Potential of mannan or dextrin nanogels as vaccine carrier/adjuvant systems

Polymeric nanogels have been sophisticatedly designed promising a new generation of vaccine delivery/adjuvant systems capable of boosting immune response, a strategic priority in vaccine design. Here, nanogels made of mannan or dextrin were evaluated for their potential as carriers/adjuvants in vaccine formulations. Since lymph nodes are preferential target organs for vaccine delivery systems, nanogels were biotin-labeled, injected in the footpad of rats, and their presence in draining lymph nodes was assessed by immunofluorescence. Nanogels were detected in the popliteal and inguinal lymph nodes by 24h upon subcutaneous administration, indicating entrapment in lymphatic organs. Moreover, the model antigen ovalbumin was physically encapsulated within nanogels and physicochemically characterized concerning size, zeta potential, ovalbumin loading, and entrapment efficiency. The immunogenicity of these formulations was assessed in mice intradermally immunized with ovalbuminmannan or ovalbumindextrin by determining ovalbumin-specific antibody serum titers. Intradermal vaccination using ovalbuminmannan elicited a humoral immune response in which ovalbumin-specific IgG1 levels were significantly higher than those obtained with ovalbumin alone, indicating a TH2-type response. In contrast, dextrin nanogel did not show adjuvant potential. Altogether, these results indicate that mannan nanogel is a material that should be explored as a future antigen delivery system.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by the Fundação para a Ciência e a Tecnologia (FCT) Portugal, post-doc grant SFRH/BPD/70524/2010 and the International Iberian Nanotechnology Laboratory (INL), PhD grant. The authors thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). The authors also acknowledge the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462)

Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calciumbinding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment

Knocking Down Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) Reverts Chemoresistance through Inactivation of Src and Bcr-Abl Proteins

The development of multidrug resistance (MDR) limits the efficacy of continuous chemotherapeutic treatment in chronic myelogenous leukemia (CML). Low molecular weight protein tyrosine phosphatase (LMW-PTP) is up-regulated in several cancers and has been associated to poor prognosis. This prompted us to investigate the involvement of LMW-PTP in MDR. In this study, we investigated the role of LMW-PTP in a chemoresistant CML cell line, Lucena-1. Our results showed that LMW-PTP is highly expressed and 7-fold more active in Lucena-1 cells compared to K562 cells, the non-resistant cell line. Knocking down LMW-PTP in Lucena-1 cells reverted chemoresistance to vincristine and imatinib mesylate, followed by a decrease of Src and Bcr-Abl phosphorylation at the activating sites, inactivating both kinases. On the other hand, overexpression of LMW-PTP in K562 cells led to chemoresistance to vincristine. Our findings describe, for the first time, that LMW-PTP cooperates with MDR phenotype, at least in part, through maintaining Src and Bcr-Abl kinases in more active statuses. These findings suggest that inhibition of LMW-PTP may be a useful strategy for the development of therapies for multidrug resistant CML

Molecular characterization of Giardia lamblia in children less than 5 years of age with diarrhoea attending the Bengo General Hospital, Angola

Introduction - Giardia lamblia is a pathogenic intestinal protozoan with high prevalence in developing countries, especially among children. Molecular characterization has revealed the existence of eight assemblages, with A and B being more commonly described in human infections. Despite its importance, to our knowledge, this is the first published molecular analysis of G. lamblia assemblages in Angola. Methods - The present study aimed to identify the assemblages of G. lamblia in children with acute diarrhoea presenting at the Bengo General Hospital, Angola. A stool sample was collected and microscopy and immunochromatographic tests were used. DNA was extracted and assemblage determination was performed through amplification of the gene fragment ssu-rRNA (175 bp) and β-giardin (511 bp) through polymerase chain reaction and DNA sequencing. Results - Of the 16 stool samples screened, 12 were successfully sequenced. Eleven isolates were assigned to assemblage B and one to assemblage A. Subassemblage determination was not possible for assemblage B, while the single isolate assigned to assemblage A was identified as belonging to subassemblage A3. Conclusion - This study provides information about G. lamblia assemblages in Bengo Province, Angola and may contribute as a first step in understanding the molecular epidemiology of this protozoan in the country. GenBank accession numbers for the ssur-RNA gene: MF479750, MF479751, MF479752, MF479753, MF479754, MF479755, MF479756, MF479757, MF479758, MF479759, MF479760, MF479761. GenBank accession numbers for the β-giardin gene: MF565378, MF565379, MF565380, MF565381.info:eu-repo/semantics/publishedVersio