Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra- or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular-targeted therapies, targeted radionuclide therapies and epigenetic modification-based therapies. These topics are trending headlines and their combination with cell-based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.     

Identification of key stabilizing interactions of amyloid-β oligomers based on fragment molecular orbital calculations on macrocyclic β-hairpin peptides

Analyzing the electronic states and inter-/intra-molecular interactions of amyloid oligomers expand our understanding of the molecular basis of Alzheimer's disease and other amyloid diseases. In the current study, several high-resolution crystal structures of oligomeric assemblies of Aβ-derived peptides have been studied by the ab initio fragment molecular orbital (FMO) method. The FMO method provides comprehensive details of the molecular interactions between the residues of the amyloid oligomers at the quantum mechanical level. Based on the calculations, two sequential aromatic residues (F19 and F20) and negatively charged E22 on the central region of Aβ have been identified as key residues in oligomer stabilization and potential interesting pharmacophores for preventing oligomer formation.     

Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on human blood lymphocytes

The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical and flow cytometry assessments, we demonstrated that addition of CHG at 1 μM concentration to human blood lymphocytes induced cytotoxicity following 6 h. The CHG‐induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species generation, mitochondrial membrane potential collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, CHG triggers oxidative stress and organelles damages in lymphocytes which are important cells in defense against foreign agents. Finally our findings suggest that using of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with CHG.     

Response surface optimized peroxyoxalate chemiluminescence of octahydro‐Schiff base derivative as new luminophor and study of the quenching effect of some cations,amino acids and cholesterol

We report the first detailed study of the characteristics of an octahydro‐Schiff base derivative as a new luminophor in the peroxyoxalate chemiluminescence (POCL) system. The effect of reagents on this new POCL system was investigated. In addition, the response surface methodology was used for evaluating the relative significance of variables in this POCL system, establishing models and determining optimal conditions. The quenching effect of some cations and compounds such as Cu²⁺, Fe³⁺, Hg²⁺, imidazole, histidine and cholesterol on an optimized POCL reaction were studied. The dynamic ranges were up to approximaterly 100 and 175 × 10^?6 M for Cu²⁺ and cholesterol respectively. The detection limits were 3.3 × 10^?6 m and 2.58 × 10^?6 m for Cu²⁺ and histidine, respectively. In all cases the relative standard deviations were 4–5% (n = 4). Copyright © 2014 John Wiley & Sons, Ltd.     

Mining the global diversity for bioenergy traits of barley straw: genomewide association study under varying plant water status

Cereal straws constitute a considerable source of biomass that can be used for bioenergy applications. Its composition is crucial for the energy value in biological or thermochemical conversion processes. Therefore, this study aimed at (i) exploring the global diversity in the composition of barley (Hordeum vulgare L.) straw; (ii) testing the effect of drought on straw composition; (iii) correlating compositional traits with energy value; and (iv) identifying loci associated with straw composition through genomewide association study (GWAS). A population of 179 barley accessions was grown in control and drought conditions, and straw was analyzed for thioglycolic acid lignin (TGAL), total phenolics (TP), carbon, crude protein (CP), C/N ratio, and ash. Substantial variability was observed in all traits. Moreover, drought treatment affected all traits leading to significant decreases in carbon, CP, ash, TGAL and TP concentrations, and a significant increase in C/N ratio. In vitro incubations in rumen fluid were used to estimate the energy value in biological energy conversion, while calorimetry was used to estimate the energy yield in thermochemical energy conversion. Thioglycolic acid lignin was singled out as the most influential trait determining energy value, as it was negatively correlated with the digestibility of organic matter and metabolizable energy in in vitro incubations, but positively correlated with gross energy measured by calorimetry. The GWAS yielded four loci significantly associated with TGAL irrespective of plant water status, which explained between 22.5% and 38.7% of the phenotypic variation. In addition, three loci significantly affected the response of TGAL to plant water status, and explained between 11.2% and 16.6% of the phenotypic variation. These loci contained plausible candidate genes that could be associated with lignin biosynthesis based on their annotations. In conclusion, this study illustrated great potential for the molecular breeding of barley varieties with enhanced straw quality for bioenergy applications.