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Abstract: Chitosan, a cationic polysaccharide, has been widely employed as dietary supplement and in pharmacological and biomedical applications. Although numerous studies have focused on its applications as pharmaceutical excipients or bioactive reagents, molecular weight (MW)-dependent pharmaceutical and bioactive properties remain unclear. As a preliminary study, we investigated the MW-dependent Caco-2 cell layer transport phenomena (in vitro) and intestinal absorption patterns after oral administration (in vivo) of water-soluble chitosans (WSCs). The absorption of chitosan was significantly influenced by its MW. As the MW increases, the absorption decreases. Compared to high-MW chitosan (WSC 230K, MW=230 kDa), absorption profiles were observed to increase more than 23 and 25 times with WSC 3.8K (MW=3.8 kDa) in both in vitro and in vivo transport experiments, respectively. Furthermore, the chitosans showed concentration- and MW-dependent cytotoxic effects, and the chitosan oligosaccharides (MW<10 kDa) showed negligible cytotoxic effect on the Caco-2 cells. In consideration with safety and absorption profiles, chitosan oligosaccharides may be considered as safe and potential candidates for pharmaceutical and biomedical applications. [Copyright &y& Elsevier]

The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for α v β 3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated. In particular, a study of the endocytic mechanism revealed processes of microtubule-dependent macropinocytosis and clathrin-mediated endocytosis. Furthermore, the PEI/WSC copolymer with a dendrimer RGD peptide (four-branched RGD moiety) as a targeting moiety suppressed the growth of a solid tumor mass in vivo mouse xenograft model generated with PC3 prostate tumor cells by silencing BCL2 mRNA. This result indicated RGD/PEI/WSC copolymer for a good candidate as a simple and biocompatible gene carrier. [ABSTRACT FROM AUTHOR]

Recent advancements in gene delivery systems that specifically target a variety of cancer types have increased demand for tissue-specific gene therapy. The current study describes the synthesis of a copolymer (GPgWSC) composed of a polyethylenimine (PEI)-grafted water-soluble chitosan (WSC) and gambogic acid (GA). It was validated as a ligand capable of enabling targeted attachment to transferrin receptors in HCT116 cancer cell lines. GPgWSC demonstrated superior antitumor activity in vitro in HCT116 compared to LoVo or MCF-7 cell lines, facilitated by the apoptotic activity of psiRNA-hBCL2. Pre-incubation of transferrin significantly inhibited GFP expression in the GPgWSC polyplex, demonstrating that GA is an extremely effective transferrin receptor targeting molecule. Additionally, in the HCT116-bearing mouse model, the tumor mass of PBS-treated mice increased to 2270 mm2 after 22 days, but the injection of GPgWSC polyplex significantly reduced the mass-increasing rate as a mass size of 248 mm2. [ABSTRACT FROM AUTHOR]

Abstract: The object of this study was to test the solubility of a methoxy poly(ethylene glycol) (MPEG)-grafted chitosan copolymer in organic solvents and aqueous solution. Water-soluble chitosan with low molecular weight (LMWSC) was used in a PEG-graft copolymerization. The MPEG was conjugated to chitosan using 4-dicyclohexylcarbodimide (DCC), and N-hydroxysuccimide (NHS). Introduction of PEG was confirmed by 1H and 13C NMR spectroscopy and FT-IR spectroscopy. The degree of substitution (DS) of MPEG into chitosan was calculated from 1H NMR data and also by estimating the molecular weight (MW) using gel permeation chromatography (GPC). The DS values obtained from 1H NMR spectroscopy and GPC were similar, indicating that MPEG-grafted LMWSC was synthesized and properly characterized. Furthermore, the introduction of PEG into chitosan increases the solubility in aqueous solutions over a range of pH values (4.0–11.0) and organic solvents such as DMF, DMSO, ethanol, and acetone. [Copyright &y& Elsevier]

Abstract Background It remains an open question whether plant phloem sap proteins are functionally involved in plant defense mechanisms. Methods The antifungal effects of two profilin proteins from Arabidopsis thaliana , AtPFN1 and AtPFN2, were tested against 11 molds and 4 yeast fungal strains. Fluorescence profiling, biophysical, and biochemical analyses were employed to investigate their antifungal mechanism. Results Recombinant AtPFN1 and AtPFN2 proteins, expressed in Escherichia coli , inhibited the cell growth of various pathogenic fungal strains at concentrations ranging from 10 to 160 μg/mL. The proteins showed significant intracellular accumulation and cell-binding affinity for fungal cells. Interestingly, the AtPFN proteins could penetrate the fungal cell wall and membrane and act as inhibitors of fungal growth via generation of cellular reactive oxygen species and mitochondrial superoxide. This triggered the AtPFN variant-induced cell apoptosis, resulting in morphological changes in the cells. Conclusion PFNs may play a critical role as antifungal proteins in the Arabidopsis defense system against fungal pathogen attacks. General significance The present study indicates that two profilin proteins, AtPFN1 and AtPFN2, can act as natural antimicrobial agents in the plant defense system. Highlights • Arabidopsis thaliana profilins, AtPFN1 and AtPFN2, exhibit antifungal activities. • The mechanism of fungal growth inhibition involves intracellular generation of ROS. • The AtPFN proteins induce cell apoptosis in cultures of diverse fungal pathogens. • The profilins may act as natural antimicrobial agents in the plant defense system. [ABSTRACT FROM AUTHOR]

Highlights: [•] Protective effect of phlorotannins from Ecklonia cava was investigated in vitro and in vivo. [•] Protective effects were determined via cell death and oxidative stress in zebra fish embryo. [•] Phlorotannins possess a protective effect against ethanol-induced apoptosis in liver cell. [ABSTRACT FROM AUTHOR]

Abstract: To develop chitosan based efficient gene carriers, highly purified chitosan oligosaccharides (COSs) were chemically modified with deoxycholic acid (DOCA). Owing to the amphiphilic characters, the DOCA-conjugated COSs (COSDs) formed self-aggregated nanoparticles in aqueous milieu. The physicochemical characterization revealed that the particle size of the nanoparticles was in the range of 200∼240 nm and the critical aggregation concentration (cacs) was 0.012∼0.046 g/L, depending on the degree of substitution (DS). As efficient gene carriers, the COSD nanoparticles showed superior gene condensation and protection of condensed gene from endonuclease attack than unmodified COSs. Furthermore, COSDs showed great potential for gene carrier with the high level of gene transfection efficiencies, even in the presence of serum. Considered with the negligible cytotoxic effects, DOCA-modified chitosan oligosaccharides can be considered as potential candidates for efficient non-viral gene carriers. [Copyright &y& Elsevier]