Impact of heat treatment on size, structure, and bioactivity of elemental selenium nanoparticles

Jinsong Zhang1, Ethan W Taylor2, Xiaochun Wan1, Dungeng Peng31School of Tea and Food Science, Anhui Agricultural University, Anhui, People's Republic of China; 2Department of Nanoscience, Joint School of Nanoscience and Nanoengineering, University of North Carolina at Greensboro, Greensboro, NC, 3Department of Biochemistry, Vanderbilt University, Nashville, TN, USABackground: Elemental selenium nanoparticles have emerged as a novel selenium source with the advantage of reduced risk of selenium toxicity. The present work investigated whether heat treatment affects the size, structure, and bioactivity of selenium nanoparticles.Methods and results: After a one-hour incubation of solution containing 80 nm selenium particles in a 90°C water bath, the nanoparticles aggregated into larger 110 nm particles and nanorods (290 nm × 70 nm), leading to significantly reduced bioavailability and phase II enzyme induction in selenium-deficient mice. When a solution containing 40 nm selenium nanoparticles was treated under the same conditions, the nanoparticles aggregated into larger 72 nm particles but did not transform into nanorods, demonstrating that the thermostability of selenium nanoparticles is size-dependent, smaller selenium nanoparticles being more resistant than larger selenium nanoparticles to transformation into nanorods during heat treatment.Conclusion: The present results suggest that temperature and duration of the heat process, as well as the original nanoparticle size, should be carefully selected when a solution containing selenium nanoparticles is added to functional foods.Keywords: nanoparticle, selenium, bioactivity, heat treatmen

Scoring Functions for Multivariate Distributions and Level Sets

Interest in predicting multivariate probability distributions is growing due to the increasing availability of rich datasets and computational developments. Scoring functions enable the comparison of forecast accuracy, and can potentially be used for estimation. A scoring function for multivariate distributions that has gained some popularity is the energy score. This is a generalization of the continuous ranked probability score (CRPS), which is widely used for univariate distributions. A little-known, alternative generalization is the multivariate CRPS (MCRPS). We propose a theoretical framework for scoring functions for multivariate distributions, which encompasses the energy score and MCRPS, as well as the quadratic score, which has also received little attention. We demonstrate how this framework can be used to generate new scores. For univariate distributions, it is well-established that the CRPS can be expressed as the integral over a quantile score. We show that, in a similar way, scoring functions for multivariate distributions can be "disintegrated" to obtain scoring functions for level sets. Using this, we present scoring functions for different types of level set, including those for densities and cumulative distributions. To compute the scoring functions, we propose a simple numerical algorithm. We illustrate our proposals using simulated and stock returns data

Digital Micromirror Device Based Microstereolithography for Micro Structures of Transparent Photopolymer and Nanocomposites

This paper describes a Digital Micromirror Device (DMD) based ultraviolet (UV) microstereolithography (µ-SL) system developed for rapid prototyping and manufacturing of micro 3D structures. Characterization experiments show that the developed the DMD-based imaging system irradiates an entire photopolymer layer at once, providing reasonable curing speed and good resolution at a low cost. 2D and 3D micro parts were fabricated. High frequency ultrasonic vibration (above 20 kHz) was experimented and verified that it can be used to significantly decrease the leveling time of viscous photopolymer. Furthermore, micro parts were also fabricated in nanocomposites, which were obtained by ultrasonic mixing of the transparent photopolymer and nano-sized ceramic particles. High quality micro models fabricated by this novel process could be used for micro scale investment casting, tooling, devices, and medical applications.Mechanical Engineerin

Regulation of NF-κB by PML and PML-RARα

Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB

Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.

OBJECTIVE: Atherosclerosis, the cause of 50% of deaths in westernized societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local proinflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. APPROACH AND RESULTS: We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic apolipoprotein E(-/-) mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines, and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis, and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. CONCLUSIONS: We propose myocardin as a guardian of the contractile, noninflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease.This work was supported by Wellcome Trust funding for MAJ (Studentship 086799/Z/08/Z), British Heart Foundation grants (PG/10/007/28184) for AT, and (RG/08/009/25841) for MRB, and SS (FS/13/29/30024), the Cambridge NIHR Biomedical Research Centre and the NIH for JM (NIH HL-117907).This is the accepted manuscript of a paper published in Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, doi: 10.1161/ATVBAHA.114.30521

8-chloro-adenosine activity in FLT3-ITD acute myeloid leukemia

Nucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor-risk FLT3-ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8-chloro-adenosine (8-Cl-Ado) is a ribose-containing, RNA-directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription. In this report, we demonstrate antileukemic activities of 8-Cl-Ado in vitro and in vivo and provide mechanistic insight into the mode of action of 8-Cl-Ado in AML. 8-Cl-Ado markedly induced apoptosis in LSC, with negligible effects on normal stem cells. 8-Cl-Ado was particularly effective against AML cell lines and primary AML blast cells harboring the FLT3-ITD mutation. FLT3-ITD is associated with high expression of miR-155. Furthermore, we demonstrate that 8-Cl-Ado inhibits miR-155 expression levels accompanied by induction of DNA-damage and suppression of cell proliferation, through regulation of miR-155/ErbB3 binding protein 1(Ebp1)/p53/PCNA signaling. Finally, we determined that combined treatment of NSG mice engrafted with FLT3-ITD (+) MV4-11 AML cells with 8-Cl-Ado and the FLT3 inhibitor AC220 (quizartinib) synergistically enhanced survival, compared with that of mice treated with the individual drugs, suggesting a potentially effective approach for FLT3-ITD AML patients.Peer reviewe