Holmgaardgadegaard8111

Despite a very active research in the field of nanomedicine, only a few nano-based drug delivery systems have reached the market. The "death valley" between research and commercialization has been partially attributed to the limited characterization and reproducibility of the nanoformulations. Our group has previously reported the potential of a peptide-based nanovaccine candidate for the prevention of SIV infection in macaques. This vaccine candidate is composed of chitosan/dextran sulfate nanoparticles containing twelve SIV peptide antigens. The aim of this work was to rigorously characterize one of these nanoformulations containing a specific peptide, following a quality-by-design approach. The evaluation of the different quality attributes was performed by several complementary techniques, such as dynamic light scattering, nanoparticle tracking analysis, and electron microscopy for particle size characterization. The inter-batch reproducibility was validated by three independent laboratories. Finally, the long-term stability and scalability of the manufacturing technique were assessed. Overall, these data, together with the in vivo efficacy results obtained in macaques, underline the promise this new vaccine holds with regard to its translation to clinical trials. Graphical abstract.Bevacizumab (as other monoclonal antibodies) has now become a mainstay in the treatment of several cancers in spite of some limitations, including poor tumour penetration and the development of resistance mechanisms. Its nanoencapsulation may be an adequate strategy to minimize these problems. The aim of this work was to evaluate the efficacy of bevacizumab-loaded nanoparticles (B-NP-PEG) on a xenograft model of human colorectal cancer. For this purpose, human serum albumin nanoparticles were prepared by coacervation, then coated with poly(ethylene glycol) and freeze-dried. B-NP-PEG displayed a mean size of about 300 nm and a bevacizumab loading of approximately 145 μg/mg. An in vivo study was conducted in the HT-29 xenograft model of colorectal cancer. Both, free and nanoencapsulated bevacizumab, induced a similar reduction in the tumour growth rate of about 50%, when compared to controls. By microPET imaging analysis, B-NP-PEG was found to be a more effective treatment in decreasing the glycolysis and metabolic tumour volume than free bevacizumab, suggesting higher efficacy. These results correlated well with the capability of B-NP-PEG to increase about fourfold the levels of intratumour bevacizumab, compared with the conventional formulation. In parallel, B-NP-PEG displayed six-times lower amounts of bevacizumab in blood than the aqueous formulation of the antibody, suggesting a lower incidence of potential undesirable side effects. In summary, albumin-based nanoparticles may be adequate carriers to promote the delivery of monoclonal antibodies (i.e. bevacizumab) to tumour tissues. Graphical abstract.An indirect aptamer-based SERS assay for insulin-like growth factor 2 receptor (IGF-IIR) protein was developed. The gold substrate and silver nanoparticles (AgNPs) were employed simultaneously to achieve double enhancement for SERS signals. Firstly, the five commercial SERS substrates including Enspectr, Ocean-Au, Ocean-AG, Ocean-SP and Q-SERS substrates were evaluated using 4-mercaptobenzoic acid (4-MBA). The Q-SERS substrate was selected based on low relative standard deviation (RSD, 8.6%) and high enhancement factor (EF, 8.7*105), using a 785 nm laser. The aptamer for IGF-IIR protein was designed to include two sequences one grafted on gold substrate to specifically capture the IGF-IIR protein and a second one forming a 3' sticky bridge to capture SERS nanotags. The SERS nanotag was composed by AgNPs (20 nm), 4-MBA and DNA probes that can hybridize with the aptamer. Due to the steric-hindrance effect, when the aptamer doesn't combine with IGF-IIR protein, it only can capture the SERS nanotags. Therefore, there was a negative correlation between the concentration of IGF-IIR protein and the intensity of 4-MBA at 1076 cm-1. The detection limit reached to 141.2 fM and linear range was from 10 pM to 1 μM. The SERS aptasensor also exhibits a high reproducibility with an average RSD of 4.5%. The interference test was conducted with other four proteins to verify the accuracy of measuring. The study provides an approach to quantitative determination of proteins based on specific recognition and nucleic acid hybridization of aptamers, to establish sandwich structure for SERS enhancement. Graphical abstractSchematic representation of surface-enhanced Raman scattering (SERS) assay on insulin-like growth factor 2 receptor (IGF-IIR) protein by combining the aptamer modified gold substrate and 4-mercaptobenzoic acid (4-MBA) and DNA probe modified silver nanoparticles.BACKGROUND Over the past few decades, DNA microarray technology has emerged as a prevailing process for early identification of cancer subtypes. Several feature selection (FS) techniques have been widely applied for identifying cancer from microarray gene data but only very few studies have been conducted on distributing the feature selection process for detecting cancer subtypes. OBJECTIVE Not all the gene expressions are needed in prediction, this research article objective is to select discriminative biomarkers by using distributed FS method which helps in accurately diagnosis of cancer subtype. Traditional feature selection techniques have several drawbacks like unrelated features that could perform well in terms of classification accuracy with a suitable subset of genes will be left out of the selection. METHOD To overcome the issue, in this paper a new filter-based method for gene selection is introduced which can select the highly relevant genes for distinguishing tissues from the gene expression dataset. In addition, it is used to compute the relation between gene-gene and gene-class and simultaneously identify subset of essential genes. Our method is tested on Diffuse Large B cell Lymphoma (DLBCL) dataset by using well-known classification techniques such as support vector machine, naïve Bayes, k-nearest neighbor, and decision tree. RESULTS Results on biological DLBCL dataset demonstrate that the proposed method provides promising tools for the prediction of cancer type, with the prediction accuracy of 97.62%, precision of 94.23%, sensitivity of 94.12%, F-measure of 90.12%, and ROC value of 99.75%. CONCLUSION The experimental results reveal the fact that the proposed method is significantly improved classification accuracy and execution time, compared to existing standard algorithms when applied to the non-partitioned dataset. Furthermore, the extracted genes are biologically sound and agree with the outcome of relevant biomedical studies.BACKGROUND There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. RESULTS Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. CONCLUSIONS Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities.The sex pheromone of the avocado moth Stenoma catenifer Walsingham has potential use in the detection of S. catenifer males in the Antillean race avocado in Chiapas, Mexico, although the study of local parameters that influence its effectiveness is required. In this study, trap type, trap height, pheromone release rate and duration of pheromone activity were evaluated to determine the effectiveness of this pheromone in field conditions in the Antillean race avocado crops of the coast of Chiapas, Mexico. The results obtained indicate that the capture of moths with the traps Pherocon III (delta type) and Pherocon 1C (wing type) was higher than that with the boat-type traps. The frequency of capture of S. catenifer males was higher when the traps were placed 4 and 6 m above ground level than that when they were 2 m high. The septum releases 85% of the amount of pheromone during the first 4 weeks, and there were no differences between the number of moth captures during the first 3 weeks, only between the fourth and the first 2 weeks. Our results suggest that the efficiency of the pheromone in Antillean race avocado depends on trap placement height and type as well as on the time of use of the pheromone septum.Genome-wide identification, together with gene expression patterns and promoter region analysis of FYVE and PHOX proteins in Physcomitrella patens, emphasized their importance in regulating mainly developmental processes in P. patens. Phosphatidylinositol 3-phosphate (PtdIns3P) is a signaling phospholipid, which regulates several aspects of plant growth and development, as well as responses to biotic and abiotic stresses. The mechanistic insights underlying PtdIns3P mode of action, specifically through effector proteins have been partially explored in plants, with main focus on Arabidopsis thaliana. In this study, we searched for genes coding for PtdIns3P-binding proteins such as FYVE and PHOX domain-containing sequences from different photosynthetic organisms to gather evolutionary insights on these phosphoinositide binding domains, followed by an in silico characterization of the FYVE and PHOX gene families in the moss Physcomitrella patens. Phylogenetic analysis showed that PpFYVE proteins can be grouped in 7 subclasses, with an additional subclass whose FYVE domain was lost during evolution to higher plants. On the other hand, PpPHOX proteins are classified into 5 subclasses. selleck Expression analyses based on RNAseq data together with the analysis of cis-acting regulatory elements and transcription factor (TF) binding sites in promoter regions suggest the importance of these proteins in regulating stress responses but mainly developmental processes in P. patens. The results provide valuable information and robust candidate genes for future functional analysis aiming to further explore the role of this signaling pathway mainly during growth and development of tip growing cells and during the transition from 2 to 3D growth. These studies would identify ancestral regulatory players undertaken during plant evolution.