Comparative analysis of cardiovascular system morphofunctional disorders’ correction in a simulated metabolic syndrome

BACKGROUND: Metabolic syndrome (MS) causes the risk of serious diseases development e.g. type 2 diabetes mellitus and cardiovascular disasters. Timely and adequate correction of MS can reduce the risk of heart disease and diabetes AIM: To investigate the development of MS and drugs for its correction on the morphofunctional state of the heart muscle and large blood vessels. MATERIALS AND METODS: A comparative analysis of morphofunctional disorders in the cardiovascular system on the fructose model of MS and its correction in adult (n=32) and young (n=50) Wistar rats was performed. The duration of fructose feeding was 24 weeks for young animals and 16 weeks for Mature animals due to their different resistance to the development of the MS model. To correct MS, the following drugs were used: resveratrol, Stilbene concentrate in a dose of 2 mg/kg, Fenokor – 1 ml/kg, azilsartan – 1 mg/kg. During the experiment, blood pressure (BP), body weight, and heart rate (HR) were measured in experimental animals. Then, after euthanasia, sections of the heart and aorta of experimental rats were examined using light microscopy. RESULTS: In MS, adult male rats developed morphological changes in the heart wall, which were primary vascular damage, and secondary – myocardial injury. In the aorta, signs of endothelial damage, lipid imbibition, and fibroelastic scaffolding were revealed. A specificity of young animals’ response to MS was functional compensation with pronounced changes in the structure of large vessels. The greatest effect of normalization of morphofunctional indicators in mature animals is provided by preparations of polyphenols. When MS was corrected with Resveratrol and Fenocor, there was no obese fibrous stroma of the heart, and there was also a normalization of the structure of the middle layer of the aortic wall. In young animals, the use of Azilsartan and Stilbene concentrate from 14th week of the experiment also led to compensation of vascular damage and hemodynamic disorders. CONCLUSION: To correct the manifestations of MS in the cardiovascular system in mature rats, the most effective drugs are resveratrol and Fenocor, and in young rats – azilsartan and Stilbene concentrate in the case of early use

A Half-Century History of Applications of Antisense Oligonucleotides in Medicine, Agriculture and Forestry: We Should Continue the Journey

Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products