Mounting evidence has implicated inflammation in ischemia-reperfusion injury following acute ischemic stroke (AIS). Microglia remain the primary initiator and participant of brain inflammation. this website Emerging evidence has indicated that uric acid has promise for the treatment of AIS, but its explicit mechanisms remain elusive. Here, we observed that uric acid reduced the severity of cerebral infarction and attenuated the activation of microglia in the cerebral cortex in a mouse middle cerebral-artery occlusion/reperfusion model. Thus, we speculated that uric acid may play a role by directly interfering with the inflammatory response of microglia. First, we investigated whether the HMGB1-TLR4-NF-κB signaling plays a role in oxygen glucose deprivation and reperfusion (OGD/R) injury of BV2 cells. Inhibition of the signaling significantly reduced the release of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL1β), and IL6 caused by OGD/R in BV2 cells. Second, uric acid weakened the decreased cell viability and lactate dehydrogenase release induced by OGD/R in BV2 cells. Finally, uric acid reduced the release of the proinflammatory cytokines TNF-α, IL1β, and IL6 caused by OGD/R in BV2 cells by dampening HMGB1-TLR4-NF-κB signaling, which was reversed by probenecid treatment, an inhibitor of the uric acid channel. Hence, uric acid halted the release of inflammatory factors and the decreased cell viability induced by ODG/R via inhibiting the microglia HMGB1-TLR4-NF-κB signaling, thereby alleviating the damage to microglia. This may be part of the molecular mechanisms by which uric acid protects mice against the brain damage of middle cerebral-artery occlusion/reperfusion.Polyphosphate, which is ubiquitous in cells in nature, is involved in a myriad of cellular functions, and has been recently focused on its metabolism related with microbial acclimation to phosphorus-source fluctuation. In view of the ecological importance of cyanobacteria as the primary producers, this study investigated the responsibility of polyphosphate metabolism for cellular acclimation to phosphorus starvation in a cyanobacterium, Synechocystis sp. PCC 6803, with the use of a disruptant (Δppx) as to the gene of exopolyphosphatase that is responsible for polyphosphate degradation. Δppx was similar to the wild type in the cellular content of polyphosphate to show no defect in cell growth under phosphorus-replete conditions. However, under phosphorus-starved conditions, Δppx cells were defective in a phosphorus-starvation dependent decrease of polyphosphate to show deleterious phenotypes as to their survival and the stabilization of the photosystem complexes. These results demonstrated some crucial role of exopolyphosphatase to degrade polyP in the acclimation of cyanobacterial cells to phosphorus-starved conditions. Besides, it was found that ppx expression is induced in Synechocystis cells in response to phosphorus starvation through the action of the two-component system, SphS and SphR, in the phosphate regulon. The information will be a foundation for a fuller understanding of the process of cyanobacterial acclimation to phosphorus fluctuation.Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro. Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress, which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21-5p (miR-21-5p). The expression of miR-21-5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21-5p overexpression reversed the effects on cell viability, inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21-5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.
Kinematic and kinetic foot models showed that computing ankle joint angles, moments and power with a one-segment foot modeling approach alters kinematics and tends to overestimate ankle joint power. Nevertheless, gait studies continue to implement one-segment foot models to assess the effect of total ankle replacement.
The objective of this pilot study was to investigate the effect of the foot modeling approach (one-segment versus multi-segment) on how total ankle replacement is estimated to benefit or degrade the patient's biomechanical performance.
Ten subjects with post-traumatic ankle osteoarthritis scheduled for total ankle replacement and 10 asymptomatic subjects were recruited. A one-segment and a multi-segment foot model were used to calculate intrinsic foot joints kinematics and kinetics during gait. A linear mixed model was used to investigate the effect of the foot model on ankle joint kinematic and kinetic analysis and the effect of total ankle replacement.
Differences in range of motion dize the clinical interest of multi-segment foot modeling when assessing the outcome of a therapeutic intervention.
Heeled footwear benefits people with movement disorder in the form of shoe lifts, wedges and inserts while its prolonged use causes foot injury in healthy people. There lies a need to detect parameters that affect COP progression of the foot and gait stability due to footwear.
Do we have bipedal models that can estimate gait parameters corresponding to different center of pressure (COP) trajectories?
In this study, we propose a COP translation model that can account for non heeled to heeled footwear. We describe the COP progression as a function of the center of mass (COM) state. This model is used to generate stable steady state walking solutions for different COP profiles. We compare these model solutions with experimental data on non-heeled and heeled-gait.
The bipedal model shows stability across different COP profiles. The model estimates GRF profile (R
=0.83 for 1.3m/s ) for non heeled normal walking qualitatively and on the temporal scale. It estimates GRF due to heeled gait (R
=0.83 for 1.08 m/s) but is limited in estimation of heeled gait parameters.this website
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