Problems of Biological Medical and Pharmaceutical Chemistry

Introduction. Cadherins are a family of calcium-dependent transmembrane glycoproteins that mediate specific cell-cell adhesion via homophilic interactions between their extracellular domains. They play a key role in the formation of cell-cell contacts, maintenance of tissue architecture, and regulation of cell polarity. Disturbances in the expression or function of cadherins are closely associated with the processes of epithelial-mesenchymal transition, invasion and metastasis of tumor cells. In addition to full-length membrane forms, cadherins can exist as soluble fragments (s-cadherins) circulating in the extracellular space or biological fluids, including blood serum. Currently, the biological and clinical significance jf the soluble form of P-cadherin (sP-cadherin) remains poorly understood. Literature data on the concentration and diagnostic or prognostic value of sP-cadherin in malignancies are extremely limited, highlighting the need for further research in this area.

The aim of the work is to analyze the potential clinical significance of sP-cadherin as a diagnostic marker for benign, borderline and malignant ovarian tumors.

Material and methods. The study included 105 patients with primary epithelial ovarian cancer (median age 58 years), 11 patients with borderline ovarian tumors (median age 56 years), 15 patients with benign ovarian tumors (median age 49 years) and 21 practically healthy women in the control group (median age 61 years), who underwent examination and treatment in the period from 2023 to 2025. The concentration of sP-cadherin was determined in the blood serum before the start of specific treatment using the Human P-Cadherin ELISA Kit (RayBiotech, USA). When comparing the indicators and analyzing their relationships, the nonparametric Mann-Whitney and Kruskal-Wallis tests were used. The analysis of the informativeness of the diagnostic method by assessing its sensitivity and specificity was carried out by constructing ROC curves and calculating the area under them (AUC).

Results. It was found that the median level of sP-cadherin in patients with ovarian cancer (8.45 ng/ml) was statistically significantly higher than the control group (3.22 ng/ml; p = 0.000002), patients with borderline ovarian tumors (3.07 ng/ml; p = 0.0012) and benign ovarian neoplasms (4.27 ng/ml; p = 0.03). ROC analysis demonstrated moderate diagnostic accuracy for differentiating malignant ovarian tumors from a control group of healthy women at a threshold serum marker level of 5.75 ng/ml; the test sensitivity was 72.4%, specificity 71.4% (AUC = 0.826; Youden index 0.438). sP-cadherin showed limited diagnostic value in borderline and benign ovarian tumors. No significant differences in sP-cadherin levels were found in subgroups of ovarian cancer patients based on stage, histological type, presence of metastases and ascites, and tumor differentiation grade.

Conclusions. A significant increase in the level of sP-cadherin in the blood serum of patients with epithelial ovarian cancer was revealed, compared with controls, borderline and benign ovarian tumors, which indicates the potential diagnostic significance of this marker. Median sP-cadherin concentrations did not differ between controls, patients with borderline and benign ovarian tumors. No significant association of sP-cadherin levels with the main clinical and morphological characteristics of ovarian cancer was found. It is necessary to continue studying sP-cadherin in patients with ovarian cancer as a diagnostic marker in multiparametric panels and validation in expanded cohorts of patients.

Early detection of diseases is a key factor for successful treatment, reducing the negative impact of the disease on both the patient and society as a whole. One of the main strategies for early diagnosis is to search for molecules whose concentration changes in biological samples indicate the development of a pathological process. Such disease indicators are called biomarkers. Considerable interest of researchers is focused on dynamic changes in the proteome, which accurately reflects the state of the organism, including against the background of disease or therapy. Among the methods of studying the proteome in general and individual protein biomarkers, diagnostic systems based on the use of antibodies are of great clinical and scientific importance.

Aptamers or chemical antibodies are definitely structured oligonucleotides or peptides capable of binding with high specificity to the target. To date, many studies have demonstrated the great potential for the use of aptamers in the development of both diagnostic platforms and means of drug delivery or therapeutic action. This allows aptamers to be considered as an alternative to antibodies in all areas of their application, including for early disease diagnosis.

This review systematizes information about the biochemical fundamentals and methods of aptamer production by systematic evolution of ligands by exponential enrichment (SELEX) and its modifications, comparative advantages over antibodies (synthetic nature, thermostability, low immunogenicity, cost-effectiveness), integration into diagnostic platforms (electrochemical, optical and mass-sensitive biosensors), as well as aptamer-based multiplexed technologies (SomaScan). Examples of successful application of aptasensors for early detection of oncological (lung, bladder, breast cancer, leukemia), infectious (SARS-CoV-2, hepatitis viruses), neurodegenerative (Alzheimer's, Parkinson's disease) and cardiovascular pathologies are analyzed. Current limitations of the technology (sensitivity to nucleases, rapid clearance, lack of standardization, regulatory barriers) and promising directions of development are discussed, including integration with artificial intelligence, microfluidics, portable point-of-care devices and personalized diagnostic solutions, which opens the way for creating more accurate, accessible and effective systems for early disease detection.

Metformin biguanide is the most widely used oral antidiabetic drug for the treatment of type 2 diabetes mellitus (T2DM). Metformin inhibits gluconeogenesis by suppressing complex I of the respiratory chain, thereby reducing oxygen consumption. In connection with the mechanism of action of metformin, it is of interest to discuss the effect of this drug on the induction or inhibition of one of the types of regulated cell death - ferroptosis. The aim of this study is to summarize the data on the effect of metformin on the development of ferroptosis and the possible use of this drug in chemotherapy through the induction or inhibition of ferroptosis. The work used review and original publications indexed in MedLine, Cochrane Library, PubMed.

The literature accumulates data on the treatment of cancer by inducing ferroptosis. Metformin can reduce the risk of cancer in patients with type 2 diabetes and inhibit cell growth of various cancers, including pancreatic cancer, colon cancer, prostate cancer, ovarian cancer, and breast cancer. Induction of ferroptosis in cancer tissue appears to be optimal when bypassing chemoresistance. Metformin induces ferroptosis by acting on the miR-324-3p/GPX4 axis. For example, in liver cancer, the combination of metformin and sorafenib induces ferroptosis through the p62-Keap1-Nrf2 pathway. Cancer cells require significantly higher concentrations of iron ions for proliferation and progression. The involvement of metformin in iron-dependent cell death has been demonstrated using breast cancer as an example. Ferroptosis is triggered by iron-dependent lipid peroxidation and its regulation is actively assisted by the cystine-glutamate antiporter SLC7A11, which works in close interaction with glutathione peroxidase 4 and glutathione, which regulates peroxidation. The SLC7A11 antiporter regulates glutathione synthesis and these three factors play a key role in the implementation of ferroptosis. A feature of the action of metformin on ferroptosis processes is the relationship with the type of pathology, activation or inhibition of ferroptosis by this agent is intended to optimize biochemical processes. A number of studies are given as examples in which metformin causes inhibition of ferroptosis. In the future, precise verification of the metabolic pathways by which metformin induces or inhibits ferroptosis is of paramount importance for the effective treatment of a wide range of pathologies.

Introduction. 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine is a promising agent for enhancing the liver's detoxifying function by inducing the cytochrome P450 system. In the pharmaceutical development of a new drug based on it, the use of a systematic Quality-by-Design approach becomes relevant, which includes the definition of the target quality profile, critical process and material parameters, as well as quality attributes of the finished product.

The aim of the study is to determine critical quality attributes and process parameters within the framework of the Quality-by-Design approach in the pharmaceutical development of a finished dosage form of a new inducer of the hepatocyte monooxygenase system - 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine.

Material and methods. The object of the study is the technology of obtaining 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine tablets by wet granulation. The method of constructing Ishikawa diagrams and Failure Mode and Effects Analysis were used to determine the critical process parameters and quality attributes of the finished product.

Results. Critical quality attributes of tablets (uniformity of dosing, disintegration, crushing strength), materials (loss-on-drying of lactose monohydrate, microcrystalline cellulose, microbiological purity of the materials, related impurities of the 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine), critical process parameters (size of granules, their drying mode, volume and concentration of the binding solution and control of residual moisture) were determined.

Conclusion. Critical parameters and attributes of the technology and the finished product have been established. Sections 5 and 9 of the pilot industrial regulations for the production of 6,8-dimethyl-2-piperidinomethyl-2,3-dihydrothiazolo[2,3-F]xanthine tablets have been substantiated.

Introduction. Reynoutria sachalinensis is a promising subject for studying the mechanisms of tannin synthesis in plants due to the high proanthocyanidins content.

This study aimed to optimize the preparation of R. sachalinensis leaf extracts to determine the activity of shikimate dehydrogenase, a key enzyme in the shikimate pathway involved in tannin biosynthesis.

Material and methods. Aqueous extraction followed by protein precipitation using 60 or 80% (v/v) acetone, with or without glycerol, was carried out. The effect of freezing at –80 °C on shikimate dehydrogenase activity was also assessed.

Results. It was found that freezing both crude and acetone-purified extracts did not decrease shikimate dehydrogenase activity, while increasing the acetone concentration to 80% (v/v) led to an increase in enzyme activity compared to 60%(v/v) acetone. Glycerol had no significant effect on enzyme activity.

Conclusion. Thus, the optimized extraction using 80% (v/v) acetone precipitation and low-temperature storage allows for efficient extraction of proteins and enzymes, particularly shikimate dehydrogenase, from R. sachalinensis leaves for subsequent biochemical studies.

Intriduction. The neurodegenerative and cerebrovascular diseases are among the leading causes of disability all over the world and the second-largest risk factor for premature mortality. A perennial plant of the Crassulaceae family, Orostachys spinosa (L.) Sweet, deserves special attention in the prevention and comprehensive treatment of these diseases. Its aboveground parts are characterized by a metabolites diversity.

The aim of the study – to evaluate the neuroprotective effect of Orostachys spinosa dry extract in cerebral ischemia/reperfusion in Wistar rats.

Material and methods. Сerebral ischemia was modeled by a five-minute occlusion of the common carotid arteries on Wistar rats.
O. spinosa extract at a dose of 100 mg/kg was administered for 14 days before modeling ischemia. After 48 hours the animals were tested in the "open field" and a conditioned passive avoidance reaction (CPAR) was developed. After 24 and 72 hours the neuron-specific enolase (NSE) level were determined in the blood serum and the growth factors (BDNF, GDNF and VEGFa) content in the brain cytolysate. Also histological studies of the brain were performed.

Research results. It has been established that O. spinosa extract increases the rearings and the animal movements number in the "open field", and also improves the development and maintenance of the CPAR. O. spinosa extract decreases the content of NSE and increases the concentration of growth factors in the brain cytolysate. O. spinosa extract decreases the number of pyknotic neurons by 24 and 30% (p <0.05) in the cerebral cortex and hippocampus, reduces the number of "shadow cells" by 20% (p <0.05).

Conclusion. O. spinosa dry extract has a neuroprotective effect during cerebral ischemia/reperfusion.

Introdаction. Every year there is an increase in the use of herbal preparations to maintain public health. Herbal medicines, as a rule, are characterized by a wider range of pharmacological activity and lower toxicity compared to synthetic drugs. Common chicory (Cichorium intybus L.) of the Asteraceae family, due to its rich content of biologically active substances and significant raw material base, is used to treat various ailments and is a promising object for the development of new medicines and feed additives for farm animals.

The aim of the work is a comparative analysis of experimental data on the toxicity of dry extracts from the aboveground part of wild and cultivated chicory with a single injection to laboratory animals of different species, age and gender to determine the prospects for the creation of medicines based on them.

Material and methods. Toxicity parameters of dry extracts from wild chicory grass (Cichorium intybus L.) and rosette leaves of a cultivated form of chicory obtained in the Department of Phytochemistry of the Center for Chemistry and Pharmaceutical Technology of the VILAR Federal State Medical University with a single intraperitoneal and intragastric administration to male and female BALB/c mice and Wistar rats aged 3 weeks, 3- and 12 months old.

Results. In previous experimental studies, the parameters of acute toxicity of the studied extracts for laboratory animals of different species, sex and age with two methods of administration were determined. A comparative analysis of the data obtained showed that the dry extract from the leaves of cultivated chicory is on average 2 to 2.5 times less toxic than the dry extract from the grass of a wild plant with both methods of administration to both mice and rats of different ages.

Conclusions. Significant differences in the content and qualitative composition of phenolic compounds determine the difference in the toxicity of dry extracts of wild and cultivated chicory and allow them to be used as raw materials for the production of medicines and feed additives for farm animals.