Acute cerebral circulation disorder is one of the most discussed issues in modern intensive care and neurology, as it is a severe condition, leading to disability or death of the patient, in the absence of immediate medical care. This review discusses general and specific biological markers of stroke, genetic markers of stroke, and current data on their diagnostic significance. The main mechanisms of brain tissue cell death in stroke, such as apoptosis, necrosis, ferroptosis, parthanatosis, sarmoptosis, autolysis, autophagy, oncosis, excitotoxic death are analyzed; the morphological features of the observed processes and their structural manifestations are reviewed. For each type of cell death in nervous tissue, the most frequently detected molecular markers are discussed: specific kinases, Toll-like receptors in the case of apoptosis; serine-threonine protein kinases, components of the polyubiquitin system detected in necrosis; transferrin 1 receptors, typical for ferroptosis; poly(ADP-ribose)-polymerase, whose activity increases in parthanatosis; slow Wallerian degeneration protein that accumulates during sarmoptosis; and other biomarkers characteristic of both individual types of nerve cell death and general pathological processes affecting the brain.

Acute cerebral circulatory disorders are characterised by various changes in brain cells, often leading to mass death. This review presents a list of markers associated with different types of cell death occurring in acute cerebral circulation disorders and identifies the importance of these markers in the diagnosis of haemorrhagic and ischaemic stroke.Acute cerebral circulation disorder is one of the most debated issues in modern resuscitation and medicine, asit is asevere condition leading to stroke and subsequent patient death, if not treated promptly. However, rapid treatment and diagnosis of stroke is difficult due to the lack of study of morphological signs and biomarkers to reliably determine the nature of the injury. Anin-depth analysis and systematization of the available information on this topic is needed.Purpose of the review:to reveal the correspondence between the molecular mechanisms of cell death in acute disorders ofcerebral circulation and their morphological manifestations.Material and Methods.A total of 50 most relevant sources of information were selected. The sources were selected from the databases of medical and biological publications PubMed, Scopus, Web of Science, RSCI, and fundamental works of scientificliterature on the considered topic were involved.Results.The main mechanisms of cell death in stroke were identified and analyzed, the morphological and histological features ofthe observed processes and their structural manifestations were reviewed. Besides, the most frequently detected molecular markers specific for each type of cell death were listed.Conclusion.The study of molecular pathways andcellular reorganization processes characteristic of different types of cell death as well as their corresponding biological markers is of important diagnostic value in the detection of cerebral circulatory disorders. Determination of morphological and molecular markers typical for this condition will allow a prompt diagnosis ofstroke and minimization of its negative consequences.

The aim of research was to study age-related changes of the human bulbourethral glands and features of their course in the benign prostatic hyperplasia. Material and methods . The study included bulbourethral glands of 44 men aged 17–90. Patients in the second period of maturity with and without benign prostatic hyperplasia composed a separate group; their cases were analyzed separately. Geometric and optical parameters allowing evaluating age-related changes in the bulbourethral glands and distinguishing their characteristics in the benign prostatic hyperplasia were measured using sections stained by the Mallory’s method and PAS-reaction. Results. A decrease in height of glandulocytes, section area of the secretory units, and in total share of parenchyma was observed in the bulbourethral glands from adolescence to senile. The optical density of the glandulocyte cytoplasm was maximal in young men and significantly reduced in the first period of adulthood. In the second period of adulthood and elderly age, changes in this parameter were minor. In the senile period, the optical density of the glandulocyte cytoplasm was minimal in all compared age groups. Presence of PAS-positive material in glandular cells indicates the preservation of the ability to secretion in old age. In men of the second period of maturity with benign prostatic hyperplasia, all morphometric parameters of the bulbourethral gland parenchyma were higher than those in cases without nodal changes in the prostate. At the same time, the optical density of PAS-positive material in the glandulocyte cytoplasm exceeded twice similar values for men without this pathology. Conclusion. Adolescence is a period of maximal activity of the bulbourethral glands. Involutive parenchyma changes occurring from the first period of adulthood up to and including the elderly age were compensated by secretory cell activity sufficient to provide the necessary level of the bulbourethral gland functioning. In old age, the bulbourethral glands retained the ability to secrete. In men of the second period of maturity with benign prostatic hyperplasia, functional activity increased compared to individuals without this pathology.

Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.

The study of the epidermis and derma histogenesis, including its epigenetic regulation, is an actively developing field of histology and embryology. The results of the study can elucidate the mechanisms of pathogenesis of some skin diseases of unknown etiology. Wnt signaling is a key regulator of the main morphogenetic processes — cell proliferation and differentiation. Downstream of Wnt signaling is carried out by canonical and non-canonical pathways. Impairments of Wnt signaling in prenatal and postnatal development lead to degenerative and tumor diseases of the skin and hair. Clinical manifestations of the prenatal disorders of skin development epigenetic regulation in the period may appear long after the birth. Identification of factors that disturb the regulation of morphogenetic processes is an important task for investigators. It was found out that activation of the mother’s immune system in the early pregnancy resulted in the development of transient alopecia in the offspring of mice. There was the correlation established between the disorders of epidermal and dermal histogenesis and alopecia as well as the development of regional dysmorphogenetic changes in the skin, which indicate the need to study the rates and features of skin development in various parts of the body.

Microfold cells (M cells) are specialized intestinal epithelial cells that initiate mucosal immune responses. These unique phagocytic epithelial cells are specialized for the transfer of a broad range of particulate antigens and microorganisms across the follicle-associated epithelium (FAE) into the gut-associated lymphoid tissue (GALT) by a process termed transcytosis. The molecular basis of antigen uptake by M cells has been gradually identified in the last decade. Active sampling of intestinal antigen initiates regulated immune responses that ensure intestinal homeostasis. The delivery of luminal substances across the intestinal epithelium to the immune system is a critical event in immune surveillance resulting in tolerance to dietary antigens and immunity to pathogens (e.g., bacteria, viruses, and parasites) and their toxins. Several specialized mechanisms transport luminal antigen across the gut epithelium. Discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted delivery oral vaccine to M cells. Recent studies demonstrated that M cells utilize several receptors to recognize and transport specific luminal antigens. Vaccination through the mucosal immune system can induce effective systemic immune responses simultaneously with mucosal immunity. How this process is regulated is largely unknown. This review aims to show a new understanding of the factors that influence the development and function of M cells; to show the molecules expressed on M cells which appear to be used as immunosurveillance receptors to sample pathogenic microorganisms in the gut; to note how certain pathogens appear to exploit M cells to inject the host; and, finally, how this knowledge is used to specifically "target" antigens to M cells to attempt to improve the efficacy of mucosal vaccines. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells.

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.

Gravitational unloading causes atrophy of muscle fibers and can lead to destruction of cytoskeletal and contractile proteins. Along with the atrophic changes, unloaded muscle frequently demonstrates significant shifts in the ratio of muscle fibers expressing fast and slow myosin heavy chain isoforms. Stretching of the m. soleus during hindlimb suspension prevents its atrophy. We supposed that neuronal NO-synthase (NOS) (which is attached to membrane dystrophin-sarcoglycan complex) can contribute to maintenance of protein metabolism in the muscle and prevent its atrophy when m. soleus is stretched. To test this hypothesis, we used Wistar rats (56 animals) in experiments with hindlimb suspension during 14 days. The group of hindlimb suspended rats with stretched m. soleus was injected with L-NAME to block NOS activity. We found that m. soleus mass and its protein content in hindlimb-suspended rats with stretched m. soleus were preserved due to prevention of protein degradation. NOS is involved in maintenance of expression of some muscle proteins. Proliferation of satellite cells in stretched m. soleus may be due to nNOS activity, but maintenance of muscle mass upon stretching is regulated not by NOS alone.

При функциональной разгрузке мышц цитоскелетные и сократительные белки подвергаются деструкции. Одновременно изменяется соотношение экспрессии тяжелых цепей миозина (ТЦМ). Мы предположили, что NO может быть сигнальной молекулой, имеющей отношение к регуляции белкового метаболизма при разгрузке мышц. Для проверки гипотезы крыс Wistar подвергали в течение 14 дней функциональной разгрузке без введения и с введением перорально L-аргинина, предшественника NO (500 мг/кг). В группе с разгрузкой без введения препарата обнаружено существенное снижение массы m. soleus, содержания в ней NO, nNOS, дистрофина, Hsp90, p-S6k, мРНК тяжелых цепей миозина I типа по сравнению с таковыми в контроле и группе разгрузки с введением L-аргинина и повышение содержания atrogin-1/MAFbx и MuRF-1 (p < 0,05). В содержании мРНК IGF-1 между всеми группами различий не было. В группе разгрузки с введением L-аргинина атрофия была существенно меньше, чем в группе разгрузки без препарата, а разрушения цитоскелетных белков не наблюдалось. Возможной причиной такого эффекта может быть отсутствие повышения содержания некоторых убиквитинлигаз в этой группе и снижения маркера интенсивности синтеза белка р70S6-киназы.

Cytoskeletal and contractile proteins degenerate during functional unloading of muscle. The ratio of myosin heavy chain (MHC) expression changes simultaneously. We have supposed that NO can be a signal molecule related to the regulation of protein metabolism upon muscle unloading. To test this hypothesis, Wistar rats underwent functional unloading for 14 days without and with peroral administration of L-arginine (500 mg/kg) as NO precursor. Significant decreases in m. soleus mass, NO, nNOS, dystrophin, Hsp90, p-S6K, and type I MHC mRNA contents were found in the group of animals with unloading without preparation compared to those in control and in the group with unloading and administration of L-arginine; at the same time, increased contents of atrogin-1/MAFbx and MuRF-1 (p < 0.05) were found. No difference in the IGF-1 mRNA content between all three groups was found. Atrophy was significantly less pronounced in the group with unloading and L-arginine administration compared to that without the amino acid, and no destruction of cytoskeletal proteins was observed. We conclude that administration of L-arginine upon functional unloading decreases the extent of m. soleus atrophy, prevents the decrease in it of type I MHC mRNA, and blocks destructive changes in some cytoskeletal proteins. Such effect can be due to the absence of increase in this group of the content of some ubiquitin ligases and decreased intensity of the p70S6 kinase synthesis marker.

The simulation model of “dry” immersion was used to evaluate the effects of plantar mechanical stimulation (PMS) and high frequency electromyostimulation (EMS) on the mechanical properties of human soleus fibers under the conditions of gravitational unloading. We examined contractile properties of single fibers by means of tensometry, transversal stiffness of sarcolemma and different areas of the contractile apparatus by means of atomic force microscopy. It was shown that there is a reduction of transversal stiffness in single muscle fibers under hypogravitational conditions. Application of different countermeasures could compensate this effect. Meanwhile pneumostimulation and electro stimulation act in quite different way. Therefore, pneumostimulation seems to be more effective. The data obtained can be considered as the evidence of the fact that such countermeasures as PMS and electromyostimulation influence on muscle fibers in quite different ways and PMS efficiency is likely to be higher. On the basis of our experimental data on transverse stiffness of mechanotransductional nodes and the contractile apparatus, we can assume that support stimulation allows prevention of destructive processes in muscle fibers. Electrostimulation seems to stimulate contractile activity only without suppression of impairment of the fiber mechanical properties.