Classification of protein binders in artist's paints by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry: an evaluation of principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA)

Proteomics techniques are increasingly applied for the identification of protein binders in historical paints. The complex nature of paint samples, with different kinds of pigments mixed into, and degradation by long term exposure to light, humidity and temperature variations, requires solid analysis and interpretation methods. In this study matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectra of tryptic-digested paint replicas are subjected to principal component analysis (PCA) and soft independent modelling of class analogy (SIMCA) in order to distinguish proteinaceous binders based on animal glues, egg white, egg yolk and milk casein from each other. The most meaningful peptide peaks for a given protein class will be determined, and if possible, annotated with their corresponding amino acid sequence. The methodology was subsequently applied on egg temperas, as well as on animal glues from different species. In the latter small differences in the MALDI-TOF mass spectra can allow the determination of a mammal or sturgeon origin of the glue. Finally, paint samples from the 16(th) century altarpiece of St Margaret of Antioch (Mlynica, Slovakia) were analysed. Several expected peaks are either present in lower abundance or completely missing in these natural aged paints, due to degradation of the paints. In spite of this mammalian glue was identified in the St Margaret samples.     

Newly Synthesized Thymol Derivative and Its Effect on Colorectal Cancer Cells

Thymol affects various types of tumor cell lines, including colorectal cancer cells. However, the hydrophobic properties of thymol prevent its wider use. Therefore, new derivatives (acetic acid thymol ester, thymol β-D-glucoside) have been synthesized with respect to hydrophilic properties. The cytotoxic effect of the new derivatives on the colorectal cancer cell lines HT-29 and HCT-116 was assessed via MTT assay. The genotoxic effect was determined by comet assay and micronucleus analysis. ROS production was evaluated using ROS-Glo™ H₂O₂ Assay. We confirmed that one of the thymol derivatives (acetic acid thymol ester) has the potential to have a cyto/genotoxic effect on colorectal cancer cells, even at much lower (IC₅₀~0.08 μg/mL) concentrations than standard thymol (IC₅₀~60 μg/mL) after 24 h of treatment. On the other side, the genotoxic effect of the second studied derivative—thymol β-D-glucoside was observed at a concentration of about 1000 μg/mL. The antiproliferative effect of studied derivatives of thymol on the colorectal cancer cell lines was found to be both dose- and time-dependent at 100 h. Moreover, thymol derivative-treated cells did not show any significantly increased rate of micronuclei formation. New derivatives of thymol significantly increased ROS production too. The results confirmed that the effect of the derivative on tumor cells depends on its chemical structure, but further detailed research is needed. However, thymol and its derivatives have great potential in the prevention and treatment of colorectal cancer, which remains one of the most common cancers in the world.     

The Last Fortress of Tin's Tyranny – Protodenitration of Nitroalkanes

Protodenitration, a direct reduction of nitroalkanes to corresponding alkanes, already spans two centuries and is enabled by various reagents. This mini-review provides a historical development of the fundamental transformation and highlights the governing position of the Ono-Tanner reaction employing tributyltin hydride. Due to the unchallenged dominance of the toxic tributyltin hydride and environmentally unpopular solvents sharply contrasting with modern ecological trends, the current situation was dubbed “the last fortress of tin's tyranny.”     

Performance in (Ultra-)high-performance liquid chromatography—How to qualify and optimize instruments in practice

This paper investigates the suitability of an ultra-high-performance liquid chromatography/high-performance liquid chromatography hybrid system for ultra-high-performance liquid chromatography applications. Thus, the effect of extra column band broadening, the gradient system, and the injection system were tested and optimized according to their capabilities. An increase of the theoretical plate number up to a factor of two is achieved by the optimization of the extra column volume into the typical ultra-high-performance liquid chromatography range (<10 μl). Moreover, for qualitative purposes injections of volumes typical for ultra-high-performance liquid chromatography methods are precise. Despite this, a lack of precision and accuracy was determined for the gradient system, and the dwell volume meets the typical specification range for conventional HPLC systems. Therefore, hybrid systems are the intercept between both spectra and are limitedly suitable for ultra-high-performance liquid chromatography applications. Another way to approximate ultra-high-performance liquid chromatography performance using a high-performance liquid chromatography system is superficially porous particles. Thus, H/u curves of 5 μm superficially porous and 3 μm fully porous particles were recorded in order to determine the effect of the particle technology resulting in comparable performance of the used stationary phases.     

Engineered Lipid Nanoparticles for the Treatment of Pulmonary Fibrosis by Regulating Epithelial-Mesenchymal Transition in the Lungs

Pulmonary fibrosis is a chronic and irreversible lung disease with limited therapeutic regimens. Advances in elucidating the pathophysiological mechanism and discovering novel therapeutic interventions are still in urgent need. Here, the engineered lipid nanoparticles (LNPs) are developed for delivering RNA therapeutics to the lungs. Three different types of LNPs (native, cationic, and ligand incorporated) are optimized to facilitate the pulmonary delivery of RNAs. Among them, the mannose incorporated LNPs (Mannose LNPs) outperform the others and show efficient delivery of siRNAs down-regulating the epithelial-mesenchymal transition (EMT) associated protein, G2 and S phase-expressed protein 1 (GTSE1). Treatment with the mannose LNPs confirms a significant decrease in collagen accumulation and EMT-related proteins in the fibrosis animal models and provides functional recovery from pulmonary fibrosis. This approach demonstrates that engineered LNPs can facilitate the delivery of RNA therapeutics to the lungs and potentially open a new regimen of treatment for pulmonary fibrosis.