Objective: to investigate the antitumor effects of various forms of vitamin B12 in combination with various synergistic vitamins and evaluate the prospects for clinical applications.

Material and methods. Cell lines BT-474 (breast ductal carcinoma) and A549 (lung carcinoma) were used as an in vitro cell model, and transplantable epidermoid Lewis lung carcinoma (LLC) was used as an in vivo animal tumor model. Animal studies of LLC were carried out on 25 male F₁ hybrid mice (age 2.5–3 months, body weight 23–26 g). In silico research was conducted as a systematic computer analysis of 9,326 scientific sources.

Results. In vitro studies on cultures of two human tumor cell lines (BT-474 and A549) confirmed the cytotoxic effect of vitamin B12 (aquacobalamin). It has been shown that vitamin B12 has weak cytotoxic properties in the concentration range of 3.125–200 μg/L (IC50>200 nM), and its hydrophobic derivative (heptamethyl cyanoquacobyric acid ester) significantly reduces the survival of tumor lines. BT-474 and A549 cells at high concentrations (100–200 µg/l, IC50~100 nM). Experimental animals with an in vivo LLС model easily tolerated a drug based on vitamin B12. Exposure to the drug up to the 21^st day of LLС development was accompanied by an increasing tendency to inhibit tumor growth by 10–20% (р=0.059). The results of a systematic in silico review of the literature show that clinical data confirmed the significant antitumor effect of vitamin B12.

Conclusion. The cellular model indicated the antitumor properties of vitamin B12 and its hydrophobic derivative. With subchronic intragastric administration of B12 to tumor-bearing animals, a steady tendency to inhibit the LLС growth was observed. Analysis of clinical data confirmed the feasibility of the antitumor use of vitamin B12 individually and in combination with synergistic vitamins.

Background. Phenol and its derivatives (eg. parabens), phthalates and a number of other aromatic compounds exhibit various toxic effects when entering the human body due to unfavorable ecology, smoking, intake with food and medications. Integrated clinical and epidemiological studies into the clinical consequences of such effects are currently lacking.

Objective: To identify patient history parameters that are significantly associated with blood and urine levels of phenols and urine levels of phthalates.

Material and methods. The database of the UNESCO Institute for Microelements was used to compile a sample of patient descriptions (n=2746) containing information on the serum and/or urine levels of phenol and urine levels of phthalates. The data sample was analyzed using the methods of Zhuravlev–Rudakov topological and metric data analysis, as well as parametric and nonparametric statistics. The data analysis was carried out in three stages: (1) identification of statistically significant pairwise interactions by the methods of topological data analysis; (2) identification of clusters of pairwise interactions; (3) description of the obtained patterns in the form of metric diagrams, topological “interaction formulas” and “interaction types”.

Results. Higher urine levels of phenol were associated with increased levels of bone and cartilage destruction markers, hematopoiesis disorders (decreased hemoglobin and mean corpuscular volume), liver and kidney dysfunction (increased creatinine and albumin levels), decreased systolic blood pressure (hypotension) in the setting of lower intake of fiber, vitamins E, A, C, B2, B6, folates, and magnesium. Higher urine phenol concentrations were correlated with higher levels of a smoking biomarker (cotinine), indicating that smoking is a significant source of phenol and its derivatives in the human body. Higher blood phenol concentrations were associated with a history of smoking, asthma, type 2 diabetes mellitus (T2DM), vasomotor paroxysms (hot flashes), and pain symptoms. Significantly higher blood phenol concentrations were found in participants not taking vitamin and mineral supplements (VMS). Higher urine phthalate levels were found in patients with chronic obstructive pulmonary disease (COPD), alcoholism, pain symptoms (headaches, lower back and leg pain), diabetic polyneuropathy, hematopoiesis disorders (increased erythrocyte distribution width), cartilage homeostasis, liver dysfunction, kidney dysfunction and, in general, a decreased quality of life. Elevated urine phthalate levels corresponded to a lower intake of vitamins A, C, B2, B12, folates, cobalt, iron and lutein n the setting of higher blood concentrations of toxic cadmium, lead and cotinine. This confirms the correlation between smoking and increased concentrations of phenol and its derivatives.

Conclusion. Elevated urine levels of phenols and phthalates and blood serum levels of phenols are associated with a number of socially significant chronic pathologies (T2DM, COPD, pain, cartilage, and bone homeostasis disorders) and with lower VMS intakes. Thus, correction of the vitamin and microelement status is an ffective approach to supporting the body's detoxification systems against the negative impact of phenol and its derivatives.

Objective: To summarize current requirements for the quality management system (QMS) in the production of reference materials (RMs) for pharmaceutical and medical applications, as well as to assess the challenges and prospects of system implementation to ensure reliable quality control of medicinal products.

Material and methods. The study analyzed international and national regulatory documents, including ISO 9001, ISO/IEC 17025, ISO 17034 standards as well as good manufacturing practice (GMP) and good laboratory practice (GLP) guidelines. Experiences in QMS implementation at RMs manufacturing enterprises in Russia and abroad was examined. The research methodology was based on a comparative analysis of requirements and practical approaches to quality assurance.

Results. Ensuring RM production quality requires integration of the international standards ISO 9001, ISO/IEC 17025, ISO 17034, and GMP/GLP guidelines. Comparative analysis showed that the Russian quality system in RM production is gradually aligning with the global benchmarks through ISO-based accreditation and international cooperation, while retaining elements of state regulation. Promising directions for QMS development include further harmonization of international standards, digitalization of quality control, and differentiation of RMs to include new medicinal product types. All this necessitates development of novel methodology.

Conclusion. An effective QMS in RM production is a critical factor in ensuring the quality and safety of pharmaceutical products. Integration of ISO standards and GMP/GLP principles enables the production of reference materials with the required accuracy, stability, and traceability, recognized at the international level. Further improvement of the quality system will provide the industry with reliable reference materials and enhance confidence in quality control results both domestically and internationally.

Nitric oxide NO is a signaling molecule involved in numerous physical and pathological processes in biological systems. Highly sensitive sensor materials for measuring NO amounts in vivo in exhaled air and in body fluids (saliva, blood, urine) can be a useful tool in diagnostics and management of patients with bronchopulmonary, cardiovascular, neurological and tumor diseases. Several approaches to measuring NO in biosubstrates (including exhaled air) have been developed: fluorescence/chemiluminescence, electron spin resonance, electrochemical/amperometric (organic and inorganic) and enzymatic/protein sensors. Semiconductors, transition metal nitrides, phthalocyanine complexes, porphyrin and cobalamin derivatives with metals can serve as materials for NO sensors. Creating sensor materials based on vitamin B12 derivatives is an urgent research task in biomedicine. The article systematizes information on using various compounds as materials for NO-sensitive and selective sensors to measure/evaluate NO levels in various biosubstrates.