Dipeptidyl alpha-fluorovinyl Michael acceptors: synthesis and activity against cysteine proteases

The synthesis of novel dipeptidyl alpha-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8DeltaCTE) revealed low biological activity. Relative rates of Michael additions of 2'-(phenethyl)thiol with vinyl sulfone and alpha-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.     

Peptide-conjugated gold nanorods for nuclear targeting

Resonant electron oscillations on the surface of noble metal nanoparticles (Au, Ag, Cu) create the surface plasmon resonance (SPR) that greatly enhances the absorption and Rayleigh (Mie) scattering of light by these particles. By adjusting the size and shape of the particles from spheres to rods, the SPR absorption and scattering can be tuned from the visible to the near-infrared region (NIR) where biologic tissues are relatively transparent. Further, gold nanorods greatly enhance surface Raman scattering of adsorbed molecules. These unique properties make gold nanorods especially attractive as optical sensors for biological and medical applications. In the present work, gold nanorods are covalently conjugated with a nuclear localization signal peptide through a thioalkyl-triazole linker and incubated with an immortalized benign epithelial cell line and an oral cancer cell line. Dark field light SPR scattering images demonstrate that nanorods are located in both the cytoplasm and nucleus of both cell lines. Single cell micro-Raman spectra reveal enhanced Raman bands of the peptide as well as molecules in the cytoplasm and the nucleus. Further, the Raman spectra reveal a difference between benign and cancer cell lines. This work represents an important step toward both imaging and Raman-based intracellular biosensing with covalently linked ligand-nanorod probes.     

Compost alleviates the negative effects of salinity via up-regulation of antioxidants in Solanum lycopersicum L. plants

The aim of this study was to investigate the effectiveness of compost in alleviating the negative impacts of salinity on tomato (Solanum lycopersicum cv. Hybrid Guardian F1) plants. An experiment was performed to evaluate the response of plants to compost addition to soil at a rate of 55 g kg^?1 soil and NaCl salinity at 0, 50, 100 mM. The results obtained showed a significant decrease in growth-related parameters, i.e. shoot- and root-fresh weight (FW), fruit FW, and fruit yield. Meanwhile, salinity resulted in a significant increase of Na⁺, electrolyte leakage, lipid peroxidation and hydrogen peroxide in the leaves, but a decrease of N, P, S, K⁺, Ca²⁺ and Mg²⁺ level, as well as K⁺/Na⁺ ratio in a dose dependent manner. Under these conditions compost nullified the above negative impacts of salinity caused by 50 mM NaCl and to some extent at 100 mM NaCl. The salinity mediated enhancement in biomarkers of oxidative stress was considerably decreased by compost application which increased the level of ascorbate (ASC) and glutathione (GSH) and the ratios of ASC/dehydroascorbate (DHA) and GSH/glutathione disulfide, as well as the activities of ASC peroxidase, monodehydroascorbate reductase, DHA reductase and GSH reductase in NaCl-treated plants, implying a better reactive oxygen species scavenging system. Data also indicated that compost application resulted in higher activities of leaf carbonic anhydrase, ribulose bisphosphate carboxylase, nitrate reductase and adenosine triphosphate-sulfurylase. These findings collectively suggest that compost plays a pivotal role in inducing salinity tolerance via enhancing an efficient antioxidant system and key C, N and S assimilatory enzymes.     

Mutations in c4orf26, encoding a Peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta

Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.     

Imparting permanent antimicrobial activity onto viscose and acrylic fabrics

Viscose and acrylic fabrics were aminated to enhance metal chelation of Cu, Zn and Ni for the purpose of imparting fabrics antimicrobial activity against Escherichia coli and Staphylococcus aureus. Fabrics were firstly epoxidized using epichlorohydrin prior amination. Optimization of the reaction conditions, e.g., temperature, medium pH, amine type and metal type and their concentrations, are reported. Aminated fabrics of viscose and acrylic were shown to be viable for chelation with divalent metal cations. The overall results revealed that antibacterial resistance of metalized aminated fabrics that the activity trend of metals is in the order Cu-complex>Zn-complex>Ni-complex with regard to fighting of microorganisms and permanent even after 10 washing. Reaction mechanism of epoxidation, amination and metal chelation of fabrics are offered supported by FT-IR structural study, nitrogen content and atomic absorption spectroscopy.     

Antiandrogen gold nanoparticles dual-target and overcome treatment resistance in hormone-insensitive prostate cancer cells

Prostate cancer is the most commonly diagnosed cancer among men in the developed countries. (1) One in six males in the U.S. (2) and one in nine males in the U.K. (3) will develop the disease at some point during their lifetime. Despite advances in prostate cancer screening, more than a quarter of a million men die from the disease every year (1) due primarily to treatment-resistance and metastasis. Colloidal nanotechnologies can provide tremendous enhancements to existing targeting/treatment strategies for prostate cancer to which malignant cells are less sensitive. Here, we show that antiandrogen gold nanoparticles-multivalent analogues of antiandrogens currently used in clinical therapy for prostate cancer-selectively engage two distinct receptors, androgen receptor (AR), a target for the treatment of prostate cancer, as well as a novel G-protein coupled receptor, GPRC6A, that is also upregulated in prostate cancer. These nanoparticles selectively accumulated in hormone-insensitive and chemotherapy-resistant prostate cancer cells, bound androgen receptor with multivalent affinity, and exhibited greatly enhanced drug potency versus monovalent antiandrogens currently in clinical use. Further, antiandrogen gold nanoparticles selectively stimulated GPRC6A with multivalent affinity, demonstrating that the delivery of nanoscale antiandrogens can also be facilitated by the transmembrane receptor in order to realize increasingly selective, increasingly potent therapy for treatment-resistant prostate cancers.     

Testosterone,gonadotropins and androgen receptor during spermatogenesis of Biomphalaria alexandrina snails (Pulmonata: Basommatophora)

Endocrine regulation of reproductive processes of the snail Biomphalaria alexandrina is poorly recognized. Thus, the aims of the study were: (1) to acquire histological images of the ovotestis; (2) to determine the hemolymph concentrations of testosterone (T) and gonadotropic hormones (luteinizing hormone: LH and follicle stimulating hormone: FSH), (3) to demonstrate androgen receptor (AR) immunolocalization in the ovotestis, and (4) to show LH and FSH protein expression in cerebral ganglia of small (diameter shell: 4–6 mm), medium (7–11 mm) and large (12–16 mm) B. alexandrina snails. These three groups represented different reproductive stages of the snail. The AR immunoexpression was found in the periphery and inside the acini of small (immature) snails as well as in spermatocytes, spermatids, Sertoli cells, the interstitial cells and the acinus lining epithelium of medium (mature) snails. Low AR immunoexpression was demonstrated in the interstitial cells of large (aged) snails. The neurons at the periphery of the cerebral ganglia and connective sheath of the ganglia showed a positive FSH and LH immunostaining. T concentration in the hemolymph was higher in medium snails than in small and large snails. In contrast, LH concentration was higher in medium snails than in small and large snails. These data suggests that gonadotropins and T play a role in the gonadal development in B. alexandrina.     

Non-phenolic antioxidant compounds from Buddleja asiatica

The methanol extract of the leaves of Buddleja asiatica Lour. (Loganiaceae) showed antioxidant activity toward the well known in vitro antioxidant tests such as total antioxidant capacity by the phosphomolybdenum method, free radical scavenging activity by the 1,1-diphenyl-2-picrylhydrazyl scavenging assay (DPPH assay) and hydrogen peroxide scavenging methods. Due to the high scavenging activity of the n-butanol successive fraction toward DPPH and H2O2 (SC50 = 11.99 and 18.54 microg/ml, respectively), this extract was subjected to chromatographic separation and isolation. Four non-phenolic compounds were isolated and identified on the basis of spectroscopic and chemical analyses: 1-O-beta-D-glucopyranosyl-2-methoxy-3-(2-hydroxy-triaconta-3,12-dienoate)-glycerol (1), 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-[beta-D-glucopyranosyl-(1-->2)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3 beta,23,28-triol (2), 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-beta-D-fucopyranosyl-olean-11,13(18)-diene-3,23,28-triol (3), and 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)]-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl-acid-olean-11,13(18)-diene-3 beta,23,28-triol (4). The four compounds were evaluated as antioxidant agents using the three antioxidant bioassay tests.     

Polyvinyl pyridine metal complex as permanent antimicrobial finishing for viscose fabric

Viscose fabrics were treated with polyvinyl pyridine (PVP) using padding technique, followed by oxidation with hydrogen peroxide or peracetic acid, which was prepared by the reaction of tetra acetyl ethylene diamine (TAED) with hydrogen peroxide. Peracetic acid gives higher oxidation of PVP than hydrogen peroxide. FTIR study proved the formation of N-oxide as a result of oxidation. Incorporation of copper and silver ion onto oxidized PVP was also proved by FTIR. The antimicrobial study emphasise that Cu/oxidized PVP and Ag/oxidized PVP have retarded the growth of bacteria significantly, and Ag/oxidized PVP has a far better biocidal activity. The antibacterial activity of both metal ions survived after washing 10 times.