Olga A. Gerasimova

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, necessitating a deeper understanding of its molecular mechanisms. Extracellular vesicles (EVs) – exosomes, microvesicles, and apoptotic bodies and less-studied subtypes – have emerged as key intercellular communication mediators in cardiovascular diseases. These nanosized particles carry bioactive molecules such as proteins, lipids, and nucleic acids, influencing processes including cardiac remodeling, inflammation, fibrosis, and angiogenesis. EVs derived from cardiomyocytes, endothelial cells, fibroblasts, and immune cells contribute to HF progression by modulating pathological signaling pathways. For instance, cardiomyocyte-derived EVs may propagate hypertrophy and apoptosis, while fibroblast-derived EVs promote extracellular matrix deposition, leading myocardial stiffness. Conversely, certain EV subpopulations exhibit cardioprotective effects, underscoring their dual role in HF pathogenesis. This review summarizes current knowledge on EV biogenesis, composition, and function in HF, highlighting their diagnostic and therapeutic potential. We discuss emerging evidence from preclinical and clinical studies, focusing on EV-based biomarkers for early diagnosis and prognosis of HF. Furthermore, we explore therapeutic applications of engineered EVs for targeted drug delivery. Despite considerable advances, unresolved issues such as EV heterogeneity, a lack of standardization isolation methods, and difficulties in applying the results in practice. Addressing these challenges is crucial for unlocking novel strategies for HF management. Integration of fundamental and clinical findings was used to analyze the role of EVs in HF and to evaluate their potential for novel diagnostic and therapeutic applications.

MicroRNA-26a (miRNA-26a) is a critical regulator of molecular processes, impacting the pathogenesis of numerous diseases due to its ability to modulate gene expression across various organ systems and tissues. This review examines the mechanisms of miRNA-26a action and its therapeutic potential, with a particular focus on its role in heart failure (HF). In HF, miRNA-26a exerts cardioprotective effects, suppressing cardiomyocyte hypertrophy, fibrosis, and electrical remodeling by targeting GATA4, CTGF, and KCNJ2. Reduced miRNA-26a expression correlates with HF progression, underscoring its role as a biomarker and therapeutic target. Interactions with other microRNAs, such as miR-1 and miR-133, amplify its effects. Beyond cardiology, miRNA-26a modulates oncological processes, e.g., inhibiting proliferation in colorectal cancer, inflammation in inflammatory bowel disease, and metabolic and neurodegenerative disorders by targeting EZH2, PTEN, and VEGF. Preclinical studies highlight the promise of miRNA-26a-mimics for HF treatment, though challenges in delivery and dosing warrant further exploration. This review article, with an emphasis on cardiovascular pathology, acknowledges the high prevalence and critical significance of HF in morbidity and mortality, advocating for research into combined strategies with other miRNAs. Overall, miRNA-26a holds significant potential for personalized medicine, offering improved outcomes for patients with HF and other related pathologies.

Both apoptotic and inflammatory caspases play a significant role in developing and maintaining an organism’s homeostasis. Recently, various studies have described various cross-interactions among various caspases. For instance, interleukin-1β activation is initiated by caspase-1 and caspase-8. Programmed cell death is launched not exclusively by internal and external factors to serve as a foundation for physiological development and realization of cellular and organism functions. The caspases involved in this process provide a complicated function related to cell homeostasis regulation. Caspases also participate in adaptation processes associated with changing environmental conditions, including microgravity. Phenotypical analysis of knockdown laboratory animals can reveal the physiological functions of caspases, giving preference to mice. For instance, this approach allows us to determine the role of caspases in the pathogenesis of different pathologic conditions, such as malignancies and autoimmune and infectious diseases. Caspases are considered by a wide spectrum of authors as therapeutic targets. In general, the topic of caspases and their functions is very broad. In this review, we only discuss some aspects of the impact of caspases on various types of cell death.

Introduction: The human body is exposed to numerous chemical and biological environmental factors. Post-exposure allergic reactions are becoming increasingly common. Interacting substances enhance each other’s health effects and aggravate allergy symptoms. Registration of a high pollen count resulting from a gradual increase in ambient temperatures leads to disappointing forecasts of a high prevalence of allergic rhinitis (hay fever). Evaluation of public health monitoring data on drinking water and food quality has revealed the significance of such pollutants as nitrates and nitrites. The interaction between pollen and nitrates has not been studied although it is of interest in terms of potential health effects of combined exposures. Objectives: To evaluate morphological changes in the quantitative composition of mast cells using an aqueous solution of molecular hydrogen in an experimental model of hay fever aggravated by exposure to chemical agents. Methods: Male Wistar rats were selected for experimental modeling of allergic rhinitis and 34 groups of six animals each were exposed to pollen and chemical agents during 55 days. To assess morphological changes in the nasal respiratory mucosa, we stained tissues with Giemsa solution and also applied a combined staining technique (Patent No. 2781558 dated October 13, 2022). Study limitations: Groups for comparison of methods of administration of the aqueous solution of molecular hydrogen against the saline solution were not included. Results: The cell morphology analysis revealed quantitative and qualitative changes in the animal groups with single and combined exposure to pollen and chemical agents and confirmed the therapeutic and prophylactic effect of the aqueous solution enriched with molecular hydrogen. Conclusion: The combined exposure to pollen allergens and nitrates and/or nitrites induces significant mast cell activation compared to control and single exposure groups. Therapeutic and preventive effects of molecular hydrogen down-regulate mast cell degranulation.

Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male Wistar rats were subcutaneously injected with a water–alcohol solution of monocrotaline or a control with an only water–alcohol solution. One group of monocrotaline-injected animals was placed in a plastic box that was constantly ventilated with atmospheric air containing 4% of molecular hydrogen, and the two groups of rats, injected with monocrotaline or vehicle, were placed in boxes ventilated with atmospheric air. After 21 days, hemodynamic parameters were measured under urethane narcosis. The results showed that, although hydrogen inhalation had no effect on the main markers of pulmonary hypertension induced by monocrotaline injection, there was a reduction in systemic blood pressure due to its systolic component, and a decrease in TGF-β expression, as well as a reduction in tryptase-containing mast cells.

High frequency of detection of various disorders of the gastrointestinal tract in patients with autism spectrum disorders (ASD) formed the basis of the first attempts to prescribe diet therapy. Despite the fact that diets are not officially included in the complex of therapeutic measures for ASD, the use of gluten-free (GFD) and casein-free diets (CFD) is widespread practice. The aim of the study was to assess the level of gliadomorphins (GM) and casomorphins (CM) in the blood of children with ASD, depending on the eating style and in comparison with healthy peers. Materials and methods of research: a prospective continuous open controlled study with the participation of 230 children aged 3–15 years. The first group included 36 patients with ASD who had been observing GFD for more than 6 months; in addition, 18 children were also on CFD. Boys in the group ware 23 (64%), girls – 13 (36%). The second group included 49 children with ASD who had no dietary restrictions. Boys – 35 (71%), girls – 14 (29%). The third (control) group consisted of 145 apparently healthy children: boys – 83 (57.3%), girls – 62 (42.7%). Determination of CM and GM levels was performed on a Multiskan Go analyzer (Thermo Fisher Scientific, Finland) by enzyme-linked immunosorbent assay using Human Gliadomorphin ELISA Kit and Human Casomorphin ELISA Kit (Hycult Biotech, Netherlands). Results: more boys than girls were included in all study groups; no statistically significant differences in gender distribution were found (p=0.2). The median age values in the 1st group was 6.5 [4.0; 8.0] (3; 15) years, in the 2nd – 6.0 [4.0; 7.0] (3; 15) years, in the 3rd – 8.0 [6.0; 11.0] (3; 15) years, the differences are statistically significant (p=0.0001). The content of GM in the blood serum of children with ASD, adhering to GFD, is statistically significantly lower by 2.6 times compared with children not adhering to diet therapy – 0.61 [0.41; 0.80] (0.12; 6.42) and 1.6 [0.70; 2.38] (0.18; 4.03) ng/ml (p0.005). The content of CM in the blood serum of children with ASD, adhering to CFD and GFD, is also 1.25 times lower than in children not adhering to diet therapy 1.85 [1.04; 2.07] (0.16; 3.83) and 2.34 [2.11; 2.72] (0.93; 3.29) pg/ml (p<0.001) and 1.3 times lower than the level of the control group – 2.45 [2.13; 2.89] (1.22; 26.88) pg/ml (p<0.001). Conclusion: the results obtained confirm the theory/possibility of exorphin intoxication of ASD development, which may be pathogenetically significant for some patients with ASD, which must be taken into account when implementing an individual approach to prescribing GFD, CFD.