Delyana Davcheva

Aim : Over the past decade, nanomedicine has made significant progress in the development of inorganic nanoparticle (iNP)-based drug delivery systems (DDSs). The aim of this narrative review is to summarize the most recent developments in iNP systems, emphasize their advantages as DDSs, and provide detailed commentary on their impact on human health. A systematic search was performed in the PubMed, Scopus, and Web of Science databases for peer-reviewed original research and review articles published between 2020 and 2025. Relevant scientific data on innovative applications of iNPs in cancer therapy were reviewed. The enormous potential of magnetic nanoparticles (NPs), metal–organic frameworks (MOFs), and iNPs used as carriers of small interfering RNAs (siRNAs) as innovative strategies for enhancing antitumor treatment is highlighted. Conclusion : Continuous progress in research strategies for synthesizing iNPs with optimal properties while minimizing adverse effects on living cells is a prerequisite for even greater translational potential of iNP-based DDSs.

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic disturbances, including insulin resistance and obesity, chronic anovulation and impaired fertility. Its pathogenesis is complex and multifactorial, involving interrelated mechanisms such as impaired insulin action and compensatory hyperinsulinemia, neuroendocrine dysregulation, altered ovarian steroidogenesis and increased adrenal androgen production. Spexin and phoenixin are novel peptides, primarily produced in the hypothalamus, implicated in the regulation of energy homeostasis and reproductive function, but their role in PCOS remains insufficiently clarified. The Perceived Stress Scale (PSS) is a validated psychological instrument used to assess subjective stress perception, which is often elevated in women with PCOS and reflects the psychosocial burden associated with the condition. The aim of the study is to investigate serum spexin levels in women with and without PCOS, the association of the novel neuropeptide with body mass index (BMI), perceived stress and the potential interrelationship between spexin and phoenixin. Methods This cross-sectional study included 168 women of reproductive age, of whom 72 were diagnosed with PCOS and 96 served as controls. According to BMI, participants were classified as underweight (n = 20), normal weight (n = 73), overweight (n = 22), and obese (n = 53). Serum spexin and phoenixin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Comparative and correlation analyses were performed to evaluate associations with BMI and PSS. Results Spexin levels were lower in women with PCOS compared to controls (203.75 ± 226.06 vs. 260.90 ± 240.20), although the difference was not statistically significant (p = 0.120). A strong positive correlation was found between spexin and phoenixin (r = 0.589, p < 0.001). Spexin demonstrated a weak negative correlation with BMI (r = − 0.135, p = 0.040). PSS scores were positively correlated with PCOS status (r = 0.274, p < 0.001). No significant correlation was found between spexin levels and the results of the Perceived Stress Scale (r r = − 0.110; p = 0.078). Conclusion Spexin levels were lower in women with PCOS compared to controls, which is consistent with and further supports previous research findings. This study provides the first simultaneous evaluation of spexin and phoenixin levels- a novel strong positive correlation between spexin and phoenixin suggests coordinated neuroendocrine regulation. Importantly, perceived stress, assessed by PSS, was significantly elevated in women with PCOS despite the lack of association with spexin levels, highlighting its independent clinical relevance with potential inclusion of PSS as a complementary tool in the diagnostic and therapeutic algorithm of PCOS. Further studies are warranted to clarify the role of these peptides in the complex metabolic and neuroendocrine mechanisms underlying PCOS.

Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. Methods: This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. Results: Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls (p < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, p = 0.001) and FT4 (r = 0.43, p = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, p = 0.007). A strong positive correlation was found between DKK-1 and SOST (p < 0.001), while DKK-1 was negatively associated with age (p < 0.05). Conclusions: Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune–bone interactions in thyroid-related changes in bone metabolism.

Background: Nutrition has been shown to significantly influence the biomarkers of both the multielement status and the lipid profile. However, there are some specific local environmental and genetic factors, that define the substantial variability of their levels in different populations. Several large studies in the last decade report that Bulgaria is among the first countries in the European Union in terms of premature death from cardiovascular diseases under the age of 65. This emphasizes the importance of the recommended annual screening of the lipid profile by adults. The essential role of the elements copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb) and magnesium (Mg) for the antioxidant and immune defense of the body has been a subject of scientific interest in the last thirty years. However, there is scarce data on the influence of nutrition habits of Bulgarians on the serum levels of Mg, Cu, Zn, Se, and Rb. Aim: To determine the serum levels of Mg, Cu, Zn, Se, Rb, total cholesterol, LDL-, HDL-cholesterol, and triglycerides, and evaluate their relationship with nutrition. Methodology: A group of 107 directly selected healthy volunteers of Bulgarian nationality (50 males and 57 females, aged 18 to 65 years) were included in the study. Exclusion criteria were acute or chronic diseases, and intake of dietary supplements containing Se, Zn, Cu, Rb and Mg in the last 6 months. Venous blood serum levels of Cu, Zn, Se, Rb, and Mg were determined via collision cell inductively coupled plasma mass spectrometry (ICP-MS). Enzymatic methods were used to measure total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Results: In participants consuming fish less than once a week, we measured significantly lower Se levels (р < 0.0001) and lower LDL-cholesterol (p = 0.038). Significantly higher total cholesterol levels were found in the group consuming meat less than twice a week (p = 0.038). We observed suboptimal Se levels (less than 80 μg/L) in 42% of the participants. Dyslipidemia was found in more than 50% of the total group: total cholesterol > 5.2 mmol/L, 50.5%; LDL-cholesterol > 2.6 mmol/L, 74.8%; HDL-cholesterol < 1.68 mmol/L for women, and < 1.45 mmol/L for men, 49.5%. Conclusion: The established suboptimal serum levels of Se and lipid profile parameters in healthy individuals from the Bulgarian population emphasizes the importance of targeted monitoring of these laboratory indicators in patient groups at increased risk of cardiovascular and autoimmune diseases. Moreover, the influence of nutrition habits on multielement and lipid profile must be considered in assessing the need for lifestyle corrections, micro- and macronutrient supplementation in these pathological conditions.

Background: Environmental and physiological factors influence human ionom, which requires the development of reliable region-specific reference intervals (RIs). This study aimed to establish population-based RIs of copper (Cu), zinc (Zn), selenium (Se), rubidium (Rb), and magnesium (Mg), in relation to age, sex, and physical activity. Methods: The RIs were established according to the CLSI EP28-A3c guidelines. A reference group of 120 directly selected healthy volunteers of Bulgarian nationality (60 males and 60 females, aged 18 to 65 years) were included in the study. The participants were separated into two groups: low (2 h/week, n=60) physical activity. Serum levels of Cu, Zn, Se, Rb, and Mg (sCu, sZn, sSe, sRb, sMg), were determined via collision cell inductively coupled plasma mass spectrometry (ICP-MS). Results: The RIs in this study are generally comparable to those in other countries. However, 43% of the participants had sSe lower than the threshold of 80 µg/L, correlating with the optimal expression of key selenoproteins. A significant sex-related difference was found for Cu (male vs female, p = 0.003), as well as an age-related significant difference for Cu between the groups of women below and above 30 years of age (p = 0.001). Conclusions: In this study, we verified the RIs of sCu, sZn, sSe, and sMg for the Bulgarian population with ICP-MS. A RI of sRb, missing up to the present was established, thus filling the gap. Specific sex-, age-, and physical activity-related associations of the elements were elucidated.

Introduction: Metal ions, released from dental alloys due to corrosion, come in contact with the cells of the surrounding tissues and may spread throughout the body via the gastrointestinal system, thus inducing dose-dependent cytopathological effects. This study aimed to assess and compare the salivary cobalt and chromium concentrations in individuals aged 18–65 years with and without dental restorations containing metal alloys. Methods: Participants were divided into two main groups according to the existence of metal alloys in the oral cavity—18 patients had fixed prosthetic restorations made of metal alloys, and 17 patients had no metal objects in their oral cavity. Each main group was subdivided into two subgroups according to the type of saliva sample—with or without additional stimulation. Salivary cobalt and chromium concentrations were measured by inductively coupled plasma mass spectrometry. A non-parametric Mann–Whitney test and Spearman’s rank correlation coefficient were applied, and the level of significance was set to p < 0.05. Results: The results showed that the chromium level in non-stimulated saliva was higher in the group of patients with metal dental restorations. No statistical difference was found in cobalt levels. There was no statistical difference in Co or Cr concentrations in stimulated saliva between the studied groups. A positive correlation was found between Cr and Co concentrations in non-stimulated saliva and between cobalt concentrations in stimulated and non-stimulated saliva. Conclusions: Metal alloys in the oral cavity induced elevated chromium levels in non-stimulated saliva, and a correlation between chromium and cobalt ion concentration was found. A detailed examination of patients and their medical history prior to prosthetic treatment is advisable in order to avoid any undesired health effects.

Thyroid dysfunction is frequently associated with disturbances of calcium and phosphorus homeostasis. Previous studies on bone and mineral metabolism in women with autoimmune thyroiditis (AIT) and hypothyroidism have conflicting results. The aim of the present work was to study the parameters of calcium-phosphorus metabolism in women with newly diagnosed autoimmune hypothyroidism and to compare them with those of the control group of healthy women. The study included 64 women with newly diagnosed autoimmune hypothyroidism. A comparison was made with the data of 75 age-, BMI- and menopausal state-matched healthy women. FT3, FT4, TSH, TPO-Ab, TG-Ab, total and ionized serum calcium, inorganic phosphate, magnesium, parathyroid hormone (PTH) and 25(OH) vitamin D were studied. Total and ionized calcium were lower in hypothyroid women in the absence of statistically significant difference compared to the controls. Intergroup analysis revealed no differences in serum phosphorus and 25(OH)D levels. Serum magnesium and PTH were significantly higher in hypothyroid group. These results coincide with some of the studies that examine the parameters of bone and mineral metabolism in hypothyroidism. Bone turnover is suppressed due to impaired mobilization of calcium from the bone, leading to decreased serum calcium levels and elevated PTH. We found a significant effect of thyroid hormones on magnesium homeostasis. The study did not find differences in vitamin D status between the groups. The observed inverse correlation between 25(OH)D and TgAb supports the concept of pathogenic relationship between vitamin D and the development of AIT.

Background. CAD/CAM technologies facilitate using powder CoCr alloys to produce metal-ceramic dental restorations. However, base alloys may induce oxidative stress in the oral cavity due to corrosion and ion release. This study evaluated resistance to corrosion and release of metal ions from 3D printed CoCr dental alloy and their effect on oral oxidative stress. Methods. Metal-ceramic crowns with 3D printed copings from CoCr alloy EOS CobaltChrome SP2 (EOS, Germany) were fabricated for 35 patients. Inductively coupled plasma mass spectrometry (ICP-MS) was used for measuring the concentration of Co and Cr ions in non-stimulated saliva before prosthetic treatment (BPT), at 2 h and 7 days after the dental treatment (APT2, APT7, respectively). Open circuit potentials (Eocp) were evaluated at APT2 and APT7. Estimating oral oxidative stress, measurements of 8-isoprostaglandin F2-alpha were conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at stages BPT, APT2, and APT7. Results. Salivary Co level increased at APT2 and decreased to the initial levels at APT7. No statistical difference was found between the levels of 8-isoPGF2-alpha measured, and between the Eocp measurements at APT2 and APT7. Conclusions. The studied alloy showed stable corrosion resistance and the metal ion release did not induce oral oxidative stress.

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