[The Peptide Drug ACTH(4-7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain].

Due to its nootropic, neuroprotective, and immunomodulatory effects, the peptide Semax is utilized in the treatment of ischemic stroke. Our earlier RNA-Seq analysis of the transcriptome in an ischemic model of transient occlusion of the middle cerebral artery showed an increase in the mRNA levels of many proinflammatory genes, and the suppression of their induction by Semax. However, for many relevant genes, including Il1a, Il1b, Il6 and Tnfa, the levels of their expression were too low for detailed quantitative evaluation. Here we utilize qRT-PCR to analyze the effects of the Semax peptide on the expression of weakly expressed mRNAs encoding several proinflammatory mediators, and show that exposure to Semax leads to a statistically significant decrease in the Il1a, Il1b, Il6, Ccl3, and Cxcl2 mRNAs, which compensates for the increase in the transcription of these genes induced by ischemia-reperfusion. We conclude that the observed protective effect of Semax in the model of stroke may be due to its anti-inflammatory effects. We also discuss the limitations of the RNA-Seq when applied to quantifying less abundant transcripts as compared to the real-time RT-PCR method.

Photodynamic Therapy of Sarcoma M-1 in Rats with Photosensitizer Photoran E6.

We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.

Effect of Vitrification on Functional Morphology and Viability of the Ovarian Tissue.

The results of a complex morphofunctional study with markers of proliferation (PCNA and Ki-67), angiogenesis (CD31 and CD34), and structural integrity of mesenchymal cells (vimentin) suggest that the pool of primordial follicles was well preserved in vitrified ovarian tissue and that viability of its cellular components can be rapidly restored during incubation at 37°C within 4 h after thawing.

[The effectiveness of fractionated exposure of sarcoma M-1 to gamma-radiation and fast neutrons].

The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

Modification of delayed radiation-induced reactions of duodenal vessels and mast cells in old rats.

Pronounced ultrastructural changes in vessels and mast cells were observed in duodenal lamina propria of Wistar rats 1 year after single whole-body gamma-irradiation in a dose of 7.5 Gy. Inhibition of adrenocortical function with methopyrone reduced structural damage and improved animal survival.