Smart Nanoparticles as Advanced Anti-Akt Kinase Delivery Systems for Pancreatic Cancer Therapy

Pancreatic cancer is one of the deadliest cancers partly due to late diagnosis, poor drug delivery to the target site, and acquired resistance to therapy. Therefore, more effective therapies are urgently needed to improve the outcome of patients. In this work, we have tested self-assembling genetically engineered polymeric nanoparticles formed by elastin-like recombinamers (ELRs), carrying a small peptide inhibitor of the protein kinase Akt, in both PANC-1 and patient-derived pancreatic cancer cells (PDX models). Nanoparticle cell uptake was measured by flow cytometry, and subcellular localization was determined by confocal microscopy, which showed a lysosomal localization of these nanoparticles. Furthermore, metabolic activity and cell viability were significantly reduced after incubation with nanoparticles carrying the Akt inhibitor in a time- and dose-dependent fashion. Self-assembling 73 ± 3.2 nm size nanoparticles inhibited phosphorylation and consequent activation of Akt protein, blocked the NF-κB signaling pathway, and triggered caspase 3-mediated apoptosis. Furthermore, in vivo assays showed that ELR-based nanoparticles were suitable devices for drug delivery purposes with long circulating time and minimum toxicity. Hence, the use of these smart nanoparticles could lead to the development of more effective treatment options for pancreatic cancer based on the inhibition of Akt

How Bulk Sensitive is Hard X-ray Photoelectron Spectroscopy: Accounting for the Cathode-Electrolyte Interface when Addressing Oxygen Redox.

Sensitivity to the "bulk" oxygen core orbital makes hard X-ray photoelectron spectroscopy (HAXPES) an appealing technique for studying oxygen redox candidates. Various studies have reported an additional O 1s peak (530-531 eV) at high voltages, which has been considered a direct signature of the bulk oxygen redox process. Here, we find the emergence of a 530.4 eV O 1s HAXPES peak for three model cathodes-Li2MnO3, Li-rich NMC, and NMC 442-that shows no clear link to oxygen redox. Instead, the 530.4 eV peak for these three systems is attributed to transition metal reduction and electrolyte decomposition in the near-surface region. Claims of oxygen redox relying on photoelectron spectroscopy must explicitly account for the surface sensitivity of this technique and the extent of the cathode degradation layer

Stent for Life in Portugal: This initiative is here to stay

AIMS: Portugal has one of the lowest rates of primary percutaneous coronary intervention (p-PCI) in Western Europe. This study assessed the progress of Portuguese p-PCI performance indicators one year after Portugal joined the Stent for Life (SFL) initiative. METHODS AND RESULTS: Two national surveys were carried out, each covering a period of one month: the first when Portugal joined the SFL in 2011 (Moment Zero), and the second one year later (Moment One). A total of 397 consecutive patients with probable ST-segment elevation myocardial infarction were enrolled (201 at Moment Zero and 196 at Moment One) from 15 centers. During this period, the number of patients who arrived at a local hospital without p-PCI decreased (62-47%; p=0.004) and transportation to a p-PCI hospital by the National Institute for Medical Emergencies (INEM) increased significantly (13-37%; p<0.001). Shorter times to revascularization were observed, due to shorter patient delay (118-102 min; p=0.008). Door-to-balloon delay and system delay remained unchanged. CONCLUSIONS: Improvements in performance indicators for p-PCI demonstrate the success of the first year of the local SFL plan, which was mainly focused on raising public awareness of the need to use the INEM emergency services, which has reduced patient delay, and on improving secondary transportation

Rationale, design, and analysis of combined Brazilian household budget survey and food intake individual data

<p>Abstract</p> <p>Background</p> <p>Data on food intake at the individual level and its statistical distribution in population groups defined by age, gender, or geographic areas are important in planning public health and nutrition programs. However, individual-based surveys in representative population samples are expensive to perform.</p> <p>Methods/Design</p> <p>In Brazil, an individual based survey is under consideration to be conducted alongside the household budget survey (HBS), which will be carried out in 2008–2009. This paper presents the methodological framework of dietary data collection and indicates the directions to combining both sources of data.</p> <p>The 2008–2009 Brazilian HBS sample will include 60,000 households. Of the selected HBS households, 30% will be randomly sampled to gather data on individual food intake. Therefore, individual dietary intake data is expected to be gathered for 70,000 individuals. Data collection procedures will comprise: completion of a diary with information regarding food purchases during a seven-day period; registration of all items consumed during two non-consecutive days for all 10 year-old or older members of the household. The sample will be large enough to capture the variation between individuals, and the two records will assure the estimation of the variation within individuals for food groups, energy and nutrients. Data on individual dietary intake and food family budget will be stratified by the five regions of the country and by rural or urban. A pilot study has been conducted in two states, and it indicated that combining individual and budgetary data in a survey is feasible.</p> <p>Discussion</p> <p>This kind of study will allow us to estimate correlations between individual intake and household purchases, overcoming the limitations of individual dietary surveys, and enhancing the HBS with information on eating out and intra-familiar distribution of food.</p

Effects of hydroxyapatite and PDGF concentrations on osteoblast growth in a nanohydroxyapatite-polylactic acid composite for guided tissue regeneration

The technique of guided tissue regeneration (GTR) has evolved over recent years in an attempt to achieve periodontal tissue regeneration by the use of a barrier membrane. However, there are significant limitations in the currently available membranes and overall outcomes may be limited. A degradable composite material was investigated as a potential GTR membrane material. Polylactic acid (PLA) and nanohydroxyapatite (nHA) composite was analysed, its bioactive potential and suitability as a carrier system for growth factors were assessed. The effect of nHA concentrations and the addition of platelet derived growth factor (PDGF) on osteoblast proliferation and differentiation was investigated. The bioactivity was dependent on the nHA concentration in the films, with more apatite deposited on films containing higher nHA content. Osteoblasts proliferated well on samples containing low nHA content and differentiated on films with higher nHA content. The composite films were able to deliver PDGF and cell proliferation increased on samples that were pre absorbed with the growth factor. nHA–PLA composite films are able to deliver active PDGF. In addition the bioactivity and cell differentiation was higher on films containing more nHA. The use of a nHA–PLA composite material containing a high concentration of nHA may be a useful material for GTR membrane as it will not only act as a barrier, but may also be able to enhance bone regeneration by delivery of biologically active molecules

First direct observation of Dirac fermions in graphite

Originating from relativistic quantum field theory, Dirac fermions have been recently applied to study various peculiar phenomena in condensed matter physics, including the novel quantum Hall effect in graphene, magnetic field driven metal-insulator-like transition in graphite, superfluid in 3He, and the exotic pseudogap phase of high temperature superconductors. Although Dirac fermions are proposed to play a key role in these systems, so far direct experimental evidence of Dirac fermions has been limited. Here we report the first direct observation of massless Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H in graphite, coexisting with quasiparticles with parabolic dispersion near another BZ corner K. In addition, we report a large electron pocket which we attribute to defect-induced localized states. Thus, graphite presents a novel system where massless Dirac fermions, quasiparticles with finite effective mass, and defect states all contribute to the low energy electronic dynamics.Comment: Nature Physics, in pres