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A review of publications devoted to the analysis of genetic polymorphisms and features of the functioning of genes that affect the pharmacokinetics and pharmacodynamics of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is presented. Objective of the study was to reveal information about genes whose polymorphism may affect the effectiveness of SGLT2i. The review was carried out in accordance with the PRISMA 2020 recommendations, the search for publications was carried out in the PubMed databases (including Medline), Web of Science, as well as Russian scientific electronic libraries eLIBRARY.RU from 1993 to 2022. Polymorphisms in the structure of several genes ( SLC5A2 , UGT1A9 , ABCB1 , PNPLA3 ) have been described that may affect the treatment of type 2 diabetes mellitus complicated by diseases such as chronic heart failure, chronic kidney disease, or non-alcoholic fatty liver disease. The information found on the genetic features of the development of the effects of SGLT2i is limited to a description of the differences in their pharmacokinetics. The relevance of currently available pharmacogenetic studies is largely constrained by small sample sizes.

A review of publications devoted to the analysis of genetic polymorphisms of the gene encoding the glucagon-like peptide type 1 receptor and some other genes directly and indirectly involved in the implementation of its physiological action is presented. The aim of the study: to search for information on genes polymorphism that can affect the effectiveness of glucagon-like peptide type 1 agonists. The review was carried out in accordance with the PRISMA 2020 recommendations, the search for publications was based on PubMed databases (including Medline), Web of Science, as well as Russian scientific electronic source eLIBRARY.RU from 1993 to 2022. The several genes polymorphisms ( GLP1R, TCF7L2, CNR1, SORCS1, WFS1, PPARD, CTRB1/2 ) that may affect the course and therapy of type 2 diabetes mellitus, metabolic syndrome and obesity, was described. Single nucleotide substitutions in some regions of these genes can both decrease and increase the clinical efficacy of the treatment of diabetes mellitus and metabolic syndrome with the help of type 1 glucagon-like peptide agonists: exenatide, liraglutide. Data on the role of genetic variations in the structure of the products of these genes in the effectiveness of other type 1 glucacone-like peptide agonists have not been found.

In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.

Activation of m-, d1-, d2- and k1-opioid receptors increases cardiac resistance to ischemia-reperfusion. The cardioprotective effect of opioids in many cases appears to be associated with the activation of the peripheral OR. However, when it comes to non-peptide agonists OR able to cross the blood-brain barrier, we cannot exclude the involvement of central opioid receptors in cardioprotection. Endogenous opioids are not involved in the regulation of cardiac tolerance to ischemia- reperfusion in non-adapted animals. Stimulation of k1- and d1-OP may exert delayed cardioprotective effect. Activation d- and k1-OP reduces the intensity of cardiomyocyte apoptosis after reperfusion. The results of studies related to the inotropic effect of opioids during reperfusion of the heart remain highly controversial.

1-[(3-chlorophenyl)phenylmethyl]urea--a compound possessing anticonvulsant activity, which has been selected by screening among 100 linear and cyclic urea derivatives, produces synchronization of spontaneous bioelectric activity, increased convulsion threshold in the motor cortex, dorsal hippocampus, and basolateral nuclei of amygdala, increased the index of low-frequency flicker acquisition, and reduced response to high-frequency oscillations in the visual cortex of rabbits. This compound also increased the extracellular content of sodium ions and reduced intracellular content of potassium ions in the motor cortex, dorsal hippocampus, and amygdala.

Choline-positive neuroprotectors citicoline and choline alfoscerate decreased blood concentration of protein S100 in clinical trial on 52 patients in the first days after acute ischemic stroke. Neuroprotective therapy has also produced stabilization of blood-brain barrier.

The purpose--to investigate the influence of hepatoprotective agents of phospholipids'structure essentiale, eplir and its combinations with amber acid on rats liver functional state, lipoperoxidation and bioenergetics, also tumor necrosis factor-a and interleukin-10 blood content in experimental isoniazid intoxication. These agents demonstrated antioxidant action, decreased the common and indirect bilirubine, tumor necrosis factor-alpha blood content, aminotransferase and alkaline phosphatase activity, increased the interleukin-10 blood content. Isonoazid uncoupled the substrate oxidation with ADP phosphorylation and inhibited the respiratory activity of liver mitochondrions. Essentiale and eplir increased the coupling of oxidation with ATP synthesis, in combination with amber acid improved kinetic characteristics of liver mitochondrions.

The influence of vinpocetine, pentoxifylline and enalapril on endothelium functions has been studied in a group of in 172 patients with chronic brain ischemia. The endothelium-protective effect of drugs was manifested as the inhibition of the Willebrand factor output during arteriovenous occlusion test and as the renewal of endothelium-depended vasodilation. The extent of neurologic deficit reduction correlated with decrease in the activated endothelium-depended output of the Willebrand factor.

The influence of vinpocetine (cavinton) on endothelium function in 87 patients with chronic cerebral ischemia has been studied. Vinpocetine exerts an endothelium protective effect which appears as a partial renewal of endothelium-dependent vasodilatation and inhibition of rejection of Willebrand factor during arteriovenous occlusion test. Leveling of neurological deficit by vinpocetine depends on the extent of renewal of endothelium-dependent vasodilatation.

The aim of the study was to examine changes in vasodilatory endothelial function in early cerebrovascular disease of atherosclerotic genesis. All the examinees underwent ultrasonic investigation, test for reactive hyperemia of the brachial artery to evaluate vasodilatory function of the endothelium. Disturbances in the flow-dependent vasodilation were detected at initial stages of the disease, aggravated with the progress of cerebrovascular disease and therefore could serve the earliest, objective indicator of atherosclerotic process.

The effects of ethomersole (50 mg/kg orally during 10 days) on local cerebral blood flow and cerebral tissue impedance were investigated in rats after left carotid artery ligation and right carotid artery narrowing (blood flow was decreased to 50%). Under these conditions, ethomersole accelerated the blood flow recovery, levelled blood flow asymmetry between the hemispheres, decreased the development of brain edema. In in vitro experiments ethomersole demonstrated a pronounced limitation of cerebral lipid peroxidation.