Platelet Mitochondrial Bioenergetics Reprogramming in Patients with Urothelial Carcinoma

Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q₁₀ (CoQ₁₀) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ₁₀ level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ₁₀ cycle (Q-junction) to CI.     

Effect of Glucocorticosteroids in Diamond-Blackfan Anaemia: Maybe Not as Elusive as It Seems

Diamond-Blackfan anaemia (DBA) is a red blood cell aplasia that in the majority of cases is associated with ribosomal protein (RP) aberrations. However, the mechanism by which this disorder leads to such a specific phenotype remains unclear. Even more elusive is the reason why non-specific agents such as glucocorticosteroids (GCs), also known as glucocorticoids, are an effective therapy for DBA. In this review, we (1) explore why GCs are successful in DBA treatment, (2) discuss the effect of GCs on erythropoiesis, and (3) summarise the GC impact on crucial pathways deregulated in DBA. Furthermore, we show that GCs do not regulate DBA erythropoiesis via a single mechanism but more likely via several interdependent pathways.     

Engineered Glycosidases for the Synthesis of Analogs of Human Milk Oligosaccharides

Enzymatic synthesis is an elegant biocompatible approach to complex compounds such as human milk oligosaccharides (HMOs). These compounds are vital for healthy neonatal development with a positive impact on the immune system. Although HMOs may be prepared by glycosyltransferases, this pathway is often complicated by the high price of sugar nucleotides, stringent substrate specificity, and low enzyme stability. Engineered glycosidases (EC 3.2.1) represent a good synthetic alternative, especially if variations in the substrate structure are desired. Site-directed mutagenesis can improve the synthetic process with higher yields and/or increased reaction selectivity. So far, the synthesis of human milk oligosaccharides by glycosidases has mostly been limited to analytical reactions with mass spectrometry detection. The present work reveals the potential of a library of engineered glycosidases in the preparative synthesis of three tetrasaccharides derived from lacto-N-tetraose (Galβ4GlcNAcβ3Galβ4Glc), employing sequential cascade reactions catalyzed by β3-N-acetylhexosaminidase BbhI from Bifidobacterium bifidum, β4-galactosidase BgaD-B from Bacillus circulans, β4-N-acetylgalactosaminidase from Talaromyces flavus, and β3-galactosynthase BgaC from B. circulans. The reaction products were isolated and structurally characterized. This work expands the insight into the multi-step catalysis by glycosidases and shows the path to modified derivatives of complex carbohydrates that cannot be prepared by standard glycosyltransferase methods.     

Essential rosemary oil protects testicular cells against DNA-damaging effects of H2O2 and DMNQ

Rosemary oil (RO) is popular in the Mediterranean region as a culinary additive which has the ability to protect delicate organs such as liver, brain and heart. We examined the effect of RO consumption on resistance of rat testicular cells (TCs) against DNA-damaging effects of the oxidative agents H₂O₂ and DMNQ and on the activity of the antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). DNA lesions were detected by conventional and modified comet assay and the activities of GSH-Px and SOD were measured spectrophotometrically. Since TCs represent a mixture of haploid, diploid and tetraploid cells, we used flow cytometry for their differentiation and calculation of DNA-damaging effects of H₂O₂ and DMNQ in cells of different ploidy. The results showed that the oxidative DNA lesions were significantly reduced in TCs from rats administered RO; however, the activity of antioxidant enzymes did not differ in TCs from control and RO-supplemented rats.     

Annular Impinging Jet Controlled by Radial Synthetic Jets

This experimental study focuses on generation and control of annular impinging jets. The annular nozzle used in the investigations was designed with an active flow control system using 12 synthetic jets issuing radially from the central nozzle body. Measurements of the control effects were made on the impingement wall. The data acquisition involved wall pressure and wall mass transfer (by the naphthalene sublimation technique) using air as the working fluid. Also measured was time-mean flow velocity (by a Pitot probe) in the jet flow field. Moreover, flow visualization was carried out. Two main flow-field patterns (A and B) were identified. The patterns differ in the size of the separated-flow recirculation regions that develop attached to the nozzle central body: While pattern A is characterized by a quite small recirculation region (bubble) extending not far from the nozzle exit, pattern B exhibits a large recirculation region, reaching up to the impingement wall, on which it forms a stagnation circle. The control action modifies the flow field, resulting in changes of the corresponding heat/mass transfer distributions. The convective transfer rate on the stagnation circle can be demonstrably enhanced by 20% at a moderate nozzle-to-wall distance, equal to 0.6 of the nozzle outer diameter.     

Elastic properties of porous oxide ceramics prepared using starch as a pore-forming agent

The elastic properties, in particular the tensile modulus (Young's modulus) and Poisson ratio, of porous alumina, zirconia, and alumina–zirconia composite ceramics are studied using the resonance frequency method and the results compared with theoretical predictions. Starch is used as a pore-forming agent, so that the resulting microstructure is essentially of the matrix-inclusion type (with large bulk pores, connected by small throats when a percolation threshold is exceeded). It is found that for this type of microstructure the porosity dependence of the Young's modulus is significantly below the upper Hashin–Shtrikman bound and the power-law prediction; it corresponds well, however, to a recently proposed exponential relation and to an empirical volume-weighted average of the upper and lower Hashin–Shtrikman bounds. Results for all three types of ceramics indicate that – in the porosity range considered, i.e. up to approximately 50% – the Poisson ratio depends only slightly on porosity.     

Multi-component adsorption of Ag(I), Cd(II) and Cu(II) by natural carbonaceous materials

Adsorption of silver, cadmium and copper from aqueous solutions by natural carbonaceous materials was investigated. The studied series of natural materials (spruce wood, pine bark, cork, peat, fusinite, lignite, oxidised lignite, bituminous coal and anthracite) was extended to include industrial carbon-rich materials: coke, activated carbon F-400 and Multisorb 100. Adsorption was tested on a single-component system and on the binary and ternary mixtures. All the materials used differ in their ability to adsorb selected metals. The adsorption of metals is significantly affected by the presence of other ions in solution. Total metal uptake was considerably higher in a mixture than single-ion adsorption. Chemical reactions, such as precipitation and reduction of metallic silver, play a role in metal uptake by bituminous coal, coke and activated carbon.     

Ecological Adaptations of Gut Microbiota Members and Their Consequences for Use as a New Generation of Probiotics

In this review, we link ecological adaptations of different gut microbiota members with their potential for use as a new generation of probiotics. Gut microbiota members differ in their adaptations to survival in aerobic environments. Interestingly, there is an inverse relationship between aerobic survival and abundance or potential for prolonged colonization of the intestinal tract. Facultative anaerobes, aerotolerant Lactobacilli and endospore-forming Firmicutes exhibit high fluctuation, and if such bacteria are to be used as probiotics, they must be continuously administered to mimic their permanent supply from the environment. On the other hand, species not expressing any form of aerobic resistance, such as those from phylum Bacteroidetes, commonly represent host-adapted microbiota members characterized by vertical transmission from mothers to offspring, capable of long-term colonization following a single dose administration. To achieve maximal probiotic efficacy, the mode of their administration should thus reflect their natural ecology.     

Tetrapyrazinoporphyrazines with different number of peripheral pyridyl rings: Synthesis,photophysical and photochemical properties

Zinc tetrapyrazinoporphyrazines comprising different numbers of pyridin-2-yl and tert-butylsulfanyl substituents were prepared by the statistical condensation of two precursors – 5,6-bis(tert-butylsulfanyl)pyrazine-2,3-dicarbonitrile (A) and 5,6-dipyridin-2-yl-pyrazine-2,3-dicarbonitrile (B). The ensuing zinc tetrapyrazinoporphyrazines were chromatographically separated on silica column and characterized. Adjacent (AABB) and opposite (ABAB) isomers were not separated. The prepared zinc tetrapyrazinoporphyrazines did not differ in their Q-band position but the B-band position was shifted hypsochromically for compounds bearing more pyridyl units; in addition, a weak band at 450–520 nm decreased with increasing number of pyridyl substituents. Singlet oxygen quantum yields (Φ_Δ in the range 0.69–0.53) decreased with increasing number of pyridyl units on the macrocyclic core, while fluorescence quantum yields showed the reverse tendency (Φ_F in the range 0.22–0.26).