Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Radiative Peristaltic Flow of Jeffrey Nanofluid with Slip Conditions and Joule Heating

Mixed convection peristaltic flow of Jeffrey nanofluid in a channel with compliant walls is addressed here. The present investigation includes the viscous dissipation, thermal radiation and Joule heating. Whole analysis is performed for velocity, thermal and concentration slip conditions. Related problems through long wavelength and low Reynolds number are examined for stream function, temperature and concentration. Impacts of thermal radiation, Hartman number, Brownian motion parameter, thermophoresis, Joule heating and slip parameters are explored in detail. Clearly temperature is a decreasing function of Hartman number and radiation parameter.     

Adsorption and immobilisation of human insulin on graphene monoxide,silicon carbide and boron nitride nanosheets investigated by molecular dynamics simulation

The adsorption and immobilisation of human insulin onto the bio-compatible nanosheets including graphene monoxide, silicon carbide and boron nitride nanosheets were studied by molecular dynamics simulation at the temperature of 310 K. After equilibration, heating and 100 ns production molecular dynamic runs, it was found that the insulin was adsorbed and immobilised onto the considered surfaces in a native folded state. The structural parameters, including root-mean-square deviation and fluctuation, surface accessible solvent area, radius of gyration (R_g) and the distance between the centre of the mass of immobilised protein and the surface of the considered nanosheets, were measured, analysed and discussed. The energetics of the studied systems such as the interaction energy between protein and nanosheet was also measured and addressed. The discussions were centred on the structural and energetic parameters of the protein and nanosheets, including charge density, hydrophobicity, hydrophilicity and residue polarity. The results also showed that the active site of C-termini of chain B played an important role in the adsorption process and this could be helpful in the protection of insulin in its smart delivery and release applications.     

The congenital cataract-causing mutations P20R and A171T are associated with important changes in the amyloidogenic feature,structure and chaperone-like activity of human αB-crystallin

Cataract is the major reason for human blindness worldwide. α-Crystallin, as a key chaperone of eye lenses, keeps the lenticular tissues in its transparent state over time. In this study, cataract-causing familial mutations, P20R and A171T, were introduced in CRYАB gene. After successful expression in Escherichia coli and subsequent purification, the recombinant proteins were subjected to extensive structural and functional analyses using various spectroscopic techniques, gel electrophoresis, and electron microscopy. The results of fluorescence and Raman assessments suggest important but discreet conformational changes in human αB-Cry upon these cataractogenic mutations. Furthermore, the mutant proteins exhibited significant secondary structural alteration as revealed by FTIR and Raman spectroscopy. An increase in conformational stability was seen in the human αB-Cry bearing these congenital cataractogenic mutations. The oligomeric size distribution and chaperone-like activity of human αB-Cry were significantly altered by these mutations. The P20R mutant protein was observed to loose most of the chaperone-like activity. Finally, these cataractogenic mutant proteins exhibited an increased propensity to form the amyloid fibrils when incubated under environmental stress. Overall, the structural and functional changes in mutated human αB-Cry proteins can shed light on the pathogenic development of congenital cataracts.     

cDNA sequence of the rat U snRNP-associated protein N: description of a potential Sm epitope.

Anti-Sm antibodies from a patient with systemic lupus erythematosus (SLE) were used to isolate cDNA clones encoding the snRNP-associated protein N from a rat brain derived cDNA library. The predicted primary structure of the 240 amino acid protein has a proline rich carboxyl terminus and shares a region of sequence similarity with other snRNP polypeptides, A and B/B'. Anti-Sm sera recognize a beta-galactosidase fusion protein containing only the carboxyl-terminal 80 amino acids of N; antibodies eluted from this fusion protein also react with A, B/B' and N on immunoblots, suggesting that these proteins share an Sm epitope located within this segment. Polyclonal antibodies raised against a 23 amino acid synthetic peptide derived from this conserved region of N recognize A, N and B/B' on immunoblots and can immunoprecipitate the Sm class of U snRNAs. These results confirm that this sequence defines a potential Sm epitope. RNA blotting analyses demonstrate that a 1.6 kb mRNA expressed predominantly in brain encodes the N polypeptide in both rats and humans. At low stringency rat N cDNA also hybridizes to a 1.3 kb mRNA species which encodes B/B', suggesting that N is structurally related to, but distinct from B/B'. Although B/B' proteins are thought to be expressed in all human cells, only N and B, but not B', are observed on immunoblots of human brain proteins probed with anti-Sm sera. The apparent difference in the complement of proteins associated with snRNP particles in human brain versus elsewhere suggests a possible mechanism for the regulation of brain-specific mRNA splicing.     

Cyclopiazonic acid in combination with aflatoxins,zearalenone and ochratoxin A in Indonesian corn

The mycotoxin, cyclopiazonic acid (CPA), was detected at concentrations as high as 9 ppm in 21 of 26 corn samples from a Bogor poultry feedmill. This is the first demonstration of the natural occurrence of CPA in Indonesia. CPA was always accompanied by other mycotoxins, especially aflatoxins, suggesting that the interactive toxicity of these mycotoxins to poultry should be investigated.     

Functional expression and CNS distribution of a beta-alanine-sensitive neuronal GABA transporter.

The synaptic action of gamma-aminobutyric acid (GABA) is terminated by high affinity, Na(+)-dependent transport processes in both neurons and glia. We have isolated a novel GABA transporter cDNA, GAT-B, which encodes a high affinity (Km = 2.3 microM), Na(+)- and Cl(-)-dependent GABA transport protein that is potently blocked by beta-alanine, a compound generally considered a selective inhibitor of glial transport. However, in situ hybridization studies indicate that GAT-B mRNA is expressed predominantly within neurons. These data indicate that the neuronal-glial distinction of GABA transporters based on inhibitor sensitivities must be reconsidered and suggest a greater diversity of GABA transporters than has been predicted by previous pharmacologic studies.     

Intracellular protein trafficking defects in human disease

Secretory proteins and integral membrane proteins travel through the secretory pathway to a variety of destinations. Their targets are often specified by signals in the amino acid sequence or signals added post-translationally. The KDEL sequence that retains soluble proteins in the endoplasmic reticulum and the mannose 6-phosphate group of lysosomal enzymes are well-characterized examples of targeting signals; other signals are less well understood. Given the complexity and importance of the intracellular trafficking pathways, it is perhaps not surprising that mutations that affect the trafficking of proteins are associated with some human genetic diseases.