Exposure to Anacardiaceae Volatile Oils and Their Constituents Induces Lipid Peroxidation within Food-Borne Bacteria Cells

The chemical composition of the volatile oils from five Anacardiaceae species and their activities against Gram positive and negative bacteria were assessed. The peroxidative damage within bacterial cell membranes was determined through the breakdown product malondialdehyde (MDA). The major constituents in Anacardium humile leaves oil were (E)-caryophyllene (31.0%) and α-pinene (22.0%), and in Anacardium occidentale oil they were (E)-caryophyllene (15.4%) and germacrene-D (11.5%). Volatile oil from Astronium fraxinifolium leaves were dominated by (E)-β-ocimene (44.1%) and α-terpinolene (15.2%), whilst the oil from Myracrodruon urundeuva contained an abundance of δ-3-carene (78.8%). However, Schinus terebinthifolius leaves oil collected in March and July presented different chemical compositions. The oils from all species, except the one from A. occidentale, exhibited varying levels of antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Oil extracted in July from S. terebinthifolius was more active against all bacterial strains than the corresponding oil extracted in March. The high antibacterial activity of the M. urundeuva oil could be ascribed to its high δ-3-carene content. The amounts of MDA generated within bacterial cells indicate that the volatile oils induce lipid peroxidation. The results suggest that one putative mechanism of antibacterial action of these volatile oils is pro-oxidant damage within bacterial cell membrane explaining in part their preservative properties.     

Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors

New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl) piperazin-1-yl)acetyl)indoline-2,3-dione (IIId) was found to be the most potent.     

A multi-pH-dependent, single optical mesosensor/captor design for toxic metals

The fabrication of low-cost, simple nanodesigns with sensing/capture functionality has been called into question by the toxicity and non-degradability of toxic metals, as well as the persistent threat they pose to human lives. In this study, a single, pH-dependent, mesocaptor/sensor was developed for the optical and selective removal of toxic ions from drinking water and physiological systems such as blood.     

Free radical scavenging, antimicrobial and immunomodulatory activities of Orthosiphon stamineus

Orthosiphon stamineus is considered an important traditional folk medicine. In this study ethanol and aqueous extracts of O. stamineus were evaluated in vitro for their antioxidant, antimicrobial as well as for their immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). The DPPH radical scavenging method was used for the determination of antioxidant activity, while the antibacterial efficacy was investigated by both disc diffusion method and Minimum Inhibitory Concentration (MIC) against four bacterial strains (Gram-positive and Gram-negative). Furthermore, the immunomodulatory potential of the extracts was investigated through the MTT assay. Aqueous extract of O. stamineus exhibited significant free radical scavenging activity with IC?? 50 9.6 μg/mL, whereas the IC?? for the ethanol extract was 21.4 μg/mL. The best antimicrobial activity was shown by the aqueous extract of O. stamineus against Staphylococcus aureus, with inhibition zone of 10.5 mm and MIC value 1.56 mg/mL. Moreover, the results observed from the MTT assay showed that both plant extracts stimulated the PBMCs proliferation in vitro in a concentration-dependent manner, but the aqueous extract has remarkable activity against PBMCs. These findings indicate that O. stamineus showed high antioxidant activity and may be considered as an immunomodulatory agent.     

Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo

Special (lipid) delivery: The role of the ionizable lipid pK(a) in the in?vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.5. The most potent cationic lipid from this study has ED(50) levels around 0.005?mg?kg(-1) in mice and less than 0.03?mg?kg(-1) in non-human primates.     

A New Method to Study Hawking Radiation from the Kerr-Newman-NUT Black Hole

Following Hamilton-Jacobi method, we have investigated the Hawking radiation of Kerr-Newman-NUT black hole. We have considered the spacetime background dynamical and incorporate the self-gravitation effect of the emitted particles when energy conservation and angular momentum conservation are taken into account. We have found that the emission rate at the event horizon is equal to the difference of Bekenstein-Hawking entropy before and after emission.     

Photophysical properties of a surfactive long-chain styryl merocyanine dye as fluorescent probe

This work deals with detailed investigations of the photophysical properties of a styryl merocyanine dye, namely 1-cetyl-4-[4′-(methoxy) styryl]-pyridinium bromide (CMSPB) of molecular rotor type. The solvatochromic analyses of the data in different solvents using the Kamlet-Taft parameters (α, β, π^?) were discussed. Optical excitation of the studied merocyanine dye populates a CT S₁ state with about 22.64 folds higher dipole moment value relative to that in the S₀ state. Moreover, the effect of solvent viscosity (glycerol at various temperatures (299.0–351.0 K)) on CMSPB fluorescent properties is analyzed to understand the molecular mechanisms of the characteristic increase in CMSPB fluorescence intensity. The results indicate that CMSPB exhibits fluorescent properties typical for molecular rotors. The results show that torsional relaxation dynamics of molecular rotors in high-viscosity solvents cannot be described by the simple stick boundary hydrodynamics defined by the Debye–Stokes–Einstein (DSE) equation. The fluorescence depolarization behavior in glycerol at various temperatures (299.0–351.0 K) shows that the molecular rotational diffusion is controlled by the free volume of the medium. Furthermore, excited state studies in ethanol/chloroform mixture revealed the formation of weak complex with chloroform of stoichiometry 1:1 with formation constant of 0.004l mol^?1. Moreover, the increase of the quantum yield values in micellar solutions of CTAB and SDS relative to that of water indicates that the guest dye molecules are microencapsulated into the hydrophobic interior of host micelle. The obtained non-zero values of fluorescence polarization in micellar solution imply reduced rotational depolarization of dye molecules via association with the surfactant. Upon comparing the spectral data in micelles with those in homogeneous solvent systems, more can be learned of the structural details of the micellar environment, which have often been used as models for more complex bioaggregates. The results point out to a possible use of this dye as a fluorescence probe for microenvironmental parameters as well as in some micellar systems.     

Dependence of magnetic properties and microstructure of mechanically alloyed Ni0.5Zn0.5Fe2O4 on soaking time

Possible soaking-time effects on the magnetic and microstructural properties of polycrystalline samples of Ni_0.5Zn_0.5Fe₂O₄ have been studied. Nanosize powder produced by mechanical alloying was sintered at 800 °C with various soaking times. All samples showed the signature peak of Ni_0.5Zn_0.5Fe₂O₄ even with one hour of soaking time. The size distributions show a slow growth of microstructural evolution related to density, porosity and also to the magnetic hysteresis loops. Within these distributions it is observed that the formation of multi-domains is not possible and probably there are the regions of superparamagnetic and single-domain grains. From the permeability studies, it is believed that the rise of the magnetic moment on the B sites give rise to the total saturation magnetization with increase of soaking time. The hysteresis loop of one-hour soaking time showed paramagnetic behavior dominating while longer soaking times showed ferromagnetic behavior starting to dominate. The coercivity was observed to increase with soaking time, signaling the increase of the anisotropy fields which was attributed to the shape anisotropy and also to the magnetocrystalline anisotropy. By correlating the morphology, phase analysis, permeability and hysteresis loops results, it is believed that there was an increase in number of crystalline-growth regions which together formed a total mass of mixed superparamagnetic and ferromagnetic grains with the latter starting to dominate the samples.     

Silent, fluorescent labeling of native neuronal receptors

We have developed a minimally-perturbing strategy that enables labeling and subcellular visualization of endogenous dendritic receptors on live, wild-type neurons. Specifically, calcium-permeable non-NMDA glutamate receptors expressed in hippocampal neurons can be targeted with this novel synthetic tri-functional molecule. This ligand-directed probe was targeted towards AMPA receptors and bears an electrophilic group for covalent bond formation with an amino acid side chain on the extracellular side of the ion channel. This molecule was designed in such a way that the use-dependent, polyamine-based ligand accumulates the chemically-reactive group at the extracellular side of these polyamine-sensitive receptors, thereby allowing covalent bond formation between an electrophilic moiety on the nanoprobe and a nucleophilic amino acid sidechain on the receptor. Bioconjugation of this molecule results in a stable covalent bond between the nanoprobe and the target receptor. Subsequent photolysis of a portion of the nanoprobe may then be employed to effect ligand release allowing the receptor to re-enter the non-liganded state, all the while retaining the fluorescent beacon for visualization. This technology allows for rapid fluorescent labeling of native polyamine-sensitive receptors and further advances the field of fluorescent labeling of native biological molecules.     

The discovery of small-molecule mimicking peptides through phage display

Using peptides to achieve the functional and structural mimicry of small-molecules, especially those with biological activity or clear biotechnological applications, has great potential in overcoming difficulties associated with synthesis, or unfavorable physical properties. Combinatorial techniques like phage display can aid in the discovery of these peptides even if their mechanism of mimicry is not rationally obvious.The major focus of this field has been limited to developing biotin and sugar mimetics. However, the full "mimicry" of these peptides has not yet been fully established as some bind to the target with a different mechanism than that of the natural ligand and some do not share all of the natural ligand's binding partners. In this article, mimicry of small-molecules by phage display-discovered peptides is reviewed and their potential in biochemical and medical applications is analyzed.