Yavor Assyov

Background/Objectives: DEFA3 and DEFA5 are alpha-defensins, which are small cationic antimicrobial peptides that are part of the innate immune system. DEFA3 encodes human neutrophil peptide-3 (HNP-3), primarily expressed in neutrophils, while DEFA5 encodes human defensin-5 (HD-5), predominantly expressed in Paneth cells of the small intestine. Both defensins show elevated levels in diabetes and are strongly associated with diabetic nephropathy, with the highest concentrations found in patients with this complication. We evaluated serum levels of DEFA3 and DEFA5 in 160 participants (93 patients with T2DM and 67 controls without carbohydrate disturbances) and their associations with diabetic nephropathy, as well as peripheral and cardiac autonomic neuropathy and anthropometric and metabolic parameters. Methods: This was a monocentric, cross-sectional, observational study conducted at the Endocrinology and Metabolic Disorders Clinic of Alexandrovska Hospital in Sofia. Main methods included detailed clinical and anthropometric assessments, diagnosis of peripheral neuropathy via the Neuropathy Disability Score (NDS), evaluation of cardiac autonomic neuropathy using heart rate variability analysis and Ewing cardiovascular reflex tests, comprehensive laboratory investigations with fasting blood samples, and measurement of serum DEFA3 and DEFA5 levels by ELISA kits. Results: Serum DEFA3 and DEFA5 levels did not differ significantly between patients with T2DM and controls without carbohydrate disturbances, nor by sex or menopausal status. Patients with diabetic nephropathy showed significantly higher levels of both DEFA3 (345.7 ± 77.9 pg/mL vs. 299.2 ± 100.3 pg/mL; p = 0.042) and DEFA5 (5.3 ± 10.1 pg/mL vs. 2.9 ± 2.9 pg/mL; p = 0.044). DEFA5 levels were also elevated in participants with increased albumin-to-creatinine ratio (4.9 ± 9.9 pg/mL vs. 2.2 ± 1.5 pg/mL; p = 0.043). No significant differences were observed in patients with peripheral neuropathy, cardiac autonomic neuropathy, retinopathy, or macroangiopathy, although a non-significant trend toward higher values was noted. DEFA3 demonstrated moderate discriminatory ability for diabetic nephropathy (AUC = 0.641; p = 0.037), superior to DEFA5 (AUC = 0.570; p = 0.303). DEFA3 showed multiple weak positive correlations with diabetes duration, body weight, BMI, total and LDL-cholesterol, serum creatinine, and uric acid, while DEFA5 correlated only with total cholesterol. Conclusions: Circulating DEFA3 and DEFA5 are associated with diabetic nephropathy and selected metabolic and renal parameters in patients with type 2 diabetes, with DEFA3 showing moderate discriminatory capacity. The associations were largely attenuated after covariate adjustment, suggesting that these alpha-defensins likely reflect downstream innate immune activation and renal stress rather than acting as independent drivers of complications.

Purpose of Review: Obesity is a growing global health challenge, with severe obesity projected to affect up to 25% of individuals with obesity by 2030. Bariatric surgery remains the most effective treatment, yet the molecular mechanisms underlying its metabolic benefits are not fully understood. This review summarizes current evidence on the role of microRNAs in bariatric/metabolic surgery and evaluates their potential as biomarkers and therapeutic targets. Recent Findings: Bariatric surgery induces significant alterations in circulating and tissue-specific miRNA profiles, particularly those involved in glucose metabolism, inflammation, and adipose tissue remodeling. Among the most frequently reported candidates, miR-122, miR-221, miR-27a, miR-126, miR-144, miR-222, miR-223, miR-375, miR-92a, and miR-155 have been associated with weight loss, improved insulin sensitivity, and diabetes remission. Emerging data suggest that these miRNAs may act not only as biomarkers of metabolic recovery but also as regulators of insulin signaling, inflammatory pathways, and adipocyte function. Summary: Current evidence supports a role for miRNAs in the metabolic adaptations observed after bariatric surgery. Although further validation is required, miRNAs show promise as minimally invasive biomarkers for predicting and monitoring treatment response and may provide insight into the molecular mechanisms underlying obesity remission and improvement of obesity-related comorbidities.

Background/Objectives: Diabetic neuropathy (DN) is one of the most common complications of type 2 diabetes mellitus (T2DM), involving complex metabolic, vascular, and epigenetic mechanisms. MicroRNA-210-3p (miR-210-3p), a hypoxia-responsive molecule, has been implicated in various diabetic complications, but its role in DN is not well defined. This study aimed to investigate the relationship between miR-210-3p expression, measured as delta Ct (ΔCt), and the presence and type of diabetic neuropathy, as well as correlations with corneal nerve parameters assessed by corneal confocal microscopy (CCM). Methods: Eighty patients with T2DM were stratified into four groups: no neuropathy, autonomic neuropathy, peripheral neuropathy, and combined neuropathy. Expression of miR-210-3p was quantified using RT-qPCR, and CCM was used to measure corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Results: ΔCt values were significantly lower in patients with combined neuropathy compared to those without neuropathy, indicating higher miR-210-3p expression. Intermediate values were observed in autonomic and peripheral neuropathy groups. CCM parameters were significantly reduced in patients with DN. ΔCt was inversely correlated with neuropathy severity but positively associated with diabetes duration. Conclusions: These findings suggest that miR-210-3p may serve as a biomarker of nerve damage and cellular stress in diabetes, and that combining gene expression profiling with CCM could improve DN diagnosis and monitoring.

Background/Objectives: Metabolic syndrome (MetS) is a complex, multifaceted disorder with significant socioeconomic and public health consequences, increasingly acknowledged as a global epidemic. Fibroblast growth factor 21 (FGF-21) is known to play a vital role in metabolic regulation; however, the precise roles and interactions of free fatty acids (FFAs) and insulin in influencing FGF-21 activity under both normal and pathological conditions are not yet fully understood. Meteorin-like protein (Metrnl) is a newly identified adipokine that appears to have the potential to regulate metabolic inflammation, which is a critical pathological factor in obesity and insulin resistance. Additionally, nesfatin-1, which is widely expressed in both central and peripheral tissues, is thought to be involved in various physiological functions beyond appetite control, such as glucose homeostasis, stress response, and cardiovascular health. Recent studies have indicated that sortilin may play a role in the pathophysiology of several metabolic disorders, including type 2 diabetes mellitus. Methods: This investigation was a cross-sectional study involving 200 individuals with obesity, which included both metabolically healthy obese participants and those experiencing obesity along with glycemic disorders. Serum levels of FGF-21, sortilin, Metrnl, and nesfatin-1 were measured using standardized enzyme-linked immunosorbent assay (ELISA) techniques. Results: The results indicated that FGF-21 levels were significantly elevated in patients with metabolic syndrome (p < 0.001), as well as those with insulin resistance (p = 0.009) and dyslipidemia (p = 0.03). Serum Metrnl levels were notably elevated in individuals meeting the criteria for insulin resistance, with a statistical significance of p < 0.001. Additionally, patients experiencing carbohydrate metabolism disorders exhibited significantly higher serum sortilin levels compared to those with normal blood glucose levels, with a p-value of 0.003. Conclusions: This research highlights FGF-21, Metrnl, nesfatin-1, and sortilin as potential biomarkers involved in the development of critical aspects of metabolic syndrome.

Background: Podocalyxin is expressed not only in glomerular podocytes but also on the endothelial cell surface outside the kidney. The aim of this cross-sectional study is to evaluate the role of serum podocalyxin as an early marker for vascular injury in patients with obesity and carbohydrate disturbances. Subjects and methods: The study group consisted of 163 patients with a mean age of 52.5 ± 11.3 years. Results: Levels of podocalyxin were significantly higher in healthy controls compared to patients with obesity, prediabetes, and newly diagnosed diabetes. Correlation analysis revealed that podocalyxin correlates negatively with BMI, waist circumference, waist-to-hip ratio, waist to stature ratio, fasting insulin, and one hour after the oral glucose tolerance test. ROC analyses determined that circulating podocalyxin levels are valuable for differentiating subjects with prediabetes and obesity. Conclusion: This study is the first to assess the role of podocalyxin in the entire spectrum of metabolic disorders.

Background: The prevalence of sarcopenic obesity among adults aged ≥65 years is increasing worldwide. It is a condition that describes the concomitant presence of sarcopenia and obesity, but it appears to be associated with greater increases in the risks for disability, morbidity, and mortality than the two conditions combined. The current review aims to summarize the available literature data on the effectiveness of lifestyle modification for the management of this high-risk geriatric syndrome. Methods: We conducted a comprehensive search across multiple databases, including PubMed, Scopus, Web of Science, and Cochrane Library, for publications published from January 1950 to June 2024. Results: The detection of early preventive and therapeutic approaches to combat sarcopenic obesity is essential for healthy aging. There is ample evidence that suggests that poor dietary habits and physical inactivity are the main reasons for the development of sarcopenic obesity and should thus be the main targets for intervention. In the absence of effective pharmacological interventions, the best effect on sarcopenic obesity is achieved by combination with proper dietary intervention and regular physical activity according to the individual’s health condition. Conclusions. Further research is needed to discover the most effective strategy for the prevention and treatment of sarcopenic obesity, as well as potential pharmacological options to improve muscle mass and function in older populations with physical restrictions.

This review elucidates the role of dietary factors in influencing myokine secretion, complementing the recognized benefits of physical activity on metabolic health. While exercise is known to positively modulate myokines, contributing to their health-promoting effects, an exploration into how diet affects these critical cytokines remains sparse. Through analysis of the literature, this work identifies dietary patterns that markedly affect myokine levels, underscoring the complex relationship between nutrition and myokine activity. The investigation reveals that specific dietary approaches can profoundly alter myokine secretion, suggesting an essential avenue for combined dietary and exercise interventions to optimize health outcomes. These insights highlight the need for further detailed study into diet-induced myokine modulation.

This review explores the intricate relationship between interleukin-6 (IL-6) and sarcopenia, a prevalent condition characterized by progressive skeletal muscle loss, particularly in aging populations. Emphasizing the rising prevalence and health challenges posed by sarcopenia, the paper delves into the multifunctional roles of IL-6 in immune response, inflammation and inflammaging associated with sarcopenia. Significantly elevated in sarcopenic individuals, IL-6 prompts an exploration of its molecular impact on muscle wasting. The review critically assesses IL-6 as a potential biomarker for sarcopenia diagnosis and prognosis while also examining therapeutic interventions targeting IL-6 signaling pathways, offering a foundation for future research and the development of targeted therapeutic strategies to alleviate the impact of this debilitating condition.