BackgroundVaccine-escaped hepatitis B virus (HBV) mutations occur within the “a” determinant area, which is located in the major hydrophilic region (MHR) of the hepatitis B surface antigen (HBsAg) protein. It is now well established that the common G145R mutation is highly capable of escaping from HBsAg immune recognition. However, the impacts of this mutation on the structure and immunogenic activity of HBsAg have been poorly investigated.ObjectivesThe present study analyzed the effects of the G145R mutation on the structure and immunogenic activity of the HBsAg.Materials and MethodsThree-dimensional (3D) structure of HBsAg for both the wild-type and G145R mutant were predicted and refined using several web tools. After quantitative evaluations, the effects of the G145R mutation on the secondary and 3D structures of the HBsAg were investigated. In parallel, the immunogenic activity of the wild-type and mutant HBsAg was also analyzed using a ClusPro docking server as well as the IEDB web tool. Further analyses were performed via molecular dynamics (MD) simulations using the GROMACS v5.0.2 simulation package.ResultsThe G145R mutation causes a considerable reduction in the immunogenic activity of the HBsAg through a conformational change in the HBsAg antigenic loops. This mutation inserts a new β-strand in the “a” determinant region of the HBsAg, leading to a reduced binding affinity to its monoclonal antibody, MAb12. The G145R mutation also increased the compactness and stability of the HBsAg by enhancing the rigidity of the “a” determinant.ConclusionsThese data will be beneficial for designing more advanced antibodies for the recognition of the HBsAg in diagnostics. In addition, the results of this study may assist in the design or development of more effective hepatitis B vaccines.

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Background Probiotics positively affect inflammatory responses, in part, through Janus kinase/signal transduction and activator of transcription (JAK/STAT) and inflammatory signaling pathways. To evaluate the precise effects of probiotics as protective treatment, we aimed to investigate the effectiveness of Lactobacillus spp., Bifidobacterium spp., and a mixture of these probiotics in modulating the JAK/STAT and inflammatory signaling pathways. Methods A quantitative real-time polymerase chain reaction (qPCR) assay was used to analyze the expression of JAK/STAT and inflammatory genes (TIRAP, IRAK4, NEMO, and RIP) following HT-29 cell line treatment with sonicated pathogens Lactobacillus spp., Bifidobacterium spp., and a mixed cocktail. A cytokine assay was also used to evaluate the IL-6 and IL-1β production following the probiotic treatment. Results The probiotic cocktail downregulated the JAK genes and TIRAP, IRAK4, NEMO, and RIP genes in the NF-kB pathway compared to sonicate pathogen treatment cells. The expression of STAT genes was variable following probiotic treatment. The IL-6 and IL-1β production decreased after probiotic treatment. Conclusions Our probiotic cocktail showed anti-inflammatory effects on HT-29 cells by modulating JAK/STAT and NF-kB pathways. Therefore, Lactobacillus spp. and Bifidobacterium spp. probiotics as nutritional supplements may reduce inflammation-associated diseases such as inflammatory bowel disease (IBD).

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