[On the issue of separate designation of the pre-Descemet's layer in the structure of the cornea]. / K voprosu o vydelenii predestsemetovogo sloya v strukture rogovitsy.

In 2013, based on the results of an experimental pneumodissection of the cornea, English ophthalmologist H. Dua postulated the existence of a previously unknown pre-Descemet's layer (PDL) with unique characteristics. However, the need to revise the traditional concepts of the corneal structure raises reasonable doubts among many researchers. This article discusses the question of whether the structural features of the pre-Descemet's layer can be a sufficient basis for designating it as a separate anatomical unit.

[Flow cytometry evaluation of the rhesus monkey cellular immunity following the Zaire ebolavirus (Filoviridae; Ebolavirus: Zaire ebolavirus) experimental infection].

INTRODUCTION: The outbreaks of the Zaire ebolavirus (ZE) disease (ZED) that have arisen in the last decade determine the need to study the infection pathogenesis, the formation of specific immunity forming as well as the development of effective preventive and therapeutic means. All stages of fight against the ZED spread require the experimental infection in sensitive laboratory animals, which are rhesus monkeys in case of this disease .The aim of the study is to evaluate the rhesus monkey cellular immunity following the ZE experimental infection by the means of flow cytometry (cytofluorimetry). MATERIAL AND METHODS: Male rhesus monkeys were intramuscularly infected by the dose of 15 LD50 (dose of the pathogen that causes 50% mortality of infected animals) of the ZE, the Zaire strain (ZEBOV). Levels of 18 peripheral blood lymphocyte populations of the animals before the ZE experimental infection and at the terminal stage of the disease were assessed using flow cytometry. RESULTS AND DISCUSSION: The certain changes in the levels of the lymphocyte populations were observed following infection, indicating simultaneous activation and suppression of the immune system during ZED. The increase in content was observed for T-lymphocytes, T-helper and cytotoxic T-lymphocytes expressing the corresponding markers of early activation. The decrease was recorded for T-lymphocytes and double-positive T-lymphocytes expressing corresponding markers of late activation, as well as natural killer cells expressing CD8 (p < 0.05). CONCLUSION: For the first time in the Russian Federation, the rhesus monkey cellular immunity before and after the ZE experimental infection was assessed using flow cytometry.

Application of Focal Photoinduced Thrombosis for Modeling Spinal Cord Ischemia.

Typical ischemic damage to neurons were detected in the focus of experimental photothrombosis and in the transition zone. They were associated with symptoms of impaired motor functions and dysfunction of pelvic organs. The applied method of focal photothrombosis can be used for simulation of spinal cord ischemia for the development of methods for pharmacological correction and restoration of impaired sensorimotor functions.

[Experience of using the chondroprotector Sustagard Artro (sashe) in the treatment of lower back pain]. / Opyt primeneniia khondroprotektora Sustagard Artro (poroshok) pri boliakh v nizhnei chasti spiny.

AIM: To compare the efficacy of oral administration of the chondroprotector (CP) Sustagard Artro and nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing lower back pain and to assess the level of blood glucose in patients taking CP. MATERIAL AND METHODS: Sixty patients with spondylarthrosis (SA) were studied. Patients were randomized into the CP group (n=30), which received Sustagard Artro (1 sachet once a day for 6 weeks), and the NSAIDs group (n=30) treated with injectable forms of different groups of NSAIDs for 3-7 days. Pain intensity was evaluated by the numerical rating scale (NRS) and the Oswestry disability index (ODI). RESULTS: The reduction in the severity of pain on NRS was similar in both groups: 5.73±1.74 before treatment and 1.43±0.33 after treatment in the CP group; 6.03±0.93 and 1.17±0.97 in the NSAIDs group, respectively. No significant difference in the efficacy was observed between two groups on ODI: 34.66% at baseline and 1.86% after 6 weeks in the CP group; 37.47% and 2.27% in the NSAIDs group, respectively. Changes in the level of glucose were within the upper limit of normal in the CP group. CONCLUSION: Oral administration of CP (Sustagard Artro, sashe) reduces pain syndrome as effectively as NSAIDs.

[Chondroitin sulfate injection in neurological practice]. / In''ektsionnaia forma khondroitina sul'fata v nevrologicheskoi praktike.

Chondroprotectors (CP) are biological agents that contribute to the regeneration of the cartilage surfaces, joint capsule, participating in the metabolism of the articular cartilage. Progressive loss of hyaline cartilage and a decrease in chondroitin sulfate (CS) is observed in osteoarthritis (OA) including low back pain. OA therapy is aimed at slowing disease progression, relief of pain symptoms, reduction of functional disorders. With this purpose, orally or injectable CP (chondroguard) are used. The optimal dosing regimen for the parenteral forms of CP is recommended: 3 injections of 1 ml (100mg) of chondroguard introduction for 1 week, 2 ml (200mg) from the 4-th injection, 25-30 injections at 200 mg in a day, with a second 6 month course.

Expression of Hif-1α, Nf-κb, and Vegf Genes in the Liver and Blood Serum Levels of HIF-1α, Erythropoietin, VEGF, TGF-ß, 8-Isoprostane, and Corticosterone in Wistar Rats with High and Low Resistance to Hypoxia.

We studied the expression of Hif-1α, Nf-κb, and Vegf genes in the liver and serum levels of HIF-1α, erythropoietin, VEGF, TGF-ß, 8-isoprostane, and corticosterone in Wistar rats with different resistance to hypoxia in 5 and 90 min after acute exposure to hypobaric hypoxia. In 5 min after hypoxic exposure, Hif-1α expression in the liver and serum levels of erythropoietin, VEGF, and TGF-ß in high-resistant rats were higher than in low-resistant animals. In highresistant rats, the increment in expression of Nf-κb gene responsible for the control over the inflammatory processes was more pronounced than in low-resistant animals. In 90 min after hypoxic exposure, the serum levels of HIF-1α, erythropoietin, VEGF, and TGF-ß returned to normal in high-resistant rats, while in low-resistant animals, an increase in 8-isoprostane and TGF-ß concentrations was observed. The rats with different resistance to hypoxia were characterized by different changes in biomolecular parameters determining predilection to inflammatory diseases.

[Effect of quercetin on morphological changes in nonalcoholic fatty liver disease in high fructose-fed rats].

The aim of this study was to examine the effect of polyphenol quercetin on morphological changes in nonalcoholic fatty liver disease (NAFLD) in rats fed high-fructose diet. For 20 weeks animals (n=8 in each group) of the 1st group were given standard diet and water; the 2nd group - standard diet and 20% fructose solution; the 3rd group - standard diet with quercetin supplementation (0.1%) and 20% fructose solution. Formalin-fixed and paraffin-embedded liver samples were sectioned, stained (hematoxilin and eosin, Van Gieson's stain), evaluated with the use of the SAF and NAS scales. Histological assessment did not reveal pathology in the structure of the liver of the 1st group rats (S0A0F0; NAS - 0, fibrosis - 0). The 2nd group rat livers disclosed micro-, mid- and macrovesicular steatosis, inflammation without ballooning, pericellular and periportal fibrosis (S2A1F2; NAS - 3, fibrosis - 2). Quercetintreated rats exhibited in liver significantly less steatosis without significant changes in inflammation and fibrosis features (S1A1F2; NAS - 2, fibrosis - 2) compared with rats of the 2nd group. The data obtained demonstrate the ability of quercetin to inhibit the development of NAFLD in rats fed a diet with a high content of fructose, by reducing the severity of hepatostatosis.

Correction of anxiety disorders: focus on a comorbid patient.

The exact cause of the development of anxiety disorders (AD) in present time has not been fully established and is a subject of debate in many countries. Interest in studying the mechanisms of action of proteins of S100 group, in particular, neurospecific protein S100b, is caused by its participation in processes of integrative activity of brain/neuron and development of diseases of nervous system. The functions of S100 proteins determine their influence on synaptic plasticity and participation in the regulation of stress-realizing and stress-limiting systems, the imbalance of which (primarily, the insufficiency of the GABA-ergic system) is the neurobiological basis of the majority of anxiety-depressive pathologies. Preparations regulating the activity of S100 protein have a distinct clinical anti-anxiety effect and additionally contribute to the restoration of neuronal plasticity processes.

[Antineoplastic mechanisms of niclosamide-loaded nanoparticles in human colorectal cancer cells]. / Molekuliarnye mekhanizmy protivoopukholevoi aktivnosti polimernoi formy niklozamida v otnoshenii kletok kolorektal'nogo raka.

Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide (PFN) and investigated molecular mechanisms underlying its antitumor activity against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was shown to be more cytotoxic against cancer cells and less cytotoxic against normal cells (human embryonic lung fibroblasts) as compared to niclosamide. Both niclosamide and its polymeric form caused mitochondrial damage (evaluated as a decrease in rhodamine 123 accumulation) and increased the levels of reactive oxygen species, particularly mitochondrial superoxide, resulting in the oxidative damage to biomolecules. Furthermore, niclosamide and PFN induced G0/G1 cell cycle arrest.

[Urethra Reconstruction with Tissue-Engineering Technology].

Urethral stricture is a disease characterized by a pathological narrowing of the urethra. Treatment for this condition often requires surgery using autologous grafts (urethroplasty). It is common practice to use patient's own tissue like genital and extragenital skin, tunica vaginalis, buccal mucosa as a source of the graft. Alternative and safer approach is to use tissue-engineered graft created in a laboratory using patient's autologous cells and biocompatible matrix (scaffold). The article presents the up-to-date achievements in lab-created tissue-engineered graft, describes all components needed to build a tissue-engineered structure of the graft for urethroplasty, and summarizes authors' thoughts on advantages and disadvantages of various approaches to choose both cellular component and the matrix of future construction. The article reviews clinical studies conducted in the field of tissue engineering of the graft material for urethraplasty.

[Age-related peculiarities of the hypothalamo-hypophyseo-adrenal system in chronic heterotypic stress].

Age-related peculiarities of the adaptation of the hypothalamo-hypophyseo-adrenal system (HHAS) to the effect of heterotypic stress was studied experimentally in the context of stress-associated behavioral reactions. Young (3 month old), mature (6 month old) and aging (12 month old) Sprague Dawley rats (total number of animals equal to 36) were exposed to chronic heterotypic stressors for 7 days with the subsequent testing of their behavioral responses. Histological changes were studied in the hypothalamus, pituitary and adrenal glands as compared to age-matched control; immunohistochemical reactions were performed to demonstrate CRF, ACTH, ED1, PCNA and caspase-3 with subsequent image analysis. In the aging organism, as compared to young and mature animals, the degree of HHAS activation indicated the dissociation in its central part and adaptive desensitization prevention, typical to young and mature animals. Specifically, in the aging animals exposed to stress, high hypothalamic CRF expression was noted in association with relatively low hypophyseal ACTH expression and high level of adrenal activity. Reduced HHAS plasticity in the aging animals as compared to that in the other age groups, corresponded to their behavioral changes, demonstrating the reduced capacity of the aging organism to adapt to the exposure of unpredictably changing stressors.

Morphological and phenotypical characteristics of human osteoblasts after short-term space mission.

Morphological and phenotypical signs of cultured readaptation osteoblasts were studied after a short-term space mission. The ultrastructure and phenotype of human osteoblasts after Soyuz TMA-11 space flight (2007) were evaluated by scanning electron microscopy, laser confocal microscopy, and ELISA. The morphofunctional changes in cell cultures persisted after 12 passages. Osteoblasts retained the drastic changes in their shape and size, contour deformation, disorganization of the microtubular network, redistribution of organelles and specialized structures of the plasmalemma in comparison with the ground control cells. On the other hand, the expression of osteoprotegerin and osteocalcin (bone metabolism markers) increased; the expression of bone resorption markers ICAM-1 and IL-6 also increased, while the expression of VCAM-1 decreased. Hence, space flight led to the development of persistent shifts in cultured osteoblasts indicating injuries to the cytoskeleton and the phenotype changes, indicating modulation of bone metabolism biomarkers.

[The problems of expertise of biomedical projects and assigning them status of breakthrough and world-class].

There was a sharp increase in the number of scientific fields, research fronts, publications and patents in biomedicine in the last five years, which complicates the work of the experts on the selection of projects for priority funding. The approaches to the identification of perspective directions of research used in the world were examined. An attempt was made of formalization of the concepts of "breakthrough research" and "world level research" in relation to the Russian biomedical projects. The rationale for information support of expert decision-making about the prospects of development of individual areas of research in biomedicine is outlined.

[Regulation of hair follicle cycle].

This review is devoted to the control of hair growth. The hair follicle undergoes cyclic transformation from the resting phase (telogen) to the growth phase (anagen). The latter phase is characterized by rapid proliferation of follicular keratinocytes and elongation and thickening of the hair shaft. The regression phase (catagen) leads to the involution of the hair follicle. These cyclic changes include rapid remodeling of both the epithelial and the dermal components. They are controlled by numerous different factors: sex hormones, neurotrophins, FGF, TGF, BMP, VEGF, Sonic Hedgehog, and other signaling pathways.

[A study of scientific output of the Russian Academy of Medical Sciences in 2011 and its qualitative and quantitative growth prospects (in concordance with official indicators and policy targets)].

The scope of bibliometric research is focused on academic output of the Russian Academy of Medical Sciences (RAMS) in 2011 by analyzing the data extracted from the Web of Science database and InCites application Research Performance Profile of RAMS. Using these analytical tools trends in dynamics of publications and citing of the RAMS researchers were calculated and the level of scientific output in some biomedical subject areas was estimated. Studies revealed the great importance of international collaboration and international coauthorship for RAMS in producing papers published in established scholarly journals. Basic metrics of scientific performance that should be required to achieve the goals declared in the recent governmental policy papers were measured for RAMS institutions as well. Another problem investigated in this research is the problem of low citedness ofRAMS journal papers indexed in WoS. Factors and reasons influenced on low citedness were discovered In conclusion authors set out priorities and reasonable goal-oriented efforts to achieve better results in publication activity.

[Investigation of possible approaches to angiogenesis regulation in vitro with the help of recombinant fragments of angiogenesis inhibitors such as endostatin, tumstatin and PEDF].

Neovascular diseases of visual organ such as age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, thrombosis of central retina vein and its branches, neovascular glaucoma, choroid and retina tumors have the leading positions in the list of ophtalmopatologies that result in blindness and incapacity. The variety of angiostatic medications of applied ophtalmology is scant. The aim of work was to study the possibile approaches to angiogenesis regulation in vitro with the help of recombinant fragments of natural inhibitors of angiogenesis such as endostatin, tumstatin and PEDF (pigment epithelial derived factor), and also theirability to be the base of potentially feasible and pharmacologically active substances. It is determined that endostatin, tumstatin and PEDF, as well as the comparison medication Bevacizumab in vitro have pro-or antiangiogenic influence. The direction of the biological effect depends on the cultivation conditions, peptide concentration in the cultural fluid and stage of angiogenesis.

[Publication activity of the Russian medicine in focus of national science policy: estimating the feasibility of policy targets].

A comprehensive review of National research policy papers issued over the past 6 years was carried out. A set of problems concerning the quality of predicted values of some bibliometric indicators reflecting the level of research performance and publication activity that were declared in governmental documents was discussed. Basic metrics of scientific performance that should be required to achieve the goals declared in the recent governmental policy papers including President's Executive Order No 599 of May 7, 2012 (increasing the share of Russian researchers' publications in the total number of publications in international scientific journals indexed in the Web of Science up to 2.44% in 2015). Taking into account the current structure of modern global science in which papers in biomedical subjects make up for approximately one third of the total world scientific output, it becomes obvious how difficult is the governmental task set up to the researchers--to double the number of journal publications indexed in Web of Science in the short-term period of the nearest three years. The priorities and reasonable goal-oriented efforts to meet the targets are proposed in the paper.

[Effects of a real and modeled microgravity influencing on some structural and metabolic parameters of skeletal muscles].

The aim of present publication is summarization of experimental results on real and modeled effects of zero gravity on the impellent device of a man and other mammals. In particular, its effects on high-speed and power characteristics of skeletal muscles depending on their metabolic activity are analyzed.

Effects of space mission factors on the morphology and function of endothelial cells.

The structure and functions of endothelial cells after space mission were studied by electron and laser confocal microscopy, image analysis, and MTT test. The endothelial cells changed significantly (proliferative activity, size, contours, shape, distribution of mitochondria and microtubules) in comparison with controls on the Earth. These changes indicated injuries in the cytoskeleton and impairment of the barrier function of the cells, which presumably contributed to the development of endothelial dysfunction.

Towards in silico identification of the human ether-a-go-go-related gene channel blockers: discriminative vs. generative classification models.

HERG potassium channels have a critical role in the normal electrical activity of the heart. The blockade of hERG channels in heart cells can result in a potentially fatal disorder called long QT syndrome. HERG channels can be blocked by compounds with diverse structures belonging to several drug classes. Presented herein are generative (Generative Topographic Maps) and discriminative (Support Vector Machines) classification models to categorize the compounds in silico into active and inactive classes by using different types of descriptors. The predictive performance of discriminative and generative classification models has been compared. Here, the possibility of using Generative Topographic Maps as an approach for applicability domain analysis and to generate probability-based descriptors was demonstrated to our knowledge for the first time. Comparison of obtained results with the models developed by other teams on the same data set has been performed.