Proteomics-based vaccine targets annotation and design of subunit and mRNA-based vaccines for Monkeypox virus (MPXV) against the recent outbreak.

Monkeypox Virus (MPXV) is a growing public health threat with increasing cases and fatalities globally. To date, no specific vaccine or small molecule therapeutic choices are available for the treatment of MPXV disease. In this work, we employed proteomics and structural vaccinology approaches to design mRNA and multi-epitopes-based vaccines (MVC) against MPXV. We first identified ten proteins from the whole proteome of MPXV as potential vaccine targets. We then employed structural vaccinology approaches to map potential epitopes of these proteins for B cell, cytotoxic T lymphocytes (CTL), and Helper T lymphocytes (HTL). Finally, 9 CTL, 6 B cell, and 5 HTL epitopes were joined together through suitable linkers to construct MVC (multi-epitope vaccine) and mRNA-based vaccines. Molecular docking, binding free energy calculation, and in silico cloning revealed robust interaction of the designed MVC with toll-like receptor 2 (TLR2) and efficient expression in E. Coli K12 strain. The immune simulation results revealed that the antigen titer after the injection reached to the maximum level on the 5th day and an abrupt decline in the antigen titer was observed upon the production of IgM, IgG and IgM + IgG, dendritic cells, IFN-gamma, and IL (interleukins), which suggested the potential of our designed vaccine candidate for inducing an immune response against MPXV.

What is the influence of grape products on liver enzymes? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis were aimed to determine the effects of grape products on liver enzymes in adults. METHODS: Databases including PubMed/Medline, Cochrane Library, ISI Web of Science, and Scopus were searched up to February 2021. Randomized clinical trials (RCTs) investigating the effect of grape products on serum concentrations of liver enzymes were included. Data were pooled using the random-effects model and weighted mean difference (WMD) was considered as the summary effect size. RESULTS: Eight RCTs enrolling 291 participants met the inclusion criteria for this meta-analysis. The overall effect illustrated no significant change in serum levels of alanine aminotransferase (ALT) (WMD: - 2.04; 95 % CI: - 5.50 to 1.42; P = 0.24; I2 = 72.5 %), and aspartate aminotransferase (AST) (WMD: - 1.40; 95 % CI: - 3.80 to 0.99; P = 0.25; I2 = 76.0 %) in intervention group compared with the control group. Subgroup analyses revealed that the effect of grape products on ALT (WMD: - 4.97; 95 % CI: - 8.73 to - 1.21; P = 0.01) and AST (WMD: - 2.89; 95 % CI: - 5.69 to - 0.08; P = 0.04) levels was significant when the intervention period was equal or more than 12 weeks. CONCLUSION: Overall, grape products had no significant effect on liver enzymes in adults. However, due to the low number of included studies, these findings must be interpreted with great caution. Larger, well-designed RCTs are still needed to further evaluate the capacity of the grape products as a complementary treatment to improve liver enzymes.