Photodynamic therapy (PDT) is a promising approach in the treatment of various tumors. The presence of three essential components: a photosensitizer, a light source and oxygen is required for generating reactive oxygen species and subsequent tumor destruction. In this study, we investigated the cell death pathway induced by Photodithazine (PD) mediated photodynamic therapy (PD-PDT). We found that PD localizes in the endoplasmic reticulum and Golgi apparatus of cancer cells. Upon irradiation at 20 J/cm2, PD induced death of tumor cells at concentrations exceeding 100 nM. Based on dying cell morphology, exposure of phosphatidylserine to the cell surface, presence of phosphorylated form of mixed lineage kinase domain like pseudokinase (pMLKL) and protective action of pan-caspase inhibitor and inhibitor of receptor-interacting protein kinase 1 (RIPK1), we hypothesize that Photodithazine forces cells to enter mixed-type cell death with features of apoptosis and necroptosis.
|7 Mechanisms of photodynamic killing of cancer cells by photodithazine.pdf||1.13 MB|
We have explored the features of PPARγ2 gene alleles expression in elderly patients with comorbid conditions such as obesity and coronary artery disease. 140 patients of both sexes (54.3% men and 45.7% women) aged 60-89 were examined. The main group included 70 pts with CHD; the control group included 70 pts without CHD. Pro12 allele carrier state in the main group was 85%, and Ala12 allele carrier state – 15%. Pro12Ala and Ala12Ala genotypes, Ala12 allele were detected more often in patients with coronary artery disease than in the control group (p = 0.0008 and p = 0.0003, respectively). Pro12Ala genotypes (OR = 2.02, CI = 1.28–3.19, p = 0.003) and Ala12Ala (OR = 2.002, CI = 1.32–3.04, p = 0.0006) of Ala12 gene PPARγ2 carrier state increases the risk of CHD developing by 2 times. It was confirmed that nuclear PPARs are capable of controlling development, differentiation, metabolic homeostasis and reproduction. The role of various genotypes of the PPARγ2 gene in the regulation of lipid metabolism and angiogenesis in comorbid conditions in elderly patients may help to identify new methods of their treatment.
Currently, radionuclide therapy of tumors using sources of alpha and beta radiation is actively developing. However, the radiosensitivity of tumor cells has been studied mainly using acute gamma radiation. In this regard, studies aimed at determining the ranges of radiosensitivity of cells of various origins in relation to beta-emission radionuclides are gaining relevance. The study was carried out on A431, CHO and SK-BR-3 cell lines using beta-emission sealed sources Sr-90+Y-90. Cell viability was assessed via MTT-assay. Dose dependences were obtained for irradiating cells with a beta source: the LD50 range was from 17 to 19 Gy, and LD37 was from 24 to 36 Gy. It was shown that at the same dose of radiation, the percentage of viable cells relative to the control of 72 hours after irradiation is significantly less than after 24 hours. The revealed LD50 values for tumor cells under chronic beta-irradiation are higher than with acute gamma-irradiation, which should be considered when selecting doses during the development of potential radiopharmaceutical treatment. Decreased cell viability in response to beta radiation is due to both cytotoxic and cytostatic manifestations.
CuO in the form of micro- and nano-sized colloidal particles enters the human body from environment. The aim of the study is the identification of morphological changes in rat liver tissues during chronic oral intake of micro- and nanosized CuO by image analysis. The experiments were performed on 45 male Wistar rats (3 groups: experimental (nanosized CuO); comparison (micro-sized CuO); control (water without CuO)). Suspensions CuO were administered to the rats orally once a day. Quantitative morphological parameters were determined by pathomorphological examination and image analysis using the method of constructing Voronoi diagrams (the ratio of cells of various shapes); average cell area; the average size of the cell perimeter and the number of cells per unit area. As a result of the analysis by the constructing Voronoi diagrams, was found that the main part of the model cells corresponding to hepatocytes has the shape of a hexagon. In the control group, their share is 35.89%, in the experience group – 29.09%, and in the comparison group – 30.59%. The density of cells’ distribution in the comparison group is 7 times higher than in the control group; in the experimental group the same indicator is 4 times higher than in the control group. Collectively, the characteristics of morphological changes in liver tissue indicate greater toxicity of nano-sized copper oxide compared to its micro-sized analogue.
The world’s biggest killer is ischemic heart disease, responsible for 16% of the world’s total deaths. Since 2000, the largest increase in deaths has been for this disease, rising by more than 2 million to 8.9 million deaths in 2019. In recent years, many studies have shown that hydrogen has therapeutic and preventive effects in various human and animal disease models. In this study, we investigated the possible antioxidant effects of molecular hydrogen in erythrocytes and blood plasma in rats with the experimentally simulated chronic heart failure. We estimated the intensity of lipid peroxidation processes by the contents of diene and triene conjugates, Schiff bases, malonic dialdehyde, catalase activity. The results from this study suggest that inhalation of 2% molecular hydrogen leads to a decrease in pro-oxidant and an increase in antioxidant parameters. The results of this study provide the basic data for the mechanism research and application of molecular hydrogen in the future.
Achieving both deep penetration of photons into biological tissue and highly sensitive recording of optical probes' response are the key goals of non-invasive optical imaging. In comparison with the traditional fluorescence imaging in the visible (400–700 nm) and near-infrared (700–900 nm) regions, optical fluorescence imaging in the second optical tissue transparency window (1000–2300 nm) demonstrates low photon scattering, deeper penetration into the tissues and lower autofluorescence. In the present study, biocompatible upconversion nanoparticles with different contents of doping lanthanides, capable of luminescence in the visible and short-wave IR regions, were obtained and characterized. Also, targeted complexes based on Gd-containing nanophosphors were obtained as potential contrast agents for magnetic resonance imaging. Selective binding of targeted complexes to the surface of tumor cells expressing the HER2 receptor was shown.
Epilepsy affects around 1% of the population in the world. Thus, it is imperative that new more effective and safe treatments be found. In order to understand the nature of epilepsy, new and better animal models are needed in that they offer valuable resources for researchers. Such models provide an opportunity to characterize seizures in the whole organism, to understand the molecular basis of these processes and to test the effectiveness of treatments and therapies. In this study, we have shown that screening after chemical mutagenesis can be used as a tool to identify new genes that may be involved in the mechanism of epilepsy formation.
|1 ENU mutagenesis as a tool for identifying novel mouse models of epilepsy.pdf||663.99 KB|
Over the past two decades, developments in the field of nanobiomedicine have come a long way despite the unresolved hindrances. The creation and development of effective theranostic agents based on nanomaterials are urgent needs of modern medicine. Upconversion nanoparticles (UCNP) appear to be the most promising agents for developing theranostics due to their unique optical properties. There has been extensive research on new approaches to obtain stable colloids capable of prolonged circulation in the bloodstream, particularly with bovine serum albumin (BSA). The present work contributes to solving the problem of obtaining stable agents based on UCNP by coating water-soluble UCNPNOBF4 with a stable protein corona layer of BSA. The assembled nanocomplex is promising for usage as a diagnostic agent and is set for further investigation.
|The Assembly оf а Photoluminescent Nanocomplex Based оn Upconversion Nanoparticles.pdf||487.42 KB|
Methylation of DNA cytosine bases is a key epigenetic modification that plays an important role in the regulation of gene expression and the formation of the epigenome. Numerous studies of the human genome show that there is a close relationship between DNA methylation, age and sex of a person. Until now, the popular model has been the linear change in the methylation level with age. Here we find a fundamentally different DNA methylation behavior, namely the nonlinear dependence of the methylation level on age. We identify CpG probes whose methylation changes exponentially with age or according to a power law, and perform Gene Ontology enrichment analysis of the latter. Our results are relevant to understanding how DNA methylation changes with age and the found nonlinear CpG sites can be used to construct new epigenetic clocks.
|DNA Methylation in Aging- Beyond the Linear Processes.pdf||729 KB|
3D bioengineering constructs are currently a promising area of research in the regeneration of various tissues. In our work, several modifications of scaffolds based on hyaluronic acid glycidyl methacrylate are presented. Scaffolds have been tested for biocompatibility with nerve cells in an in vivo model of traumatic brain injury. Throughout the experiment, the neurological status of the animals was monitored, and at the end, a histological examination of the brain was carried out. It has been shown that scaffolds are non-toxic to nerve cells and reduce the development of neurological deficit in animals in the post-traumatic period. The possibility of using the scaffold with a lower biodegradation rate as a carrier of a therapeutic drug has also been demonstrated.