Highlights

The possibility of using biodegradable microneedles from a copolymer of polylactate glycolic acid for the delivery of drugs such as sibutramine and metformin has been demonstrated. Significant differences in the rate of release were revealed depending on the type of drug: metformin release was significantly faster than sibutramine and was characterized by a maximum release rate in the first 2 hours, reaching a plateau after 24 hours and maintaining the release rate after 48 hours, in total, 7% of metformin loaded into microneedles was released into the buffer solution. During the same period of time (48 hours), only 1% of the total amount of sibutramine loaded into microneedles passed into the buffer solution. At the same time, the release rate was also highest in the first 2 hours, after which the release of the drug slowed down, but without reaching a “plateau”. Mixing of these drugs slows down their release.

Aim. Evaluation of metformin and sibutramine drugs release rate from the developed microneedles made of poly(lactic acid glycolic acid) copolymer PLGA using high-performance liquid chromatography coupled with high-resolution mass spectrometry when loading them separately into microneedles and when loading a mixture of two drugs.

Methods. The objects of the study were biosoluble microneedles made of PLGA 50:50 copolymer (10,000–40,000 g/mol, LA tolerance 48–52%, GA 48–52%, solvent – ​​acetone) filled with either metformin or sibutramine alone in different concentrations, or a mixture of both drugs. A series of model experiments were conducted: 1) the analysis of drug release from microneedles containing metformin; 2) the analysis of drug release from microneedles containing sibutramine; 3) the analysis of a mixture of drugs release from microneedles with metformin and sibutramine. Quantitative determination of metformin and sibutramine in samples was performed by high-performance liquid chromatography in combination with high-resolution mass spectrometry

Results. Metformin demonstrated the highest release rate during the initial period (the first two hours), with a gradual slowdown in the release rate and reaching a “plateau”, where the amount of substance released over 24 hours becomes comparable to the amount released over 48 hours. Sibutramine showed a significantly slower release rate than metformin under similar conditions. In samples containing a mixture of drugs, the release efficiency was significantly reduced compared to the release of the same drugs loaded into the microneedles separately

Conclusion. The developed PLGA system is suitable for providing gradual release of drugs at the required concentration in the tissue. Differences in release rates were revealed depending on the drug type and the presence or absence of admixture with another drug. Metformin demonstrated the fastest release from microneedles, while the drugs mixing resulted in a significant reduction in the release efficiency of both drugs.

Highlights
The results obtained in this study demonstrate the feasibility of further investigation of the diagnostic ability of myocardial fibrosis markers in hypertension. This will further enable the exploration and implementation of more intensive treatment strategies to prevent hypertrophic and fibrotic myocardial remodeling, which can lead to complications in hypertension, as well as the study of the effects of other drugs on myocardial fibrosis.

Aim. To evaluate the effect of sacubitril/valsartan on myocardial fibrosis and galectin-3 and transforming growth factor-beta-1 levels in rats with arterial hypertension using morphological and biochemical methods.
Methods. Arterial hypertension was modeled by unilateral nephrectomy in 32 male Wistar rats. Animals were divided into four groups: control (sham-operated, n = 8), experimental (no treatment, n = 16), treatment-25 (model + sacubitril/valsartan 25 mg, n = 4), and treatment-50 (model + drug 50 mg, n = 4). Blood pressure was measured for 8 months. Cytokine levels were determined using enzyme-linked immunosorbent assay, and myocardial fibrosis was assessed using histological and morphometric methods.
Results. In the experimental group without drug administration, a significant increase in blood pressure, cardiomyocyte hypertrophy, an increase in TGF-β1 (13.1 ± 4.18 ng/mL), and fibrosis (median final score 4) were observed. Sacubitril/valsartan 50 mg reduced blood pressure (SBP 94.0 ± 1.6 mmHg) and TGF-β1 levels (8.44 ± 0.95 ng/mL) and prevented hypertrophy but had no effect on final fibrosis (median 4 points). However, fibrosis was absent in the interventricular and interatrial septa. Sacubitril/valsartan 25 mg had no effect on blood pressure or final fibrosis (median 6 points). Galectin-3 levels did not differ between groups. ROC analysis showed low diagnostic significance of the studied cytokines (AUC < 0.73).
Conclusion. Sacubitril/valsartan 50 mg exerted a significant hypotensive and antihypertrophic effect, partially preventing fibrosis in the interatrial and interventricular septa, but did not prevent the development of overall myocardial fibrosis.

Highlights     

• Coronary microvascular dysfunction (CMD) is a pathophysiological condition characterized by impaired regulation of coronary microvascular tone and structure in the absence of obstructive epicardial artery disease. CMD is now recognized as a major contributor to myocardial ischemia, particularly in patients with angina and normal coronary angiograms (INOCA), as well as in cases of myocardial infarction with non-obstructive coronary arteries (MINOCA). The key mechanisms underlying CMD include impaired endothelium-dependent vasodilation, excessive vasoconstriction, inflammation, and capillary remodeling.
• The molecular regulation of coronary blood flow involves a complex network of signaling cascades, including ion channels, nitric oxide (NO), endothelin-1, cytokines, and regulatory non-coding RNAs. Single nucleotide polymorphisms (SNPs) in genes encoding these mediators and enzymes significantly affect microvascular function. Notably, SNPs in NOS3, KCNJ11, JAK2, HMOX1, VEGFA, and other genes have been associated with altered vasomotor reactivity, oxidative stress, inflammatory activation, and impaired angiogenesis.
• MicroRNAs (miRNAs) play a particularly important role in the pathogenesis of CMD by regulating gene expression at the post-transcriptional level. Dysregulation of miRNAs such as miR-126, miR-155, and miR-30 has been linked to endothelial dysfunction, reduced capillary density, and impaired myocardial energy metabolism. The interplay of molecular and genetic factors provides a mechanistic framework for CMD and offers new opportunities for personalized approaches in the diagnosis, prognosis, and treatment of microvascular forms of ischemic heart disease.

Abstract

Coronary microvascular dysfunction (CMD) has increasingly been recognized as an independent and clinically significant pathophysiological mechanism of myocardial ischemia, even in the absence of obstructive coronary artery disease. CMD is caused by both functional impairments, such as imbalance between vasodilation and vasoconstriction–and structural alterations of the microcirculatory network. Recent research highlights the crucial role of molecular and genetic factors in the development of CMD, including single nucleotide polymorphisms (SNPs) in genes encoding endothelial nitric oxide synthase (NOS3), ion channel subunits (KCNJ11, CACNA1C), inflammatory and angiogenic mediators (JAK2, VEGFA, HMOX1). In addition, the antioxidant system plays an important role in the pathogenesis of coronary microcirculatory dysfunction, which is involved in maintaining vascular homeostasis and protecting against oxidative stress. The main studied genes of the antioxidant system include SOD1–3, GPX1, CAT, HMOX1 and NOX2/NOX4, which provide a balance of production and utilization of reactive oxygen species and play a significant role in the pathophysiology of the vascular wall. Of particular interest are microRNAs that regulate the expression of genes involved in vascular reactivity, angiogenesis, oxidative stress, and inflammation. Dysregulation of microRNAs such as miR-126, miR-155, and miR-30 has been associated with endothelial dysfunction and capillary remodeling. This review explores key signaling pathways and molecular mechanisms underlying CMD, with a focus on their genetic and epigenetic modulation. A better understanding of these processes opens new perspectives for the development of personalized diagnostic and therapeutic approaches in microvascular forms of ischemic heart disease.

Highlights      

• Sorbs2 is an adaptor and cytoskeletal protein predominantly expressed in the cardiovascular system-specifically in cardiomyocytes, vascular smooth muscle cells, and endothelial cells. It plays a critical role in maintaining myocardial structural integrity, regulating contractility, and facilitating intercellular communication. In addition, Sorbs2 functions as an RNA-binding protein, influencing the stability and translation of mRNAs that encode essential ion channels and junctional proteins.
• Sorbs2 dysfunction is associated with a wide range of cardiovascular diseases, from cardiomyopathies and arrhythmias to dyslipidemia, hypertension, and diabetic angiopathy. Sorbs2 expression varies depending on the type of pathology and disease stage. For example, in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, Sorbs2 levels are decreased, correlating with the severity of fibrosis, disruption of intercalated disc structure, and reduced ejection fraction. In pressure overload conditions (aortic constriction model), a compensatory increase in Sorbs2 expression has been observed during myocardial hypertrophy. Conversely, in diabetic vasculopathy, Sorbs2 expression in coronary arteries is reduced, which is linked to impaired BK-channel activity and decreased coronary perfusion.
• Given its multifunctionality and involvement in key processes underlying cardiovascular pathology, Sorbs2 is emerging as a promising molecular target. Its role in regulating inflammation, ion homeostasis, and myocardial structure suggests that Sorbs2 could serve as both a biomarker and a therapeutic target in cardiovascular diseases. However, further experimental and clinical studies are required to validate its diagnostic value and explore its full therapeutic potential.

Abstract

Sorbin and SH3 domain-containing protein 2 (Sorbs2) is a multifunctional adaptor protein that plays a key role in regulating cellular architecture, signal transduction, and gene expression in the cardiovascular system. Sorbs2 is highly expressed in cardiomyocytes, vascular smooth muscle cells, and endothelial cells, contributing to both the mechanical stability and electrical excitability of cardiac tissue. Recent studies have demonstrated that Sorbs2 is involved in the pathogenesis of a wide range of cardiovascular diseases, including dyslipidemia, atherosclerosis, hypertension, cardiomyopathies, arrhythmias, atrial fibrillation, congenital heart defects, diabetic vasculopathy, and aortic aneurysms. Beyond its structural role as part of the cytoskeleton, Sorbs2 functions as an RNA-binding protein that regulates the stability and translation of mRNAs encoding proteins of ion channels and intercellular junctions, which are essential for cardiac conduction.. Dysregulation of Sorbs2 has been associated with myocardial fibrosis, atrial remodeling, and impaired cardiac contractility. Notably, the data on its role in inflammation are contradictory, highlighting the need for further investigation. This review summarizes current knowledge on the molecular biology of Sorbs2, its regulatory mechanisms, and its pathophysiological relevance in the context of cardiovascular diseases. The potential of Sorbs2 as a diagnostic biomarker and therapeutic target is discussed. A deeper understanding of Sorbs2 may open new avenues for personalized medicine and targeted treatment strategies in cardiovascular pathology.

Highlights

• Artificial intelligence is transforming cardiology by enabling more accurate diagnosis, personalized therapy, and prediction of cardiovascular complications.
• The study provides a comprehensive systematization of current approaches to machine learning, neural networks, and big data analytics in clinical cardiology.
• Key directions for integrating AI into Russian healthcare are highlighted, considering ethical, legal, and organizational aspects.

Abstract

Modern cardiology is undergoing a rapid digital transformation driven by artificial intelligence (AI). The application of machine learning and deep learning algorithms provides unprecedented opportunities for diagnosis, monitoring, and prediction of cardiovascular diseases (CVDs). This review summarizes current evidence on the integration of AI across key domains of cardiovascular care–from data acquisition and analysis to personalized treatment optimization. The article highlights successful applications of AI in electrocardiogram interpretation, cardiovascular imaging, hemodynamic assessment, and prediction of heart failure exacerbations. Particular attention is paid to ethical, legal, and organizational aspects of AI implementation, including transparency, data security, and clinical accountability. International and national frameworks, such as the EU Artificial Intelligence Act, GDPR, and Russian federal regulations, are discussed as foundations for safe and equitable adoption of AI in healthcare. The review also outlines the Russian Federation’s initiatives in digital health transformation, including the development of domestic diagnostic algorithms and unified medical data repositories. Future perspectives include the use of quantum computing, emotional AI, and integration of digital competencies into medical education. Artificial intelligence is viewed as a transformative tool to enhance diagnostic accuracy, treatment efficiency, and preventive strategies in cardiology, provided that human oversight and clinical validation remain central.