Serum VEGF Predicts Clinical Improvement Induced by Cerebrolysin Plus Donepezil in Patients With Advanced Alzheimer's Disease.

Serum vascular endothelial growth factor (VEGF) increases with Alzheimer's disease (AD) severity and may prevent cognitive decline. However, information on the influence of AD drug therapy on circulating VEGF is limited. This study assessed changes in serum VEGF levels and its association with clinical and functional responses in mild to moderate AD patients who were treated with Cerebrolysin, donepezil, or the combined therapy in a randomized, controlled trial. Treatment with Cerebrolysin plus donepezil reduced elevated serum VEGF levels and improved functioning and cognition significantly compared with donepezil alone in patients with advanced AD, and treatment differences were more pronounced in patients with higher VEGF levels. Our results indicate that the combined therapy reversed the increase of serum VEGF in advanced AD, which was associated with cognitive and functional responses, particularly in patients with high baseline VEGF.

Using IC-Tagging Methodology for Production and Purification of Epitope-Loaded Protein Microspheres for Vaccination.

Particulate material is more efficient in eliciting immune responses. Here we describe the production of microspheres formed by protein muNS-Mi from avian reoviruses, loaded with foreign epitopes by means of IC-Tagging, for their use as vaccines.

VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi microspheres elicit a protective immune response in IFNAR(-/-) mice.

Vaccination is critical for controlling the spread of bluetongue virus (BTV). The inactivated BTV vaccines that are now being used in Europe are effective in preventing outbreaks of BTV but secondary effects associated to repetitive inoculation of aluminum-containing adjuvants and the need to develop safer, cross-reactive, and more efficacious vaccines with differential diagnostic capability have re-stimulated the interest in developing improved vaccination strategies against BTV. We have engineered a subunit BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 incorporated into avian reovirus (ARV) muNS-Mi microspheres (MS-VP2/MS-VP7/MS-NS1). IFNAR(-/-) mice immunized with MS-VP2/MS-VP7/MS-NS1 without adjuvant generated significant levels of neutralizing antibodies specific to BTV-4. In addition, vaccination stimulated specific T cell responses, predominantly CD4+, against the virus. Immunized mice were fully protected against a homologous challenge with a lethal dose of BTV-4 and partially cross-protected against a heterologous challenge with a lethal dose of BTV-1. These results support MS-VP2/MS-VP7/MS-NS1 as a promising subunit vaccine candidate against multiple serotypes of BTV as well as the use of microspheres as an alternative delivery method with potent intrinsic adjuvant activity.

IC-tagged proteins are able to interact with each other and perform complex reactions when integrated into muNS-derived inclusions.

We have recently developed a versatile tagging system (IC-tagging) that causes relocation of the tagged proteins to ARV muNS-derived intracellular globular inclusions. In the present study we demonstrate (i) that the IC-tag can be successfully fused either to the amino or carboxyl terminus of the protein to be tagged and (ii) that IC-tagged proteins are able to interact between them and perform complex reactions that require such interactions while integrated into muNS inclusions, increasing the versatility of the IC-tagging system. Also, our studies with the DsRed protein add some light on the structure/function relationship of the evolution of DsRed chromophore.