Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H₂ results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the ¹H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan ¹H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.     

Properties of Non-Aminoglycoside Compounds Used to Stimulate Translational Readthrough of PTC Mutations in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare disease with autosomal recessive inheritance, caused mostly by bi-allelic gene mutations that impair motile cilia structure and function. Currently, there are no causal treatments for PCD. In many disease models, translational readthrough of premature termination codons (PTC-readthrough) induced by aminoglycosides has been proposed as an effective way of restoring functional protein expression and reducing disease symptoms. However, variable outcomes of pre-clinical trials and toxicity associated with long-term use of aminoglycosides prompt the search for other compounds that might overcome these problems. Because a high proportion of PCD-causing variants are nonsense mutations, readthrough therapies are an attractive option. We tested a group of chemical compounds with known PTC-readthrough potential (ataluren, azithromycin, tylosin, amlexanox, and the experimental compound TC007), collectively referred to as non-aminoglycosides (NAGs). We investigated their PTC-readthrough efficiency in six PTC mutations found in Polish PCD patients, in the context of cell and cilia health, and in comparison to the previously tested aminoglycosides. The NAGs did not compromise the viability of the primary nasal respiratory epithelial cells, and the ciliary beat frequency was retained, similar to what was observed for gentamicin. In HEK293 cells transfected with six PTC-containing inserts, the tested compounds stimulated PTC-readthrough but with lower efficiency than aminoglycosides. The study allowed us to select compounds with minimal negative impact on cell viability and function but still the potential to induce PTC-readthrough.     

Sorption,solubility, and mass changes of hydroxyapatite‐containing composites in artificial saliva,food simulating solutions,tea, and coffee

The purpose of this study was to evaluate the influence of preparation/storage conditions on the sorption, solubility, and mass changes of new proposed hydroxyapatite‐containing resin‐based composites. Seventy cylindrical samples of composite were prepared according to the ISO 4049 and stored in different storage solutions (distilled water, artificial saliva, 10% ethanol, 3% acetic acid, heptane, tea, and coffee) for 7, 14, and 28 days at 37°C. Principal component analysis and analysis of the variance were used to determine the impact of the preparation and storage conditions (e.g., curing time, storage time, and type of storage solution) on the changes of stability of examined material. Sorption, solubility, and mass changes of examined samples were specified. The tendency of these changes depending on the curing time, storage time, and type of storage solutions were presented. Due to the observed behavior, three groups of storage solutions were distinguished: “aqueous,” acidic, and hydrophobic (“fat”) solutions. Investigated properties changed in different way, characteristic for each of the above groups. No general tendency of the influence of storage and curing time was observed. The type of storage solution has the greatest impact on the sorption, solubility, and mass changes of examined material. The influence of the curing and storage time may be neglected. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39856.     

Anwendung eines Stranggieß-Simulationsmodells bei Štore Steel – II

This paper represents the elements and the use of the upgraded simulation system, developed in the last half decade for ?tore Steel billet caster. The simulation system is used in the context of the state-of-the-art automation and information of the twenty-five year-old three-strand Concast billet continuous caster for dimensions square 140 and 180 mm with the capacity of 160,000 tons/year. The simulation system is used in the off-line and on-line modes. The off-line mode is used in order to set the proper process parameters and to calculate the temperature field, macrosegregation, and grain structure of the strand. It is also used to calculate the changes in the caster design such as the secondary cooling and the position of the SEN. The on-line model is used in automatic casting control system. The paper represents an update of our BHM publication of 2005 (Application of Continous Casting Simulation at ?tore Steel, BHM, Vol. 150, No. 9, 300–306).     

Characterization of light‐cured,dental‐resin‐based biocomposites

The dependence of the depth of cure (DOC) and degree of conversion (DC) on the depth of experimental and commercial materials were determined according to ISO 4049 procedure and with the use of Raman spectroscopy, respectively. Moreover, an attempt was made to find the correlation between the DOC and DC and the depth of the material. The hypothesis was that curing time recommended by the manufacturers is appropriate for curing both commercial and experimental materials to achieve comparable values of the examined properties. The impact of the filler characteristic was clearly observed. The longer curing time provides a deeper curing (DOC values) and higher reaction rate (DC); however, the dependence between the DC values and DOC values was not visible. Instead, a logarithmic trend in the relation of the DOC and curing time was clearly observed. The results of this study suggest that the experimental materials give some hope for potential clinical applications and should be further investigated. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42812.     

Composition, soaking, cooking properties and thermal characteristics of starch of chickpeas, wrinkled peas and smooth peas

We investigated both the distribution of protein, ash and starch in legume (chickpeas, smooth and wrinkled peas) cotyledons, and the soaking and cooking characteristics, including gelatinization and retrogradation, of the starch. There were large differences in composition between different types of legumes and also between the outer and inner parts of legume cotyledons. Wrinkled peas exhibited much higher water absorption during prolonged soaking and there were higher hardness value determined for cooked seeds compared with chickpeas and smooth peas. While the hardness of cooked seeds decreased continuously as cooking time increased to 110 min, all legume starch was fully gelatinized after cooking for 70 min.     

Synthesis and characterization of cross‐linked poly(sodium acrylate)/sodium silicate hydrogels

Transparent and intumescent polymer‐silicate hydrogels were synthesized by free‐radical polymerization, in the presence of the redox initiators system (potassium persulphate/sodium thiosulphate) and cross‐linking monomer (N,N′‐methylenebisacrylamide). Hydrogels obtained in such a manner were rheologically tested and it was found that the same sample with a different sodium acrylate concentration polymerized faster when its content was lower. The spectroscopic and thermal analysis proved that the polymer combines with sodium silicate by hydrogen bonds and during thermal degradation only small polymer fragments and water molecules were released. NMR studies have shown that the content of water glass causes shorter relaxation times. Conducted fire tests showed that glass panes systems filled with the tested hydrogels meet the relevant construction standards and what is their big advantage, a thin 1 mm layer of polymer‐silicate gel is sufficient for this purpose. We believe that these results will contribute to the development of intumescent hydrogels with enhanced fire‐retardant properties. POLYM. ENG. SCI., 59:1279–1287 2019. © 2019 Society of Plastics Engineers     

Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells

Transition metal coordination compounds play an important role in the treatment of neoplastic diseases. However, due to their low selectivity and bioavailability, as well as the frequently occurring phenomenon of drug resistance, new chemical compounds that could overcome these phenomena are still being sought. The solution seems to be the synthesis of new metal complexes conjugated with drug carriers, e.g., dendrimers. Numerous literature data have shown that dendrimers improve the bioavailability of the obtained metal complexes, solving the problem of their poor solubility and stability in an aqueous environment and also breaking down inborn and acquired drug resistance. Therefore, the aim of this study was to synthesize a novel imidazole platinum(II) complex conjugated with and without the second-generation PAMAM dendrimer (PtMet2–PAMAM and PtMet2, respectively) and to evaluate its antitumor activity. Cell viability studies indicated that PtMet2–PAMAM exhibited higher cytotoxic activity than PtMet2 in MCF-7 and MDA-MB-231 breast cancer cells at relatively low concentrations. Moreover, our results indicated that PtMet2–PAMAM exerted antiproliferative effects in a zebrafish embryo model. Treatment with PtMet2–PAMAM substantially increased apoptosis in a dose-dependent manner via caspase-9 (intrinsic pathway) and caspase-8 (extrinsic pathway) activation along with pro-apoptotic protein expression modulation. Additionally, we showed that apoptosis can be induced by activating POX, which induces ROS production. Furthermore, our results also clearly showed that the tested compounds trigger autophagy through p38 pathway activation and increase Beclin-1, LC3, AMPK, and mTOR inhibition. The high pro-apoptotic activity and the ability to activate autophagy by the imidazole platinum(II) complex conjugated with a dendrimer may be due to its demonstrated ability to reverse multidrug resistance (MDR) and thereby increase cellular accumulation in breast cancer cells.