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.

Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA.

Over the past decade, the detection and analysis of liquid biopsy biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have advanced significantly. They have received recognition for their clinical usefulness in detecting cancer at an early stage, monitoring disease, and evaluating treatment response. The emergence of liquid biopsy has been a helpful development, as it offers a minimally invasive, rapid, real-time monitoring, and possible alternative to traditional tissue biopsies. In resource-limited settings, the ideal platform for liquid biopsy should not only extract more CTCs or ctDNA from a minimal sample volume but also accurately represent the molecular heterogeneity of the patient's disease. This review covers novel strategies and advancements in CTC and ctDNA-based liquid biopsy platforms, including microfluidic applications and comprehensive analysis of molecular complexity. We discuss these systems' operational principles and performance efficiencies, as well as future opportunities and challenges for their implementation in clinical settings. In addition, we emphasize the importance of integrated platforms that incorporate machine learning and artificial intelligence in accurate liquid biopsy detection systems, which can greatly improve cancer management and enable precision diagnostics.

The role of microRNA-185 in the pathogenesis of human diseases: A focus on cancer.

MicroRNAs (miRNAs) are a widely-studied class of non-coding RNAs characterized by their short length (18-25 nucleotides). The precise functions of miRNAs are not well-elucidated; however, an increasing number of studies suggest their involvement in various physiologic processes and deregulation in pathologic conditions. miRNA-185 (miR-185) is among the mostly-studied miRNAs in human diseases, which is found to play putative roles in conditions like metabolic disorders, asthma, frailty, schizophrenia, and hepatitis. Notably, many cancer studies report the downregulation of miR-185 in cell lines, tumor tissues, and plasma specimens of patients, while it demonstrates a suppressing role on the malignant properties of cancer cells in vitro and in vivo. Accordingly, miR-185 can be considered a tumor suppressor miRNA in human malignancies, while a few studies also report inconsistent findings. Being suggested as a prognostic/diagnostic biomarker, mi-185 is also found to offer clinical potentials, particularly for early diagnosis and prediction of the prognosis of cancer patients. In this review, we have outlined the studies that have evaluated the functions and clinical significance of miR-185 in different human diseases with a particular focus on cancer.