Iranian Biomedical Journal
Volume:28 Issue: 4, Jul 2024

Feasible diagnostic assays are required to detect new TB cases and monitor treatment. This study aimed to evaluate evidence on Trp and its metabolites as proposed biomarkers for TB. Through specific keyword searches, we identified 170 relevant literature sources and included seven publications (from 2013 to 2023). The biomarker used in these studies were IDO activity, IDO-1 gene expression, and plasma IDO protein, measured using ELISA, LC-MS, UPLC, and transcriptional profiling. The studies encompassed a pediatric case-control and six studies involving adults, pregnant women with TB-HIV, and individuals with MDR-TB, active TB, and latent TB. The assessment of IDO activity and IDO protein level demonstrated promising performance in distinguishing active TB from controls and in evaluating treatment failure and recurrent cases to controls. Trp and its metabolites fulfilled nearly all of TPP criteria for detecting active TB. This study highlights the potential of utilizing host Trp and its metabolites as non-based biomarker for TB infection.

The growing threat of antibiotic resistance and Klebsiella pneumoniae infection in healthcare settings highlights the urgent need for innovative solutions, such as vaccines, to address these challenges. This study sought to assess the potential of using K. pneumoniae OmpA as a vaccine candidate through both in silico and in vivo analyses.

The study examined the OmpA protein sequence for subcellular localization, antigenicity, allergenicity, similarity to the human proteome, physicochemical properties, B-cell epitopes, MHC binding sites, tertiary structure predictions, molecular docking, and immune response simulations. The ompA gene was cloned into the pET-28a (+) vector, expressed, purified and confirmed using Western blotting analysis. IgG levels in the serum of the immunized mice were measured using ELISA with dilutions ranging from 1:100 to 1:6400, targeting rOmpA and K. pneumoniae ATCC 13883. The sensitivity and specificity of the ELISA method were also assessed.

The bioinformatics analysis identified rOmpA as a promising vaccine candidate. The immunized group demonstrated significant production of specific total IgG antibodies against rOmpA and K. pneumoniae ATCC1 13883, as compared to the control group (p < 0.0001). The titers of antibodies produced in response to bacterial exposure did not show any significant difference when compared to the anti-rOmpA antibodies (p > 0.05). The ELISA test sensitivity was 1:3200, and the antibodies in the serum could accurately recognize K. pneumoniae cells.

This study is a significant advancement in the development of a potential vaccine against K. pneumoniae that relies on OmpA. Nevertheless, additional experimental analyses are required.

Despite the widespread use of opioids to manage severe pain, its systemic administration results in side effects. Among the subcutaneous and transdermal drug delivery systems developed to deal with adverse effects, microneedles have drawn attention due to their rapid action, high drug bioavailability, and improved permeability. SUF is an effective injectable opioid for treating severe pain. In this study, we investigated the analgesic effects of SUF using dissolvable microneedles.

SUF polymeric dissolvable microneedles were constructed through the mold casting method and characterized by SEM and FTIR analysis. Its mechanical strength was also investigated using a texture analyzer. Fluorescence microscopy was applied in vitro to measure the penetration depth of microneedle arrays. Irritation and microchannel closure time, drug release profile, and hemocompatibility test were conducted for the validation of microneedle efficiency. Hot plate test was also used to investigate the analgesic effect of microneedle in an animal model.

Local administration of SUF via dissolving microneedles had an effective analgesic impact. One hour after administration, there was no significant difference between the subcutaneous and the microneedle groups, and the mechanical properties were within acceptable limits.

Microneedling is an effective strategy in immediate pain relief compared to the traditional methods.

Cutaneous leishmaniasis is a major health problem caused by an intracellular pathogen of the genus Leishmania. CL results in morphologically distinct skin injuries, ranging from nodules to plaques and ulcers, which persist as a recuperating incessant injury depending on the type of contaminating parasite. There is still no effective treatment to reduce the skin lesions in patients infected with CL. The aim of this study was to develop strategies to treat skin lesions in CL patients.

We retrieved the transcriptomic data of skin lesions from patients with CL and normal skin from the GEO database. The PPIN was constructed using the STRING database and Cytoscape v3.10.1 software. Critical genes were identified by topological network analysis and cluster detection. Finally, gene ontology and repurposing drugs for critical genes were determined.

CD8A, IFNG, IL-6, PTPRC, CCR7, TLR2, GSTA5, CYBB, IL-12RB2, ITGB2, FCGR3A, CTLA4, and IFNG were identified as the critical genes in PPIN and subnetworks. Enrichment analysis revealed that T-cell receptor signaling, TLR signaling, cytokine-cytokine receptor interaction, graft-versus-host disease, leishmaniasis, chemokine signaling, primary immunodeficiency, and Th17 cell differentiation were the major pathways associated with critical genes. The drug repurposing results identified cyclosporine, rituximab, infliximab, blinatumomab, and methylprednisolone as candidates for treatment of CL.

After validating our model with available experimental data, we found that critical molecules and drug candidates play a crucial role in
the treatment of skin lesions caused by Leishmania in prospective studies.

Since the beginning of the SARS-CoV-2 pandemic, there have been mutations caused by new SARS-CoV-2 variants, such as Alpha, Beta, Gamma, Delta, and Omicron, recognized as the VOC worldwide. These variants can affect vaccine efficacy, disease control, and treatment effectiveness. The present study aimed to evaluate the levels of total and neutralizing antibodies produced by PastoCoAd vaccine candidates against the VOC strains at different time points.

Two vaccine candidates were employed against SARS-CoV-2 using adenoviral vectors: prime only (a mixture of rAd5-S and rAd5 RBD-N) and heterologous prime-boost (rAd5-S/SOBERANA vaccine). The immunogenicity of these vaccine candidates was assessed in mouse, rabbit, and hamster models using ELISA assay and virus neutralization antibody test.

The immunogenicity results indicated a significant increase in both total and neutralizing antibodies titers in the groups receiving the vaccine candidates at various time points compared to the control group (p < 0.05). The results also showed that the PastoCoAd vaccine candidates Ad5 S & RBD-N and Ad5 S/SOBERANA could neutralize the VOC strains in the animal models.

The ability of vaccine candidate to neutralize the VOC strains in animal models by generating neutralizing antibodies at different time points may be attributed to the use of the platform based on the Adenoviral vector, the N proteins in the Ad5 S & RBD-N vaccine candidate, and the SOBERANA Plus booster in the Ad5 S/SOBERANA vaccine candidate.