Characterization of exclusively non-commensal Neisseria gonorrhoeae pangenome to prioritize globally conserved and thermodynamically stable vaccine candidates using immune-molecular dynamic simulations.

Neisseria gonorrhoeae (Ngo) has emerged as a global threat leading to one of the most common sexually transmitted diseases in the world. It has also become one of the leading antimicrobial resistant organisms, resulting in fewer treatment options and an increased morbidity. Therefore, in recent years, there has been an increased focus on the development of new treatments and preventive strategies to combat its infection. In this study, we have combined the most conserved epitopes from the completely assembled strains of Ngo to develop a universal and a thermodynamically stable vaccine candidate. For our vaccine design, the epitopes were selected for their high immunogenicity, non-allergenicity and non-cytotoxicity, making them the ideal candidates for vaccine development. For the screening process, several reverse vaccinology tools were employed to rigorously extract non-homologous and immunogenic epitopes from the selected proteins. Consequently, a total number of 3 B-cell epitopes and 6 T-cell epitopes were selected and joined by multiple immune-modulating adjuvants and linkers to generate a promiscuous immune response. Additionally, the stability and flexible nature of the vaccine construct was confirmed using various molecular dynamic simulation tools. Overall, the vaccine candidate showed promising binding affinity to various HLA alleles and TLR receptors; however, further studies are needed to assess its efficacy in-vivo. In this way, we have designed a multi-subunit vaccine candidate to potentially combat and control the spread of N. gonorrhoeae.

Identification of Differentially Expressed Genes Associated with the Prognosis and Diagnosis of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis.

Objective: The goal of this study was to understand the possible core genes associated with hepatocellular carcinoma (HCC) pathogenesis and prognosis. Methods: GEO contains datasets of gene expression, miRNA, and methylation patterns of diseased and healthy/control patients. The GSE62232 dataset was selected by employing the server Gene Expression Omnibus. A total of 91 samples were collected, including 81 HCC and 10 healthy samples as control. GSE62232 was analysed through GEO2R, and Functional Enrichment Analysis was performed to extract rational information from a set of DEGs. The Protein-Protein Relationship Networking search method has been used for extracting the interacting genes. MCC method was used to calculate the top 10 genes according to their importance. Hub genes in the network were analysed using GEPIA to estimate the effect of their differential expression on cancer progression. Results: We identified the top 10 hub genes through CytoHubba plugin. These included BUB1, BUB1B, CCNB1, CCNA2, CCNB2, CDC20, CDK1 and MAD2L1, NCAPG, and NDC80. NCAPG and NDC80 reported for the first time in this study while the remaining from a recently reported literature. The pathogenesis of HCC may be directly linked with the aforementioned genes. In this analysis, we found critical genes for HCC that showed recommendations for future prognostic and predictive biomarkers studies that could promote selective molecular therapy for HCC.