The positive feedback loop between Nrf2 and phosphogluconate dehydrogenase stimulates proliferation and clonogenicity of human hepatoma cells

© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.Recent studies report that nuclear factor-erythroid-2-related factor 2 (Nrf2) facilitates tumor progression through metabolic reprogramming in cancer cells. However, the molecular mechanism underlying the oncogenic functions of Nrf2 is not yet well understood. Some of the pentose phosphate pathway (PPP) enzymes are considered to play a role in the cancer progression. The present study was intended to explore the potential role of phosphogluconate dehydrogenase (PGD), one of the PPP enzymes, in the proliferation and migration of human hepatoma HepG2 cells. Genetic ablation of Nrf2 attenuated the expression of PGD at both transcriptional and translational levels. Notably, Nrf2 regulates the transcription of PGD through direct binding to the antioxidant response element in its promoter region. Nrf2 overexpression in HepG2 cells led to increased proliferation, survival, and migration, and these events were suppressed by silencing PGD. Interestingly, knockdown of the gene encoding this enzyme not only attenuated the proliferation and clonogenicity of HepG2 cells but also downregulated the expression of Nrf2. Thus, there seems to exist a positive feedback loop between Nrf2 and PGD which is exploited by hepatoma cells for their proliferation and survival. Treatment of HepG2 cells with ribulose-5-phosphate, a catalytic product of PGD, gave rise to a concentration-dependent upregulation of Nrf2. Collectively, the current study shows that Nrf2 promotes hepatoma cell growth and progression, partly through induction of PGD transcription.

A study on soil loss rate assessment of vegetation mat measures

The hydraulic stability of the high-water revetment with and without vegetation mat was tested in both laboratory-scale hydraulic experiments, as well as prototype-scale experiments. Experimental cases cover a wide range of cross-sectional average velocity (0.2-2.0 m/s), different slopes of the embankment, and two different types of soils. For each experimental condition, measurements of velocity field and scouring profile on the embankment were repeated for the cases with and without vegetation mat, respectively, to assess the efficiency of the vegetation mat in protecting the embankment. A dramatic reduction in soil loss rate was observed in the cases with the vegetation mat installed. The experimental results were recast in terms of Froude number and the soil loss rate appears to be proportional to the square of Froude number. Also a functional relationship between the soil loss rate and the cross-sectional average velocity was also deduced so that it could guide actual design practices of such high-water revetments. To the authors' best knowledge, the current study is the first to attempt to provide a practical design guideline. (C) 2016 International Association for Hydro-environment Engineering and Research, Asia Pacific Division. Published by Elsevier B.V. All rights reserved.OAIID:RECH_ACHV_DSTSH_NO:T201636125RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080988CITE_RATE:1.429FILENAME:pub11_Han_etal_2016JHER.pdfDEPT_NM:건설환경공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/d2364169-3df0-4c7a-b814-21a91426dbc8/linkY

An experimental study on water surface profiles of high Froude number flows

Motivated by need to study supercritical overbank flows on floodplain, we experimentally investigate if initially supercritical flow in a rectangular flume would maintain its state throughout. Varying upstream gate opening, flow rate and angle of the slope, a total of 37 experimental cases were carried out. The experimental results are compared to two existing theories: an inviscid theory based on nonlinear shallow water equations and jump conditions and a hydraulic theory that takes friction into account. The experimental data are consistent with the two theories. Flows on downward slope were stable, while those on upward slope had unstable hydraulic jump and transformed into subcritical flow. The reported results should serve well in designing a laboratory flume with the supercritical inflow and in conducting hydraulic model experiments on overbank flows.OAIID:RECH_ACHV_DSTSH_NO:T201834776RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A080988CITE_RATE:.94FILENAME:2018KSCE22Park-etal.pdfDEPT_NM:건설환경공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/7f084c6c-e938-4359-acd7-76c6151612bc/linkN

Flavonoids Isolated from Korea Citrus aurantium L. Induce G2/M Phase Arrest and Apoptosis in Human Gastric Cancer AGS Cells

Aim of the Study. Citrus species is used in traditional medicine as medicinal herb in several Asian countries including Korea. Flavonioids became known as various properties, such as anti-oxidants, anti-inflammation and anti-cancer, and so forth. The present study, the anti-cancer effect of flavonioids isolated from Citrus aurantium L. in human gastric cancer AGS cells has been investigated. Materials and Methods. The anti-proliferative activity was assayed using MTT assay. Cell cycle analysis was done using flow cytometry and apoptosis detection was done using by hoechst fluorescent staining and Annexin V-propidium iodide double staining. Western blot was used to detect the expression of protein related with cell cycle and apoptosis. Results. Flavonoids isolated from Citrus aurantium L. have the effect of anti proliferation on AGS cells with IC50 value of 99 μg/mL. Flavonoids inhibited cell cycle progression in the G2/M phase and decrease expression level of cyclin B1, cdc 2, cdc 25c. Flavonoids induced apoptosis through activate caspase and inactivate PARP. Conclusions. Flavonoids isolated from Citrus aurantium L. induced G2/M phase arrest through the modulation of cell cycle related proteins and apoptosis through activation caspase. These finding suggest flavonoids isolated from Citrus aurantium L. were useful agent for the chemoprevention of gastric cancer

Dialysis specialist care and patient survival in hemodialysis facilities: a Korean nationwide cohort study

Background It is important for the dialysis specialist to provide essential and safe care to hemodialysis (HD) patients. However, little is known about the actual effect of dialysis specialist care on the survival of HD patients. We therefore investigated the influence of dialysis specialist care on patient mortality in a nationwide Korean dialysis cohort. Methods We used an HD quality assessment and National Health Insurance Service claims data from October to December 2015. A total of 34,408 patients were divided into two groups according to the proportion of dialysis specialists in their HD unit, as follows: 0%, no dialysis specialist care group, and ≥50%, dialysis specialist care group. We analyzed the mortality risk of these groups using the Cox proportional hazards model after matching propensity scores. Results After propensity score matching, 18,344 patients were enrolled. The ratio of patients from the groups with and without dialysis specialist care was 86.7% to 13.3%. The dialysis specialist care group showed a shorter dialysis vintage, higher levels of hemoglobin, higher single-pool Kt/V values, lower levels of phosphorus, and lower systolic and diastolic blood pressures than the no dialysis specialist care group. After adjusting demographic and clinical parameters, the absence of dialysis specialist care was a significant independent risk factor for all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03–1.18; p = 0.004). Conclusion Dialysis specialist care is an important determinant of overall patient survival among HD patients. Appropriate care given by dialysis specialists may improve clinical outcomes of patients undergoing HD

Gene duplication of type-B ARR transcription factors systematically extends transcriptional regulatory structures in Arabidopsis

Many of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, we examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures.1

Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets

Perilla frutescens is a culinary and medicinal herb which has a strong anti-inflammatory and antioxidative effects. In the present study, we investigated the effects of Perilla frutescens extract (PE) against dextran sulfate sodium (DSS)-induced mouse colitis, an animal model that mimics human inflammatory bowel disease (IBD). Five-week-old male ICR mice were treated with a daily dose of PE (20 or 100 mg/kg, p.o.) for 1 week, followed by administration of 3% DSS in double distilled drinking water and PE by gavage for another week. DSS-induced colitis was characterized by body weight loss, colon length shortening, diarrhea and bloody stool, and these symptoms were significantly ameliorated by PE treatment. PE administration suppressed DSS-induced expression of proinflammatory enzymes, including cyclooxygenase-2 and inducible nitric oxide synthase as well as cyclin D1, in a dose-dependent fashion. Nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) are major transcriptional regulators of inflammatory signaling. PE administration significantly inhibited the activation of both NF-κB and STAT3 induced by DSS, while it elevated the accumulation of Nrf2 and heme oxygenase-1 in the colon. In another experiment, treatment of CCD841CoN human normal colon epithelial cells with PE (10 mg/ml) resulted in the attenuation of the tumor necrosis factor-α-induced expression/activation of mediators of proinflammatory signaling. The above results indicate that PE has a preventive potential for use in the management of IBD