In situ phase formation during high-temperature synthesis in clad mechanocomposites based on the Ti-Al system.

An in situ synchrotron experimental study of phase formation dynamics in clad mechanocomposites of Ti-Al systems during high-temperature synthesis was performed. Cladding of the obtained mechanocomposites was carried out with an SiO target, with a deposition time of 40 min. The high-temperature synthesis was performed using the thermal explosion method based on a microwave induction heater in the in situ mode on an experimental setup adapted to synchrotron radiation time-resolved diffractometry.

[Digital transformation of healthcare: a competency-based approach].

The article substantiates the relevance of the study of the essence, tools and mechanisms of digital transformation of the health sector. A comparative assessment of the current health care system in the cities of the world is presented, trends in the use of end-to-end technologies for improving the health care system in Russia are revealed. The development of the health sector in modern conditions is based on the introduction of new information and communication technologies, for the proactive use of which, it is necessary to increase the digital skills and awareness of health workers and the population.

Rogue versus chromothriptic cell as biomarker of cancer.

New molecular cytogenetic biomarkers may significantly contribute to biodosimetry, whose application is still globally diverse and not fully standardized. In 2011, a new term, chromothripsis, was introduced raising great interest among researchers and soon motivating further investigations of the phenomenon. Chromothripsis is described as a single event in which one or more chromosomes go through severe DNA damage very much resembling rogue cells (RC) described more than 50 years ago.

Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.

Background: Investigation of basic chronic inflammatory mechanisms and development of new therapeutics targeting the respiratory tract requires appropriate testing systems, including those to monitor long- persistence. Human precision-cut lung slices (PCLS) have been demonstrated to mimic the human respiratory tract and have potential of an alternative, ex-vivo system to replace or augment in-vitro testing and animal models. So far, most research on PCLS has been conducted for short cultivation periods (≤72 h), while analyses of slowly metabolized therapeutics require long-term survival of PCLS in culture.

Evaluation of inflammatory and immune responses in long-term cultured human precision-cut lung slices.

The development of systems that are more accurate and time-efficient in predicting safety and efficacy of target products in humans are critically important in reducing the cost and duration of pharmaceutical development. To circumvent some of the limitations imposed by the use of animal models, ex vivo systems, such as precision-cut lung slices (PCLS), have been proposed as an alternative for evaluating safety, immunogenicity and efficacy of vaccines and pharmaceuticals. In this study, we have established a human PCLS system and methodology for PCLS cultivation that can provide long-term viability and functionality in culture.

Lymphocytes with multiple chromosomal damages in a large cohort of West Siberia residents: Results of long-term monitoring.

Cells with specific multiple chromosome aberrations, defined as rogue cells (RC) have been described in different populations, predominantly those exposed to radiation. The frequency, etiology and related health risks have still not been elucidated due to their low frequency of occurrences and rarely performed studies. This study reports RC frequency using chromosome aberration (CA) assay in peripheral lymphocytes in the group of 3242 subjects, during a 30-year long follow-up study in a general rural and urban population, children environmentally exposed to radon, occupationally exposed population and lung cancer patients from the Kemerovo region (Siberia, Russian Federation).

Assessing the level of chromosome aberrations in peripheral blood lymphocytes in long-term resident children under conditions of high exposure to radon and its decay products.

In this study, the frequency and spectrum of chromosomal aberrations were analysed in samples of peripheral blood from 372 (mean age = 12.24 ± 2.60 years old) long-term resident children in a boarding school (Tashtagol city, Kemerovo Region, Russian Federation) under conditions of high exposure to radon and its decay products.

[Cytogenetic effects in the population in agricultural regions of the Kemerovo region].

There was performed an analysis of chromosomal aberrations in peripheral blood lymphocytes of the inhabitants of 9 settlements from 6 agricultural regions of the Kemerovo region. 267 children-adolescents and 124 adults not involved in the industry were examined. The average level of chromosomal aberrations was 2.

Plant-produced human recombinant erythropoietic growth factors support erythroid differentiation in vitro.

Clinically available red blood cells (RBCs) for transfusions are at high demand, but in vitro generation of RBCs from hematopoietic stem cells requires significant quantities of growth factors. Here, we describe the production of four human growth factors: erythropoietin (EPO), stem cell factor (SCF), interleukin 3 (IL-3), and insulin-like growth factor-1 (IGF-1), either as non-fused proteins or as fusions with a carrier molecule (lichenase), in plants, using a Tobacco mosaic virus vector-based transient expression system. All growth factors were purified and their identity was confirmed by western blotting and peptide mapping.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.

Regulatory T cells (T(reg) cells) are essential for self-tolerance and immune homeostasis. Lack of effector T cell (T(eff) cell) function and gain of suppressive activity by T(reg) cells are dependent on the transcriptional program induced by Foxp3. Here we report that repression of SATB1, a genome organizer that regulates chromatin structure and gene expression, was crucial for the phenotype and function of T(reg) cells.

[Spread of carcinogenic and mutagenic effects in the population of Gornaia Shoria].

Mutagenic and carcinogenic effects were studied in the population of Gornaya Shoria, Kemerovo Region. The carcinogenic effects were evaluated on the basis of the data given by the Kemerovo regional cancer registry over 1990-2008. The standardized cancer morbidity index in Gornaya Shoria (342 per 100,000 population) exceeded the average index in the Kemerovo Region (286 per 100,000) in the same period.

Retinoic acid and rapamycin differentially affect and synergistically promote the ex vivo expansion of natural human T regulatory cells.

Natural T regulatory cells (Tregs) are challenging to expand ex vivo, and this has severely hindered in vivo evaluation of their therapeutic potential. All trans retinoic acid (ATRA) plays an important role in mediating immune homeostasis in vivo, and we investigated whether ATRA could be used to promote the ex vivo expansion of Tregs purified from adult human peripheral blood. We found that ATRA helped maintain FOXP3 expression during the expansion process, but this effect was transient and serum-dependent.

The inducible costimulator (ICOS) is critical for the development of human T(H)17 cells.

Human T helper 17 (T(H)17) cells regulate host defense, autoimmunity, and tumor immunity. Although cytokines that control human T(H)17 cell development have been identified, the costimulatory molecules important for T(H)17 cell generation are unknown. Here, we found that the inducible costimulator (ICOS) was critical for the differentiation and expansion of human T(H)17 cells.

[Toxic and genetic risk assessments in children of Gornaya Shoria].

This comprehensive study assessed a number of environmental factors that were potentially able to induce genotoxic effects in man. A set of radiological, physicochemical, and bioindication techniques was used to estimate the quality of water, air, and soil in the places of residence and education of children and adolescents from the boarding school of the town of Tashtagol and schoolchildren from the village of Krasnoye, Kemerovo Region. Excess radon levels in the air of living spaces and classes, a small excess of the maximum allowable concentration of gross forms of heavy metals in individual soil samples, and high toxic effects in the Drosophila gametes exposed to air samples were revealed in the Tashtagol children having higher genotoxic effects in the lymphocyte than those in the Krasnoye village ones.

Regulatory T cells: overcoming suppression of T-cell immunity.

Regulatory T cells inhibit cellular immunity and represent an obstacle for the development of cancer immunotherapy. The understanding of Treg cellular biology has exponentially increased during the last 10 years, driven primarily by elegant in vivo studies of mouse models systems and in vitro studies of human cells. Numerous clinical strategies are under active investigation to achieve Treg depletion or inhibition in patients with cancer, including low-dose cyclophosphamide and interleukin-2 or anti-interleukin-2R immunotoxins.

Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs.

Histone/protein deacetylases (HDACs) decrease histone and protein acetylation, typically leading to suppression of gene transcription and modulation of various protein functions. We found significant differences in expression of HDAC before and after stimulation of human T regulatory (Treg) and T effector cells, suggesting the potential for future selective targeting of Tregs with HDAC inhibitors (HDACi). Use of various HDACi small molecules enhanced, by up to 4.

[Genome sensitivity and genotoxic effects features in children-teenagers affected by radon radiation in living and educational environment].

The results of chromosomal aberration level and spectrum study in 48-hours peripheral blood lymphocytes cultures of 10-19 years old children-teenagers (n = 132, mean 14.2 +/- 0.16 years old) living in the south part of Kemerovskaya area Gornaya Shoria are presented.

[Quantitative characteristics of chromosomal aberration frequency in the residents of the regions with different levels of cancer incidences].

We present the results of cytogenetic monitoring of the districts in Kemerovo region, which differ in standardized indices of cancer incidence. It has been shown that residents of the districts with high incidence of malignancies had higher average frequency of metaphases with chromosomal aberrations than the control group (4.06 +/- 0.

Adoptive immunotherapy: good habits instilled at youth have long-term benefits.

Many recent advances in basic cell biology and immunology are a harbinger of progress in adoptive cell therapy (ACT) including (1) the finding that host lymphodepletion enhances engraftment and efficacy, (2) the recognition that in vitro T cell functions may not correlate with in vivo efficacy, and (3) the development of advanced ex vivo culture methods to expand lymphocytes to therapeutically effective numbers. In this article, we focus on the development of artificial antigen presenting cells (aAPCs) in our laboratory and their applicability to augment ACT protocols. We also describe how aAPCs can be used to broaden ACT to treat patients with a wide variety of cancers, chronic infectious diseases, and autoimmune manifestations.

Distinct effects of IL-18 on the engraftment and function of human effector CD8 T cells and regulatory T cells.

IL-18 has pleotropic effects on the activation of T cells during antigen presentation. We investigated the effects of human IL-18 on the engraftment and function of human T cell subsets in xenograft mouse models. IL-18 enhanced the engraftment of human CD8(+) effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD).

CD28 costimulation is essential for human T regulatory expansion and function.

The costimulatory requirements required for peripheral blood T regulatory cells (Tregs) are unclear. Using cell-based artificial APCs we found that CD28 but not ICOS, OX40, 4-1BB, CD27, or CD40 ligand costimulation maintained high levels of Foxp3 expression and in vitro suppressive function. Only CD28 costimulation in the presence of rapamycin consistently generated Tregs that consistently suppressed xenogeneic graft-vs-host disease in immunodeficient mice.

Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells.

Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)-coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor beta (TGF-beta) secretion and the potency of Treg suppressor function.

Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin.

Addition of rapamycin to cultures of expanding natural CD4+CD25+Foxp3+ T regulatory cells (Tregs) helps maintain their suppressive activity, but the underlying mechanism is unclear. Pim 2 is a serine/threonine kinase that can confer rapamycin resistance. Unexpectedly, pim 2 was found to be constitutively expressed in freshly isolated, resting Tregs, but not in CD4+CD25- T effector cells.