16 research outputs found
Antiproliferative and pro-apoptotic effects of Pseudevernia furfuracea (L.) Zopf extract and its active component physodic acid via oxidative stress and DNA damage in breast cancer cells
No full textBackgroundMammary gland malignancies are the most diagnosed oncological diseases in women. The currently available treatment faces several problems, including resistance to cytostatics and the relatively high recurrence rates. These limitations have led to an increasing interest in natural substances as potential anticancer agents. Therapeutic approaches using a combination of natural anticancer agent and conventional cytostatic drug could also be beneficial in minimising the risk of chemotherapy. In the present study, we evaluated the anticancer effect of Pseudevernia furfuracea (L.) Zopf extract (PSE) and isolated the secondary metabolite physodic acid (PHY) in in vitro models of breast cancer subtypes (ER+, HER2+, and triple negative).MethodsTo investigate the effects of tested compounds, a range of assays were employed. BrdU and clonogenic assays were used to evaluate antiproliferative activity. Flow cytometry and Western blot were used to demonstrate apoptotic cell death, oxidative stress, DNA damage, and immune checkpoint modulation in a time-dependent manner (24, 48, and 72 h).ResultsPSE and PHY induced cycle arrest at a G1 checkpoint with modulation of cell cycle-related proteins. Furthermore, activation of intrinsic apoptotic pathway, involving changes in Bcl-2 family proteins, caspase-3/-7 activity, caspase-9 cleavage, cytochrome c release, and PARP cleavage, was detected in all BC cells. Moreover, we determined the PSE- and PHY-mediated generation of ROS and RNS, which led to DNA damage and the activation of the DNA damage response.ConclusionsTreatment with PSE and PHY in BC cells resulted in mitochondrial apoptosis associated with oxidative stress and DNA damage. Furthermore, modulation of immune checkpoint PD-1/PD-L1 was demonstrated. Based on the results, we assume the use of PSE and PHY as promising targeted agents for BC
Molecular detection of ureaplasma urealyticum infection from clinical urogenital swabs
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Polyphosphoinositide Metabolism in Polymorphonuclear Cells From Healthy and Thermally Injured Rats: Effect of the Immunomodulator RU 41740
No full textAbstract
Burn trauma is associated with alterations of various components of host defenses, including impaired neutrophil functions. In an animal model of experimental thermal injury, we studied if the modifications of cellular reactivity result from alterations in signalling systems by comparing polyphosphoinositide breakdown, particularly the production of inositol phosphates (IP, IP2 IP3), in healthy and burned rat polymorphonuclear neutrophil leukocytes (PMNs).
Neutrophil activators such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) and serum-opsonized zymosan increased in vitro production of inositol phosphates in PMNs from healthy rats. The immunomodulator RU 41740 had no effect by itself, but decreased the stimulating effect of fMLP and zymosan. In PMNs from burned rats, the stimulating effects of fMLP and zymosan were decreased, while RU 41740 stimulated inositol phosphate generation. In vivo treatment with RU 41740 inhibited the activation of phosphoinositide metabolism by fMLP or zymosan in healthy rat PMNs. Similar treatment of burned rats after injury restored the stimulating effect of fMLP and zymosan on inositol phosphate accumulation in PMNs.
Thus, RU 41740 can modulate fMLP and zymosan receptor-mediated signal transduction, inducing an attenuation of the phosphatidylinositol hydrolysis response. After burn injury, when the activating effects of fMLP and zymosan are inhibited, RU 41740 can, on the contrary, stimulate phospholipase C-mediated polyphosphoinositide turnover and the formation of intracellular messengers such as IP3.
These data show that RU 41740 has different effects on polyphosphoinositide metabolism in rat PMNs, according to the physiological and pathological state of the animals. Interestingly, it has a beneficial action on the post-burn decrease in PMN reactivity.</jats:p
YPSP01-12 - Lipid Metabolism Changes After Switching To Ziprasidone
No full textIntroductionIncreasing numbers of reports concerning lipid dysregulation, diabetes and hyperglycaemia in patients treated with atypical antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications.ObjectivesThe available literature notes that ziprasidone is a weight-neutral antipsychotic and that lipids anomalies improve when patient are switched from other atypical antipsychotics to ziprasidone.AimsThe purpose of this study was to examine the association of treatment with ziprasidone and changes in serum levels of cholesterol, triglycerides, serum levels of glucose and BMI changes.MethodsProspective, cohort, multicenter, open design in 373 in- and outpatients treated with ziprasidone for broad spectrum of psychotic disorders in flexible dose manner. The analysis was done in group of patients with no previous antipsychotic treatment or discontinuation of antipsychotic treatment longer than 3 months compared to group of patients directly switched from another antipsychotic treatment to ziprasidone.ResultsChanges in fasting serum levels of total cholesterol were significant from baseline at week 24 in subgroup of patients directly switched from another antipsychotic treatment to ziprasidone (5,12 vs 4,94 mmol/l, p< 0,05, ANOVA).ConclusionsWe have observed statistical significant difference in fasting serum levels of total cholesterol in patients directly switched from another antipsychotic treatment to ziprasidone.</jats:sec
Cytogenetic abnormalities predict treatment-free interval and response to therapy in previously untreated chronic lymphocytic leukemia patients
No full textHistamine H2 receptors and histidine decarboxylase in normal and leukemic human monocytes and macrophages
No full text Spontaneous and all-trans-retinoic acid (RA)-induced differentiation of normal human monocytes and of leukemic THP-1 monocytes into macrophages resulted in a progressive loss of adenosine 3',5'-cyclic monophosphate production induced by histamine via typical H2 receptors (H2R). In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H2R gene fourfold, suggesting transcriptional control by a RA response element. Scatchard plots of [3H]tiotidine binding indicated the expression of H2R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes into macrophages decreased H2R density from 91.8 to 43.1 fmol/mg protein, with no change in affinity (Kd = 9.9 to 11.2 nM). In THP-1 macrophages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced H2O2 formation via the activation of H2 receptors. Expression of the H2R gene, histamine accumulation, and histidine decarboxylase activity were also demonstrated in normal human monocytes/macrophages and peripheral lymphocytes. Histamine and H2R may therefore affect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors and lineages in the bone marrow and peripheral tissues. </jats:p
