Possible role of TGF-B pathways in schizophrenia

© 2016, University of Kragujevac, Faculty of Science. All Rights Reserved. The phenomenological uniqueness of each patient with schizophrenia is determined by complex symptomatology, particularly the overlapping of symptoms and their prominence in certain phases of this mental disorder. Establishing biological markers is an important step in the further objectivisation and quantification of schizophrenia. Identifying the cytokine profiles that precede a psychotic episode could direct the strategies for relapse prevention and be useful in predicting disease progression and treatment response. In the context of inflammation, TGF-β exerts potent anti-inflammatory and immunosuppressive functions by inhibiting pro-inflammatory cytokine synthesis, but it can also have pro-inflammatory functions through its stimulatory effects on inflammatory 17 cells. It has been shown that the T helper cell type-1 and type-17 responses are reduced and type-2 response is increased in patients with schizophrenia. Both data from the literature and our results also indicate the presence of an anti-inflammatory response through production of the TGF-β regulatory cytokine. A meta-analysis of plasma cytokine alterations suggested that TGF-β is the state marker for acute exacerbation of schizophrenia, and we showed that TGF-β can also be a valuable marker for psychosis. Hyperactivity of TGF-β signalling pathways in schizophrenia may be both a neuroprotective mechanism and a possible therapeutic target

IL-33/ST2 axis in innate and acquired immunity to tumors

Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation. The role of IL-33/ST2 axis in cancer is not elucidated. Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity

AN INTEGRATED APPROACH FOR DESIGN AND MANUFACTURE OF PLASTIC PRODUCTS

The aim of this paper is to present an integrated design procedure for plastic part development and manufacture. Reverse engineering (RE), re-engineering (ReE) and mold design have been incorporated to infuse agile characteristics in the proposed design and development process. The integration of RE and ReE presented in this paper accelerate the design process and provide information necessary for complete injection molding process of plastic parts. The purpose is to create a new object geometrically similar to the existing object. The new object must have better mechanical properties and more favorable geometry from the standpoint of mold ability. This paper also, describes a methodology for quality geometry check of the manufactured part that is need for verified the used integrated CAD/CAE technologies

IL-33/ST2 Pathway and Galectin-3 as a New Analytes in Pathogenesis and Cardiometabolic Risk Evaluation in Psychosis

Schizophrenia and treatment of this disorder are often accompanied with metabolic syndrome and cardiovascular issues. Alterations in the serum level of innate immune mediators, such as interleukin-33 (IL-33) and its receptor IL-33R (ST2) and Galectin-3 (Gal-3) were observed in these conditions. Moreover, these parameters are potential prognostic and therapeutic markers. There is also accumulating evidence that these molecules play a role in neuroinflammation. Therefore, in this study we have investigated the serum level of Gal-3, IL-33 and soluble ST2 (sST2) in different stages of schizophrenia. Gal-3 levels were elevated in remission and lower in schizophrenia exacerbation in comparison with controls. Levels of IL-33 and sST2 are higher in schizophrenia exacerbation in comparison with controls and patients in remission. This initial analysis of new markers of neuroinflammation suggested their involvement in schizophrenia pathophysiology and/or cardiometabolic comorbidity

Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+T cells in aged rats

Background: Aging influences immune response and susceptibility to EAE in a strain specific manner. The study was designed to examine influence of aging on EAE induction in Albino Oxford (AO) rats. Results: Differently from 3-month-old (young) rats, which were resistant to EAE induction, the majority of aged (24-26-month-old) rats developed mild chronic form of EAE. On 16th day post-immunization, when in aged rats the neurological deficit reached plateau, more mononuclear cells, including CD4+ T lymphocytes was retrieved from spinal cord of aged than young rats. The frequencies of IL-17+ and GM-CSF+ cells within spinal cord infiltrating CD4+ lymphocytes were greater in aged rats. To their increased frequency contributed the expansion of GM-CSF + IL-17 + IFN-gamma+ cells, which are highly pathogenic in mice. The expression of the cytokines (IL-1 beta and IL-23/p19) driving GM-CSF + IL-17 + IFN-gamma + cell differentiation in mice was also augmented in aged rat spinal cord mononuclear cells. Additionally, in aged rat spinal cord the expansion of GM-CSF + IL-17-IFN-gamma- CD4+ T lymphocytes was found. Consistently, the expression of mRNAs for IL-3, the cytokine exhibiting the same expression pattern as GM-CSF, and IL-7, the cytokine driving differentiation of GM-CSF + IL-17-IFN-gamma- CD4 + lymphocytes in mice, was upregulated in aged rat spinal cord mononuclear cells, and the tissue, respectively. This was in accordance with the enhanced generation of the brain antigen-specific GM-CSF+ CD4+ lymphocytes in aged rat draining lymph nodes, as suggested by (i) the higher frequency of GM-CSF+ cells (reflecting the expansion of IL-17-IFN-gamma- cells) within their CD4+ lymphocytes and (ii) the upregulated GM-CSF and IL-3 mRNA expression in fresh CD4+ lymphocytes and MBP-stimulated draining lymph node cells and IL-7 mRNA in lymph node tissue from aged rats. In agreement with the upregulated GM-CSF expression in aged rats, strikingly more CD11b + CD45(int) (activated microglia) and CD45(hi) (mainly proinflammatory dendritic cells and macrophages) cells was retrieved from aged than young rat spinal cord. Besides, expression of mRNA for SOCS1, a negative regulator of proinflammatory cytokine expression in innate immunity cells, was downregulated in aged rat spinal cord mononuclear cells. Conclusions: The study revealed that aging may overcome genetic resistance to EAE, and indicated the cellular and molecular mechanisms contributing to this phenomenon in AO rats

Cybersecurity for industrial Internet of Things: architecture, models and lessons learned

Modern industrial systems now, more than ever, require secure and efficient ways of communication. The trend of making connected, smart architectures is beginning to show in various fields of the industry such as manufacturing and logistics. The number of IoT (Internet of Things) devices used in such systems is naturally increasing and industry leaders want to define business processes which are reliable, reproducible, and can be effortlessly monitored. With the rise in number of connected industrial systems, the number of used IoT devices also grows and with that some challenges arise. Cybersecurity in these types of systems is crucial for their wide adoption. Without safety in communication and threat detection and prevention techniques, it can be very difficult to use smart, connected systems in the industry setting. In this paper we describe two real-world examples of such systems while focusing on our architectural choices and lessons learned. We demonstrate our vision for implementing a connected industrial system with secure data flow and threat detection and mitigation strategies on real-world data and IoT devices. While our system is not an off-the-shelf product, our architecture design and results show advantages of using technologies such as Deep Learning for threat detection and Blockchain enhanced communication in industrial IoT systems and how these technologies can be implemented. We demonstrate empirical results of various components of our system and also the performance of our system as-a-whole