Aggregated proteins in malignant and benign neoplasms.

AIM: To evaluate the presence of the aggregated proteins in malignant and benign neoplasms for clarifying the role of impaired protein metabolism in the formation of the altered tissues. OBJECT AND METHODS: The histological specimens prepared from the operative materials of 196 patients with different forms of malignant and benign neoplasms were stained with Congo red and Thioflavin T and studied under the light and polarization microscope. RESULTS: The various forms of ß-stacked protein aggregates (ß-SPA) inclusions were detected in amyloids, keloid tissue, benign polyps, and several malignant tumors. CONCLUSION: The formation of non-functional protein aggregates proves the complex character of the impairment of protein metabolism resulting in local or systemic accumulation of secondary protein toxins results in ß-SPA formation as the self-sustaining complex of parametabolic processes. The ß-SPA formation is of considerable interest since their properties lead to the impairment of the normal physiological processes in adjacent tissues ensuring the chronic course of the pathology.

The potential beneficial role of isoflavones in type 2 diabetes mellitus.

Diabetes is a chronic global disease afflicting a substantial number of people worldwide. Different mechanisms have been highlighted in the progression of this disease such as dysfunction of pancreatic ß-cells, insulin resistance, elevated levels of free fatty acids which result in overproduction of reactive oxygen species, as well as pancreatic ß-cell failure and apoptosis. Isoflavones, are polyphenolic phytochemicals found in most leguminous plants, and have been identified as potentially useful antidiabetic agents. The pleiotropic effects of isoflavones include the targeting of numerous cell signaling pathways involved in the pathogenesis of diabetes. Several observational studies have supported the direct relationship between isoflavones intake and a lowered risk of diabetes. The aim of this review was to summarize relevant findings on the effects of isoflavone intake and risk of type II diabetes mellitus (T2DM), and to highlight some of the possible anti-diabetic molecular mechanisms of these polyphenols. Despite the promising therapeutic effects of isoflavones to moderate risk of T2DM, the underlying mechanisms for their preventive effects are still largely unknown. The acceptable human dosage levels of these polyphenols remain a debatable topic as these have a profound influence on the observed benefits. Considerable numbers of well-controlled, long-term human clinical studies of these phytochemicals are highly recommended. Furthermore, combinations of isoflavones and their derivatives in combination with other naturally isolated compounds, and perhaps even those drugs currently used therapeutically to control diabetes mellitus in clinical practice, may be worth exploring in the future.

Interactions of Bimodal Magnetic and Fluorescent Nanoparticles Based on Carbon Quantum Dots and Iron-Carbon Nanocomposites with Cell Cultures.

Interactions of bimodal (fluorescent and magnetic) nanoparticles with HeLa cells were studied. The nanoparticles, characterized by high magnetic moment and relaxing capacity, exhibited fluorescence sufficient for their use as labels in confocal microscopy and flow cytometry. Penetration of these nanoparticles into the cell depended on their surface charge: positively charged nanoparticles of this structure penetrated inside, while negatively charged particles were not found in the cells.

[The proapoptotic p53 (C72G) and p21 (C31A) polymorphisms as the risk factors for the development of primary open-angle glaucoma in Transbaikalian region].

The incidence of p53 (C72G) and p21 (C31A) proapoptotic polymorphisms is studied in Russian and Buryat population of Transbaicalian region and prognostic value of these polymorphisms in development of primary open-angle glaucoma (POAG) is assessed. Significant difference in incidence of p53 and p21 was found between healthy subjects and glaucoma patients in both ethnic groups. The incidence of C and G variants of p53-gene and C and A variants of p21-gene differ in glaucoma patients and healthy subjects. The study lets us propose that p53 (C72G) and p27 (C31A) polymorphisms contribute to the risk of POAG onset in Russian and Buryat population as well.

[Patterns of somatic embryo formation in Siberian larch: embryological aspects].

Somatic embryogenesis was induced in Siberian larch by in vitro culturing zygotic embryos at different developmental stages. Cultures were grown in modified Murashige and Skoog medium supplemented with hormones 2,4-dichlorophenoxyacetic acid (2 mg/l) and 6-benzylaminopurine (0.5-1 mg/l). The success of somatic embryogenesis in this species depended on the tree genotype and developmental stage of embryos used for culturing. Somatic embryogenesis from immature zygotic embryos at the stage of cotyledon initiation was most active. After 5-10 days, such embryos formed the embryogenic tissue including two cell types--elongated highly vacuolated embryonic tubes and small embryonic cells. Somatic embryos were isolated from proliferating embryogenic tissues after 2 months of culture.

Androgen receptor gene haplotype is associated with male infertility.

The purpose of the current study was to evaluate the importance of androgen receptor (AR) gene haplotypes and polymorphic CAG/GGN microsatellites in the aetiology of male infertility. We genotyped six haplotype-tagging single nucleotide polymorphisms and CAG/GGN microsatellites of the AR gene in 112 infertile and 212 control Estonian men. A total of 13 AR haplotypes (HAP1-13) were identified, among which HAP4 was found to confer increased risk for male infertility (OR = 5.15, 95% CI = 1.75-15.15, p = 0.003). However, infertile patients and controls had similar lengths and distributions of both AR CAG (mean +/- SD number of repeats 21.1 +/- 2.5 vs. 21.2 +/- 2.3, respectively) and GGN (mean +/- SD number of repeats 22.5 +/- 1.5 vs. 22.4 +/- 1.9, respectively) repeats. In addition, HAP2 was associated with more CAG repeats (r = 1.17, p = 0.033) and HAP3 with fewer CAG repeats (r = -2.93, p < 0.001) than the major haplotype HAP1. HAP3 and HAP4 were associated with more GGN repeats (r = 1.35, p = 0.001 and r = 1.36, p = 0.002, respectively) than HAP1. In conclusion, our results implicated the AR-HAP4 gene haplotype in increased risk for male infertility, while no association was found between AR CAG/GGN microsatellites and impaired spermatogenesis.

[The comprehensive diagnosis and treatment of lymphosarcoma of the pharynx]. / Kompleksnaia diagnostika i lechenie limfosarkomy glotki.

Modern methods (intrascopic and other instrumental) were used to increase the diagnostic efficiency and extension of the tumour process in 22 patients with lymphosarcoma of the pharynx. Optimal treatment efficacy is achieved in lymphosarcoma of the pharynx by combined use of surgical, radiation (non-traditional course) treatment as well as chemotherapy which is used at early stages as an adjunctive method.

[Molecular and cellular mechanisms of the induction of differentiation of tumor cells]. / Molekuliarnye i kletochnye mekhanizmy induktsii differentsirovki opukholevykh kletok.

Recent data on the mechanism of animal and human tumour cell differentiation induced by different natural and synthetic agents, including antitumour drugs are reviewed. The central role of plasma membranes of the tumour cells and their receptor patterns in the commitment and terminal differentiation of cells is emphasized. Development of a new approach to the cancer therapy based on the combination of tumour cell differentiation induction and cytotoxic effects is discussed.

[Bacteria decomposing technical oils]. / Bakterii, razrushaiushchee tekhnicheskie masla.

Fifty bacterial cultures were isolated from technical oils stored for different periods of time. Twenty out of the fifty strains decomposed technical oils. The bacteria were identified and classified as Bacillus strains. Bacillus subtilis, strains 7 and 10, and B. pumilus, strain 13, isolated from oils MK-8 + 10% Akor-1 and MT-16p as well as from AMG-10 were found to be most active and can be recommended as test cultures to study the resistance of technical oils against bacterial degradation.

[Interaction of sarcolysine with beta-adrenoreceptors in tumor cells]. / O vzaimodeistvii sarkolizina s beta-adrenoretseptorami opukholevykh kletok.

The sites of specific binding of 3H-L-dihydroalprenolol (3H-DHA) were identified on the surface of ascites sarcoma 37 cells, using competitive displacement and binding of the beta-adrenergic antagonists, 3H-DHA and L-propranolol. These binding sites possessed the properties of beta-adrenergic receptors coupled with adenylate cyclase. Analysis of 3H-DHA binding by the Scatchard method revealed the presence of beta-adrenergic receptors of two types, i. e., with a high (Kd = 0.9-1.0 nM) and low (Kd = 15-20 nM) affinity for 3H-DHA. The number of high affinity receptors was (5.0-7.5) X 10(3); that of low affinity receptors was (20-30) X 10(3) on a per cell basis. Sarcolysine at concentrations of 1-10 microM displaced receptor-bound 3H-DHA, competed with the ligand for the common binding sites and caused, similar to isoproterenol, a short-term elevation of the intracellular cAMP content. Sarcolysine within the same concentration range (2.5-25 microM) caused non-competitive inhibition of the cAMP phosphodiesterase (PDE2) activity of plasma membranes isolated from ascites sarcoma 37 cells. The data obtained point to the functional coupling between beta-adrenergic receptors, adenylate cyclase and membraneous PDE2 of tumour cells as well as to its possible role in the antitumour effect of sarcolysine.

[Evaluation of biochemical criteria for sensitivity of tumor cells to methotrexate by means of mathematic simulation]. / Otsenka biokhimicheskikh kriteriev chuvstvitel'nosti opukholevykh kletox k metotreksatu s pomoshch'iumetodov matematicheskogo modelirovaniia.

A mathematical model of the folic acid cycle and of thymidylate, purines, methionine and serine biosynthetic reactions in leukemia L-1210 and Ehrlich ascite tumour cells was developed. This model was used for an analysis of biochemical criteria of different sensitivity of these tumours to methotrexate, such as differences in the rates of methotrexate transport into the cells, levels of target enzyme, dihydrofolate reductase, its affinity for the inhibitor and the capacity of "salvage" pathways of tetrahydrofolate formation. It was shown that low sensitivity of the Ehrlich ascite tumour cells to methotrexate is due to mainly a high activity of methionine synthetase, which represents a "salvage" pathway of tetrahydrofolic acid regeneration in the presence of methotrexate. The results of this analysis were used to predict a combined utilization of methotrexate and methionine synthetase inhibitor. The pretreatment of the tumour cells of the methionine synthetase inhibitor enhances the effects of methotrexate on the thymidylate and purines syntheses, thus increasing their sensitivity to this drug.

Search for the biochemical parameters of tumor cell sensitivity and resistance to antimetabolites.

The metabolism of murine tumors sensitive and resistant to 6-theopurines and 5-fluorouracil (5-FU) was studied. A positive correlation between the tumor sensitivity to thiopurines, the level of hypoxanthine-guanine-phosphoribosyl transferase and the rates of the antimetabolite incorporation into RNA and DNA was shown. The sensitivity of tumors to 5-FU correlated with the rates of pyrimidine nucleosides and antimetabolite uptake and the time of retention of labeled 5-FU in RNA. The activites of orotate-phosphoribosyl transferase, uridine kinase, the degree of thymidylate synthetase inhibition of 5-FU and ratio of the de novo to salvage pathways of thymidylate biosynthesis are also important.

[Mathematical description and study of the folic acid cycle reactions]. / O matematicheskom opisanii i issledovanii zakonomernostei funktsionirovaniia tsikla folievoi kisloty.

A general description of the folic acid cycle and associate reactions of thymidilate, purines, methionine and serine biosyntheses is presented as a system of differential equations. The concrete models of this reaction complex as well as methotrexate transport into the leukemia L 1210 and Ehrlich ascite tumour cells and the dynamic inhibition of the target enzyme--dihydrofolate reductase--by methotrexate have been described and investigated. The adequacy of mathematical models to the experimental data has been demonstrated.