The regulation of microRNA in each of cancer stage from two different ethnicities as potential biomarker for breast cancer.

miRNA has recently emerged as a potential biomarker for breast cancer. Even though many studies have identified ethnic variation affecting miRNA regulation, the effect of cancer stage within specific ethnicities on miRNA epigenetic remains unclear. The present study is designed to investigate miRNA regulation from two distinct ethnicities in specific cancer stages (non-Hispanic white and non-Hispanic black) using the TCGA dataset. Differentially expressed miRNAs were calculated by using the edgeR package. miRNAs with the highest or lowest log fold Change from each cancer stage were selected as a potential biomarker. miRNA-gene interaction was analyzed by using spearman correlation analysis, CLUEGO, and DIANA-mirpath. The association of biomarker candidates with diagnostic and prognostic performance was assessed using ROC and Kaplan-Meier survival analysis. miRNA-gene interaction analysis revealed the involvement of selected miRNAs in cancer progression. From eleven selected aberrant miRNAs, four of the miRNAs (hsa-mir-495, hsa-mir-592, hsa-mir-6501, and hsa-mir-937) are significantly detrimental to breast cancer diagnosis and prognosis. Hence, our result provides valuable information to explore miRNA's role in each cancer stage between non-Hispanic white and non-Hispanic black.

Immunogenicity and structural efficacy of P41 of Plasmodium sp. as potential cross-species blood-stage malaria vaccine.

Vaccine based strategies offer a promising future in malaria control by generating protective immunity against natural infection. However, vaccine development is hindered by the Plasmodium sp. genetic diversity. Previously, we have shown P41 protein from 6-Cysteine shared by Plasmodium sp. and could be used for cross-species anti-malaria vaccines. Two different approaches, ancestral, and consensus sequence, could produce a single target for all human-infecting Plasmodium. In this study, we investigated the efficacy of ancestral and consensus of P41 protein. Phylogenetic and time tree reconstruction was conducted by RAXML and BEAST2 package to determine the relationship of known P41 sequences. Ancestral and consensus sequences were reconstructed by the GRASP server and Unipro Ugene software, respectively. The structural prediction was made using the Psipred and Rosetta program. The protein characteristic was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the immunogenicity score for B-cell, T-cell, and MHC was determined using an immunoinformatic approach. The result suggests that ancestral and consensus have a distinct protein characteristic with high immunogenicity scores for all immune cells. We found one shared conserved epitope with phosphorylation modification from the ancestral sequence to target the cross-species vaccine. Thus, this study provides detailed insight into P41 efficacy for the cross-species anti-malaria blood-stage vaccine.

Structural and immunogenicity analysis of reconstructed ancestral and consensus P48/45 for cross-species anti malaria transmission-blocking vaccine.

The development of the anti-malaria vaccine holds a promising future in malaria control. One of the anti-malaria vaccine strategies known as the transmission-blocking vaccine (TBV) is to inhibit the parasite transmission between humans and mosquitoes by targeting the parasite gametocyte. Previously, we found that P48/45 included in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties possessed by all human-infecting Plasmodium and could be used as a cross-species anti-malaria vaccine. In this study, we investigated the efficacy of P48/45 through the ancestral and consensus reconstruction approach. P48/45 phylogenetic and time tree analysis was done by RAXML and BEAST2. GRASP server and Ugene software were used to reconstruct ancestral and consensus sequences, respectively. The protein structural prediction was made by using a psipred and Rosetta program. Each protein characteristic of P48/45 was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the Epitope sequence for B-cell, T-cell, and HLA was determined using an immunoinformatics approach. Lastly, molecular docking simulation was done to determine native binding interactions of P48/45-P230. The result showed a distinct protein characteristic of ancestral and consensus sequences. The immunogenicity analysis revealed the number of epitopes in the ancestral sequence is greater than the consensus sequence. The study also found a conserved epitope located in the binding site and consists of specific Post-Translational Modification sites. Hence, our research provides detailed insight into ancestral and consensus P48/45 efficacy for the cross-species anti-malaria vaccine.