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The infiltration of immune cells is a hallmark of most forms of malignancy. It is well known that in Tumor Microenvironment (TME), monocytes undergo reprogramming process to differentiate into Tumor Associated Macrophages (TAMs) (M2 macrophages). Interestingly, this reprogramming process depends on signals provided by tumors. Hence, tumors from several tissues are infiltrated by functionally distinct TAMs populations. Tumor Protein p53(TP53) plays a role in the regulation or progression of DNA damage and repair through multiple mechanisms of the cell cycle, apoptosis, and genomic stability. Although, TP53 acts as a physiological break for M2 macrophages polarization; the potential regulatory function of TP53 in the infiltration of macrophages is still unknown. We used the Cancer Genomic Atlas (TCGA) clinical data from 10,009 samples across 30 types of cancer via the Tumor IMmune Estimation Tool (TIMER) (https://cistrome.shinyapps.io/timer/) to investigate whether TP53 status has an important clinical outcome on macrophages infiltration in different cancer types. Our analysis of TCGA showed that Ovarian Serous Cystadenocarcinoma (OV) patients with mutant TP53 had significantly higher macrophages infiltration than those with wild-type TP53 (P-value < 0.05) and poor prognosis associated. In contrast, Stomach Adenocarcinoma (STAD) patients with wild-type TP53 had considerably higher macrophages infiltration than those with mutant TP53 (P-value < 0.01) and poor clinical outcomes. Herein, our study sheds light on the novel clinical role of TP53 in macrophages infiltration in TME of OV and STAD patients. Furthermore, the modulation of TP53 and its co-regulators may serve as promising targets for OV and STAD patients.

Circulating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood.To investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model. We showed the effect of OC exosomal miR-1246 uptake on macrophages by co-culture experiments.Substantial expression of oncogenic miR-1246 OC exosomes was found. We showed that Cav1 gene, which is the direct target of miR-1246, is involved in the process of exosomal transfer. A significantly worse overall prognosis were found for OC patients with high miR-1246 and low Cav1 expression based on TCGA data. miR-1246 expression were significantly higher in paclitaxel-resistant OC exosomes than in their sensitive counterparts. Overexpression of Cav1 and anti-miR-1246 treatment significantly sensitized OC cells to paclitaxel. We showed that Cav1 and multi drug resistance (MDR) gene is involved in the process of exosomal transfer. Our proteomic approach also revealed that miR-1246 inhibits Cav1 and acts through PDGFβ receptor at the recipient cells to inhibit cell proliferation. miR-1246 inhibitor treatment in combination with chemotherapy led to reduced tumor burden in vivo. Finally, we demonstrated that when OC cells are co-cultured with macrophages, they are capable of transferring their oncogenic miR-1246 to M2-type macrophages, but not M0-type macrophages.Our results suggest that cancer exosomes may contribute to oncogenesis by manipulating neighboring infiltrating immune cells. This study provide a new mechanistic therapeutic approach to overcome chemoresistance and tumor progression through exosomal miR-1246 in OC patients.

The nature of separations arising in hot-rolled plates from high-toughness steels of the new generation like 05G2B and of cleavages arising in traditional building steels of type 09G2S is studied. Like and unlike features of separations and cleavages are determined. The concept of “critical stress $$ {\upsigma}_{\mathrm{b}}^{\mathrm{cr}} $$ ” describing the strength of the interlayer boundaries responsible for formation of layered cracks is used to analyze various factors responsible for the susceptibility of rolled plates to layered fracture.

The paper discusses computer modeling of an extensive crack propagating in a gas pipeline, which (the modeling) plays an important role in determining resistivity of pipe steels to various types of failure. A modified local Gurson-Tvergaard- Niedelman (GTNm) model is presented which makes it possible to describe straight and oblique cuts, as well as a combination thereof, in viscous failure of small-size objects (bars, plates, shells). Details of the implementation of the GTNm model in the parallel FE computer program DANKO (developed in Russian Federal Nuclear Center - All-Russian Research Institute of Experimental Physics) are given. Parameters of the GTNm model have been determined based on laboratory experiments with specimens of a pipe steel of the K65 strength class. Numerical examples are given, demonstrating “working efficiency” of the GTNm model. The results are designed for numerically studying deformation, failure of specimens during tests, dynamic crack propagation in a pipeline. Keywords: steels of gas mains, small-dimension objects, viscous failure, oblique cuts, computer modeling, finite element method, modified local Gurson − Tvergaard − Niedelman (GTNm) model.

The applicability of the modified Gurson - Tvergaard - Niedelman (GTNm) model to computations is considered; in the frame of numerical modeling, the model makes it possible to obtain failure surfaces, realized in experiments with samples, which include scroll-type surfaces. Tests on static tension of plates (prismatic samples) with a herringbone lateral notch, which initiates the nucleation of a crack, have been modeled using the computer. This type of tests is included into the normative documents of the “Gazprom” JSC with the view of preventing propagation of extended viscous failure in gas mains. Specimens are made of a K65 strength class 1420 mm-diameter tube with a 27.7 mm-thick wall. Keywords: plastic deformation, viscous failure of specimens, numerical modeling, modified Gurson − Tvergaard − Niedelman (GTNm) model, comparison of computational and experimental results.

Background: The efficacy of corticosteroids significantly varies between patients with acute exacerbation of COPD (AECOPD), therefore prediction of steroid response is necessary for the prescription of adequate treatment. Aim: The aim of the present study was to establish whether cytokines levels and percentages of lymphocytes subpopulations in peripheral blood of patients with AECOPD could predict the response of alveolar macrophages to glucocorticoids. Methods: A total of 45 patients (39 men and 6 women) entered the study. All patients were hospitalized due to AECOPD and underwent bronchoscopy. On the basis of interleukin 8 (IL-8) secretion by alveolar macrophages isolated from bronchoalveolar lavage fluid and exposed to lipopolysaccharide and six different concentrations of dexamethasone (0.01 – 1000 nM) all patients were devided into steroid sensitive (SS, n=27) and steroid resistant (SR, n=18). Results: There was a greater improvement in quality of life assessed by CAT score in SS compared with SR after 15 days of systemic steroid therapy. Plasma concentration of macrophage migration inhibitory factor (MIF) was higher in SR compared with SS. There were no significant differences in the levels of IL-4, IL-6, IL-8, IL-17A, tumor necrosis factor a, granulocyte chemotactic protein 2 and the percentages of CD3+, CD3+CD4+, CD4+CD25+CD127-, CD3+CD8+, CD3-CD56+, CD3+CD56+, CD19+, CD14+ cells between SR and SS patients. At a cut-off value of 2.24 ng/mL the corresponding sensitivity, specificity and area under ROC curve of MIF as a predictor of steroid resistance were 72.2%, 70.4%, and 0.740. Conclusion: MIF can be used for the prognosis of steroid response.

Background: Eosinophil blood count is a reliable predictor of steroid response in patients with COPD. Whether other parameters of routine blood count can serve as biomarkers of steroid resistance is currently unknown. Aim: The aim of the present study was to determine the significance of platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) in predicting response to glucocorticoids in patients with acute exacerbation of COPD (AECOPD). Methods: Forty five patients with AECOPD undergoing bronchoscopy and complete blood count measurement were recruited for the study. Alveolar macrophages (AM) isolated from bronchoalveolar lavage fluid were cultured with lipopolysaccharide (LPS, 1 µg/ml) and dexamethasone (Dex, 0.01 – 1000 nM). Supernatants were analyzed for the levels of interleukin 6 (IL-6), IL-8 and tumor necrosis factor a (TNF-a). Results: The maximal inhibition of IL-6, IL-8 and TNF-a release from AM was observed at Dex concentration of 100 nM, and maximal cell response variability was found at 10 nM. IL-6 and TNF-a were more sensitive to inhibition by Dex than IL-8. All patients were separated into steroid sensitive (SS, =50% inhibition of LPS-induced IL-8 release, n=27) and steroid resistant (SR, Conclusion: NLR and PLR can serve as prognostic markers of steroid resistance.

Serine protease (SPs) is one of the immune enzyme's molecules that play a main role in the variation of a physiological process by controlling protease actions in vertebrates. For example, signaling cells, protector and improvement, which are included in melanization, are utilized to cascade with the meddling pathogens and defense the harmed tissue in insects. In this study, we explore the biochemical process of (SP-22) from Bombyx mori. Reverse-transcription polymerase chain reaction (RT-PCR) discloses that BmSP-22 is expressed in all tissues including the fat body. The formative expression profile of BmSP-22 reveal that BmSP-22 messenger RNA is expressed constitutively in larvae. Injection of recombinant BmSP-22 into B. mori larvae reduces significantly the transcript levels of antimicrobial peptides in the fat body. Our results suggest that BmSP-22 plays an important role in the innate immunity of B. mori and possibly in other insects.

The method of orientation microscopy (EBSD) is used to study the texture of low-carbon, low-alloy pipe steel sheets with a bainitic structure made by controlled thermomechanical processing. The specimens analyzed are inclined or not inclined towards forming separations (secondary cracks) in a fracture during mechanical testing. Formation of separations during failure of steel with a bainitic structure is connected with the presence in the material of regions with uniform orientation (001) extended in the cold rolling direction. Formation of the regions is a consequence of features of γ→α shear transformation that commences at special boundaries between deformed austenite grains.

In 2015, more than 1.6 million new cancer cases with 589,430 deaths were estimated over worldwide. Cancer is a complex disease with abnormal cell growth control which is hallmarked by chromosome misalignment and consequently genomic instability. Mitosis is a well-known target for chemotherapy as taxol and colchicines inhibit tumor cell division by inhibiting mitotic spindle plasticity. Accumulating evidence has revealed that the Centromere-associated Protein E (CENP-E) is expressed during mitosis and plays critical roles in inaccurate chromosome alignment. Thus, CENP-E might represent a druggable target for several solid tumors which do not have targeted therapy. Moreover, CENP-E appears during the mitotic phase of cell cycle and not implicates in the neuronal function. Hence, we will shed light on CENP-E as an emerging target for chemotherapy in clinical oncology and highlight challenges and excitement down the road.

Figure S3. Grx6 catalyses for the chemical reduction of glutathione (GSH) and NADP(+), which forms glutathione disulfide (GSSG), NADPH and FAD. The Grx6s contain cysteine in their active site making them suitable for oxidation/reduction reactions (Fig. 2). Whereas ScGrx6 can reduce ROS in the cytoplasm, ScGrx6 has the ability to reduce NADP(+) and ScGrx6 catalyses S-glutathionylation to protect SH-groups from oxidation and restore functionally active thiols. ScGrx6 catalyses the reaction only via a monothiol mechanism. Additionally, it has been suggested to have antioxidant capabilities, but their mechanisms are less understood. (PDF 3599 kb)

В статье представлены результаты исследования сывороток крови свиней животноводческих ферм и частного сектора выращиваемых на территории Могилевской и Минской областей Беларуси (n=625) на наличие антител к вирусу гепатита Е. Среди животных антитела к вирусу гепатита Е были обнаружены у 71 из 665 свиней, что составило 10,7%. Из обследованных 43 свиноводческих хозяйств Могилёвской (21) и Минской (22) областей в 30 хозяйствах обнаружено наличие у свиней антител (70%). На основании этого доказана циркуляция вируса гепатита Е среди животных в Республике Беларусь. = Introduction. Interest in the problem of viral hepatitis E (VGE) has grown in the past decade. In studies conducted in various countries, Hepatitis E virus was detected in animals (wild boars, pigs, birds, wild rats, etc.), and the role of hepatitis E in the occurrence of acute hepatitis E in humans has been demonstrated. Animals support the circulation of the hepatitis E virus in nature, i.e. hepatitis E is a zooanthroponotic infection. In countries where VHE has been identified and serological studies have been conducted among pigs, it has been shown that most pigs over the age of 3-4 months are carriers of anti-HBV. The goal of the work was to conduct studies to determine the presence of hepatitis E virus in swine in the Republic of Belarus. Materials and methods. To determine the serological markers of infection with the hepatitis E virus, an enzyme immunoassay method was used to determine the anti-VGE-IgG, M using the Vector-Best Cytogenesis-E IgG and IgM test system, Novosibirsk. A method for detecting IgG using a solution of Staphylococcus aureus protein conjugated with horseradish peroxidase was tested. The sera of pigs from livestock farms and the private sector of various regions of Belarus (n = 625) were tested for antibodies to hepatitis E. Results of research and discussion. Among the animals, antibodies to the hepatitis E virus were detected in 71 of 665 pigs, which was 10.7%. In 30 of 43 surveyed pig-breeding farms in Mogilev (21) and Minsk (22) regions the presence of antibodies to the hepatitis E virus was detected in 70% of pigs. Conclusions and prospects for further research. Based on this, the circulation of the hepatitis E virus among animals in the Republic of Belarus has been proved, its approximate scales have been determined.

Figure S1. Hydrophobic interaction between the two subunit of ScGrx6. The distance between two Tyr138 residues is approximately 4.1Â Ă , which is small enough for their hydrophobic interaction. The hydrophobic interaction between hydrophobic side chains of Tyr138 from both subunits in the interface contributes to the formation of the dimeric interface and helps to stabilize the cluster by reducing the solvent accessibility. (PDF 148 kb)

Table S2. Enzymes cleaving ScGrx6 and the positions of cleavage sites. (DOCX 16 kb)

В статье показаны результаты применения иммуноферментного анализа при диагностике гепатита Е у свиней. Проведены исследования по разработке тест-системы для выявления антител к вирусу гепатита Е у свиней – в качестве антигена целесообразно использовать генно-инженерные полипептиды с антигенной последовательностью вируса гепатита Е 1 и 3 генотипа, коньюгированные с бета-галактозидазой. Сорбцию полипептидов на полистироловые планшеты проводили после предварительной обработки их ультрафиолетовым излучением, в оптимальной концентрации полипептидов для сорбции на полистироловые планшеты – 8 мкг/мл в 0,005 М карбонатном буфере рН-9,5, разведение конъюгата – кроличьих антииммуноглобулиновых сыворток против IgG свиньи антител – 1:10000. Проведенные исследования показали, что 98,2% сывороток свиней содержат специфические антитела к вирусу гепатита Е человека в различной концентрации, что свидетельствует о циркуляции вируса гепатита Е среди свинопоголовья на территории Республики Беларусь. = Studies on the development of a test system for the detection of antibodies to HEV in pigs have shown that it is advisable to use as an antigen the geneengineering polypeptides with antigenic sequence of the virus 1 and 3 genotype, conjugated with beta-galactosidase, for the sorption of polypeptides to polystyrene plates after pretreatment with ultraviolet radiation to increase the adhesion in sorption of recombinant antigen, in order to optimize the concentration of polypeptides. Sorption on polystyrene plates was 8 µg/ml in 0.005 M carbonate buffer pH-9.5, and breeding conjugate – rabbit antibody against IgG pigs TS30 antibodies is 1:10000. In the study of 1047 blood sera of pigs from farms and private farms 98.2% of samples contained specific antibodies to HEV human in different concentrations, which indicates the circulation of this virus in pig population in the Republic of Belarus. In the study of 1,047 sera of pigs from different farms, 98.2% of pigs’ sera contained specific antibodies to the human HEV in various concentrations, which indicates that it circulates among the pigs in Republic of Belarus.