Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl6 mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.

Introduction: The study aim was to explore a neuroprotective action of magnesium (LKhT-317) and zinc (LKhT-318) taurine salts on experimental models of reperfusion brain damage in rats and cell culture. Materials and methods: The study was performed on male Sprague Dawley rats, and rat’s hippocampal mixed neuroglial cell culture. Magnesium- (LKhT-317) and zinc-containing (LKhT-318) derivatives of taurine were studied. Reperfusion brain damage was induced 30 min after intraluminal cerebral middle artery occlusion. Severity of the injury was assessed by local blood flowmetry, neurological symptoms scaling and brain tissue staining. Levels of IL-1b, IL-10 and TNF-alpha in tissue were determined by qualitative ELISA. Caspase-3 and Bcl-2 expressions were detected by IHC. Neurons survival was assessed by cytochemistry. Cellular calcium responses were detected by fluorescent microscopy of Fura-2-containig cells. Results and discussion: Metal-containing taurine derivatives – LKhT-317 and LKhT-318 – demonstrated a sufficient neuroprotective property in rats with a reperfusion-induced brain injury. Both derivatives effectively prevented severity of the animals’ brain damage, motor deficiency, reduction of microvascular perfusion, and proinflammatory cytokines production. Magnesium-containing compound LKhT-317 was comparatively more effective than zinc-containing one. LKhT-317 possessed an anti-apoptotic action in vivo, and protected neurons from OGD-mediated cell death in mixed hippocampal culture. The aforementioned actions may be associated with an LKhT-317 inhibitory effect on NMDA-induced cellular Ca2+ response and, therefore, the anti-excitotoxic property of the compound. Conclusion: Magnesium- and zinc-containing taurine derivatives may be considered as promising neuroprotectors in the reperfusion-induced brain injury.

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The aim of the work was to determine the viability, proliferative potential and adhesive properties of fibroblasts seeded on the surface and in the volume of a biocomposite formed using laser radiation and solders in in vitro experiments. Materials and methods. For the study, Wistar rat fibroblasts obtained at the National Research Center of Epidemiology and Microbiology named after Honorary Academician N.F. Gamalei were used. The biocomposite was formed using laser radiation and solders. The viability of cells on the surface of the biocomposite was assessed using the multiparametric RTCA iCELLigence cell culture analysis system (USA). The cytotoxicity of the biocomposite was determined in combination with triphenyltetrazolium bromide (MTT test, Merck Sigma-Aldrich, Switzerland). The proliferative potential and adhesive properties of fibroblasts were studied using a FEI Helios NanoLab 650 scanning electron microscope. Results and conclusions. The viability of cells on the surface and in the volume of a biocomposite formed using laser radiation and solder was proved using an electrophysical system for analyzing cell cultures. The absence of cytotoxicity of the biocomposite under the action of triphenyltetrazolium bromide in the spectrophotometric MTT test was demonstrated. It was found that during incubation of rat fibroblasts in the volume of the biocomposite, cell death is not observed, but, on the contrary, their proliferative potential is stimulated by increasing adhesion, which contributes to the formation of a dense cell layer. Conclusions. Biocomposite as a whole, as well as its individual elements, creates a favorable environment for the growth of fibroblast culture and can be used to restore the integrity of blood vessels using laser radiation and solder.

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