The Influence of Circadian Rhythm on the Activity of Oxidative Stress Enzymes

The circadian system synchronizes daily with the day–night cycle of our environment. Disruption of this rhythm impacts the emergence and development of many diseases caused, for example, by the overproduction of free radicals, leading to oxidative damage of cellular components. The goal of this study was to determine the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione transferase (GST), glutathione reductase (R-GSSG), and the concentration of glutathione (GSH) in the circadian rhythm. The study group comprised 66 healthy volunteers (20–50 years; 33 women; 33 men). The blood was collected at 2, 8 a.m., and 2, 8 p.m. All samples marked the serum melatonin concentration to confirm the correct sleeping rhythm and wakefulness throughout the day. The activity of study enzymes and the concentration of GSH were measured by the spectrophotometric method. Confirmed the existence of circadian regulation of oxidative stress enzymes except for GST activity. The peak of activity of study enzymes and GSH concentration was observed at 2 a.m. The increased activity of enzymes and the increase in GSH concentration observed at night indicate that during sleep, processes allowing to maintain of the redox balance are intensified, thus limiting the formation of oxidative stress.     

Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspase-8, HSP60, and p53. These results demonstrate the effectiveness of AD-O51.4 protein in CRC preclinical models and identify the potential mechanism underlying acquired resistance. Progression of AD-O51.4 to clinical trials is expected.     

Central Apparatus,the Molecular Kickstarter of Ciliary and Flagellar Nanomachines

Motile cilia and homologous organelles, the flagella, are an early evolutionarily invention, enabling primitive eukaryotic cells to survive and reproduce. In animals, cilia have undergone functional and structural speciation giving raise to typical motile cilia, motile nodal cilia, and sensory immotile cilia. In contrast to other cilia types, typical motile cilia are able to beat in complex, two-phase movements. Moreover, they contain many additional structures, including central apparatus, composed of two single microtubules connected by a bridge-like structure and assembling numerous complexes called projections. A growing body of evidence supports the important role of the central apparatus in the generation and regulation of the motile cilia movement. Here we review data concerning the central apparatus structure, protein composition, and the significance of its components in ciliary beating regulation.     

Dynamics and Motion Planning of Trident Snake Robot

The trident snake robot is a mechanical device that serves as a demanding testbed for motion planning and control algorithms of constrained non-holonomic systems. This paper provides the equations of motion and addresses the motion planning problem of the trident snake with dynamics, equipped with either active joints (undulatory locomotion) or active wheels (wheeled locomotion). Thanks to a partial feedback linearization of the dynamics model, the motion planning problem basically reduces to a constrained kinematic motion planning. Two kinds of constraints have been taken into account, ensuring the regularity of the feedback and the collision avoidance between the robot’s arms and body. Following the guidelines of the endogenous configuration space approach, two Jacobian motion planning algorithms have been designed: the singularity robust Jacobian algorithm and the imbalanced Jacobian algorithm. Performance of these algorithms have been illustrated by computer simulations.     

Structural perfection of laterally overgrown GaN layers grown in polar- and non-polar directions

The structural quality of GaN overgrown layers was evaluated using Transmission Electron Microscopy methods. Growth on polar and non-polar substrates was compared. Independent from growth polarity much better structural quality of the overgrown areas compared to the seed areas was obtained, but overgrowth on non-polar substrates is more difficult. For the latest samples, two wings on the opposite sites of the seed area grow in two different polar directions with different growth rates. Wings grown with Ga polarity are much wider than wings grown with N-polarity making coalescence of these layers difficult. Defects formed in the overgrown wings were characterized and their density was compared. It is shown that two-step growth (using two different temperatures) lead to much smaller misorientation between the wings than one step growth     

Isomerization of Eugenol Under Ultrasound Activation Catalyzed by Alkali Modified Mesoporous NbMCM-41

The present paper discloses a new alternative method for the isomerization of eugenol to isoeugenol where mesoporous materials containing niobium are used as solid base catalysts, affording good yields of isomerized product and being environmentally friendly. Nb-containing MCM-41 mesoporous materials were modified with alkaline cations (Li, Na, K, Rb and Cs) and characterized by BET, FTIR, XRD, and UV–vis techniques. The prepared materials were tested in the isomerization of eugenol to isoeugenol by sonochemical and thermally-activated reactions. Li, Na, K, Rb, and Cs/NbMCM-41 catalysts are active catalyst for the preparation of isoeugenol, and selective to the trans-isomer. Rb/NbMCM-41 sample is the optimum catalysts for the reaction. This result is in accordance with the calculated basicity observed during the Knoevenagel probe reaction of basicity. Conversions around 90% are obtained when using Rb-NbMCM-41 catalysts, with 90% selectivity to trans-isoeugenol, under ultrasound activation. In contrast, conversion around 72% with 90% selectivity is attained under classical thermal activation. The catalysts were reused four times without a substantial decrease of activity.     

The influence of ceramic additives on intumescence and thermal activity of epoxy coatings for steel

The article presents results of the research on the influence of graphite/kaolin and graphite/titanium oxide systems on thermal properties, intumescence degree and the integrity of the structure of intumescent protective films based on epoxy resins for steel. The TG/DTG/DSC analysis showed that graphite/kaolin system shifted the decomposition reaction of epoxy resin towards higher temperatures, even by about 30°C. Fire endurance tests and the SEM analysis confirmed these results because more thermally resistant (T_500°C reached after 37.5 min for 1.1 coating thickness), swollen (about 20 times) and homogeneous coatings were obtained. The presented results suggest that ceramic fire retardants can successfully cooperate with organic components in intumescent protective coatings for steel elements.     

Altered Elemental Distribution in Male Rat Brain Tissue as a Predictor of Glioblastoma Multiforme Growth—Studies Using SR-XRF Microscopy

Glioblastoma multiforme (GBM) is a particularly malignant primary brain tumor. Despite enormous advances in the surgical treatment of cancer, radio- and chemotherapy, the average survival of patients suffering from this cancer does not usually exceed several months. For obvious ethical reasons, the search and testing of the new drugs and therapies of GBM cannot be carried out on humans, and for this purpose, animal models of the disease are most often used. However, to assess the efficacy and safety of the therapy basing on these models, a deep knowledge of the pathological changes associated with tumor development in the animal brain is necessary. Therefore, as part of our study, the synchrotron radiation-based X-ray fluorescence microscopy was applied for multi-elemental micro-imaging of the rat brain in which glioblastoma develops. Elemental changes occurring in animals after the implantation of two human glioma cell lines as well as the cells taken directly from a patient suffering from GBM were compared. Both the extent and intensity of elemental changes strongly correlated with the regions of glioma growth. The obtained results showed that the observation of elemental anomalies accompanying tumor development within an animal’s brain might facilitate our understanding of the pathogenesis and progress of GBM and also determine potential biomarkers of its extension. The tumors appearing in a rat’s brain were characterized by an increased accumulation of Fe and Se, whilst the tissue directly surrounding the tumor presented a higher accumulation of Cu. Furthermore, the results of the study allow us to consider Se as a potential elemental marker of GBM progression.     

The Antibacterial Effect of PEGylated Carbosilane Dendrimers on P. aeruginosa Alone and in Combination with Phage-Derived Endolysin

The search for new microbicide compounds is of an urgent need, especially against difficult-to-eradicate biofilm-forming bacteria. One attractive option is the application of cationic multivalent dendrimers as antibacterials and also as carriers of active molecules. These compounds require an adequate hydrophilic/hydrophobic structural balance to maximize the effect. Herein, we evaluated the antimicrobial activity of cationic carbosilane (CBS) dendrimers unmodified or modified with polyethylene glycol (PEG) units, against planktonic and biofilm-forming P. aeruginosa culture. Our study revealed that the presence of PEG destabilized the hydrophilic/hydrophobic balance but reduced the antibacterial activity measured by microbiological cultivation methods, laser interferometry and fluorescence microscopy. On the other hand, the activity can be improved by the combination of the CBS dendrimers with endolysin, a bacteriophage-encoded peptidoglycan hydrolase. This enzyme applied in the absence of the cationic CBS dendrimers is ineffective against Gram-negative bacteria because of the protective outer membrane shield. However, the endolysin—CBS dendrimer mixture enables the penetration through the membrane and then deterioration of the peptidoglycan layer, providing a synergic antimicrobial effect.