Changes of structural organization of human olfactory bulbs under conditions of severe forms of pneumonia and cerebrovascular pathology

The role of human olfactory bulbs remains one of the most interesting questions concerning work of the brain, because this organ is one in which neurogenesis is continuously generated in post-natal and adult periods. Impaired sense of smell is not a pathology that threatens human life, therefore, often remains unnoticed. However, it can directly affect the quality of life, as it leads to malnutrition and certain problems in interpersonal relationships. The study of the functional structure of the olfactory analyzer plays an important role both in clinical and experimental studies, but the question of its features in humans needs detailed research. The material of the research was 18 pairs of the olfactory bulbs of males and females aged from 30 to 90 years that were received at the Poltava Regional Department of Pathology. In order to objectify the data obtained on micropreparations, the following morphometric indices were determined: the specific gravity of the location of cellular elements; the proportion of mitral neurocytes in the entire cell population; percentage ratio of relative quantity between cellular elements, blood microvessels, fibrillar component and homogeneous eosinophilic structures. Correlation analysis of morphometric indices in the general sample revealed the existence of an inverse communication of average strength between the relative number of homogeneous eosinophilic cells and the relative number of cellular elements and blood microvessels, which in turn indicates the etiopathogenetic mechanisms of the formation of these structures. The conducted research makes it possible to conclude that mitral cells as one of the most differentiated in olfactory bulbs are sensitive to the development of hypoxic states; under the conditions of cerebrovascular pathology, the relative amount of the blood vessels of the microvessels decreases, which leads to the disorder of the trophy of the nervous tissue and as a result can lead to neurocytolysis of mitral cells. Changes in the vascular and cellular com­ponent indicate a different pathogenesis of changes in human olfactory bulbs in these pathologies and suggest that eosinophilic homogeneous cells are the result of apoptotic neurocytolysis against the background of development of hypoxic states.

MiRNA-92a Promote Angiogenesis in Colorectal Cancer by Inhibiting the Expression of PTEN

Background: The microRNA (miRNA) miRNA-92a has been implicated in colorectal cancer (CRC) pathology. Methods: Here, we examined miRNA-92a involvement in CRC-associated angiogenesis, including examining a mechanism by which miRNA-92a may exert such effects. MiRNA-92a expression in 25 clinical CRC samples and in HT29, SW620, SW480 and HCT116 CRC cells was detected with quantitative real-time polymerase chain reaction (qRT-PCR). Blood microvessels were labeled by immunohistochemistry (IHC) with an anti-CD31 antibody. MiR-92a mimic or inhibitor were transfected into HCT116 and SW620 cells to up- and down-regulate miRNA-92a expression, respectively. The effects of altering miRNA-92a expression levels on HUVEC (human umbilical vein endothelial cell) tubule formation and PTEN protein expression were measured. Results: MiRNA-92a was more highly expressed in CRC tissues and cell lines than in matched adjacent tissues (p <0.01) and normal epithelial cells (p <0.05), respectively. Microvessel density (MVD) was elevated in CRC tissues relative to adjacent tissues (p <0.01), and miRNA-92a levels correlated with MVDs in CRC tissues (Pearson coefficient r = 0.580, p = 0.01). The cells culture supernatant of CRC cell with miRNA-92a overexpression (or suppression) can promoted (or reduced) the formation of HUVEC tubules (P <0.05). Elevated miRNA-92a expression was associated with reduced PTEN expression in CRC cells (p <0.01). Conclusion: Modulation of miR-92a, which is highly expressed in CRC cells and tissues, is associated directly with differences in CRC angiogenesis. MiR-92a could promote tumor angiogenesis in CRC by inhibiting the expression of PTEN.

FEATURES OF ANGIOARCHITECTURE OF THE ALBINO RATS STOMACH AND SMALL INTESTINE

Introduction: The stomach and small intestine are important organs of the digestive system and, to date, they are the subject of research by morphologists, endocrinologists, immunologists, gastroenterologists, and other researchers. The aim: The paper is aimed at the study and systematization of the features of angioarchitecture of the albino rats stomach and small intestine. Materials and methods: The study based on the injection of the blood vasculature of abdominal organs of 20 albino male rats with 5% gelatin solution, colored with filtered black ink, was performed. The specimens were subject to photographing from different aspect angles in their original state, and then, after dehydration in alcohols with the transition to pure acetone, they were embedded in the epoxy. Photographing of the obtained specimens was made by a digital camera, as well as a binocular magnifier MBS-9, equipped with a digital photoattachment Sigeta DCM-900 9.0MP. Results and conclusions: The results of injecting of blood vasculature of albino rats’ gastrointestinal tract with ink mass clearly demonstrate the specific difference in the intraorganic angioarchitecture of its different regions, which depends entirely on their functional purpose in the digestive process. In the stomach, the highest concentration of blood microvessels is in its glandular part, which is explained by the increased nutrient needs of the secretory process of the gastric glands, while the mucous membrane of its fundus (pre-stomach) contains a scattered network of exchange microvessels that only promote the process of regeneration of the stratified squamous (partially keratinized) covering epithelium. In the small intestine, the typical principle of the organization of the microvasculature of its mucous membrane is somewhat modified in the duodenum, which is associated with the presence of mucous (Brunner’s) glands in it, as well as in those sites (starting from the duodenum) where the group lymph nodes (Peyer’s patches) are localized.

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake.

A MATHEMATICAL AND COMPUTATIONAL MODEL OF BLOOD FLOW REGULATION IN MICROVESSELS: APPLICATION TO THE EYE RETINA CIRCULATION

This paper presents a mathematical model and a computational framework for the resolution of large networks of distensible blood microvessels characterized by a hierarchy of different diameters. We analyze the contribution of different distensibility relations, representing both active and passive responses in the case of the microvascular network in the eye retina. Model predictions indicate that, depending on the geometrical (hierarchical) location in the network, distensibility effects may be significantly different and lead, over long times, to possible geometrically-driven remodeling processes.

Juvenile Traumatic Brain Injury Induces Long-Term Perivascular Matrix Changes Alongside Amyloid-Beta Accumulation

In our juvenile traumatic brain injury (jTBI) model, emergence of cognitive dysfunctions was observed up to 6 months after trauma. Here we hypothesize that early brain injury induces changes in the neurovascular unit (NVU) that would be associated with amyloid-beta (Aβ) accumulation. We investigated NVU changes for up to 6 months in a rat jTBI model, with a focus on the efflux protein P-glycoprotein (P-gp) and on the basement membrane proteins perlecan and fibronectin, all known to be involved in Aβ clearance. Rodent-Aβ staining is present and increased after jTBI around cerebral blood microvessels, and the diameter of those is decreased by 25% and 34% at 2 and 6 months, respectively, without significant angiogenesis. P-glycoprotein staining in endothelium is decreased by 22% and parallels an increase of perlecan and fibronectin staining around cerebral blood vessels. Altogether, these results strongly suggest that the emergence of long-term behavioral dysfunctions observed in rodent jTBI may be related to endothelial remodeling at the blood–brain barrier alongside vascular dysfunction and altered Aβ trafficking. This study shows that it is important to consider jTBI as a vascular disorder with long-term consequences on cognitive functions.