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Previously, autophagy was termed as a mechanism used by the cells with a lack of essential nutrients supporting homeostasis. Over the decade of studies, autophagy proved to be a more complex, ambiguous mechanism. Its activation depends on the nature of stimulus, type of immune cells and the final result. Both canonical and non-canonical autophagy, being similar in molecular events, but showing their own distinctive features, are key processes in protecting the body from penetration of intracellular pathogens, maintaining the required level of nutrients in the cell, and removing damaged organelles and cells. Canonical autophagy probably evolved as a homeostatic response to cellular stress and nutritional deficiencies, whereas non-canonical autophagy emerged as a response to suppression of inflammation. Non-canonical autophagy, hereinafter referred to as LC3-associated phagocytosis (LAP), combines the molecular mechanism of phagocytosis with an autophagy mechanism characterized by ingestion of exogenous pathogens, formation of phagosomes (laposomes) and enhanced fusion with lysosomes, followed by degradation of their contents.Significant differences were found between the processes of LAP- and canonical autophagy, which are similar in its mechanism of action. The presence of PI3K complexes in both processes, utilization and intracellular degradation of the “cargo” which is not required for the cells and organism proceeding in the lysosomes, and involvement of almost the same proteins provide similarity of their mechanisms. However, there are differences in the initiation of the processes, e.g., different types of PI3K complexes (in autophagy, PI3K III class 1 and 2 types; in LAP PI3K III, class 3 type), usage of reactive oxygen species in LAP, different types of regulatory proteins involved (ULK1, FIP200, ATG13 , Ambra1, WIPI2, ATG14 in autophagy; and Rubicon and NOX2 in LC3-associated phagocytosis), different number of layers in the membrane structure in which lysis occurs (double-membrane autophagolysosome and single-layer membrane in laposomes) clearly depict the variety of canonical and non-canonical autophagy. The two pathways are directed for different types of biological objects, i.e., intracellular pathogens, dysfunctional proteins and organelles in autophagy, and extracellular pathogens, apoptotic bodies, bacteria, utilized in LAP, thus making these mechanisms completely different in their significance.Collectively, the new data indicate that autophagy performed via both canonical and non-canonical pathways, has evolved into a host defense mechanism capable of resisting immunological and pathogenic stress and mediating immunological tolerance to both intra- and extracellular threats. The present review discusses fundamental molecular differences between these mechanisms, as well as their role in immunity, based on the latest literature data.

In western European countries prostate cancer is one of the most common malignant disease among male population. Due to innovations in molecular genetics research technology over recent years genetic features of etiology and pathogenesis of prostate cancer have been discovered and this helped to distinguish people with high risk of prostate cancer development. Hereditary forms of malignant tumors occupy a special position due to association with mutations in BRCA1/2 gene in a group of patients with prostate cancer. The most important part of examination of patients with malignant diseases is medico-genetic counseling. It helps to reveal the hereditary of the disease. The detection of germinal mutations in BRCA1/2 gene helps to personify diagnostic measures for primary prophylaxis and treatment of prostate cancer.Here is a case of one patient with hereditary feature of prostate cancer with a mutation in BRCA1 gene. It is important to note that revealing mutations in BRSA gene helps to early diagnose malignant neoplasms. Screening measures to reveal germinal mutations in healthy population can improve early detection of such malignant diseases as breast cancer, prostate cancer and other malignant neoplasms.

Lung cancer holds a leading position in the cancer mortality pattern worldwide. The emergence of knowledge about driver mutations heralded a new era in the targeted therapy for lung carcinomas. ALK translocation is identified in 5–7% of non-small cell lung cancer cases. ALK-positive lung adenocarcinomas are associated with specific clinical features, including no or light smoking history and younger age. Alectinib is a novel ALK inhibitor that has been granted a breakthrough therapy status by the FDA to accelerate approval as a second-line therapy after progression during crizotinib therapy.Here, the case of a patient with metastatic ALK-positive lung adenocarcinoma treated with alectinib has been discussed. Molecular genetic testing for driver mutations makes it possible to personalize approaches to anticancer drug therapy. At the same time, the custom-compounded targeted therapy is more often accompanied by significant objective responses and moderate symptoms of toxicity, which is relevant for patients in critical condition. The experience in using alectinib demonstrates the possibility of its long-term administration with high efficiency and a controlled safety profile.

Aim. To analyze the expression of key apoptosis (Bcl-2, caspase-3) and autophagy (Beclin 1, Vps34, p62 and LC3) proteins regulators in peripheral blood T-lymphocytes of patients with systemic lupus erythematosus. Methods. The object of the study was peripheral blood T-lymphocytes of healthy donors and patients with systemic lupus erythematosus. To obtain T cells, we used the immunomagnetic separation method. Protein expression was analyzed using the Western blot method. Statistically analyzing the results was performed using the R software environment. The data was represented using boxplots. Groups were compared using the MannWhitney test. Results. According to the results of the study of the apoptotic proteins, we found an increased content of caspase-3 and the absence of significant changes in the content of the anti-apoptotic protein Bcl-2 in patients with lupus, which indicates active apoptotic activity. A comparative analysis of Beclin 1 and Vps34 showed their increased content in the cells of patients, which indicates the activation of autophagy. The analysis of two isoforms of LC3 protein revealed their low content in the group of patients. Since the scatter of indicators was very different from the average value, we analyzed these indicators depending on the severity of the disease. In the acute course group, high content of protein LC3-I was detected, the content of form II was lower. In the group with the subacute course, the number of both isoforms is lower than in the other groups. In the group with a chronic course, significant increases of protein LC3-II and a decrease in the ratio of LC3-I/LC3-II were found. Conclusion. The study showed that depending on the severity of systemic lupus erythematosus, the content of protein LC3 isoforms changes, which can be used for differential diagnosis of disease forms.

The six different crystals of the versatile clathrate host racemic 1,1‘-binaphthyl-2,2‘-dicarboxylic acid (BNDA) that are obtained from its solution in 1,4-dioxane at varying crystallization temperatures from 15 to 35 °C are reported. They involve four solvates (1, 2BNDA/dioxane; 2, BNDA/dioxane; 3, 2BNDA/2dioxane; 4, BNDA/2dioxane), one mixed 1,4-dioxane solvate with water (5, BNDA/3dioxane/H3O+), and one guest-free form. The framework structures are characterized by 0D associates (1, 3, and 4) that either include (3, 4) or don't include (1) guest molecules and by 1D zigzag chains with (5) or without (2) participation of guest molecules. The pseudotetramorphic solvates 1−4 are formed in accordance with a previously formulated rule for pseudopolymorphic clathrates, which is as follows: (i) the guest:host ratio decreases as the crystallization temperature increases, and (ii) the higher the formation temperature of the clathrate modification, the closer the space occupied by guest molecules.

At room temperature trans-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid forms different clathrates with ethyl and butyl acetate in a 1:1 host-guest ratio. Increasing the formation temperature up to 40°C gives rise to pseudodimorphic clathrates with half the content of the guest component. All the clathrates studied feature intersecting channels of guest molecules within their structures.

Depending on crystallization conditions, dianilinegossypol and ethylacetate form low (ambient temperature, α-phase) and high temperature (t = 35°C, β-phase) clathrate modifications. The structure of the α-phase has been discussed earlier [1]. Crystals of the 1 : 1 β-phase complex, C42H40O6N2·C4O2H8, are monoclinic, space group P21/c, a = 11.362(6), b = 19.479(9), c = 19.085(9) A, β = 103.21(4)°, V = 4112(3)A3, Z = 4, R = 0.084 for 3210 observed reflections.

Crystal structures of the α- and β-phase inclusion complexes of dianilinegossypol with acetone obtained at 20° and 30 °C, respectively, have been determined by X-ray structure analysis. Crystal data of the α-phase complex are: C42H40O6N2⋅2C3H6O, orthorhombic, space group Pccn, a = 29.501(9), b = 10.866(2), c = 13.756(3) A, V = 4409(1) A3, Z = 4, Dx = 1.18 g cm-3. The structure has been refined to a final R value of 0.117 for 1401 observed reflections. The host–guest ratio for the β-phase complex is the same (1 : 2) and the crystals are monoclinic, space group C2/c, a = 28.352(6), b = 11.836(2), c = 13.196(1) A, β = 93.05(1)°, V = 4422(2) A3, Z = 4, Dx =1.18 g cm-3. The structure has been refined to a final R value of 0.077 for 1414 observed reflections.

Nonsymmetrical aldehyde derivatives of gossypol, a yellow polyphenolic pigment of cottonseed, were synthesized by reactions with ammonia, aniline, 4-aminoantipyrine, and barbituric acid. Their structures were determined by UV spectrophotometry and IR and (1)H NMR spectroscopy methods. Their acute toxicities in white mice were compared with those of gossypol and the corresponding symmetrical analogues. It was demonstrated that in general, the fewer free aldehyde groups that contained the gossypol derivative, the lower its acute toxicity. Only in the case of a nonsymmetrical gossypol derivative bearing a 4-aminoantipyrine residue did we observe a deviation from the above correlation: its symmetrical counterpart was even more toxic, but still less toxic than gossypol.

A generalization of information relating to the use of refractory concrete in heat-using equipment resulted in the design development of standardized blocks, panels, and steel and ceramic securing elements. The standardization is based on multiples of the dimensions of standard brick (with an allowance for the joints), The number of block types for a given furnace should be minimal (not more than five).

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Cytochemical studies of the components of intracellular microbicidal system of leukocytes were performed on rabbits. Two experimental models of Salmonella infection were used. With the oral infection by S. typhimurium the mild form of experimental salmonellosis was noticed. The decrease in myeloperoxidase activity and cation protein and lipid content, as well as an increase in glycogen content and NBT-test activity were observed. Intravenous injection of S. typhimurium endotoxin produced the clinical pattern of endotoxin shock. The activity of all the variables tested was decreased. It returned to standard values 120-240 hours after endotoxin injection.

Electron microscopy was used to examine renal glomerules and tubules, as well as the renal neuro-endocrine apparatus 3 and 24 hours after intravenous injection of 2 mg/kg S. typhimurium endotoxin. The studies demonstrated swelling and vacuolization of the endothelial cells and an increase in the glomerular capillaries of the number of polymorphonuclear leukocytes with lysosomal sequestration and fibrin emergence 3 hours after endotoxin injection, intravascular coagulation, accumulation of polymorphonuclear leukocytes in the peritubular capillaries, fat dystrophy of the mesangial cells and nephrocytes in the proximal tubules after 24 hours. The method for mathematical estimation of granulation in the juxtaglomerular apparatus (JGA), designed by the authors, from the density of the contents of epithelioid cell granules enabled the detection of JGA activation, particularly 24 hours after endotoxin injection. The reduction of the number of granules in the interstitial cells of the renal medulla might be due both to JGA activation and endotoxin action that stimulates the synthesis of prostaglandins.

In recent years, there have been reports of the development of thrombohemorrhagic syndrome in patients with salmonellosis. We also observed 7 patients with salmonellosis who had clinically pronounced thrombohemorrhagic syndrome. The course of the disease in one of them was complicated by massive bleeding into the parenchyma of the lungs, in the other by hemorrhage into the brain substance. In 2 patients, thrombosis of mesenteric vessels was detected, in 3 multiple hemorrhages in the mucous membranes of the small intestine and in 3 colon. Thrombohemorrhagic syndrome developed against the background of toxic and infectious shock, which led to fatal outcomes. It is known that with salmonella intoxication in the patient's body, not only hemodynamic disorders develop, but also symptoms of the direct effect of endotoxin on the tissues of various organs and systems are revealed.