Dysregulated genes targeted by microRNAs and metabolic pathways in bladder cancer revealed by bioinformatics methods.

The present study aimed to identify bladder cancer-associated microRNAs (miRNAs) and target genes, and further analyze the potential molecular mechanisms involved in bladder cancer. The mRNA and miRNA expression profiling dataset GSE40355 was downloaded from the Gene Expression Omnibus database. The Limma package in R was used to identify differential expression levels. The Human microRNA Disease Database was used to identify bladder cancer-associated miRNAs and Target prediction programs were used to screen for miRNA target genes. Enrichment analysis was performed to identify biological functions. The Database for Annotation, Visualization and Integration Discovery was used to perform OMIM_DISEASE analysis, and then protein-protein interaction (PPI) analysis was performed to identify hubs with biological essentiality. ClusterONE plugins in cytoscape were used to screen modules and the InterPro database was used to perform protein domain enrichment analysis. A group of 573 disease dysregulated genes were identified in the present study. Enrichment analysis indicated that the muscle organ development and vascular smooth muscle contraction pathways were significantly enriched in terms of disease dysregulated genes. miRNAs targets (frizzled class receptor 8, EYA transcriptional coactivator and phosphatase 4, sacsin molecular chaperone, calcium voltage-gated channel auxiliary subunit ß2, peptidase inhibitor 15 and catenin α2) were mostly associated with bladder cancer. PPI analysis revealed that calmodulin 1 (CALM1), Jun proto-oncogene, AP-1 transcription factor subunit (JUN) and insulin like growth factor 1 (IGF1) were the important hub nodes. Additionally, protein domain enrichment analysis indicated that the serine/threonine protein kinase active site was enriched in module 1 extracted from the PPI network. Overall, the results suggested that the IGF signaling pathway and RAS/MEK/extracellular signal-regulated kinase transduction signaling may exert vital molecular mechanisms in bladder cancer, and that CALM1, JUN and IGF1 may be used as novel potential therapeutic targets.

Preparations of hyperbranched polymer nano micelles and the pH/redox controlled drug release behaviors.

Hyperbranched polymer nano micelles (NMs) were prepared through a nucleophilic ring opening polymerization between cystamine and polyethylene glycol diglycidyl ether, followed by a reaction of amino groups and dimethyl maleic anhydride. The NMs showed spheric morphologies with hydrodynamic diameters of 106-120nm. Doxorubicin was loaded in the NMs with loading rate as high as 15.38wt%; The NMs possessed negative zeta potentials in aqueous solutions of pH7.4 due to the carboxyl ions on the particle surfaces, but the zeta potentials were converted to positive ones due to the hydrolysis of amide bonds at pH5.0-6.5, leading to the leaving of carboxyl groups and remaining of amino groups. The disulfide bonds in cystamine were designed in the hyperbranched polymer structures of the NMs, and bonds could be broken by a reducing agent l-glutathione (GSH) (10mM), resulting in a targeted drug release. The smart NMs displayed good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field.

Phytochemistry and pharmacological activities of the genus Prunella.

Prunella is a genus of perennial herbaceous plants in the Labiatae family. There are approximately 15 species worldwide, distributed widely in the temperate regions and tropical mountains of Europe and Asia. In the genus Prunella, P. vulgaris is the most studied, following a several thousand-year history as a traditional antipyretic and antidotal Chinese herb. Furthermore, since ancient times, P. vulgaris has been widely used as a cool tea ingredient and consumed as a vegetable. The genus Prunella contains triterpenoids and their saponins, phenolic acids, sterols and associated glycosides, flavonoids, organic acids, volatile oil and saccharides. Modern pharmacological studies have revealed that Prunella possess antiviral, antibacterial, anti-inflammatory, immunoregulatory, anti-oxidative, anti-tumor, antihypertensive and hypoglycemic functions. The active components related to these functions are mainly triterpenoids, phenolic acids, flavonoids and polysaccharides. This review mainly summarizes recent advances in traditional usage, chemical components and pharmacological functions.

Surface Charge Convertible and Biodegradable Synthetic Zwitterionic Nanoparticles for Enhancing Cellular Drug Uptake.

To enhance drug cellular uptake, a biodegradable terpolymer is synthesized using taurine, N,N-Bis (acryloyl) cystamine, and dodecylamine as raw materials by Michael addition terpolymerization. The terpolymer is transformed to zwitterionic nanoparticles (NPs) through self-assembly. The surface charge of the NPs is convertible from negative at pH 7.4 to positive at pH 6.5, which endows the NPs' excellent nonfouling feature in bloodstream and effective uptake in tumor cells. The NPs display varied morphologies from solid micelles to polymersomes and nanorods depending on molar ratios of the structural units involved. The NPs can be biodegraded in l-glutathione (GSH) solution due to the split of disulfide bonds in main chains of the terpolymers. The NPs demonstrate good pH/reducing responsiveness in drug delivery and can be potentially used as anticancer drug vehicles for enhancement of cellular uptake of anticancer drug.

A novel fluorescent biosensor for sequence-specific recognition of double-stranded DNA with the platform of graphene oxide.

A fluorescent biosensor for sequence-specific recognition of double-stranded DNA (dsDNA) was developed based upon the DNA hybridization between dye-labeled single-stranded DNA (ssDNA) and double-stranded DNA. The fluorescence of FAM-labeled single-stranded DNA was quenched when it adsorbed on the surface of graphene oxide (GO). Upon addition of the target dsDNA, a homopyrimidine·homopurine part of dsDNA on the Simian virus 40 (SV40) (4424-4440, gp6), hybridization occurred between the dye-labeled DNA and the target dsDNA, which induced the dye-labeled DNA desorbed from the surface of GO, and turned on the fluorescence of the dye. Under the optimum conditions, the enhanced fluorescence intensity was proportional to the concentration of target dsDNA in the range 40.0-260 nM, and the detection limit was found to be 14.3 nM alongside the good sequence selectivity.

An amperometric immunosensor based on an electrochemically pretreated carbon-paraffin electrode for complement III (C3) assay.

An electrochemical immunosensor based on the adsorption of anti-complement III antibody onto an electrochemical pretreated carbon-paraffin electrode has been proposed for the detection of complement III (C(3)). The competitive immunoassay format was adopted with horseradish peroxide-C(3) (HRP-C(3)) as a tracer, 3,3'5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide as the enzyme substrates. In order to measure the amount of HRP-C(3) binding onto the electrode surface, the product of the enzyme catalytic reaction was detected at 100 mV (vs. Ag/AgCl reference electrode). The system was optimized to realize a reliable determination of C(3) in the range of 0.06-10 microg/ml. It exhibits some advantages, such as simplicity of fabrication, rapidity of measurement, and satisfactory sensitivity and reproducibility.