Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology. LncRNA H19 has been recently shown to be upregulated and play important roles in several cancers such as breast cancer, bladder cancer, and gastric cancer. However, the role of H19 in clear cell renal carcinoma (ccRCC) remains largely unknown.The expression levels of lncRNA H19 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress H19 expression in renal cancer cell lines. In vitro assays were performed to further explore its role in tumor progression.The relative level of H19 was significantly higher in ccRCC compared to the adjacent normal renal tissues. And higher expression of H19 was found in renal cancer cells compared to the nonmalignant renal cells HK-2. Furthermore, The ccRCC patients with higher H19 expression had more advanced clinical stage and poorer prognosis than those with lower expression, Kaplan-Meier analysis revealed that patients with higher H19 expression had a poorer overall survival and H19 expression could be an independent prognostic marker for ccRCC patient. The results of in vitro assays indicated that knockdown of H19 reduced cell proliferation, invasion, and migration. Our data suggested that lncRNA H19 might be considered as a potential prognostic indicator and a target for gene therapy of ccRCC.

The first two authors contributed equally to this work Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) ofAR were evaluated to determine the severity ofAR. Cytokines in the nasal lavage fluid (NALF), including interferon-y (IFN-y), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (T reg ) and T helper cells 17 (Thl7) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-y level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+T reg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+T h17 cells, which were significantly increased inAR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between T reg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.

BackgroundClara cell 10-kDa protein (CC10) is a multifunctional protein with anti-inflammatory and immunomodulatory effects. Induction of CC10 expression by gene transfection may possess potential therapeutic effect. Nuclear factor κB (NF-κB) plays a key role in the inflammatory processes of airway diseases.Method/ResultsTo investigate potential therapeutic effect of CC10 gene transfection in controlling airway inflammation and the underlying intracellular mechanisms, in this study, we constructed CC10 plasmid and transfected it into bronchial epithelial cell line BEAS-2B cells and CC10 knockout mice. In BEAS-2B cells, CC10's effect on interleukin (IL)-1β induced IL-8 expression was explored by means of RT-PCR and ELISA and its effect on NF-κB classical signaling pathway was studied by luciferase reporter, western blot, and immunoprecipitation assay. The effect of endogenous CC10 on IL-1β evoked IL-8 expression was studied by means of nasal explant culture. In mice, CC10's effect on IL-1β induced IL-8 and nuclear p65 expression was examined by immunohistochemistry. First, we found that the CC10 gene transfer could inhibit IL-1β induced IL-8 expression in BEAS-2B cells. Furthermore, we found that CC10 repressed IL-1β induced NF-κB activation by inhibiting the phosphorylation of IκB-α but not IκB kinase-α/β in BEAS-2B cells. Nevertheless, we did not observe a direct interaction between CC10 and p65 subunit in BEAS-2B cells. In nasal explant culture, we found that IL-1β induced IL-8 expression was inversely correlated with CC10 levels in human sinonasal mucosa. In vivo study revealed that CC10 gene transfer could attenuate the increase of IL-8 and nuclear p65 staining in nasal epithelial cells in CC10 knockout mice evoked by IL-1β administration.ConclusionThese results indicate that CC10 gene transfer may inhibit airway inflammation through suppressing the activation of NF-κB, which may provide us a new consideration in the therapy of airway inflammation.