[Drug therapy's new options in the treatment of the severe irritable bowel syndrome].

BACKGROUND: Stress, individual characteristics of each patient, visceral hypersensitivity and intestinal motility have the key importance in the pathogenesis of irritable bowel syndrome (IBS). In recent years, there has been growing interest in the use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the complex therapy of IBS patients with somatoform disorders. AIM: To examine the effectiveness of the SNRIs antidepressant therapy in the treatment of patients with IBS and diarrhea (IBS-D) with extraintestinal manifestations. MATERIALS AND METHODS: 42 patients with severe IBS and diarrhea (IBS-D) were examined, among them 22 female with a median age of 32 years old (22; 38), and 20 male with a median age of 31 years old (25; 35). Treatment with duloxetine 60 mg/day was prescribed. The effectiveness of the therapy was assessed after eight weeks. The IBS clinical symptoms dynamics were assessed by the intensity of pain syndrome and bloating, which were determined using Visual Analogue Pain Scale (VAS), stool frequency and shape based on the Bristol stool scale; Visceral sensitivity threshold was assessed according to the Balloon dilatation test. There was studied the effect of the duloxetine on the extraintestinal manifestations of IBS. The psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale by psychiatrist, neurologist-vegetol. RESULTS: All patients showed positive dynamics after eight weeks duloxetine treatment: the decrease of pain syndrome from 9 (9; 10) to 2 (2; 3) points, bloating from 8 (8; 9) points to 2,5 (1; 3) points according to VAS, and defecation frequency from 10 (9; 12) to 2 (1; 2) times a day; the change of stool consistency from 6th (6; 7) to 3rd (3; 4) type. The visceral sensitivity threshold increased: the time of appearance of the first urge to defecate increased from 56 (34; 74) ml to 95 (80; 98) ml. Significantly decreased extraintestinal manifestations of IBS. In reassessing each patient's individual characteristics there were the decrease of the depression level according to the Beck scale from 26 (23; 32) to 11.5 (10; 13) points and personal personal anxiety level according to the Spielberger-Khanin scale from 42.5 (35; 53) to 22 (20; 24) points, as well as the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points. CONCLUSION: The severe course of IBS-D is mainly associated with the patients' individual characteristics and anxiety or anxiety-depressive syndromes. The positive impact of duloxetine therapy in severe IBS-D with extraintestinal manifestations is associated with the regulation of serotonergic and noradrenergic activity of the central.

Miniaturization does not change conserved spider anatomy, a case study on spider Rayforstia (Araneae: Anapidae).

Miniaturization is an evolutionary trend observed in many animals. Some arachnid groups, such as spiders and mites, demonstrate a strong tendency toward miniaturization. Some of the most miniaturized spiders belong to the family Anapidae. In this study, using light and confocal microscopy and 3D modelling, we provide the first detailed description of the anatomy of a spider of the genus Rayforstia, which is only 900 µm long. In comparison with larger spiders, Rayforstia has no branching of the midgut in the prosoma and an increased relative brain volume. In contrast to many miniature insects and mites, the spider shows no reduction of whole organ systems, no allometry of the digestive and reproductive systems, and also no reduction of the set of muscles. Thus, miniature spider shows a more conserved anatomy than insects of a similar size. These findings expand our knowledge of miniaturization in terrestrial arthropods.

Reconstruction and analysis of the gene regulatory network for cell wall function in Arabidopsis thaliana L. leaves in response to water deficit.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit. The adaptation mechanisms of the cell wall to water loss are of interest for identifying important genetic factors determining plant drought resistance and provide valuable information on biomarkers for further selection aimed at increasing the yield of crop plants. Using ANDSystem, a gene network describing the regulation of CWPs under water restriction conditions was reconstructed. The analysis of the gene network and the transcriptome data analysis allowed prioritizing transcription factors (TF) based on their enrichment of differentially expressed genes regulated by them. As a result, scores were calculated, acting as indicators of the association of TFs with water deficit. On the basis of the score values, eight most significant TFs were selected. The highest priority was given to the TF GBF3. CWPs were prioritized according to the criterion of summing up the scores of transcription factors regulating these genes. Among the most prioritized CWPs were the AT5G03350 gene encoding a lectin-like protein, AT4G20860 encoding BBE-like 22 required for the oxidation of cellulose degradation products, and AT4G37800 encoding xyloglucan endotransglucosylase/ hydrolase 7. Overall, the implemented algorithm could be used for prediction of regulatory interactions between transcription factors and target genes encoding cell wall proteins in plants.

Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication.

The participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of drug resistance to the existing drugs remain the main obstacles to fighting HCV. Identifying the host factors, exploring their role in HCV RNA replication, and studying viral effects on their expression is essential for understanding the mechanisms of viral replication and developing novel, effective curative approaches. It is known that the host factors PREB (prolactin regulatory element binding) and PLA2G4C (cytosolic phospholipase A2 gamma) are important for the functioning of the viral replicase complex and the formation of the platforms of HCV genome replication. The expression of PREB and PLA2G4C was significantly elevated in the presence of the HCV genome. However, the mechanisms of its regulation by HCV remain unknown. In this paper, using a text-mining technology provided by ANDSystem, we reconstructed and analyzed gene networks describing regulatory effects on the expression of PREB and PLA2G4C by HCV proteins. On the basis of the gene network analysis performed, we put forward hypotheses about the modulation of the host factors functions resulting from protein-protein interaction with HCV proteins. Among the viral proteins, NS3 showed the greatest number of regulatory linkages. We assumed that NS3 could inhibit the function of host transcription factor (TF) NOTCH1 by protein-protein interaction, leading to upregulation of PREB and PLA2G4C. Analysis of the gene networks and data on differential gene expression in HCV-infected cells allowed us to hypothesize further how HCV could regulate the expression of TFs, the binding sites of which are localized within PREB and PLA2G4C gene regions. The results obtained can be used for planning studies of the molecular-genetic mechanisms of viral-host interaction and searching for potential targets for anti-HCV therapy.

Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium.

Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain inadequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) methods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD.

[Visceral sensitivity in diagnostics and treatment of severe irritated bowel syndrome].

BACKGROUND: Irritable bowel syndrome (IBS) is a biopsychosocial model based on the malfunction of "brain-intestinal linking". AIM: To improve diagnostics of the severe IBS accompanied with somatoform disorders by using balloon dilatation test (BDT) and optimize the therapy by using antidepressants from the serotonin and noradrenaline reuptake inhibitor type. MATERIALS AND METHODS: 61 patients with severe IBS and diarrhea were examined, among them 29 female with a median age of 31 years old (24; 36), and 31 male with a median age of 31 (24; 36) years old. All patients were randomized into two groups, group 1 consisted of 30 patients (15 female, 15 male), group 2 consisted of 31 patients (15 female, 16 male). The symptoms of all patients were assessed using the Visual Analogue Pain Scale (VAS Pain), visceral sensitivity index (VIS) was assessed according to the J. Labus questionnaire (2007) and visceral sensitivity threshold was assessed according to the BDT, the psycho-emotional state was assessed using the Beck scale of anxiety and depression and the Spielberger-Khanin scale. Both group patients underwent a comparative effectiveness evaluation between the therapy based on the use of Trimebutine at a dose of 600 mg per day and the SNRI-Duloxetine therapy at a dose of 60 mg per day for 8 weeks. RESULTS: Patients from group with severe IBS and diarrhea who had undergone the antidepressant therapy showed the decrease of pain syndrome from 7 (5; 7) to 2.5 (2; 3) points according to VAS Pain; normalization of stool frequency from 7 (6; 9) to 2 (1; 2) times a day; normalization of stool consistency from 6 (6; 7) to 3 (3; 4) type; and decrease of VIS: first urge from 56 (34; 74) to 95 (80; 98) ml.; as well as the decrease of the depression level (Beck scale) from 26 (23; 32) to 11.5 (10; 13) points and anxiety according to Beck scale from 38 (31; 45) to 11 (10; 12), the decrease of personal anxiety level (Spielberger-Khanin scale) from 42.5 (35; 53) to 22 (20; 24) points, and the decrease of situational anxiety from 40 (37; 49) to 22 (21; 36) points. During the trimebutine therapy in group 1, the clinical symptoms of IBS have persisted. According to the BDT, the visceral sensitivity (HF) threshold remained at a low level. And the indicators of anxiety and depression remained at a high level according to the psychometric scales. CONCLUSION: The insufficient effect of the trimebutine therapy can be explained by the somatoform disorders persistence in patients from group 1. Meanwhile SNRI-duloxetine therapy in group 2 showed a clinical remission of IBS: such as a reliable relief from pain and diarrheal syndrome, as well as an increase in the HF threshold. Thus, Duloxetine is a promising treatment for severe IBS with somatoform disorders. BDT can be used as an objective criterion to diagnose and evaluate the effectiveness of therapy in patients with IBS.

[Reduced Expression of the Tissue-Specific Oct-IL Isoform Exerts an Antitumor Effect on Namalwa Burkitt's Lymphoma Cells].

Increased expression levels of the Oct-1 transcription factor is considered to be one of the key markers of poor cancer prognosis. In addition to the ubiquitous Oct-1A isoform, which is found in all cells, there also exists a tissue-specific Oct-1L isoform, which is expressed in hematopoietic cells. Oct-1L increases cell resistance to different stresses and also regulates the expression of genes controlling differentiation of hematopoietic and immune system cells. The tissue-specific Oct-1L isoform levels are significantly increased in the B-cell lymphoblastoma Namalwa and Raji lines and the T-cell lymphoblastoma Jurkat line compared to normal B and T cells. Apparently, aberrant Oct-1L overexpression not only enhances stress resistance but also leads to the disruption of developmental pathways in the cells promoting their malignant transformation. We report here that targeted suppression of the tissue-specific Oct-1L isoform expression reduces the proliferation rate of Namalwa B-lymphoblastic Burkitt's lymphoma cells, significantly increases cell death rate under hypoxic conditions, and makes cells more sensitive to chemotherapeutic agents such as docetaxel and doxorubicin. These results indicate that targeted therapy aimed at the suppression of the Oct-1 isoforms with increased expression levels in tumor cells rather than the total Oct-1, thus avoiding the traumatic effects of total Oct-1 knockdown, may be promising. Selective suppression of Oct-1 isoforms is a promising strategy in the treatment of lymphoid tumors and may contribute to mitigating the disease course and increasing survival rates in cancer patients.

Structure of the Brain of the Smallest Coleoptera.

The structure of the brain of the smallest coleopteran, Scydosella musawasensis Hall, 1999, is described for the first time. As in other extremely small beetles, the brain of S. musawasensis displays signs of miniaturization: displacement to the thorax, compactization, and a small number and size of the neurons. The body size of the studied smallest beetle is similar to that of the minute hymenopteran Megaphragma, which has a nearly anucleate nervous system. However, the structure of the brain of the studied smallest beetle is similar to that of large representatives of the order and is characterized by a high number of nuclei in the brain and a significant volume of the cell body rind. The neuropil of S. musawasensis occupies 60% of the brain volume, confirming the neuropilar constant rule.

The Emergence of a New Isoform of POU2F1 in Primates through the Use of Egoistic Mobile Genetic Elements.

The emergence of new genes and functions is of paramount importance in the emergence of new animal species. For example, the insertion of the mobile element Tigger 2 into the sequence of the functional gene POU2F1 in primates led to the formation of a new chimeric primate-specific isoform POU2F1Z, the translation of which is activated under cellular stress. Its mRNA was found in all species of monkeys, starting with macaques. Analysis of the fragments of the Tigger2 copy corresponding to the human exon Z showed that the splicing sites of exon Z are homologous in humans and in most monkeys, with the exception of lemurs and galagos. The stop codon introduced into the mRNA by the Tigger2 sequence is present in all primates, starting with macaques. The internal ATG codon is also present in all primates, with the exception of lemurs and galagos. In the course of evolution, other MGEs, mainly of the SINE type, were inserted into the Tigger2 copy. In the course of evolution, both the location and the number of mobile SINE elements within the POU2F1 gene changed. Starting with macaques, the pattern of the arrangement of SINE elements within the Tigger2 copy in the studied region of the POU2F1 gene was fixed and then remained unchanged in other primates and humans, which may indicate its functional significance.

[POU2F1 (Oct-1) Differently Autoregulates the Alternative Promoters of Its Own Gene by Binding to Different Regulatory Sites].

The POU2F1 gene, which plays an important role in regulating the mammalian genome and development, has both a ubiquitous (U) and a tissue-specific (L) promoter and is subject to intricate regulation. Regions of POU2F1 gene were found to contain multiple binding sites for its product POU2F1 (Oct-1), a transcription factor. Interspecies homology in these regions was found to exceed 90% among the human, mouse, rat, pig, and dog genomes, almost all of the Oct-1 binding sites being identical. Some of the sites cluster in the vicinity of each of the two alternative promoters, while others are in the 5' noncoding region 6 kb upstream of the transcription start site. The presence of Oct-1 at the sites was demonstrated by chromatin immunoprecipitation and the electrophoretic mobility shift assay (EMSA). A POU2F1 knockdown activated the U promoter and downregulated the L promoter in Namalwa cells, while Oct-1 overexpression exerted an opposite effect. Thus, Oct-1 acts via negative feedback to autoregulate the U promoter through low-affinity Oct-1 binding sites and positive feedback to autoregulate the L promoter through high-affinity canonical (oct) sites when increasing in concentration in a natural context.

Redox reactions between acetonitrile and nitrogen dioxide in the interlayer space of fluorinated graphite matrices.

The interlayer space of 2D materials can be a slit reactor where transformations not typical for the gas phase occur. We report redox reactions involving acetonitrile and nitrogen oxide guests in galleries of fluorinated graphite. Fluorinated graphite intercalation compounds with acetonitrile are treated with dinitrogen tetraoxide and the synthesis products are studied by a set of experimental methods. Data analysis reveals that N2O4 dissociates in fluorinated graphite matrices to form nitrogen-containing species NO3, NO2, NO, and N2. The interaction of NO3 with acetonitrile yields HNO3, which predominates as a guest in the synthesis products independently of the fluorination degree of the matrix. This reaction is accompanied by the removal of fluorine atoms weakly bonded to the graphite layers, leading to partial defluorination of the matrices. Our work demonstrates the possibility of using fluorinated graphite as a test nanoreactor whose dimension can be controlled by fluorination of the layers.

GSK3 Kinase Inhibitor, CHIR, Suppress Transcription of Tissue Specific POU2F1 Isoform in Burkitt Namalwa Lymphoma Cells.

POU2F1 (Oct-1) is a transcription factor, the overexpression of which is found in many human malignant tumors; a significant increase in its level in cells determines the malignant potential of the tumor. POU2F1 is represented in cells by several isoforms that are transcribed from alternative promoters. In Burkitt's B-cell lymphoma Namalwa, the concentration of tissue-specific isoform Oct-1L is several times higher than in normal B cells. We tested the potential to inhibit the transcription of individual Oct-1 isoforms using the GSK3 kinase inhibitor CHIR, an aminopyrimidine derivative. We have shown that CHIR specifically affects the expression of the tissue-specific isoform Oct-1L, significantly reducing the level of mRNA and Oct-1L protein. However, CHIR does not change the amount of mRNA and protein of the ubiquitous isoform Oct-1A in Namalwa tumor cells. The results obtained show that it is possible to develop a system for selective inhibition of Oct-1 transcription factor isoforms in human cells to suppress drug resistance of tumor cells with a high POU2F1 content.

[The role of visceral hypersensitivity in the pathogenesis of irritable bowel syndrome].

This research includes visceral sensitivity and its mechanisms involved in the development of irritable bowel syndrome. Visceral hypersensitivity occupies the key place. The research has the description of etiological factors that form visceral hypersensitivity and also visceral sensitivity instrumental research methods, based on the use of the balloon dilation. The research also has the schemes of drug therapy for irritable bowel syndrome meanwhile the special attention is paid to the possible use of the sorbed probiotics and psychopharmacological drugs.

Electronic Structure of Nitrogen- and Phosphorus-Doped Graphenes Grown by Chemical Vapor Deposition Method.

Heteroatom doping is a widely used method for the modification of the electronic and chemical properties of graphene. A low-pressure chemical vapor deposition technique (CVD) is used here to grow pure, nitrogen-doped and phosphorous-doped few-layer graphene films from methane, acetonitrile and methane-phosphine mixture, respectively. The electronic structure of the films transferred onto SiO2/Si wafers by wet etching of copper substrates is studied by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy using a synchrotron radiation source. Annealing in an ultra-high vacuum at ca. 773 K allows for the removal of impurities formed on the surface of films during the synthesis and transfer procedure and changes the chemical state of nitrogen in nitrogen-doped graphene. Core level XPS spectra detect a low n-type doping of graphene film when nitrogen or phosphorous atoms are incorporated in the lattice. The electrical sheet resistance increases in the order: graphene < P-graphene < N-graphene. This tendency is related to the density of defects evaluated from the ratio of intensities of Raman peaks, valence band XPS and NEXAFS spectroscopy data.

Structure of Diamond Films Grown Using High-Speed Flow of a Thermally Activated CH4-H2 Gas Mixture.

Diamond films are advanced engineering materials for various industrial applications requiring a coating material with extremely high thermal conductivity and low electrical conductivity. An approach for the synthesis of diamond films via high-speed jet deposition of thermally activated gas has been applied. In this method, spatially separated high-speed flows of methane and hydrogen were thermally activated, and methyl and hydrogen radicals were deposited on heated molybdenum substrates. The morphology and structure of three diamond films were studied, which were synthesized at a heating power of 900, 1700, or 1800 W, methane flow rate of 10 or 30 sccm, hydrogen flow rate of 1500 or 3500 sccm, and duration of the synthesis from 1.5 to 3 h.The morphology and electronic state of the carbon on the surface and in the bulk of the obtained films were analyzed by scanning electron microscopy, Raman scattering, X-ray photoelectron, and near-edge X-ray absorption fine structure spectroscopies. The diamond micro-crystals with a thick oxidized amorphous sp2-carbon coating were grown at a heating power of 900 W and a hydrogen flow rate of 1500 sccm. The quality of the crystals was improved, and the growth rate of the diamond film was increased seven times when the heating power was 1700-1800 W and the methane and hydrogen flow rates were 30 and 3500 sccm, respectively. Defective octahedral diamond crystals of 30 µm in size with a thin sp2-carbon surface layer were synthesized on a Mo substrate heated at 1273 K for 1.5 h. When the synthesis duration was doubled, and the substrate temperature was decreased to 1073 K, the denser film with rhombic-dodecahedron diamond crystals was grown. In this case, the thinnest hydrogenated sp2-carbon coating was detected on the surface of the diamond crystals.

Structure and Ultrastructure of the Acrotrichis grandicollis (Coleoptera: Ptiliidae) Compound Eyes and the Eye Features Related to Miniaturisation.

Here is the first description of the visual organ of Acrotrichis grandicollis, a member of Ptiliidae family that includes the smallest free-living insects. The apposition eyes of A. grandicollis have the acone-type crystalline cone; a fused rhabdom is formed by eight retinula cells and surrounded by primary pigment cells. Secondary pigment cells are located only in the distal part of the ommatidium under the lens. The eye consists of about 50 facets about 12 µm in diameter. The A. grandicollis ommatidium ultrastructure has been compared with that of large Coleoptera. The results obtained enabled us to emphasize the compound eye specific features associated with the small body size.

Charge polarization in partially lithiated single-walled carbon nanotubes.

Investigation of carbon/lithium interfaces is of great importance for elaboration of energy storage devices. Here, the effect of vacuum thermal deposition of lithium on single-walled carbon nanotubes (SWCNTs) is investigated by in situ X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy. From the XPS data, the composition of lithiated sample is LiC24. That corresponds to the presence of two types of carbon atoms on the SWCNT surface, namely, those located closely and far away from the adsorbed lithium. Quantum-chemical modeling of XPS valence-band spectra and calculation of atomic charges and molecular electrostatic potential map found that the former type of carbon atoms is in strong positive electric field created by lithium, whereas the Li-free SWCNT areas are charged negatively. An alternation of areas of positive potential and negative potential on the surface of partially lithiated SWCNTs can significantly affect processes in an electrochemical cell.

[Afalaza in the management of patients with chronic pelvic pain syndrome].

INTRODUCTION: Currently, chronic pelvic pain syndrome (CPPS) is one of the most prevalent urological diseases, but due to the multifactorial nature of the disease and the lack of consensus on its pathogenesis, the issue of adequate therapy remains open. Since the vascular factor plays the major role in the pathogenesis of CPPS, we hypothesized that this category of patients has microcirculatory disturbances of the prostate. AIM: Detection of microcirculatory disturbances of the prostate, their correction, and evaluation of the effect on the course of CPPS. MATERIALS AND METHODS: The study comprised 60 healthy, sexually active men with clinical manifestations of CPPS lasting from 6 months to 5 years. After a comprehensive examination, all patients received Afalaza 2 tablets twice daily for 16 weeks. At the end of week 16, patients were re-examined. RESULTS: In patients with CPPS, therapy with Afalaza resulted in a significant improvement in microcirculation in the prostate thus leading to the reduction of the severity of disease manifestations.