Gunteradair2304

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. 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. GLPG0187 concentration 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/CD44 axis and circIFI30 could be a novel diagnostic/prognostic marker and therapeutic target for TNBC patients.The etiology of schizophrenia is still unknown, and the MTHFR gene has been shown to be associated with SCZ. Previous studies have shown that patients with schizophrenia exhibit sex differences in symptoms and cognitive function. However, no study has been conducted to investigate the sex difference in the association between C677T polymorphism and symptoms and cognitive impairment in Chinese patients with schizophrenia. The C677T polymorphism was genotyped in 957 patients with schizophrenia and 576 controls. Patients were also rated on the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The results showed that there were significant differences in MTHFR C677T genotype and allele distributions between male patients and male controls (both p0.05). Further analysis showed that there were significant sex differences in the association between C677T genotype and negative symptoms, immediate memory or attention index score in schizophrenia (p less then 0.05). This study suggests that the complex interactive effect between MTHFR C677T polymorphism and sex plays an important role in some clinical characteristics of patients with schizophrenia.Unstructured There has been a growth in the number of web-based trials of web-based interventions, adding to an increasing evidence base for their feasibility and effectiveness. However, there are challenges associated with such trials, which researchers must address. This discussion paper follows the structure of the Down Your Drink trial methodology paper, providing an update from the literature for each key trial parameter (recruitment, registration eligibility checks, consent and participant withdrawal, randomization, engagement with a web-based intervention, retention, data quality and analysis, spamming, cybersquatting, patient and public involvement, and risk management and adverse events), along with our own recommendations based on designing the Relatives Education and Coping Toolkit randomized controlled trial for relatives of people with psychosis or bipolar disorder. The key recommendations outlined here are relevant for future web-based and hybrid trials and studies using iterative development and test models such as the Accelerated Creation-to-Sustainment model, both within general health research and specifically within mental health research for relatives.