Bondesenwatson1979

Astragaloside III (AS-III) is a triterpenoid saponin contained in Astragali Radix and has potent anti-inflammatory effects on vascular endothelial cells; however, underlying mechanisms are unclear. In this study, we provided the first piece of evidence that AS-III induced phosphorylation of TNF-α converting enzyme (TACE) at Thr735 and enhanced its sheddase activity. As a result, AS-III reduced surface TNFR1 level and increased content of sTNFR1 in the culture media, leading to the inhibition of NF-κB signaling pathway and attenuation of downstream cytokine gene expression. Furthermore, AS-III induced TACE-dependent epidermal growth factor receptor (EGFR) transactivation and activation of downstream ERK1/2 and AKT pathways. Finally, AS-III induced activation of p38. Both TACE activation and EGFR transactivation induced by AS-III were significantly inhibited by p38 inhibitor SB203580. Taken together, we concluded that AS-III activates TACE-dependent anti-inflammatory and growth factor signaling in vascular endothelial cells in a p38-dependent fashion, which may contribute to its cardiovascular protective effect. © 2020 John Wiley & Sons, Ltd.INTRODUCTION People with haemophilic arthropathy (PWHA) have impairments in postural control. However, little is known about the effects of demanding conditions, including the unipedal stance and dual tasks, on postural control in PWHA. AIM Determine the effects of performing dual tasks while in the one-leg stance on postural sway and postural control complexity in PWHA vs. healthy active (HAG) and non-active (HNAG) groups of individuals. METHODS Fifteen PWHA and 34 healthy subjects (18 active and 16 non-active) were recruited. Vertical (V), mediolateral (ML) and anteroposterior (AP) centre of mass signals were acquired using a 3-axis accelerometer placed at the L3/L4 vertebrae of subjects as they performed the one-leg stance under single and dual-task conditions. Sway balance and the complexity of postural control were studied via root mean square (RMS) acceleration and sample entropy, respectively. Increased complexity of postural sway was attributed to increased automatism of postural control. RESULTS RMS values for PWHA were higher than HAG under both conditions for the V and ML axes, and higher than HNAG under the dual-task condition for the ML axis. Sample entropy was lower in PWHA than healthy individuals under the dual-task condition for V and ML axes, and the single-task condition for the ML axis (P  less then  .05). CONCLUSION PWHA had poorer postural sway and decreased postural control complexity when performing a one-leg stance than healthy people, especially when the dual-task condition was applied. These results may help to design new approaches to assess and improve postural control in PWHA. © 2020 John Wiley & Sons Ltd.The force response of cardiac muscle undergoing a quick stretch is conventionally interpreted to represent stretching of attached myosin crossbridges (phase 1) and detachment of these stretched crossbridges at an exponential rate (phase 2), followed by crossbridges reattaching in increased numbers due to an enhanced activation of the thin filament (phases 3 and 4). We propose that, at least in mammalian cardiac muscle, phase 2 instead represents an enhanced detachment rate of myosin crossbridges due to stretch, phase 3 represents the reattachment of those same crossbridges, and phase 4 is a passive-like viscoelastic response with power-law relaxation. To test this idea, we developed a two-state model of crossbridge attachment and detachment. Unitary force was assigned when a crossbridge was attached, and an elastic force was generated when an attached crossbridge was displaced. IDE397 Attachment rate, f(x), was spatially distributed with a total magnitude f0. Detachment rate was modeled as g(x) = g0+ g1x, where g0 is a constant and g1 indicates sensitivity to displacement. The analytical solution suggested that the exponential decay rate of phase 2 represents (f0 + g0) and the exponential rise rate of phase 3 represents g0. The depth of the nadir between phases 2 and 3 is proportional to g1. We prepared skinned mouse myocardium and applied a 1% stretch under varying concentrations of inorganic phosphate (Pi). The resulting force responses fitted the analytical solution well. The interpretations of phases 2 and 3 were consistent with lower f0 and higher g0 with increasing Pi. This novel scheme of interpreting the force response to a quick stretch does not require enhanced thin-filament activation and suggests that the myosin detachment rate is sensitive to stretch. Furthermore, the enhanced detachment rate is likely not due to the typical detachment mechanism following MgATP binding, but rather before MgADP release, and may involve reversal of the myosin power stroke. © 2020 Palmer et al.The prevalence of symptomatic insomnia and the prevalence of restless legs syndrome (RLS) are known to be higher among patients with rheumatic diseases compared to the general population. The prevalences of insomnia and RLS reported in a questionnaire by Japanese patients with rheumatic diseases at an outpatient clinic were analyzed herein. The association between the patients' disease activity and their sleep quality was analyzed. Of 121 rheumatic disease patients, 70 were enrolled. The median (interquartile range) age at enrollment was 62.0 (47.8-68.0) years. There were 58 women (82.9%) and 12 men (17.1%), and 43 patients (61.4%) with rheumatoid arthritis (RA), nine (12.9%) with systemic lupus erythematosus (SLE), and 18 (25.7%) with other rheumatic diseases. Twenty patients (28.6%) had one or more moderate-to-severe insomnia symptoms, and 10 (14.3%) were diagnosed with RLS. Among the patients with RA, the swollen joint count based on a 28-joint assessment (SJC28) was significantly higher in the insomnia group (n = 13) compared to the non-insomnia group (n = 30) (p = 0.006). A classification and regression tree (CART) analysis showed that the cut-off points of ≥3 mg/day prednisolone (PSL) treatment and less then 16.54% as the transferrin saturation (TSAT) value would best predict RLS in rheumatic disease. Patients with rheumatic disease had a high prevalence of symptomatic insomnia and RLS. A higher dose of PSL and lower TSAT were associated with the occurrence of RLS.