• Title/Summary/Keyword: EX527

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Induction of Nuclear Enlargement and Senescence by Sirtuin Inhibitors in Glioblastoma Cells

  • Kyoung B. Yoon;Kyeong R. Park;Soo Y. Kim;Sun-Young Han
    • IMMUNE NETWORK
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    • v.16 no.3
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    • pp.183-188
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    • 2016
  • Sirtuin family members with lysine deacetylase activity are known to play an important role in anti-aging and longevity. Cellular senescence is one of the hallmarks of aging, and downregulation of sirtuin is reported to induce premature senescence. In this study, we investigated the effects of small-molecule sirtuin inhibitors on cellular senescence. Various small molecules such as tenovin-1 and EX527 were employed for direct sirtuin activity inhibition. U251, SNB-75, and U87MG glioblastoma cells treated with sirtuin inhibitors exhibited phenotypes with nuclear enlargement. Furthermore, treatment of rat primary astrocytes with tenovin-1 also increased the size of the nucleus. The activity of senescence-associated β-galactosidase, a marker of cellular senescence, was induced by tenovin-1 and EX527 treatment in U87MG glioblastoma cells. Consistent with the senescent phenotype, treatment with tenovin-1 increased p53 expression in U87MG cells. This study demonstrated the senescence-inducing effect of sirtuin inhibitors, which are potentially useful tools for senescence research.

Analysis of radioactivity levels and hazard assessment of black sand samples from Rashid area, Egypt

  • Abdel-Rahman, Mohamed A.E.;El-Mongy, Sayed A.
    • Nuclear Engineering and Technology
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    • v.49 no.8
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    • pp.1752-1757
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    • 2017
  • The aim of this study is to evaluate the radioactivity levels and radiological impacts of representative black sand samples collected from different locations in the Rashid area, Egypt. These samples were prepared and then analyzed using the high-resolution gamma ray spectroscopy technique with a high-purity germanium detector. The activity concentration ($A_c$), minimum detectable activity, absorbed gamma dose rate, external hazard index ($H_{ex}$), annual effective dose rate equivalent, radium equivalent, as well as external and internal hazard index ($H_{ex}$ and $H_{in}$, respectively) were estimated based on the measured radionuclide concentration of the $^{238}U$($^{226}Ra$) and $^{232}Th$ decay chains and $^{40}K$. The activity concentrations of the $^{238}U$, $^{232}Th$ decay series and $^{40}K$ of these samples varied from $45.11{\pm}3.1Bq/kg$ to $252.38{\pm}34.3Bq/kg$, from $64.65{\pm}6.1Bq/kg$ to $579.84{\pm}53.1Bq/kg$, and from $403.36{\pm}20.8Bq/kg$ to $527.47{\pm}23.1Bq/kg$, respectively. The activity concentration of $^{232}Th$ in Sample 1 has the highest value compared to the other samples; this value is also higher than the worldwide mean range as reported by UNSCEAR 2000. The total absorbed gamma dose rate and the annual effective dose for these samples were found to vary from 81.19 nGy/h to 497.81 nGy/h and from $99.86{\mu}Sv/y$ to $612.31{\mu}Sv/y$, which are higher than the world average values of 59 nGy/h and $70{\mu}Sv/y$, respectively. The $H_{ex}$ values were also calculated to be 3.02, 0.47, 0.63, 0.87, 0.87, 0.51 and 0.91. It was found that the calculated value of $H_{ex}$ for Sample 1 is significantly higher than the international acceptable limit of <1. The results are tabulated, depicted, and discussed within national and international frameworks, levels, and approaches.

Blood Lead Level in Populations Resident in Some Abandoned Mine Area (충청북도 일부 폐광산 지역 주민의 만성 납 노출 정도 평가)

  • Song, Sun-Ho;Eom, Sang-Yong;Kim, Yong-Dae;Kim, Heon;Hong, Jang-Soo
    • Journal of Environmental Science International
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    • v.19 no.4
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    • pp.527-532
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    • 2010
  • Exposure to lead, particularly at chronic low-dose levels, is still a major public health concern. The present study is aimed to evaluate the blood lead levels in populations resident in some abandoned mine areas of Chungbuk, Korea. Eight hundreds and sixty-six subjects who reside in abandoned mine area located in Chungbuk, Korea, were enrolled this study. We evaluated the blood lead level according to the age, gender, and working history in mines. For statistical analysis, SPSS ver 12.0 was used. The geometric mean blood lead levels was $2.93\;{\mu}g/{\ell}$ and nobody showed levels over the guidelines of WHO. Ex-smokers and current-smokers showed significantly higher blood lead levels compared to that of non-smokers. The blood lead levels in individuals with a history of working in a mine was higher than those in individuals without such histories. The populations resident in some Chungbuk abadoned mine area showed low levels of lead in blood. This suggest that lead poisoning might not be induced by abandoned mine in Chungbuk, Korea.

Chemical composition, antioxidant and antifungal activities of rhizome essential oil of Kaempferia parviflora Wall. ex Baker grown in Vietnam

  • Dang-Minh-Chanh Nguyen;Thi-Hoan Luong;Tien-Chung Nghiem;Woo-Jin Jung
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.15-22
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    • 2023
  • The aim of the present study was to evaluate the chemical composition and antioxidative activity of rhizome essential oil of Kaempferia parviflora Wall. ex Baker. The essential oil extracted by hydrodistillation was chemically profiled by GC/MS analysis. The antioxidative activity was determined and evaluated spectroscopically by the 2,2-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays. According to the results, the major essential oil components were camphene (18.03%), β-pinene (14.25%), a-pinene (12.38%), endo-borneol (10.23%), β-copaene (8.38%), and linalool (8.20%). K. parviflora rhizome oil possessed antioxidant potential, exhibiting DPPH and ABTS radical scavenging activities as high as 80.90 and 94.04%, respectively, at a concentration of 10 mg/mL. The corresponding IC50 values were 0.451±0.051 and 0.527±0.022 mg/mL, respectively (IC50 values for ascorbic acid, as the standard, were 0.209±0.016 and 0.245±0.022 mg/mL, respectively). The mycelium of F. oxysporum was distorted and collapsed when treated with 0.5 mg/mL of the EO of K. parviflora rhizome for 3 days treatment, which may provide an important information for exploring the metabolism of the fungicide K. parviflora rhizome and its derived compounds against F. oxysporum. This study provides the chemical properties of the essential oil of K. parviflora rhizome grown in Vietnam and their potential antioxidant and antifungal activities.

Sweroside plays a role in mitigating high glucose-induced damage in human renal tubular epithelial HK-2 cells by regulating the SIRT1/NF-κB signaling pathway

  • Xiaodan Ma;Zhixin Guo;Wenhua Zhao;Li Chen
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.6
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    • pp.533-540
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    • 2023
  • Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

Awareness as Correlate of Undergraduate Students' Utilisation of Library Software in Universities in South-West, Nigeria

  • Odunola, Oluwole Akanmu;Tella, Adeyinka;Oyetola, Solomon Olusegun
    • International Journal of Knowledge Content Development & Technology
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    • v.14 no.2
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    • pp.47-63
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    • 2024
  • This study investigated the awareness and utilisation of library software by undergraduate students in universities in South-west Nigeria. The descriptive research design of the ex post facto was adopted using a sample of 1,527 selected from the total population of 239,048 undergraduate students in the universities. A questionnaire was used to collect the data. The finding of the study revealed that the extent of utilisation of library software by undergraduate students was high. Also, the majority of undergraduate students utilised library software in the university libraries between two to three times a week. Similarly, the findings show that awareness had an influence on the utilisation of library software by undergraduate students in the universities (r = 0.563, N = 1333, P < 0.05). The study concluded that awareness influenced the utilisation of library software by undergraduate students in universities. The study, therefore, recommends that the importance of the awareness of library software should be emphasized in the library to enhance its utilisation by the students in the university libraries.

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages

  • Lee, Jina;Choi, Jae-Won;Han, Hye Young;Kim, Woo Sik;Song, Ha-Yeon;Byun, Eui-Baek;Byun, Eui-Hong;Lee, Young-Ha;Yuk, Jae-Min
    • Parasites, Hosts and Diseases
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    • v.58 no.1
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    • pp.7-14
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    • 2020
  • Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human population worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effective drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4-HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expression of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1-mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

TOPK inhibition accelerates oxidative stress-induced granulosa cell apoptosis via the p53/SIRT1 axis

  • Jung‑Hwan Park;Sang‑Ah Park;Young‑Ju Lee;Na‑Rae Joo;Jongdae Shin;Sang‑Muk Oh
    • International Journal of Molecular Medicine
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    • v.46 no.5
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    • pp.1923-1937
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    • 2020
  • It has been suggested that oxidative stress involving reactive oxygen species (ROS) induces granulosa cell apoptosis, leading to follicular atresia, and that T-lymphokine-activated killer cell-originated protein kinase (TOPK) suppresses cancer cell apoptosis induced by several stimuli. However, it remains to be determined whether TOPK affects oxidative stress-induced granulosa cell apoptosis. The present study demonstrates that TOPK inhibition increases human granulosa COV434 cell apoptosis induced by hydrogen peroxide (H2O2). Co-treatment with the TOPK inhibitor, OTS514, in combination with H2O2 increased p53 acetylation and its expression, whereas it decreased Sirtuin 1 (SIRT1) expression, contributing to the promotion of apoptosis. In addition, the SIRT1 activator, resveratrol, or the SIRT1 inhibitor, Ex527, reduced or elevated H2O2-induced COV434 cell apoptosis, respectively. Furthermore, the p53 inhibitor, Pifithrin-μ, diminished the augmentation in poly(ADP-ribose) polymerase (PARP) cleavage induced by OTS514 plus H2O2, while the Mdm2 antagonist, Nutlin 3, increased PARP cleavage. Moreover, OTS514 further decreased the SIRT1 transcriptional activity decreased by H2O2, but promoted the H2O2-induced p53 or p21 transcriptional activity. Notably, the expression of exogenous p53 reduced SIRT1 transcriptional activity. Taken together, the findings of the present study demonstrate that TOPK inhibition promotes p53-mediated granulosa cell apoptosis through SIRT1 downregulation in response to H2O2. Therefore, it can be concluded that TOPK suppresses H2O2-induced apoptosis through the modulation of the p53/SIRT1 axis, suggesting a potential role of TOPK in the regulation of human granulosa cell apoptosis, leading to the promotion of abnormal follicular development.