Mesenchymal stem (stromal) cells (MSCs) are self-renewing, cultured adult stem cells which secrete a complex set of multiple soluble biologically active molecules such as chemokines, and cytokines, cell adhesion molecules, lipid medi­ators, interleukins (IL), growth factors (GFs), hormones, micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), exosomes, as well as microvesicles, the secretome. MSCs of various origin, including adipose-derived stem cells (ASCs), bone marrow derived mesenchymal stem cells (BM-MSCs), human uterine cervical stem cells (hUCESCs), may be good candidates for obtaining secretome-derived products. Different population of MSCs can secret different factors which could have anti-inflammatory, anti-apoptotic, anti-fibrotic activities, a neuroprotective effect, could improve bone, muscle, liver regeneration and wound healing. Therefore, the paracrine activity of condi­tioned medium obtained when cultivating MSCs, due to a plethora of bioactive factors, was assumed to have the most prominent cell-free therapeutic impact and can serve as a better option in the field of regenerative medicine in future.

Ti(50-x)Zr38NbxTa8Sn4 high-entropy alloys with x = 0, 10, and 20 at.% were produced by vacuum arc melting in a high-purity argon atmosphere. The initial microstructures consisted of equiaxial bcc grains with sizes of 115 ± 30 µm, 250 ± 60 µm, and 280 ± 70 µm for the Ti30Nb20, Ti40Nb10, and Ti50Nb0 alloys, respectively. The Ti30Nb20 and Ti40Nb10 alloys showed untypical mechanical behavior with a short strain-hardening stage followed by a gradual decrease in flow stress after reaching the yield point. Although these two alloys had some inclination toward macroscopic strain localization, their tensile elongation was similar to that obtained in the Ti50Nb0 alloy, which had a more extended stage of uniform deformation. The differences were associated with distinct microstructures observed after deformation to fracture. The formation of dislocation bands and the activation of cross-slip at the microscale, as well as the appearance of kink bands at the mesoscale, can result in plastic instability. In contrast, a lamellar-like microstructure with parallel dislocation bands, such as the one observed in the Ti50Nb0 alloy, can ensure a more stable mechanical behavior. The developed alloys (Ti30Nb20 and Ti40Nb10) have properties that make them highly attractive for biomedical application due to a combination of very high yield strengths (1090 and 930 MPa, respectively), low Young’s moduli (~78 and ~69 GPa, respectively), reasonable ductility, and excellent biocompatibility.

The therapeutic effect of multipotent mesenchymal stem cells has been proven on various disease models. One of the mechanisms is the paracrine effect of the cells on the surrounding tissues.The aim. To investigate the secretome effectiveness of the multipotent mesenchymal stem cells in the treatment of adjuvant arthritis and contact-allergic dermatitis in Wistar rats.Materials and methods.Adjuvant arthritis was simulated in 26 female rats by the administration of Freund's complete adjuvant and then treated with the administration of 100 µl of multipotent mesenchymal stem cell secretome or saline. Contact-allergic dermatitis was modeled on 30 female rats by applying 200 μl of an oil solution of dinitrofluorobenzene to the skin on days 1, 5 and 6. Then the rats were treated with fluocinolone ointment (a positive control), baby cream (a negative control), baby cream with a secretome of native multipotent mesenchymal stem cells or from the cells processed with dexamethasone.Results.Judging by the indicators of the longitudinal and transverse dimensions of the paws in rats and a histological examination, the secretome did not have any anti-inflammatory effect on adjuvant arthritis. A cream with a secret from multipotent mesenchymal stem cells processed with dexamethasone, was the most effective on the model of contact-allergic dermatitis: the clinical improvement occurred on the 2^ndday. The secretome from native multipotent mesenchymal stem cells and fluocinolone had a therapeutic effect on the 3^rdday of application, the negative control - on the 4^thday. The lymphocytic infiltration coefficient was significantly lower (p <0.05) in all the cases compared to the negative control (2.8 ± 0.1). However, the lowest infiltration was observed when the cream with secretome from native (1.75 ± 0,1) and dexamethasone-stimulated (1.76 ± 0.1) multipotent mesenchymal stem cells was being used.Conclusion.The cream with the secretome of multipotent mesenchymal stem cells suppresses lymphocytic infiltration more strongly than the highly active topical glucocorticosteroid - fluocinolone - on the model of contact-allergic dermatitis, which is a classic local delayed-type hypersensitivity reaction. However, a further study of the therapeutic effect of the secretome on models of systemic inflammatory diseases is required after its preliminary purification from large-molecular proteins.

Introduction. The drugs affecting a mitochondrial dysfunction, oxidative stresses, apoptosis and inflammation of the vascular wall, have a high potential for the prevention and treatment of atherosclerotic lesions. In this regard, the use of EPOR/CD131 heteroreceptor agonists which have a similar spectrum of pharmacological effects, is one of the promising strategies in the treatment of cardiovascular diseases.Materials and Methods. The study was carried out on 68 C57Bl/6J male mice. Atherosclerosis was simulated in transgenic animals with an endotheliospecific knockdown of the Polg gene by simulating a balloon injury and keeping on a Western diet. Then, the studied drugs were injected once every 3 days at the dose of 20 μg/kg for 27 days. On the 28-th day, the animals were euthanized and the area of atherosclerotic plaques was assessed. The gene expression associated with the processes of inflammation, antioxidant protection, apoptosis, and angiogenesis was also determined in the aortic tissues. In addition, the endothelium protective effect of peptides on primary cultures of endothelial cells of wild and transgenic Polg-D257A mice was studied.Results. No statistically significant effect of drugs on the area of lipid infiltration have been found. However, the studied peptides have significantly reduced the expression of proinflammatory genes (iNos, Icam1, Vcam1, Sele, Il6, Tnfa), the genes associated with angiogenesis (Vegfa, Kdr, and Hif1a), the expression of proapoptic factors; they decreased the Bax/Bcl-2 ratio by more than 1.5 times. In addition, when supplemented with H2 O2 in vitro, peptides dose-dependently increased endothelial cell survival.Conclusion. The erythropoietin-based peptides can be used to improve the functional state of the vascular wall against the background of atherosclerotic lesions and have a depressing effect on pathobiological processes associated with a mitochondrial dysfunction. In addition, the studied peptides have a significant endothelial protective effect in the induction of oxidative stress in vitro.

TiNbZr-(Ti,Nb)B composites were produced by vacuum arc melting; the weights of TiB₂ in the charge mixture were 0.7 wt. % (Alloy A) and 4.0 wt. % (Alloy B). In addition, unreinforced TiNbZr alloy specimens were fabricated without the addition of TiB₂. The microstructure of the TiNbZr-(Ti,Nb)B composites consisted of the TiNbZr β matrix and (Ti,Nb)B fibers. The (Ti,Nb)B fibers had a needle-like shape with an average diameter of ~0.4 and ~2.0 µm for Alloys A and B, respectively. The volume fraction of borides was found to be ~2.5 and ~12.4% for Alloys A and B, respectively. The presence of 12.4 vol.% of (Ti,Nb)B reduced the corrosion resistance of Alloy B in comparison with that of the TiNbZr alloy and Alloy A, which showed rather similar values of corrosion resistance. It was found that the addition of the TiB₂ to the TiNbZr alloy led to a decrease in the friction coefficient; when adding 0.7% TiB₂ to the alloy (Alloy A), the friction coefficient decreased from 1.15 to 1.13, and when the percentage of TiB₂ in the alloy increased to 4% (Alloy B), the friction coefficient decreased by ~2 times from 1.15 to 0.58. The full biocompatibility of TiNbZr-(Ti,Nb)B composites was demonstrated; no significant differences from the unreinforced state and alloy were found.