Endogenous Regeneration of Alveolar Bone by Decellularized Tooth Matrix.

The efficiency of bone tissue regeneration by decellularized tooth matrix, demineralized tooth matrix, and commercial xenograft Bio-Oss Spongiosa was compared on the model of a critical-size circular defect in the alveolar bone of the upper jaw of adult Wistar rats. The defect healing dynamics was assessed using histological, histomorphometrical, and immunohistochemical methods on days 30 and 60. In contrast to demineralized matrix and commercial xenograft, decellularized matrix induces the formation of the new bone tissue by day 60. Decellularized matrix can be considered as a biomaterial for cell-free tissue engineering for alveolar bone restoration in dentistry and maxillofacial surgery.

[Nutrition and adipose tissue distribution in low cardiovascular risk individuals, depending on the central obesity].

The low cardiovascular risk group according to SCORE in relation to the clinical and laboratory characteristics of patients is very heterogeneous, which leads to the presence of a residual risk of cardiovascular events. This category may include individuals with a family history of cardiovascular disease at a young age, with abdominal obesity (AO), endothelial dysfunction, and high levels of triglyceride-rich lipoproteins. In this regard, an active search is underway for new metabolic markers within the low cardiovascular risk group. The purpose of the study was to compare the nutrition, the adipose tissue distribution in low cardiovascular risk individuals, depending on the AO. Material and methods. The study included 86 healthy low risk (SCORE<1%) patients (mean age 42.6±2 years), who were divided into 2 groups: with AO [waist circumference (WC) >=94 cm in men and >=80 cm in women] - 44 patients (32% of men) and without AO - 42 patients (38% of men). The body composition was carried out using the bioimpedance analyzer. The distribution of ectopic fat deposits in the liver, pancreas and epicardial region was studied using ultrasound methods. A frequency questionnaire (Diet Risk Score) was used to assess nutrition. Results. In low risk patients with AO, signs of unhealthy diet are statistically significantly more common (in 52 in the main group vs 2% in the control group, p<0.01), ectopic deposition of adipose tissue in the liver (53 vs 9%, p<0.001), pancreas (56% in the main group, absent in the control group, p<0.001), epicardia l region (the epicardial fat thickness median is 4.24 mm in the main group vs 2.15 mm in the control group) compared with a control group. Conclusion. The low cardiovascular risk group is very heterogeneous. One of the markers of heterogeneity is central obesity - a marker of unhealthy diet, subclinical ectopic fat deposition and hypertriglyceridemia. Patients with AO of the low cardiovascular risk group require a more thorough examination with the obligatory determination of waist circumference, ultrasound assessment of the liver and pancreas parenchyma, and determination of the epicardial fat thickness. Using a short nutrition questionnaire allows you to quickly identify signs of unhealthy diet and discuss them with the patient.

[Piecewise linear regression model of hemostasis dynamics in donors and patients with schizophrenia]. / Kusochno-lineinaya regressionnaya model' dinamiki gemostaza u donorov i bol'nykh shizofreniei.

OBJECTIVE: This work is to develop and use a new approach to the analysis of differences between the velocity profiles of registered light signals in groups of patients with schizophrenia and healthy donors. MATERIAL AND METHODS: The present study involved 62 patients (all female) with schizophrenia or schizoaffective disorders in the acute period (observational study - 2016-2017). 44 patients were diagnosed with paranoid schizophrenia with an attack-progredient type of course (F20.01 according to ICD-10) or with a continuous type of course (F20.02). The fibrinodynamics test (FD) was performed on the T-2 thrombodynamics device (Hemacore LLC, Moscow), which makes it possible to monitor the processes of coagulation and fibrinolysis in the cuvette channels filled with fresh blood plasma. The result of the test are the brightness profiles of the clot. RESULTS: In the proposed approach, each profile is characterized by a vector of distances between it and other analyzed profiles. At that the distances between the profiles are calculated as the sum of the modules of differences at different points of the observation interval. This method makes it possible to overcome a certain loss of information that occurs when using a standard method based on the calculation of several parameters that characterize the analyzed velocity profiles. The method includes the construction of all kinds of statistically significant piecewise linear regression models that link the distances to two profiles. The velocity profiles corresponding to the points lying on opposite sides of the break point of such models have significantly different shapes. In practice, it turns out that for many piecewise linear regression models, the break points also significantly separate the velocity profiles for the compared groups of donors and patients with schizophrenia. Statistically significant deviations at the level p≤0.01 exist for 16.1% of 3143 statistically significant piecewise linear models. CONCLUSION: The developed method makes it possible to visually establish the relationship between the shape of the velocity profile and the presence of the disease.

[Epithelial-stromal interactions in pancreatic adenocarcinoma: the role of stroma in disease progression]. / Epitelial'no-stromal'nye vzaimodeistviya v adenokartsinome podzheludochnoi zhelezy: rol' stromy v progressirovanii zabolevaniya.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and difficult to treat form of pancreas cancer. PDAC and other solid cancers contain both tumor cells and normal connective tissue cells called stromal cells, which are responsible for the excess production of extracellular matrix. It is known that in more than 90% of PDAC tumors and in many other types of cancer, mutations of the KRAS gene are observed, the reciprocal signaling of which has been shown between tumor and stromal cells in vitro. Pancreatic stromal stellate cells are considered precursors of activated or tumor-associated fibroblasts (CAFs), which are an increasing population of cells that proliferate in situ or are recruited into the tumor. CAFs are a heterogeneous population of stromal fibroblasts with different molecular profiles that change during tumorigenesis. Both immunosuppressive and immunosuppressive subsets of CAFs can coexist in the stroma of a single tumor. Based on the heterogeneity of the intertumor stroma, attempts are being made to classify PDAC and predict the course of the disease.

[Is there a claudin-low phenotype of breast cancer?] / Sushchestvuet li «nizkoklaudinovyi¼ fenotip raka molochnoi zhelezy?

The novel molecular subtype of breast cancer (BC), named "claudin-low", was described in 2007. It was characterized by the consistently low expression of genes involved in the formation of epithelial tight junctions in combination with the high activation of genes associated with the epithelial-to-mesenchymal transition, as well as tumor stem cell markers. The similar claudin- low subtype was later identified at the transcriptional level in bladder cancer, gastric cancer, and serous ovarian cancer. However, only in relation to BC, attempts were made to create a surrogate panel for immunohistochemical identification of this subtype in a manner like the intrinsic molecular BC subtypes identified using three main markers, such as ER, PR, and HER-2. At the same time, the ambiguity in the expression of claudins among the subtypes of BC, which is defined by various authors at the immunohistochemical level, as well as the absence of both the confirmed set of immunohistochemical criteria and a unified approach to their assessment, complicate these efforts. The purpose of the review is to show that the immunohistochemical identification of claudin-low subtype of BC is a separate problem that has significant limitations, needs standardization and has not yet reached diagnostic value.

[Application of machine learning for predicting the outcome of treatment of patients with schizophrenia according to the indicators of «Thrombodynamics¼ test]. / Primenenie mashinnogo obucheniya dlya prognozirovaniya iskhoda lecheniya bol'nykh shizofreniei po pokazatelyam testa «Trombodinamika¼.

OBJECTIVE: To identify relationships between thrombodynamic values and the severity of the condition in patients with schizophrenia spectrum disorders (SSD) before and after treatment. MATERIAL AND METHODS: The study included 92 patients in an acute state of schizophrenia or schizotypal disorder, aged 16 to 57 years (median age [Q1; Q3] - 25 years). All patients received complex psychopharmacotherapy adequate to their psychopathological state. The PANSS was used to assess the severity of symptoms in patients. The coagulation parameters were determined by the thrombodynamics test, in which the growth of fibrin clots in platelet free plasma are observed from special activator. The patient population was divided into two groups with weak and strong response to treatment. Data analysis included machine learning (ML) techniques: logistic regression, random forests, decision trees, support vector machines with radial basis functions, statistically weighted syndromes, permutation method. RESULTS: An analysis using permutation method revealed statistically significant different thrombodynamics values between groups of patients with weak and strong responses. There are significant differences between thrombodynamics values: T1D, T2D, T2Tlag and DTlag, and values characterizing the severity of positive symptoms before and after treatment (T1PposTot, T2PposTot), severity of psychopathological symptoms before treatment (T1Ppsy1, T1Ppsy6, T1Ppsy13). All ML techniques showed the relationship between thrombodynamics values and response to treatment. The best statistical significance was for statistically weighted syndromes method. CONCLUSION: The combination of the results of different ML techniques at a high level of statistical significance identifies the thrombodynamic predictors of weak effect of treatment of SSD.

Prognostic Model of Prehypertension Risk Based on Molecular Markers.

The prognostic models assessing the risk of prehypertension in coming 1-2-year period for 30-60-year-old subjects were developed with the help of computer recognition technology using 6 recognition methods. These models are based on the content of molecular markers in blood serum and the risk factors for the development of prehypertension in men and women who had "optimal" BP for last 3 years and in patients with newly diagnosed prehypertension. The models were compared for their prediction power. The most effective model was obtained with gradient boosting method based on the content of molecular markers. It is characterized with a high predictive power (ROC AUC=0.76), specificity (96.4%), and overall accuracy (86.6%) accompanied with close relationship between prognosis and actual symptoms of prehypertension (p=0.001).

Serum Level of HLDF24 Peptide as an Objective Marker of Prehypertension.

The concentrations of the key factors of molecular pathogenesis of prehypertension (angiotensin II, HLDF24, S100b, endothelin, autoantibodies to these molecules, and VEGF) were analyzed in subjects with optimal BP (<120/80 mm Hg) and prehypertension (120-139/80-89 mm Hg). Comparative and correlation analysis of the levels of these molecules was performed. A statistically significant decrease in HLDF24 level in prehypertension in comparison optimal BP was observed. Specific features and interactions between the studied factors in optimal BP and in prehypertension were studied. The mechanisms underlying the observed associations between serum concentration of HLFF24 and the development of prehypertension were discussed.

Reprogramming of Human Retinal Pigment Epithelial Cells under the Effect of bFGF In Vitro.

We studied the effect of bFGF on human retinal pigment epithelial cells in vitro In ARPE-19 cells, enhanced expression of KLF4 mRNA and reduced expression of PAX6, MITF, and OTX2 mRNA specific for retinal pigment epithelium were observed after bFGF application. The expression of KLF4 mRNA peaked in 72 h after bFGF application and then sharply decreased, which was accompanied by a 3-fold increase in TUBB3 mRNA expression (neuronal marker). Immunocytochemical analysis showed that in the presence of bFGF, some cells retained epithelial properties and showed positive staining for connexin-43, while others had long axon-like processes and demonstrated positive staining for ßIII-tubulin, which attests to their neuronal transdifferentiation. Despite the prevalence of the epithelial properties, ARPE-19 cells under the influence of bFGF can show proneuronal properties.

Heterogeneity of Retinal Pigment Epithelial Cells from Adult Human Eye in Different Culturing Systems.

We studied the behavior of retinal pigment epithelial cells from adult human eye derived from different donors in different culturing systems: on plastic, in collagen gel, and on decellularized neural retina substrate. The cells diverge into two subpopulations similar by their morphology and behavior: one subpopulation migrated to the surface of the dense substrate and the other formed spheroid structures consisting of aggregated cells. This fact confirms the data on genetically-predetermined phenotypic heterogeneity of retinal pigment epithelium cells that should be taken into account when using these cells in tissue engineering.

Effect of hrWnt7a on Human Retinal Pigment Epithelial Cells In Vitro.

Human recombinant protein Wnt7a (hrWnt7a) inhibits cell proliferative activity and triggers cell polarization. Although cell polarization process was maintained only over a short time, probably via microenvironmental stimuli, hrWnt7a is involved in the transformation of the retinal pigment epithelium. Analysis of Wnt signaling pathway and its regulation will help to understand the processes in retinal pigment epithelial cells under pathological conditions, which can be useful in developing new generation drugs.

Molecular markers of arterial hypertension in patients with normotony, pre-hypertension and hypertension.

We studied concentrations of angiotensin II, HLDF24 peptide, endothelin proteins, S100B, and autoantibodies to them and serum levels of blood natriuretic peptide in patients with different categories of "normal" arterial BP and hypertension. The relationship between blood levels of the above factors and normotony, pre-hypertension, and hypertension in the examined groups was analyzed. The results suggest that the studied molecular factors can serve as potential predictors of arterial hypertension and used for personalized hypertension risk assessment.

[Tumor stem cells in breast cancer].

High mortality from breast cancer is associated with the high heterogeneity of tumor and the frequent recurrences of the pathological process, which are due to the presence of tumor stem cells. The review considers the biological properties of tumor stem cells, the molecular mechanisms of their regulation, interaction with the microenvironment, and their role in the heterogeneity of the morphological and clinical forms of breast cancer.

Effect of transplants of retinal pigment epithelial cells from adult human eye on degenerative processes in the brain of rats with experimental acute hypoxia.

Stimulation of cell regeneration in the brain and eye retina in various degenerative processes is a pressing problem in neurobiology. A promising approach is transplantation of somatic cells reprogrammed towards neural lineage. We studied the effect of transplantation of retinal pigment epithelial cells from adult human eye transdifferentiated in culture on degenerative processes in the brain of rats subjected to acute hypoxia. Immunohistochemical and molecular genetic analysis suggests that retinal pigment epithelial cells transdifferentiate in vitro and express markers of low-differentiated neural cells. The cells transplanted into rat brain survive for at least 20 days. During this period, they stimulate compensatory and reparative processes that protected cortical neurons in the recipients from hypoxia-induced degeneration.

[Molecular epidemiological analysis of the HIV infection in the Blagoveshchensk and Khabarovsk Area (Russian Far East)].

The results of the molecular-epidemiological analysis of the HIV-1 variants circulating in Blagoveshchensk and Khabarovsk (Russian Far East) were presented. In Blagoveshchensk HIV-1 IDU-A variants were dominated (92.5%), similar to the regions of the European part of Russia. In Khabarovsk the heterogeneity of circulating HIV-1 variants was noted. In addition to IDU-A variants (66.0%), the strains of subtype B (12.6%), C (4.4%) and recombinant strain form CRF02_AG (17.0%) were identified. Using the phylogenetic analysis method the version of the penetration of HIV-1 variants from China and Japan was not supported.

[Experimental models of human retinal degenerations: genetic models].

Existing approaches in experimental animal modeling of human retinal degenerations, genetic models in particular, that allow to study the pathogenesis are reviewed.

[Experimental models of human retinal degenerations: induced models].

Existing approaches in experimental animal modeling of human retinal degenerations are reviewed, in particular models, in which pathological processes in animals were induced by chemical, biological and physical exposure.

Expression of multipotent and retinal markers in pigment epithelium of adult human in vitro.

Immunoperoxidase and molecular genetic analysis showed that retinal pigment epithelial cells from adult human eye undergo morphogenetic changes in vitro. They lose expression of tissue-specific protein RPE65 and start to express stem cell markers: Oct4 (POU5F1), Nanog, Prox1, Musashi 1, and Pax6, which indicates their differentiation. Expression of Musashi 1 and Pax6 attest to neural differentiation, which is also confirmed by the expression of ßIII-tubulin, a neuroblast marker, and markers of differentiated neuronal cells, tyrosine hydroxylase and neurofilament proteins. These findings attest to the capacity of retinal pigment epithelium from adult human eye to transdifferentiation into neural lineage cells, which makes them an interesting object for cell therapy in neurodegeneration.

[Adult human retinal pigment epithelial cells - a potential source of cells for regeneration retina].

Retinal pigment epithelium (RPE) arises from neuroectoderm and plays a key role in support of photoreceptor functions. Several degenerative eye diseases, such as macular degeneration or retinitis pigmentosa, are associated with impaired RPE function that may lead to photoreceptor loss and blindness. RPE cell culture derived from adult human eyes autopsy could be an important source for transplantation to cure such retinal degenerative diseases. RPE cells subsequent isolation and maintenance in culture are described. Besides the results of immunocytochemical analysis that characterizes dedifferentiated state of cultured adult human RPE cells are given. Our findings demonstrate that mature human RPE cells have the capacity to express neural markers in response to conditions that promote dedifferentiation.

Phenotypic plasticity of retinal pigment epithelial cells from adult human eye in vitro.

Phenotypic plasticity of retinal pigment epithelial cells from adult human eye was studied by immunohistochemical methods under different culturing conditions. It was found that retinal pigment epithelium in adult human eye is a heterogeneous population of cells demonstrating different behavior in vitro. Some cells retain epithelial morphology for a long time in culture, while others are rapidly transformed into fibroblast-like cells and synthesize proteins typical of proneural, neural, glial, and photoreceptor cells. However, irrespective of initial morphological features differentiation of retinal pigment cells can be modulated by varying culturing conditions.