Focused ultrasound-mediated bbb disruption is associated with an increase in activation of AKT: experimental study in rats

Background  

The Blood Brain Barrier (BBB) maintains the homeostasis of central nervous system by preventing the free passage of macromolecules from the systemic circulation into the brain. This normal physiological function of the BBB presents a challenge for delivery of therapeutic compounds into the brain. Recent studies have shown that the application of focused ultrasound together with ultrasound contrast agent (microbubbles) temporarily increases the permeability of the BBB. This effect is associated with breakdown of tight junctions, the structures that regulate the paracellular permeability of the endothelial cell layer. The influence of this ultrasound effect on the activation of intracellular signaling proteins is currently not well understood. Therefore, the aim of this study was to investigate the activation of cell survival signaling molecules in response to ultrasound-mediated BBB opening;     

Isolation and structure of a pseudopeptide gamma-L-glutamyl-L-aspartic acid from Datura stramonium that impairs learning retention in mice

Datura stramonium contains a compound that impairs learning retention in mice. It has been purified to homogeneity and its structure has been established as that of a gamma-L-glutamyl-L-aspartate. The biological activity of this pseudodipeptide has been found to be identical with that of the corresponding synthetic one. It has also been compared to those of various synthetic di- and tripeptides containing L- and/or D-enantiomers of the constitutive amino acids. The results show that the activity is associated with a peptidic structure containing only one type of enantiomer.     

Sleep disturbances and risk of sick leave: systematic review and meta-analysis

Sleep and Biological Rhythms - Sleep disturbances have multiple negative effects on psychological, social, and occupational aspects. The effects of sleep disturbances on the risk of taking sick...     

Antifeedant Properties of Destruxins and their Potential Use with the Entomogenous Fungus Metarhizium anisopliae for Improved Control of Crucifer Pests

Destruxins A, B and E, produced by the entomogenous fungus Metarhizium anisopliae, are insecticidal but comparatively low doses have antifeedant properties. Treatment of cabbage leaf discs with destruxins significantly reduced feeding by larvae of Plutella xylostella and Phaedon cochleariae in both choice and no-choice assays. The Antifeedant Index (AI) was dose related and there were significant differences between treated and untreated leaves. The AI and acute toxicity assays suggest that insect death was due to a combination of the starvation and toxicity effects of destruxins. In whole plant experiments, adults and larvae of P. cochleariae were found to be more susceptible to infection by M. anisopliae V245 if it was used in conjunction with a crude destruxin mixture. Destruxins drove larvae off the plant, irrespective of which leaf surface was treated. Adults could be forced to the adaxial or abaxial surface of leaves using the crude destruxin. Mortality was usually more consistent and generally greater if adults were forced to abaxial than adaxial surfaces inoculated with the fungus. High humidity on the abaxial surface favoured conidia germination and infection. Mortality was also greater for adults dusted with the pathogen and forced to the abaxial rather than to the adaxial leaf surface. The increased movement and starvation associated with destruxin treatment may also have stressed the insects making them more susceptible to infection.     

Maternal Urinary Iodine Concentration and Pregnancy Outcomes: Tehran Thyroid and Pregnancy Study

Biological Trace Element Research - Long-term use of hair dyes has potential effects on metal content in hair. However, little research dissects the specific distribution and composition variations...     

Longevity of Toxocara cati Larvae and Pathology in Tissues of Experimentally Infected Chickens

This study was conducted to determine the distribution patterns and duration of stay of Toxocara cati larvae in organs of chickens and to investigate chronic phase and potential zoonotic risk of toxocariasis in chickens. Chickens were orally infected with 1,000 embryonated T. cati eggs and necropsied 240 days post-infection. Organs of the chickens were examined at gross and microscopic levels; tissues were digested to recover larvae. Peribronchiolitis with infiltration of lymphocytes, and hyperplasia of bronchiolar associated lymphatic tissues (BALT) and goblet cells, were evident in the lungs of infected chickens. There were mild hemorrhages and infiltration of lymphocytes and a few eosinophils in the meninges. Larvae were recovered from 30% of the exposed chickens. Larvae recovery indicated that T. cati larvae stay alive for at least 240 days in the chicken brain. Therefore, chickens may potentially act as a paratenic host in nature and transfer T. cati larvae to other hosts.     

Spectroscopic,electrochemical, docking and molecular dynamics studies on the interaction of three oxovanadium (IV) Schiff base complexes with bovine serum albumin and their cytotoxicity against cancer

This study was designed to investigate the interaction of three oxovanadium (IV) Schiff base complexes with bovine serum albumin (BSA) by means of various spectroscopic and electrochemical methods along with molecular docking study and molecular dynamics simulations. Binding constants were estimated by fluorescence and UV-Vis spectroscopy. The results indicated a good affinity of the complexes for BSA in which furyl derivative had more activity. Molecular docking study showed that these complexes have the similar binding modes and located within subdomain IB in site III of BSA. The supporting of molecular docking and molecular dynamics results by experimental data, confirms the validity of the interactions data obtained by these methods. Biological activity against cancer cell showed that furyl derivative has higher activity than other complexes. Pharmaceutical analysis also showed that, these complexes potentially can be used as anticancer agents.     

Evaluation of Efficiency of Modified Polypropylenimine (PPI) with Alkyl Chains as Non-viral Vectors Used in Co-delivery of Doxorubicin and TRAIL Plasmid

In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations. PPI G5-Alkyl 30% indicated a decreased drug release may be due to alkyl chains on the surface of PPI, which serve as an additional hindrance for drug diffusion. In vitro cytotoxicity experiments demonstrated that co-delivery system induced apoptosis of tumor cells more efficiently than each of delivery system alone. Furthermore, these results revealed that our combined delivery platform of pTRAIL and DOX using Alkyl-modified PPI G5 can significantly improve the anti-tumor activity and this strategy might develop a new therapeutic window for cancer treatment.