Iranian Biomedical Journal最新文献

Background: Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and study, we integrated metabolomics and transcriptomics data to gain deeper molecular mechanisms of Leishmania major metacyclogenesis.

Methods: The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis conducted to distinguish different metabolites between the two forms. Metabolic pathway analysis was performed using the KEGG database to identify the metabolic pathways that significantly altered and overrepresented in the metabolomic profile. Finally, the differential gene expression and pathway enrichment analyses were conducted on transcriptomic data retrieved from public repositories.

Result: Multivariate statistical analysis revealed that 44 metabolites and ten pathways were significantly different between the two forms. Transcriptome genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.

Conclusion: Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.

Background: Urinary tract infection caused by uropathogenic E. coli (UPEC) is a common infectious disease. The growing frequency of antibiotic resistance highlights the need for alternative strategies, such as vaccines, to combat UTIs. This study aimed to evaluate the immunogenicity of a novel vaccine candidate targeting UPEC.

Methods: Different bioinformatics servers were used to design a vaccine candidate composed of PapG II and FimH antigens from UPEC, along with the N- (1-173) and C-terminal (401-495) domains of FliC from Salmonella typhimurium. The final construct was cloned into the pET28a vector, expressed, purified, and confirmed using SDS-PAGE and Western blotting. Mice were immunized with the recombinant protein, both with and without alum adjuvant, and antibody responses were measured using ELISA.

Results: The final vaccine construct included one domain of PapG II (81 aa) and FimH (83 aa). The conserved domains of FliC were incorporated into the construct. SDS-PAGE and Western blot confirmed the purification of the protein, with a size of 53 kDa. Immunization of mice with PapG.FimH.FliC protein induced significantly higher levels of serum IgG, IgG isotypes, IgA, as well as mucosal IgA and IgG responses compared to the controls (p < 0.05). The addition of alum to the protein significantly enhanced serum IgG1 and IgA and mucosal IgG, compared to the protein without alum (p < 0.05).

Conclusion: The vaccine construct induced significant humoral responses in the mouse model, suggesting its potential as a promising candidate against UPEC. However, additional experimental analyses are required to validate the efficacy of the vaccine construct.