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.     

Dipeptides of S-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis,Complexing Abilities and Antiproliferative Properties

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.     

Bacteriophages vB_Sen-TO17 and vB_Sen-E22, Newly Isolated Viruses from Chicken Feces,Specific for Several Salmonella enterica Strains

Two newly discovered bacteriophages, isolated from chicken feces and infecting Salmonella enterica strains, are described in this report. These phages have been named vB_Sen-TO17 and vB_Sen-E22, and we present their molecular and functional characterization. Both studied viruses are able to infect several S. enterica strains and develop lytically, but their specific host ranges differ significantly. Electron microscopic analyses of virions have been performed, and full genome sequences were determined and characterized, along with molecular phylogenetic studies. Genomes of vB_Sen-TO17 (ds DNA of 41,658 bp) and vB_Sen-E22 (dsDNA of 108,987 bp) are devoid of homologs of any known or putative gene coding for toxins or any other proteins potentially deleterious for eukaryotic cells. Both phages adsorbed efficiently (>95% adsorbed virions) within 10 min at 42 °C (resembling chicken body temperature) on cells of most tested host strains. Kinetics of lytic development of vB_Sen-TO17 and vB_Sen-E22, determined in one-step growth experiments, indicated that development is complete within 30–40 min at 42 °C, whereas burst sizes vary from 9 to 79 progeny phages per cell for vB_Sen-TO17 and from 18 to 64 for vB_Sen-E22, depending on the host strain. Virions of both phages were relatively stable (from several percent to almost 100% survivability) under various conditions, including acidic and alkaline pH values (from 3 to 12), temperatures from −80 °C to 60 °C, 70% ethanol, chloroform, and 10% DMSO. These characteristics of vB_Sen-TO17 and vB_Sen-E22 indicate that these phages might be considered in further studies on phage therapy, particularly in attempts to eliminate S. enterica from chicken intestine.     

The Mechanical Properties of the Novel Nanocrystalline Refractory Tantalum Alloys

Protection of Metals and Physical Chemistry of Surfaces - The nanocrystalline tantalum alloys were investigated in terms of mechanical properties. The materials were obtained by powder metallurgy...     

Utilization of linseed cake as a postagricultural functional filler for poly(lactic acid) green composites

Linseed cake (LC), a byproduct of linseed oil extraction, is used as a functional filler for production of biodegradable composites. To determine the influence of residual linseed crude oil contained in lignocellulosic filler on the properties of the poly(lactic acid) (PLA)-based composites with 5–30% filler content, two types of LC were analyzed: a defatted and an unmodified one. Complex analysis of the composites' properties change was conducted in relation to their structure modification caused by the addition of a waste filler. It was found that the addition of LC resulted in simultaneous plasticization and improved crystallization of PLA. Lignocellulosic particles and crude linseed oil contained in the LC powder provided a modifying effect, influencing the level of crystallinity and mechanical and thermomechanical properties. Using LC may thus overcome one of the main drawbacks of PLA, which is brittleness and low crystallinity. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47152.     

Complex modification effect of linseed cake as an agricultural waste filler used in high density polyethylene composites

Linseed cake (LC) is a by-product of agricultural industry which does not have any large-scale industrial applications. The possibilities of its utilization as filler with plasticizing ability for high density polyethylene (HDPE)-based composites have been investigated. Composites containing 5, 10, 20 and 30 wt% of the waste filler have been prepared using a melt mixing method. The influence of the LC on the mechanical and thermomechanical properties of the composites, as well as their water absorption and morphology, have been evaluated by the following methods: static tensile test, impact strength assessment using Dynstat method, hardness measurements, differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy observations, measurements of Vicat’s softening temperature and water uptake test. Application of different measuring techniques allows for describing complex modification effects of the composites’ properties changes induced by the presence of lignocellulosic filler with high oil content. The results of the study proved a pronounced influence of LC on high density polyethylene-based composites, especially a plasticizing effect of crude linseed oil contained by the waste filler particles. LC also has been assumed to affect the polymeric matrix crystallization process. It was found that complex modification of polyethylene results from simultaneously occurring different phenomena including: plasticization of the HDPE by linseed oil, improved crystallinity of the semicrystalline matrix, presence of the rigid lignocellulosic particles dispersed in polymer and accumulation of the oil in the interfacial regions.     

Nonisothermal crystallization of highly‐filled polyolefin/calcium carbonate composites

Nonisothermal crystallization kinetics of highly‐filled polyolefin composites was studied by means of differential scanning calorimetry (DSC). Two types of commercial calcium carbonate based fillers (modified with stearic acid and nonmodified one) were used for our investigations. In order to evaluate the crystallization kinetics changes of composites, the Avrami theory modified by Jeziorny was used. Validity of mineral fillers modification with stearic acid has been proved by thermal analysis. Because of the suppression of the heterogeneous nucleation effect resulting from calcium carbonate with stearic acid modification, an increase in the processability of highly‐filled polyolefin cast films might occur. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41201.     

Simulation of the interactions between hydraulic and natural fractures using a fracture mechanics approach

HYDROCK method aims to store thermal energy in the rock mass using hydraulically propagated fracture planes. The hydraulic fractures can interact with the pre-existing natural fractures resulting in a complex fracture network, which can influence the storage performance. This study investigates the interactions between hydraulic and natural fractures using a fracture mechanics approach. The new functionality of the fracture mechanics modelling code FRACOD that enables crossing of hydraulically driven fracture by a pre-existing fracture is presented. A series of two-dimensional numerical models is prepared to simulate the interaction at different approach angles in granitic rock of low permeability. It is demonstrated that multiple interaction mechanisms can be simulated using the fracture mechanics approach. The numerical results are in agreement with the modified Renshaw and Pollard analytical criterion for fracture crossing. The results show that for large approach angles, the hydraulic fracture crosses the natural fracture, whereas for small approach angles, the hydraulic fracture activates the natural fracture and the wing-shaped tensile fractures are propagated from its tips. Thus, the presence of fractures with low dip angles can lead to the growth of more complex fracture network that could impair the thermal performance of the HYDROCK method.     

The Peculiar Structure of Acetobacter pasteurianus CIP103108 LPS Core Oligosaccharide

Acetobacter pasteurianus, a member of the Alphaproteobacteria, is an acetic acid-producing bacterium present on sugar-rich substrates such as such as fruits, flowers and vegetables and traditionally used in the production of fermented food. The preferred living habitat associated with acid conditions makes the structure of the bacterial cell wall interesting to study, due to expected uncommon features. We have used a combination of chemical, analytical and NMR spectroscopy approaches to define the complete structure of the core oligosaccharide from A. pasteurianus CIP103108 LPS. Interestingly, the core oligosaccharide displays a high concentration of negatively charged groups, structural features that might contribute to reinforcing the bacterial membrane.