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IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis ( M. tb) infection. However, IGRAs with these antigens cannot discriminate between active tuberculosis (ATB) and latent tuberculosis infection (LTBI). M. tb heparin-binding-hemagglutinin (HBHA) induces relatively high IFN-γ responses in LTBI individuals and low responses in ATB patients, but purification of the native methylated HBHA from cultures of M. tb for immunological tests is complex and time-consuming. To overcome these cumbersome procedures, we constructed a recombinant Mycobacterium smegmatis strain that over-expressed HBHA under control of a strong furA promoter. The methylated activity of purified protein was verified by hybridization with anti-methylated Lys antibody, and the methylated HBHA (mHBHA) was further evaluated for antigen-specific IFN-γ responses in BCG-vaccinated Chinese population. A total of 138 individuals including 86 active TB (ATB) patients, 15 latent TB infection (LTBI) cases, and 37 healthy controls (HC) were tested by using an IFN-γ enzyme-linked immunospot (ELISPOT) assay. The results showed that T-cell responses against mHBHA were always lower in ATB patients than in LTBI individuals, regardless of the site of infection or the results of bacteriological tests. This allowed for a good discrimination between these two groups of M. tb-infected individuals, even in the BCG-vaccinated and high TB-incidence setting that is China. Additionally, combination of mHBHA and RD1 antigens in an IFN-γ release assay enhanced diagnostic efficacy for active TB cases. Taken together, inclusion of the immune response to mHBHA can discriminate healthy LTBI cases from ATB patients. [ABSTRACT FROM AUTHOR]

Hepatocarcinoma represents one of the most malignant cancer types. Esophageal cancer-related gene 2 (ECRG2) is found to be critical in the process of carcinogenesis. It regulates urokinase-type plasmin activator receptor and extracellular matrix function and its polymorphism in exon 4 is associated with cancer relapse. To explore new strategies to fight against cancer, here we first systematically evaluated the therapeutic potential as a biological tool using adenoviral vector (Ad-ECRG2). Ad-ECRG2 is exogenously expressed in cytoplasm and is potent to suppress the growth of cancer cell by inducing apoptosis as effective as Ad-p53. Ad-ECRG2 is able to suppress the invasion and adhesion of cancer cells at low titers. It alters the expression of a panel of cancer-related molecules, including nuclear factor-kB, matrix metalloproteinase 2 and E-cadherin, contributing to reverse malignancy phenotype of cancer cells. In vivo experiments show a significant inhibition of cancer growth by intratumoral Ad-ECRG2 administration. No evident toxicity was observed in the model animal during the study. We concluded that ECRG2 is a potential molecular target in biological therapy strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

Objective:Abundant evidence has demonstrated that long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous study reveals a significant association between promoter polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which suggests possible roles of IL-4 in metabolism. In this study, we focused on examining the putative regulation of glucose and lipid metabolism by IL-4.Methods:C57BL/6 mice were intraperitoneally injected with either adenovirus containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for mimicking the status of transient and long-term IL-4 overexpression, respectively, and the effects of the overexpressed IL-4 to glucose/lipid metabolism and insulin sensitivity were subsequently investigated.Results:Our results reveal that IL-4 improves insulin sensitivity and glucose tolerance through upregulating Akt phosphorylation while attenuating GSK-3β activities. IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat tissues, which lead to decreased weight gain and fat mass.Conclusions:Our results suggest that IL-4 regulates glucose and lipid metabolism by promoting insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study uncovers the novel roles of IL-4 in metabolism and provides new insights in the interaction between cytokines/immune responses, insulin sensitivity and metabolism. [ABSTRACT FROM AUTHOR]