In Vitro Photodynamic Therapy with Chlorin e6 Leads to Apoptosis of Human Vascular Smooth Muscle Cells

Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However, the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated in vitro using human vascular smooth muscle cells (TG/HA-VSMCs) as one of the cell types crucial in the development of restenosis. PDT-induced cell death was studied on many levels, including annexin V staining, measurement of the generation reactive oxygen species (ROS) and caspase-3 activity, and assessment of changes in mitochondrial membrane potential and fragmentation of DNA. Photosensitization of TG/HA-VSMCs with a 170 μM of chlorin e6 and subsequent illumination with the light of a 672-nm diode laser (2 J/cm2) resulted in the generation of ROS, a decrease in cell membrane polarization, caspase-3 activation, as well as DNA fragmentation. Interestingly, the latter two apoptotic events could not be observed in photosensitized and illuminated NIH3T3 fibroblasts, suggesting different outcomes of the model of PDT in various types of cells. The results obtained with human VSMCs show that chlorin e6 may be useful in the PDT of aerial restenosis, but its efficacy still needs to be established in an animal model

Publishing series for youth “The Seven Adventures Club ” (1960-1991)

Przedmiotem pracy jest młodzieżowa seria wydawnicza Klub Siedmiu Przygód ukazująca się nakładem Instytutu Wydawniczego „Nasza Księgarnia” w latach 1960-1991. Praca jest próbą zlokalizowania cyklu na rynku księgarskim Polski Ludowej pośród podobnych inicjatyw wydawniczych. W kolejnych rozdziałach została zaprezentowana krótka historia rozwoju serii dla dzieci i młodzieży na ziemiach polskich, a następnie sytuacja serii na rynku wydawniczym w omawianym przedziale czasowym. Dokonana została analiza materiału źródłowego zebranego w Bibliografii serii „Klub Siedmiu Przygód” pod kątem ilościowym, merytorycznym jak również pod kątem recepcji opublikowanych tytułów przez krytykę literacką.The subject of youth work is publishing a series of “The Seven Adventures Club” appearing by the Institute of Publishing "Our Bookstore" in the years 1960-1991. The work is an attempt to locate this series on the book market among the Polish People's Republic of publishing similar initiatives. In subsequent chapters, was presented a brief history of the development series for children and youth in the Polish lands, then the situation of the series in the publishing market in this timeframe. The analysis of the source material collected in the Bibliography series "The Seven Adventures Club" in terms of quantity, content and reception in terms of titles published by literary criticism

Expression of recombinant forms of human 21.5 kDa myelin basic protein and proteolipid protein in CHO cells

MBP and PLP are major structural protein components of myelin. Both proteins play a functional role in formation of myelin sheath and in maintenance of its compaction. Immune responses to MBP and PLP have been implicated in the pathogenesis of multiple sclerosis (MS), an auto-immune disease of the central nervous system. Recombinant forms of both proteins isolated and purified from bacterial or insect cell systems are commonly used to study the specificity of auto-response in MS. We have prepared recombinant forms of MBP and PLP stably expressed in CHO cells. Several clones with proper cytoplasmic MBP or surface PLP localization were obtained and characterized by flow cytometry and indirect immunostaining. CHO cells expressing the recombinant forms of MBP and PLP can be very useful in studies on the autoimmune mechanism of MS

The mitochondrial localization of RelB and NFATx in immature T cells

In order to exert their activity, transcription factors must be transported to the nucleus. Certain transcription factors have also been found on mitochondria. Here, the localization of RelB and NFATx in the mitochondrial fractions of normal thymocytes and thymic lymphoma cells is shown for the first time. CREB was only found in the nucleus, while p50 (NFkappaB) was found in both the nucleus and the cytoplasm, but outside the mitochondria. The translocation of transcription factors to the mitochondria is differentially regulated. Unlike RelB, which is always present in the mitochondrial fraction, NFATx appeared on the mitochondria in cells treated with ionomycin together with an immunosuppressant and inhibitor of calcineurin (FK506). This data reveals that the mitochondrial localization of some transcription factors is precisely controlled by a calcium signal sensitive to FK506 in T cells

The Contrasting Delayed Effects of Transient Exposure of Colorectal Cancer Cells to Decitabine or Azacitidine

(1) Background: Decitabine and azacitidine are cytosine analogues representing the class of drugs interfering with DNA methylation. Due to their molecular homology and similar clinical application, both drugs are often regarded as interchangeable. Despite their unique mechanism of action the studies designed for observation and comparison of the prolonged activity of these drugs are rare. (2) Methods: The short-time (20–72 h) and long-term (up to 20 days) anti-cancer activity of decitabine and azacitidine has been studied in colorectal cancer cells. We observe the impact on cell culture’s viability, clonogenicity, proliferation, and expression of CDKN1A, CCND1, MDM2, MYC, CDKN2A, GLB1 genes, and activity of SA-β-galactosidase. (3) Results: Decitabine has much stronger anti-clonogenic activity than azacitidine. We show that azacitidine, despite significant immediate toxicity, has negligible long-term effects. Contrary, decitabine, which does not exert initial toxicity, profoundly worsened the condition of the cells over time. On the 13th day after treatment, the viability of cells was decreased and proliferation inhibited. These functional changes were accompanied by up-regulation of expression CDKN1A, CCND1, and CDKN2A genes and increased activation of SA-β-galactosidase, indicating cellular senescence. (4) Conclusions: Our head-to-head comparison revealed profound differences in the activities of decitabine and azacitidine important in their anti-cancer potential and clinical application. The effects of decitabine need relatively long time to develop. This property is crucial for proper design of studies and therapy concerning decitabine and undermines opinion about the similar therapeutic mechanism and interchangeability of these drugs

Analysis of the Relationship of the Degree of Aviation Sector Development with Greenhouse Gas Emissions and Measures of Economic Development in the European Union Countries

The rapid growth of aviation over the past fifty years has resulted in numerous negative environmental impacts due to the combustion of fossil fuels in aircraft engines. This paper presents the relationship between air transport and GHG emissions. Based on data on the development of aviation, the level of GHG emissions from transport, environmental tax revenues and the amount of GDP per capita in the countries of the European Union, an attempt was made to create a typification that would illustrate the interaction of GHG emissions with air transport, environmental taxes and GDP in the years 2009–2018. The next step to confirm the obtained results was the application of statistical methods: the TOPSIS (Technique for Order of Preference by Similarity to Ideal Solution) method of linear ordering and the Perkal index. Based on the study findings, the analyzed countries were divided into three groups: the group of innovators, the stable group and the group of students. The analysis revealed the relationship of all three analyzed variables with air transport. The development of the aviation sector leads to a significant increase in GHG emissions from transport, increased revenues from environmental taxes and acceleration of the rate of economic growth of a country

E-Government Development in European Countries: Socio-Economic and Environmental Aspects

The purpose of the paper is to analyse the relationship between digitalisation of public services (e-government) and ESG factors (environmental, social and economic factors). As public administration is a major stakeholder influencing sustainable development and state governments are aiming to digitise their services, there is a need to better understand the effect of the digital revolution on ESG. This article aims to study the relationship between the E-Government Development Index (EGDI) and ESG factors in 26 European countries. The linear ordering method TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) was used for the study, followed by the Perkal index and the method of optimal predictors’ selection—the Hellwig method. The study is based on the Eurostat data (in the period 2003–2020), and the analysis includes ten variables: Share of environmental taxes in GDP; Exposure to dust air pollution; Greenhouse gas emissions by source sector—carbon dioxide, methane, nitrous oxide, etc. (energy, industry, agriculture, forestry, waste management) (thousands of tonnes); Passenger transport volume in relation to GDP; At risk of poverty or social exclusion; Percentage of people satisfied with their financial situation among people aged 16+; Share of the ICT sector in GDP; Unemployment rate of people aged 20–64; Research and development expenditure in all sectors; GDP per capita. The in-depth analysis offers a matrix that represents the relationships between environmental taxes and the development of e-government. The main finding reveals statistically significant relationships between the EGDI and aggregate variables representing the environmental, social and economic spheres. It indicates a genuine, positive impact of digitalised administrative processes on sustainable development. It also seems to confirm that investments in digital infrastructure and government e-services bring multiple long-term benefits and contribute directly to all three domains relevant to the sustainability of modern development. The results of the analysis can be found useful by governments and governmental institutions as informing digitalisation strategies aimed at balancing the development of e-services and their support infrastructure. Nowadays, when planning strategic actions, one should take into account the social, economic and environmental impact of the digitalisation processes

Photoactive Liposomal Formulation of PVP-Conjugated Chlorin e6 for Photodynamic Reduction of Atherosclerotic Plaque

Background: Liposomes serve as delivery systems for biologically active compounds. Existing technologies inefficiently encapsulate large hydrophilic macromolecules, such as PVP-conjugated chlorin e6 (Photolon). This photoactive drug has been widely tested for therapeutic applications, including photodynamic reduction of atherosclerotic plaque. Methods: A novel formulation of Photolon was produced using “gel hydration technology”. Its pharmacokinetics was tested in Sus scrofa f. domestica. Its cellular uptake, cytotoxicity, and ability to induce a phototoxic reaction were demonstrated in J774A.1, RAW264.7 macrophages, and vascular smooth muscle (T/G HA-VSMC) as well as in vascular endothelial (HUVEC) cells. Results: Developed liposomes had an average diameter of 124.7 ± 0.6 nm (polydispersity index (PDI) = 0.055) and contained >80% of Photolon). The half-life of formulation in S. scrofa was 20 min with area under the curve (AUC) equal to 14.7. The formulation was noncytotoxic in vitro and was rapidly (10 min) and efficiently accumulated by macrophages, but not T/G HA-VSMC or HUVEC. The accumulated quantity of photosensitizer was sufficient for induction of phototoxicity in J774A.1, but not in T/G HA-VSMC. Conclusions: Due to the excellent physical and pharmacokinetic properties and selectivity for macrophages, the novel liposomal formulation of Photolon is a promising therapeutic candidate for use in arteriosclerosis treatment when targeting macrophages but not accompanying vascular tissue is critical for effective and safe therapy