Alexander Maazovich Aimaletdinov

Humic substances, including humic acid and fulvic acid, are a class of naturally occurring complex compounds found in soil, water and sediments. In aquatic ecosystems, humic substances have an important influence on the properties and functions of natural aquatic systems, as they play a direct role in shaping the physical and chemical environment of a water reservoir. Artificial fish farming has become necessary not only to meet the demand for edible animal proteins, but also to replenish and conserve depleted stocks and endangered fish populations. Humic substances have positive effects on many organisms, also improve some vital parameters of fish such as growth performance, stress tolerance and immune response. The fungistatic effect of humic substances on Saprolegnia parasitica, a common parasite of freshwater and marine fish, is known. Humic substances reduce the number of pathogens Vibrio harveyi and Acinetobacter in the intestines of fish. However, the addition of humic acid in high concentrations to the feed of juvenile common carp (Сyprinus carpio) caused not only improved growth and feed eating efficiency, but also had detrimental effects on gill, liver and kidney tissues. This article is a literature review that explores the advantages and disadvantages of using humic substances in aquaculture.

Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention.

In this study, the effects of different combinations of the genes Vegf, Ang, and Gdnf injected both using direct virus-mediated injection (adenovirus, Ad5) and umbilical cord blood mononuclear cells (UCBCs) on the processes of stimulation of post-ischemic innervation, angiogenesis, and regeneration in skeletal muscle were investigated in a rat hindlimb chronic ischemia model. It was shown that more pronounced stimulation of angiogenesis and restoration of post-ischemic innervation were achieved both in the early (28 days post-ischemia, dpi) and late (42 dpi) terms of the experiment in the calf muscle when UCBCs delivered the combination of Ad5-Vegf and Ad5-Ang compared to the direct injection of the same vector combination into the area of ischemia. At the same time, the inclusion of Ad5-Gdnf in the combination of Ad5-Vegf and Ad5-Ang directly injected or administered by UCBCs provided a significant increase in the number of centronuclear muscle fibers, indicating stimulation of post-ischemic reparative myogenesis. This study allowed us to determine the most effective gene combinations for angiogenesis and neurogenesis, which, in the future, may serve as the basis for the development of gene and gene cell products for the treatment of chronic lower limb ischemia.

Extracellular vesicles are released by all cell types including stem cells. Stem cell-released extracellular vesicles have therapeutic effects similar to those of their parent cells and have regenerative effects in tissues. They also have an immunomodulating effect when down-regulating some proinflammatory factors, without exerting effects on cell proliferation, modulating angiogenesis or altering cellular functions in recipient cells. Modern veterinary research explores vesicles and creates or advances methods of using them in regenerative and reproductive medicine, applications of these technologies are under development.