SCID mice model in vivo evaluation of autologous and allogeneic dendritic cells activity on B-cell chronic lymphocytic leukemia.

In the present study we investigated in vivo therapeutic potential of DCs vaccines in B-cell chronic lymphocytic leukemia (B-CLL). On the day 0 the SCID mice were intraperitoneally inoculated with peripheral blood mononuclear cells (PBMC) of B-CLL patients at a dose of 10-30 x 10(6) and left untreated (controls) or i.p. injected on the day 7 with 0.2 - 14.0 x 10(6) dendritic cells. DCs were generated in vitro from peripheral blood monocytes of B-CLL donors (autologous DCs) or healthy donors (allogeneic cells) and pulsed with B-CLL antigens. On the day 14, the effect of implanted cells interactions was evaluated by a counting of CD19+CD5+ human leukemic cells and human T cells in the peritoneal fluid of mice. We found, that mean numbers of CD19+CD5+ leukemic cells as well as human T cells were lowered in peritoneal fluid of mice treated with allogeneic APCs. However, we did not observe similar effects with autologous DCs

Antifungal Activity and Mechanism of Action of the Co(III) Coordination Complexes With Diamine Chelate Ligands Against Reference and Clinical Strains of Candida spp.

Although many antifungal agents are available in clinical treatment, increasing resistance of fungi, especially Candida species, to the available drugs requires the development of new safe and non-toxic compounds with novel modes of action as effective treatment against resistant microorganisms. Cobalt complexes are very interesting and attractive as potential candidates with antimicrobial activity. Their therapeutic uses as antiviral, antibacterial antifungal, antiparasitic, antitumour, transferrin transporters, and anti-inflammatory agents are being intensively investigated. In this study we examined the antifungal activity of Co(III) complexes with diamine chelate ligands against a broad spectrum of Candida species. Minimum inhibitory concentration was determined by the microbroth dilution method and with serial passaging assay; the synergistic antimicrobial activity of the tested complexes combined with two antifungal drugs (ketoconazole and amphotericin B) was made by checkerboard assay. The effects of Co(III) complexes on yeast cell morphology were studied by optical and transmission electron microscopy. The mode of action of Co(III) complexes on the yeast cell wall (sorbitol assay) and cell membrane (ergosterol assay) were investigated. The cytotoxic effects of the tested compounds on red blood cells and the human keratinocyte (HaCaT) cell line were also evaluated. The analyzed compounds revealed significant antifungal activity for selected strains of Candida species; [CoCl2(dap)2]Cl (1) and [CoCl2(en)2]Cl (2) were more effective than ketoconazole. Its probable mechanism of action did not involve the cell wall or ergosterol binding. However, the checkerboard assay showed, that the antifungal activity of ketoconazole increased in combination with the tested complexes of Co(III). Our results suggest that both diamine complexes with Co(III) analogs caused damage to mitochondrial membrane or the membrane of the endoplasmic reticulum. The effect was observed by transmission electron microscope. Co(III) complexes with diamine chelate ligands are non-toxic at concentrations active against Candida species. This study provides new data on potential antifungal drugs, especially against Candida species

Antimicrobial photodynamic therapy with fulleropyrrolidine : photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies

A family of N-methylpyrrolidinium fullerene iodide salts has been intensively studied to determine their applicability in antimicrobial photodynamic therapy (APDT). This study examined in vitro the efficacy of a C60 fullerene functionalized with one methylpyrrolidinium group to kill upon irradiation with white light gram-negative and gram-positive bacteria, as well as fungal cells, and the corresponding mechanism of the fullerene bactericidal action. The in vitro studies revealed that the high antistaphylococcal efficacy of functionalized fullerene could be linked to their ability to photogenerate singlet oxygen and superoxide anion. Following Staphylococcus aureus photoinactivation, no modifications of its genomic DNA were detected. In contrast, photodamage of the cell envelope seemed to be a dominant mechanism of bactericidal action. In in vivo studies, a 2 log10 reduction in the average bioluminescent radiance between treated and non-treated mice was reached. One day post APDT treatment, moist and abundant growth of bacteria could be observed on wounds of non-fulleropyrrolidine and dark control mice. APDT-treated wounds stayed visibly clear up to the third day. Moreover, cytotoxicity test on human dermal keratinocytes revealed great safety of using the sensitizer toward eukaryotic cells. These data indicate potential application of functionalized fullerene as antistaphylococcal sensitizer for superficial infections

Mapping the Human Brain in Frequency Band Analysis of Brain Cortex Electroencephalographic Activity for Selected Psychiatric Disorders

There are still no good quantitative methods to be applied in psychiatric diagnosis. The interview is still the main and most important tool in the psychiatrist work. This paper presents the results of electroencephalographic research with the subjects of a group of 30 patients with psychiatric disorders compared to the control group of healthy volunteers. All subjects were solving working memory task. The digit-span working memory task test was chosen as one of the most popular tasks given to subjects with cognitive dysfunctions, especially for the patients with panic disorders, depression (including the depressive phase of bipolar disorder), phobias, and schizophrenia. Having such cohort of patients some results for the subjects with insomnia and Asperger syndrome are also presented. The cortical activity of their brains was registered by the dense array EEG amplifier. Source localization using the photogrammetry station and the sLORETA algorithm was then performed in five EEG frequency bands. The most active Brodmann Areas are indicated. Methodology for mapping the brain and research protocol are presented. The first results indicate that the presented technique can be useful in finding psychiatric disorder neurophysiological biomarkers. The first attempts were made to associate hyperactivity of selected Brodmann Areas with particular disorders

Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy

Estrogen receptor (ER)-positive breast cancer accounts for around two-thirds of breast cancer occurrences, with endocrine therapy serving as first-line therapy in most cases. Targeting estrogen signaling pathways, which play a central role in regulating ER+ breast cell proliferation and survival, has proven to improve patient outcomes. However, despite the undeniable advantages of endocrine therapy, a subset of breast cancer patients develop acquired or intrinsic resistance to ER-targeting agents, limiting their efficacy. The activation of downstream ER signaling pathways upregulates pro-survival mechanisms that have been shown to influence the response of cells to endocrine therapy. The Bcl-2 family proteins play a central role in cell death regulation and have been shown to contribute to endocrine therapy resistance, supporting the survival of breast cancer cells and enhancing cell death evasion. Due to the overexpression of anti-apoptotic Bcl-2 proteins in ER-positive breast cancer, the role of these proteins as potential targets in hormone-responsive breast cancer is growing in interest. In particular, recent advances in the development of BH3 mimetics have enabled their evaluation in preclinical studies with ER+ breast cancer models, and BH3 mimetics have entered early ER+ breast cancer clinical trials. This review summarizes the molecular mechanisms underlying the regulation of Bcl-2 family proteins in ER+ breast cancer. Furthermore, an overview of recent advances in research regarding the efficacy of BH3 mimetics in ER+ breast cancer has been provided

Molecular Research and Treatment of Breast Cancer

Breast cancer is the leading cause of cancer-related deaths in the female population [...