha-Weyl's$ theorem.

Supplementation with psyllium seed husk reduces myocardial damage in a rat model of ischemia/reperfusion

  • Lim, Sun Ha;Lee, Jongwon
    • Nutrition Research and Practice
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    • v.13 no.3
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    • pp.205-213
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    • 2019
  • BACKGROUND/OBJECTIVES: Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model. MATERIALS/METHODS: Rats were fed diets supplemented with PSH (1, 10, or 100 mg/kg/d) for 3 d. The rats were then subjected to 30 min ischemia through ligation of the left anterior descending coronary artery, followed by 3 h reperfusion through release of the ligation. The hearts were harvested and cut into four slices. To assess infarct size (IS), an index representing heart damage, the slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC). To elucidate underlying mechanisms, Western blotting was performed for the slices. RESULTS: Supplementation with 10 or 100 mg/kg/d of PSH significantly reduces the IS. PSH supplementation (100 mg/kg/d) tends to reduce caspase-3 generation and increase BCL-2/BAX ratio. PSH supplementation also upregulates the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and its target genes including antioxidant enzymes such as glutathione S-transferase mu 2 (GSTM2) and superoxide dismutase 2 (SOD2). PSH supplementation upregulates some sirtuins ($NAD^+$-dependent deacetylases) including SIRT5 (a mitochondrial sirtuin) and SIRT6 and SIRT7 (nuclear sirtuins). Finally, PSH supplementation upregulates the expression of protein kinase A (PKA), and increases phosphorylated cAMP response element-binding protein (CREB) (pCREB), a target protein of PKA. CONCLUSIONS: The results from this study indicate that PSH consumption reduces myocardial I/R injury in rats by inhibiting the apoptotic cascades through modulation of gene expression of several genes located upstream of apoptosis. Therefore, we believe that PSH can be developed as a functional food that would be beneficial in the prevention of MI.