To assay new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we carried out a descriptive cross-sectional study. We recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C); among them, 22 presented MVC. Peripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO), nitrite levels in plasma (NOx). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to the CG. The DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased expression of miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive values for vascular complications presence: (1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484 (Exp(B) = 0.926, chi² = 34.093, p < 0.001; AUC = 0.913). (2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484 (Exp(B) = 0.958, Chi² = 33.863, p < 0.001; AUC = 0.938). Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values (Exp(B) = 0.528, p = 0.024, Chi² = 28.214, AUC = 0.904) than classical variables (Exp(B) 0.462, p = 0.007, Chi² = 18.814, AUC = 0.850). miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.

To evaluate new circulating markers related to macrovascular complications (MVC) in type 2 diabetes mellitus (T2DM), we recruited 30 controls (CG), 34 patients with T2DM (DG), and 28 patients with T2DM and vascular complications (DG+C), among them, 22 presented MVC. Pe-ripheral blood was used to determine redox status (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; glucose-6-phosphate dehydrogenase, G6PD) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid pe-roxidation, LPO). Inflammatory markers (IL-1β, IL-6, IL-10, IL-18, MCP-1, TNF-α) and the relative expression of c-miRNAs were analyzed. The real-time PCR results showed that the expressions of miR-155-5p, miR-21-5p, miR-146a-3p, and miR-210-3p were significantly higher in the DG group compared to CG. DG+C group presented statistically relevant differences with CG for four miRs: the increased expression of miR-484-5p, miR-21-5p, and miR-210-3p, and decreased for miR-126a-3p. Moreover, miR-126a-3p was significantly less expressed in DG+C compared to DG. The application of binary logistic regression analysis and construction of receiving operator characteristic curves (ROC) revealed two models with high predictive value for vascular complications presence: 1) HbAc1, creatinine, total cholesterol (TC), LPO, GPx, SOD, miR-126, miR-484. 2) HbAc1, creatinine, TC, IL-6, LPO, miR-126, miR-484. Moreover, our data demonstrated that gender, TC, GPx, CAT, and miR-484 were associated with MVC and exhibited higher predictive values than classical variables. miR-126, miR-484, IL-6, SOD, CAT, and GPx participate in vascular damage development in the studied diabetic population and should be considered for future studies.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to its high prevalence and association with chronic complications, highlighting the need for reliable predictive tools to support clinical decision-making. Methods: This study proposes a two-stage hierarchical prediction system based on a Random Forest (RF) classifier. In Stage 1, the model performs multiclass classification into healthy (H), T2DM without complications (D), and T2DM with complications (C). In Stage 2, patients classified as C are further stratified into microvascular or macrovascular complications. The dataset included 31 biochemical, molecular, inflammatory, and oxidative stress variables from Mexican and Spanish cohorts. Feature selection was performed using Pearson correlation, and feature relevance was further assessed using RF importance measures. Model training used stratified cross-validation, with additional evaluation on a hold-out set to approximate real-world performance. Results: The optimized RF achieved an accuracy of 92% and a macro F1-score of 0.92, outperforming baseline models, with an AUC-ROC of 0.89 for complication prediction. Key predictive features included IL-18, miR-126, duration of T2DM, HbA1c, and IL-10. Conclusions: The novelty of this study lies in integrating heterogeneous biomarkers within a hierarchical predictive framework, rather than in the machine learning algorithm itself. This multimodal approach, combined with interpretable machine learning techniques, is designed to deliver clinically meaningful insights for patient stratification and personalized management in T2DM.

The physiological condition of young-of-the-year mirror carp (Cyprinus carpio) reared under pond aquaculture conditions and infected with myxosporeans was investigated. The study aimed to assess the effects of myxosporean infection on the physiological and hematological parameters of cyprinid fishe. Infected individuals exhibited pronounced clinical signs of the disease, frequently accompanied by mortality. Hematological analysis revealed high levels of monocytes, neutrophils (32.68%), and white blood cells (257.6× 10⁹/L) compared to the norm. Elevated differential leukocyte counts indicate an increased defense reaction of the organism under conditions of parasitic invasion. Histological examination of gills, heart, intestine, hepatopancreas and musculature revealed the presence of intracellular, interstitial, and diffuse localization of parasitic mucous spores (Myxozoa: Myxosporea: Myxobolidea). Necrosis, desquamation, hyperplasia and a dramatic increase of mast cells in the gills of the studied fish are due to both small intracellular plasmodia and spores located inside tissue cysts. The increase in the number of mast cells in the gills of fish in localization of mucous parasites is associated with the need to maintain homeostasis of the immune system. The pathological effect of myxosporean plasmodia on organs of the digestive tract were established, causing necrosis, disruption of cell absorption and transport processes, as well as reduction of the height of prismatic epithelial cells with degeneration of microvilli on their apical surface. Intracellular parasitism of uninucleate and binucleate mucous myxosporeans were also observed in the cells of the hepatopancreas and heart. Necrotic foci located on the skin of the fish were a manifestation of the inflammatory process and hemorrhages in the muscles due to parasitic invasion.

The process of cell damage resulting from the action of free radicals – reactive oxygen species (ROS) – is called oxidative stress. Most ROS are constantly formed in the cell – about 5 % of the oxygen consumed by tissues is converted into free radicals, but their level is normally so small that the cell inactivates them with the help of an antioxidant system. Different organs and tissues are exposed to different degrees of ROS and demonstrate different stability during the implementation of oxidative stress. The mechanisms of ROS formation by mitochondria under oxidative stress are still unclear. At the same time, it was found that mitochondrial dysfunction and the accumulation of mitochondrial mutations in tissues make a significant contribution to the aging process, as well as to the pathogenesis of a number of diseases characterized by neurodegeneration. Mutations lead to increased generation of free radicals, reduced ATP levels, and energy failure of cells. Coenzyme Q10 is a component of the mitochondrial respiratory chain. Violation of the biosynthesis of coenzyme Q10 can lead to a number of mitochondrial diseases. When coenzyme Q10 is deficient, sulfide metabolism plays a critical role. Sulfide metabolism in mammalian cells includes trans-sulfuration (biosynthetic) and hydrogen sulfide oxidation (H2S) (catabolic). Violation of H2S oxidation may contribute to oxidative stress in coenzyme Q deficiency or may play a synergistic role with oxidative stress in the pathogenesis of tissue specificity in coenzyme Q deficiency.