Influence of Hypoxia on Radiosensitization of Cancer Cells by 5-Bromo-2′-deoxyuridine

Radiotherapy is a crucial cancer treatment, but its outcome is still far from satisfactory. One of the reasons that cancer cells show resistance to ionizing radiation is hypoxia, defined as a low level of oxygenation, which is typical for solid tumors. In the hypoxic environment, cancer cells are 2–3 times more resistant to ionizing radiation than normoxic cells. To overcome this important impediment, radiosensitizers should be introduced to cancer therapy. When modified with an electrophilic substituent, nucleosides may undergo efficient dissociative electron attachment (DEA) that leaves behind nucleoside radicals, which, in secondary reactions, are able to induce DNA damage, leading to cancer cell death. We report the radiosensitizing effect of one of the best-known DEA-type radiosensitizers—5-bromo-2′-deoxyuridine (BrdU)—on breast (MCF-7) and prostate (PC3) cancer cells under both normoxia and hypoxia. MCF-7 and PC3 cells were treated with BrdU to investigate the effect of hypoxia on cell proliferation, incorporation into DNA and radiosensitivity. While the oxygen concentration did not significantly affect the efficiency of BrdU incorporation into DNA or the proliferation of tumor cells, the radiosensitizing effect of BrdU on hypoxic cells was more evident than on normoxic cells. Further mechanistic studies performed with the use of flow cytometry showed that under hypoxia, BrdU increased the level of histone H2A.X phosphorylation after X-ray exposure to a greater extent than under normal oxygenation conditions. These results confirm that the formation of double-strand breaks in hypoxic BrdU-treated cancer cells is more efficient. In addition, by performing stationary radiolysis of BrdU solution in the presence of an ^●OH radical scavenger, we compared the degree of its electron-induced degradation under aerobic and anaerobic conditions. It was determined that radiodegradation under anaerobic conditions was almost twice as high as that under aerobic conditions.     

Novel Mode of Trisiloxane Application Reduces Spider Mite and Aphid Infestation of Fruiting Shrub and Tree Crops

Silicon - Application of pesticides leads to contamination of the natural environment, which entails the necessity to seek solutions that use substances which do not pose ecological hazards. The...     

Simulation of the effect of scale deposition on a geothermal turbine

Dissolved chemicals contained in geothermal steam can lead to corrosion, erosion and deposition of scale on turbine blades, reducing their useful life. In addition, deposits on the blading system reduce the flow area of the turbine. The first-stage nozzle group is typically most affected by deposition of scale although scale may be present in other parts of the system. The most common deposits are of silica and calcium carbonate. This decreases the output capacity and efficiency of the turbine. This paper presents the results of simulations on the effect of scale deposition in the first-stage nozzle group on the steam pressure before and after the first stage, output capacity and efficiency of the turbine. By measuring the steam pressure before and after the first stage the change in the flow area can be estimated. A method of monitoring the percentage of nozzle plugging in real time is proposed. The method can be applied to any turbine that is susceptible to scale deposition.     

Pathogenesis of Dementia

According to Alzheimer’s Disease International, 55 million people worldwide are living with dementia. Dementia is a disorder that manifests as a set of related symptoms, which usually result from the brain being damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, usually accompanied by emotional problems, difficulties with language, and decreased motivation. The most common variant of dementia is Alzheimer’s disease with symptoms dominated by cognitive disorders, particularly memory loss, impaired personality, and judgmental disorders. So far, all attempts to treat dementias by removing their symptoms rather than their causes have failed. Therefore, in the presented narrative review, I will attempt to explain the etiology of dementia and Alzheimer’s disease from the perspective of energy and cognitive metabolism dysfunction in an aging brain. I hope that this perspective, though perhaps too simplified, will bring us closer to the essence of aging-related neurodegenerative disorders and will soon allow us to develop new preventive/therapeutic strategies in our struggle with dementia, Alzheimer’s disease, and Parkinson’s disease.     

The Effect of the BCO2 Genotype on the Expression of Genes Related to Carotenoid,Retinol, and α-Tocopherol Metabolism in Rabbits Fed a Diet with Aztec Marigold Flower Extract

This study investigated the effect of the BCO2 genotype and the addition of Aztec marigold flower extract to rabbit diets on the expression of BCO1, BCO2, LRAT, and TTPA genes in the liver. The levels of lutein, zeaxanthin, β-carotene, retinol, and α-tocopherol in the liver and blood serum of rabbits, as well as plasma biochemical parameters and serum antioxidant enzyme activities were also determined. Sixty male Termond White growing rabbits were divided into three groups based on their genotype at codon 248 of the BCO2 gene (ins/ins, ins/del and del/del); each group was divided into two subgroups: one subgroup received a standard diet, and the other subgroup was fed a diet supplemented with 6 g/kg of marigold flower extract. The obtained results indicate that the BCO2 genotype may affect the expression levels of BCO1 and BCO2 genes in rabbits. Moreover, the addition of marigold extract to the diet of BCO2 del/del rabbits may increase the expression level of the BCO2 gene. Finally, an increase in the amount of lutein in the diet of rabbits with the BCO2 del/del genotype contributes to its increased accumulation in the liver and blood of animals without compromising their health status or liver function.     

High-Resolution Crystal Structure of Muscle Phosphoglycerate Mutase Provides Insight into Its Nuclear Import and Role

Phosphoglycerate mutase (PGAM) is a glycolytic enzyme converting 3-phosphoglycerate to 2-phosphoglycerate, which in mammalian cells is expressed in two isoforms: brain (PGAM1) and muscle (PGAM2). Recently, it was shown that besides its enzymatic function, PGAM2 can be imported to the cell nucleus where it co-localizes with the nucleoli. It was suggested that it functions there to stabilize the nucleolar structure, maintain mRNA expression, and assist in the assembly of new pre-ribosomal subunits. However, the precise mechanism by which the protein translocates to the nucleus is unknown. In this study, we present the first crystal structure of PGAM2, identify the residues involved in the nuclear localization of the protein and propose that PGAM contains a “quaternary nuclear localization sequence (NLS)”, i.e., one that consists of residues from different protein chains. Additionally, we identify potential interaction partners for PGAM2 in the nucleoli and demonstrate that 14-3-3ζ/δ is indeed an interaction partner of PGAM2 in the nucleus. We also present evidence that the insulin/IGF1–PI3K–Akt–mTOR signaling pathway is responsible for the nuclear localization of PGAM2.     

Possible Mechanisms of Resistance Development to Photodynamic Therapy (PDT) In Vulvar Cancer Cells

Photodynamic therapy (PDT) is a low-invasive treatment method that can be used to treat VIN patients. A photosensitizer (PS) applied to a patient is activated with use of the appropriate wavelength of light, which in an oxygen environment leads to the formation of a reactive oxygen species (ROS) that destroys the tumor. However, cells can protect themselves against these cytotoxic products by increasing their antioxidant mechanisms and repair capacity. Changes in the cytoskeleton may also influence resistance to PDT. Our results revealed that PDT-resistant cells changed the amount of ROS. Cells resistant to PDT A-431 exhibited a decreased ROS level and showed higher viability after oxidizing agent treatment. Resistant Cal-39 cells exhibited a decreased O₂⁻ level but increased other ROS. This provides protection from PDT but not from other oxidizing agents. Moreover, PDT leads to alterations in the cytoskeleton that may result in an epithelial-mesenchymal transition (EMT) or increased adhesion. Both EMT and cell adhesion may activate signaling pathways involved in survival. This means that resistance to PDT in vulvar cancer may be at least in part a result of changes in ROS level and alterations in the cytoskeleton.