17 research outputs found
Antiproliferative activity and apoptosis induced by 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline on cells of leukemia lines
Quinazolines are known to be multitarget agents with broad spectrum of biological activity. Aim: To investigate anticancer activity of newly prepared 6-bromo-2-(morpholin-1-yl)-4-anilinoquinazoline (BMAQ) towards L1210, HL-60 and U-937 leukemia cells. Materials and Methods: Growth inhibition of BMAQ-treated cells was determined by cell counting using trypan blue staining technique. Apoptosis and cell cycle profile changes were analysed using internucleosomal DNA fragmentation assay, fluorescence microscopy and flow cytometry. Activity of caspase-3 was determined using colorimetric method. Results: Cell proliferation assay showed that BMAQ caused significant decrease of cell number in a dose-dependent manner. BMAQ induced cell death by apoptosis, based on results from DNA fragmentation, fluorescence microscopy and caspase-3 assays. Conclusion: Presented results clearly demonstrate that BMAQ is a promising anticancer agent with significant antiproliferative and apoptotic activities towards leukemia cells in vitro.ΠΠ²ΠΈΠ½Π°Π·ΠΎΠ»ΠΈΠ½Ρ ΠΈΠ·Π²Π΅ΡΡΠ½Ρ ΠΊΠ°ΠΊ Ρ
ΠΈΠΌΠΈΠΎΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΡΠΈΡΠΎΠΊΠΎΠ³ΠΎ ΡΠΏΠ΅ΠΊΡΡΠ° Π΄Π΅ΠΉΡΡΠ²ΠΈΡ. Π¦Π΅Π»Ρ: Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Π»Π΅ΠΉΠΊΠΎΠ·Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΉ L1210,
HL-60 ΠΈ U-937 ΠΈΠ·ΡΡΠΈΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½ΠΎΠ²ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° 6-Π±ΡΠΎΠΌΠΎ-2-(ΠΌΠΎΡΡΠΎΠ»ΠΈΠ½-1-ΠΈΠ»)-4-Π°Π½Π°Π»ΠΈΠ½ΠΎΠΈΠ½Π°Π·ΠΎΠ»ΠΈΠ½Π°
(BMAQ). ΠΠ΅ΡΠΎΠ΄Ρ: ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡΡΠ° ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ BMAQ ΠΈΠ·ΡΡΠ°Π»ΠΈ ΠΏΡΡΠ΅ΠΌ ΠΏΠΎΠ΄ΡΡΠ΅ΡΠ° ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΊΠ»Π΅ΡΠΎΠΊ,
ΠΎΠΊΡΠ°ΡΠ΅Π½Π½ΡΡ
ΡΡΠΈΠΏΠ°Π½ΠΎΠ²ΡΠΌ ΡΠΈΠ½ΠΈΠΌ. ΠΠΏΠΎΠΏΡΠΎΠ· ΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π° ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎΠΉ
ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΠΈ, ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π° ΠΠΠ ΠΈ ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ. ΠΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΊΠ°ΡΠΏΠ°Π·Ρ-3 ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ ΠΊΠΎΠ»ΠΎΡΠΈΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ BMAQ Π²ΡΠ·ΡΠ²Π°Π΅Ρ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΠΎΠ΅ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° Π»Π΅ΠΉΠΊΠΎΠ·Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΡΠΈ ΡΡΠΎΠΌ ΠΊΠ»Π΅ΡΠΊΠΈ, ΠΎΠ±ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΠ΅ BMAQ, ΠΏΠΎΠ³ΠΈΠ±Π°ΡΡ ΠΏΡΡΠ΅ΠΌ Π°ΠΏΠΎΠΏΡΠΎΠ·Π°, ΡΡΠΎ Π΄Π°Π΅ΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅Π»Π΅Ρ, ΠΌΠ΅ΠΆΠ½ΡΠΊΠ»Π΅ΠΎΡΠΎΠΌΠ½ΠΎΠΉ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΠΈΠ΅ΠΉ ΠΠΠ ΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠ΅ΠΉ ΠΊΠ°ΡΠΏΠ°Π·Ρ-3. ΠΡΠ²ΠΎΠ΄Ρ: ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ
ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ BMAQ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ ΠΈ ΠΏΡΠΎΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ
Π»Π΅ΠΉΠΊΠΎΠ·Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ in vitro
Combined methotrexate and coenzyme Q₁₀ therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress
Fungal vaccines and immunotherapeutics: current concepts and future challenges
Purpose of review The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy. Recent findings Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches. Summary We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.ThisworkwassupportedbytheNorthernPortugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a CiΓͺncia e Tecnologia (FCT) (contracts IF/00735/ 2014 to A.C., and SFRH/BPD/96176/2013 to C.C).info:eu-repo/semantics/publishedVersio
Structure and viscosity of a transformer oil-based ferrofluid under an external electric field
Various structural changes of ferrofluids have been intensively studied under external magnetic fields. In this work we present an experimental evidence of similar changes induced by an electric field. In the context of the electric field effect on ferrofluids structure, we studied a simple ferrofluid consisting of iron oxide nanoparticles coated with oleic acid and dispersed in transformer oil. The structural changes have been observed both on macroscopic and microscopic scale. We also demonstrate a remarkable impact of the electric field on the ferrofluid viscosity in relation to the reported structural changes. It was found that the electric field induced viscosity changes are analogous to the magnetoviscous effect. These changes and the electroviscous effect are believed to stem from the dielectric permittivity contrast between the iron oxide nanoparticles and transformer oil, giving rise to the effective electric polarization of the nanoparticles. It is highlighted that this electrorheological effect should be considered in studies of ferrofluids for high voltage engineering applications, as it can have impact on the thermomagnetic convection or the dielectric breakdown performance
The role of redox imbalance in relation to immunological process in adjuvant arthritis
The model of adjuvant arthritis (AA) is well characterized concerning the immunological processes involved. However knowledge on the participation of redox imbalance in the progression of AA is scarce. The link between oxidative stress (OS) and immunological status in arthritis should be more precisely investigated. In our experiments, we focused on AA development in the time domain. AA was induced in rats by a single intradermal injection of Mycobacterium butyricum in incomplete Freundβs adjuvant. All experiments included healthy animals (HC) and arthritic animals not treated. We confirmed that the clinical parameters hind paw volume and body weight became significantly modified starting around day 14 after AA induction and this change was maintained until the end of the experiment (day 28). We obtained a good agreement of clinical parameters with parameters of OS. Measurements of plasmatic protein carbonyls revealed damage of proteins caused by OS. Progression of lipid peroxidation in AA was described by analysis of TBARS, HNE- /MDA-protein adducts and F2 isoprostane levels in plasma. Total antioxidant status analyzed in plasma was decreased significantly in both the acute (day 21) and the subchronic phase (day 28) of AA. Further we focused on evaluating CoQ9 plasmatic levels. The arthritic process increased significantly the level of CoQ9 in comparison to HC. Evidently, the arthritic process stimulates the synthesis of CoQ9 and its transport to plasma. In the model of AA, we observed already on experimental day 7 that AA was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as phorbol myristate acetate stimulated chemiluminescence. As the changes in neutrophils occur before the clinical parameter HPV starts to be increased, for further evaluation of neutrophil functionality we chose experimental day 7. The functionality of peripheral blood neutrophils in AA was described by phagocytosis, oxidative burst and metabolic activity. Both phagocytosis and oxidative burst were increased due to arthritis, and that despite the decreased metabolic activity. Analysis of OS in tissue showed changed GGT activity in spleen and joint homogenate accompanied by increased chemiluminescence. The OS parameters were in close relationship with time profiles of selected cytokines, chemokine MCP-1 and of C-reactive protein levels in plasma. Measurements of the immunoregulatory index in peripheral blood and lipoxygenase tissue activity (lung, liver) were also included. Our observations have evidenced the importance of pharmacological regulation of redox imbalance in arthritis. (VEGA 2/0090/08, COST B35, APVV-51-017905, APVV-21-055205