The condensed 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole scaffold, combining indole and 1,2,4-triazole pharmacophores, represents a promising source of anti-inflammatory, antimicrobial and anticancer agents. In silico assessment of their toxicity, pharmacokinetics and molecular properties provides a rational basis for synthesis and biological evaluation. The aim of this study is to apply in silico approaches to investigate the physicochemical, pharmacokinetic and toxicological properties of 1,2,4-triazolo-[1′,5′:1,6]pyrido[3,4-b]indole derivatives and to explore their potential as multitarget agents through molecular docking. Materials and methods. The pharmacological properties of 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives were evaluated using in silico modeling approaches. Toxicity prediction was performed with the US EPA TEST software package, while physicochemical and pharmacokinetic parameters were assessed using SwissADME. Molecular docking was conducted to analyze ligand interactions with cyclooxygenase-2, lanosterol 14α-demethylase, peptide deformylase of E. coli and S. aureus and anaplastic lymphoma kinase. Results. The 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives were characterized by moderate oral toxicity and low mutagenic risk, except for compounds 1 and 5. Drug-likeness analysis confirmed compliance with criteria for orally active agents, while ADME modeling indicated high gastrointestinal absorption, limited central nervous system penetration (except compound 10) and potential CYP450 interactions. Docking studies revealed strong binding to COX-2 and CYP51, with compounds 2, 5, 8 and 10 showing affinities comparable to fluconazole. Several derivatives also exceeded actinonin in binding to E. coli peptide deformylase and displayed diverse interactions with S. aureus PDF. Compounds 2, 5 and 10 demonstrated binding energies against ALK close to crizotinib. Overall, these findings suggest favorable pharmacokinetic profiles and multitarget potential for anti-inflammatory, antimicrobial and anticancer applications, with lipophilicity and CYP450 interactions identified as possible limitations. Conclusions. In silico modeling demonstrated that 1,2,4-triazolo[1′,5′:1,6]pyrido[3,4-b]indole derivatives possess favorable pharmacokinetic properties, relatively low predicted toxicity, and strong affinities toward multiple pharmacologically relevant targets. These findings provide a rationale for further experimental validation and the development of novel multitarget drug candidates.

Aim. To evaluate the clinical efficacy of radiofrequency ablation in high-risk patients with localized renal cell carcinoma and to assess the limitations of glomerular filtration rate in post-ablation renal function assessment. Materials and methods. This single-center retrospective cohort included 24 patients with localized renal tumors treated with radiofrequency ablation between 2008 and 2019 at the Zaporizhzhia Regional Antitumor Center. Indications comprised solitary kidney (n = 5), bilateral tumors (n = 3), and local treatment in the setting of recurrent or metastatic disease (n = 18); categories were not mutually exclusive. A percutaneous approach was used in 21 (87.5 %) patients, laparoscopic in 1 (4.2 %), and open in 2 (8.3 %). Core-needle tissue samples from macroscopically intact parenchyma adjacent to the ablation zone were obtained intraoperatively and 72 hours after ablation. Immunohistochemical analysis of CD34 and HIF-1α expression was performed and correlated with estimated glomerular filtration rate. The Wilcoxon signed-rank test was used for statistical evaluation. Results. Complete tumor necrosis was observed in 75–100 % of cases. Most complications were minor (Clavien–Dindo I–II: 29.2 %), while serious adverse events (IIIa–IV) occurred in three patients (12.5 %). The mean hospital stay was 3.0 ± 0.8 days. Clear cell carcinoma was the predominant histology – (83.3 %), with papillary carcinoma in 16.7 %. Tumor size ranged from 2.1 cm to 4.0 cm (mean 3.2 ± 0.5 cm); 37.5 % of patients had lesions >3 cm. Postoperative immunohistochemistry showed a significant decrease in CD34 expression (100 ± 15 vs. 58 ± 12; p = 0.014) and an increase in HIF-1α levels (25 ± 8 vs. 78 ± 14; p = 0.008) despite a stable estimated glomerular filtration rate (62.4 ± 7.8 mL/min/1.73 m2 vs. 61.9 ± 8.1 mL/min/1.73 m2, p = 0.74). Conclusions. Radiofrequency ablation is an effective nephron-sparing option for high-risk patients with localized renal cell carcinoma. However, stable estimated glomerular filtration rate values may mask subclinical parenchymal injury; tissue-level biomarkers capture structural and microvascular alterations. These findings support prospective validation.

The aim of the work is to analyze and evaluate data from professional literature sources regarding comorbid conditions among patients with community-acquired pneumonia combined with coronavirus disease. Materials and methods. Using primary sources from the scientometric databases Scopus, Web of Science, PubMed, a retrospective analysis of literature data on the issue of comorbidity in patients with community-acquired pneumonia combined with coronavirus disease for 2020–2025 was conducted. Results. This article examines the impact of comorbid cardiovascular diseases during COVID-19 and the mortality rate. Literature analysis shows that the presence of cardiovascular diseases increases the chances of developing a severe course of COVID-19 by three times. Elderly people and patients with hypertension and diabetes have the worst prognosis for COVID-19. Studies indicate increased morbidity and mortality among patients with diabetes, as well as the relationship between glucose levels and disease severity. The works of various authors emphasize the importance of early diagnosis and hospitalization, as well as the need for an integrated approach to treatment, including the cooperation of cardiologists and pulmonologists. It is also noted that patients with chronic diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are at higher risk of severe COVID-19. The article also discusses the mechanisms of inflammatory damage to the heart that are detected during the disease and their relationship with prognosis. Conclusions. Timely diagnosis and treatment of comorbid conditions are need to reduce the risk of complications in patients with COVID-19. The article emphasizes the important role of family doctors in monitoring and managing chronic diseases, which can significantly alleviate the course of COVID-19. The prospects for further research are to identify markers of the immunoinflammatory response to predict the course in patients with community-acquired pneumonia associated with coronavirus infection with comorbid pathology.

This study investigates the ADME properties of newly synthesized derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. Aim: to evaluate the effect of structural modifications, such as alkylation, chain elongation, and introduction of substituents, on absorption, distribution, metabolism, and excretion parameters, with an emphasis on drug-likeness and medicinal potential. Materials and methods. Computational approaches using SwissADME tools were applied to predict key physicochemical and pharmacokinetic descriptors, including molecular weight, TPSA, lipophilicity (LogP), solubility, gastrointestinal absorption, P-glycoprotein substrate recognition, and cytochrome P450 (CYP) inhibition profiles. Radar plots and comparative tables were employed to visualize differences between structural analogues. Results. The analysis showed that most derivatives maintain acceptable lipophilicity and solubility ranges, while some analogues demonstrated promising profiles in terms of balanced polarity and molecular size. Several compounds were predicted as potential inhibitors of CYP3A4 and CYP2C9 isoenzymes, highlighting their possible pharmacological activity. Despite moderate limitations in oral bioavailability, certain molecules exhibited favorable characteristics suggesting a good balance between stability and pharmacokinetic behavior. Structural features, such as alkyl chain length and substitution patterns, significantly influenced solubility, permeability, and drug-likeness scores. The data suggest that further optimization of polarity and molecular weight could improve gastrointestinal absorption while retaining beneficial pharmacological interactions. The antioxidant and antihypoxic potential of these molecules is supported by their structural features and predicted bioactivity, positioning them as attractive candidates for future biological screening. Conclusions. The study provides a computational basis for selecting the most promising triazole-based derivatives for subsequent in vitro and in vivo testing, facilitating the design of compounds with optimized ADME properties and potential therapeutic application.

The aim of the work was to investigate the clinical course of adolescent arterial hypertension detected at the age of 17 based on a 15-year follow-up in order to clarify the frequency and conditions under which adult hypertension develops. Materials and methods. The observation began at 2009. First-year medical students were involved who were diagnosed with stable or labile arterial hypertension or state of high normal blood pressure at the age of 17. Over 15 years the follow-up data were collected from 37 doctors of various specialties who reached this moment the age of 32–33. Results. In the long-term follow-up (15 years later), blood pressure levels were assessed in men and women participating in the study, their complaints were analyzed, and the need for treatment tailored to the characteristics of arterial hypertension that had originated in adolescence was emphasized. Hypertensive disease developed in 38.7 % of respondents in the follow-up study. Males with stable and labile adolescent arterial hypertension in the past predominated. Conclusions. The highest risk of chronic hypertension is in young men with stable (54.5 %) and labile (41.7 %) juvenile hypertension. This occurs at the age of 30–40 in the form of hypertension. The risk of developing hypertension in adulthood for male adolescents with “high blood pressure” is 21.4 %. The implementation of physical rehabilitation programs is an effective factor in forming adherence to a healthy lifestyle and controlling blood pressure. There is a need to further improve clinical and diagnostic approaches to juvenile hypertension with the development of a single concept of diagnosis in adolescence and young adulthood.

Inflammation is a fundamental protective biological mechanism; however, its chronic progression can lead to severe pathologies. Conventional anti-inflammatory drugs, such as corticosteroids and non-steroidal anti-inflammatory drugs, are often associated with considerable adverse effects. This necessitates the urgent search for novel, safer therapeutic agents, particularly among medicinal plants. Myrtus communis L. is well-recognized for its therapeutic properties, and its leaves have been traditionally utilized in folk medicine for the management of various inflammatory conditions. The aim of the work was to comparatively evaluate the anti-inflammatory activity and acute toxicity of thick extracts obtained from the leaves of Myrtus communis L., cultivated in natural conditions (in vivo) and those obtained by microclonal propagation (in vitro), given the growing demand for effective and safe natural anti-inflammatory agents. Materials and methods. Thick extracts of Myrtus communis leaves were obtained using fractional maceration with 70 % ethanol, followed by concentration via a rotary evaporator. Anti-inflammatory activity was assessed on the serotonin-induced edema model in white rats, by measuring the increase in paw volume. Experimental groups received the extracts (100 mg/kg) or ibuprofen (25 mg/kg). Additionally, the influence of the extracts on biochemical markers of inflammation (C-reactive protein, TBARS) and the blood protein profile was studied. Acute toxicity assessment was conducted in accordance with OECD guidelines, starting with a dose of 2000 mg/kg. Results. The myrtle leaf extracts demonstrated potent anti-exudative activity, reducing paw edema by 33.55 % (in vivo extract) and 35.69 % (in vitro extract), results that are comparable to the effect observed with ibuprofen (42.11 %). The mechanism of action is likely linked to antagonism against serotonin receptors. Furthermore, the extracts significantly reduced the levels of inflammation and oxidative stress markers, concurrently contributing to the restoration of the serum protein profile. The extract obtained through microclonal propagation (in vitro) exhibited slightly superior efficacy, suggesting a potential advantage for this biotechnological approach. Acute toxicity assessment confirmed that both extracts belong to Category 5 of the toxicity classification (LD50 ≥5000 mg/kg for the in vivo thick extract and LD50 2000–5000 mg/kg for the in vitro thick extract), confirming their low acute toxicity. Conclusions. Concentrated Myrtus communis leaf extracts derived from plants grown under natural conditions and via microclonal propagation demonstrate marked anti-inflammatory and anti-exudative activity. Biotechnological cultivation approaches may offer a promising means of obtaining raw materials with enhanced biological efficacy.

In modern forensic practice, molecular genetic studies play an extremely important role, especially in wartime. DNA identification allows you to identify a person by traces of biological origin, which has become critically important for the identification of the dead and missing. The effectiveness of such studies largely depends on the choice of the optimal method of DNA extraction, which ensures the reliability and speed of results. In this regard, the choice of the most reliable, sensitive and resource-efficient method of DNA extraction becomes not only a technical but also a strategic task that directly affects the success of investigations and the reduction of the number of missing persons, which is extremely important in the humanitarian dimension of modern war. Aim. Comparative analysis of two commercial kits for manual DNA extraction — PrepFiler™ Forensic DNA Extraction Kit (Applied Biosystems) and NucleoSpin® DNA Forensic (Macherey-Nagel) — to determine the feasibility of their use for different types of biological samples and traces and categories of expert workload. Materials and methods. The study was conducted on the basis of the analysis of samples of trace biological material, in particular blood stains, saliva, tissue fragments and traces from the surfaces of objects. Two sets of reagents were used for DNA extraction: PrepFiler™ Forensic DNA Extraction Kit (Thermo Fisher Scientific) and NucleoSpin® DNA Forensic (Macherey-Nagel), 100 reactions each. DNA extraction was carried out according to the protocols provided by the manufacturers. The quality and quantity of the isolated DNA were determined by real-time polymerase chain reaction using the Applied Biosystems 7300 Real-Time PCR System. Further genotyping was performed by capillary electrophoresis on the Applied Biosystems 3500 Genetic Analyzer. Results. Comparative analysis showed that NucleoSpin® DNA Forensic is optimal for fast and convenient DNA isolation from simple reference samples such as saliva or blood, where no significant degradation or inhibitors are observed. It provides sufficient DNA concentration in a short time, however, in cases of working with complex or degraded samples (especially bone remains), partial STR profiles were more often observed. In contrast, PrepFiler™ and, in particular, PrepFiler™ BTA demonstrated better performance under such difficult conditions, providing complete profiles even in the presence of inhibitors or prolonged degradation. This makes it a reasonable choice for forensic cases with problematic samples, despite the higher cost. Conclusions. Molecular genetic research is a key tool in modern forensic practice, in particular for identifying a person from biological samples. The use of DNA identification methods based on polymerase chain reaction (PCR) ensures high accuracy and reliability of forensic examinations in criminal and civil cases, and also plays an important role in the identification of the deceased and missing, especially in wartime conditions. A comparative analysis of two commercial kits for manual DNA extraction — PrepFiler™ Forensic DNA Extraction Kit and NucleoSpin® DNA Forensic — showed that both kits have their advantages and can be effectively used depending on the type of biological material and the conditions of the examination. The choice of the optimal DNA extraction method significantly affects the quality and quantity of the obtained genetic material, which, in turn, determines the reliability of DNA profiling and the speed of the expert laboratory.

Limited solubility of a significant number of active pharmaceutical ingredients (APIs) is a substantial issue that reduces their bioavailability. Consequently, the search for effective approaches to enhance API solubility remains a relevant focus in modern pharmaceutical science. One of the promising strategies to overcome the problem of low API solubility is the use of solid dispersion systems (SDSs), in which the active substance is uniformly distributed within a polymer matrix. Particular attention is drawn to the creation of such systems in the form of nonwoven materials based on ultrafine fibres, which provide a high surface area and promote solubility improvement. Electrospinning involves the use of an electrostatic field to produce nonwoven materials made of ultrafine fibres from a solution or melt, enabling control over their morphology. A review of scientific sources confirms the application of this technology for developing solid dispersion systems with improved solubility of APIs from various pharmacological groups.The selection of electrospinning parameters depends on the requirements for the morphology of nonwoven materials, their mechanical properties, production scale, and economic factors. The aim: to investigate the potential of electrospinning technology for the development of SDSs with improved solubility of APIs. Materials and methods. The review was prepared based on an analysis of scientific and patent publications covering the use of electrospinning technology to produce SDS with enhanced API solubility. Source selection considered topic relevance, scientific novelty, data reliability, and completeness of results description. The subsequent analysis involved systematizing information on types of polymer matrices and APIs, electrospinning process parameters, solubility evaluation methods, and examples of the practical implementation of the technology in pharmaceutical development. Results. Analysis of the scientific literature has shown that electrospinning technology is an effective method for producing solid dispersion systems with improved API solubility. Appropriate polymer selection and optimization of process parameters ensure uniform API distribution within the fibres, determine the morphology and properties of the material, and influence the dissolution rate and bioavailability. Literature data confirm the high potential of this technology as an innovative approach in pharmaceutical development. Conclusions. Electrospinning technology is a promising method for creating SDS to improve API solubility. An optimal choice of polymer matrix and process parameters ensures uniform distribution of the substance within the fibres and increases both dissolution rate and bioavailability.

Leading pharmacopoeias of the world regulate performing chromatographic determination of enalapril in the substance using gradient elution (for 30 min) and a chromatographic column of 4.1 mm × 15 cm, 5 μm, class L21, at a temperature of 70 °C, with a flow rate of 1.5 ml/min, and in tablets on a column of class L7, at a temperature of 50 °C, with a flow rate of 2.0 ml/min, using isocratic elution with acetonitrile (ACN) and buffer (sodium dihydrogen phosphate solution in water, adjusted with phosphoric acid to pH 2.2) (250:750). In scientific literature, researchers have proposed HPLC methods for determining enalapril in pharmaceutical products; however, such methods have drawbacks (asymmetrical peaks, elution near the “dead volume”, etc.). We propose the use of salts of chaotropic anions in the mobile phase on a C18 chromatographic column as a promising approach to obtain a symmetrical enalapril peak that elutes not near the “dead volume”. The aim of the work was to develop a green, rapid, and simple HPLC method for the determination of enalapril in tablets using salts of chaotropic anions. Materials and methods. The study used a Shimadzu LC-2050C and Agilent 1260 liquid chromatograph with a diode array detector; LabSolutions software was used for obtaining chromatograms and integrating results. Other analytical equipment included analytical electronic laboratory balances “RAD WAG AS 200/C”; ultrasonic bath (Elmasonic Easy 40 H, Germany); pH meter (Mettler-Toledo, model LE438, Switzerland). The chromatographic column Luna C18 (100 × 4.6 mm, 3 µm) was purchased from Phenomenex. Enalapril maleate reference standard (purity ≥99 %) was acquired from Sigma-Aldrich Chemicals Co., and “Enap” tablets (20 mg, KRKA, Slovenia) were used. Results. The use of salts of chaotropic anions in the mobile phase during HPLC determination of enalapril made it possible to reduce analysis time (without performing the determination near the dead volume) and to improve the symmetry of the enalapril peak. During the conducted experimental studies, the optimal chromatographic conditions for the quantitative determination of enalapril in tablets were established: Luna C18 chromatographic column (100 × 4.6 mm, 3 μm), mobile phase – 2 % ACN and 98 % KPF6 buffer solution 40 mM, pH 2.43, column temperature – 30 °C, detection at a wavelength of 210 nm. The method was linear in the concentration range of 40–120 μg/mL. Regression equation: y = 14166x – 9589.2, correlation coefficient R2 = 0.9972. Low limit of determination (LOD) – 8.52 μg/mL, low limit of quantification (LOQ) – 25.80 μg/mL. Modern tools for assessing greenness, AGREE (score 0.74), MoGAPI (score 81), Complex MoGAPI (score 81), AGSA (score 77.78), CaFRI (score 82), and CACI (score 79), confirmed that the proposed HPLC method is green. Conclusions. A green, rapid, and simple HPLC method for the determination of enalapril in tablets using chaotropic anion salts has been developed. The proposed approach enabled the production of symmetrical peaks with excellent chromatographic system parameters and allowed analysis in a short time. In addition, reducing the mobile phase flow rate to 0.6 ml/min made the analysis greener. The developed HPLC method for determining enalapril in tablets can be applied both in routine pharmaceutical analysis and in testing by independent laboratories.

Infectious diseases are an important problem worldwide for medicine and pharmacy. The search for natural antibacterial agents has gained significant interest recently, driven by the growing concerns over antibiotic resistance and the desire for natural alternatives. Blackberry leaf, known for their rich nutritional profile and high antioxidant content, have attracted attention for their potential antibacterial properties. Understanding the antibacterial potential of blackberries could provide insights into their use in natural medicine and food preservation. The aim of work was to study a correlation between antimicrobial and antioxidant activities with biologically active compounds in blackberry leaf extracts. Materials and methods. The spectrophotometric method was applied for quantification of the total amount of biologically active compounds. The antiradical activity of obtained blackberry leaf extracts was determined with the potentiometric method; antimicrobial activity was estimated by the “well” method. Results. Results demonstrate that the highest amount of polyphenols, catechins, flavonoids were 3.72 %, 1.88 % and 1.48 % in 60 % EtOH extract, respectively. The organic acids were dominant in the aqueous extract (1.96 %). The most potent antioxidant property possessed 60 % EtOH extract of blackberry leaf (204.68 mmol-eqv./mdry res.). The blackberry leaf extracts showed antimicrobial effects against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtillis, Proteus vulgaris, and Candida albicans. Statistical analysis revealed a highly significant interdependence between the concentration of catechins, the magnitude of antioxidant activity, and the strength of the antimicrobial effect against the tested microorganisms (S. aureus, P. vulgaris, P. aeruginosa, and C. albicans). Conclusions. These findings show the great potential of blackberry extracts in the development and creation of new medicines with antimicrobial, antioxidant effects that are not inferior to the action of synthetic analogues.