Vol 17, No 5 (2019)

There are presented data about rejuvenating mesencephalic astrocyte-derived neurotrophic factor (MANF) and its physiological functions. This is a new neurotrophic factor, produced by the mesencephalic astrocytes and it is different from other factors by its activity concerning not only the nervous tissue but other tissues. The MANF main function is a protection of the dopamine neuron endoplasmic reticulum (ER) from the stress and apoptosis. The high concentrations of MANF were detected in the brain cortex, hippocampus, cerebellum. MANF is expressed actively in the synovial tissues, cardiomyocytes, pancreas cells, liver tissue. The MANF provides an increase of the regenerative processes, affecting the immune cells. The MANF ability to modulate the cell regenerative functions and the neuroprotection, and also an increase of the stem cell function, plays a great role in the so-named “rejuvenating” functions of MANF. It was detected, using the method of the heterochronic parabiosis, that the MANF concentration is increased highly in the blood of the old mice by an increase of the neuron quantity in the brain, and also by the improvement of the heart, liver function. MANF can protect the cilia of dopaminergic neurons at the early stage of Parkinson disease, it has the neuroprotective effect in the early stages of the brain damage, produced by the subarachnoidal bleeding in the mice. The MANF protein, possessing many functions, plays the basic role in the processes of the recovery of the neuron functions in both Alzheimer and Parkinson diseases, insults and traumatic damages of the brain. There are data presented about rejuvenating mesencephalic astrocyte-derived neurotrophic factor (MANF) and its physiological functions. This is a new neurotrophic factor, produced by the mesencephalic astrocytes and it is different from other neurotrophic factors by its activity concerning not only the nervous tissue but many other tissues. The MANF main function is a protection of the dopamine neuron endoplasmic reticulum (ER) from the stress and apoptosis development. The relatively high concentrations of MANF were detected in the brain cortex, hippocampus and in the cerebellum Purkinje cells. Moreover, MANF is expressed actively in the synovial tissues by their infiltration with the inflammatory cells, in the cardiomyocytes, pancreas cells, in the B hepatitis liver tissue. The MANF immunomodulating function provides an increase of the regenerative processes, affecting directly the immune cells. The MANF ability to modulate the cell regenerative functions by the synchronous stimulation of the neuroprotection, and also of an increase of the stem cell function, plays a great role in the so-named «rejuvenating» functions of this protein. It was detected, using the method of the heterochronic parabiosis (the creation of the common blood circulation in the young and old animals), that the MANF concentration is increased highly in the blood of the old mice by an increase of the neuron quantity in the brain, (especially in the hippocampus), and also by the improvement of the heart, liver function. MANF can protect the cilia of dopaminergic neurons at the early stage of Parkinson disease, and also it has the neuroprotective effect in the early stages of the brain damage, produced by the subarachnoidal bleeding in the mice. The MANF protein, possessing many functions, plays the basic role in the processes of regeneration, increase and recover of the neuron functions in both Alzheimer and Parkinson diseases, insults and traumatic damages of the brain.

The growing interest in the group of highly sulfated heteropolysaccharides, defined as fucoidans, is due to a wide spectrum of their biological activity. The expansion of the direction of their application is associated with the search for applications in the development of medicinal materials, in particular, the targeted drug delivery system. The main types of nano- and microstructural systems created using fucoidan are objects formed by the electrostatic attraction forces of oppositely charged polyelectrolytes (layer-by-layer adsorption, polyelectrolyte complexes), emulsions, metal-polymer complexes. The use of fucoidan as a coating for bio magnets also allows its application in theranostics. The resulting carriers containing fucoidan, are applicable for targeted delivery of therapeutic agents such as doxorubicin, curcumin, poly-L-lysine, low molecular weight anti-TB drugs, etc. The shipping method also varies. There are developing carriers with the use of fucoidan for oral, inhalation, intravenous route of administration. However, such systems have low toxicity, are biodegradable. Degradation products do not accumulate in the body but are metabolized. In addition, it is possible to obtain a hollow matrix with a high degree of loading. All this will expand the possibilities of the use of this polysaccharide in the pharmaceutical industry and clinical therapy.

Introduction. The difference in the responsibility of organisms’ influences on the results of biological experiments and medical intervention. The chromatin conformational state is one of the main factors determining the cell response to the effect of different factors. Aim of the study. Analysis of individual features of the chromatin conformation variation in a case of hyperthermia (heat shock), irradiation and exposure to the low-frequency magnetic field. Material and Methods. The research is performed using blood cells of white outbred male rats and human blood cells in vitro. The chromatic conformational state was determined with the help of the anomalous viscosity time dependence method. Results. The effect of the studied factors led to a stereotyped chromatin conformation change expressed as decondensation. The individual particulars in a case of heat shock and irradiation are manifested themselves in the dependence on the decondensation degree on the chromatin conformational state prior to the exposure. After the exposure to the magnetic field, the initial differences in the chromatin conformational state and reactivity indices became less expressed. Conclusion. There are individual differences in the chromatin conformation variations as a result of exposure to different factors and they determine the opportunity of predicting the individual features based on the initial conformational state evaluation.

Introduction. The correct functioning of the circulatory system allows providing stability of the brain and prevents the progression of pathological processes. The search for prognostic markers which make it possible to predict the appearance and adverse course of neurodegenerative diseases plays a key role in the vascular system research. The values indicating deviations in the blood supply to different regions or the organ as a whole relate to the topological characteristics of the vascular tree. The aim of the study was to identify the geometrical markers of the created vascular system, capable of indicating the possibility of the development of a pathological process in the organ under consideration. Methods. The model of the arterial tree of the rat brain was used as an experimental object in the work. The vascular network was structurally divided into deterministic and stochastic parts. The first part includes the main arteries that form the circle of Willis; the second one consists of the smaller vessels, realized in the form of a binary tree. The total bifurcation angles and fractional anisotropy which are the parameters characterizing the topological complexity of the network were estimated. The calculation of the fractional anisotropy of the constructed arterial systems was made on the basis of the standard methods using a weighted average covariance matrix. Results. It was shown that the value of the total bifurcation angle does not fall below the experimentally measured physiological threshold value (73°) in the constructed arterial model under the theoretically justified bifurcation exponent of 3.0. The value of the calculated fractional anisotropy in this case is equal to 0.014. With an increase in the bifurcation exponent, the vasculature becomes more isotropic, while vessels with a smaller caliber have a more uniform distribution density. Conclusion. The threshold value of fractional anisotropy corresponding to the physiologically correct arterial system was estimated on the basis of the total bifurcation angle. This parameter is proposed to be used as an indicator of vascular pathologies, since the experimental assessment of anisotropy is performed using the results of clinical studies and does not require additional manual segmentation, in contrast to the calculation of the bifurcation angles.

Introduction. Cancer stem cells (CSCs), which are less sensitive to chemotherapeutic drugs than other tumor cells, play a key role in the initiation and development of the tumor process. Maintenance of CSCs determines the risk of cancer recurrence. The aim of the study. To study the effect of docetaxel on CSCs survival and self-renewal in the human mammary adenocarcinoma MCF-7 cells cultured as mammospheres. Methods. The effect of docetaxel on the CSCs survival was studied after 72 and 120 h of cultivation with the drug at concentrations of 0, 1, 10 and 100 nmol/l. For this purpose, the total number of living cells was counted, the fraction of CSCs with CD44+/CD24-/low phenotype was determined using flow cytometry, and the absolute number of CSCs was calculated in each sample. The effect of docetaxel on the CSCs repopulation was determined by counting mammospheres formed 7 days after cells were washed from docetaxel after 120 h cultivation with the drug at concentrations 0, 1, 10 and 100 nmol/l. Results. The cultivation of mammospheres with docetaxel for 72 h resulted in an insignificant decrease in both of the total cell number and the CSCs fraction. At the same time, there was a significant decrease in the number of CSCs. The cultivation of mammospheres at all studied docetaxel concentrations for 120 hours resulted in a significant decrease in the total number of cells, the proportion and the number of CSCs and their clonogenic activity that represents the ability of the CSC to repopulate. Conclusion. CSCs of MCF-7 mammospheres were shown to be highly sensitive to docetaxel after prolonged cultivation (120 h). Docetaxel inhibited the ability of CSCs to self-renewal, which plays a crucial role in the tumor and metastasis initiation