Background. The hypoxia inducible factor 1a (HIF1a) is an important transcription factor regulating gene expression for an adaptive response to low oxygen level in human cells. Earlier, we observed a ...decrease of HIF1a and CALR mRNA, but not MPL expression in whole blood samples of patients with Ph-negative myeloproliferative neoplasm (MPN) compared with healthy volunteers (Gorbenko A., et al., Haematologica, 2017; Gorbenko A., et al., Blood, 2016). Recent transcriptome studies in granulocytes and CD34+ blood cells from MPN patients confirmed a decrease of mRNA CALR, but also revealed an increase of the relative mRNA level of HIF1a and JAK2 (Cokic VP, et al., PLoS ONE, 2015). These changes in the regulation of number genes expression may depend on the mutation JAK2V617F as was also shown (Berkofsky-Fessler W, et al., Clin Cancer Res. 2010). But some studies demonstrated transcriptomes data of the isolated blood cells from patients with lymphoproliferative disease did not find significant changes in the expression of these genes (Liao W, et al., BMC Cancer, 2015).
Aims. Investigate HIF1a, CALR and JAK2 mRNA expression in patients with lymphoproliferative and myeloproliferative cancer.
Methods. 10 healthy volunteers (average age 42 years, range 20-63 years, 80% of men) and 80 (average age 54 years, range 30-83 years, 46% of man), patients with MPN, also 36 (average age 62 years, range 28-79 years, 78% of man) patients with lymphoproliferative cancer after signing an informed consent were included in this study. In our study, we investigated the expression level of mRNA genes in whole blood samples obtained in test tubes with an RNA stabilizer (LTD “Formula of gene”, Russia) in order to exclude the factors of preanalytical cell hypoxia. Quantitative real-time PCR was performed to determine the levels of HIF1a, CALR and JAK2 mRNA transcripts using TaqMan probes on the CFX96 (Bio-Rad). The results were calculated by ΔCt method in the software package of “R”. The threshold cycles (Ct) genes and housekeeping genes (TBP, GUS, ABL) was determined using Cy0 method. The results were normalized by these reference genes. Mann-Whitney U-test was used to evaluate significance of differences between the groups, the degree of correlation (r) was assessed using Spearman test.
Results. We observed that HIF1a and JAK2 mRNA expression was significantly lower in whole blood samples of all patients with MPN and lymphoproliferative cancer compared with a group of healthy volunteers (p<0,001) (Figure). We discovered a strong correlation between JAK2 and HIF1a expression in all myeloproliferative and lymphoproliferative neoplasms (r=0.83 and r=0.93 respectively, p<0,001) (Figure). It should be noted that the correlation in the blood samples of patients with MPN was observed only when the total expression of wild and mutated transcripts JAK2 (JAK2+JAK2 V617F) was assessed. No correlation was found between the level of mRNA expression and the cellular number of granulocytes or lymphocytes. The expression level of CALR mRNA also decreases in the blood cells of MPN and lymphoproliferative cancer patients (p<0.05), but we did not observe its correlation with HIF1a or JAK2 mRNA.
Conclusion. We assume that the studied gene expression changes reflect the regulated metabolic processes in the cancer stem cells. Probably, the activation of the associated signaling pathways HIF1a and JAK2/STAT in the white blood cells of patients with chronic blood cancer leads to the adoptive enhancement of autophagy, causing a chronic course of the disease. The assume that the opposite shifts of HIF1a and JAK2 in the microarray research (Cokic VP, et al., PLoS ONE, 2015) can be associated with the procedure of blood cells isolation and the absence of a group of healthy people as a control. Reduced expression of CALR mRNA in patient blood cells requires further investigation.
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The surface modification of polymer microspheres by complex plasma was studied. Melamine-formaldehyde spherical microparticles, falling into neon dc glow discharge, acquired an electric charge on ...their surface and hung in a dust trap, where the electric field strength was strong enough. They were long trapped, forming three-dimensional ordered structures. Depending on the exposure time, the particle sizes and surface properties changed. Scanning electron microscopy provided insight in the particle morphology changing. The dependence of the particle size on the exposure in plasma was measured; the modification of the surface structure was investigated. The results of the statistical processing of the surface structure are presented.
Perovskite manganites derived from LaMnO3 have recently become the subject of intensive study following the discovery of 'colossal' magnetoresistance (a magnetically induced change in electrical ...resistance of up to several orders of magnitude) in several members of this family of compounds. The manganites exhibit a broad range of electronic and magnetic phases, ranging from low-resistance ferromagnetic metals to high-resistance insulators, which are extremely sensitive to variation of composition, temperature and pressure. A recent study showed that such sensitivity also extends to oxygen isotope exchange: replacing 16O with 18O in La0.8Ca0.2MnO3 produces an unusually large change in the magnetic properties (a 21-kelvin decrease in the Curie temperature). The magnitude of this isotope shift is evidence for the essential role played by electron-phonon coupling in determining the transport properties of these materials. Here we show that this sensitivity to oxygen isotope exchange can be even more extreme. In its normal state, the compound La0.175Pr0.525Ca0.3MnO3 undergoes an insulator-to-metal transition as it is cooled below ∼95 K. But we find that, after substituting 18O for 16O, the compound remains an insulator down to 4.2 K, so providing a vivid demonstration of the importance of lattice vibrations in these materials.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Type 2 diabetes mellitus is known to double mortality from cardiovascular diseases (CVD), in which oxidative stress plays an important role. It is suggested that the impact of diabetes on CVD risk ...may vary depending on gender. The aim of the study was to assess oxidative stress parameters in the heart of 12 weeks old male and female Wistar rats with type 2 diabetes mellitus (T2DM) induced by high-calorie diet followed by intraperitoneal streptozotocin injections. The level of advanced oxidation protein products, superoxide dismutase, glutathione reductase and glutathione peroxidase activity in the isolated heart mitochondria and NADPH-oxidase and xanthine oxidase activity in the post-mitochondrial supernatant fraction were determined. It was shown that T2DM induced more pronounced oxidative stress confirmed by the increased level of advanced oxidation protein products in the heart mitochondria of males than females. The data obtained indicate that the main reason of oxidative stress in the heart of diabetic males is the activation of non-mitochondrial sources of reactive oxygen species. While in the heart of diabetic female rats it is the decrease in antioxidant enzymes activity in mitochondria. These results justify the necessity of gender-specific therapy for the prevention and management of diabetic CVD.
Increasing evidence suggests that oxidative stress and induction of mitochondrial permeability transition in cardiomyocytes are linked to tissue damage and the development of diabetic cardiovascular ...complications. The aim of this study was to assess the effects of quercetin (Q) on oxidative stress and mitochondrial permeability transition in the heart of rats with type 2 diabetes mellitus (DM). Type 2 DM was induced in 12-week-old male Wistar rats by intraperitoneal injections of 25 mg/kg streptozotocin twice per week followed by a high-fat diet during four weeks. The rats were divided into three groups: control intact group (C, n = 8), untreated diabetic group (Diabetes, n = 8) and diabetic rats treated with Q (50 mg/kg/day per os for 8 weeks) after diabetes induction (Diabetes+Q, n = 8). Administration of Q increased insulin sensitivity and normalized the functional state of cardiac mitochondria due to increased aconitase and succinate dehydrogenase activities in rats with type 2 DM. Q also ameliorated oxidative stress, decreasing the level of advanced oxidation protein products and increasing the activity of thioredoxin-reductase in heart mitochondria of diabetic rats. In addition, Ca2+-induced opening of the mitochondrial permeability transition pore was significantly inhibited in diabetic rats treated with Q in comparison with the untreated diabetic group. These data demonstrate that Q can protect against oxidative stress, mitochondrial permeability transition induction and mitochondrial dysfunction in cardiomyocytes of diabetic rats. We suggest that the use of Q may contribute to the amelioration of cardiovascular risk in type 2 DM.
Algorithms of cell segmentation on two-dimensional phase images and three-dimensional distributions of a refractive index obtained by means of digital holographic microscopy and tomography are ...developed. The proposed algorithms are optimized for determining cell morphology characteristics including the cell volume, projection area, and surface area. A comparative analysis of the error of cell volume determination by holographic methods using the proposed cell segmentation algorithms and the standard method of confocal fluorescence microscopy has been performed.
Iron oxide nanoparticles coated with polyethylene glycol were synthesized by coprecipitation for use in the magnetic separation of DNA (deoxyribonucleic acid). The blocking temperature of ...nanoparticles was studied by the methods of Mössbauer spectroscopy, ferromagnetic resonance, and using magnetometric measurements. The blocking temperature calculated from the temperature dependence of the coercive force was ~ 200 K. The calculation of the blocking temperature from the relaxation time obtained using Mössbauer spectroscopy gave a value of ~ 450 K. The blocking temperature obtained using ferromagnetic resonance was ~ 910 K. The relationship between the obtained blocking temperatures is in good agreement with the Néel-Brown formula. The constants of effective and surface anisotropy were determined by the method of ferromagnetic resonance. Isolation of DNA from blood using prepared particles and separation in a permanent magnet field revealed sufficient productivity, high speed, and the “chemical delicacy” of this approach.
The formation of previously unknown hexagonal modifications of orthoferrites RFeO3 (R = Eu−Lu) was observed on ZrO2(Y2O3) (111) substrates at 900 °C. XRD and HREM studies reveal epitaxial growth of ...the hexagonal film. The structure of the hexagonal RFeO3 was assigned to the ferroelectric space group P63 cm. The typical structural defects in the hexagonal RMnO3 films on ZrO2(Y2O3) (111) are described. Parallel deposition on perovskite substrates results in the stable perovskite phase. The epitaxial stabilization concept successfully explains the experimental results.
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