ACTIVATION MECHANISMS OF GUT-ASSOCIATED LYMPHOID TISSUE UNDER CHRONIC SOCIAL STRESS CONDITIONS

Stress-induced immune disregulation is a risk factor of autoimmune and inflammatory diseases, but, so far, the mechanisms for this effect are not fully known. Expression levels of specific mRNAs were assessed in gut-associated lymphoid tissue (GALT) from Wistar rats subjected to chronic social stress (CSS). Gene expression was evaluated for NR3C1, Adrβ2, as well as IL-1β, IL-17α pro-inflammatory cytokines, and Nlrp, an inflammasome gene. Under the CSS conditions, we have shown altered distribution of RORγt +, FoxP3+, LMP2+, XBP1+ lymphocytes in GALT.The experiments were carried out with female Wistar rats aged 5–6 months. Specific mRNA expression for the target genes was determined by means of real-time PCR performed in a CFX96™ thermocycler («BioRadLaboratories, Inc»,USA). Relative levels of a target gene expression were quantified by the ΔΔCt method, being compared with rat GAPDH reference gene expression. Statistical analysis was performed with available «BioRad СFX Manager 3.1» software. Specific monoclonal rat antibodes were used for detection of immunopositive lymphocytes by means of indirect immunofluorescence technique.CSS development leads to decreased levels of mRNA expression for Nr3c1 and Adrβ2-genes in the GALT cells, being accompanied with unidirectional changes, i.e., increased transcription of pro-inflammatory cytokine mRNAs (IL-1β, IL-17α) and Nlrp3-inflammasome genes. These changes are accompanied by decreased FoxP3+/RORγt + cell ratio and predominant Th17 differentiation accompanied by suppressor failure. In addition, CSS development was characterized by unidirectional tendency for increasing total number of LMP2+ lymphocytes and reduced ХВР1+ cell population density in lymphoid structures of rat ileum.The events observed in GALT cell populations under CSS conditions are opposing classical paradigm of the stress response. The CSS-associated effects do not promote immunosuppression, however, are able to cause activation of immune system and inflammatory process

Peculiarities of Endoplasmic Reticulum Stress Regulator XBP1 Expression in the Gut-Associated Lymphoid Tissue of Wistar Rats under Chronic Stress

The aim of the present work was to study the expression level of XBP1 mRNA, proin flammatory cytokines IL,1β, IL,17α in intestinal associated lymphoid tissue in Wistar rats in experimental models of CS

Shear wave propagation in layered composites with degraded matrices at locations of imperfect bonding

Biodegradable polymers find an increasing number of applications in different fields of engineering and medicine due to their environmental-friendly degradation. The process of degradation of biodegradable polymer constituents and the bonding quality between the constituents in composites can be identified by the analysis of the phononic band structure. The present article considers a layered composite, in which the matrix degradation is modeled by a multitude of layers with decreasing values of their mechanical properties. Bonding between the inclusion and the degrading matrix is taken into account by a linear elastic bonding model in the first case and by a viscoelastic model in the second case

Quality of reporting internal and external validity data from randomized controlled trials evaluating stents for percutaneous coronary intervention

<p>Abstract</p> <p>Background</p> <p>Stents are commonly used to treat patients with coronary artery disease. However, the quality of reporting internal and external validity data in published reports of randomised controlled trials (RCTs) of stents has never been assessed.</p> <p>The objective of our study was to evaluate the quality of reporting internal and external validity data in published reports of RCTs assessing the stents for percutaneous coronary interventions.</p> <p>Methods</p> <p>A systematic literature review was conducted. Reports of RCTs assessing stents for percutaneous coronary interventions indexed in MEDLINE and the Cochrane Central Register of Controlled Trials and published between January 2003 and September 2008 were selected. A standardized abstraction form was used to extract data. All analyses were adjusted for the effect of clustering articles by journal.</p> <p>Results</p> <p>132 articles were analyzed. The generation of the allocation sequence was adequate in 58.3% of the reports; treatment allocation was concealed in 34.8%. Adequate blinding was reported in one-fifth of the reports. An intention-to-treat analysis was described in 79.5%. The main outcome was a surrogate angiographic endpoint in 47.0%. The volume of interventions per center was described in two reports. Operator expertise was described in five (3.8%) reports. The quality of reporting was better in journals with high impact factors and in journals endorsing the CONSORT statement.</p> <p>Conclusion</p> <p>The current reporting of results of RCTs testing stents needs to be improved to allow readers to appraise the risk of bias and the applicability of the results.</p

Mesodermal fate decisions of a stem cell: the Wnt switch

Stem cells are a powerful resource for cell-based transplantation therapies in osteodegenerative disorders, but before some kinds of stem cells can be applied clinically, several aspects of their expansion and differentiation need to be better controlled. Wnt molecules and members of the Wnt signaling cascade have been ascribed a role in both these processes in vitro as well as normal development in vivo. However some results are controversial. In this review we will present the hypothesis that both canonical and non-canonical signaling are involved in mesenchymal cell fate regulation, such as adipogenesis, chondrogenesis and osteogenesis, and that in vitro it is a timely switch between the two that specifies the identity of the differentiating cell. We will specifically focus on the in vitro differentiation of adipocytes, chondrocytes and osteoblasts contrasting embryonic and mesenchymal stem cells as well as the role of Wnts in mesenchymal fate specification during embryogenesis

SOX2 expression correlates with lymph-node metastases and distant spread in right-sided colon cancer

<p>Abstract</p> <p>Background</p> <p>The transcription factor SOX2, which is involved in the induction of pluripotent stem cells and contributes to colorectal carcinogenesis, is associated with a poor prognosis in colon cancer (CC). Furthermore, SOX2 is a repressor of the transcriptional activity of β-catenin in vitro. Since the majority of CC develop via an activation of the Wnt/β-catenin signalling pathway, indicated by nuclear expression of β-catenin, we wanted to investigate the expression patterns of SOX2 and β-catenin and correlate them with the occurrence of lymph node and distant metastases as indicators of malignant progression.</p> <p>Methods</p> <p>The expression of SOX2 and β-catenin was investigated in a case control study utilizing a matched pair collection (N = 114) of right-sided CCs with either corresponding distant metastases (N = 57) or without distant spread (N = 57) by applying immunohistochemistry.</p> <p>Results</p> <p>Elevated protein expression of SOX2 significantly correlated with the presence of lymph node- (<it>p </it>= 0.006) and distant metastases (<it>p </it>= 0.022). Nuclear β-catenin expression correlated significantly only with distant metastases (<it>p </it>= 0.001). Less than 10% of cases showed a coexpression of high levels of β-catenin and SOX2. The positivity for both markers was also associated with a very high risk for lymph-node metastases (<it>p </it>= 0.007) and distant spread (<it>p </it>= 0.028).</p> <p>Conclusion</p> <p>We demonstrated that increased expression of either SOX2 or nuclear β-catenin are associated with distant metastases in right-sided CC. Additionally, SOX2 is also associated with lymph-node metastases. These data underline the importance of stemness-associated markers for the identification of CC with high risk for distant spread.</p

Methods for visual mining of genomic and proteomic data atlases

<p>Abstract</p> <p>Background</p> <p>As the volume, complexity and diversity of the information that scientists work with on a daily basis continues to rise, so too does the requirement for new analytic software. The analytic software must solve the dichotomy that exists between the need to allow for a high level of scientific reasoning, and the requirement to have an intuitive and easy to use tool which does not require specialist, and often arduous, training to use. Information visualization provides a solution to this problem, as it allows for direct manipulation and interaction with diverse and complex data. The challenge addressing bioinformatics researches is how to apply this knowledge to data sets that are continually growing in a field that is rapidly changing.</p> <p>Results</p> <p>This paper discusses an approach to the development of visual mining tools capable of supporting the mining of massive data collections used in systems biology research, and also discusses lessons that have been learned providing tools for both local researchers and the wider community. Example tools were developed which are designed to enable the exploration and analyses of both proteomics and genomics based atlases. These atlases represent large repositories of raw and processed experiment data generated to support the identification of biomarkers through mass spectrometry (the PeptideAtlas) and the genomic characterization of cancer (The Cancer Genome Atlas). Specifically the tools are designed to allow for: the visual mining of thousands of mass spectrometry experiments, to assist in designing informed targeted protein assays; and the interactive analysis of hundreds of genomes, to explore the variations across different cancer genomes and cancer types.</p> <p>Conclusions</p> <p>The mining of massive repositories of biological data requires the development of new tools and techniques. Visual exploration of the large-scale atlas data sets allows researchers to mine data to find new meaning and make sense at scales from single samples to entire populations. Providing linked task specific views that allow a user to start from points of interest (from diseases to single genes) enables targeted exploration of thousands of spectra and genomes. As the composition of the atlases changes, and our understanding of the biology increase, new tasks will continually arise. It is therefore important to provide the means to make the data available in a suitable manner in as short a time as possible. We have done this through the use of common visualization workflows, into which we rapidly deploy visual tools. These visualizations follow common metaphors where possible to assist users in understanding the displayed data. Rapid development of tools and task specific views allows researchers to mine large-scale data almost as quickly as it is produced. Ultimately these visual tools enable new inferences, new analyses and further refinement of the large scale data being provided in atlases such as PeptideAtlas and The Cancer Genome Atlas.</p

Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

After percutaneous transluminal coronary angioplasty (PTCA), stress-echocardiography and gated single photon emission computerized tomography (g-SPECT) are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD) six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR) and color Tissue Doppler (C-TD) dobutamine stress. Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio) and C-TD at rest and during dobutamine stress to quantify myocardial systolic (S(m)) and diastolic (E(m )and A(m), E(m)/A(m )ratio) peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI) and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p < 0.002) and septal S(m )at high-dose dobutamine (p < 0.01), with higher WMSI (p < 0.05) and stress-echo positivity of LAD territory in 5/11 patients. In the overall population, CFR was related negatively to high-dobutamine WMSI (r = -0.50, p < 0.01) and positively to high-dobutamine S(m )of middle septum (r = 0.55, p < 0.005). In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD