Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

Thermal transport and chemical conversion in single reacting sorbent particles

The effects of particle size and carbon dioxide concentration on chemical conversion in engineered spherical particles undergoing calcium oxide looping are investigated. Particles are thermochemically cycled in a furnace under different carbon dioxide concentrations. Changes in composition due to chemical reactions are measured using thermogravimetric analysis. Gas composition at the furnace exit is evaluated with mass spectroscopy. A numerical model of thermal transport phenomena developed previously is adapted to match the physical system investigated in the present study. The model is used to elucidate effects of reacting medium characteristics on particle temperature and reaction extent. Experimental and numerical results show that (1) an increase in particle size results in a decrease in carbonation extent, and (2) the carbonation step consists of fast and slow reaction regimes. The reaction rates in the fast and slow carbonation regimes increase with increasing carbon dioxide concentration. The effect of carbon dioxide concentration and the distinction between the fast and slow regimes become more pronounced with increasing particle size.     

Examining the Impact of Squaric Acid as a Crosslinking Agent on the Properties of Chitosan-Based Films

Hydrogels based on chitosan are very versatile materials which can be used for tissue engineering as well as in controlled drug delivery systems. One of the methods for obtaining a chitosan-based hydrogel is crosslinking by applying different components. The objective of the present study was to obtain a series of new crosslinked chitosan-based films by means of solvent casting method. Squaric acid—3,4-dihydroxy-3-cyclobutene-1,2-dione—was used as a safe crosslinking agent. The effect of the squaric acid on the structural, mechanical, thermal, and swelling properties of the formed films was determined. It was established that the addition of the squaric acid significantly improved Young’s modulus, tensile strength, and thermal stability of the obtained materials. Moreover, it should be stressed that the samples consisting of chitosan and squaric acid were characterized by a higher swelling than pure chitosan. The detailed characterization proved that squaric acid could be used as a new effective crosslinking agent.     

Corrosion of structural constituents of 2017 aluminium alloy in acidic solutions containing inhibitors

The objective of this study is to establish the corrosion behaviour of the most important structural constituents of the aluminium alloy 2017 in orthophosphoric acid solutions containing heteropolyoxomolybdate, tungstate and vanadate. These are potential candidates for replacing toxic hexavalent chromium species in stripping solution for anodic coatings. The corrosion rate of the alloy is estimated with linear polarisation method. It decreases from 0.58 mA cm⁻² in uninhibited solution to 0.10 mA cm⁻² in a solution containing heteropolyoxomolybdate species. Microscopic studies reveal that heteropolyoxomolybdate species inhibit corrosion of the matrix and intermetallic Al₁₅(Fe,Mn)₃(Si,Cu)₂ but not Mg₂Si. Intermetallic Al₂Cu remains not corroded. Heteropolyoxotungstate species virtually do not inhibit the corrosion of the alloy. The solution containing vanadium species is not stable with time and the corrosion rate is not determined. Nevertheless, corrosion of the matrix is inhibited, but intermetallics Al₁₅(Fe,Mn)₃(Si,Cu)₂ together with Mg₂Si are dissolved. X-ray photoelectron spectroscopy is used for examination of a corrosion product precipitated on the surface.     

Role of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation and Subsequent Immune Challenge in the Behaviour and Microglial Cell Trajectory in Adult Offspring: A Study of the Neurodevelopmental Model of Schizophrenia

Multiple lines of evidence support the pathogenic role of maternal immune activation (MIA) in the occurrence of the schizophrenia-like disturbances in offspring. While in the brain the homeostatic role of neuron-microglia protein systems is well documented, the participation of the CX3CL1-CX3CR1 and CD200-CD200R dyads in the adverse impact of MIA often goes under-recognized. Therefore, in the present study, we examined the effect of MIA induced by polyinosinic:polycytidylic acid (Poly I:C) on the CX3CL1-CX3CR1 and CD200-CD200R axes, microglial trajectory (MhcII, Cd40, iNos, Il-1β, Tnf-α, Il-6, Arg1, Igf-1, Tgf-β and Il-4), and schizophrenia-like behaviour in adult male offspring of Sprague-Dawley rats. Additionally, according to the “two-hit” hypothesis of schizophrenia, we evaluated the influence of acute challenge with Poly I:C in adult prenatally MIA-exposed animals on the above parameters. In the present study, MIA evoked by Poly I:C injection in the late period of gestation led to the appearance of schizophrenia-like disturbances in adult offspring. Our results revealed the deficits manifested as a diminished number of aggressive interactions, presence of depressive-like episodes, and increase of exploratory activity, as well as a dichotomy in the sensorimotor gating in the prepulse inhibition (PPI) test expressed as two behavioural phenotypes (MIA_PPI-low and MIA_PPI-high). Furthermore, in the offspring rats subjected to a prenatal challenge (i.e., MIA) we noticed the lack of modulation of behavioural changes after the additional acute immune stimulus (Poly I:C) in adulthood. The important finding reported in this article is that MIA affects the expression and levels of the neuron-microglia proteins in the frontal cortex and hippocampus of adult offspring. We found that the changes in the CX3CL1-CX3CR1 axis could affect microglial trajectory, including decreased hippocampal mRNA level of MhcII and elevated cortical expression of Igf-1 in the MIA_PPI-high animals and/or could cause the up-regulation of an inflammatory response (Il-6, Tnf-α, iNos) after the “second hit” in both examined brain regions and, at least in part, might differentiate behavioural disturbances in adult offspring. Consequently, the future effort to identify the biological background of these interactions in the Poly I:C-induced MIA model in Sprague-Dawley rats is desirable to unequivocally clarify this issue.     

Transmittance Measurements in Non-alternating Magnetic Field as Reliable Method for Determining of Heating Properties of Phosphate and Phosphonate Coated Fe3O4 Magnetic Nanoparticles

Different phosphates and phosphonates have shown excellent coating ability toward magnetic nanoparticles, improving their stability and biocompatibility which enables their biomedical application. The magnetic hyperthermia efficiency of phosphates (IDP and IHP) and phosphonates (MDP and HEDP) coated Fe₃O₄ magnetic nanoparticles (MNPs) were evaluated in an alternating magnetic field. For a deeper understanding of hyperthermia, the behavior of investigated MNPs in the non-alternating magnetic field was monitored by measuring the transparency of the sample. To investigate their theranostic potential coated Fe₃O₄-MNPs were radiolabeled with radionuclide ¹⁷⁷Lu. Phosphate coated MNPs were radiolabeled in high radiolabeling yield (>?99%) while phosphonate coated MNPs reached maximum radiolabeling yield of 78%. Regardless lower radiolabeling yield both radiolabeled phosphonate MNPs may be further purified reaching radiochemical purity of more than 95%. In vitro stabile radiolabeled nanoparticles in saline and HSA were obtained. The high heating ability of phosphates and phosphonates coated MNPs as sine qua non for efficient in vivo hyperthermia treatment and satisfactory radiolabeling yield justifies their further research in order to develop new theranostic agents.

     

Use of Fourier-Transform Infrared Spectroscopy (FT-IR) for Monitoring Experimental Helicobacter pylori Infection and Related Inflammatory Response in Guinea Pig Model

Infections due to Gram-negative bacteria Helicobacter pylori may result in humans having gastritis, gastric or duodenal ulcer, and even gastric cancer. Investigation of quantitative changes of soluble biomarkers, correlating with H. pylori infection, is a promising tool for monitoring the course of infection and inflammatory response. The aim of this study was to determine, using an experimental model of H. pylori infection in guinea pigs, the specific characteristics of infrared spectra (IR) of sera from H. pylori infected (40) vs. uninfected (20) guinea pigs. The H. pylori status was confirmed by histological, molecular, and serological examination. The IR spectra were measured using a Fourier-transform (FT)-IR spectrometer Spectrum 400 (PerkinElmer) within the range of wavenumbers 3000–750 cm⁻¹ and converted to first derivative spectra. Ten wavenumbers correlated with H. pylori infection, based on the chi-square test, were selected for a K-nearest neighbors (k-NN) algorithm. The wavenumbers correlating with infection were identified in the W2 and W3 windows associated mainly with proteins and in the W4 window related to nucleic acids and hydrocarbons. The k-NN for detection of H. pylori infection has been developed based on chemometric data. Using this model, animals were classified as infected with H. pylori with 100% specificity and 97% sensitivity. To summarize, the IR spectroscopy and k-NN algorithm are useful for monitoring experimental H. pylori infection and related inflammatory response in guinea pig model and may be considered for application in humans.     

Genome-Wide Analyses of the Temperature-Responsive Genetic Loci of the Pectinolytic Plant Pathogenic Pectobacterium atrosepticum

Temperature is one of the critical factors affecting gene expression in bacteria. Despite the general interest in the link between bacterial phenotypes and environmental temperature, little is known about temperature-dependent gene expression in plant pathogenic Pectobacterium atrosepticum, a causative agent of potato blackleg and tuber soft rot worldwide. In this study, twenty-nine P. atrosepticum SCRI1043 thermoregulated genes were identified using Tn5-based transposon mutagenesis coupled with an inducible promotorless gusA gene as a reporter. From the pool of 29 genes, 14 were up-regulated at 18 °C, whereas 15 other genes were up-regulated at 28 °C. Among the thermoregulated loci, genes involved in primary bacterial metabolism, membrane-related proteins, fitness-corresponding factors, and several hypothetical proteins were found. The Tn5 mutants were tested for their pathogenicity in planta and for features that are likely to remain important for the pathogen to succeed in the (plant) environment. Five Tn5 mutants expressed visible phenotypes differentiating these mutants from the phenotype of the SCRI1043 wild-type strain. The gene disruptions in the Tn5 transposon mutants caused alterations in bacterial generation time, ability to form a biofilm, production of lipopolysaccharides, and virulence on potato tuber slices. The consequences of environmental temperature on the ability of P. atrosepticum to cause disease symptoms in potato are discussed.     

Effect of microstructural features on the corrosion behavior of severely deformed Al–Mg–Si alloy

The aim of this study was to determine the influence of severe plastic deformation processing and the changes in microstructure resulting therefrom on the corrosion resistance of an Al–Mg–Si alloy. The alloy was processed using incremental equal channel angular pressing, which caused a reduction in grain size from 15 to 0.9 µm. The grain refinement was accompanied by an increase in the number of grain boundaries and dislocations, and by changes in grain orientation. However, there was no change in the size and number of intermetallic particles, which presumably resulted in a constant number of galvanic couplings. Electrochemical experiments revealed only slight differences between the samples before and after processing. Higher potential transients/oscillations upon immersion and increased corrosion currents in the vicinity of corrosion potential point to slightly higher reactivity of the most refined material. This indicates that intermetallic particles are the most crucial microstructural elements in terms of corrosion resistance. Their impact exceeds that of grain boundaries, in particular, at the stage of corrosion initiation. The development of corrosion attack is controlled more by the microstructure of the matrix as the grain refinement resulted in a less pronounced corrosion attack in comparison with the coarse-grained sample.     

Associations between Oil Yield and Profile of Fatty Acids,Sterols, Squalene,Carotenoids, and Tocopherols in Seed Oil of Selected Japanese Quince Genotypes during Fruit Development

Tocopherols, phytosterols, carotenoids, and squalene are present in mature seeds of Japanese quince. Yet, little is known about the relationship between these compounds and oil yield during fruit and seed development. The profile change of lipophilic compounds during fruit and seed development in Japanese quince cultivars “Darius,” “Rondo,” and “Rasa” is investigated. It is shown here that during fruit and seed development, there is a significant reduction, three‐ to over tenfold, in the concentration of minor bioactive compounds in seed oil. It is recorded that delay between synthesis of tocopherols and oil in Japanese quince seeds during the fruit development results in a logarithmic relationship between the oil content and tocopherols concentration in the seed oil (R² = 0.980). Similar trends are observed between oil yield and phytosterols, and carotenoids (R² = 0.927 and R² = 0.959, respectively). The profile of fatty acids during the development of the seeds significantly is changed. The reduction of linoleic, palmitic, and gondoic acids levels and increment of oleic acid is noted. The oil content, profile of fatty acids, and concentration of bioactive compounds in all three genotypes of Japanese quince do not change significantly statistically during the last month of fruit development. Practical Applications: Some fruits are harvested at different degrees of maturity mainly due to a logistic issue and uneven ripening of fruits, which affects the chemical composition of whole fruit including seeds. Therefore, it would be good to know how the chemical composition is changing in plant material during development especially in the last month before harvest. Production of Japanese quince continues to rise year to year and with it the volume of generated by‐products such as seeds. This study demonstrates how it changes the oil content, profile of fatty acid, and concentration of tocopherols, squalene, phytosterols, and carotenoids in the seeds and seed oil of three Japanese quince cultivars “Rondo,” “Darius,” and “Rasa” during plant development. The provided information can be very useful for the manufactories oriented on the processing of by‐products, mainly seeds, generated by other branches of industry, for instance, fruit‐processing.