This study aims to comprehensively analyze the phosphatidylinositol-specific phospholipase C (PI-PLC) gene family in Leishmania infantum and Leishmania major genomes. By elucidating the roles of PI-PLC enzymes in parasite biology and their potential as therapeutic targets, the research contributes to understanding molecular mechanisms underlying parasite proliferation and pathogenesis. Genomic screening, gene structure analysis, phylogenetics, chromosomal distribution, and expression profiling of PI-PLC genes in L. infantum and L. major were conducted. RNA-seq data from susceptible and resistant L. infantum strains to antimony treatment were analyzed to assess gene expression patterns. Molecular docking and molecular dynamics simulations explored Evodone’s interaction within the active sites of proteins 2B4W and 4TYZ. A total of 22 PI-PLC genes were identified in both L. infantum and L. major genomes, characterized by conserved domains and biochemical properties. Phylogenetic analysis revealed evolutionary relationships and clustering patterns of these genes. Chromosomal distribution and expression profiling provided insights into their functional diversity and potential involvement in drug resistance mechanisms. This study highlights the significant roles of PI-PLC enzymes in Leishmania biology and their potential as targets for novel therapeutic interventions. Understanding their involvement in parasite pathogenesis and drug resistance mechanisms could pave the way for developing effective treatments against leishmaniasis.

Background: This study aims to comprehensively analyze the phosphatidylinositol-specific phospholipase C (PI-PLC) gene family in Leishmania infantum and Leishmania major genomes. By elucidating the roles of PI-PLC enzymes in parasite biology and their potential as therapeutic targets, the research contributes to understanding molecular mechanisms underlying parasite proliferation and pathogenesis. Methods: Genomic screening, gene structure analysis, phylogenetics, chromosomal distribution, and expression profiling of PI-PLC genes in L. infantum and L. major were conducted. RNA-seq data from susceptible and resistant L. infantum strains to antimony treatment were analyzed to assess gene expression patterns. Molecular docking and molecular dynamics simulations explored Evodone’s interaction within the active sites of proteins 2B4W and 4TYZ. Results: A total of 22 PI-PLC genes were identified in both L. infantum and L. major genomes, characterized by conserved domains and biochemical properties. Phylogenetic analysis revealed evolutionary relationships and clustering patterns of these genes. Chromosomal distribution and expression profiling provided insights into their functional diversity and potential involvement in drug resistance mechanisms. Conclusion: This study highlights the significant roles of PI-PLC enzymes in Leishmania biology and their potential as targets for novel therapeutic interventions. Understanding their involvement in parasite pathogenesis and drug resistance mechanisms could pave the way for developing effective treatments against leishmaniasis.

The anti-cancer activity of glycyrrhizin (licorice) against various types of breast cancer (BC) has been reported so far. However, a complete investigation for understanding the pathways that could be affected by this herbal compound as an anti-breast cancer agent has not been performed yet. This study tends to investigate the proteins and pathways involved in the anti-BC activity of glycyrrhizin. For this purpose, the target genes of glycyrrhizin were obtained from the ChEMBL database. The BC-associated genes for three kinds of BC were retrieved from DisGeNET. The target genes of glycyrrhizin and the BC-associated genes were compared, and the genes with disease specificity index (DSI > 0.6) were selected for further evaluation using in silico methods and bioinformatics tools. The protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. The results revealed 80 common genes among the glycyrrhizin target genes and breast carcinoma-associated genes. Ten genes had a DSI greater than 0.6. The binding affinity of glycyrrhizin to these proteins and binding characteristics were assessed using molecular docking and binding free energy calculations (MM/GBSA). POLK, TBXAS1, and ADRA1A showed the highest binding affinity with -8.9, -9.3, and -9.6 kcal/mol, respectively. ErbB signaling pathway and PD-L1 expression and PD-1 checkpoint pathway in cancer are the potent pathways for the anti-BC activity of glycyrrhizin. By affecting the obtained targets and modulating the mentioned pathways, glycyrrhizin can influence and control BC efficiently.