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AbstractObjectiveMethodsResultsConclusionOne of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs).The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed.Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups.Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans. [ABSTRACT FROM AUTHOR]

Background. Psoriasis is a noncontagious auto‐inflammatory chronic skin disease. So far, some of the inflammatory genes were upregulated in mouse model of psoriasis. This study examined changes in skin mRNA expression of L‐kynureninase (Kynu), cathelicidin antimicrobial peptide (Camp), beta‐defensin 2 (Defb2), and proenkephalin (Penk) in a mouse model of imiquimod‐induced psoriasis. Materials and Methods. Tree groups of C57BL/6 female mice were allocated. The imiquimod (IMQ) cream was administered to the mice dorsal skin of the two groups to induce psoriatic inflammation. In the treatment group, IMQ was administered 10 min after hydrogel‐containing M7 anti‐IL‐17A aptamer treatment. Vaseline (Vas) was administered to the negative control group. The psoriatic skin lesions were evaluated based on the psoriasis area severity index (PASI) score, histopathology, and mRNA expression levels of Kynu, Camp, Defb2, and Penk using real‐time PCR. In order to assess the systemic response, the spleen and lymph node indexes were also evaluated. Results. The PASI and epidermal thickness scores were 6.01 and 1.96, respectively, in the IMQ group, and they significantly decreased after aptamer administration to 1.15 and 0.90, respectively (P < 0.05). Spleen and lymph node indexes showed an increase in the IMQ group, followed by a slight decrease after aptamer treatment (P > 0.05). Additionally, the mRNA expression levels of Kynu, Defb2, Camp, and Penk genes in the IMQ‐treated region showed a significant 2.70, 4.56, 3.29, and 2.61‐fold increase relative to the Vas mice, respectively (P < 0.05). The aptamer‐treated region exhibited a significant decrease in these gene expression levels (P < 0.05). A positive correlation was found between Kynu, Penk, and Camp expression levels and erythema, as well as Camp expression with PASI, scaling, and thickness (P < 0.05). Conclusion. According to our results, it seems that Kynu, Camp, and Penk can be considered appropriate markers for the evaluation of psoriasis in IMQ‐induced psoriasis. Also, the anti‐IL‐17 aptamer downregulated these important genes in this mouse model. [ABSTRACT FROM AUTHOR]

Background: Abnormal expressions of microRNAs are related to various cancers such as breast cancer for which paclitaxel is widely used as a chemotherapeutic agent. We aimed to investigate the effect of paclitaxel treatment on the expression level of miR-199a-5p and miR-10b, involved in epithelial-mesenchymal transition (EMT) process in breast cancer cell lines. Methods: Human breast cancer cell lines BT-474, SKBR-3, MDA-MB-231, and MCF-7 were cultured and MTT assay was used to determine IC50 of paclitaxel. RNA was extracted, cDNA was synthesized, and the expression level of miRNAs and genes was quantitatively determined using real-time PCR. Results: After treatment with paclitaxel, the expression level of miR-199a-5p significantly decreased in MCF-7 and SKBR-3 cell lines, while it increased in MDAMB-231 and BT-474. The expression level of miR-10b was also significantly reduced in MCF-7, MDA-MB-231, and SKBR-3 and increased in BT-474 cell lines following treatment with paclitaxel. Our results further indicated that paclitaxel reduced the expression level of vimentin and MMP-9 in MDA-MB-231 cell line. Conclusion: Our findings revealed the increased expression of EMT-inhibitor miR-199a-5p and the decreased expression of metastamir miR-10b after treatment of MDA-MB-231 metastatic breast cancer cell line. Reduced expressions of vimentin and MMP-9 were also observed, corroborating the inhibition of metastasis markers in this type of breast cancer. The therapeutic effect of paclitaxel may in part be due to the change in the balance of EMT-promoting and EMT-inhibiting miRNAs. [ABSTRACT FROM AUTHOR]

Introduction: MicroRNAs (miRNAs) are short non-coding single-stranded RNAs. Involving in post-transcriptional gene silencing, miRNAs are thought to play important roles in many cancers such as breast cancer. Paclitaxel is used widely in the treatment of breast cancer. In this study, we investigated the effect of paclitaxel treatment on the expression levels of two oncomirs (oncomiRs), miR-21 and miR-203, in breast cancer cell lines. Materials and methods: MTT assay was performed to determine IC50 of paclitaxel for human breast cancer cell lines including MCF-7, MDA-MB-231, SKBR3 and BT-474. After RNA extraction and cDNA synthesis, the expression levels of miRNAs were then quantitatively evaluated using real-time PCR. Results: Our results showed that after treatment, the expression levels of both miR-21 and miR-203 were significantly increased in HER2-positive cell lines, BT-474 and SKBR3. HER2-negative cell lines, MCF-7 and MDA-MB-231, in contrast had significantly decreased expression of both assessed oncomiRs. Conclusion: Our results showed that the expression levels of oncomiRs were increased in HER-2 positive breast cancer cells and this finding is in line with previous studies. Our findings present a probable mechanism of resistance against paclitaxel chemotherapy in HER2-positive breast cancers. [ABSTRACT FROM AUTHOR]