Phenolic Compounds and Sesquiterpene Lactones Profile in Leaves of Nineteen Artichoke Cultivars.

Leaves of globe artichoke are food industry byproducts gaining interest due to their therapeutic and nutraceutical potential. The total phenolics, flavonoids, and flavonols content as well as radical scavenging capacity and reducing antioxidant power were determined in leaves of 19 artichoke cultivars. An untargeted analysis based on high-resolution mass spectrometry was then carried out to profile phenolic compounds and sesquiterpene lactones (STLs). The phenolic profile of leaf extracts from different cultivars was widely diverse and included flavonoids, hydroxycinnamic acids, tyrosols, and lignans. Grosheimin and its derivative were the most abundant STLs in all artichoke cultivars. Among the examined cultivars, "Campagnano", "Grato 1", and "Violetto di Provenza" were found to be the richest in polyphenols and presented the highest antioxidant activity, whereas "Blanca de Tudela" and "Carderas" were characterized by a high STLs content. Hence, specific artichoke cultivars can be selected as the source of natural antioxidants with a desired profile of nutraceutical compounds like phenolics and STLs.

Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB/p65 co-operative activity and NR4A2 can interact with NF-kappaB/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

Exercise and manual physiotherapy arthritis research trial (EMPART): a multicentre randomised controlled trial.

BACKGROUND: Osteoarthritis (OA) of the hip is a major cause of functional disability and reduced quality of life. Management options aim to reduce pain and improve or maintain physical functioning. Current evidence indicates that therapeutic exercise has a beneficial but short-term effect on pain and disability, with poor long-term benefit. The optimal content, duration and type of exercise are yet to be ascertained. There has been little scientific investigation into the effectiveness of manual therapy in hip OA. Only one randomized controlled trial (RCT) found greater improvements in patient-perceived improvement and physical function with manual therapy, compared to exercise therapy. METHODS AND DESIGN: An assessor-blind multicentre RCT will be undertaken to compare the effect of a combination of manual therapy and exercise therapy, exercise therapy only, and a waiting-list control on physical function in hip OA. One hundred and fifty people with a diagnosis of hip OA will be recruited and randomly allocated to one of 3 groups: exercise therapy, exercise therapy with manual therapy and a waiting-list control. Subjects in the intervention groups will attend physiotherapy for 6-8 sessions over 8 weeks. Those in the control group will remain on the waiting list until after this time and will then be re-randomised to one of the two intervention groups. Outcome measures will include physical function (WOMAC), pain severity (numerical rating scale), patient perceived change (7-point Likert scale), quality of life (SF-36), mood (hospital anxiety and depression scale), patient satisfaction, physical activity (IPAQ) and physical measures of range of motion, 50-foot walk and repeated sit-to stand tests. DISCUSSION: This RCT will compare the effectiveness of the addition of manual therapy to exercise therapy to exercise therapy only and a waiting-list control in hip OA. A high quality methodology will be used in keeping with CONSORT guidelines. The results will contribute to the evidence base regarding the clinical efficacy for physiotherapy interventions in hip OA.