Vol 19, No 3 (2021)

Lung cancer occupies the leading position in at the structure of oncological morbidity in the developed countries. The overall five-year survival rate for lung cancer isn’t exceed to 10-20% even using of the entire modern arsenal of therapeutic methods. Multiple drug resistance is an important aspect of the ineffectiveness of the treatment of lung cancer and it also is an urgent direction in the study of tumors. Pharmacokinetic aspects such as absorption, distribution, metabolism and excretion reduce the amount of chemotherapeutic agent that effectively reaches cancer cells. The development of the drug resistance limits the effectiveness of chemotherapeutic treatment of cancer and a failure rate of the treatment of metastatic tumors becomes more than 90%. Results of the study have shown that the soluble calcium-binding protein sorcin is involved in a development of the multidrug resistance in different types of human tumors. However, the potential molecular mechanism underlying at the ability of sorcin to regulate the development of multidrug resistance in human lung cancer is not complettely understood. There is an urgent need for new therapeutic strategies and further research on the role of sorcin in the development of the multidrug resistance phenotype that will help to identify sorcin as a new diagnostic and therapeutic marker for various types of lung cancer. This review is devoted to the analysis of modern research in this direction.

Recently, the involvement of histamine in the regulation of the function of cells in the immune system has been actively studied, including the ability of the mediator to modulate inflammatory responses of different cell types to infectious agents by activating the expression of pattern-recognition receptors. The correlation of histamine with the development of visceral hypersensitivity has also been actively discussed since the mediator can act as a sensitizing agent that alters the activity of nociceptive vanilloid receptors. At the same time, although a significant amount of records has been accumulated disclosing the molecular pathways of histamine biosynthesis and metabolism, intracellular signal transduction schemes with its participation, as well as its main physiological and pathological effects in the organism, there is still no clear understanding of the role of histamine and histamine receptors in neuroimmune interactions. This work presents a review of the current state of the problem and, in particular, summarizes the information reported in the literature considering the effect of histamine on many biological functions of the organism in the context of neuroimmune interactions. The analysis of the studies has allowed establishing the physiological effects of this mediator, in particular, to be realized through innate immunity Toll-like receptors (TLRs). At that, TLRs seem to be able to regulate the expression pattern of vanilloid receptor TRPV1 on sensory neurons in a histamine-dependent manner. Hopefully, further research in this area will contribute to a better understanding of the general mechanisms of inflammatory and pain response formation.

Introduction. The identification of molecular components contributes to the realization of the targeted properties of multicomponent drugs to study their molecular mechanism and therapeutic targets. The polypeptide complex isolated from cattle thymus (thymalin), and short peptides KE (Lys-Glu), EDP (Glu-Asp-Pro), designed and then synthesized based on the analysis of its amino acid composition, have similar biological effects. The dipeptide EW was previously found in the thymalin medicine. The aim of the study. Identification of short peptides KE and EDP as part of the thymus polypeptide complex. Method. In order to confirm the presence of these peptides in thymalin, the method of ultra-efficient liquid chromatography-mass spectrometry was used. Results. As a result of the study, the short peptides KE and EDP were found to be a part (minor components) of the thymus polypeptide complex (thymalin). Conclusion. The biological and therapeutic activity of the thymalin medicine is due to the effects of the short peptides KE and EDP found in this study, and the dipeptide EW, which was previously discovered in its composition.

Introduction. The oral cavity is the beginning of the human digestive system and the presence of pathological changes in it: a shift in the dynamic balance, composition, and types of microorganisms inhabiting the oral cavity; color change; the appearance of pain and discomfort; etc., all this may indicate pathological changes in other body systems. The accuracy and safety of non-invasive diagnostics at the cellular and subcellular levels is ensured by modern optical systems. However, optical radiation has difficulty in transporting probe radiation deep into biological tissues due to significant scattering of radiation in the visible and near-infrared spectral ranges. It is possible to increase the penetration of radiation using the method of optical clearing. The aim of the study. To evaluate the effectiveness of optical enlightenment of tissues of attached pig gingiva after full immersion in 87.5% glycerol, and also to determine its diffusion coefficient and degree of tortuosity (porosity) of pig gingival tissue. Methods. The diffuse reflection and total transmission spectra were recorded on a Shimadzu UV-2550 spectrophotometer with an integrating sphere. The completion of the immersion process was evaluated by stopping the change in the diffuse reflection spectra. To assess the kinetics of the optical clearing process, the diffusion coefficient of glycerol into the gingival tissue was calculated using the free diffusion model. The effectiveness of «optical clearing» was evaluated using experimental data on the spectra of the complete transmission. Results. On average, the ex-vivo diffusion coefficient of glycerol in pig gingival tissue was (3.2±().7)'W6 cm2/s. The tortuosity (porosity) for the layer of the own gingival plate is estimated as S&3.4. Highest efficiency optical clearing is achieved at a wavelength of200 nm and amounts to 1860%, with sufficiently small absolute transmittance values. Conclusion. Three dynamic transparency windows have been identified in the UV range of the spectrum, with gingival immersion in 87.5% glycerol, from 200 to 250 nm, from 250 to 300 nm and from 300 to 400 nm. This can be used to develop non-invasive optical diagnostic and therapeutic methods and needs further study.

Introduction: nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. But it remains unclear what factors influence the progression of the disease. It is interesting to study the influence of the genetic aspect on the course of NAFLD. The aim of the study: to investigate the influence of PNPLA3, SERPINA1, HFE gene polymorphisms on the development of NAFLD. Methods: 59 NAFLD patients were examined. Anthropometric data and biochemical indices were assessed. Hereditary liver diseases were excluded. The degree of steatosis and the stage of hepatic fibrosis were assessed using transient elastometry on a Fibroscan. Genotyping of point mutations in genes PNPLA3 (rs738409), SERPINA1 (rs17580 and rs28929474) and HFE (rs1799945, rs1800730 and rs1800562) was performed by real-time PCR. Results: polymorphisms in the PNPLA3 gene were found in 61%, in the SERPINA1 gene - in 10.2%, and in the HFE gene - in 28.8% of cases. In carriers of the I148Mpolymorphism of the PNPLA3 gene the ALT level was significantly higher in the comparison groups ofhetero- and homozygous carriers and the normal genotype (p=0.012 and p=0.017). The AST level was also significantly higher in carriers of the MZ genotype of the SERPINA1 gene (p=0.049). The ALT level was higher in carriers of the H63D and C282Ypolymorphisms of the HFE gene compared with the normal genotype (p=0.02 and p=0.03). The same relationship was demonstrated for carriers of C282Y and AST level (p=0.017). When assessing the level of steatosis, the average CAP was higher in the group of homozygous carriers ofI148M of the PNPLA3 gene (p=0.045) and carriers of polymorphism C282Y (p=0.021) compared with the normal genotype. Authors found no relationship between pathological polymorphisms in the PNPLA3, SERPINA1, and HFE genes and the severity of fibrotic changes. Patients with a BMI > of 35 kg/m2 had a higher liver fibrosis rate (p=0.037). Conclusion: the presence ofpolymorphisms of the PNPLA3, SERPINA1, and HFE genes in NAFLD is associated with an increase in laboratory markers of hepatocellular damage, as well as the severity of hepatic steatosis.