Search

Baran Marzena, Miziak Paulina, Bonio Katarzyna. The use of proteasome inhibitors in anti-cancer therapy. Journal of Education, Health and Sport. 2020;10(7):231-235. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.07.026 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.07.026 https://zenodo.org/record/3963020 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.07.2020. Revised: 15.07.2020. Accepted: 27.07.2020. The use of proteasome inhibitors in anti-cancer therapy Marzena Baran1, Paulina Miziak1, Katarzyna Bonio2 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2 Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin Abstract Proteins are the basic building blocks of the human body. Most proteins, after fulfilling their function, are degraded with the help of a multi-catalytic proteolytic complex - the 26S proteasome, thanks to its prior labeling with a poly-ubiquitin chain. The ubiquitin-proteasome complex is involved in the control of many important cellular processes. It is involved in the cell cycle, cell proliferation and growth, apoptosis, control of receptor function, quality of proteins in the endoplasmic reticulum, immune response, stress response and other extracellular factors. The dysfunction of the ubiquitin-proteasome pathway plays an important role in the development of many neurodegenerative and neoplastic diseases, as well as diseases with an immune and infectious origin. Accordingly, research is being conducted where the UPS complex is the target of therapeutic activities. Specific proteasome inhibitors are used in cancer therapy. The first to be approved by the FDA was bortezomib, which is a peptide derivative of boric acid. It has the ability to initiate the process of apoptosis by inhibiting the activity of the NF-κB protein, which is a transcription factor. This compound is used in the treatment of multiple myeloma and malignant lung and breast cancers. There are also studies on the combination of proteasome inhibitors with other chemotherapeuticam. There is still growing interest in research aimed at obtaining substances that allowed to control the mechanisms of proteolytic degradation. Key words: Ubiquitin, proteasome, proteasome inhibitors, anti-cancer therapy

Baran Marzena, Miziak Paulina, Bonio Katarzyna. Characteristic of warfarin. Journal of Education, Health and Sport. 2020;10(8):78-80. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.009 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.009 https://zenodo.org/record/3969341 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.07.2020. Revised: 25.07.2020. Accepted: 01.08.2020. Characteristic of warfarin Marzena Baran1, Paulina Miziak1, Katarzyna Bonio2 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin Abstract In modern pharmacology, compounds of natural origin are gaining more and more recognition. One of them is warfarin, which is a compound of organic coumarin derivatives. It is used medicinally in the anticoagulant doctor. This compound was commercially introduced to the United States in the 1950s. It has been available on the Polish market since 2006. Warfarin is an antagonist of vitamin K. It works by inhibiting the synthesis of vitamin K in the liver and thus blocking the synthesis of vitamin K dependent blood clotting factors (II, VII, IX, X). It is widely used by people suffering from cardiovascular diseases such as venous thrombosis and venous embolism. Adopted by patients with suspected or after a heart attack. Despite its undisputed positive effect, one should remember about the numerous side effects resulting from long-term use of warfarin. They may be due to intolerance to this compound, which causes nausea, vomiting, and allergic reactions. Moreover, recent studies show that it may have a destructive effect on the liver and cause calcification of blood vessels. Keep in mind that warfarin can interact with many substances you are taking for other medical conditions. Agents that increase the effects of warfarin include antibiotics such as erythromycin, deoxicillin, commonly used drugs containing caffeine, acetylsalicylic acid and naturally derived compounds found in ginkgo, garlic and sage. Compounds that weaken the effect of warfarin are barbiturates, cyclosporine, vitamin C, and St. John's wort. Key words: warfarin, cumarine, vitamin K antagonist, medicine, anticoagulants

Breast cancer (BC) is the leading cause of death in women all over the world. Currently, combined chemotherapy with two or more agents is considered a promising anti-cancer tool to achieve better therapeutic response and to reduce therapy-related side effects. In our study, we demonstrated an antagonistic effect of cytostatic agent-cisplatin (CDDP) and histone deacetylase inhibitor: cambinol (CAM) for breast cancer cell lines with different phenotypes: estrogen receptor positive (MCF7, T47D) and triple negative (MDA-MB-231, MDA-MB-468). The type of pharmacological interaction was assessed by an isobolographic analysis. Our results showed that both agents used separately induced cell apoptosis, however, applying them in combination ameliorated antiproliferative effect for all BC cell lines indicating antagonistic interaction. Cell cycle analysis showed that CAM abolished cell cycle arrest in S phase, which was induced by CDDP. Additionally, CAM increased cell proliferation compared to CDDP used alone. Our data indicate that CAM and CDDP used in combination produce antagonistic interaction, which could inhibit anti-cancer treatment efficacy, showing importance of preclinical testing.

Miziak Paulina, Baran Marzena, Bonio Katarzyna, Piech Piotr. Nanoparticles in medicine. Journal of Education, Health and Sport. 2020;10(8):17-21. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.002 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.002 https://zenodo.org/record/3967771 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.07.2020. Revised: 15.07.2020. Accepted: 30.07.2020. Nanoparticles in medicine Paulina Miziak1, Marzena Baran1, Katarzyna Bonio2, Piotr Piech3 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin 3Human Anatomy Department, Medical University of Lublin, Poland Abstract Nanotechnology is a new, interdisciplinary field of science, the products of which are nanoparticles, i.e. structures that, thanks to their unique physical and chemical properties conditioned by their nanometric dimensions, have found wide application in medicine, pharmacy and biotechnology. Currently, they play a particularly important role as drug carriers, antibacterial and antiviral substances. They are also used in diagnostics, genetic tests, and increasing the accuracy of biological tests. The enormous possibilities of nanoparticles concern their potential use as drug delivery systems, factors improving the quality of anticancer radiotherapy and supporting molecular imaging, as well as compounds with highly bactericidal, fungicidal and antiviral properties. Therefore, it is crucial to implement therapies based on nanoparticles into clinical trials, as they can be an excellent diagnostic and therapeutic tool for many diseases, including cancer. However, it is necessary to overcome certain barriers due to the nature of some nanoparticles, such as problems with biodegradability and porosity. Despite the benefits of using nanostructures, the possibility of side effects caused by the action of metal nanoparticles absorbed by organisms has not been ruled out. Key words: nanoparticle, medicine, drug delivery, peptide, tissue

Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in Mtb. The precise biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl a denosine m ono s ulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and FACL enzymes. We identified several potent compounds including 12-azidododecanoyl-AMS 28, 11-phenoxyundecanoyl-AMS 32, and nonyloxyacetyl-AMS 36 with minimum inhibitory concentrations (MICs) against M. tuberculosis ranging from 0.098 to 3.13 μM. Compound 32 was notable for its impressive biochemical selectivity against FAAL28 (apparent Ki = 0.7 μM) versus FACL19 (Ki > 100 μM), and uniform activity against a panel of multidrug and extensively drug-resistant TB strains with MICs ranging from 3.13 to 12.5 μM in minimal (GAST) and rich (7H9) media. The SAR analysis provided valuable insights for further optimization of 32 and also identified limitations to overcome.

This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α 1 -adrenoceptors, with exception of 6d, and are selective over α 2 receptor. The most potent compound 5f displayed 62-fold α 2 / α 1 selectivity with K i value of 27.3 nM for α 1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α 1 -adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α -adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.

The aim of the article is to discuss the possibilities of using the concept of task­based teaching and its methodology to improve intercultural competencies of people learning Polish as a foreign language. The author of the article claims that such methods and strategies within CERF can be extremely effective in improving intercultural competencies. The article concludes with a list of tasks suggested by the author as suitable to achieve this goal.

This paper describes the synthesis of a series of new N-arylpiperazine derivatives of pyridine and 2-pyridone. The in vitro pharmacological study indicated that all of the compounds possess affinity towards α1-adrenoceptors, with exception of 6d, and are selective over α2 receptor. The most potent compound 5f displayed 62-fold α2/α1 selectivity with Ki value of 27.3 nM for α1 receptor. Selectivity of other ligands ranged from 6 to more than 146-fold. Hydrochlorides of selected compounds with the best α1-adrenoceptor affinity (7b, 7e, 7f, 8b) were tested in vivo (hypotensive activity test in rats) and the results proved their α-adrenoreceptor antagonistic activity. Furthermore, the lipophilicity of the investigated compounds has been assessed experimentally and in silico.

Fused dihydrooxazoles are produced by the reaction of 8-bromoteophylline (1), 6-bromo-2-pyridone (7), or 2-bromobenzimidazole (11) with an N-substituted N-(2,3-epoxypropyl)amine. The product derived from 1 undergoes rearrangement to a fused dihydrooxazine while the fused dihydrooxazoles derived from 7 and 11 are stable. J. Heterocyclic Chem., (2011).