Extrapineal and pineal melatonin is the marker of the aging rate of organism making it possible to characterize functional condition of the neuro-immuno-endocrine system. In this article we have used the new method for non-invasive diagnostics of melatonin expression in buccal epithelium and determination of the main melatonin metabolite 6-hydroxymelatonin sulfate (6-HMS) in urine of elderly people. Normal, impaired and enhanced melatonin expression was documented in 20.5%, 43.2% and 36.30% of the patients respectively. Such comprehensive melatonin and 6-COMT studies can be recommended for elderly patients with oncological, neurodegenerative, cardiovascular diseases, and ageing macular dystrophy. Moreover, melatonin expression analysis in buccal cells can be used for integral investigation of biorhythms in elderly people.
Expression of transcription proteins PAX1, Hoxa3, and TLP regulating differentiation of thymic epithelial cells is detected in human thymus starting from gestation week 22 until the age of 95 years. Expression of transcription factors significantly decreased during aging. Apart from the decrease in the expression of signal differentiation factors in cultured thymic epithelial cells, proliferative activity of T lymphocytes cocultured with thymic epithelial cells also decreased in aging cultures, which demonstrated the important regulatory effect of transcription proteins on maturation and maintenance of T lymphocytes. Taking into account the important role of transcription proteins in the regulation of proliferation and function of T lymphocytes, whose number sharply decreases during aging, the maintenance of the level of expression of transcription factors during aging is a promising trend in modern biogerontology.
Stroke is a global epidemic issue and the second leading cause of death in the world and in Ukraine. According to official statistics, every year 100-110 thousand Ukrainians suffer acute cerebrovascular disorders. One third of such patients are of working age, up to 50 % will have a disability, and only one in ten will fully return to full life. So far, promising experimental data on the treatment of neurological dysfunction using mesenchymal stromal cells (MSCs) have been obtained. The aim of study is to compare the effect of MSCs of different origins on mortality and neurologic deficit in rats with acute cerebral ischemia-reperfusion injury (CIRI). Materials and methods. Transient bilateral 20-minute occlusion of internal carotid arteries was modeled in male Wistar rats aged 4 months and animals were injected intravenously with MSCs derived from human umbilical cord Wharton's-jelly (hWJ-MSC), human and rat adipose tissue. Other groups of experimental animals were injected intravenously with rat fetal fibroblasts and cell lysate from hWJ-MSC. The last group of rats received Citicoline at a dose of 250 mg/kg as a reference drug. Control animals were injected intravenously with normal saline. The cerebroprotective effect of therapy was assessed by mortality and neurologic deficit in rats on the McGraw's stroke index score. Results. After 12 hours of observation in the crucial period in the development of experimental acute cerebrovascular disorders with the administration of hWJ-MSC, mortality was only 10 % against 45 % of animals in the control group. The use of rat fetal fibroblasts reduced the mortality of animals compare to the control group by an average of 25 %. CIRI in rats caused severe neurologic deficits: paralysis, paresis, ptosis, circling behavior. On the 7th day of observation in the control group of animals, the mean score on the McGrow's stroke index indicated severe neurological disorders. On the 14th day of observation in this group of animals there was no complete recovery of lost central nervous system functions. Compared with the control group of animals, all the treatment agents for acute CIRI (MSCs of various origins, MSC's lysate and Citicoline) contributed to a significant regression of neurologic deficit. Conclusions. Thus, transplantation of human Wharton's jelly-derived MSCs and rat fetal fibroblasts reduced mortality and alleviated neurological symptoms in rats with experimental ischemic stroke. hWJ-MSC, rat fetal fibroblasts, and rat adipose-derived MSCs reduced the incidence of neurological disorders better than Citicoline, which was accompanied by a regression of neurologic deficit dynamics on the 14th day of follow-up. The ability of stem cells of different origins to reduce neurologic deficit indicates the feasibility of their use in experimental acute cerebral ischemia.
Every year, about 150,000 strokes occur in Ukraine, and more than 100,000 people die from the consequences of stroke and other circulatory disorders in the brain. So far, promising experimental data on the treatment of neurological dysfunction using mesenchymal stromal cells (MSCs) have been obtained. Purpose: to characterize the impact of MSCs of various origins, lysate of Wharton’s jelly-derived MSCs and citicoline on the dynamics of destructive changes in the hippocampal CA1 area of rats with model of acute cerebral ischemia according to morphometric data. Materials and methods. An experiment was performed using 4-month-old male Wistar rats, which were subjected to transient bilateral 20-minute ischemia-reperfusion (IR) of the internal carotid arteries. After modeling, the animals were injected intravenously with Wharton’s jelly-derived MSCs, human and rat adipose-derived MSCs at a dose 106 cells/animal. Other groups were intravenously injected with rat fetal fibroblasts at a dose of 106 cells/animal and lysate from Wharton’s umbilical cord MSCs at a dose of 0.2 mL/animal. Control animals were injected with 0.2 mL of saline. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7th and 14th day, the total number of neuron nuclei per 1 mm2 brain section was counted in the hippocampal CA1 area, and the ratio of the number of intact neuron nuclei and nuclei with changes (karyorrhexis and karyopyknosis) was determined. Results. The transplantation of MSCs, lysate of Wharton’s jelly-derived MSCs, or citicoline contributed to a greater value of the number of nuclei in the hippocampal CA1 area, and the number of nuclei that did not undergo pathological changes also increased. The transplantation of Wharton’s jelly-derived MSCs had the most positive effect. The number of neuron nuclei per 1 mm2 in the hippocampal CA1 area in this group of animals approached the number of nuclei in the group of sham-operated animals. At the same time, the number of nuclei that did not undergo pathological changes significantly exceeded the number of nuclei with signs of destruction. Conclusion. A significant increase in the number of neurons without signs of pathological changes was observed in all experimental groups of rats during the modeling of ischemic brain injury after the administration of various types of studied mesenchymal stromal cells, lysate or citicoline. The most positive result in the hippocampal CA1 area was achieved after the administration of Wharton’s jelly-derived MSCs.
Ischemic stroke is the second leading cause of death and the leading cause of disability worldwide. So far, promising experimental data have been obtained regarding the elimination of neurological dysfunction and the reduction of the area of ischemic damage when using mesenchymal stromal cells (MSCs). Purpose: to characterize the influence of MSCs of different origin, MSC lysate of human Wharton cells and citicoline on the dynamics of destructive changes in the somatosensory cortex of rats with acute cerebrovascular accident according to light microscopy and micromorphometry data. Materials and methods. An experiment was performed using 190 -4-month-old male Wistar rats weighing 160-190 g, which were subjected to transient bilateral 20-minute ischemia-reperfusion (IR) of the internal carotid arteries. After modeling the pathology, the animals were injected into the femoral vein with obtained from human umbilical cord Wharton’s jelly-derived MSCs, human and rat adipose tissue-derived MSCs at a dose of 106 cells/animal. Other groups of experimental animals were intravenously injected with fetal rat fibroblasts at a dose of 106 cells/animal in 0.2 ml of physiological solution and lysate of human umbilical cord Wharton’s jelly-derived MSCs at a dose of 0.2 ml/animal. Control animals were injected IV with 0.2 ml of physiological solution. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. The studies were conducted on the 7th and 14th day. In the somatosensory cortex, the total number of neuron nuclei per 1 mm2 was counted, and the ratio of the number of intact neuron nuclei and nuclei with pathological changes (karyorrhexis and karyopyknosis) was also determined. Results: The transplantation of stem cells, lysate of human umbilical cord Wharton’s jelly-derived MSCs, or citicoline contributed to an increase in the number of neurons with nuclei in the somatosensory cortex, as well as an increase in the number of nuclei that did not undergo pathological changes. The transplantation of human umbilical cord Wharton’s jelly-derived MSCs had the most positive effect. The number of neuron nuclei in 1 mm2 that did not undergo pathological changes in the somatosensory cortex in this group of animals approached the number of nuclei in the group of pseudo-operated animals, while the number of nuclei that did not undergo pathological changes significantly exceeded the number of nuclei with signs of destruction. Conclusion: A significant increase in the number of neurons without signs of pathological changes was observed in all experimental groups of rats during the simulation of ischemic brain damage after the introduction of various types of studied mesenchymal stromal cells, lysate or citicoline. The most positive result in the somatosensory cortex was achieved after the introduction of human umbilical cord Wharton’s jelly-derived MSCs.
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