Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.     

Carotenoids from Marine Sources as a New Approach in Neuroplasticity Enhancement

An increasing number of people experience disorders related to the central nervous system (CNS). Thus, new forms of therapy, which may be helpful in repairing processes’ enhancement and restoring declined brain functions, are constantly being sought. One of the most relevant physiological processes occurring in the brain for its entire life is neuroplasticity. It has tremendous significance concerning CNS disorders since neurological recovery mainly depends on restoring its structural and functional organization. The main factors contributing to nerve tissue damage are oxidative stress and inflammation. Hence, marine carotenoids, abundantly occurring in the aquatic environment, being potent antioxidant compounds, may play a pivotal role in nerve cell protection. Furthermore, recent results revealed another valuable characteristic of these compounds in CNS therapy. By inhibiting oxidative stress and neuroinflammation, carotenoids promote synaptogenesis and neurogenesis, consequently presenting neuroprotective activity. Therefore, this paper focuses on the carotenoids obtained from marine sources and their impact on neuroplasticity enhancement.     

On the Nature and Location of Organic Template Molecules and Their Effect on the Stability and Redox Properties of Microporous CoAlPO-34 Catalyst

Small-pore CoAlPO-34 materials were synthesized with a variety of organic template molecules and were characterized in detail, employing microcrystal diffraction, powder diffraction and in situ combined XRD/XAS techniques. We found that, when two template molecules or two nitrogen atoms of a single template molecule are present inside the chabazitic cage, the concentration of cobalt present in the system is ca. 25?at%, which introduces instability in the framework structure during the removal of the organic template. In contrast, when only one template molecule is present, it is possible to control the concentration of Co(II) ions in the framework to ca. 10?at%; these systems show good structural integrity and redox chemistry that was exploited for the regio-selective conversion of linear alkane molecules.     

Studies on obtaining of aluminium ammonium calcium phosphates

Aluminium ammonium calcium phosphates were prepared with the use of AlCl₃, CaCO₃, H₃PO₄. The influence of the process parameters (pH 5 ± 3, the molar ratios of Ca²⁺:Al⁺³:PO₄^?3 in the substrates, respectively 0.31:0.62:1; 0.5:0.5:1; 0.72:0.36:1, temperature 40 ± 20 °C) on the phase composition and the product properties was determined. The process parameters that enable to obtain the material with expected physicochemical properties were determined based on the statistical evaluation of the experiments (fractional factorial design at three levels 3^(k?p)27). The phase composition of the obtained samples was studied with the use of XRD analysis. The specific surface area was calculated with the use of S_BET method and the particle size was determined by the laser scanning microscopy. The materials with the molar ratio of Al³⁺/NH₄⁺ and Al³⁺/Ca²⁺ in the range of 0.70–27.93 and 0.47–24.48, respectively, with an absorption oil number of 95–157 g/100 g paraffin oil, the S_BET within 25–118 m²/g, the pore volume within 0.14–0.74 cm³/g and the particle size in the range of 168–285 nm were obtained.     

Magnetic resonance studies of cement based materials in inhomogeneous magnetic fields

Single-sided magnets give hope that Nuclear Magnetic Resonance (NMR) might in future be used for in situ characterisation of hydration and water transport in the surface layers of concrete slabs. Towards that end, a portable NMR-MOUSE (MObile Universal Surface Explorer) has been used to follow the hydration of gypsum based plaster, a Portland cement paste and concrete mortar. The results compare favourably to those obtained using a standard laboratory bench-top spectrometer. Further, stray field imaging (STRAFI) based methods have been used with embedded NMR detector coils to study water transport across a mortar/topping interface. The measured signal amplitudes are found to correlate with varying sample conditions.     

The influence of electron beam irradiation,plastic deformation,and re‐irradiation on crystallinity degree,mechanical and sclerometric properties of GUR 1050 used for arthroplasty

The article describes the influence of an electron beam irradiation (I), plastic deformation (D), and re‐irradiation (R) on the properties of ultrahigh molecular weight polyethylene (GUR 1050). It was found that the modification through irradiation entailed a gradual increase in the degree of crystallinity (after irradiation–I). After plastic deformation and re‐irradiation (IDR) the degree of crystallinity decreases which had a direct influence on the mechanical properties. The polymer irradiation only (technique I) resulted in an increase in the maximum stress as compared with the material in the initial state. The application of deformation and re‐irradiation (technique IDR) allowed increasing the deformation resistance by more than 40%. Moreover, the irradiation with an electron beam resulted in the increase in hardness (H) and Young's modulus (E) proportionally to the applied irradiation dose and in the reduction of total indentation work (W_tot) and its components. After deformation and re‐irradiation the polyethylene hardness went down. The application of technique (I) caused an improvement to the material abrasion resistance (reduction of parameter PD–working scratch depth) with the increasing irradiation dose. The introduction of deformation and re‐irradiation did not have a material impact on parameter (PD) increasing at the same time elastic properties of UHMWPE (increase in parameter NPS–elastic recovery). Modification IDR has changed the wear mechanism (β) toward ploughing and has increased the abrasion‐resistance index (W_β) and also significantly reduced the coefficient of friction (μ) of GUR 1050. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43683.     

The Periplasmic Oxidoreductase DsbA Is Required for Virulence of the Phytopathogen Dickeya solani

In bacteria, the DsbA oxidoreductase is a crucial factor responsible for the introduction of disulfide bonds to extracytoplasmic proteins, which include important virulence factors. A lack of proper disulfide bonds frequently leads to instability and/or loss of protein function; therefore, improper disulfide bonding may lead to avirulent phenotypes. The importance of the DsbA function in phytopathogens has not been extensively studied yet. Dickeya solani is a bacterium from the Soft Rot Pectobacteriaceae family which is responsible for very high economic losses mainly in potato. In this work, we constructed a D. solani dsbA mutant and demonstrated that a lack of DsbA caused a loss of virulence. The mutant bacteria showed lower activities of secreted virulence determinants and were unable to develop disease symptoms in a potato plant. The SWATH-MS-based proteomic analysis revealed that the dsbA mutation led to multifaceted effects in the D. solani cells, including not only lower levels of secreted virulence factors, but also the induction of stress responses. Finally, the outer membrane barrier seemed to be disturbed by the mutation. Our results clearly demonstrate that the function played by the DsbA oxidoreductase is crucial for D. solani virulence, and a lack of DsbA significantly disturbs cellular physiology.     

Fentanyl Structure as a Scaffold for Opioid/Non-Opioid Multitarget Analgesics

One of the strategies in the search for safe and effective analgesic drugs is the design of multitarget analgesics. Such compounds are intended to have high affinity and activity at more than one molecular target involved in pain modulation. In the present contribution we summarize the attempts in which fentanyl or its substructures were used as a μ-opioid receptor pharmacophoric fragment and a scaffold to which fragments related to non-opioid receptors were attached. The non-opioid ‘second’ targets included proteins as diverse as imidazoline I₂ binding sites, CB₁ cannabinoid receptor, NK₁ tachykinin receptor, D₂ dopamine receptor, cyclooxygenases, fatty acid amide hydrolase and monoacylglycerol lipase and σ₁ receptor. Reviewing the individual attempts, we outline the chemistry, the obtained pharmacological properties and structure-activity relationships. Finally, we discuss the possible directions for future work.     

The influence of mining factors on seismic activity during longwall mining of a coal seam

In this article an attempt to determine the influence of mining factors on the seismic activity during the longwall mining of the upper layer of coal seam no. 405/2 in one of the Polish hard coal mines in the Upper Silesian Coal Basin was conducted. Two longwall panels were mined in analogous geological conditions and based on the same mining system and technology. However, there was significant difference with regards to the mining factors, which was reflected in the observed seismic activity. Some tools used in mining seismology were applied to illustrate the aforementioned influence of mining factors, e.g. the frequency-energy distribution, the frequency-magnitude distribution, the 2 D distribution of released seismic energy, the relationship between released seismic energy and the volume of mined coal, the Benioff strain release, and the Gutenberg-Richter(GR) b coefficient distribution(b is the proportion between high and low energy tremors). Concerning the Benioff strain release, a new solution, based on the slope of a fitted line in a moving time window, is proposed.