Medical University of Varna

Purpose. This review aims to present recent data from contemporary scientific literature on the anti-neuroinflammatory effects of selected herbs from the Lamiaceae family. Material and methods. A literature search was conducted to obtain current information on the role of phenolic compounds from Lamiaceae species in neuroinflammation. The Lamiaceae family, widely represented across Europe by genera such as Salvia, Mentha, Melissa, Origanum, Ocimum, Thymus, and Satureja, is a rich source of bioactive phenolic compounds with antioxidant, anti-inflammatory, and emerging neuroprotective potential. Results. Species belonging to the Lamiaceae family, including rosemary, sage, mint, thyme, oregano, and others, are rich in phenolic compounds, particularly phenolic acids and flavonoids. These herbs demonstrate promising anti-neuroinflammatory and neuroprotective properties, largely attributed to their phenolic content. Conclusion. Phenolic compounds from Lamiaceae plants modulate key neuroinflammatory pathways by suppressing microglial activation, downregulating pro-inflammatory mediators, and activating antioxidant defences. Through these mechanisms, they mitigate oxidative stress and promote neuronal survival, thereby exerting protective effects in experimental models of neuroinflammation and neurodegenerative disorders. Thus, phenolic compounds from Lamiaceae species represent promising multifunctional agents for targeting neuroinflammation and potentially slowing the progression of neurodegenerative diseases.

Chronic kidney disease [CKD] is associated with profound alterations of both gut microbiota composition and functions, commonly referred to as gut dysbiosis. These changes are driven by several factors such as dietary restrictions, medications, and uremia, which further contribute to patients with CKD to their pro-inflammatory and immunocompromised state. Recent evidence suggests that dysbiosis may also increase susceptibility to infections, which remain a leading cause of morbidity and mortality in CKD patients. In this review, we aimed at examining the features of the altered gut microbiome in patients with CKD, its potential role in promoting infection risk, and current therapeutic strategies targeting the gut microbiota to mitigate CKD-related complications.

Background: Geraniaceae species are widely used in traditional medicine. Pelargonium radula and Geranium macrorrhizum are aromatic medicinal plants traditionally used in Bulgaria for their antimicrobial, anti-inflammatory, and wound-healing properties. Comparative phytochemical data on Pelargonium radula and Geranium macrorrhizum cultivated in Bulgaria, however, remain limited. The present work aimed to characterize and compare the chemical composition of essential oils and main phenols, in support of future pharmacological evaluation. Methods: Essential oils from aerial parts of both species were obtained by hydrodistillation and analyzed by GC-MS. Through HPLC-UV, ethanol extracts were evaluated to quantify the major phenolic acids and flavonoids. Results: The yield of essential oils was 0.10% for P. radula and 0.03% for G. macrorrhizum, dominated by oxidized monoterpenes, mainly citronellol and geraniol-type compounds. HPLC analysis revealed marked differences in their phenolic profiles. P. radula showed a composition with six phenolic acids-primary protocatechuic and ferulic acids, and very low levels of flavonoids, with rutin being the only quantifiable glycoside. In contrast, G. macrorrhizum contained nine phenolic acids and four flavonoids, with remarkably high levels of salicylic, rosmarinic, and p-coumaric acids, as well as catechins, absent in P. radula. Conclusions: The two species showed different phytochemical characteristics in both their volatile and non-volatile fractions. P. radula is characterized by a citronellol/geraniol-rich essential oil and a moderate phenolic profile, while G. macrorrhizum exhibits significantly higher phenolic diversity and abundance. These findings expand the current phytochemical knowledge of both taxa and provide a solid basis for future chemotaxonomic and pharmacological studies. The obtained results suggest that Geranium macrorrhizum may be more promising for antioxidant and anti-inflammatory applications, while Pelargonium radula may be preferentially explored for ant-microbial purposes.

Letrozole and other aromatase inhibitors are increasingly recognized as first-line ovulation induction (OI) medications, offering an efficient and physiologic approach to ovarian stimulation that enhances outcomes in reproductive medicine. By selectively inhibiting aromatase and maintaining lower peripheral estrogen levels, letrozole supports mono- or bi-follicular development while reducing the risk of supraphysiologic estradiol exposure seen with traditional gonadotropin regimens. These pharmacological characteristics have contributed to its expanding use not only in OI but also in various assisted reproductive technologies. To evaluate the clinical benefits, effectiveness, and safety of using letrozole in in vitro fertilization (IVF), in vitro maturation (IVM), and OI, with particular attention to reproductive outcomes, ovarian response, endometrial effects, cycle characteristics, and treatment-related adverse events. A comprehensive systematic search covering the period from December 2000 to November 2025 was conducted across major electronic databases including PubMed, Embase, the Cochrane Library, and Google Scholar. The search strategy incorporated predefined keywords related to letrozole, aromatase inhibition, OI, IVF, and IVM. Studies involving randomized controlled trials, observational cohorts, and meta-analyses were included, while non-clinical and non-reproductive data were excluded. Relevant outcomes were extracted and synthesized qualitatively. Letrozole demonstrates broad clinical utility in reproductive medicine, spanning assisted reproductive techniques, ovarian stimulation strategies, and the management of ovarian hyperstimulation syndrome risk, ectopic pregnancy, and endometriosis-related infertility. Its targeted estrogen suppression, cost-effectiveness, and favorable safety profile make it a valuable component of individualized treatment protocols. Nonetheless, further high-quality research is required to refine optimal dosing strategies, identify ideal patient populations, and clarify long-term reproductive and obstetric safety.

Introduction: An odontogenic keratocyst (OKC) is a developmental cyst of the jaws characterized by aggressive growth and a high recurrence rate, leading to ongoing challenges in its classification and management. Aim: This article aims to provide a comprehensive overview of the OKC, examining its etiology, clinical and radiographic features, histopathology, and current treatment strategies. Materials and Methods: This review synthesizes information from relevant literature, including historical accounts of OKC classification, clinical case reports, and studies detailing its pathogenesis, histopathology, and treatment modalities. Results: OKC presents with variable clinical features, often in the mandible, and radiographically appears as a well-defined radiolucent lesion. Histologically, it is characterized by a thin, parakeratinized epithelium. Treatment typically involves surgical removal, but recurrence is a concern. Conclusion: An OKC remains a clinically significant lesion requiring careful diagnostic evaluation and tailored management to minimize recurrence and associated morbidity.

Background/Objectives: Atrial fibrillation (AF) is currently the most common arrhythmia worldwide, and it is linked to increased mortality and morbidity, hence the need for a better clinical stratification of AF patients. Histone complexes or nucleosomes, released into the blood circulation, are found elevated in acute conditions such as stroke, trauma, and sepsis. The aim of this pilot single-centre study was to assess whether circulating histone levels could be used for diagnostic purposes in patients with AF. Methods: A total of 40 patients, well characterised for their biochemical and clinical characteristics, were recruited from outpatient clinics. Patients were randomly recruited into two groups (n = 20 per group), i.e., persistent AF and hypertensive controls. A multi-channel flow imaging methodology based on ImageStreamX was used with a well-optimised protocol to image and quantify five individual histones (H2A, H2B, H3, H4, and macroH2A1.1) together with the dimers (H2A/H2B, and H3/H4). Results: In the AF groups, plasma levels of histone dimers H2A/H2B and H3/H4 were elevated compared to hypertensive controls, 1.8% vs. 1.06% (p-value = 0.03). H2A/H2B dimer levels were increased in AF patients irrespective of gender, smoking status, diabetes, and pharmacological therapy. In the overall population, an inverse correlation between H2A and BMI was detected. Conclusions: Our pilot study, although limited in sample size, suggests that circulating histone complexes may be epigenetic sentinels for AF, offering mechanistic insights while addressing unmet needs in risk stratification.

Abstract The fragrant organic monoterpene anethole is a component of anise and fennel essential oils. The research intended to evaluate the effects of anethole on spatial memory and oxidative stress in rats on a calorie-dense diet (CDD). Male Wistar rats ( n = 50) were allocated into 5 groups: Control, CDD, CDD + A62.5, CDD + A125, and CDD + A250. The dietary intervention lasted for 10 weeks, during which anethole at doses 62.5, 125, and 250 mg kg −1 was daily orally administered to the last three groups. In the 9th week, the open field test (OFT) for locomotor activity and the spatial object recognition test for spatial memory assessment were carried out. At the end of the experiment, the endogenous antioxidant enzyme superoxide dismutase (SOD) was measured in serum, and the thiobarbituric acid reactive substances (TBARS) were measured in whole-brain homogenate as markers of lipid peroxidation. The OFT showed no significant differences in the locomotor activity across the groups. The consumption of CDD resulted in a decline in spatial memory manifested by the decrease of the recognition index, while anethole treatment prevented this effect in a concentration-dependent manner. In CDD group, the activity of SOD was significantly reduced ( P < 0 .05 vs. Control), while the brain TBARS were significantly elevated ( P < 0 .05 vs. Control). SOD level in CDD + A250 group was comparable to that of the control group. TBARS levels in all anethole-treated groups did not differ significantly from the control value. In conclusion, anethole prevented CDD-induced spatial memory impairment and reduced oxidative stress in rats on a calorie-dense diet.

Abstract Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs for the treatment of a number of oncological diseases by harnessing the immune system to coun-teract malignant cells. However, their use as antitumor agents is accompanied by a wide range of immune-mediated adverse effects, including endocrinopathies. Among the latter, thyroid dysfunction stands out as one of the most common. This article presents six different clinical cases of thyroid damage with an emphasis on thorough clinical examination aided by imaging and precise interpretation of hormonal studies. The management of thyroid-related immune-mediated side effects requires an individualized approach, taking into account the severity and dynamics of the abnormalities, the clinical condition of the patient and the stage of the malignancy.

Cerebral palsy (CP) and autism spectrum disorder (ASD) are neurodevelopmental conditions that affect physical growth and developmental outcomes. While distinct, both can influence neuropsychological development, yet limited research has examined how growth indicators relate to developmental profiles in these groups. This pilot cross-sectional study examines the relationship between physical growth and neuropsychological development in children with CP and ASD, and compares their developmental characteristics. This cross-sectional study included 27 children (CP: n=14; ASD: n=13). Anthropometric assessments included height-for-age (HAZ), weight-for-age (WAZ), BMI-for-age (BMIAZ), mid-upper arm circumference-for-age (MUACAZ), and skinfold thickness Z-scores (TSFAZ, SSFAZ). Neuropsychological development was measured using the Developmental Profile 3 (DP-3), covering physical, adaptive, cognitive, social-emotional, and communication domains. Children with ASD had significantly higher scores in physical development (median: 83.5 vs. 54.0, p=0.006), adaptive behavior (81.0 vs. 53.0, p=0.003), and overall development (78.0 vs. 58.0, p=0.035) than those with CP. No differences were found in cognitive, social-emotional, or communication domains. In the full sample, WAZ significantly correlated with adaptive behavior (r=0.491, p=0.015) and overall development (r=0.439, p=0.032). MUACAZ and TSFAZ were also associated with specific developmental domains (e.g., MUACAZ and adaptive behavior: r=0.445, p=0.033). Linear regression analysis confirmed that WAZ significantly predicted neurodevelopmental scores (β=6.20, p=0.022), explaining 46.5% of the variance when adjusted for age, gender, and parental age (Adjusted R²=0.465; p=0.040). Children with CP show greater growth and developmental delays than those with ASD. Weight-for-age is a key predictor of neurodevelopment, especially adaptive behavior. These findings support integrating nutritional and developmental care in neurodevelopmental interventions.