Potential use of histone deacetylase inhibitors in cancer therapy

Epigenetics is a branch of science that focuses on mechanisms related to control and modification of expression of genetic material without any changes to its sequences. Such mechanisms include post-translational modifications of histones. It is widely known that carcinogenesis is related to hypoacetylation of genes that influence apoptosis, the cell cycle, cell signaling, the immunologic response, angiogenesis and occurrence of metastasis. Currently conducted research focuses on several strategies related to epigenetic therapy. One such strategy is based on the use of histone deacetylase inhibitors. This paper presents mechanisms through which these compounds work and a summary of their characteristics. It also includes a review of clinical tests related to histone deacetylase inhibitors, as well as their relationship with other chemotherapeutic methods. A better understanding of the involved mechanisms will provide a rational basis to improve the therapeutic outcome of available antitumor agents

Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals

Objective. Oxidized cholesterol derivatives are thought to exert atherogenic effect thus adversely affecting vascular endothelium. The aim of the study was to assess the effect of 5α,6α-epoxycholesterol on experimentally induced hypercholesterolemia in rabbits, and the levels of homocysteine (HCY), asymmetric dimethylarginine (ADMA), paraoxonase-1 (PON-1), and inflammatory parameters (IL-6, TNF-α, CRP). Material and methods. The rabbits were divided into 3 groups, 8 animals each, and fed with basic fodder (C), basic fodder plus cholesterol (Ch) or basic fodder plus 5α,6α-epoxycholesterol, and unoxidized cholesterol (ECh). Serum concentrations of studied parameters were determined at 45-day intervals. The study was continued for six months. Results. We demonstrated that adding 5α,6α-epoxycholesterol to basic fodder significantly affected lipid status of the experimental animals, increasing total cholesterol and LDL cholesterol levels, as well as HCY and ADMA levels, whilst leaving the PON-1 activity unaffected. Additionally, the ECh group presented with significantly higher concentrations of inflammatory biomarkers (IL-6, TNF-α, and CRP). In the Ch group, lower yet significant (as compared to the C group) changes of levels of studied parameters were observed. Conclusion. Exposure of animals with experimentally induced hypercholesterolemia to 5α,6α-epoxycholesterol increases dyslipidaemia, endothelial dysfunction, and inflammatory response

5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Oxidative Stress in Rats on Low-Cholesterol Diet

Objective. Cholesterol oxidation products have an established proatherogenic and cytotoxic effect. An increased exposure to these substances may be associated with the development of atherosclerosis and cancers. Relatively little, though, is known about the effect of phytosterol oxidation products, although phytosterols are present in commonly available and industrial food products. Thus, the aim of the research was to assess the effect of 5α,6α-epoxyphytosterols, which are important phytosterol oxidation products, on redox state in rats. Material and Methods. The animals were divided into 3 groups and exposed to nutritional sterols by receiving feed containing 5α,6α-epoxyphytosterols (ES group) and 5α,6α-epoxycholesterol (Ech group) or sterol-free feed (C group). The levels of malondialdehyde (MDA), conjugated dienes (CD), and ferric reducing antioxidant potential (FRAP) were assayed in the plasma; anti-7-ketocholesterol antibodies and activity of paraoxonase-1 (PON1) were determined in serum, whereas the activity of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), S-glutathione transferase (GST), and superoxide dismutase (SOD) were assayed in RBCs. Results. During the experiment, the levels of lipid peroxidation products increased, such as CD and anti-7-ketocholesterol antibodies. At the same time, the plasma levels of FRAP and serum activity of PON1 decreased alongside the reduced activity of GPx, GR, and SOD in RBCs. There was no effect of the studied compounds on the plasma MDA levels or on the activity of CAT and GST in RBCs. Conclusions. Both 5α,6α- epoxyphytosterols and 5α,6α-epoxycholesterols similarly dysregulate the redox state in experimental animal model and may significantly impact atherogenesis

5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Nitrosative Stress and Inflammatory Cytokine Production in Rats on Low-Cholesterol Diet

Objective. Oxidized cholesterol derivatives are compounds with proven atherogenic and mutagenic effects. However, little is known about the effect of oxidized plant sterol derivatives (oxyphytosterols), whose structure is similar to the one of oxycholesterols. Our previous studies indicate that they have a similar profile of action, e.g., both exacerbate disorder of lipid metabolism and oxidative stress in experimental animals. The aim of the present study was to assess the effect of epoxycholesterol and epoxyphytosterols (mainly sitosterol) on the severity of nitrosative stress and the concentration of selected proinflammatory cytokines in blood and liver tissue of rats on a low-cholesterol diet. Material and Methods. Forty-five male Wistar rats were fed with feed containing 5α,6α-epoxyphytosterols (ES group, n: 15), 5α,6α-epoxycholesterol (ECh group, n: 15), and oxysterol-free feed (C group, n: 15) for 90 days (daily dose of oxysterols: 10 mg/kg). At the end of the experiment, nitrotyrosine, TNF-α, IL-1β, IL-6, and lipid metabolism parameters were determined in blood serum. Furthermore, nitrotyrosine, TNF-α, cholesterol, and triglyceride content were determined in liver homogenates. Results. Serum nitrotyrosine, IL-1β, and TNF-α concentrations as well as TNF-α content in the liver were significantly higher in both groups exposed to oxysterols (ECh and ES groups) as compared to the C group. The serum IL-6 level and nitrotyrosine content in the liver were significantly higher in the ECh group, as compared to the C and ES groups. There was evidence to support the dyslipidemic effect of studied compounds. Conclusions. The results indicate that oxidized plant sterols have a similar toxicity profile to that of oxycholesterols, including nitrosative stress induction, proinflammatory effect, and impaired lipid metabolism

Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals

Objective. Oxidized cholesterol derivatives are thought to exert atherogenic effect thus adversely affecting vascular endothelium. The aim of the study was to assess the effect of 5α,6α-epoxycholesterol on experimentally induced hypercholesterolemia in rabbits, and the levels of homocysteine (HCY), asymmetric dimethylarginine (ADMA), paraoxonase-1 (PON-1), and inflammatory parameters (IL-6, TNF-α, CRP). Material and methods. The rabbits were divided into 3 groups, 8 animals each, and fed with basic fodder (C), basic fodder plus cholesterol (Ch) or basic fodder plus 5α,6α-epoxycholesterol, and unoxidized cholesterol (ECh). Serum concentrations of studied parameters were determined at 45-day intervals. The study was continued for six months. Results. We demonstrated that adding 5α,6α-epoxycholesterol to basic fodder significantly affected lipid status of the experimental animals, increasing total cholesterol and LDL cholesterol levels, as well as HCY and ADMA levels, whilst leaving the PON-1 activity unaffected. Additionally, the ECh group presented with significantly higher concentrations of inflammatory biomarkers (IL-6, TNF-α, and CRP). In the Ch group, lower yet significant (as compared to the C group) changes of levels of studied parameters were observed. Conclusion. Exposure of animals with experimentally induced hypercholesterolemia to 5α,6α-epoxycholesterol increases dyslipidaemia, endothelial dysfunction, and inflammatory response

The role of vitamin D in the development and course of SARS-CoV-2 infection and other viral diseases

Witamina D jest rozpuszczalnym w tłuszczach prohormonem. Wykazuje wielokierunkowe działanie, wpływając m.in. na procesy mineralizacji kości. Bierze również udział w modulacji układu immunologicznego. Z uwagi na wskazane właściwości prowadzone są badania dotyczące wpływu witaminy D na rozwój zakażenia SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Postulowanym mechanizmem działania witaminy D w zakażeniu koronawirusem jest oddziaływanie na równowagę ACE2/ACE (angiotensin converting enzyme) oraz hamowanie burzy cytokin. Badania wskazują, że niskie poziomy 25(OH)D w surowicy mogą zwiększać zachorowalność. Wyniki badań wpływu hipowita-minozy na ciężkość przebiegu COVID-19 (coronavirus disease 19) oraz śmiertelność z powodu tej choroby są niejednoznaczne. Witamina D odgrywa również rolę w zakażeniach innymi wirusami, na przykład wirusem grypy. W celu jednoznacznego określenia funkcji witaminy D w infekcji koronawirusem potrzebne są dalsze randomizowane badania.Vitamin D is a prohormone soluble in fats. It has multidirectional effects, among others on bone mineralizator processes and modulation of the immune system. Due to these properties, research is being conducted on the influence of vitamin D on the development of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. The postulated mechanism of action of vitamin D in coronavirus infection is that it affects the ACE2/ACE (angiotensin converting enzyme) balance and inhibits the cytokine storm. Research shows that low serum levels of 25(OH)D can increase morbidity. The results of studies on the influence of hypovitaminosis on the severity of the course of COVID-19 (coronavirus disease 19) infection and mortality are inconclusive. Vitamin D also plays a role in infections caused by other viruses, such as the flu virus. Further randomized studies are needed to clearly define the function of vitamin D in coronavirus infection

Role of selected MGMT polymorphisms in cancer development

Materiał genetyczny komórki jest nieustannie narażony na działanie czynników mutagennych. Odpowiednie mechanizmy chroniące przed szkodliwym wpływem mutagenów są niezwykle ważne dla prawidłowego funkcjonowania oraz kontroli proliferacji komórek. Jednym z mechanizmów naprawczych jest działanie enzymu MGMT, który odpowiada za ochronę DNA komórki przed czynnikami alkilującymi. Różnice w aktywności enzymu, wynikające z występowania wielu odmian polimorficznych jego genu, mogą prowadzić niekiedy do zwiększonego ryzyka zachorowania na nowotwory. Tematem pracy jest omówienie roli niektórych polimorfizmów genu MGMT w rozwoju oraz terapii chorób nowotworowych.Cell DNA is constantly exposed to mutagenic factors. DNA repair mechanisms are very important to provide proper cell functioning and proliferation control. One of the DNA repair mechanisms is based on the O6-methylguanine-DNA methyltransferase enzyme, which provides protection against alkylating agents. Differences in MGMT enzyme activity may be caused by MGMT gene polymorphisms. MGMT polymorphisms may increase cancer risk, e.g. lung cancer or esophageal cancer. In this review we have described the role of some MGMT polymorphisms in cancer development and therapy

Role of selected MGMT polymorphisms in cancer development

Materiał genetyczny komórki jest nieustannie narażony na działanie czynników mutagennych. Odpowiednie mechanizmy chroniące przed szkodliwym wpływem mutagenów są niezwykle ważne dla prawidłowego funkcjonowania oraz kontroli proliferacji komórek. Jednym z mechanizmów naprawczych jest działanie enzymu MGMT, który odpowiada za ochronę DNA komórki przed czynnikami alkilującymi. Różnice w aktywności enzymu, wynikające z występowania wielu odmian polimorficznych jego genu, mogą prowadzić niekiedy do zwiększonego ryzyka zachorowania na nowotwory. Tematem pracy jest omówienie roli niektórych polimorfizmów genu MGMT w rozwoju oraz terapii chorób nowotworowych.Cell DNA is constantly exposed to mutagenic factors. DNA repair mechanisms are very important to provide proper cell functioning and proliferation control. One of the DNA repair mechanisms is based on the O6-methylguanine-DNA methyltransferase enzyme, which provides protection against alkylating agents. Differences in MGMT enzyme activity may be caused by MGMT gene polymorphisms. MGMT polymorphisms may increase cancer risk, e.g. lung cancer or esophageal cancer. In this review we have described the role of some MGMT polymorphisms in cancer development and therapy

Prevalence of Borrelia burgdorferi Sensu Lato Genospecies in Ixodes ricinus Ticks from Recreational Areas of Silesia Częstość występowania genogatunków Borrelia burgdorferi sensu lato w populacji kleszczy Ixodes ricinus na terenach rekreacyjnych województ

Abstract Background. Lyme borreliosis is a multisystem disorder caused by the genetically diverse spirochetes Borrelia burgdorferi sensu lato. Different species of pathogenic Borrelia are able to cause various symptoms. Borrelia is transmitted to humans by ticks