Molecular imaging of cell death in vivo by a novel small molecule probe

Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo

Bioanalytical Application of SERS Immunoassay for Detection of Prostate-Specific Antigen

We demonstrate the possible application of the sandwich type surface-enhanced Raman scattering (SEES) immunoassay using antigen-antibody binding for detection of prostate-specific antigen (PSA) in cancer cells. In this sandwich type of SERS immunoassay, to capture antigens onto the immobilized layer of antibodies on the gold substrate we prepared the monolayer of gold nanoparticles on the A PTMS-derivatized surface of a glass slide by using the SAM technique. This sandwich type of SERS immunoassay in which antigens on the substrate specifically capture antibodies on a Raman reporter (DSNB coated gold nanoparticles with R6G) could successfully detect PSA at low levels. A strong SERS spectrum of Raman reporter was observed only with a substrate in which PSA is present.X111815sciescopuskc

Characteristics of PVdF copolymer/Nafion blend membrane for direct methanol fuel cell (DMFC)

For direct methanol fuel cell, blends of vinylidene fluoride- hexafluoropropylene copolymer (P(VdF-co-HFP)) and Nafion were prepared the different equivalent weight of Nafion. The investigations of the blend morphology were performed by means of permeability test, uptake measurement, differential-scanning calorimetry (DSC), and scanning electron microscopy. In the blend membranes, many pores were created as the content of Nafion in blend increased. Then, the methanol uptake was sharply increased. But the methanol permeability was not sharply increased because the methanol permeation through blend membranes is diffusion-controlled process. The methanol permeability of N10 (low equivalent weight) series was similar to that of N11 series (high equivalent weight). The proton conductivity of N10 series was around one and a half times higher than that of N11 series. The cell performance of the blend was much enhanced when the equivalent weight of Nafion was 1000.close576

Anti-methicillin-resistant Staphylococcus aureus (MRSA) substance from the marine bacterium Pseudomonas sp. UJ-6

A multivalent approach to discover a novel antibiotic substance against methicillin-resistant Staphylococcus aureus (MRSA), a marine bacterium, UJ-6, exhibiting an antibacterial activity against MASA was isolated from seawater. The isolated strain was identified to be Pseudomonas sp. by the morphology, biochemical, and genetical analyses. The ethyl acetate extract of Pseudomonas sp. 133-6 culture showed significant ant-MRSA activity. Bioassay-guided isolation of the extract using a growth inhibitory assay led to the isolation and identification of an active compound exhibiting anti-MRSA activity. Based on the analyses of the physicochemical and spectroscopic data including nuclear magnetic resonance and mass, the compound was identified to be 1-acetyl-beta-carboline. The minimum inhibitory concentration (MIC) of the compound was determined to be in a range of 32-128 mu g/ml against MRSA strains. The MIC values against MRSA were superior or equal to those of other natural compounds such as catechins, suggesting that 1-acetyl-beta-carboline would be a good candidate in applications of the treatment of MRSA infection. (C) 2012 Elsevier B.V. All rights reserved.1199sciescopu

Systemic PEGylated TRAIL Treatment Ameliorates Liver Cirrhosis in Rats by Eliminating Activated Hepatic Stellate Cells

Liver fibrosis is a common outcome of chronic liver disease that leads to liver cirrhosis and hepatocellular carcinoma. No US Food and Drug Administration-approved targeted antifibrotic therapy exists. Activated hepatic stellate cells (aHSCs) are the major cell types responsible for liver fibrosis; therefore, eradication of aHSCs, while preserving quiescent HSCs and other normal cells, is a logical strategy to stop and/or reverse liver fibrogenesis/fibrosis. However, there are no effective approaches to specifically deplete aHSCs during fibrosis without systemic toxicity. aHSCs are associated with elevated expression of death receptors and become sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. Treatment with recombinant TRAIL could be a potential strategy to ameliorate liver fibrosis; however, the therapeutic application of recombinant TRAIL is halted due to its very short half-life. To overcome this problem, we previously generated PEGylated TRAIL (TRAIL(PEG)) that has a much longer half-life in rodents than native-type TRAIL. In this study, we demonstrate that intravenous TRAILPEG has a markedly extended half-life over native-type TRAIL in nonhuman primates and has no toxicity in primary human hepatocytes. Intravenous injection of TRAILPEG directly induces apoptosis of aHSCs in vivo and ameliorates carbon tetrachloride-induced fibrosis/cirrhosis in rats by simultaneously down-regulating multiple key fibrotic markers that are associated with aHSCs. Conclusion: TRAIL-based therapies could serve as new therapeutics for liver fibrosis/cirrhosis and possibly other fibrotic diseases.111510sciescopu