Pluronic polymer capped biocompatible mesoporous silica nanocarriers

A facile self-assembly method is described to prepare PEGylated silica nanocarriers using hydrophobic mesoporous silica nanoparticles and a pluronic F127 polymer. Pluronic capped nanocarriers revealed excellent dispersibility in biological media with cyto- and blood compatibilities. © 2013 The Royal Society of Chemistry

Inhibition of Akt signaling in hepatoma cells induces apoptotic cell death independent of Akt activation status

Cataloged from PDF version of article.The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is involved in cell survival and anti-apoptotic signaling. Akt has been shown to be constitutively expressed in a variety of human tumors including hepatocellular carcinoma (HCC). In this report we analyzed the status of Akt pathway in three HCC cell lines, and tested cytotoxic effects of Akt pathway inhibitors LY294002, Wortmannin and Inhibitor VIII. In Mahlavu human hepatoma cells Akt was constitutively activated, as demonstrated by its Ser473 phosphorylation, downstream hyperphosphorylation of BAD on Ser136, and by a specific cell-free kinase assay. In contrast, Huh7 and HepG2 did not show hyperactivation when tested by the same criteria. Akt enzyme hyperactivation in Mahlavu was associated with a loss of PTEN protein expression. Akt signaling was inhibited by the upstream kinase inhibitors, LY294002, Wortmannin, as well as by the specific Akt Inhibitor VIII in all three hepatoma cell lines. Cytotoxicity assays with Akt inhibitors in the same cell lines indicated that they were all sensitive, but with different IC50 values as assayed by RT-CES. We also demonstrated that the cytotoxic effect was through apoptotic cell death. Our findings provide evidence for its constitutive activation in one HCC cell line, and that HCC cell lines, independent of their Akt activation status respond to Akt inhibitors by apoptotic cell death. Thus, Akt inhibition may be considered as an attractive therapeutic intervention in liver cancer. © Springer Science+Business Media, LLC 2010

Angiogenic Peptide Nanofibers Improve Wound Healing in STZ-Induced Diabetic Rats

Low expressions of angiogenic growth factors delay the healing of diabetic wounds by interfering with the process of blood vessel formation. Heparin mimetic peptide nanofibers can bind to and enhance production and activity of major angiogenic growth factors, including VEGF. In this study, we showed that heparin mimetic peptide nanofibers can serve as angiogenic scaffolds that allow slow release of growth factors and protect them from degradation, providing a new therapeutic way to accelerate healing of diabetic wounds. We treated wounds in STZ-induced diabetic rats with heparin mimetic peptide nanofibers and studied repair of full-thickness diabetic skin wounds. Wound recovery was quantified by analyses of re-epithelialization, granulation tissue formation and blood vessel density, as well as VEGF and inflammatory response measurements. Wound closure and granulation tissue formation were found to be significantly accelerated in heparin mimetic gel treated groups. In addition, blood vessel counts and the expressions of alpha smooth muscle actin and VEGF were significantly higher in bioactive gel treated animals. These results strongly suggest that angiogenic heparin mimetic nanofiber therapy can be used to support the impaired healing process in diabetic wounds. © 2016 American Chemical Society

Screening and selection of novel animal probiotics isolated from bovine chyme

Probiotics, gut-colonizing microorganisms capable of conferring a number of health benefits to their hosts, are highly desirable as animal feed supplements. Members of the Gram-positive genus Bacillus are often utilized as probiotics, since endospores formed by those bacteria render them highly resistant to environmental extremes and therefore capable of surviving gastrointestinal tract conditions. In this study, 84 distinct bacterial colonies were obtained from bovine chyme and 29 isolates were determined as Bacillus species. These isolates were principally screened for their antimicrobial activity against a group of two Gram-positive and fourGram-negative bacteria, including known human and animal pathogens such as Salmonella enterica, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Seven strains displaying strong antimicrobial activity against the test cohort were further evaluated for other properties desirable from animal probiotics, including high spore-forming capacity and adhesiveness, resistance to pH extremes and ability to form biofilms. The isolates were found to resist simulated gastrointestinal conditions and most of the antibiotics tested. In addition, plasmid presence was checked and cytotoxicity tests were performed to evaluate the potential risks of antibiotic resistance transfer and unintended pathogenic effects on host, respectively. We propose that the bacterial isolates are suitable for use as animal probiotics. © Springer-Verlag Berlin Heidelberg and the University of Milan 2012

Designing an intracellular fluorescent probe for glutathione: Two modulation sites for selective signal transduction

A selective probe for glutathione was designed and synthesized. The design incorporates spatial and photophysical constraints for the maximal emission signal. Thus, pHs, as well as the intracellular thiol concentrations, determine the emission signal intensity through a tight control of charge-transfer and PeT processes. The probe works satisfactorily inside the human breast adenocarcinoma cells, highlighting GSH distribution in the cytosol. © 2014 American Chemical Society

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

p53Psi is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state

Although much is known about the underlying mechanisms of p53 activity and regulation, the factors that influence the diversity and duration of p53 responses are not well understood. Here we describe a unique mode of p53 regulation involving alternative splicing of the TP53 gene. We found that the use of an alternative 3' splice site in intron 6 generates a unique p53 isoform, dubbed p53Psi. At the molecular level, p53Psi is unable to bind to DNA and does not transactivate canonical p53 target genes. However, like certain p53 gain-of-function mutants, p53Psi attenuates the expression of E-cadherin, induces expression of markers of the epithelial-mesenchymal transition, and enhances the motility and invasive capacity of cells through a unique mechanism involving the regulation of cyclophilin D activity, a component of the mitochondrial inner pore permeability. Hence, we propose that p53Psi encodes a separation-of-function isoform that, although lacking canonical p53 tumor suppressor/transcriptional activities, is able to induce a prometastatic program in a transcriptionally independent manner

Cytotoxic and bioactive properties of different color tulip flowers and degradation kinetic of tulip flower anthocyanins

This study was conducted to determine the potential use of anthocyanin-based extracts (ABEs) of wasted tulip flowers as food/drug colorants. For this aim, wasted tulip flowers were samples and analyzed for their bioactive properties and cytotoxicity. Total phenolic contents of the extracts of the claret red (126.55. mg of gallic acid equivalent (GAE)/g dry extract) and orange-red (113.76. mg GAE/g dry extract) flowers were the higher than those of the other tulip flowers. Total anthocyanin levels of the violet, orange-red, claret red and pink tulip flower extracts were determined as 265.04, 236.49, 839.08 and 404.45. mg pelargonidin 3-glucoside/kg dry extract, respectively and these levels were higher than those of the other flowers. The extracts were more effective for the inhibition of Listeria monocytogenes, Staphylococcus aureus and Yersinia enterocolitica compared to other tested bacteria. Additionally, the cytotoxic effects of five different tulip flower extracts on human breast adenocarcinoma (MCF-7) cell line were investigated. The results showed that the orange red, pink and violet extracts had no cytotoxic activity against MCF-7 cell lines while yellow and claret red extracts appeared to be toxic for the cells. Overall, the extracts of tulip flowers with different colors possess remarkable bioactive and cytotoxic properties. © 2013 Elsevier Ltd

VERITAS Search for VHE Gamma-ray Emission from Dwarf Spheroidal Galaxies

Indirect dark matter searches with ground-based gamma-ray observatories provide an alternative for identifying the particle nature of dark matter that is complementary to that of direct search or accelerator production experiments. We present the results of observations of the dwarf spheroidal galaxies Draco, Ursa Minor, Bootes 1, and Willman 1 conducted by VERITAS. These galaxies are nearby dark matter dominated objects located at a typical distance of several tens of kiloparsecs for which there are good measurements of the dark matter density profile from stellar velocity measurements. Since the conventional astrophysical background of very high energy gamma rays from these objects appears to be negligible, they are good targets to search for the secondary gamma-ray photons produced by interacting or decaying dark matter particles. No significant gamma-ray flux above 200 GeV was detected from these four dwarf galaxies for a typical exposure of ~20 hours. The 95% confidence upper limits on the integral gamma-ray flux are in the range 0.4-2.2x10^-12 photons cm^-2s^-1. We interpret this limiting flux in the context of pair annihilation of weakly interacting massive particles and derive constraints on the thermally averaged product of the total self-annihilation cross section and the relative velocity of the WIMPs. The limits are obtained under conservative assumptions regarding the dark matter distribution in dwarf galaxies and are approximately three orders of magnitude above the generic theoretical prediction for WIMPs in the minimal supersymmetric standard model framework. However significant uncertainty exists in the dark matter distribution as well as the neutralino cross sections which under favorable assumptions could further lower the limits.Comment: 21 pages, 2 figures, updated to reflect version published in ApJ. NOTE: M.D. Wood added as autho