Artyom I. Trofimenko

This article presents a review of the pathogenesis of cardiovascular-kidney-metabolic syndrome – a multifactorial condition in which cardiovascular, renal, and metabolic disorders mutually aggravate each other. Insulin resistance serves as the central link of the syndrome, leading to compensatory hyperinsulinemia. The latter activates the sympathetic nervous system and the renin-angiotensin-aldosterone system, promoting sodium retention, endothelial dysfunction, arterial hypertension, and atherosclerosis. In the kidneys, hyperglycemia triggers PKC and JAK-STAT/NF-κB signaling pathways as well as the accumulation of advanced glycation end products (AGEs), resulting in inflammation, fibrosis, and progression of diabetic nephropathy.

Numerous studies addressing the fundamental aspects of atherosclerosis emphasize the importance of systematically organizing the accumulated data. The second part of this lecture provides an analysis of the critical mechanisms involved in the development of atherosclerosis. This analysis includes a discussion on the roles of inflammasomes, hemodynamic disorders within the vascular wall, vasa vasorum pathology, endothelial cell dysfunction, matrix metalloproteinases, and the Notch and Wnt signaling pathways in the process of atherogenesis. Additionally, it explores the specific characteristics of the pathogenesis of vascular calcification associated with atherosclerosis. A dedicated section thoroughly reviews contemporary pharmacotherapeutic strategies for managing atherogenic dyslipidemia. A comprehensive analysis of current concepts regarding the pathogenesis of atherosclerosis, along with promising approaches to drug therapy, will facilitate the identification of future research directions within the field of lipidology. This endeavor has the potential to elevate preventive cardiology to a new standard.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are now uncovering new possibilities in the field of internal medicine owing to their diverse protective effects. In the second part of the literature review, we explore potential applications of SGLT2i in hepatology, neurology, ophthalmology, and oncology, mechanisms of action of such drugs as dapagliflozin, empagliflozin, canagliflozin, etc, and their effect on different organs and systems.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a revolutionary class of drugs with far-reaching protective effects in multiple organs. The protective potential of SGLT2i is much broader than that of the classical concept of glucose control and consists of an entire conglomerate of associated pleiotropic effects. This study aims to provide a descriptive review of the pleiotropic therapeutic potential of SGLT2i. The first part of the literature review examined the use of SGLT2i in cardiology and nephrology. The use of SGLT2i represents an innovative approach to improving patients’ quality of life and course of heart failure and chronic kidney disease, regardless of left ventricular ejection fraction and type 2 diabetes.

Introduction: The aim of this work was to develop a prototype of a modular extrusion bioprinter capable of performing 2D and 3D printing with hydrogels based on sodium alginate and gelatin. Materials and methods: The bioprinter uses Cartesian coordinate system, the print head is movable in Y and Z axes, the printing platform is in X axis and equipped with cooling system. Constructs were printed with 3 types of gels: based on gelatin with the addition various concentrations of xanthan gum; based on combination of gelatin and sodium alginate; based on gelatin and xanthan gum with the addition of carbon nanotubes. Results: The constructs from various gels corresponded to the structure determined by their digital models. Conclusions: The developed system allows performing 2D and 3D printing with gels based on gelatin, sodium alginate, including those containing carbon nanotubes and/or xanthan gum for a wide range of experimental tasks.

Background: Data published by task groups of the Ministry of Health of the Russian Federation, the European Society of Cardiology, and other medical associations and institutions show that chemotherapy-induced cardiomyopathy is still a challenging issue that requires further research.Objective: To compare the cardioprotective potential of trimetazidine and dapagliflozin in a rat model of doxorubicin-cyclophospha-mide cardiomyopathy.Materials and methods: Our randomized in vivo experimental study included 80 Wistar female rats. Doxorubicin and cyclophosphamide were administered at a dose of 15 mg/kg and 150 mg/kg, respectively. Trimetazidine (42 mg/kg) and dapagliflozin (14 mg/kg) were additionally administered to groups 3 and 4, respectively. The total duration of the experiment was 14 days.Results: Doxorubicin+cyclophosphamide mode of chemotherapy induces the development of toxic-ischemic cardiomyopathy. The trimetazidine and dapagliflozin administration was accompanied by stabilization of cardiovascular parameters. Comparison of both drugs’ cardioprotective properties revealed a clear advantage of dapagliflozin over trimetazidine, especially in terms of such an important indicator as N-terminal pro-B-type natriuretic peptide.Conclusions: Further research aimed at exploring the cardioprotective potential of dapagliflozin against cardiovascular complications of chemotherapy is justified from a pathogenetic point of view.

Bioprinting allows additive fabrication of bioengineered constructs with defined two- or three-dimensional organization using live cells, biopolymers and other materials. This article reviews main bioprinting technologies and their capabilities in clinical and experimental ophthalmology. Analysis of literature sources helped reveal and describe the main types of bioprinting technologies: inkjet, laser-assisted, and extrusion. Extrusion bioprinting is the most widely used method, providing the ability to use various types of bioinks and a wide range of cell concentrations. The following materials can be used as the base for bioinks: alginate, collagen, gelatin, hyaluronic acid, chitosan, fibrin, as well as their different combinations. These materials can be modified for best bioprinting properties by adding various functional groups. The major directions of application of bioprinting technologies in ophthalmology are tissue engineering for regenerative medicine and fabrication of model systems for fundamental and preclinical studies. Experiments in creating a bioprinted cornea are being conducted in the field of regenerative medicine. Furthermore, there are studies on fabricating retinal tissue equivalents, although tissue engineering of this structure is a task of great complexity. Model systems, which can be fabricated by bioprinting, are represented by tissue equivalents of ocular structures and the appendages of the eye, as well as by microphysiological organ-on-a-chip systems. Another promising application of bioprinting is fabrication of biocompatible implantable electrode arrays for visual neuroprostheses.

This review discusses the role of capsule endoscopy in diagnosing suspected small bowel bleeding and compares guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), the American College of Gastroenterology (ACG), the American Society for Gastrointestinal Endoscopy (ASGE), the Canadian Association of Gastroenterology (CAG), and the consensus document of 4 Japanese medical societies. European and North American experts recommend capsule endoscopy as a first-line diagnostic modality for suspected small bowel bleeding without life-threatening signs in adult patients when ileocolonoscopy and esophagogastroduodenoscopy failed to be informative. Japanese experts, on the contrary, prefer cross-sectional imaging “from the chest to the pelvis” and consider capsule endoscopy as an alternative.

Background. Transcranial electrical stimulation is a promising method for correction of malnutrition-induced hyperlipidemia, in the absence of indications for drug hypolipidemic therapy in young and middle-aged patients with low and moderate cardiovascular risk. Objectives — to study the effect of transcranial electrical stimulation on lipid metabolism in a high-fructose/high-fat (HFHF) diet in rats.Methods. An experimental randomized trial was performed to study the effect of transcranial electrical stimulation on lipid metabolism in a high-calorie diet enriched with fructose and saturated animal fat in rats. The experiments involved 180 outbred male rats and were carried out on the basis of the vivarium of Kuban State Medical University. The animals were divided into three groups: group 1 (control group, n = 60) — followed a standard diet; group 2 (comparison group, n = 60) — followed a HFHF diet; group 3 (experimental group, n = 60) — underwent transcranial electrical stimulation against the background of a HFHF diet. According to the target reference point of the study, the groups were divided into three equal subgroups of 20 rats each: subgroup A — day 30, subgroup B — day 60, and subgroup C — day 90 (biomaterial sampling and euthanasia were carried out on those days). In the obtained blood samples, the following lipid metabolism parameters were evaluated: total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and atherogenic index. Statistical analysis was performed using Microsoft Office Excel 2021 (Microsoft, USA), GraphPadPrism 9 (GraphPad Software, USA) and Statistica 13.3 (StatSoft, USA).Results. On the 30th day of the study, it was noted that in group 3, the concentration of low-density lipoprotein cholesterol was 14.9% lower and the atherogenic index was 30.8% lower (p < 0.05) than in group 2, while total cholesterol concentration, triglycerides, and high-density lipoprotein cholesterol had no statistically significant differences (p > 0.05). On the 60th day of the study, in group 3, when compared to group 2, the concentration of total cholesterol was 18.7% lower, low-density lipoprotein cholesterol was 42.9% lower, high-density lipoprotein cholesterol was 16.7% higher, and the atherogenic index was 56.3% lower (p < 0.05), while triglycerides had no statistically significant differences (p > 0.05). On the 90th day of the study, in group 3, when compared to group 2, the concentration of total cholesterol was 29.2% lower, the concentration of triglycerides was 36.0% lower, low-density lipoprotein cholesterol was 42.8% lower, and the atherogenic index was 57.0% lower (p < 0.05), while the concentration of high-density lipoprotein cholesterol had no statistically significant differences (p > 0.05).Conclusion. High-fructose/high-fat diet leads to a progressive increase in the serum concentration of low-density lipoprotein cholesterol, total cholesterol, triglycerides, as well as to a moderate decrease in high-density lipoprotein cholesterol and a growth in the atherogenic index. Transcranial electrical stimulation has a moderate lipid-lowering effect, manifested in the form of a decrease in the serum concentration of low-density lipoprotein cholesterol, total cholesterol and atherogenic index, while the effect on the concentration of triglycerides and high-density lipoprotein cholesterol is insignificant.

The study aims to conduct a transcranial electrical stimulation therapy trial in rats influencing the indicators of systemic inflammation dynamics and the percentage content of visceral adipose tissue in a highfat fructose diet. The study included 180 male outbred rats, which were randomly distributed into three groups: the first group had a standard diet; the second group received the high-fat fructose diet; and the third group received both transcranial electrical stimulation therapy and the high-fat fructose diet. Tumor necrosis factor-α, interleukin-15, and interleukin-19 concentrations were measured in blood serum. The percentage of visceral adipose tissue in relation to body weight was calculated. The percentage content of visceral adipose tissue and serum concentration of tumor necrosis factor-α were lower, and interleukin-19 was higher in rats that received transcranial electrical stimulation with a high-fat fructose diet in comparison to the second group, which did not undergo the stimulation. Interleukin-19 level in the blood serum of rats in the second group grew as the trial progressed, whereas the opposite occurred in the third group. There was an inverse relation between the predictive variables of transcranial electrical stimulation, interleukin-19, and the variable of tumor necrosis factor-α. The data obtained in the experiment may also indicate that interleukin-15 cannot be unequivocally considered as a key factor associated with a decrease in visceral adipose tissue content when introducing a high fructose and animal-based saturated fat diet to rats.