Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice

AIM:To compare free and nanoparticle (NP)-encapsulated epigallocatechin-3-gallate (EGCG) for the treatment of Huntington’s disease (HD)-like symptoms in mice. MATERIALS & METHODS: EGCG was incorporated into PEGylated poly(lactic-co-glycolic) acid NPs with ascorbic acid (AA). HD-like striatal lesions and motor deficit were induced in mice by 3-nitropropionic acid-intoxication. EGCG and EGCG/AA NPs were co-administered and behavioral motor assessments and striatal histology performed after 5 days. RESULTS: EGCG/AA NPs were significantly more effective than free EGCG in reducing motor disturbances and depression-like behavior associated with 3-nitropropionic acid toxicity. EGCG/AA NPs treatment also mitigated neuroinflammation and prevented neuronal loss. CONCLUSION: NP encapsulation enhances therapeutic robustness of EGCG in this model of HD symptomatology. Together with our previous findings, this highlights the potential of EGCG/AA NPs in the symptomatic treatment of neurodegenerative diseases

Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer's disease mice model

Epigallocatechin-3-gallate (EGCG) is a candidate for treatment of Alzheimer's disease (AD) but its inherent instability limits bioavailability and effectiveness. We found that EGCG displayed increased stability when formulated as dual-drug loaded PEGylated PLGA nanoparticles (EGCG/AA NPs). Oral administration of EGCG/AA NPs in mice resulted in EGCG accumulation in all major organs, including the brain. Pharmacokinetic comparison of plasma and brain accumulation following oral administration of free or EGCG/AA NPs showed that, whilst in both cases initial EGCG concentrations were similar, long-term (5–25 h) concentrations were ca. 5 fold higher with EGCG/AA NPs. No evidence was found that EGCG/AA NPs utilised a specific pathway across the blood-brain barrier (BBB). However, EGCG, empty NPs and EGCG/AA NPs all induced tight junction disruption and opened the BBB in vitro and ex vivo. Oral treatment of APPswe/PS1dE9 (APP/PS1) mice, a familial model of AD, with EGCG/AA NPs resulted in a marked increase in synapses, as judged by synaptophysin (SYP) expression, and reduction of neuroinflammation as well as amyloid β (Aβ) plaque burden and cortical levels of soluble and insoluble Aβ(1-42) peptide. These morphological changes were accompanied by significantly enhanced spatial learning and memory. Mechanistically, we propose that stabilisation of EGCG in NPs complexes and a destabilized BBB led to higher therapeutic EGCG concentrations in the brain. Thus EGCG/AA NPs have the potential to be developed as a safe and strategy for the treatment of AD

Total Absorption Spectroscopy Study of 92^{92}Rb Decay: A Major Contributor to Reactor Antineutrino Spectrum Shape

The antineutrino spectra measured in recent experiments at reactors are inconsistent with calculations based on the conversion of integral beta spectra recorded at the ILL reactor. $^{92}$Rb makes the dominant contribution to the reactor spectrum in the 5-8 MeV range but its decay properties are in question. We have studied $^{92}$Rb decay with total absorption spectroscopy. Previously unobserved beta feeding was seen in the 4.5-5.5 region and the GS to GS feeding was found to be 87.5(25)%. The impact on the reactor antineutrino spectra calculated with the summation method is shown and discussed.Comment: 6 pages, 3 figure

The reg4 Gene, Amplified in the Early Stages of Pancreatic Cancer Development, Is a Promising Therapeutic Target

BACKGROUND: The aim of our work was to identify the genes specifically altered in pancreatic adenocarcinoma and especially those that are altered early in cancer development. METHODOLOGY/PRINCIPAL FINDINGS: Gene copy number was systematically assessed with an ultra-high resolution CGH oligonucleotide microarray in DNA from samples of pancreatic cancer. Several new cancer-associated variations were observed. In this work we focused on one of them, involving the reg4 gene. Gene copy number gain of the reg4 gene was confirmed by qPCR in 14 cancer samples. It was also found with increased copy number in most PanIN3 samples. The relationship betweena gain in reg4 gene copy number and cancer development was investigated on the human pancreatic cancer cell line Mia-PaCa2 xenografted under the skin of nude mice. When cells were transfected with a vector allowing reg4 expression, they generated tumors almost twice larger in size. In addition, these tumors were more resistant to gemcitabine treatment than control tumors. Interestingly, weekly intraperitoneal administration of a monoclonal antibody to reg4 halved the size of tumors generated by Mia-PaCa2 cells, suggesting that the antibody interfered with a paracrine/autocrine mechanism involving reg4 and stimulating cancer progression. The addition of gemcitabine resulted in further reduction, tumors becoming 5 times smaller than control. Exposure to reg4 antibody resulted in a significant decrease in intra-tumor levels of pAkt, Bcl-xL, Bcl-2, survivin and cyclin D1. CONCLUSIONS/SIGNIFICANCE: It was concluded that adjuvant therapies targeting reg4 could improve the standard treatment of pancreatic cancer with gemcitabine

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Approaching the precursor nuclei of the third r-process peak with RIBs

The rapid neutron nucleosynthesis process involves an enormous amount of very exotic neutron-rich nuclei, which represent a theoretical and experimental challenge. Two of the main decay properties that affect the final abundance distribution the most are half-lives and neutron branching ratios. Using fragmentation of a primary $^{238}$U beam at GSI we were able to measure such properties for several neutron-rich nuclei from $^{208}$Hg to $^{218}$Pb. This contribution provides a short update on the status of the data analysis of this experiment, together with a compilation of the latest results published in this mass region, both experimental and theoretical. The impact of the uncertainties connected with the beta-decay rates and with beta-delayed neutron emission is illustrated on the basis of $r$-process network calculations. In order to obtain a reasonable reproduction of the third $r$-process peak, it is expected that both half-lives and neutron branching ratios are substantially smaller, than those based on FRDM+QRPA, commonly used in $r$-process model calculations. Further measurements around $N\sim126$ are required for a reliable modelling of the underlying nuclear structure, and for performing more realistic $r$-process abundance calculations.The rapid neutron nucleosynthesis process involves an enormous amount of very exotic neutron-rich nuclei, which represent a theoretical and experimental challenge. Two of the main decay properties that affect the final abundance distribution the most are half-lives and neutron branching ratios. Using fragmentation of a primary 238U beam at GSI we were able to measure such properties for several neutron-rich nuclei from 208Hg to 218Pb. This contribution provides a short update on the status of the data analysis of this experiment, together with a compilation of the latest results published in this mass region, both experimental and theoretical. The impact of the uncertainties connected with the beta-decay rates and with beta-delayed neutron emission is illustrated on the basis of r-process network calculations. In order to obtain a reasonable reproduction of the third r-process peak, it is expected that both half-lives and neutron branching ratios are substantially smaller, than those based on FRDM+QRPA, commonly used in r-process model calculations. Further measurements around N ~ 126 are required for a reliable modelling of the underlying nuclear structure, and for performing more realistic r-process abundance calculations

First Measurement of Several β -Delayed Neutron Emitting Isotopes beyond N=126

The β-delayed neutron emission probabilities of neutron rich Hg and Tl nuclei have been measured together with β-decay half-lives for 20 isotopes of Au, Hg, Tl, Pb, and Bi in the mass region N126. These are the heaviest species where neutron emission has been observed so far. These measurements provide key information to evaluate the performance of nuclear microscopic and phenomenological models in reproducing the high-energy part of the β-decay strength distribution. This provides important constraints on global theoretical models currently used in r-process nucleosynthesis. © 2016 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the http://creativecommons.org/licenses/by/3.0/Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI

Removal of fumonisin B1 and B2 from model solutions and red wine using polymeric substances

Fumonisins are a group of mycotoxins found in various foods whose consumption is known to be harmful for human health. In this study, we evaluated the ability of three polymers (Polyvinylpolypyrrolidone, PVPP,; a resin of N-vinyl-2-pyrrolidinone with ethylene glycol dimethacrylate and triallyl isocyanurate, PVP-DEGMA-TAIC; and poly(acrylamide-co-ethylene glycol-dimethacrylate), PA-EGDMA) to remove fumonisin B-1 (FB1) and fumonisin B-2 (FB2) from model solutions and red wine. Various polymer concentrations (1, 5 and 10 mg mL(-1)) and contact times (2, 8 and 24 h) were tested, with all polymers exhibiting fumonisin removal capacities (monitored by LC-MS). The impact of all polymers on polyphenol removal was also assessed. PA-EGDMA showed to be the most promising polymer, removing 71% and 95% of FB1, and FB2, respectively, with only a 22.2% reduction in total phenolics

Effect of olive pruning wood extract on lipid oxidation in sunflower oil Efecto del extracto de madera de poda de olivo sobre la oxidación lipídica en aceite de girasol

© 2017, Pontificia Universidad Catolica de Chile, Facultad de Agronomia e Ingenieria Forestal. All rights reserved. The production of high quality natural Antioxidants from olive pruning wood extracts and their application to prevent the oxidation of vegetable oils were evaluated. The production of antioxidants from branches of olive pruning wood (OPW) using Soxhlet extraction and ethanol was optimized, evaluating the use of dry and fresh OPW, with extraction of an initial mass of 1 and 3 g and extraction times of 2, 4 and 8 h. For the evaluation of the antioxidant properties of the OPW extracts (OPWEs), the 2.2-diphenyl-1-picrylhydrazyl (DPPH) radical bleaching and ORAC-FL assays were performed. Additionally, the phenolic profile of the OPWEs was obtained by using HPLC-DAD, and the total phenolic composition was quantified by the Folin-Ciocalteu assay. The OPWE obtained from dry OPW using 1 g of initial mass showed the highest content of phenolic compounds and better antioxidant capa