Search

Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, Nr3c1). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5–6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5–2-fold), the inhibition of HS biosynthetic system mainly due to the -3–3.5-fold down-regulation of N-deacetylase/N-sulfotransferases (Ndst1 and Ndst2) and sulfatase 2 (Sulf2) expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (Ext1/2, Ndst1/2, Glce, Hs2st1, Hs6st1/2), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.

In the treatment of coronary heart disease, the most promising approach for replacing lost contractile elements involves obtaining cardiomyocytes through cardiac differentiation of pluripotent cells. The objective of this study is to develop a technology for creating a functional layer of cardiomyocytes derived from iPSCs, capable of generating rhythmic activity and synchronous contractions. To expedite the maturation of cardiomyocytes, a renal subcapsular transplantation model was employed in SCID mice. Following explantation, the formation of the cardiomyocyte contractile apparatus was assessed using fluorescence and electron microscopy, while the cytoplasmic oscillation of calcium ions was evaluated through visualization using the fluorescent calcium binding dye Fluo-8. The results demonstrate that transplanted human iPSC-derived cardiomyocyte cell layers, placed under the fibrous capsules of SCID mouse kidneys (for up to 6 weeks), initiate the development of an organized contractile apparatus and retain functional activity along with the ability to generate calcium ion oscillations even after removal from the body.

Histological and immunohistochemical studies require high-quality paraffin blocks, where proper fixation of tissue samples with formalin is a key point. However, in some cases, the possibility to preserve biological samples prior to the formalin fixation or to use deposited tissues from biobanks is important. RNA-stabilizing reagent RNALater represents a potential option, but its suitability for pathological and immunohistochemical studies remains underinvestigated. Here, comparative study of formalin-fixed tissues and those had undergone preservation with RNALater was performed for different SCID mice tissues (brain, liver, kidney, and lung) using histological staining (hematoxylin-eosin and Weigert-van Gieson) or immunostaining for b-actin, glial fibrillary acidic protein, and glycosaminoglycan chondroitin sulfate. It was shown that RNALater preservation for 7-14 days was suitable for histological characterisation of mouse lung tissue, whereas all other tissues demonstrated some changes. Immunoreactivity of all the studied tissues was affected to a different extent, and the observed changes were detected at the 7th day already and continued to get worse by the 14th day. Overall, RNALater preservation affects immunogenicity of normal mouse tissues (brain, liver, kidney, and lung) making them unsuitable for immunohistochemistry. Some tissues retain their morphology (lung tissue) or demonstrate moderate changes (brain, liver, kidney), suggesting a restricted suitability of the RNALater-preserved tissues for histological analysis.

Adjuvant chemoradiotherapy is a standard treatment option for glioblastoma multiforme (GBM). Despite intensive care, recurrent tumors developed during the first year are fatal for the patients. Possibly contributing to this effect, among other causes, is that therapy induces changes of polysaccharide heparan sulfate (HS) chains in the cancer cells and/or tumor microenvironment. The aim of this study was to perform a comparative analysis of heparanase (HPSE) expression and HS content in different normal and GBM brain tissues. Immunohistochemical analysis revealed a significant decrease of HPSE protein content in the tumor (12-15-fold) and paratumorous (2.5-3-fold) GBM tissues compared with normal brain tissue, both in cellular and extracellular compartments. The relapsed GBM tumors demonstrated significantly higher intertumor and/or intratumor heterogeneity of HPSE and HS content and distribution compared with the matched primary ones (from the same patient) (n = 8), although overall expression levels did not show significant differences, suggesting local deterioration of HPSE expression with reference to the control system or by the treatment. Double immunofluorescence staining of various glioblastoma cell lines (U87, U343, LN18, LN71, T406) demonstrated a complex pattern of HPSE expression and HS content with a tendency towards a negative association of these parameters. Taken together, the results demonstrate the increase of intratumor heterogeneity of HPSE protein in relapsed GBM tumors and suggest misbalance of HPSE expression regulation by the adjuvant anti-GBM chemoradiotherapy.

Meningeal tumors are neoplasms with different histologic manifestations of both benign and malignant types that determine the prognosis of tumor recurrence and its consistency. The risk of surgical treatment depends on the location, size, and consistency of the tumor. Magnetic resonance imaging (MRI) sequences can be used to identify the features of tumors, but these MRI characteristics are not well understood. The present study describes an advanced mathematical algorithm to analyze MRI data and distinguish histologic types of meningeal tumors before surgery.Forty-eight patients underwent surgical removal of meningeal brain tumor. All patients had preoperative MRI with a 1.5-T scanner. One radiologist and 2 neurosurgeons evaluated MRI histogram peaks of the whole tumor volume using the advanced computer algorithm.Three specialists received the following mean value of histogram peaks: 15.99 ± 0.23 (± standard error of the mean [SEM]) for meningoteliomatous meningiomas; 21.24 ± 0.3 (±SEM) for fibroplastic meningiomas; 19.0 ± 0.28 (±SEM) for transitional meningiomas; 10.7 ± 0.27 (±SEM) for anatypical, anaplastic meningiomas, 11.03 ± 0.51 (±SEM) for primary intracranial fibrosarcomas and 25.72 ± 0.29 (±SEM) for meningeal hemangiopericytomas. A one-way analysis of variance test proved the difference between group means: F = 70.138, P0.01. The Tukey test and the Games-Howell test indicated that the difference between the tumor groups was significant. Mean deviation in agreement index between specialists was 0.98 ± 0.007 (±SEM).The advanced algorithm proved high specificity, sensitivity, and interoperator repeatability.

Aspergillus aortitis is a rare, often fatal infection. Here, we report successful treatment of an aortotomy site that became infected by Aspergillus spp. after valve replacement. Surgical debridement, combined with antifungal therapy, allowed a favorable outcome.

Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50–55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues. Heterogeneous HS distribution in the HS-positive tumours was more related to the necrosis or glandular-like brain zones rather than glioma cells with high or low Ki-67 index. According the Kaplan–Meier curves, HS accumulation in glioma cells was associated with low relapse-free survival (RS) of the GBM patients (p

Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell–cell and cell–matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades. RT-PCR analysis showed that the overall transcriptional activity of the main HS biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) was decreased by 1.5–2-fold in Grade II-III glioma (p < 0.01) and by 3-fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue. The inhibition was mainly due to the elongation (a decrease in EXT1/2 expression by 3–4-fold) and 6-O-sulfation steps (a decrease in 6OST1/2 expression by 2–5-fold) of the HS biosynthesis. Heparanase (HPSE) expression was identified in 50% of GBM tumours by immunostaining, and was characterised by a high intratumoural heterogeneity of the presence of the HPSE protein. The detected disorganisation of the HS biosynthetic system in gliomas might be a potential molecular mechanism for the changes of HS structure and content in tumour microenvironments, contributing to the invasion of glioma cells and the development of the disease.

Ultrastructural changes in endothelial cells (EC) of myocardial capillaries were studied in 24 dogs which underwent hypothermia without perfusion. Biopsy specimens for electron microscopy were taken from the left ventricle of each dog in the control group, during anesthesia (prior to active cooling), and at the end of moderate (28–30°) and deep (22–24°) artificial body cooling. The following morphological types of the EC were identified both in the control group and in all test groups: those with moderately dense cytoplasm, light, dark, and irreversibly damaged cells. Dark cells showed increased numbers of plasmalemmal vesicles and appeared to be more transport-specialized as opposed to other types. In all stages of the experiment the amount of dark cells continuously increased (to 23.80, 34.62, and 47.17%, respectively). On cooling to 28–30°, subcellular manifestation of reduced synthetic activity of organelles (nucleus, Golgi complex, and rough endoplasmic reticulum) was observed in all types of the EC. These changes persisted, or even increased, at the end of deep hypothermia. The transport activity of the EC changed differently in three experimental groups in all cell types. Micropinocytotic activity increased under spontaneous mild hypothermia (34–35°) during anesthesia and tended to decrease with subsequent artificial lowering of the temperature to 22–24°. These ultrastructural changes seem to make up an integral part of the process of capillary endothelium adaptation to body surface cooling, and they might contribute to the development of tolerance to subsequent ischemic exposure during cardiac arrest.

In the process of evolution of powder metallurgy in Russia the task permanently formulated was the following: to improve strength properties of P/M superalloys without application of additional complex HIPed blanks deformation operation. On the other hand development of a turbine disk material structure to ensure an improvement in aircraft engine performance requires the use of special HIP and heat treatment conditions. To ensure maximum strength properties of disk materials it is necessary to form a structure which would have optimum size of solid solution grains, γ′-phases and carbides. Along with that heating of the material up to a temperature determined by solvus of an alloy ensures a stable and reproducible level of mechanical properties of the disks. The above-said can be illustrated by successful mastering of new complex-alloyed VVP-class superalloys with the use of powder size − 100 μm. Application of special HIP and heat treatment conditions for these superalloys to obtain the desired grain size and the strengthening γ′-phase precipitates allowed a noticeable improvement in ultimate tensile strength and yield strength up to ≥1600 MPa and ≥1200 MPa respectively. 100 hrs rupture strength at 650 ∘ C and 750 ∘ C was improved up to 1140 MPa and 750 MPa respectively. P/M VVP nickel-base superalloys offer higher characteristics in comparison with many superalloys designed for the same purposes. HIPed disc compacts manufactured from PREP-powder have a homogeneous micro- and macrostructure, a stable level of mechanical properties.

In the present article questions of the public subjects which are carrying out legal regulation of taking to administrative responsibility of officials in the Republic of Tajikistan activity organization for the purpose of clarification of the role of Agency of the President of the Republic of Tajikistan on financial control and fight against corruption as a public subject of legal regulation are considered. In the modern science, questions of subjects of public law are discussed in several planes, some synonymous concepts are used at the same time: "subject of public law", "subject carrying out public functions", "subject of the public legal relationship" and "the public subject". So, such public subjects are the government bodies authorized by the administrative legislation of the Republic of Tajikistan and the specifics of it’s legal impact on the relevant group of public relations are the activities of the above in settlement of the official's administrative responsibility in the Republic of Tajikistan. Activity of such public subjects of the administrative responsibility legal regulation of officials in the Republic of Tajikistan represents a set of legal means by which the legal impact on the public relations arising at involvement of officials to the administrative responsibility in connection to the commission of administrative offenses by the official is analyzed. In the article offers of changes to the current legislation are given.