Preferential Killing of Cancer Cells and Activated Human T-Cells Using ZnO Nanoparticles

Here we disclose the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (-28-35X) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. The novel findings of cell selective toxicity towards potential disease causing cells indicate a potential utility of ZnO nanoparticle in the treatment of cancer and/or autoimmunity

Fluorescent Particles Comprising Nanoscale ZnO Layer and Exhibiting Cell-Specific Toxicity

Multifunctional smart nanostructures are disclosed that include fluorescein isothiocyanate (FITC)-encapsulated SiO2 core-shell particles with a nanoscale ZnO finishing layer, wherein an outer ZnO layer is formed on the SiO2-FITC core. These ~200 nm sized particles showed promise toward cell imaging and cellular uptake studies using the bacterium Escherichia coli and Jurkat cancer cells, respectively. The FITC encapsulated ZnO particles demonstrated excellent selectivity in preferentially killing Jurkat cancer cells with minimal toxicity to normal primary immune cells (18% and 75% viability remaining, respectively, after exposure to 60 μg/mL) and inhibited the growth of both gram-positive and gram-negative bacteria at concentrations .gtoreq.250-500 μg/mL (for Staphylococcus aureus and Escherichia coli, respectively). These results indicate that the FITC encapsulated multifunctional particles with nanoscale ZnO surface layer can be used as smart nanostructures for particle tracking, cell imaging, antibacterial treatments and cancer therapy

Comprehensive Control of Optical Polarization Anisotropy in Semiconducting Nanowires

The demonstration of strong photoluminescence polarization anisotropy in semiconducting nanowires embodies both technological promise and scientific challenge. Here we present progress on both fronts through the study of the photoluminescence polarization anisotropy of randomly oriented nanowire ensembles in materials without/with crystalline anisotropy, small/wide bandgap, and both III-V/II-VI chemistry (InP/ZnO nanowires, respectively). Comprehensive control of the polarization anisotropy is realized by dielectric matching with conformally deposited Ta2O5 (dielectric ratios of 9.6:4.41 and 4.0:4.41 for InP and ZnO, respectively). After dielectric matching, the polarization anisotropy of the nanowire ensembles is reduced by 86% for InP:Ta2O5 and 84% for ZnO:Ta2O5

Synthesis, spectral characterization, anti-bacterial, cytotoxic evaluation and docking studies of new urea and thiourea derivatives

Isoniazid is one of the main API’s used in the combination treatment of tuberculosis recommended by the WHO. Urea and its derivatives are an important class of heterocyclic compounds that possess a wide range of therapeutic and pharmacological properties, while thiourea is an organosulphur compound in that it resembles urea except that the atom oxygen has been replaced by a Sulphur atom, but the properties of urea and thiourea are significantly different. The current work concerns the synthesis of a new class of urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates in the presence of trimethylamine. The IR and NMR spectral data were performed for the urea and thiourea derivatives of the compounds [(3c & 3f) & (3d & 3e)], respectively. Molecular docking studies of the compounds (3a-h) revealed the binding mode involved in the active site of DNA gyrase. The synthesized urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates were tested for their antibacterial activity against gram-positive and gram-negative bacteria using the “disc diffusion method”. Of all compounds tested, the urea derivatives (3a &3d), the thiourea derivatives (3e & 3g) showed more potent activity than the other compounds. The MTT assay revealed concentration dependent cytotoxic effects over a concentration range 25-200 µg/mL

Growth and insect assays of Beauveria bassiana with neem to test their compatibility and synergism

Beauveria bassiana is being used as a biopesticide for many insect pests. Neem oil (azadirachtin) is an eco-safe popular botanical pesticide. A biopesticde with a neem compatible isolate of B. bassiana will enable their simultaneous use in pest management. A sample of 30 isolates of B. bassiana from culture collections was screened for compatibility with a commercial formulation of neem oil (Margoside®) at the field recommended dose (0.3%, v/v). Compatibility was tested in vitro through germination and growth assays. In all isolates, conidial germination was delayed but not significantly decreased by neem. In the growth assays, 23 isolates were found compatible with neem. In the neem sensitive isolates, growth was decreased but not totally inhibited. The effect of combined treatment with B. bassiana and neem in comparison to single treatments with either of them on Spodoptera litura was tested in laboratory bioassays. The combined treatment was found to have synergistic effect on insect mortality when a B. bassiana isolate compatible with neem was used, while, with an isolate sensitive to neem, an antagonistic effect was observed

Identification of Stage-Specific Breast Markers using Quantitative Proteomics

YesMatched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Cyprus Research Promotion Foundation, Yorkshire Cancer Researc

Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy

Background: The stress reaction induced by surgery and associated pain may be detrimental for patient recovery and should be minimized. The neuropeptide chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in humans. Little is known about CGA and its derived peptides, catestatin (CST) and vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for stress and pain behavior in dogs before and after ovariohysterectomy. Methods: Thirty healthy privately owned female dogs admitted for elective ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior VAS, and stress behavior VAS were recorded and saliva and blood samples were collected before surgery, 3h after extubation, and once at recall 7–15 days after surgery. Dogs were premedicated with morphine and received carprofen as analgesia for 7 days during the postoperative period. Results: At 3h after extubation, CMPS-SF and pain behavior VAS scores had increased (p<0.0001) and stress behavior VAS scores, temperature, respiratory rate (p<0.0001), plasma CST concentrations (p=0.002) had decreased significantly compared to before surgery. No significant differences were observed in the subjective and physiological parameters between before surgery and at recall, but plasma CST (p=0.04) and serum cortisol (p=0.009) were significantly lower at recall. Plasma VS, saliva CST, and heart rate did not differ significantly at any observed time. Conclusion: Study parameters for evaluating surgery-induced stress and pain changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS usefulness as pain biomarkers, studies on dogs in acute painful situations are warranted