Allergen specific immunotherapy with plasmid DNA encoding OVA-immunodominant T cell epitope fused to Tregitope in a murine model of allergy.

BACKGROUND: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy. METHODS: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined. RESULTS: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-ß expression were increased. Moreover, OVA-specific IgE levels were also decreased. CONCLUSION: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy.

Investigation of antibacterial and anticancer effects of novel niosomal formulated Persian Gulf Sea cucumber extracts.

Pharmaceutical companies worldwide are scrambling to develop new ways to combat cancer and microbiological pathogens. The goal of this research was to investigate the antibacterial, anticancer, and apoptosis effects of novel niosomal formulated Persian Gulf Sea cucumber extracts (SCEs). Sea cucumber methanolic extracts were prepared and encapsulated in niosome nanoparticles using thin-film hydration. The compound was made up of Span 60 and Tween 60 blended with cholesterol in a 3:3:4 M ratios. Characterization of niosome-encapsulated SCE evaluated by scanning electron microscopy and transmission electron microscopy. The disk diffusion method and microtiter plates were used to investigate the antimicrobial activity. The effect of niosome-encapsulated SCE on cell proliferation and apoptosis induction was studied using MTT and Annexin V, respectively. The expression of apoptosis-related genes, including Bax, Fas, Bax, Bak, and Bcl2, was studied using quantitative real-time PCR. Niosome-encapsulated SCE with a size of 80.46 ± 1.31 and an encapsulation efficiency of 79.18 ± 0.23 was formulated. At a concentration of 100 µg/ml, the greatest antimicrobial effect of the niosome-encapsulated SCE was correlated to Staphylococcus aureus, with an inhibition zone of 13.16 mm. The findings of the study revealed that all strains were unable to produce biofilms at a concentration of 100 µg/ml niosome-encapsulated SCE (p < 0.001). The survival rate of cancer cells after 72 h of exposure to niosome-encapsulated SCE was 40 ± 3.0%. Encapsulated SCE in niosomes inhibited cell progression in MCF-7 cells by increasing G0/G1 and decreasing S phase relative to G2/M phase; as a result, it activated the apoptosis signaling pathway and led to the induction of apoptosis in 69.12 ± 1.2% of tumor cells by increasing the expression of proapoptotic genes (p < 0.001). The results indicate that sea cucumber species from the Persian Gulf are a promising source of natural chemicals with antibacterial and anticancer properties, paving the path for novel marine natural products to be discovered. This is the first demonstration that niosome-encapsulated SCE contains antibacterial and anticancer chemicals that, according to their specific characteristics, boost antitumor activity.

Effects of Imipenem-containing Niosome nanoparticles against high prevalence methicillin-resistant Staphylococcus Epidermidis biofilm formed.

We aim to assess the antibacterial and anti-biofilm properties of Niosome-encapsulated Imipenem. After isolating Staphylococcus epidermidis isolates and determining their microbial sensitivity, their ability to form biofilms was examined using plate microtiter assay. Various formulations of Niosome-encapsulated Imipenem were prepared using the thin-film hydration method, Minimum Biofilm Inhibitory Concentration (MBIC) and Minimum Inhibitory Concentration (MIC) were determined, and biofilm genes expression was examined. Drug formulations' toxicity effect on HDF cells were determined using MTT assay. Out of the 162 separated S. epidermidis, 106 were resistant to methicillin. 87 MRSE isolates were vancomycin-resistant, all of which could form biofilms. The F1 formulation of niosomal Imipenem with a size of 192.3 ± 5.84 and an encapsulation index of 79.36 ± 1.14 was detected, which prevented biofilm growth with a BGI index of 69% and reduced icaD, FnbA, EbpS biofilms' expression with P ≤ 0.001 in addition to reducing MBIC and MIC by 4-6 times. Interestingly, F1 formulation of niosomal Imipenem indicated cell viability over 90% at all tested concentrations. The results of the present study indicate that Niosome-encapsulated Imipenem reduces the resistance of MRSE to antibiotics in addition to increasing its anti-biofilm and antibiotic activity, and could prove useful as a new strategy for drug delivery.