The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis. However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33 and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of EGFR and ERK which were required for induction of IL-25, IL-33, and TSLP expression. In two atopic dermatitis models, Itln knockdown suppressed expression of Il-33, Tslp and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of atopic dermatitis. We conclude that intelectin contributes to allergen-induced Il-25, Il-33 and Tslp expression in asthma and atopic dermatitis.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use

Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. According to recent studies, circRNAs are involved in the pathogenesis of cancer, but the roles of circRNAs in lung adenocarcinoma are largely unknown. Methods: In this study, we identified a novel upregulated circRNA, hsa_circ_0000326, in human lung adenocarcinoma tissues using microarray analysis and qRT-PCR. We then explored the biological role of hsa_circ_0000326 using gainand loss-of-function assays in adenocarcinoma cells. Bioinformatics databases were used to screen for potential target miRNAs and the luciferase reporter assays and RNA-FISH further validated the interaction. Downstream protein was detected by western blot. Finally, we established xenografts in nude mice to assess the function of hsa_circ_0000326 in vivo. Results: We found that high expression of hsa_circ_0000326 was correlated with tumor size, regional lymph node status and differentiation in human lung adenocarcinoma. Additionally, we conducted gain-and loss-of-function assays and found that hsa_circ_0000326 acted as a positive regulator of cell proliferation and migration and a negative regulator of apoptosis. Mechanistic studies showed that hsa_circ_0000326 acted as a miR-338-3p sponge and altered the function of miR-338-3p, which in turn upregulated the expression of the downstream target RAB14 and affected the proliferation, migration and apoptosis of lung adenocarcinoma cells. Conclusions: Collectively, our study results reveal crucial roles for hsa_circ_0000326 in the proliferation, migration and apoptosis of lung adenocarcinoma cells and suggest that hsa_circ_0000326 may represent a potential therapeutic target in patients with lung adenocarcinoma.

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HMGA1 is an important susceptibility locus that confers a high cross-race risk of the development of type 2 diabetes.

Antimicrobial peptides (AMPs) are regarded as promising alternatives for antibiotics due to their inherent capacity to prevent microbial drug resistance. Amphibians are rich source of bioactive molecules, which provide numerous AMPs with various structures as drug candidates. Here, we isolated and identified a novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog, Pelophylax kl. esculentus. In vitro studies revealed that it showed broad antimicrobial activities against S. aureus, E. coli and C. albicans with low cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats. The wound closure outcomes revealed that B-2Ta effectively restrained the bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC) during the 14 days of the wound healing process. Ultra-structure analyses showed that B-2Ta caused structural damage to the microorganism, and bacterial culture found that the number of microbes was significantly reduced by the end of treatment. Immunohistochemistry for the inflammatory marker IL-10 and the endothelial cell marker CD31 suggested positive effects on inflammatory status and epithelial migration and angiogenesis following treatment of the infected granulation tissues with B-2Ta. These results exhibited the continuous phase of inflammation reduction and wound healing acceleration in the B-2Ta-modulated re-epithelialisation of K. pneumoniae infected rats. Taken together, these data demonstrated that B-2Ta has great potential to be developed as antibacterial agents in clinic.

No abstract

The emergence of multi-drug resistant Pseudomonas aeruginosa necessitates the search for treatment options other than antibiotic use. The use of bacteriophages is currently being considered as an alternative to antibiotics for the treatment of bacterial infections. A number of bacteriophages were introduced to treat pneumonia in past reports. However, there are still lack of knowledge regarding the dosages, application time, mechanism and safety of phage therapy against P. aeruginosa pneumonia. We used the bacteriophage KPP10 against P. aeruginosa strain D4-induced pneumonia mouse models and observed their outcomes in comparison to control models. We found that the nasal inhalation of highly concentrated KPP10 (MOI = 80) significantly improved survival rate in pneumonia models (P < 0.01). The number of viable bacteria in both lungs and in serum were significantly decreased (P < 0.01) in phage-treated mice in comparison to the control mice. Pathological examination showed that phage-treated group had significantly reduced bleeding, inflammatory cell infiltration, and mucus secretion in lung interstitium. We also measured inflammatory cytokine levels in the serum and lung homogenates of mice. In phage-treated models, serum TNFα, IL-1β, and IFN-γ levels were significantly lower (P < 0.05, P < 0.01, and P < 0.05, respectively) than those in the control models. In the lung homogenate, the mean IL-1β level in phage-treated models was significantly lower (P < 0.05) than that of the control group. We confirmed the presence of phage in blood and lungs, and evaluated the safety of bacteriophage use in living models since bacteriophage mediated bacterial lysis arise concern of endotoxic shock. The study results suggest that phage therapy can potentially be used in treating lung infections caused by Pseudomonas aeruginosa.

Abstract. Asthma is a chronic T helper type 2 (Th2) cell-mediated inflammatory disease characterized by airway hyperresponsiveness (AHR) and airway inflammation. Although the majority of patients with asthma can achieve a good level of control with existing treatments, asthma runs a chronic course and the effectiveness of current treatment is not satisfactory for certain patients. MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the post-transcriptional level; their role in regulating allergic inflammation remains largely unknown. The present study aimed to explore the role of miRNA-155 in the pathogenesis of asthma and its potential as a target for treatment. The expression of miRNA-155 increased in ovalbumin-sensitized and challenged mice compared with control mice, and lentiviral vector-delivered small interfering (si)RNA targeting miRNA-155 resulted in reduced AHR, airway inflammation and Th2 cytokine production. The data from the present study indicate that miRNA-155 serves an important role in the pathogenesis of asthma, and that lentiviral vector-delivered siRNA targeting miRNA-155 may serve as a novel approach for the treatment of allergic asthma.