Agger Ramos (tramppants67)

Background Dysregulation of L-arginine metabolism has been proposed to occur in severe asthma patients. The effects of L-arginine supplementation on L-arginine metabolite profiles in these patients is unknown. We hypothesized that severe asthmatics with low fractional exhaled nitric oxide (FeNO) would have fewer asthma exacerbations with the addition of L-arginine to their standard asthma medications compared to placebo and would demonstrate the greatest changes in metabolite profiles. Methods Participants were enrolled in a single-center, cross-over, double-blinded, L-arginine intervention trial at the University of California-Davis (NCT01841281). Subjects received placebo or L-arginine, dosed orally at 0.05mg/kg (ideal body weight) twice daily. The primary endpoint was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects. Results A cohort of 50 subjects was included in the final analysis. L-arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P-value = 0.005 and 2.51 x 10-9 respectively). Higher AAI was associated with lower exacerbation events. selleck chemicals The eicosanoid prostaglandin H2 (PGH2) and Nα-Acetyl-L-arginine were found to be good predictors for differentiating clinical responders and non-responders. Conclusions There was no statistically significant decrease in asthma exacerbations in the overall cohort with L-arginine intervention. PGH2, Nα-Acetyl-L-arginine and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.Breast cancer is the leading cause of cancer death in women worldwide. Long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) has been reported to be involved in human diseases, including cancer. Here, we found that SNHG1 expression was significantly upregulated in human breast cancer tissues and cell lines. We explored the function of SNHG1 in breast cancer cells using in vitro and in vivo experiments and found that SNHG1 promotes breast cancer metastasis and proliferation. The potential molecular mechanism of SNHG1 in breast cancer cells may involve SNHG1 acting as a sponge of miR-193a-5p to activate the expression of the oncogene HOXA1. In summary, our study reveals a novel SNHG1/miR-193a-5p/HOXA1 competing endogenous RNA regulatory pathway in breast cancer progression and may provide new strategies for breast cancer therapy.Growing evidence suggests that circRNAs exert a critical role in tumorigenesis and cancer progression. To date, the molecular mechanisms underlying circRNAs in triple-negative breast cancer (TNBC) are still poorly known. Here, circRNA expression profile was investigated by RNA sequencing in TNBC tissues and matched para-carcinoma tissues. We found that circIFI30 was significantly up-regulated in TNBC tissues and cells using quantitative real-time PCR and in situ hybridization. High circIFI30 expression was positively correlated with clinical TNM stage, pathological grade and poor prognosis of TNBC patients. Functionally, a series of in vivo and in vitro experiments showed that knockdown of circIFI30 could markedly inhibit TNBC cell proliferation, migration, invasion and cell cycle progression, induce apoptosis as well as suppress tumorigenesis and metastasis. Up-regulation of circIFI30 exerted an opposite effect. Mechanistically, we demonstrated that circIFI30 might act as a competing endogenous RNA (ceRNA) of miR-520b-3p to abolish the suppressive effect on target gene CD44 by fluorescent in situ hybridization (FISH), dual luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assays. Therefore, our work uncovers the mechanism by which circIFI30 could promote TNBC progression through circIFI30/miR-520b-3p