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Abstract 3D-bioprinting is a promising technology for a tissue scaffold fabrication in the case of damaged tissue/organ replacement. Collagen is one of the most appropriate hydrogel for the purpose, due to its exceptional biocompatibility. However, the use of collagen with conventionally low concentration makes bioprinting process difficult and does not provide its high accuracy. The purpose of the study was evaluation of suitability of collagen with high concentration in case of chondrocyte-laden scaffold fabrication via 3D-bioprinting for cartilage regeneration in vitro and in vivo. The results of the study showed that inherent porosity of 4% collagen was not enough for cell survival in the case of long-term incubation in vitro. With the beginning of the scaffold incubation, cell migration to the surface and out of the scaffold was observed. The residual cells died mostly within 4 weeks. As for in vivo study, in 2 weeks after implantation of the scaffold, a weak granulomatous inflammation was observed. In 6 weeks, a connective tissue was formed in the area of implantation. In the tissue, macrophages and groups of small cells with round nuclei were found. In accordance with morphological criteria, these cells could be considered as young chondrocytes. However, its amount was not enough to initiate the formation of cartilage.

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.

It was demonstrated that confocal Raman microscopy (CRM) could be used for domain imaging in the calcium orthovanadate Ca3(VO4)2 single crystals. The domain contrast could be achieved using noticea...

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.

The variation of elastic and electromechanical properties of microtubes of diphenylalanine dipeptide as a function of the degree of filing of nanochannels by water molecules is reported in this paper. Quantum chemical calculations reveal different contributions of water layers in the microtubes to Young's modulus and the effective piezoelectric coefficient. The application of diphenylalanine microtubes in micro-electromechanical systems is also discussed.

We have switched polarization in calcium orthovanadate single crystal with as-grown domain structure consisting of isolated domains with charged domain walls (CDWs) located in the bulk using pretreatment by ac field and subsequent switching in dc field at the elevated temperature. The formation of the domain ledges at the CDW in the bulk and their growth in the polar direction has been revealed. The isolated domains with optically well-defined walls appeared when the ledge tops reached the surface, their shape and sizes remaining constant during further switching. Unlike usual continuous domain wall motion, we have observed the discrete switching by arising of the isolated domains without any input of the traditional domain nucleation at the polar surface. The obtained results have been explained under the assumption that at the used experimental conditions, the applied field is above the threshold value for ledge nucleation at CDW in the bulk, but below the threshold for domain wall motion at the surface. Thus, we have obtained the discrete switching by ledge growth without any sideways motion of the domain walls and domain coalescence. The nonuniform evolution of the domain structure at the surface is due to the dependence of the switching rate on the distance from CDW to the polar surface, which is random in the studied domain structure.

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.

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.

In this work, we investigated the influence of piezoelectric ZnO and nonpiezoelectric SiO2 and TiO2 nanoparticles on the structure and some physical properties of composite structures based on microtubes of diphenylalanine. We demonstrated that all types of used nanoparticles promoted formation of voids and cavities in diphenylalanine microtubes thus reducing the effective Young's modulus and lateral piezoelectric coefficient of the composite. At the same time, embedding of piezoelectric ZnO nanoparticles provides noticeable vertical piezoresponse normally absent in single-component diphenylalanine microtubes. The obtained results demonstrate the ability to control the properties of self-assembling composite biomaterials by nanoparticles.

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.

Stress-induced local polarization reversal was studied in La doped BiFeO3 ceramics under the action of Berkovich-type prism indentation. Piezoresponse force microscopy was used for detailed study of domain structure before and after local polarization reversal. Two mechanisms of domain formation under the action of the mechanical loading were revealed: (1) direct stress-induced and (2) stress mediated by grain clamping. Critical stress value for local polarization reversal was extracted from the dependence of the switched area on the applied loading force. © 2019, © 2019 Taylor & Francis Group, LLC.

In this work, we formulate novel data-driven assays for exploring the structure-property linkages for high-manganese austenitic wear-resistant steel 110G13L (Hadfield steel). Steel 110G13L has the following chemical composition, wt.%: C(0.95-1.50)-Mn(11.5-15.0). These assays are built on recent advances in high resolution quantification of material structure using correlations and principal analyses of electron backscatter diffraction (EBSD) data, as well as in the mechanical characterization using nanoindentation. These novel protocols are demonstrated on a steel 110G13L that exhibits various polycrystalline microstructures. A comparative analysis of EBSD data was carried out for samples of manganese steel 110G13L obtained by various methods. Analysis of the diffraction patterns of backscattered electrons allowed us to plot orientation maps, Schmid factor maps and distributions for austenite dendrites. Schmid factor maps are used to determine the degree of homogeneity of a possible deformation. The results of the measurement of hardness and Young's modulus for the austenite dendrites indicate the heterogeneity of the mechanical properties of the material in submicro-volumes due to lattice defects (dislocations) inside the crystallites. © Published under licence by IOP Publishing Ltd. Russian Foundation for Basic Research, RFBR: 19-33-90198 The equipment of the Ural Centre for Shared Use “Modern nanotechnology” UrFU was used. The reported study was funded by RFBR (project No. 19-33-90198).

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.

Immunohistochemical and morphometric analyses have demonstrated long-distance stimulatory effects of the natural volatile components of the urine of intact mice on the proliferation of splenic lymphocytes in mice exposed to a single total γ-irradiation in a dose of 1 Gy. These results are in line with the data on stimulation of the humoral immune response to thymus-dependent antigen in irradiated mice exposed to urine specimens of intact animals.

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.

Studies of the effects of vilon and epithalon on functional morphology of the thymus, spleen, and duodenum in intact rats and rats exposed to single whole-body γ-irradiation in a dose of 6 Gy showed that vilon stimulated proliferative activity of thymocytes and enhanced proliferative potential of stem cells in the intestine, thus stimulating the postradiation recovery of critical organs. Epithalon decelerated metabolic processes in the duodenal mucosa and suppressed hemopoiesis and lymphopoiesis in the spleen.

The hormone of melatonin is the main regulator of biological rhythms. It was first found in the pineal gland in 1958. Melatonin is involved in the regulation of many vital physiological processes: maturation and development of genitalias, metabolism of pigments and free radicals, immune response, mood and sleep, and cell proliferation and differentiation. The pineal gland is not the only organ synthesizing melatonin. Extrapineal melatonin is widely dis-tributed in humans and animals. Melatonin-producing cells are found in the gastrointestinal and respiratory tracts, pancreas, adrenal and thyroid glands, thymus, cerebellum, urogenital system, placenta, and other organs. Melatonin is intensely synthesized in non-endocrine cells: mast cells, natural killers, eosinophilic leukocytes, platelets, and endotheliocytes. Such a wide distribution of melatonin reflects its key role as an intercellular neuroendocrine regulator and coordinator of many complex and interrelated biological processes.

Highly specific polyclonal rabbit antimetallothionein antibodies are isolated and characterized. The possibility of using these antibodies in immunohistochenical assay was verified on normal and tumor mammary tissues, the common metallothionein-positive models.

A mathematical model for catalytic oxidation of CO on a spherical platinum catalyst with allowance for the influence of gas diffusion is developed and studied. The model explains the origin of the effects of bifurcation and oscillation of a steady reaction rate. The model is based on the four-stage catalytic Elley-Ridley mechanism. In contrast to the case where gas diffusion retardation is ignored and only one basic form of catalyst phase plane exists, owing to the consideration of the effect of gas diffusion, we found two additional regimes of catalyst operation. These additional regimes make it possible to explain the origin of the effects of bifurcation and oscillation of the steady reaction rate by which the reaction rate for a steady-state surface is meant. When the surface concentrations of adsorbing reagents or free catalytic sites vary in the course of the reaction, the regime of catalyst operation is called unsteady. The reaction rate when the catalyst reaches a steady state is determined for all possible regimes of catalyst operation. Based on analysis of the results obtained, we give some practical recommendations on an increase in the reaction rate. The hysteresis of the reaction rate is explained.

We study for the first time the process of dynamic oxidation of CO on a spherical Pt catalyzer with account for the influence of exodiffusion. In contrast to the case when exodiffusional retardation is neglected and there exists only a single basic form of the catalyzer phase plane, in the present work (thanks to account for the influence of exodiffusion), we find four additional regimes of catalyzer operation. These additional regimes make it possible to explain the discontinuous nature of the dependence of the steady-state reaction rate on the mixture pressure and the reagent concentrations. It is established that the time dependence of the reaction rate upon catalyzer transition to the stationary state may be nonmonotonic and influenced by the initial state of the catalyzer and the dimensionless governing parameters. It is shown that (depending on the values of the external governing parameters) there may exist six, five, four, and two stationary states, which are singular points of the “saddle” or “nodal” type in the phase plane.

We studied the effects of systemic transplantation of mesenchymal stem cells obtained after culturing of autologous bone marrow on psychophysiological status of Wistar rats after diffuse brain trauma. Two months after systemic injection of mesenchymal stem cells we observed a decrease in manifestations of emotional behavioral reactions (anxiety and excitability) and shortening of the time of realization of drinking behavior in a T-maze. A significant positive effect of systemic transfusion of mesenchymal stem cells on avoidance conditioning in a shuttle box was observed 3 months after brain injury.

Immunohistochemical and morphometric analysis showed that epithalamin and epithalon produced similar effects on the functional morphology of the spleen in pinealectomized rats. Both peptides prevented hyperplasia of lymphoid cells in follicular germinative centers induced by pinealectomy and potentiated the decrease in extramedullary hemopoiesis. These findings confirm the data on functional relationships between the pineal gland and immune system. The effects of epithalamin and epithalon on cell and tissue homeostasis in the spleen of old pinealectomized rats can be regarded as a manifestation of the general regulatory effect of these peptides.

During the last decade, attention has centered on melatonin (MT), one of the hormones of the diffuse neuroendocrine system (DNES) which for many years was considered only as a hormone of the pineal gland. Currently, MT has been identified not only in the pineal gland but also in extrapineal tissues such as the retina, harderian gland, gut mucosa, cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, ovary, testis, carotid body, placenta, and endometrium as well as in nonendocrine cells like mast cells, natural killer cells, eosinophilic leukocytes, platelets, and endothelial cells. The above list of the cells storing MT indicates that MT has a unique position among the hormones of the DNES, being found in practically all organ systems. Functionally, MT-producing cells are certain to be part and parcel of the DNES as a universal system of response and control of protection to the organism. Taking into account the large number of MT-producing cells in many organs, the wide spectrum of its biological activities and, especially, its main property as a universal regulator of biological rhythms, it should be possible to consider extrapineal MT as a key paracrine signal molecule for the local coordination of intercellular relationships. Analysis of the experimental results described here shows the direct participation and active role of extrapineal MT and related APUD hormones in both the pathogenesis of tumor growth and the modification of antitumor therapy.

Studies of the effects of vilon and epithalon on functional morphology of the thymus, spleen, and duodenum in intact rats and rats exposed to single whole-body gamma-irradiation in a dose of 6 Gy showed that vilon stimulated proliferative activity of thymocytes and enhanced proliferative potential of stem cells in the intestine, thus stimulating the postradiation recovery of critical organs. Epithalon decelerated metabolic processes in the duodenal mucosa and suppressed hemopoiesis and lymphopoiesis in the spleen.

Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.

The paper presents a review of the results obtained by the authors on the study of external (gamma) and internal (I-131) radiation effects on the functional morphology and linkage of the diffuse neuroendocrine system (DNES) and amine precursor uptake and decarboxylation (APUD) cells of the stomach and duodenum. The investigations performed enabled us to determine that the morphological changes noted in APUD cells had a dose and time dependency. The present study supports the point of view that the radiation initiates serotonin release from APUD cells, which appears to initiate the mechanism of early postirradiation dysfunctions of the gastrointestinal tract and the subsequent adaptive response of DNES. Analysis of our results, together with a review of the literature, indicates that APUD cells actively participate both in pathogenesis of radiation injury and development of organ and tissue radiosensitivity.

Endocrine cells in the stomach of pinealectomized rats after injection of epithalone (pineal gland peptide) were studied by immunohistochemical tests, morphometry, and image analysis microscopic images. A functional relationship was found between the pineal gland and stomach, which is regulated by peptides produced by the pineal gland.

Effects of systemic transplantation of mesenchymal stem cells obtained by culturing of autologous bone marrow on proliferative activity of cells and functional morphology of neurons after diffuse brain injury were studied in Wistar rats. Comparative analysis of the results indicated that systemic injection of mesenchymal stem cells in a syngeneic organism produced proliferotropic, angiogenic, and, presumably, neurotrophic effects. The therapeutic effect visually manifested on day 2 after intravenous injection of mesenchymal stem cells during the early period of reparative regeneration of ischemic cell and tissue structures of the brain. The neuroprotective effect of mesenchymal stem cells was more pronounced against the background of basic therapy.