CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress-responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant -acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144 endothelial microparticles. Furthermore, CD144 microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.
Poly(lactic acid) (PLA) suture can be absorbed by the human body, and so have wide applications in modern surgery operations. The degradation period of PLA suture is expected to meet with the healing time of different types of wounds. In order to control the degradation period of the PLA suture, the carbon nanotubes (CNTs) were composited with PLA suture, and the degradation experiment in vitro was performed on sutures. The structure and properties of sutures during degradation, such as surface morphology, breaking strength, elongation, mass and chemical structure, were tracked and analyzed. The results indicated that the degradation brought about surface defects and resulted in 13.5 weeks for the strength valid time of the original PLA suture. By contrast, the strength valid time of the CNTs/PLA suture was increased to 26.6 weeks. Whilst the toughness of both the pure PLA and CNTs/PLA sutures decreased rapidly and almost disappeared after 3 to 4 weeks of degradation. The mass loss demonstrated that the time required for complete degradation of the two sutures was obviously different, the pure PLA suture 49 weeks, while CNTs/PLA sutures 63 to 73 weeks. The research proved that CNTs delayed PLA degradation and prolonged its strength valid time in degradation.
Polylactic acid (PLA) surgical suture can be absorbed by human body. In order to avoid surgical site infections (SSIs), the drug is usually loaded on the PLA suture, and then the drug can release directly to the wound. Because the different types of wounds heal at different times, it is needed to control the drug release rate of PLA suture to consistent to the wound healing time. Two biopolymers, polyglycolide (PGA) and polycaprolactone (PCL), were selected as the carrier of ciprofloxacin (CPFX) drug, and then the CPFX-PCL/PGA was coated on the PLA suture. The degradation rate of drug-carrier can be controlled by adjusting the proportion of PCL/PGA, which can regulate the rate of CPFX drug release from PLA suture. The results show that the surface of PLA suture, coating with PCL/PGA, was very rough, which led to increased stitching resistance when we were suturing the wound. These materials, such as the PLA suture, the PCL/PGA carriers and the CPFX drug, were just physically mixed rather than chemically reacted, which was very useful for ensuring the original efficacy of CPFX drug. With the increasing of PCL in the carriers, both the breaking strength and elongation of these un-degraded sutures increased. During degradation, the breaking strength of all sutures gradually decreased, and the more PCL in the coating materials, the longer effective strength-time for the suture. With the increasing of PCL in the drug-carrier, the rate of drug releasing became lower. The drug release mechanism of CPFX-PCL/PGA was a synergistic effect of drug diffusion and PCL/PGA carrier dissolution.
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