Tumor necrosis factor-α-308 G/A polymorphisms and risk of hepatocellular carcinoma: A meta-analysis

Context: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor- α (TNF- α) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-α promoter (TNF- α -308) andHCCrisk has been confirmed in various reports. Evidence Acquisition: The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF-₋₃₀₈ and the risk of HCC. To determine this association, odds ratios (ORs) and 95 confidence intervals (95 CIs) were calculated. Results: A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4 vs. 8.4). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95 CI = 1.26-2.50; P value < 0.002). In addition to the allelic model, the dominant model (AA +AGvs. GG) was significantly associated withHCCrisk (OR = 1.80; CI = 1.29-2.51; P value< 0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG + GG), no trustworthy associations with the risk of HCC development were observed. Conclusions: This meta-analysis indicated that the TNF- α -308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF- α -308 G/A polymorphisms associated with HCC. © 2016, Kowsar Corp

Roles of GM-CSF in the Pathogenesis of Autoimmune Diseases: An Update.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Conversely, a protective role has also been described in other autoimmune diseases where humoral responses are detrimental such as myasthenia gravis (MG), Hashimoto\u27s thyroiditis (HT), inflammatory bowel disease (IBD), and systemic lupus erythematosus (SLE). In this review, we aimed for a comprehensive analysis of literature data on the multiple roles of GM-CSF in autoimmue diseases and possible therapeutic strategies that target GM-CSF production

An investigation of a Ɣ-type MTD Stirling engine prototype

This is the author accepted manuscript. The final version is available from UKACM via the link in this recordAlthough thermal efficiency of moderate temperature differential (MTD) Stirling engines is higher than low temperature (LTD) engines, the complexity of design of MTD engines has led to the lack of research in this field. In this work, a prototype of Ɣ-type moderate-temperature differential Stirling engine was manufactured, evaluated and structurally optimised. A mathematical evaluation was carried out based on a finite-dimension thermodynamics approach. The swept volume ratio was optimised based on the temperature difference of 450 . 0 . A computer program was thus written to simulate the Stirling engine performance under the assumed working conditions. Based on the mentioned temperature difference, the swept volume ratio of the engine was found to be 3. The engine dimensions were then adjusted to fulfil the computed swept volume ratio. The bore and stroke for power piston were chosen as 60 mm and 40 mm, respectively. For the displacer, they were selected as 90 mm and 60 mm, respectively based on the chosen swept volume ratio

Elevated Serum Levels of Interleukin-15 in Pemphigus Vulgaris Patients: a Potential Therapeutic Target

Introduction: Pemphigus vulgaris (PV) is a rare autoimmune disease that causes painful blistering. Interleukin-15 (IL-15) as a member of the immunoregulatory cytokines family is associated with the development of the chronic inflammatory or autoimmune disease. There is not much information available in the literature on the exact role IL-15 plays in PV. Objectives: The goal of this study was to evaluate the serum levels of IL-15 in patients with PV and assess the association of IL-15 with anti-desmoglein antibodies and the severity of the disease. Methods: Fifty-three individuals affected with active PV and 38 age- and gender-matched healthy controls were participated in this study. Disease severity was assessed using Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Serum levels of IL-15 (pg/mL) and anti-desmoglein antibodies (Dsg1, 3) were determined. Results: In the patient group, IL-15 serum levels were statistically higher than those in the control group (3.71 } 1.5 vs. 0.79 } 1.03, P \u3c 0.001). A positive correlation was found between serum levels of IL-15 and ABSIS (r = 0.5, P = 0.04). We found no significant correlation between serum concentrations of IL-15 and antidesmoglein antibodies (Dsg1 or Dsg3). Conclusions: An increase in serum level of IL-15 in patients with PV and its relationship with disease severity suggest that this cytokine possibly contributes to the pathogenesis of the disease and targeting IL-15 will likely provide a new insight into the treatment of this disease

miR-455-5p downregulation promotes inflammation pathways in the relapse phase of relapsing-remitting multiple sclerosis disease

MicroRNA-455-5p (miR-455-5p) seems to have an anti-inflammatory role in the immune system since its expression is induced by IL-10 cytokine. Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the central nervous system that is caused by an autoimmune inflammatory attack against the myelin insulation of neurons. The expression level of miR-455-5p and its role in MS pathogenesis has yet to be elucidated. We found that miR-455-5p expression was highly correlated with disease severity in MS patients. miR-455-5p expression inversely correlates with its inflammatory-predicted targets (MyD88 and REL) in relapse- and remitting-phase patients. Luciferase assays confirm that MyD88 and REL are direct targets of miR-455-5p. This study represents the first report of the miR-455-5p acts as an anti-inflammatory role in MS, at least partially through targeting MyD88 and REL. This study may provide important information for the use of miR-455-5p as a novel strategy to improve the severity of disease and control inflammation and attack in MS patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

Tyrosine Kinases in Autoimmune and Inflammatory Skin Diseases

Tyrosine kinases relay signals from diverse leukocyte antigen receptors, innate immune receptors, and cytokine receptors, and therefore mediate the recruitment and activation of various leukocyte populations. Non-receptor tyrosine kinases of the Jak, Src, Syk, and Btk families play major roles in various immune-mediated disorders, and small-molecule tyrosine kinase inhibitors are emerging novel therapeutics in a number of those diseases. Autoimmune and inflammatory skin diseases represent a broad spectrum of immune-mediated diseases. Genetic and pharmacological studies in humans and mice support the role of tyrosine kinases in several inflammatory skin diseases. Atopic dermatitis and psoriasis are characterized by an inflammatory microenvironment which activates cytokine receptors coupled to the Jak-Stat signaling pathway. Jak kinases are also implicated in alopecia areata and vitiligo, skin disorders mediated by cytotoxic T lymphocytes. Genetic studies indicate a critical role for Src-family kinases and Syk in animal models of autoantibody-mediated blistering skin diseases. Here, we review the various tyrosine kinase signaling pathways and their role in various autoimmune and inflammatory skin diseases. Special emphasis will be placed on identification of potential therapeutic targets, as well as on ongoing preclinical and clinical studies for the treatment of inflammatory skin diseases by small-molecule tyrosine kinase inhibitors

Genetic algorithm-based identification of transfer function parameters for a rectangular flexible plate system

This paper focuses on an identification technique based on geneticalgorithms (GAs) with application to rectangularflexibleplatesystems for active vibration control. A real coded GA with a new truncation-based selection strategy of individuals is developed, to allow fast convergence to the global optimum. A simulation environment characterizing the dynamic behavior of aflexiblerectangularplatesystem is developed using the central finite difference (FD) techniques. The plate thus developed is excited by a uniformly distributed random disturbance and the input–output data of the system acquired is used for black-box modeling the system with the GA optimization using an autoregressive model structure. Model validity tests based on statistical measures and output prediction are carried out. The prediction capability of the model is further examined with unseen data. It is demonstrated that the GA gives faster convergence to an optimum solution and the model obtained characterizes the dynamic system behavior of the system well