Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2+CD9+ subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1+ and PLVAP+ endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.

Visualization and Cytotoxicity of Fluorescence-Labeled Dimeric Magnetite-Gold Nanoparticles Conjugated with Prostate-Specific Membrane Antigen in Mouse Macrophages.

We demonstrated the possibility of penetration of magnetite-gold nanoparticles conjugated with prostate-specific membrane antigen into mouse macrophages. It was found that after 3-h incubation with nanoparticles in a concentration of 15 mg/liter at 37oC, they were seen in only 13% macrophages. In about 90% cells, the nanoparticles were detected within the cytoplasm. Under these conditions, membrane damage was revealed in 25% cells. These results should be taken into account in further development and application of nanomaterials for diagnostic and therapeutic purposes in oncology.

Novel method for rapid toxicity screening of magnetic nanoparticles.

Iron oxide nanoparticles have attracted a great deal of research interest and have been widely used in bioscience and clinical research including as contrast agents for magnetic resonance imaging, hyperthermia and magnetic field assisted radionuclide therapy. It is therefore important to develop methods, which can provide high-throughput screening of biological responses that can predict toxicity. The use of nanoelectrodes for single cell analysis can play a vital role in this process by providing relatively fast, comprehensive, and cost-effective assessment of cellular responses. We have developed a new method for in vitro study of the toxicity of magnetic nanoparticles (NP) based on the measurement of intracellular reactive oxygen species (ROS) by a novel nanoelectrode. Previous studies have suggested that ROS generation is frequently observed with NP toxicity. We have developed a stable probe for measuring intracellular ROS using platinized carbon nanoelectrodes with a cavity on the tip integrated into a micromanipulator on an upright microscope. Our results show a significant difference for intracellular levels of ROS measured in HEK293 and LNCaP cancer cells before and after exposure to 10 nm size iron oxide NP. These results are markedly different from ROS measured after cell incubation with the same concentration of NP using standard methods where no differences have been detected. In summary we have developed a label-free method for assessing nanoparticle toxicity using the rapid (less than 30 minutes) measurement of ROS with a novel nanoelectrode.

[Capabilities of breast sonotomography (automated breast volume sonography) in the evaluation of the glandular structure of the breast in the context of its cancer risk].

Objective: To study the capabilities of a procedure for sonotomography (STG) versus that of X-ray mammography (MG) in patients from different age groups who have different radiological types of the breast structure and to estimate the diagnostic possibilities of the STF and X-ray MG procedures in detecting cancer in patients its the X-ray dense background. Materials and Methods: The investigation enrolled 143 patients aged 38 to 77 years who had undergone STG after primary X-ray MG. Particular emphasis was placed on a methodological approach to optimizing STG in patients from different age groups with a varying radiological type of the breast structure in different physiological periods. The international breast imaging and reporting data system was used to standardize detected breast masses. Results: Out of the 143 patients, 102 persons, including 16 patients with verified breast cancer (BC), were found to have space-occupying lesions. During the performed investigation, computed processing of 3D scans at the working station confirmed the entire quadrant-by-consentaneity of the glandular structure of the breast at STG and X-ray MG. There were a higher proportion of abnormal breast masses with increased percentage ratio of glandular tissue in the breast. Emphasis was laid on the role of STG as an additional examination technique in patients from all age groups with the radiologically dense breast in order to detect cancer due to a high sensitivity of 100% and a specificity of 96%. Conclusion: The procedure of STG versus that of X-ray MS showed a high degree of compatibility of opinions as to the type of the breast structure in the patients. Due to the fact that standard-projection STG scans can be compared, during mammography the procedure of STG must hold a firm place in the examination algorithm of the breast in women with its X-ray dense structure.

[Mathematical model of plant accumulation of radionuclides and heavy metals from soil].

Equilibrium model is based on the hypothesis of sorptive mechanisms of absorption of chemical elements in the soil solid phase-soil solution-plant system. The characteristics of the model are in the line with basic experimental relationships: dependence of concentrations of radionuclides or heavy metals in plant on: a) concentration of radionuclides or heavy metals in soil; b) sorptive capacity of plant; c) concentration of macro element-analogue in soil; d) soil fertility. The accumulation of elements by plants depends on ratio of cation capacities of plant and soil as well as the ratio of sorption-desorption of an element in the soil solid phase (plant)-soil solution system.

[Obsessive-phobic disorders with the phenomena of mysophobia in slowly progressing schizophrenia]. / Obsessivno-fobicheskie rasstroistva s iavleniiami mizofobii pri vialotekushchei shizofrenii.

54 patients, 24 men and 30 women, (mean age 27 years) were examined. Two types of obsessive-phobic disorders with the phenomena of mysophobia were distinguished: obsession of the external (extracorporal) threat and obsession of contamination. Disorders of the first type (25 cases) were observed in psychopathic-like schizophrenia. They were characterized by a fear of possible contacts with different pathogenic agents--toxic substances, sharp small subjects, bacteria. Obsessions presented with a system of actions preventing phobic situations (rituals). With progression of the disease there was a decrease of both the degree and affective saturation of phobic disorders together with preserving rituals. Negative disorders presented with rough psychopathic-like changes with features of the "verschroben" defect. The disorders of the second type (29 patients) were observed in neurosis-like schizophrenia. Mysophobia manifested with both the repeated control and the fear of contamination accomplished. Ritual behavior presented with repeated actions and repeated control of the "sterility" of the own body and the surrounding subjects. Dynamics of these disorders was characterized by a tendency to more severe rituals of the control and persisting anxiety. Deficit disorders manifested with mental infantilism with psychopathic-like disorders of schizo-anancastic sphere. The above types of the obsessive-phobic disorders have a differential-diagnostic significance in respect of clinical variations of schizophrenia and determination of the state acuity with possible reversibility of the disorders (in neurosis-like schizophrenia).

[The study of interaction between 134Cs and potassium in system peat soil-plant under increasing concentration of macroelement in soil]. / Issledovanie vzaimodeistviia 134Cs i kaliia v sisteme torfianaia pochva-rastenie v usloviiakh vozrastaiushchikh kontsentratsii makroanaloga v pochve.

The interaction between analogous elements K and 134Cs in the system "peat-soil-plant" was investigated. The values of some parameters of sorption model for uptake of radionuclides by plants from soil were determined. An attempt to interpret the processes going on in the studied system under pot experiment from the viewpoint of soil chemistry was done. Two intervals of potassium concentration in peat-soil were displayed, with different effect on 134Cs uptake by plants.

[137Cs accumulation by grasses from peat soil under increasing amounts of potassium and nitrogen fertilizers]. / Nakoplenie 137Cs travami iz torfianoi pochvy pri vozrastaiushchikh dozakh kaliinykh i azotnykh udobrenii.

The three-chamber model of radionuclides uptake from soil was proposed. This model permit to analyse the transfer factors as the function of the some properties of the radionuclides, macroelement-analogs, soil and plants. The field experiment results (Novozybkov District) was analysed. In this experiment the uptake 137Cs in Bromopsis inermis L. from peat soil under increasing K- and N-fertilizer doses was investigated.