The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes

The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients’ poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.     

Benefits of Usage of Immobilized Silver Nanoparticles as Pseudomonas aeruginosa Antibiofilm Factors

The aim of this study was to assess the beneficial inhibitory effect of silver nanoparticles immobilized on SiO₂ or TiO₂ on biofilm formation by Pseudomonas aeruginosa—one of the most dangerous pathogens isolated from urine and bronchoalveolar lavage fluid of patients hospitalized in intensive care units. Pure and silver doped nanoparticles of SiO₂ and TiO₂ were prepared using a novel modified sol-gel method. Ten clinical strains of P. aeruginosa and the reference PAO1 strain were used. The minimal inhibitory concentration (MIC) was determined by the broth microdilution method. The minimal biofilm inhibitory concentration (MBIC) and biofilm formation were assessed by colorimetric assay. Bacterial enumeration was used to assess the viability of bacteria in the biofilm. Silver nanoparticles immobilized on the SiO₂ and TiO₂ indicated high antibacterial efficacy against P. aeruginosa planktonic and biofilm cultures. TiO₂/Ag⁰ showed a better bactericidal effect than SiO₂/Ag⁰. Our results indicate that the inorganic compounds (SiO₂, TiO₂) after nanotechnological modification may be successfully used as antibacterial agents against multidrug-resistant P. aeruginosa strains.     

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-3-methylbutanoic Acid as a Potential Anti-Breast Cancer Molecule

It was established that the synthesis of hybrid molecules containing a thiazolidinone and a (2Z)-2-chloro-3-(4-nitrophenyl)prop-2-ene structural fragments is an effective approach for the design of potential anticancer agents. Given the results of the previous SAR-analysis, the aim of the study was to synthesize a novel 4-thiazolidinone derivative Les-3331 and investigate its molecular mechanism of action in MCF-7 and MDA-MB-231 breast cancer cells. The cytotoxic properties and antiproliferative potential of Les-3331 were determined. The effect of the tested compound on apoptosis induction and mitochondrial membrane potential was checked by flow cytometry. ELISA was used to determine caspase-8 and caspase-9, LC3A, LC3B, Beclin-1, and topoisomerase II concentration. Additionally, PAMPA, in silico or in vitro prediction of metabolism, CYP3A4/2D6 inhibition, and an Ames test were performed. Les-3331 possesses high cytotoxic and antiproliferative activity in MCF-7 and MDA-MB-231 breast cancer cells. Its molecular mechanism of action is associated with apoptosis induction, decreased mitochondrial membrane potential, and increased caspase-9 and caspase-8 concentrations. Les-3331 decreased LC3A, LC3B, and Beclin-1 concentration in tested cell lines. Topoisomerase II concentration was also lowered. The most probable metabolic pathways and no DDIs risk of Les-3331 were confirmed in in vitro assays. Our studies confirmed that a novel 4-thiazolidinone derivative represents promising anti-breast cancer activity.     

Changes in volatile, sensory and microbial profiles during preparation of smoked ewe cheese

BACKGROUND: Oscypek is a special type of Polish smoked ewe cheese with a unique flavour described as slightly sour, piquant, salted and smoked. In this study the volatile, sensory and microbial profiles of Oscypek cheese were analysed during its various preparation stages of curding, scalding, brining and smoking. RESULTS: The smoked ewe cheese was characterised by 54 volatile compounds belonging to nine different chemical groups (free fatty acids, esters, ketones, alcohols, aldehydes, furans/furanones, phenols, sulfur compounds, terpenes). The sensory aroma profile analysis of unsmoked and smoked cheese showed an important correlation with the analysis of volatile compounds. The microbial profile data indicated that in smoked cheese such as Oscypek the levels of selected bacteria diminished after the curding stage as a result of the subsequent scalding, brining and smoking stages. CONCLUSION: From the results it can be concluded that, although the analysed smoked cheese consisted of three groups of compounds, the first derived from biochemical reactions (free fatty acids, esters, ketones, alcohols, aldehydes, sulfur compounds), the second from smoking (furans and furanones, phenols) and the third from milk flavour (terpenes), it is the smoking process that mainly influences its typical flavour. Copyright © 2011 Society of Chemical Industry     

Synthesis and Biological Studies of Novel Aminophosphonates and Their Metal Carbonyl Complexes (Fe,Ru)

The quest to find new inhibitors of biologically relevant targets is considered an important strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates 8a–c and their metallocarbonyl iron 9a–c and ruthenium 10a–c complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC₅₀. Metallocarbonyl derivatives, in general, did not show significant inhibition activity against these enzymes, the most potent inhibitor was the (aminomethyl)benzylphosphonate 8a (IC₅₀ = 1.215 µM against AChE). Molecular docking analysis of AChE and (aminomethyl)benzylphosphonates 8a–c showed the strongest interactions of 8a and AChE compared to isomers 8b and 8c. Cytotoxicity studies of synthesized compounds towards the V79 cell line were also performed and discussed.     

Maternal High-Energy Diet during Pregnancy and Lactation Impairs Neurogenesis and Alters the Behavior of Adult Offspring in a Phenotype-Dependent Manner

Obesity is one of the biggest and most costly health challenges the modern world encounters. Substantial evidence suggests that the risk of metabolic syndrome or obesity formation may be affected at a very early stage of development, in particular through fetal and/or neonatal overfeeding. Outcomes from epidemiological studies indicate that maternal nutrition during pregnancy and lactation has a profound impact on adult neurogenesis in the offspring. In the present study, an intergenerational dietary model employing overfeeding of experimental mice during prenatal and early postnatal development was applied to acquire mice with various body conditions. We investigated the impact of the maternal high-energy diet during pregnancy and lactation on adult neurogenesis in the olfactory neurogenic region involving the subventricular zone (SVZ) and the rostral migratory stream (RMS) and some behavioral tasks including memory, anxiety and nociception. Our findings show that a maternal high-energy diet administered during pregnancy and lactation modifies proliferation and differentiation, and induced degeneration of cells in the SVZ/RMS of offspring, but only in mice where extreme phenotype, such as significant overweight/adiposity or obesity is manifested. Thereafter, a maternal high-energy diet enhances anxiety-related behavior in offspring regardless of its body condition and impairs learning and memory in offspring with an extreme phenotype.     

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer’s Disease Research

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer’s disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties. Based on these results, the final two most promising radioconjugates, [⁶⁸Ga]Ga-NODAGA-Bn-NH(CH₂)₉Tac and [⁶⁸Ga]Ga-THP-NH(CH₂)₉Tac, were selected for biodistribution studies. The latter compound was proven to be a good inhibitor of cholinesterases with significant affinity toward the lungs, according to the biodistribution studies. On the basis of molecular modelling combined with in vitro studies, we unraveled which structural properties of the developed tacrine derivatives are crucial for high affinity toward acetylcholinesterase, whose increased levels in lung tissues in the course of coronavirus disease indicate the onset of pneumonia. The radiopharmaceutical [⁶⁸Ga]Ga-THP-NH(CH₂)₉Tac was ultimately selected due to its increased accuracy and improved sensitivity in PET imaging of lung tissue with high levels of acetylcholinesterase, and it may become a novel potential diagnostic modality for the determination of lung perfusion, including in inflammation after COVID-19.     

Environmental aspects and economic evaluation of new green hydrolysis method for waste feather processing

Clean Technologies and Environmental Policy - In recent years, an increase in the chicken meat process industry has been growing quickly, which brings a large amount of difficult to process waste,...     

Application of the Basalt Powder as a Filler for Polypropylene Composites With Improved Thermo‐Mechanical Stability and Reduced Flammability

The influence of the basalt powder (BP) on mechanical properties as well as on thermal stability and flammability of the isotactic polypropylene (iPP) composites was investigated. Thermo‐mechanical stability of the pure polypropylene and composite materials containing from 5 up to 40 wt% BP was defined in static and dynamic testing conditions with the use of the heat distortion temperature measurement, vicat softening point temperature test, and dynamic mechanical thermal analysis. All measurements showed, unequivocally, a significant improvement of thermo‐mechanical stability of the composite materials which was directly related to an increasing amount of inorganic filler. A research conducted on the mechanical properties revealed that stiffness and hardness of polypropylene‐based composites was affected by the addition of the filler, leading to a strong increase of both mechanical parameters. Moreover, the application of thermogravimetric analysis and cone calorimetry measurements allowed to determine the composites with highest thermal stability, which was dependent on the concentration of the filler. Changes observed in the polypropylene‐based composites properties were related to an increase of thermal diffusivity caused by presence of the BP measured by modified Angstrom method. POLYM. ENG. SCI., 59:E71–E79, 2019. © 2018 Society of Plastics Engineers