Nikolay Stoynev

Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder influenced not only by environmental exposure but also by genetic susceptibility Recent advances in molecular genetics have enabled the identification of many candidate genes and genome-wide associations contributing to COPD development and its systemic manifestations. Cachexia in COPD is a syndrome that is associated with increased protein catabolism, severe weight loss, and reduction of muscle and adipose mass. The imbalance between protein synthesis and degradation, impaired skeletal muscle regeneration, and inflammatory activation are central mechanisms in its pathogenesis. The loss of muscle mass can be affected by mechanisms that participate in the balance between protein synthesis and protein breakdown. Thus, the impaired ability to regenerate skeletal muscle mass might contribute to the reduction of muscle mass in COPD and cachexia. Cachexia in these patients drastically increases treatment cost. Several genetic factors have demonstrated a significant association with both COPD and cachexia. Subjects with alpha- 1-antitrypsin deficiency (SERPINA1) are at increased risk of developing both conditions. Early candidate gene studies have implicated ACE, bradykinin receptor, vitamin D receptor, secretory phospholipase A2, and inflammatory cytokines (IL-1 /3, IL-6, TNF) in muscle loss and systemic inflammation. More recent GWAS and transcriptomic analyses have identified associations with EFNA2, BAIAP2, FTO, NEB, TPM1, and TPM2, highlighting molecular pathways involved in muscle remodeling, regeneration, and hypoxia response. The aim of this review is to summarize current evidence on the genetic factors contributing to cachexia in COPD, integrating findings from candidate gene studies and genome-wide analyses, and to discuss their potential biological and clinical implications.

The aim of this study was to evaluate ambulatory blood pressure characteristics in subjects with prediabetes who have not been treated with antihypertensive drugs. The assessment was not only targeting undiagnosed hypertension but also the “white-coat” hypertension (WCH), masked hypertension (MaskH) and abnormal circadian blood pressure patterns (non-dippers, extreme dippers). One hundred and twenty subjects (56 males, 64 females), of mean age 44.72 ± 12.49 years, were included in the study. After evaluation of glucose tolerance the participants were divided into two groups: Group 1 – subjects with prediabetes; and Group 2 (Control group) – subjects with normal glucose tolerance (NormGT). All participants were without previously diagnosed hypertension and had never received any antihypertensive drug. Standard anthropometric parameters – weight, height and waist circumference, were measured in all subjects. Blood pressure was measured by ambulatory blood pressure monitoring. No significant differences in the anthropometric parameters have been observed. The ambulatory blood pressure monitoring identified higher prevalence of undiagnosed hypertension among the subjects with prediabetes (52.17% vs 43.24% in the control group). The prevalence of masked hypertension was lower among the subjects with prediabetes (13.33%), compared to NormGT (28.88%). For WCH the prevalence in prediabetes (27.27%) was slightly lower than in the control group (34.48%). The analysis of the circadian pattern of ambulatory blood pressure demonstrated higher prevalence of “non-dippers” in the group with prediabetes (36.96% vs 28.38%), while the prevalence of “extreme dippers” was close to that of the control group (8.69% vs 9.46%). The high prevalence of undiagnosed hypertension among subjects with prediabetes suggests that ambulatory blood pressure monitoring could be used on a regular basis in the evaluation of subjects with prediabetes considered normotensive. The method could also be important to identify “non-dippers” as the prevalence of this pattern tends to be higher in prediabetes.

Background/Objectives: Autism spectrum disorder (ASD) has a wide-ranging impact on individuals’ quality of life and development, and there is a critical need for greater awareness, early intervention, and comprehensive support strategies to effectively address the unique needs of those affected by ASD. Recent studies highlight the gut microbiome’s potential role in modulating ASD symptoms via the gut–brain axis, but specific microbial biomarkers remain unclear. This study aims to investigate differences in gut microbiota composition between ASD patients and neurotypical controls in a novel approach, specifically assessing ratios of Firmicutes/Bacteroidetes (F/B), Actinobacteria/Proteobacteria (A/P), and Prevotella/Bacteroides (P/B) as potential biomarkers. Methods: We analyzed gut microbiome samples from 302 Bulgarian children and adolescents diagnosed with ASD (aged 2–19 years). Microbial ratios (F/B, A/P, and P/B) were calculated and compared against previously reported reference meta-analytic means from European neurotypical populations. The statistical significance of deviations was assessed using parametric (t-tests), non-parametric (Wilcoxon signed-rank tests), and proportion-based (binomial tests) methods. Effect sizes were quantified using Cohen’s d. Significant differences between ASD cases and neurotypical reference values were observed across several age groups. Results: Notably, children with ASD demonstrated significantly lower F/B and A/P ratios, with the youngest cohort (0–4 years) exhibiting the greatest differences. Deviations in the P/B ratio varied across age groups, with a significant elevation in the oldest group (≥10 years). Collectively, ASD cases consistently exhibited microbiota profiles indicative of dysbiosis. Conclusions: Our findings support gut microbiome dysbiosis as a potential biomarker for ASD, highlighting significantly altered bacterial ratios compared to neurotypical controls. These microbiome shifts could reflect early-life disruptions influencing neurodevelopment. Future studies should adopt longitudinal and mechanistic approaches to elucidate causal relationships and evaluate therapeutic microbiome modulation strategies.

Aim: To evaluate the expression of atherosclerosis-associated genes in peripheral blood of drug-naïve hypertensive subjects with newly-diagnosed type 2 diabetes mellitus. Materials and methods: Eighteen subjects (15 males, 3 females), mean age 46.27 ± 12.07 years, divided into two groups: studied group - subjects with newly-diagnosed hypertension and newly-diagnosed type 2 diabetes (n = 9), control group – normotensive individuals with newly-diagnosed type 2 diabetes (n = 9) Gene expression analysis was performed with Human Atherosclerosis RT2 Profiler PCR Array. Results: In gene expression analysis, 5 genes with increased expression in the studied group were found – CD44, ITGA5, ITGB2, PPARA and RXRA. No genes with decreased expression matching the criteria were found. Conclusion: The presence of arterial hypertension in subjects with newly diagnosed type 2 diabetes tends to increase the expression of CD44, ITGA5, ITGB2, PPARA and RXRA in the peripheral blood.

The perception of „stress” triggers many physiological and behavioral responses, collectively called the stress response. Such a complex process allows for coping with stress and also triggers severe pathology. Because of the multidirectional effect of stress on the body, multiple systems participate in its pathogenesis, with the endogenous cannabinoid and the serotoninergic ones among them. These two systems also take part in the pain perception decrease, known as stress-induced analgesia (SIA), which can then be taken as an indirect indicator of the stress response. The aim of our study was to study the changes in cold SIA (c-SIA) resulting from the exogenous activation of cannabinoid receptor type 1 (CB1) and 5-hydroxytryptamine (5-HT, serotonin) receptor type 1_A (5-HT1A). Various combinations of agonists and/or antagonists of CB1 and 5-HT1A, before or after 1 h of cold exposure, were applied, since we presumed that the exogenous activation of the receptors before the cold exposure would influence the pathogenesis of the stress response, while their activation after the stressful trigger would influence the later development. Our results show that the serotonergic system “maintained” c-SIA in the pre-stress treatment, while the cannabinoids’ modulative effect was more prominent in the post-stress treatment. Here, we show the interactions of the two systems in the stress response. The interpretation and understanding of the mechanisms of interaction between CB1 and 5-HT1A may provide information for the prevention and control of adverse stress effects, as well as suggest interesting directions for the development of targeted interventions for the control of specific body responses.