Production and Evaluation of Ag85B:HspX:hFcγ1 Immunogenicity as an Fc Fusion Recombinant Multi-Stage Vaccine Candidate Against Mycobacterium tuberculosis.

An urgent need is to introduce an effective vaccine against Mycobacterium tuberculosis (M.tb) infection. In the present study, a multi-stage M.tb immunodominant Fcγ1 fusion protein (Ag85B:HspX:hFcγ1) was designed and produced, and the immunogenicity of purified protein was evaluated. This recombinant fusion protein was produced in the Pichia pastoris expression system. The HiTrap-rPA column affinity chromatography purified and confirmed the fusion protein using ELISA and Western blotting methods. The co-localisation assay was used to confirm its proper folding and function. IFN-γ, IL-12, IL-4, and TGF-ß expression in C57BL/6 mice then evaluated the immunogenicity of the construct in the presence and absence of BCG. After expression optimisation, medium-scale production and the Western blotting test confirmed suitable production of Ag85B:HspX:hFcγ1. The co-localisation results on antigen-presenting cells (APCs) showed that Ag85B:HspX:hFcγ1 properly folded and bound to hFcγRI. This strong co-localisation with its receptor can confirm inducing proper Th1 responses. The in vivo immunisation assay showed no difference in the expression of IL-4 but a substantial increase in the expression of IFN-γ and IL-12 (P ≤ 0.02) and a moderate increase in TGF-ß (P = 0.05). In vivo immunisation assay revealed that Th1-inducing pathways have been stimulated, as IFN-γ and IL-12 strongly, and TGF-ß expression moderately increased in Ag85B:HspX:hFcγ1 group and Ag85B:HspX:hFcγ1+BCG. Furthermore, the production of IFN-γ from splenocytes in the Ag85B:HspX:hFcγ1 group was enormously higher than in other treatments. Therefore, this Fc fusion protein can make a selective multi-stage delivery system for inducing appropriate Th1 responses and is used as a subunit vaccine alone or in combination with others.

Probiotics as a Promising Therapy in Improvement of Symptoms in Children With ADHD: A Systematic Review.

BACKGROUND: ADHD is widely recognized as the most prevalent neurodevelopmental disorder in children. Recently, the potential role of gut microbiota as an etiological factor in ADHD has gained attention. This systematic review aims to investigate the potential impact of probiotic supplements on alleviating ADHD symptoms and influencing behavior. METHODS: PubMed, Web of Science, Cochrane Library, and SCOPUS were searched from inception to May 2023. Only randomized controlled trials that have suitable data of the effects of probiotics/synbiotics on children with ADHD were enrolled. The risk of bias of the included studies was assessed by Cochrane Collaboration risk of bias tool. RESULTS: Five related randomized controlled trial were evaluated in the current review. Types of interventions ranged from single/multi strain probiotics to synbiotic. The duration of intervention in all of the studies were 2 to 3 months. The assessed outcomes were very diverse and different tools were used to report the symptoms in children. Among those which used Conners' Parent Rating Scale, a decrease in the total score occurred in the probiotic group, compared to the placebo group. An improvement in both intervention and control groups was seen in one study which used ADHD-Rating Scale. CONCLUSION: In summary, the combined findings from the reviewed studies suggest that probiotic supplements might potentially serve as a complementary intervention for ADHD. However, given the small number of studies, limited sample sizes, and the diversity of probiotic strains, further research is needed to clarify the effects of probiotics in children with ADHD. The observed tolerability of probiotics is noteworthy as none of the studies report adverse effects.

Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis.

The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.

The therapeutic potential of Wild Bitter Melon to ameliorate muscle atrophy in a murine model.

Objective: Muscle atrophy due to immobility is a common complication of many diseases and a consequence of therapeutic processes. Immobility and inactivity have been shown to be associated with increased inflammation. The aim of this study was to investigate the therapeutic potential of Wild Bitter Melon (WBM) (Momordica charantia Linn) on muscle atrophy due to immobility in a mouse model. Materials and Methods: This study was performed in two phases of atrophy and recovery on male BALB/c mice which were divided into 3 groups: control, immobilized, and experimental. The treatment period with WBM at a dose of 400 mg/kg daily by gavage was 17 days, including 7 days of being immobilized and 10 days of recovery. At the end of each phase, half of the mice from each group were examined regarding the four limb grip strength, and then histological and biochemical analyses were done. Results: The tissue level of malondialdehyde (MDA) oxidative stress index in the atrophy phase in the atrophy group (5.4567±0.522) nmol/g compared to the control group (3.455±0.065) nmol significantly (p 0.001) <) increased. Also, the tissue level of MDA in the WBM group (3.87±0.035) showed a significant decrease compared to the atrophy group (p<0.01). The strength percentage of four limbs in the mice of the treatment group (-23.46±2.45) was significantly higher than that of the atrophy group (-30.60±3.15) at the end of the atrophy phase. Conclusion: The results suggest that the use of WBM reduces the degree of inflammation, oxidative stress and muscle damage, as well as muscle atrophy, which may improve the muscle atrophy in mice.