We introduce a method of azimuthally invariant 3D Mueller-matrix (MM) layer-by-layer mapping of the phase and amplitude parameters of anisotropy of the partially depolarizing layers of benign (adenoma) and malignant (carcinoma) prostate tumours. The technique is based on the analysis of spatial variations of Mueller matrix invariant (MMI) of histological sections of benign (adenoma) and malignant (carcinoma) tissue samples. The phase dependence of magnitudes of the first-to-fourth order statistical moments is applied to characterize 3D spatial distributions of MMI of linear and circular birefringence and dichroism of prostate tumours. The high order statistical moments and phase sections of the optimal differentiation of the polycrystalline structure of tissue samples are revealed. The obtained results are compared with the results obtained by conventional methods utilizing polarized light, including 2D and 3D Mueller matrix imaging.

Introduction. Rare-earth orthovanadate nanoparticles (ReVO4:Eu3+, Re = Gd, Y or La) are promising agents for photodynamic therapy of cancer due to their modifiable redox properties. However, their toxicity limits their application. Objective. The aim of this research was to elucidate pro-eryptotic effects of GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles with identification of underlying mechanisms of eryptosis induction and to determine their pharmacological potential in eryptosis-related diseases. Methods. Blood samples (n=9) were incubated for 24 h with 0-10-20-40-80 mg/L GdVO4:Eu3+ or LaVO4:Eu3+ nanoparticles, washed and used to prepare erythrocyte suspensions to analyze the cell membrane scrambling (annexin-V-FITC staining), cell shrinkage (forward scatter signaling), reactive oxygen species (ROS) generation through 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) staining and intracellular Ca2+ levels via FLUO4 AM staining by flow cytometry. Internalization of europium-enabled luminescent GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles was assessed by confocal laser scanning microscopy. Results. Both nanoparticles triggered eryptosis at concentrations of 80 mg/L. ROS-mediated mechanisms were not involved in rare-earth orthovanadate nanoparticles-induced eryptosis. Elevated cytosolic Ca2+ concentrations were revealed even at subtoxic concentrations of nanoparticles. LaVO4:Eu3+ nanoparticles increased intracellular calcium levels in a more pronounced way compared with GdVO4:Eu3+ nanoparticles. Our data disclose that the small-sized (15 nm) GdVO4:Eu3+ nanoparticles were internalized after a 24 h incubation, while the large-sized (~30 nm) LaVO4:Eu3+ nanoparticles were localized preferentially around erythrocytes. Conclusions. Both internalized GdVO4:Eu3+ and non-internalized LaVO4:Eu3+ nanoparticles (80 mg / L) promote eryptosis of erythrocytes after a 24 h exposure in vitro via Ca2+ signaling without involvement of oxidative stress. Eryptosis is a promising model for assessing nanotoxicity.

No abstract

e17015 Background: It is thought that the occurrence and progression of tumors, such as prostate cancer (PCа), may be due to decreased levels of tumor-inhibiting microRNAs and/or overexpression of oncogenic microRNAs, but their specificity and role in tumor progression are contradictory. That is why the study of the possibility of using miRNAs as prognostic markers is especially relevant. Objective: to investigate the features of tumor -associated microRNAs-21 and -221 expression in PCa tissue with different risk of progression and to determine the relationship of their indicators with the molecular profile of tumors. Methods: The study was conducted on the clinical material of 60 patients with PCa stage II-III, who were treated in Rivne Regional Hospital and Rivne oncological center during 2018-2021 years. Determination of the risk of PCa progression was performed by D'Amico et al. (1998). Immunohistochemical study of Ki-67 expression (clone MIB -1) and androgen receptors (AR) (clone 441) were performed on paraffin sections of tumor tissue using the Ultra Vision LP Detection System (Thermo Scientific, USA). Determination of microRNA-21 and -221 levels were determined using real-time quantitative PCR. Statistical processing of the results was performed using GraphPad Prism 8. Results: It is determined that a characteristic feature of PCa with a low risk of progression by D'Amico et al . are low expression of oncogenic miRNA-21 and -221 in tumor tissue. In particular, in the PCa samples of high risk of progression (n = 30) the level of miRNA-21 was 3.2 times (p < 0.05), and miRNA-221 was 1.35 times (p < 0.05) higher compared to tumor tissue of patients with low progression (n = 30). The existence of a direct correlation between the expression of miRNA-21 and the proliferative activity of PCa (ρ = 0.63; p < 0.05) is shown. We found that the expression of miRNA-221 is associated with a high level of AR expression (ρ = 0.43; p < 0.05) . Conclusions: The obtained data indicate the relationship of tumor -associated microRNA-21 and -221 with the risk of tumor progression and such molecular biological characteristics of tumors as proliferative activity and receptor status, which indicates the prospects for their further study as additional markers for predicting of PCa course.

No abstract