Antioxidative and Antimutagenic Activities of 70% Ethanolic Extracts from Four Fungal Mycelia-Fermented Specialty Rices

The health-promoting potential of 70% ethanolic extracts of 4 rice varieties fermented with Monascus ruber, Phellinus linteus, Cordyceps sinensis and Agaricus blazei was evaluated mainly focusing on their antioxidative and antimutagenic capacities based on the following parameters: phenolic compound and phytic acid content; inhibitory activity on lipid peroxidation; scavenging activity on DPPH radical; suppressing ability on mitomycin C-induced mutagenesis in E. coli cells; and protective effect on 4-nitroquinoline oxide-triggered DNA lesion in V79 hamster cells. The fermented rice extracts were superior in overall health-promoting parameters compared to the source material. The higher antimutagenic activity of the fermented rice extracts might be in part caused by a larger amount of antioxidant constituents such as phenolic compounds or phytic acid. Of the fungal species, Monascus ruber was found to impart a marked increase in both the antioxidative and antimutagenic abilities to the source material. The current study suggests a possibility that such fermented rice may contribute to the prevention of lifestyle-related diseases such as cancer through a daily intake of rice-based diets

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Interfacial architecture for extra Li+ storage in all-solid-state lithium batteries

The performance of nanocomposite electrodes prepared by controlled ball-milling of TiS2 and a Li2S-P2S5 solid electrolyte (SE) for all-solid-state lithium batteries is investigated, focusing on the evolution of the microstructure. Compared to the manually mixed electrodes, the ball-milled electrodes exhibit abnormally increased first-charge capacities of 416 mA h g-1and 837 mA h g-1 in the voltage ranges 1.5-3.0 V and 1.0-3.0 V, respectively, at 50 mA g-1 and 30??C. The ball-milled electrodes also show excellent capacity retention of 95% in the 1.5-3.0 V range after 60 cycles as compared to the manually mixed electrodes. More importantly, a variety of characterization techniques show that the origin of the extra Li+ storage is associated with an amorphous Li-Ti-P-S phase formed during the controlled ball-milling process.open1

Optimum Design of a Pultruded FRP Bridge Deck.

In this paper, an optimum design of GFRP bridge deck having a pultruded cellular cross-section is presented. The optimization process utilizes a modified genetic algorithm with the index technique. Based on the optimum design, viable cross-sectional dimension, volumes of fibers and matrix, fiber orientation, and stacking sequence for GFRP decks suitable for the pultrusion process are proposed

REGNET: Mining context-specific human transcription networks using composite genomic information

Background: Genome-wide expression profiles reflect the transcriptional networks specific to the given cell context. However, most statistical models try to estimate the average connectivity of the networks from a collection of gene expression data, and are unable to characterize the context-specific transcriptional regulations. We propose an approach for mining context-specific transcription networks from a large collection of gene expression fold-change profiles and composite gene-set information.Results: Using a composite gene-set analysis method, we combine the information of transcription factor binding sites, Gene Ontology or pathway gene sets and gene expression fold-change profiles for a variety of cell conditions. We then collected all the significant patterns and constructed a database of context-specific transcription networks for human (REGNET). As a result, context-specific roles of transcription factors as well as their functional targets are readily explored. To validate the approach, nine predicted targets of E2F1 in HeLa cells were tested using chromatin immunoprecipitation assay. Among them, five (Gadd45b, Dusp6, Mll5, Bmp2 and E2f3) were successfully bound by E2F1. c-JUN and the EMT transcription networks were also validated from literature.Conclusions: REGNET is a useful tool for exploring the ternary relationships among the transcription factors, their functional targets and the corresponding cell conditions. It is able to provide useful clues for novel cell-specific transcriptional regulations. The REGNET database is available at http://mgrc.kribb.re.kr/regnet.open0

Effects of paramagnetic fluctuations on the thermochemistry of MnO (100) surfaces in the oxygen evolution reaction

We investigated the effects of paramagnetic (PM) fluctuations on the thermochemistry of the MnO(100) surface in the oxygen evolution reaction (OER) using the "noncollinear magnetic sampling method \textit{plus} $U$" (NCMSM$+U$). Various physical properties, such as the electronic structure, free energy, and charge occupation, of the MnO (100) surface in the PM state with several OER intermediates, were reckoned and compared to those in the antiferromagnetic (AFM) state. We found that PM fluctuation enhances charge transfer from a surface Mn ion to each of the intermediates and strengthens the chemical bond between them, while not altering the overall features, such as the rate determining step and resting state, in reaction pathways. The enhanced charge transfer can be attributed to the delocalized nature of valence bands observed in the PM surface. In addition, it was observed that chemical-bond enhancement depends on the intermediates, resulting in significant deviations in reaction energy barriers. Our study suggests that PM fluctuations play a significant role in the thermochemistry of chemical reactions occurring on correlated oxide surfaces.Comment: Maintext: 15 pages, 3 figures 2 tables; SI: 3 pages, 2 figure

Development of a dental handpiece angle correction device

Background Preparation of a uniform angle of walls is essential for making an ideal convergence angle in fixed prosthodontics. We developed a de novo detachable angle-correction apparatus for dental handpiece drills that could help the ideal tooth preparation. Methods We utilized a gyro sensor to measure the angular velocities to calculate the slope of an object by integrating the values, acceleration sensor to calculate the slope of an object by measuring the acceleration relative to gravity, and Kalman filter algorithm. Converting the angulation of the handpiece body to its drill part could be performed by a specific matrix formulation set on two reference points (2° and 6°). A flexible printed circuit board was used to minimize the size of the device. For convergence angle investigation, 16 volunteers were divided randomly into two groups for performing tooth preparation on a mandibular first molar resin tooth. All abutments were scanned by a 3D scanner (D700®, 3Shape Co., Japan), the convergence angle and tooth axis deviation were analyzed by a CAD program (SolidWorks 2013®, Dassault Systems Co., USA) with statistical analysis by Wilcoxon signed-rank test (α = 0.05) using SPSS statistical software (Version 16.0, SPSS Inc.). Results This device successfully maintained the stable zero point (less than 1° deviation) at different angles (0°, 30°, 60°, 80°) for the first 30 min. In single tooth preparation, without this apparatus, the average bucco-lingual convergence angle was 20.26° (SD 7.85), and the average mesio–distal (MD) convergence angle was 17.88° (SD 7.64). However, the use of this apparatus improved the average BL convergence angle to 13.21° (SD 4.77) and the average MD convergence angle to 10.79° (SD 4.48). The angle correction device showed a statistically significant effect on reducing the convergence angle of both directions regardless of the order of the directions. Conclusions The angle correction device developed in this study is capable of guiding practitioners with high accuracy comparable to that of commercial navigation surgery. The volume of the angle correction device is much smaller than that of any other commercial navigation surgery system. This device is expected to be widely utilized in various fields of orofacial surgery.This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (2017R1D1A1B03036054)

Oligonol Ameliorates CCl 4

Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4-) induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg) reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB) p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinases (MAPKs) as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt