Ex Vivo Analysis of an Association of Mechanical Strength of Dilated Ascending Aorta with Tissue Matrix Metalloproteinases and Cytokines.

We analyzed the associations of the mechanical strength of dilated ascending aorta wall (intraoperative samples from 30 patients with non-syndromic aneurysms) with tissue MMPs and the cytokine system. Some samples were stretched to break on an Instron 3343 testing machine and the tensile strength was calculated; others were homogenized and the concentrations of MMP-1, MMP-2, MMP-7, their inhibitors (TIMP-1 and TIMP-2), and pro- and anti-inflammatory cytokines were determined by ELISA. Direct correlations between aortic tensile strength and concentrations of IL-10 (r=0.46), TNFα (r=0.60), and vessel diameter (r=0.67) and an inverse correlation with patient's age (r=-0.59) were revealed. Compensatory mechanisms supporting the strength of the ascending aortic aneurysm are possible. No associations of MMP-1, MMP-7, TIMP-1, and TIMP-2 with tensile strength and aortic diameter were found.

[Atypical fibroxanthoma]. / Atipicheskaya fibroksantoma.

Atypical fibroxanthoma (AFX) is a rare skin tumor characterized by a combination of a «malignant¼ morphological features and non-aggressive clinical course. Diagnosing AFX is challenging due to histological «diversity¼ and heterogeneous immunophenotype. The presented review describes the history and evolution of AFX as a nosological form of cancer, its histogenetic origin, pathogenesis and biological potential. The clinical, morphological, immunohistochemical, molecular cytogenetic characteristics and histological subtypes of the tumor as well as differential diagnosis have been presented in detail.

Association of coronary microvascular dysfunction and cardiac muscle injury in acute myocardial infarction: results of comparison of dynamic SPECT and cardiac MRI.

Aim      To study the interrelation of changes in coronary microcirculation by data of dynamic single photon emission computed tomography (SPECT) and myocardial injury by data of magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI).Material and methods  The study included patients admitted to the emergency cardiology department with new-onset AMI. Contrast-enhanced cardiac MRI was performed for all patients on day 2-7 of admission. Dynamic SPECT of the myocardium with evaluation of semiquantitative and quantitative parameters of perfusion was performed on day 7-10.Results All patients were divided into two groups based on the type of MR contrast agent accumulation: 1) patients with the ischemic type of contrast enhancement (n=34; 62 %); 2) patients with the non-ischemic type of contrast enhancement (n=21; 38 %). According to data of myocardial perfusion scintigraphy (MPS), the group of ischemic MR pattern had larger perfusion defects at rest and during a stress test. Moreover, this group was characterized by lower global stress-induced blood flow and absolute and relative myocardial flow reserve (MFR). When the study group was divided into patients with transmural (n=32; 58 %) and non-transmural (n=23; 42 %) accumulation of the MR-contrast agent, lower values of global stress-induced blood flow and of absolute and relative MFR were observed in the group of transmural MR-enhancement pattern. A moderate inverse correlation was found between the stress-induced myocardial blood flow and the volume of myocardial edema (r= -0.47), infarct area (r= -0.48) and microvascular obstruction area (r= -0.38).Conclusion      The variables of dynamic SPECT characterizing microcirculatory disorders that are independent on or due to injuries of the epicardial coronary vasculature reflect the severity and depth of structural changes of the myocardium in AMI. In this process, quantitative variables of myocardial perfusion are interrelated with the myocardial injury more closely than semiquantitative MPS indexes. The findings of the present study can also contribute to the heterogenicity of a patient group with acute coronary syndrome and AMI. Further study is required for understanding the prognostic significance of dynamic SPECT parameters.

[State of the art mathematical methods of the coronary blood flow modelling: background and clinical value].

X-ray computed tomography coronary angiography (CTCA) is a current method for diagnosing ischemic heart disease. Although this method has a high specificity and a negative predictive value in diagnosing coronary obstructions, there are limitations in determining the hemodynamic significance of the stenosis. Extensive use of noninvasive methods for evaluation of coronary hemodynamics, specifically evaluation of the fractional flow reserve (FFR) is limited due to its high cost and risks of complications. Mathematical modeling of coronary circulation and its reserve based on CTCA data is an up-to-date method that has been experimentally confirmed and clinically validated. This method showed a high diagnostic efficacy in several large studies that used the invasive determination of FFR as a "gold standard". This review addresses the current state of studies on mathematical modeling for fractional coronary reserve in patients with ischemic heart disease, as well as the limitations and prospects of this method.

[Bilary anastomotic strictures after right lobe living donor liver transplantation: a single-center experience]. / Biliarnye anastomoticheskie striktury posle transplantatsii pravoi doli pecheni ot zhivogo rodstvennogo donora: opyt odnogo transplantatsionnogo tsentra.

OBJECTIVE: To determine the incidence of AS after right lobe living donor liver transplantation with various biliary reconstructions and to identify the predictors of this complication. MATERIAL AND METHODS: A retrospective and prospective analysis included 245 RLLDLTs for the period 2011-2018 at the Burnazjan Federal Medical Biophysical Center. The results of transplantations in 207 patients aged 19-68 years (median 43 years) were assessed. There were 82 men and 125 women. Follow-up period ranged from 10 to 98 months (median 35 months). We analyzed the relationship between surgical characteristics (preoperative data of recipients and donors, graft parameters, technical features of biliary reconstruction and features of post-transplantation period) and incidence of anastomotic strictures. A total of 58 parameters were analyzed. RESULTS: AS occurred in 20 (9.7%) recipients. Median AS-free period was 5 months (range 1-44). In 17 (85%) patients, AC developed within a year after surgery. Cumulative 1-, 2- and 5-year incidence of AS was 8.3%, 8.9%, and 11%, respectively. Significant predictors of AS were impaired arterial blood supply to the graft (HR 7.8, 95% CI 2.3-26.0, p<0.001), biliary leakage ISGLS class B or C (HR 5.0, 95% CI 2.0-12.8, p<0.001), early allograft dysfunction (HR 4.2, 95% CI 1.5-11.6, p=0.006) and female recipient (HR 3.2, 95% CI 1.1-9.9, p=0.04). In our sample, variant biliary anatomy of the graft and recipient liver, as well as technical features of biliary reconstruction did not affect the risk of AS. CONCLUSION: Variant biliary anatomy of potential donor alone should not be considered as a contraindication for organ donation and right liver lobe transplantation. Precise surgical technique, high transplantation activity, as well as experience of reconstructive interventions on the bile ducts during other operations can significantly reduce the incidence of AS after RLLDLT up to 9.7%.

[Biphasic (dedifferentiated) osteosarcoma of the lung in the light of current ideas on biphasic tumors]. / Bifaznaia ('dedifferentsirovannaia') osteosarkoma legkogo v svete sovremennykh predstavlenii o bifaznykh opukholiakh.

The paper presents a case of biphasic (dedifferentiated) osteosarcoma arising primarily on the lung, which has not previously encountered in the literature. It provides a detailed description of its clinical, instrumental, and morphological pattern. It also analyzes the literature on the study of primary pulmonary osteosarcoma and extraskeletal osteosarcoma with high-grade transformation. This clinical case is a clear example of classic biphasic sarcoma interpreted in the context of the phenomenon of biphasic tumors. Their most important aspects (terminology, morphology, biological behavior, and a mechanism of dedifferentiation) are highlighted; the key characteristics of biphasic sarcomas are listed.

[Metabolomic profiling in patients with metabolic syndrome].

OBJECTIVE: To identify biomarkers, which are most specific for patients with metabolic syndrome (MS) using metabolomic profiling. MATERIALS AND METHODS: Metabolomic profiling of patients with MS and comparison of their profile with the profile of volunteers was performed using high-performance liquid chromatography-mass-spectrometry. RESULTS: The metabolomic profile of MS patients differed in several amino acids, including choline, cysteine, and serine and in the acylcarnitine group (р<0.05 for all comparisons). CONCLUSION: The metabolites most specific for MS patients were identified. Increased concentrations of a combination of amino acids and carnitines can be considered as possible additional risk factors for cardiovascular diseases.

Ultrastructural evidence for nutritional relationships between a marine colonial invertebrate (Bryozoa) and its bacterial symbionts.

Autozooids of the cheilostome bryozoan Aquiloniella scabra contain rod-like bacteria in the funicular bodies - the complex swellings of the funicular strands. Each funicular body contains symbionts in the central cavity surrounded by a large, synthetically active internal "sheath-cell" (bacteriocyte) and a group of the flat external cells. The tightly interdigitating lobes of these cells form a capsule well-isolated from the body cavity. Slit-like spaces between bacteria are filled with electron-dense matrix and cytoplasmic processes of various sizes and shapes (often branching) produced by the "sheath-cell". The cell ultrastructure and complex construction of the funicular bodies as well as multiplication of the bacteria in them suggest metabolic exchange between host and symbiont, involving the nourishment of bacteria. We suggest that the bacteria, in turn, influence the bryozoan mesothelial tissue to form the funicular bodies as capsules for bacterial incubation. We present ultrastructural data, discuss possible variants in the development of the funicular bodies in Bryozoa, and propose the possible role of bacteria in the life of their bryozoan host.

Renal denervation with a resistant arterial hypertension: the results of a five-year follow-up.

AIM: To evaluate the 5-year results of renal denervation (RDN) in patients with resistant arterial hypertension (AH). MATERIALS AND METHODS: The study included 14 patients to whom, during the 2011-2013 period RDN has been completed. Before and after the intervention, office blood pressure, quality of life indicators according to the EQ-5D questionnaire, mass index bodies, indicators of kidney function were duly assessed. RESULTS: Five years after RDN, office BP decreased from 165/110 to 139/95 mm Hg. Art. (p<0.05), with the average number of of drugs decreased from 4.6 to 3.1. 12 months after the RDA, the quality of Life, based on the questionnaire EQ-5D has increased from 60 to 80 points, by the fifth year the indicator fell to 74 points. Body mass index during 5 years decreased from 33.8 ± 3.5 to 30.9 ± 3.0 kg/m2. Mean plasma creatinine initially and after 5 years remained within the normal range, the mean the GFR score after 5 years being decreased by 9.5 ml/min/1.73 m2. CONCLUSION: RDN can be regarded as effective and safe method of additional treatment of patients with resistant hypertension.

Proteomic Analysis of Escherichia coli Protein Fractions Resistant to Solubilization by Ionic Detergents.

Amyloids are protein fibrils adopting structure of cross-beta spine exhibiting either pathogenic or functionally significant properties. In prokaryotes, there are several groups of functional amyloids; however, all of them were identified by specialized approaches that do not reveal all cellular amyloids. Here, using our previously developed PSIA (Proteomic Screening and Identification of Amyloids) approach, we have conducted a proteomic screening for candidates for novel amyloid-forming proteins in Escherichia coli as one of the most important model organisms and biotechnological objects. As a result, we identified 61 proteins in fractions resistant to treatment with ionic detergents. We found that a fraction of proteins bearing potentially amyloidogenic regions predicted by bioinformatics algorithms was 3-5-fold more abundant among the identified proteins compared to those observed in the entire E. coli proteome. Almost all identified proteins contained potentially amyloidogenic regions, and four of them (BcsC, MukB, YfbK, and YghJ) have asparagine- and glutamine-rich regions underlying a crucial feature of many known amyloids. In this study, we demonstrate for the first time that at the proteome level there is a correlation between experimentally demonstrated detergent-resistance of proteins and potentially amyloidogenic regions predicted by bioinformatics approaches. The data obtained enable further comprehensive characterization of entirety of amyloids (or amyloidome) in bacterial cells.

Cancer risk among workers of a secondary aluminium smelter.

BACKGROUND: Cancer risk in secondary aluminium production is not well described. Workers in this industry are exposed to potentially carcinogenic agents from secondary smelters that reprocess aluminium scrap. AIMS: To evaluate cancer risk in workers in a secondary aluminium plant in Spain. METHODS: Retrospective cohort study of male workers employed at an aluminium secondary smelter (1960-92). Exposure histories and vital status through 2011 were obtained through personal interviews and hospital records, respectively. Standardized mortality (SMRs) and incidence ratios (SIRs) were calculated. RESULTS: The study group consisted of 98 workers. We found increased incidence and mortality from bladder cancer [SIR = 2.85, 95% confidence interval (CI) 1.23-5.62; SMR = 5.90, 95% CI 1.58-15.11]. Increased incidence was also observed for prostate cancer and all other cancers but neither were statistically significant. No increased risk was observed for lung cancer. CONCLUSIONS: Results of this study suggest that work at secondary aluminium smelters is associated with bladder cancer risk. Identification of occupational carcinogens in this industry is needed.

[FUNCTIONAL DIFFERENTIATION IN BRYOZOAN COLONY: A PROTEOMIC ANALYSIS].

Bryozoans are typical modular organisms. They consist of repetitive structural units, the zooids. Bryozoan colonies grow by zooidal budding, with the distribution pattern of the budding loci underlying the diversity of colony forms. Budding is usually restricted to the zooids at the periphery of the colony, which form a "growing edge" or local terminal growth zones. Non-budding parts of the colony can be functionally subdivided, too. In many species colonies consists of regular, often repetitive zones of feeding and non-feeding modules, associated with a periodical degeneration and regeneration of the polypide, retractile tentacle crown with a gut and the accompanying musculature. So, there is functional differentiation in bryozoan colonies but its mechanisms are unknown. Presumably, budding and/or polypide recycling in different colony parts are induced or inhibited by certain determinants of functional specialization. An effective tool of their identification is the comparison of proteomes of functionally different zones. Here we report the results of proteomic analysis of three bryozoan species from the White Sea, which have a different colony form: Flustrellidra hispida, Terminoflustra membranaceotruncata and Securiflustra securifrons. Using differential two-dimensional electrophoresis (2D-DIGE), we compared proteomes of the growing edge and the zones consisting of feeding and non-feeding zooids in these species. We estimated the overall proteome variability, revealed proteins whose relative abundance gradually changed along the proximal-distal colony axis and suggested that they might be involved in the functional differentiation of the colony.

[PROTEOMIC ANALYSIS OF ADAPTIVE MECHANISMS TO SALINITY STRESS IN MARINE GASTROPODS LITTORINA SAXATILIS].

Salinity is one of the most important abiotic environmental factors affecting marine animals. If salinity deviate from optimum, adaptive mechanisms switch on to maintain organism's physiological activity. In this study, the reaction of the snails Littorina saxatilis from natural habitats and in response to experimental salinity decreasing was analyzed on proteomic level. The isolation of all snails inside their shells and gradually declining mortality was observed under acute experimental salinity decrease (down to 10 per hundred). Proteomic changes were evaluated in the surviving experimental mollusks compared to control individual using differential 2D gel-electrophoresis (DIGE) and subsequent LC-MS/MS-identification of proteins. Approximately 10% of analyzed proteins underwent up- or down regulation during the experiment. Proteins of folding, antioxidant response, intercellular matrix, cell adhesion, cell signaling and metabolic enzymes were identified among them. Proteome changes observed in experimental hypoosmotic stress partially reproduced in the proteomes of mollusks that live in conditions of natural freshening (estuaries). Possible mechanisms involved in the adaptation process of L. saxatilis individuals to hypo-osmotic stress are discussed.

Orphan gene in Littorina: An unexpected role of symbionts in the host evolution.

Mechanisms of reproductive isolation between closely related sympatric species are of high evolutionary significance as they may function as initial drivers of speciation and protect species integrity afterwards. Proteins involved in the establishment of reproductive barriers often evolve fast and may be key players in cessation of gene flow between the incipient species. The five Atlantic Littorina (Neritrema) species represent a notable example of recent radiation. The geographic ranges of these young species largely overlap and the mechanisms of reproductive isolation are poorly understood. In this study, we performed a detailed analysis of the reproductive protein LOSP, previously identified in Littorina. We showed that this protein is evolutionary young and taxonomically restricted to the genus Littorina. It has high sequence variation both within and between Littorina species, which is compatible with its presumable role in the reproductive isolation. The strongest differences in the LOSP structure were detected between Littorina subgenera with distinctive repetitive motifs present exclusively in the Neritrema species, but not in L. littorea. Moreover, the sequence of these repetitive structural elements demonstrates a high homology with genetic elements of bacteria, identified as components of Littorina associated microbiomes. We suggest that these elements were acquired from a symbiotic bacterial donor via horizontal genetic transfer (HGT), which is indirectly confirmed by the presence of multiple transposable elements in the LOSP flanking and intronic regions. Furthermore, we hypothesize that this HGT-driven evolutionary innovation promoted LOSP function in reproductive isolation, which might be one of the factors determining the intensive cladogenesis in the Littorina (Neritrema) lineage in contrast to the anagenesis in the L. littorea clade.

The Molecular Mechanisms of Gametic Incompatibility in Invertebrates.

Fertilization (gamete fusion followed by zygote formation) is a multistage process. Each stage is mediated by ligand-receptor recognition of gamete interaction molecules. This recognition includes the movement of sperm in the gradient of egg chemoattractants, destruction of the egg envelope by acrosomal proteins, etc. Gametic incompatibility is one of the mechanisms of reproductive isolation. It is based on species-specific molecular interactions that prevent heterospecific fertilization. Although gametic incompatibility may occur in any sexually reproducing organism, it has been studied only in a few model species. Gamete interactions in different taxa involve generally similar processes, but they often employ non-homologous molecules. Gamete recognition proteins evolve rapidly, like immunity proteins, and include many taxon-specific families. In fact, recently appeared proteins particularly contribute to reproductive isolation via gametic incompatibility. Thus, we can assume a multiple, independent origin of this type of reproductive isolation throughout animal evolution. Gametic incompatibility can be achieved at any fertilization stage and entails different consequences at different taxonomic levels and ranges, from complete incompatibility between closely related species to partial incompatibility between distantly related taxa.

[Brain-derived neurotrophic factor in multiple sclerosis]. / Mozgovoi neirotroficheskii faktor pri rasseiannom skleroze.

The review presents data on brain-derived neurotrophic factor (BDNF), its structure and functions, the effect on the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis (MS). The correlation of BDNF level with clinical manifestations of MS and the changes of its level during disease-modifying therapy is considered.