Raman intensity: An important tool to study the structure and phase transitions of amorphous/crystalline materials

The measurements of the Raman intensity are used mainly to determine quantitatively the amount, distribution and degree of crystallisation of different phases in a material, i.e. the Raman mapping. Our studies reveal that the analysis of relative and absolute Raman intensity is a very powerful tool, which allows to investigate and characterize the modifications of the structure in covalent bonded compounds, e.g. due to: (i) changes of BO₆ octahedra by the substitution of the B site by lanthanides or rare earth elements and the incorporation of protons in the case of high temperature protonic conductors, (ii) changes of the long range order correlations as the function of the nanoregion organization: continuous evolution of the local symmetry towards the long range cubic one in the case of PbMg_1/3Nb_2/3O₃–xPbTiO₃ (PMN–PT) relaxor ferroelectrics, (iii) changes of the Si–O network caused by the depolymerisation resulting from the substitution of the Si⁴⁺ ions (covalent bonds) by the M⁺ cations (ionic bonds) or by the incorporation of the metallic nanoprecipitates and (iv) changes caused by the lixiviation/protonation of the surface layers of the Cultural Heritage stained glasses as a function of their corrosion degree and age.     

Chemistry towards Biology—Instruct: Snapshot

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.     

Targeting DNA Methylation in Leukemia,Myelodysplastic Syndrome,and Lymphoma: A Potential Diagnostic,Prognostic, and Therapeutic Tool

DNA methylation represents a crucial mechanism of epigenetic regulation in hematologic malignancies. The methylation process is controlled by specific DNA methyl transferases and other regulators, which are often affected by genetic alterations. Global hypomethylation and hypermethylation of tumor suppressor genes are associated with hematologic cancer development and progression. Several epi-drugs have been successfully implicated in the treatment of hematologic malignancies, including the hypomethylating agents (HMAs) decitabine and azacytidine. However, combinations with other treatment modalities and the discovery of new molecules are still the subject of research to increase sensitivity to anti-cancer therapies and improve patient outcomes. In this review, we summarized the main functions of DNA methylation regulators and genetic events leading to changes in methylation landscapes. We provide current knowledge about target genes with aberrant methylation levels in leukemias, myelodysplastic syndromes, and malignant lymphomas. Moreover, we provide an overview of the clinical trials, focused mainly on the combined therapy of HMAs with other treatments and its impact on adverse events, treatment efficacy, and survival rates among hematologic cancer patients. In the era of precision medicine, a transition from genes to their regulation opens up the possibility of an epigenetic-based approach as a diagnostic, prognostic, and therapeutic tool.     

Fraxetin Interacts Additively with Cisplatin and Mitoxantrone,Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis

Malignant melanoma is a skin cancer characterized by rapid development, poor prognosis and high mortality. Due to the frequent drug resistance and/or early metastases in melanoma, new therapeutic methods are urgently needed. The study aimed at assessing the cytotoxic and antiproliferative effects of scoparone and fraxetin in vitro, when used alone and in combination with three cytostatics: cisplatin, mitoxantrone, and docetaxel in four human melanoma cell lines. Our experiments showed that scoparone in the concentration range tested up to 200 µM had no significant effect on the viability of human malignant melanoma (therefore, it was not possible to evaluate it in combination with other cytostatics), while fraxetin inhibited cell proliferation with IC₅₀ doses in the range of 32.42–73.16 µM, depending on the cell line. Isobolographic analysis allowed for the assessment of the interactions between the studied compounds. Importantly, fraxetin was not cytotoxic to normal keratinocytes (HaCaT) and melanocytes (HEMa-LP), although it slightly inhibited their viability at high concentrations. The combination of fraxetin with cisplatin and mitoxantrone showed the additive interaction, which seems to be a promising direction in melanoma therapy. Unfortunately, the combination of fraxetin with docetaxel may not be beneficial due to the antagonistic antiproliferative effect of both drugs used in the mixture.     

Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity

Aryl hydrocarbon receptor (AHR) plays pivotal roles in intestinal physiology and pathophysiology. Intestinal AHR is activated by numerous dietary, endogenous, and microbial ligands. Whereas the effects of individual compounds on AHR are mostly known, the effects of real physiological mixtures occurring in the intestine have not been studied. Using reporter gene assays and RT-PCR, we evaluated the combinatorial effects (3520 combinations) of 11 microbial catabolites of tryptophan (MICTs) on AHR. We robustly (n = 30) determined the potencies and relative efficacies of single MICTs. Synergistic effects of MICT binary mixtures were observed between low- or medium-efficacy agonists, in particular for combinations of indole-3-propionate and indole-3-lactate. Combinations comprising highly efficacious agonists such as indole-3-pyruvate displayed rather antagonist effects, caused by saturation of the assay response. These synergistic effects were confirmed by RT-PCR as CYP1A1 mRNA expression. We also tested mimic multicomponent and binary mixtures of MICTs, prepared based on the metabolomic analyses of human feces and colonoscopy aspirates, respectively. In this case, AHR responsiveness did not correlate with type of diet or health status, and the indole concentrations in the mixtures were determinative of gross AHR activity. Future systematic research on the synergistic activation of AHR by microbial metabolites and other ligands is needed.     

Comparison of Lupinus angustifolius protein digestibility in dependence on protein,amino acids,trypsin inhibitors and polyphenolic compounds content

Lupine seeds are proposed as a source of valuable protein in human and animal nutrition. However, not only protein content but its bioavailability is important. Thus, the protein digestibility of twenty Lupinus angustifolius varieties seeds and the impact of some factors (protein and polyphenols content, trypsin inhibition and amino acids composition) on the protein digestion were discussed. Composition as well as the digestibility of these seeds was influenced by variety, weather conditions (precipitations) and place of cultivation (soil quality). The average digestibility of the seeds was 46%. The positive impact on the digestibility had the extractivity of the protein. Higher than it was expected activity of trypsin inhibitors (even up to ~32%) in some varieties influenced the protein availability, while the lysine and phenolic compounds content did not affect digestibility. The content of compounds influencing protein digestibility depends both on variety as well as on agronomical conditions.     

Organosilicon resin-based carbon/ceramic polygranular composites with improved oxidation resistance

We examined the thermo-mechanical properties of carbon materials modified with silicon oxycarbide (Si-O-C) and silicon carbide (Si-C). These compounds were obtained by the impregnation of carbon components with a silicon-containing polymer resin. Graphite and anthracite powders were used as carbon components, and poly[methyl(phenyl) siloxane] resin (P) was used as the ceramic precursor. Carbon/polymer compositions (C/P) were subjected to two-stage annealing, first to 1,000 °C and next to 2,000 °C in an inert atmosphere, leading to the formation of C/Si-O-C and C/Si-C composite samples, respectively. The materials were then examined under conditions of isothermal oxidation to determine their oxidation resistance and the mechanical properties before and after oxidation tests. The structure of the samples before and after oxidation was studied. C/Si-C composites, despite their high porosity, proved to have enhanced resistance to oxidation at 600 °C, although they had lower mechanical properties in comparison to C/Si-O-C samples.     

Electrical and mechanical properties of granular-fibrous carbon-carbon composites with recycled carbon fibres

In the following study, the electrical and mechanical properties of granular-fibrous carbon-carbon composites with short recycled carbon fibres have been investigated. The examined composites contained from 0 to 12?wt% of three types of recycled carbon fibres that differ in length. The conducted study has proven that it is not the type of applied fibre, but rather the resultant porosity of composites that exerts the predominant influence on the electrical resistivity and mechanical properties of the tested materials. The curve fitting revealed mathematical formulas correlating the studied properties with the apparent density of the composite samples. Owing to the addition of the shortest carbon fibres, the mechanical and electrical properties were significantly improved (50.14% and 24.06% increase in modulus of elasticity and flexural strength respectively for the sample with 12?wt% of the shortest fibres). A 21.39% decline in the resistivity ($?=161.26\mu \Omega ?\mathrm{m}$) of the composite containing 4% of shortest fibres was noted in comparison with the reference sample. Unlike powdered fibres, the addition of longer fibres caused an increase in porosity and deterioration of microstructure, which resulted in a significant decline in the key properties of the investigated composites.     

Hot corrosion behaviour of Ni3Al in sulphate-chloride mixtures in the atmosphere

Hot corrosion of Ni₃Al intermetallic compound in the presence of sulphate-chloride mixtures was studied. A comminuted Ni₃Al mixed with NaCl-Na₂SO₄, NaCl-Li₂SO₄, LiCl-Na₂SO₄, LiCl-Li₂SO₄ additions was oxidized in the air up to 1000 °C with linearly increasing temperature and isothermally within the temperature range of 500-700 °C. The corrosion process was observed by thermogravimetric method using Mettler thermoanalyzer.The experiments indicated that LiCl (∼10 wt.%)-Li₂SO₄ mixture was the most corrosive agent. It was also found that by addition of MgO the corrosion of Ni₃Al was reduced. Phase composition of the corrosion products was established by X-ray diffraction analysis; there were detected Al₂O₃, Al₂S₃, NaAlO₂ (or LiAlO₂) as intermediate products, nickel sulphides, NiO and NiAl₂O₄. NiAl₂O₄ spinel was formed only at the highest temperatures, while at lower temperatures alumina was present instead of spinel.Hot corrosion behaviour of Ni₃Al in sulphate-chloride mixtures in air atmosphere.