76 research outputs found

    Microbiome Responses to an Uncontrolled Short-Term Diet Intervention in the Frame of the Citizen Science Project

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    Personalized nutrition is of increasing interest to individuals actively monitoring their health. The relations between the duration of diet intervention and the effects on gut microbiota have yet to be elucidated. Here we examined the associations of short-term dietary changes, long-term dietary habits and lifestyle with gut microbiota. Stool samples from 248 citizen-science volunteers were collected before and after a self-reported 2-week personalized diet intervention, then analyzed using 16S rRNA sequencing. Considerable correlations between long-term dietary habits and gut community structure were detected. A higher intake of vegetables and fruits was associated with increased levels of butyrate-producing Clostridiales and higher community richness. A paired comparison of the metagenomes before and after the 2-week intervention showed that even a brief, uncontrolled intervention produced profound changes in community structure: resulting in decreased levels of Bacteroidaceae, Porphyromonadaceae and Rikenellaceae families and decreased alpha-diversity coupled with an increase of Methanobrevibacter, Bifidobacterium, Clostridium and butyrate-producing Lachnospiraceae- as well as the prevalence of a permatype (a bootstrapping-based variation of enterotype) associated with a higher diversity of diet. The response of microbiota to the intervention was dependent on the initial microbiota state. These findings pave the way for the development of an individualized diet.</p

    Tumor inflating lymphocytes. Purification, expanding and cytotoxicity analisys on primary tumor cultures

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    Background. Tumor Infiltrating Lymphocytes (TILs) is one of the most promising sources of autologous cytotoxic T-cells for adoptive immunotherapy, which has already shown high efficiency in the treatment of metastatic melanoma. However, the isolation of TILs from solid tumors is technically difficult. A suppressive tumor microenvironment, in particular, a high level of expression of check-point inhibitors PD-1 CTLA4, tissue hypoxia and other factors cause that T cells isolated from the tumor do not proliferate well and do not exhibit cytotoxic properties. Aims. In this study, we isolated TILs from surgical material obtained by resection of solid tumors (primary and metastatic adenocarcinomas of various localization, melanoma, glioblastoma), studied their population composition and developed protocols for the purification expanding, and activation of CD4+, CD8+ cytotoxic antitumor lymphocytes. Methods. An urgent task is the activation of TILs, turning off immunosuppressive mechanisms and increasing their antitumor cytotoxic activity. Various approaches are used for this: activation by a cocktail of cytokines and antibodies, editing the lymphocyte genome by knocking out suppressor genes or, conversely, transduction of activating genes, coincubation with feeder cells, etc. Cells were obtained from samples of resected tumors in 16 patients; in each case we obtain an autologous pair: the primary tumor culture and the TILs culture. Results. We could isolate viable lymphocytes in 100% of cases. Isolated TILs were successfully expanded in our specialized medium using various combinations of IL-2, IL-15, IL-21, IL-7, anti-CD3 and anti-CD28. Immunophenotyping showed that the obtained TILs are a heterogeneous mixture of CD4+, CD8+ cells containing populations of CD3+CD8+CD45+(CTL) CD3+CD4+CD45+ (T-helpers), CD4+CD25+CD127- (Т-regulatory cells), CD3-CD56+CD45+ (NK-cells), CD3+CD56+CD45+ (Т-NK-cells). The initial cultures of TILs were also characterized by a high level of PD1 expression, indicating their low antitumor cytotoxicity. Using different protocols of isolation, expansion, and activation, we obtained a cell preparation containing 80% of CD8+ PD-1- activated TILs in an amount sufficient for adoptive therapy (500106 or more). An in vitro study of the cytotoxicity of obtained TILs in primary cultures of homologous tumors using RTCA Icelligence showed high cytotoxicity, providing almost 100% tumor cell death. Conclusion. Our developed protocol for the production and activation of TILs can be recommended for the phase III clinical trials of adoptive immunotherapy of recurrent, highly metastatic solid tumors

    The role of the extracellular matrix and its molecular and cellular regulators in cancer cell plasticity

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    The microenvironment encompasses all components of a tumor other than the cancer cells themselves. It is highly heterogenous, comprising a cellular component that includes immune cells, fibroblasts, adipocytes, and endothelial cells, and a non-cellular component, which is a meshwork of polymeric proteins and accessory molecules, termed the extracellular matrix (ECM). The ECM provides both a biochemical and biomechanical context within which cancer cells exist. Cancer progression is dependent on the ability of cancer cells to traverse the ECM barrier, access the circulation and establish distal metastases. Communication between cancer cells and the microenvironment is therefore an important aspect of tumor progression. Significant progress has been made in identifying the molecular mechanisms that enable cancer cells to subvert the immune component of the microenvironment to facilitate tumor growth and spread. While much less is known about how the tumor cells adapt to changes in the ECM nor indeed how they influence ECM structure and composition, the importance of the ECM to cancer progression is now well established. Plasticity refers to the ability of cancer cells to modify their physiological characteristics, permitting them to survive hostile microenvironments and resist therapy. Examples include the acquisition of stemness characteristics and the epithelial-mesenchymal and mesenchymal-epithelial transitions. There is emerging evidence that the biochemical and biomechanical properties of the ECM influence cancer cell plasticity and vice versa. Outstanding challenges for the field remain the identification of the cellular mechanisms by which cancer cells establish tumor-promoting ECM characteristics and delineating the key molecular mechanisms underlying ECM-induced cancer cell plasticity. Here we summarize the current state of understanding about the relationships between cancer cells and the main stromal cell types of the microenvironment that determine ECM characteristics, and the key molecular pathways that govern this three-way interaction to regulate cancer cell plasticity. We postulate that a comprehensive understanding of this dynamic system will be required to fully exploit opportunities for targeting the ECM regulators of cancer cell plasticity.Valentina Poltavets, Marina Kochetkova, Stuart M. Pitson and Michael S. Samue

    Триботехнічні дослідження поверхонь тертя на основі полімерних композитних матеріалів

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    The technique of controlling coefficients of friction and temperature was developed. As a result of application of a tribometer, which excludes misalignment of the sample and the counter sample, it was possible to avoid the macro-alignment. Applicability of the Euler’s formula for calculating friction coefficients was proved both when operating by the scheme «shaft – sleeve» and when operating with a flexible steel belt – the counter sample. The developed technique of controlling the mode of friction and lubrication by the character of oscillograms and by measuring temperature change rate ΔT/Δt allowed determining the region of boundary friction. This is the range of small velocities of up to 0.1 m/s, on which at an increase of sliding velocity V, temperature increase rate ΔT/Δt also grows.Comparative research into tribotechnical characteristics of the polymeric material «Moglice» and the developed new polymeric composite material DC-6 were conducted. Coefficients of sliding friction of the couples «cast iron – DC-6» and «cast iron – moglice» are close in magnitude and are within 0.050…0.058. Temperature of friction of materials «Moglice» and «DC-6» increases with an increase in sliding velocity up to 0.078 m/s and reaches 60 °C and 70 °C, respectively.Thus, to restore damaged or worn friction surfaces of metal-cutting machine tools, it is possible to apply such polymeric materials as «Moglice» and «DC-6». The composite polymeric material «DC-6» has friction coefficients and thermal resistance, which are similar to those of the polymer «Moglice» and can replace the more expensive repair material «Moglice».This result opens up broad prospects for the application of new polymeric material that would significantly reduce the cost of repairing and restoration work of the guides of machine tools. Выполнены сравнительные исследования триботехнических характеристик полимерного композитного материала «Moglice» и разработанного материала ДК-6. Испытания выполнялись на парах трения «чугун – моглайс» и «чугун – ДК-6». Исследования необходимы для практического применения материалов ДК-6 или «Moglice» при восстановлении изношенных поверхностей трения. Получены положительные результаты сравнительных испытаний полимерного композитного материала ДК-6 по сравнению с «Moglice»Виконано порівняльні дослідження триботехнічних характеристик полімерного композитного матеріалу «Moglice» і розробленого матеріалу ДК-6. Випробування виконувалися на парах тертя «чавун - моглайс» і «чавун - ДК-6». Дослідження необхідні для практичного застосування матеріалів ДК-6 або «Moglice» при відновленні зношених поверхонь тертя. Отримано позитивні результати порівняльних випробувань полімерного композитного матеріалу ДК-6 в порівнянні з «Moglice

    Application of vertical gardening technology in high-rise construction

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    In the modern world, urban areas are gradually replacing natural areas, which, in turn, negatively affects the environmental situation of the city. To solve this problem, people began to think about greening megalopolises in such a way that it did not occupy useful areas of the urban environment. The solution to this problem is possible by using vertical gardening technology in high-rise construction, which turns gray walls into vertical gardens. This technology allows not only decorating city streets, but also to significantly increase energy efficiency, create a natural environment, and have a positive impact on the psycho-emotional state of a person. This paper discusses various vertical gardening technologies for high-rise construction

    Tribotechnical Research Into Friction Surfaces Based on Polymeric Composite Materials

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    The technique of controlling coefficients of friction and temperature was developed. As a result of application of a tribometer, which excludes misalignment of the sample and the counter sample, it was possible to avoid the macro-alignment. Applicability of the Euler's formula for calculating friction coefficients was proved both when operating by the scheme «shaft – sleeve» and when operating with a flexible steel belt – the counter sample. The developed technique of controlling the mode of friction and lubrication by the character of oscillograms and by measuring temperature change rate ΔT/Δt allowed determining the region of boundary friction. This is the range of small velocities of up to 0.1 m/s, on which at an increase of sliding velocity V, temperature increase rate ΔT/Δt also grows.Comparative research into tribotechnical characteristics of the polymeric material «Moglice» and the developed new polymeric composite material DC-6 were conducted. Coefficients of sliding friction of the couples «cast iron – DC-6» and «cast iron – moglice» are close in magnitude and are within 0.050…0.058. Temperature of friction of materials «Moglice» and «DC-6» increases with an increase in sliding velocity up to 0.078 m/s and reaches 60 °C and 70 °C, respectively.Thus, to restore damaged or worn friction surfaces of metal-cutting machine tools, it is possible to apply such polymeric materials as «Moglice» and «DC-6». The composite polymeric material «DC-6» has friction coefficients and thermal resistance, which are similar to those of the polymer «Moglice» and can replace the more expensive repair material «Moglice».This result opens up broad prospects for the application of new polymeric material that would significantly reduce the cost of repairing and restoration work of the guides of machine tools
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