An epicutaneous therapeutic pollen-allergen extract delivery system in an allergic rhinitis mouse model: based on allergen loading on DC-specific aptamers conjugated nanogolds.

BACKGROUND: Gold nanoparticles (GNPs) have previously been suggested as appropriate carriers for allergen-specific immunotherapy (AIT). In this study, we assessed efficacy of GNPs and dendritic cells (DC)-specific aptamer-modified GNPs (Apts-GNP) for epicutaneous immunotherapy (EPIT) in the case of pollen allergen extracts containing a variety of allergenic and non-allergenic components. METHODS: BALB/c mice were sensitized to the total protein extract of Platanus orientalis pollen and epicutaneously treated in different groups either with free P. orientalis total pollen extract, naked GNPs, total extract loaded GNPs, and total extract loaded Apts-GNPs with and without skin-penetrating peptides (SPPs). Then, the specific IgE level (sIgE), total IgE concentration (tIgE) in the serum sample, IL-4, IL-17a, IFN-γ, and IL-10 cytokine concentrations in re-stimulated splenocytes with the total extract and mixture of recombinant allergens, nasopharyngeal lavage fluid (NALF) analysis, and histopathological analysis of lung tissue were evaluated. RESULTS: This study indicated the total extract-loaded GNPs, especially Pla. ext (50 µg)-GNPs, significantly decreased sIgE, tIgE, IL-17a, and IL-4 concentrations, immune cells and eosinophils infiltration in NALF, and increased IL-10 and IFN-γ concentrations compared with the PBS-treated group. In addition, the histopathological analysis of lung tissue showed a significant decrease in allergic inflammation and histopathological damage. The DC-targeted group revealed the most significant improvement in allergic-related immune factors with no histopathological damage compared with the same dose without aptamer. CONCLUSION: Loading total protein extract on the GNPs and the Apt-modified GNPs could be an effective approach to improve EPIT efficacy in a pollen-induced allergic mouse model.

Topical anti-TNF-a ssDNA aptamer decreased the imiquimod induced psoriatic inflammation in BALB/c mice.

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) is a pro-inflammatory factor that plays a pivotal role in psoriasis. Due to limitations of monoclonal antibody-based therapies, it is needed to discover new anti-TNF-α factors instead of usual anti-TNF-α monoclonal antibodies. Compared to antibodies, single-stranded DNA or RNA molecules named aptamers, have advantages such as time-saving, less risk for immunogenicity and cost-effectiveness. Therefore, the aim of the present study was to assess the therapeutic effects of T1-T4 dimer anti-TNF-ɑ ssDNA aptamer topical treatment in the imiquimod (IMQ)-induced psoriasis animal model. METHODS: 5% IMQ cream was prescribed on the right ear of BALB/c to induce psoriasis model. The hydrogel-containing anti-TNF-ɑ aptamer or treatment control aptamer (anti- Interleukin (IL)17A) was topically prescribed to the mice's ears 10 min before IMQ cream treatment. The psoriasis area severity index (PASI) score was used to evaluate psoriasis intensity. Histopathology analysis was done for mice ears sections. Mass, size, and cell number of mice spleens were measured. The IL-17 level was determined in culture supernatants of axillary lymph node cells using ELISA. The mRNA expression levels of IL-17A, IL-1ß, STAT3, and S100a9, were evaluated in mice treated ear with quantitative Real Time-PCR. RESULTS: The anti-TNF-ɑ ssDNA aptamer lower doses had significant decrease in IMQ-induced PASI score (p < 0.05). In addition, in these groups, the IL-17A, STAT3, and S100a9 mRNA levels were significantly lower than the IMQ group (p < 0.05). CONCLUSION: According to our findings, this aptamer seems to be a prospective candidate for treating psoriatic inflammation especially in lower concentrations.

Anti-IL-17A ssDNA aptamer ameliorated psoriasis skin lesions in the imiquimod-induced psoriasis mouse model.

OBJECTIVES: IL-17 is an important player in the psoriasis pathogenesis, which recruits inflammatory cells to the psoriatic lesions, induced keratinocyte proliferation and plaque formation. Three monoclonal antibodies that block IL-17 have been approved for psoriasis treatment in the last decade. Compared to monoclonal antibodies, aptamers which are single-stranded DNA or RNA, bind with high affinity to proteins or other molecules and are more cost-effective. We previously showed that M2 and M7 anti-IL17A ssDNA aptamers could block IL-17 in vitro. The current study evaluated the therapeutic effects of M2 and M7 anti-IL17A ssDNA aptamers in the imiquimod (IMQ)-induced psoriasis mouse model. METHODS: IMQ cream and Vaseline (Vas) were administered on the back skin of C57BL/6 mice as IMQ-induced psoriasis and Vas control groups, respectively. In addition, hydrogel-containing aptamers were topically administered on the back skin of the mice, 10 min before IMQ treatment. Psoriatic lesions were evaluated by histology, clinical factors, and psoriasis area severity index (PASI) score. The mRNA expression levels of inflammatory factors, including IL-17A, IL-1ß, and S100a9, were assessed with quantitative reverse transcriptase-polymerase chain reaction in the mice back skin. RESULTS: Application of anti-IL-17A aptamers significantly ameliorated IMQ-induced keratinocyte proliferation, psoriatic lesions cumulative PASI score, IL-17A, IL-ß, and S100a9 inflammatory factors mRNA expression levels (p < 0.05). CONCLUSION: According to our results, it seems that M2 in high concentration and M7 in low concentration can be appropriate candidates to alleviate psoriasis lesions.

The Accuracy of Ultrasonography in Detection of Ulnar Collateral Ligament of Thumb Injuries; a Cross-Sectional Study.

INTRODUCTION: Timely diagnosis and treatment of traumatic injury to ulnar collateral ligament (UCL) of thumb is of special importance for preserving the full function of the hand. Therefore, the present study has been designed with the aim of evaluating the accuracy of ultrasonography in detection of these injuries. METHODS: The present diagnostic accuracy study was performed on trauma patients over 15 years old who had clinical evidence of injury to UCL of thumb and were admitted to the emergency department. All patients were evaluated regarding injury to the mentioned ligament via ultrasonography and MRI and finally, the accuracy of ultrasonography in this regard was measured considering MRI as the reference test. RESULTS: 20 individuals with the mean age of 38.60 ± 13.45 (16 - 64) years were evaluated (60% male). Based on ultrasonography and MRI findings 7 (35%) individuals and 7 (35%), respectively had complete ligament rupture (kappa: 0.560 (95% CI: 0.179 - 0.942)). Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of ultrasonography in detecting injuries of the mentioned ligament were 71.42 (30.25 - 94.88), 84.61 (53.66 - 97.28), 71.42 (30.25 - 94.88), 84.61 (53.66 - 97.28), 2.5 (0.71 - 8.82), and 0.18 (0.04 - 0.67), respectively. CONCLUSION: Based on the findings of the present study, performance of ultrasonography by a radiologist in the emergency department has 80% accuracy in detecting traumatic injuries of UCL of the thumb.