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This review aims to cast a look at endometriosis as a chronic and progressive gynecological disease.Endometriosis-affected tissues show a variety of pathologic features: alterations in cell growth, apoptosis, activation, angiogenesis, cell adhesion, and cytokine production. Fresh endometriotic lesions are associated with induction of an inflammatory reaction represented by overproduction of prostaglandins (PGE2), metalloproteinases (MMP-2, -3, -9), cytokines (IL-1β, IL-8, IFN-γ, TNF-α, MCP-1 and MIF) and adhesive molecules (ICAM-1, VCAM-1) and activation of synthesis of reactive oxygen and nitrogen species. The inflammatory process may lead to defective folliculogenesis by an altered follicular milieu. An increase in the number and change in function of macrophages, T- and B-lymphocytes and reduction of NK cells have been reported. Treg lymphocytes are known to play an extremely important role in controlling and modulating changes in the aberrant immune response in endometriosis. Dysregulation of the immune system results in both increased progression of endometriosis and its severity. In inflammatory conditions the immune cells provide immune defense at the local level - in peritoneal fluid - and could further cause: 1) a decrease of the number of NK CD16+ cells with expression of KIRs and an increase of NK CD57+; 2) increased numbers of CD8+ cells and CD11b

Intestinal microbes involved in many physiological processes owner, contributes to the formation and maintenance of immune homeostasis by regulating immune responses to protect against colonization by pathogens. A special role in the differentiation of various subpopulations of T-lymphocytes play the segmental filamentous bacteria (Segmented filamentous bacteria, SFB), capable of inducing a gut-associated lymphoid tissue (GALT) differentiation proinflammatory Th17-cells and members of the genus Clostridium (cluster IV and XIVa) and Bacteroides fragilis (polysaccharide A [PSA]), stimulating the formation of regulatory T-cells (Treg) and production of suppressor of cytokine IL-10. Important metabolites of B. fragilis are short-chain fatty acids (SCFA), which are able to activate GALT cells through the FFAR2 receptor. Lowering of the SCFA concentration leads to the reduction of the number of Treg in the intestine and breaks Th17/Treg balance. These changes lead to direct reducing of mRNA FFAR2, Foxp3 expression and increasing in RORyt GALT. Therefore, the goal was to determine the level of the key in the edge immunoregulatory bacteria intestinal microflora rats and their effects on the transcriptional activity of the genes Foxp3 and RORyt in GALT with Salmonella-induced inflammation and during administration of vancomycin and B. fragilis. To determine the genus and species of bacteria, as well as their number in the microflora of rats, was used the method of polymerase chain reaction (PCR-RV) with their identification by 16S rDNA genes. To study the transcriptional activity of genes using polymerase chain reaction reverse transcription real-time (RT-PCR). During the experiment with the introduction of animals vancomycin and Salmonella there was an increase in the level of SFB and a decrease in A. muciniphila, F. prausnitzii. Also, during infecting rats with S. Enteritidis and S. Typhimurium on the background of pre-treatment with vancomycin, there was an increase in the number of SFBs against the background of a pronounced decrease in Bacteroides—Prevotela group, A. muciniphila, Clostridium spp. clusters XIV, IV, and F. prausnitzii, which led to a decrease in the expression level of Foxp3+ mRNA and an increase in RORyt+, respectively. However, administration of B. fragilis to animals receiving S. Enteritidis or S. Typhimurium against pretreatment with vancomycin caused a decrease in the level of SFB and mRNA RORyt+, and, conversely, increased the number of Bacteroides—Prevotela group, A. muciniphila, Clostridium spp. clusters XIV, IV, F. prausnitzii and expression of Foxp3+ genes, which indicates the restoration of the homeostasis of the intestinal microbiome. The obtained results showed that B. fragilis can be successfully used in the treatment of inflammatory bowel diseases or diseases with impaired intestinal barrier function.

The paper reports on the production of the maral recombinant chymosin in the Escherichia coli expression system (SHaffle express strain) and the study of its biochemical properties relevant for the cheese-making industry. The highest maral recombinant prochymosin content in inclusion bodies was observed when producer cells were cultured at 25°C for 6 h after the introduction of an inducer, 10 mM isopropyl-β-D-1-thiogalactopyranoside. The biochemical properties of the obtained enzyme were compared with those of bovine and dromedarian recombinant chymosins. It is shown that total proteolytic activity of the maral recombinant chymosin was comparable with that of the bovine enzyme and that it exceeded the activity of the dromedarian enzyme by about 3.8 times. The thermal stability of the recombinant chymosin from maral was found to be 5–10°C higher than that of the chymosins from the cow and dromedary. The patterns of dependence of milk-clotting activity on the pH level and calcium chloride concentration in cow’s milk on the enzyme from maral met the requirements set by the cheese industry. Its high proteolytic activity and thermal stability limits the scope of application of maral recombinant chymosin to the production of cheeses with short ripening and short storage times.

The review discusses the basic biochemical properties of the known recombinant chymosins that are currently used in cheesemaking or may potentially be used as industrial milk coagulants. The parameters of the Michaelis–Menten kinetics, milk-clotting activity, proteolytic activity, specificity, and the dependence of coagulation ability on pH and calcium-ion concentration are considered.

We derive a nice representation for point symmetry transformations of the (1+1)-dimensional linear heat equation and properly interpret them. This allows us to prove that the pseudogroup of these transformations has exactly two connected components. That is, the heat equation admits a single independent discrete symmetry, which can be chosen to be alternating the sign of the dependent variable. We introduce the notion of pseudo-discrete elements of a Lie group and show that alternating the sign of the space variable, which was for a long time misinterpreted as a discrete symmetry of the heat equation, is in fact a pseudo-discrete element of its essential point symmetry group. The classification of subalgebras of the essential Lie invariance algebra of the heat equation is enhanced and the description of generalized symmetries of this equation is refined as well. We also consider the Burgers equation because of its relation to the heat equation and prove that it admits no discrete point symmetries. The developed approach to point-symmetry groups whose elements have components that are linear fractional in some variables can directly be extended to many other linear and nonlinear differential equations., Comment: 21 pages, published version, minor corrections, the application of an approach from arXiv:2205.13526 to the heat equation

We carry out the extended symmetry analysis of an ultraparabolic Fokker-Planck equation with three independent variables, which is also called the Kolmogorov equation and is singled out within the class of such Fokker-Planck equations by its remarkable symmetry properties. In particular, its essential Lie invariance algebra is eight-dimensional, which is the maximum dimension within the above class. We compute the complete point symmetry pseudogroup of the Fokker-Planck equation using the direct method, analyze its structure and single out its essential subgroup. After listing inequivalent one- and two-dimensional subalgebras of the essential and maximal Lie invariance algebras of this equation, we exhaustively classify its Lie reductions, carry out its peculiar generalized reductions and relate the latter reductions to generating solutions with iterative action of Lie-symmetry operators. As a result, we construct wide families of exact solutions of the Fokker-Planck equation, in particular, those parameterized by an arbitrary finite number of arbitrary solutions of the (1+1)-dimensional linear heat equation. We also establish the point similarity of the Fokker-Planck equation to the (1+2)-dimensional Kramers equations whose essential Lie invariance algebras are eight-dimensional, which allows us to find wide families of exact solutions of these Kramers equations in an easy way., Comment: 33 pages, 2 tables, corrected version

Recombinant chymosins (rСhns) of the cow and the camel are currently considered as standard milk coagulants for cheese-making. The search for a new type of milk-clotting enzymes that may exist in nature and can surpass the existing "cheese-making" standards is an urgent biotechnological task. Within this study, we for the first time constructed an expression vector allowing production of a recombinant analog of moose chymosin in the expression system of Escherichia coli (strain SHuffle express). We built a model of the spatial structure of moose chymosin and compared the topography of positive and negative surface charges with the correspondent structures of cow and camel chymosins. We found that the distribution of charges on the surface of moose chymosin has common features with that of cow and camel chymosins. However, the moose enzyme carries a unique positively charged patch, which is likely to affect its interaction with the substrate. Biochemical and technological properties of the moose rChn were studied. Commercial rСhns of cow and camel were used as comparison enzymes. In some technological parameters, the moose rChn proved to be superior to the reference enzymes. Сompared with the cow and camel rСhns, the moose chymosin specific activity is less dependent on the changes in CaCl2 concentration in the range of 1-5 mM and pH in the range of 6-7, which is an attractive technological property. The total proteolytic activity of the moose rСhn occupies an intermediate position between the rСhns of cow and camel. The combination of biochemical and technological properties of the moose rСhn argues for further study of this enzyme.Эталонными коагулянтами молока для сыроделия в настоящее время считаются рекомбинантные химозины (рХн) коровы и верблюда. Нахождение молокосвертывающих ферментов, способных превзойти эталонные коагулянты молока, является актуальной биотехнологической задачей. Нами сконструирован экспрессирующий вектор, который позволил впервые получить рекомбинантный аналог химозина лося в системе экспрессии Escherichia coli (штамм SHuffle Express). Построена модель пространственной структуры химозина лося, и проведено сравнение топографии положительных и отрицательных поверхностных зарядов с соответствующими структурами химозинов коровы и верблюда. Обнаружено, что распределение зарядов на поверхности химозина лося имеет общие черты с распределением зарядов химозинов коровы и верблюда. Отличительная особенность химозина лося – наличие положительно заряженного поверхностного участка, который, вероятно, влияет на его взаимодействие с субстратом. Исследованы основные биохимические и технологические свойства рХн лося. В качестве ферментов сравнения использовали коммерческие рХн коровы и верблюда. Установлено, что по некоторым технологическим показателям рХн лося превосходил ферменты сравнения. По сравнению с рХн коровы и верблюда специфическая активность рХн лося в меньшей степени зависит от изменения концентрации CaCl2 в диапазоне 1–5 мМ и рН в диапазоне 6–7, что является привлекательным технологическим свойством. По общей протеолитической активности рХн лося занимает промежуточное положение между ферментами коровы и верблюда. Совокупность биохимических и технологических свойств рХн лося свидетельствует о необходимости дальнейшего изучения этого фермента.

Summary.Changes in the state of gut-associated lymphoid tissue (GALT) and the composition of the intestinal microbiome, both in experimental STZ-induced diabetes and in development of type 1 diabetes in humans as well as chronic inflammation due to stimulation of innate immunity are crucially important in the development of type 1 diabetes mellitus. One of the most important mediators for interactions between the intestinal microbiome and GALT are specialized M cells of the follicle-associated epithelium, providing transcytotic delivery of antigens to the underlying lymphoid structures. TNFα-signaling also plays a supporting role in the formation of M cells. Therefore, the aim of our work was to study some features of TLRs expression and transcriptional activity of the Gp2, Spi-B, Nf-kB1, c-Rel, TNFα and TNFr genes in GALT in experimental diabetes mellitus (EDM), and after pentoxifylline administration. To identify TLR2+ cells and TLR4+ cells, an immunofluorescence method was used with monoclonal antibodies to corresponding pattern-recognizing receptors. To study the transcriptional activity of genes, the method of real-time reverse transcription polymerase chain reaction (RT-PCR) was used. In the course of developing experimental pathology, at the terms of 2 and 4 weeks, a decrease in the total density of TLR2+ and TLR4+ lymphocytes was observed in lamina propria of villus (villus) and subepithelial zone isolated lymphoid follicles (ILF) of rat ileum. At the same time, the density of TLR2 on the membrane of immunopositive cells was increased for small lymphocytes, and TLR4 density has became higher in medium and small lymphocytes. The pentoxifylline administration to diabetic rats resulted in a decrease in the total density of TLR2+ cells at the 2nd week of development of the pathology, and an increase in this index at the 4th week. The total density of TLR4+ cells showed changing growth rates only in villus at the 2nd week of EDM development in the presence of pentoxifylline. Changes in the density of TLR2 and TLR4 on the surface of lymphocytes were multidirectional. The development of diabetes is also reflected in the transcriptional induction of genes of the key transcription factors NF-kB1 and c-Rel in GALT cells at both the 2nd and 4th week of the development of EDM. Meanwhile, administration of pentoxifylline resulted in a significantly reduced level of normalized expression of NF-kB1 mRNA during the entire observation period and increased this indicator for c-Rel mRNA at the 2nd week. The growth of normalized expression of markers of M cells Gp2 and Spi-B was observed both on the 2nd and on the 4th week of the development of experimental pathology. Administration of pentoxifylline to diabetic animals was largely reflected in the change in the intensity of mRNA expression of the mature M cell Gp2 marker. This parameter was increased during the 2nd week of developing pathology, and on the 4th week, a downward trend was shown. The development of EDM led to a significantly increased level of near-normalized expression of proinflammatory TNFα cytokine and its receptor TNFr, and demonstrated a trend towards their decrease following pentoxifylline administration in diabetic animals.

This paper discusses biochemical properties of the recombinant chymosin in alpaca (Vicugnapacos), which influence the production of rennet cheeses. These properties determine its value in the production of rennet cheeses. Recombinant bovine chymosins are used as a control. In comparison to them, the recombinant alpaca chymosin is characterized by a high specificity towards bovine κ-casein: the threshold for its thermal inactivation is 10–15°C higher and reaches 60°C. The nature of the relation of its specific activity to the pH and concentration of CaCl meets the requirements for the use of milk-clotting enzymes in the production of rennet cheeses.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.

The article is devoted to the studying the processes of establishing oscillations in the generator on backward wave. The superregenerative mode has been considered within the framework of the linear theory. In the analysis, a complex frequency is introduced, the imaginary part of which characterizes the increase in oscillations over time. One of the main peculiarities of considered two-dimensional model is accounting focusing magnetic field effect. In the presence of longitudinal magnetic field of finite magnitude the transverse high frequency displacements in electron beam occur in addition to the longitudinal ones. The method of successive approximations has been used in analysis. The case of cyclotron resonance is considered separately, when only a slow cyclotron wave is excited in the electron beam, which noticeably simplifies the original problem and the initial relations.

Due to the scarcity of natural rennet, in this study we have considered an option of using in cheesemaking a milk-clotting enzyme produced by the Irpex lacteus fungus. We describe main properties of I. lacteus coagulant: milk-clotting activity (МА), overall proteolytic activity (PA), thermal stability, MА dependence on рН level and calcium ions content. Partially purified preparations of I. lacteus milk-clotting enzyme was obtained by salting out and gel-filtration. Technological properties of the I. lacteus coagulant were compared to natural calf rennet and cow pepsin (CP). МА of I. lacteus enzyme amounted to 29.1 ± 0.7 RU/ml, with protein content of 23 mg/ml. The coagulant was completely inactivated at 60○С. Thermal stability of I. lacteus milk-clotting enzyme, MA sensitivity to pH variations and Ca2+ content were comparable to respective parameters of calf rennet and CP. Overall PA of the I. lacteus coagulant exceeded CP and calf rennet activity by 33 and 220 times, respectively. As for enzymatic specificity, the following order was observed: calf rennet (100%) > CP (14.9%) > I. lacteus coagulant (0.5%). These findings suggest that there is a need to increase the MA of I. lacteus coagulant in order to be able to use it in cheesemaking. We have considered chemical, biochemical, and genetic corrective actions applicable to technological properties of microfungal milk coagulants.

Background Recovery-oriented models of care are evidence based and have been shown to improve patient satisfaction and outcomes as well as decrease the percentage of readmissions to inpatient psychiatric units. Methods This quality improvement project was implemented on a 16-bed inpatient adult mental health unit in a Veterans Affairs Medical Center. Percentages of readmissions were compared throughout the course of implementation of the recovery model. Readmissions during the months of July-September were tabulated over 3 subsequent years and compared readmission percentages before recovery implementation, during the early stage of recovery implementation, and finally, during ongoing recovery implementation. Results A decrease in readmission percentages was seen with implementation of recovery-oriented care when comparing the same 3-month period over 3 years. Conclusion After implementation of recovery-oriented care measures, there was a decrease in percentage of readmissions to the unit. In addition, this decrease was sustained and was shown to improve over time as recovery-oriented programming was further developed on the unit. These data suggest that Veterans Affairs Medical Centers should consider adding tools and procedures to successfully implement recovery programming on inpatient units and efforts should include direct involvement of patients in their own recovery journey, revision of policies and procedures to reflect the importance of recovery, thorough training of frontline staff regarding recovery principles, and transfer of recovery information directly from inpatient units to outpatient providers.

Delaware and Maryland have a long history of commercial production of lima bean (Phaseolus lunatus) for the processing market. In 2015, we observed lima bean plants that had irregular tan lesions with reddish borders in two fields in Sussex County, DE. Lesions ranged from 0.4 to 2.0 cm in diameter. Approximately 10% of leaves were symptomatic, and severity ranged between 5 and 10%. Symptomatic leaves (n = 6 to 10) were collected in September and October from each field for isolation and evaluation. Similar symptoms were observed on lima bean plants at the University of Maryland Lower Eastern Shore Research and Education Center in 2018, and additional symptomatic leaves (n = 6) were collected. Isolations were conducted from six diseased leaves per field (n = 18) by placing 2- to 4-mm sections of leaf on potato dextrose agar (PDA). All lesions resulted in isolates that appeared similar in morphology. Hyphae from the representative colonies were placed on water agar, and after 24 h, hyphal tips were excised. The hyphal tip procedure was repeated once to obtain pure cultures. Six isolates from Delaware and one from Maryland were stored at –80°C until use. Morphological evaluation of isolates grown on oat agar (OA), malt extract agar (MEA), and PDA revealed conidial morphology and dimensions consistent with previously published reports of Didymella americana (Aveskamp et al. 2010; Gorny et al. 2016). Two isolates, De15-002 and Md18-06, were selected for molecular analysis. DNA was extracted from colonies grown on OA; the internal transcribed spacer (ITS) region was amplified with primers ITS1/ITS4, and the partial actin locus region was amplified with primers act-512/act-783. Basic local alignment searches compared sequences to the ITS (GenBank accession no. FJ426972) and partial actin (FJ426870) sequences of D. americana reference strain CBS 185.85 (Chen et al. 2017; Gorny et al. 2016). The ITS sequences of isolates De15-002 and Md18-06 (MN698269 and MN944417, respectively) shared a 100% similarity with the reference strain. The partial actin sequences of isolates De15-002 (MN820723) and Md18-06 (MN820722) were also identical and differed from the reference sequence by 1 bp (99% similarity). To fulfill Koch’s postulates, four 3-week-old lima bean plants (cv. C-Elite) were sprayed with a conidial suspension (3 × 10⁵ conidia/ml) from 30-day-old cultures grown on MEA or with distilled water (control). Following 28 days of incubation at approximately 20°C, lesions were observed on all plants that were inoculated with isolates De15-001, De15-002, De15-004, De15-005, De15-007, De15-009, and Md18-06, but not on the water-inoculated control plants. Reisolations (n = 4 per isolate) onto water agar and MEA were examined after 7 days to confirm morphology similar to the original isolates. Based on the morphological and molecular characteristics, the pathogen was identified as D. americana. This is the first report of D. americana on lima bean in the Mid-Atlantic region of the United States. Lima bean is the most widely grown vegetable crop in Delaware, and in 2018, the state led production nationally. A new disease on the crop is important to the agricultural economy of Delaware, and the yield loss potential of this pathogen needs assessment in the region. This species has only been reported in 2016 on lima bean, in New York (Gorny et al. 2016).

The expression of motility-associated proteins in 18 patients with epithelial ovarian cancer was investigated. The study of actin-binding proteins (Arp3, gelsolin, cofilin-1 and thymosin-β4) and p45 Ser β-catenin revealed peculiarities of their expression with respect to clinicalmorphological parameters of ovarian cancer. Differences in cofilin expression with respect to histological type of the tumor were shown. The expression levels of Arp3, the most important protein of Arp2/3 actin-branching complex, and cofilin, which is able to break down actin filaments, were higher in peritoneal metastases than in omental metastases. It was found that the level of p45 Ser β-catenin and the percentage of cells expressing gelsolin and thymosin-4 were associated with pathological response to neoadjuvant chemotherapy (NACH) and were significantly higher in patients with complete and partial responses as compared to those observed in patients with no response. The obtained results can be used for identification of new prognostic factors, metastasis markers and predictive marker of pathological response after NACT.

A new information about optical technique in diagnostics for the endometrium structure has been proposed. The model of Mueller-matrix description of mechanisms responsible for optical anisotropy of these objects (optical activity, birefringence as well as linear and circular dichroism) has been suggested. The ensemble of informationally topical azimuthally stable Mueller-matrix invariants has been determined. Using the statistical analysis of the distribution parameters, the objective criteria for differentiation of endometrium taken from healthy women and patients with endometriosis were determined. From the viewpoint of probative medicine, the operational characteristics (sensitivity, specificity and accuracy) of the information-optical method applied to Mueller-matrix mapping of endometrium histological section have been found and its efficiency in diagnostics of endometriosis and infertility has been demonstrated.

A new azimuthally stable polarimetric method for processing microscopic images of optically anisotropic structures for different biological layers of histological sections has been proposed. A new model that enables to determine phase anisotropy of biological tissues by using superposition of Mueller matrices of linear birefringence and optical activity has been proposed. The matrix element M₄₄ has been chosen as the main information parameter, which value is independent of rotation angle of both sample and probing beam polarization plane.

The paper consists of two parts. The first part presents short theoretical basics of the method of azimuthally-invariant Mueller-matrix description of optical anisotropy of biological tissues. It was provided experimentally measured coordinate distributions of Mueller-matrix invariants (MMI) of linear and circular birefringences of skeletal muscle tissue. It was defined the values of statistic moments, which characterize the distributions of amplitudes of wavelet coefficients of MMI at different scales of scanning. The second part presents the data of statistic analysis of the distributions of amplitude of wavelet coefficients of the distributions of linear birefringence of myocardium tissue died after the infarction and ischemic heart disease. It was defined the objective criteria of differentiation of the cause of death.

The paper presents the results of Jones-matrix mapping of uterine wall histological sections with second-degree and third-degree endometriosis. The technique of experimental measurement of coordinate distributions of the modulus and phase values of Jones matrix elements is suggested. Within the statistical and cross-correlation approaches the modulus and phase maps of Jones matrix images of optically thin biological layers of polycrystalline films of plasma and cerebrospinal fluid are analyzed. A set of objective parameters (statistical and generalized correlation moments), which are the most sensitive to changes in the phase of anisotropy, associated with the features of polycrystalline structure of uterine wall histological sections with second-degree and third-degree endometriosis are determined.

Summary A study of potential oil and gas opportunities and highlight potential sites Ayoluengo field, located in northern Spain was provided. In the result 6 plays and 5 potential prospects were identified. There were also evaluated the risks and chances of success for the development of these fields.

TLRs in Epithelium of the oral cavity can be effected as due to the dental as general somatic pathology. TLR availability in the external membrane of neutrophils, macrophages, keratocytes was found to be a starting point in triggering inflammation in the periodontal tissues ensuring molecular reception of a pathogen with further involvement of important components in the inherited immunity. These effectors possess phagocytic and killer activities, ensure a number of signals activating and directing antigen-specific response by the cells of the adaptive immune system. The aim of the study was to study mRNA TLR-2, TLR-4 in the epithelium of the oral cavity in children with chronic catarrhal gingivitis and diabetes mellitus taking to account revealed metabolic disorders. Materials and methods. 30 children with chronic catarrhal gingivitis and diabetes mellitus type I were included into Іst group, 30 children with chronic catarrhal gingivitis were included into the ІInd group and 30 absolutely healthy children -ІII group. Polymerase chain reaction with reverse transcription in the regime in real time (RT-RRT) was used to analyze gene expression. Buccal epithelium was used as an object for molecular-genetic study. Results. Content of mRNA TLR-2 (90.0755) in diabetes mellitus patients was in 5.5 times higher as compared to children with CCG – 15.1505. Expression of mRNA TLR-4 in children of I group increased in 6 times as compared to the children from II group. Conclusion. Relative quantity of mRNA TLR-2 and TLR-4 in the epithelium of the oral cavity in children with diabetes mellitus was considerably higher than in patients without chronic inflammatory disease.

We report the results of studying the polarisation manifestations of laser autofluorescence of optically anisotropic structures in biological tissues. A Mueller-matrix model is proposed to describe their complex anisotropy (linear and circular birefringence, linear and circular dichroism). The relationship is established between the mechanisms of optical anisotropy and polarisation manifestations of laser autofluorescence of histological sections of rectal tissue biopsy in different spectral regions. The ranges of changes in the statistical moments of the 1st-to-4th orders, which describe the distribution of the azimuth-invariant elements of Mueller matrices of rectal tissue autofluorescence, are found. Effectiveness of laser autofluorescence polarimetry is determined and the histological sections of biopsy of benign (polyp) and malignant (adenocarcinoma) tumours of the rectal wall are differentiated for the first time.

In endometrial hyperplasia the total proteasome activity was not changed however the 26S proteasome activity was increased in comparison with the normal tissues. In endometrial cancer the high total proteasome activity and activities of 26S and 20S proteasomes wer e revealed. The changes in proteasome activities were correlated with the decreased content of α1α2α3α5α6α7 proteasome subunits and increased con- tents of LMP2, LMP7 and PA28β proteasome subunits compared to that in nonaltered tissues. Low content of α1α2α3α5α6α7 proteasome subunits was revealed at the second stage of cancer patients in comparison with that at the first stage.

Activity of the proteasome, polyfunctional enzymatic complex, is known to undergo changes during cancer development. This phenomenon is, probably, caused by the changes in subunit composition of proteasomes. In present work, we studied chymotrypsin-like activity of proteasomes, subunit composition and their association in breast cancer, head and neck squamous cell carcinoma, endometrial cancer, renal cancer, bladder cancer, stomach cancer and colorectal cancer. The increase of proteasome activity was revealed in most cancer tissues compared with adjacent tissues except for the renal cell carcinoma. Changes in proteasome activity in cancer tissues compared with correspondent normal tissues were accompanied by modification of its subunit composition. High proteasome activity was observed in combination with an increased expression of immune subunits and/or proteasome activator PA28, associated with activity of 20S proteasome. In breast cancer, head and neck squamous cell carcinoma, bladder cancer, stomach cancer and colorectal cancer we additionally found higher expression of Rpt6 subunit of 26S proteasome. Correlations between chymotrypsin like proteasome activity and subunit expressions were found in human cancer tissues. In summary, we suggest that proteasome ac- tivation and changes in its subunit composition plays an important role in cancer pathogenesis.

microRNAs (miRNAs) are dysregulated in a variety of disease states, suggesting that this newly discovered class of gene expression repressors may be viable therapeutic targets. A microarray of miRNA changes in ALS-model superoxide dismutase 1 (SOD1)(G93A) rodents identified 12 miRNAs as significantly changed. Six miRNAs tested in human ALS tissues were confirmed increased. Specifically, miR-155 was increased 5-fold in mice and 2-fold in human spinal cords. To test miRNA inhibition in the central nervous system (CNS) as a potential novel therapeutic, we developed oligonucleotide-based miRNA inhibitors (anti-miRs) that could inhibit miRNAs throughout the CNS and in the periphery. Anti-miR-155 caused global derepression of targets in peritoneal macrophages and, following intraventricular delivery, demonstrated widespread functional distribution in the brain and spinal cord. After treating SOD1(G93A) mice with anti-miR-155, we significantly extended survival by 10 days and disease duration by 15 days (38%) while a scrambled control anti-miR did not significantly improve survival or disease duration. Therefore, antisense oligonucleotides may be used to successfully inhibit miRNAs throughout the brain and spinal cord, and miR-155 is a promising new therapeutic target for human ALS.

The authors have examined 32 patients with chronic fatigue syndrome, having established in them various changes (degrees I-III of immune disturbances) of the absolute and relative quantity of the leading immunocompetent cells and immunohematological indices and coeffients, as well as the cellular and humoral factors of nonspecific antiinfections defense.

The development of endometrial cancer is related to the status of the intracellular proteasome system. Total proteasome activity and pools 26S and 20S activities are higher in tumor tissue than in intact endometrium, and their composition is different. The expression of α1α2α3α5α6α7 is lower in endometrial cancer tissue in comparison with intact endometrium and the content of immune subunits LMP7, LMP2, and PA28β is increased. Total proteasome activity depends on the disease stage.

Insulin-like growth factors (IGFs) and the nuclear factor κB (NF-κB) are known to play an important role in pathogenesis of endometrial cancer. However, there is still uncertainty about their proteolytic regulation. We studied the correlation between chymotrypsin-like activity of proteasomes and IGF-I, IGF-II, and NF-κB levels in endometrial cancer tissues. The total activity of proteasomes and the 20S and 26S proteasome activities were shown to be significantly higher in malignant tumors than in the unaltered endometrium. Negative correlations were found between the proteasome activity of 26S and the p50 level of NF-κB, as well as between the 26S and 20S proteasome activities and IGF-I level. The obtained data indicate the possible proteasome regulation of growth and transcription factors. As the major pool of IGF-I is considered to be located in the extracellular space, it is likely that extracellular proteasomes also take part in the regulation of the IGF-I content. The positive correlation between the IGF-I level and PAPP-A metalloproteinase is evidence that this proteolytic enzyme is another important regulator of the level of growth factor, which ensures the proteolysis of IGF-I binding proteins and, thus, increases the concentration of IGF-I in tissues. The present data show the possibility of the proteolytic regulation of growth and nuclear factors that can play an important role in cancer pathogenesis.

The compositions of wear-resistant steels used as the material for grinding media are validated in order to obtain the optimal relation between the wear resistance and cost. Mathematical experiment planning reveals that low-alloyed hypereutectiod steels with the austenite-martensite structure without secondary carbides and eutectoid steels with the tempered martensite structure are the most promising for impact-abrasivecorrosive wear conditions.

Laboratory tests of iron-based alloys for abrasive wear show that the best wear resistance of the alloys with both the martensite and austenite metallic matrix is achieved in the iron-carbon system. The greater the content of alloying elements in the austenite, the more pronounced is the reduction of its wear resistance due to alloying. It is revealed that the content of the alloying elements in the wear-resistant alloys for grinding media must be as low as possible, but yet sufficient to ensure the required manufacturability of articles.

Proteasomes (multiproteinase protein complexes) are known to play an important role in cancer pathogenesis, however, few information about their activity in human tumor tissues is available so far. We studied chymotrypsin-like activity of proteasomes in tissues of breast cancer (BC) and endometrial cancer (EC). The chymotrypsin-like total proteasome activity and the 20S and 26S proteasome activity in malignant tissues were shown to be significantly higher in malignant tumors than in normal tissues. No increase in proteasome activity was registered with larger tumor size in both BC and EC, whereas proteasome activity was changed with respect to the extent of tumor involvement. In breast cancer tissues, significant reductions in the total and the 26S proteaome activities were observed in tumors with regional lymph node metastases as compared to tumors without metastases. In endometrial cancer tissues, the total proteasome activity and the 20S and 26S proteasome activities were increased as the depth of myometrial invasion. The data obtained indicate that the proteasome acyivity is significantly changed in the process of cancerogenesis and further study is needed to develop new additional prognostic criteria and effective anti-tumor agents in molecular-directed therapy.

Frictional heating is analyzed to check the wear resistance of major structural components of undoped ferricarbonic alloys during abrasive wear. It is established that the wear resistance of austenite drops twofold once the temperature leaps to 130°C. The wear resistance of other structural components (ferrite, perlite, and martensite) diminishes in heating less intensively, but the wear resistance of unstable austenite is at the maximum level at any temperature within the studied range (up to 290°C).

The effect of the methods for hardening-finish treatment on the structure, phase composition, surface layer parameters, and fatigue resistance of blades for stage III of a low-pressure compressor is considered.

This research presents investigation results of the diagnostic efficiency of an azimuthally stable Mueller-matrix method of analysis of laser autofluorescence of polycrystalline films of dried uterine cavity peritoneal fluid. A model of the generalized optical anisotropy of films of dried peritoneal fluid is proposed in order to define the processes of laser autofluorescence. The influence of complex mechanisms of both phase (linear and circular birefringence) and amplitude (linear and circular dichroism) anisotropies is taken into consideration. The interconnections between the azimuthally stable Mueller-matrix elements characterizing laser autofluorescence and different mechanisms of optical anisotropy are determined. The statistical analysis of coordinate distributions of such Mueller-matrix rotation invariants is proposed. Thereupon the quantitative criteria (statistic moments of the first to the fourth order) of differentiation of polycrystalline films of dried peritoneal fluid, group 1 (healthy donors) and group 2 (uterus endometriosis patients), are determined.

The theoretical background of azimuthally stable method Jones matrix mapping of histological sections of biopsy of uterine neck on the basis of spatial-frequency selection of the mechanisms of linear and circular birefringence is presented. The comparative results of measuring the coordinate distributions of complex degree of mutual anisotropy formed by polycristalline networks of blood plasma layers of donors (group 1) and patients with endometriosis (group 2). The values and ranges of change of the statistical (moments of the 1st - 4th order) parameters of complex degree of mutual anisotropy coordinate distributions are studied. The objective criteria of diagnostics of the pathology and differentiation of its severity degree are determined.

A new information optical technique of diagnostics of the structure of polycrystalline films of blood plasma is proposed. The model of Mueller-matrix description of mechanisms of optical anisotropy of such objects as optical activity, birefringence, as well as linear and circular dichroism is suggested. The ensemble of informationally topical azimuthally stable Mueller-matrix invariants is determined. Within the statistical analysis of such parameters distributions the objective criteria of differentiation of films of blood plasma taken from healthy women and breast cancer patients were determined. From the point of view of probative medicine the operational characteristics (sensitivity, specificity and accuracy) of the information-optical method of Mueller-matrix mapping of polycrystalline films of blood plasma were found and its efficiency in diagnostics of breast cancer was demonstrated. Considered the prospects of applying the method in experimental medicine for differentiation of tissues of internal organs of healthy and diabetic rats.

It is known that the course of all pathological processes in the human body occurs with immune regulation participation and is characterized by a certain balance of pro- or antiinflammatory cytokines, among recent inflammatory and immunosuperessive function Interleukin-10 (IL- 10) has sever among them. Although IL-10 is sufficiently studied cytokine high interest in it remains in the aspect of studying the immunopathogenesis of diseases that are " uncertain " or insufficiently clarified Th1 \ Th2 (Th17, Treg) cytokine profile. One of these conditions is endometriosis - a disease characterized by lesions, structurally similar to endometrium, localized outside the uterus. Endometriosis is the cause of 45 % of female infertility. The purpose of the work was to study the level of IL-10 in serum and peritoneal fluid in women suffering from endometriosis associated with infertility. The study involved 65 women with endometriosis associated with infertility, the control group consisted of 33 patients with infertility without endometriosis. In assessing the results of the study it has been found that in women with endometriosis associated with infertility in comparison with the control group a pronounced increase in the level of IL -10 in the peritoneal fluid (p

In the development of endometriosis and infertility, associated with it, immunological processes play an important role, ant they are characterized by high activity of cytokines and growth factors (e.g., transforming growth factor -β (TGF-β)) and increased invasiveness of ectopic endometrium, including activity of matrix metalloproteinases (MMP). TGF-β exhibits different biological properties and plays a key role in the migration, proliferation and differentiation of cells. The concentration of TGF-β in serum and peritoneal fluid of 65 women with external genital endometriosis and infertility has been studied. We found an increase of TGF -β in peritoneal fluid, which is associated with an increased activity of MMP9 in the ectopic endometrium.

Problems of alloying of high-temperature nickel alloys resistant to high-temperature corrosion in combustion products of low-grade fuel are considered. The relationship between the structure and properties of alloys and the alloying set that provides high service characteristics is studied. The obtained dependences are used to create new alloys resistant to high-temperature corrosion. Their structure and properties are described.