Myocardial infarction, among other ischemic heart diseases, is the major cause of mortality and morbidity for patients who have heart diseases. Timely reperfusion of the ischemic myocardium is the most effective way to treat myocardial infarction. However, blood reperfusion to the ischemic tissues leads to an overproduction of toxic reactive oxygen species (ROS), which can further exacerbate myocardial damage on top of ischemic injury. ROS has been used as a diagnostic marker and therapeutic target for ischemia‐reperfusion (I/R) injury and as an environmental stimulus to trigger drug release. In this study, a ROS‐sensitive cross‐linked poly(vinyl alcohol) (PVA) hydrogel is synthesized to deliver basic fibroblast growth factor (bFGF) for myocardial repair. The therapeutic gel is injected into the pericardial cavity. Upon delivery, the hydrogel spread on the surface of the heart and form an epicardiac patch in situ. In a rat model of I/R injury, bFGF released from the gel could penetrate the myocardium. Such intervention protects cardiac function and reduces fibrosis in the post‐I/R heart, with enhanced angiomyogenesis. Furthermore, the safety and feasibility of minimally invasive injection and access into the pericardial cavity in both pigs and human patients are demonstrated.
Background
Metabolic syndrome severity, expressed by the continuous metabolic syndrome risk score (MetS score), has been demonstrated to be able to predict future health conditions. However, little is known about the association between MetS score and renal function.
Methods
A total of 22,719 participants with normal renal function abstracted from the Kailuan Study were followed from 2006 to 2016. The new onset of chronic kidney disease (CKD) was defined as eGFR <60 ml/min per 1.73 m2 and/or proteinuria >300 mg/dl. Progressive decline in renal function was defined as an annual change rate of eGFR below the 10th percentile of the whole population.
Results
In the multivariate‐adjusted model, we found that the risk of progressive decline in renal function increased consistently with the MetS score, with an odds ratio of 1.49 (95% CI, 1.28, 1.73) for those subjects>75th percentile compared with those <25th percentile. Additionally, a high MetS score was found to be associated with an increased risk of CKD, with a hazard ratio of 1.53 (95% CI, 1.33, 1.78) for subjects >75th percentile compared with those <25th percentile.
Conclusions
Our findings suggested that the MetS score was associated with an increased risk of a progressive decline in renal function and was also a strong and independent risk factor for the development of CKD. These findings provide evidence of the potential clinical utility of the MetS score for assessing metabolic syndrome severity to detect the risk of decreased renal function and CKD.
ObjectiveThe present study focused on the development of a poloxamer 407 thermosensitive hydrogel loaded with keratinocyte growth factor-2 (KGF-2) and fibroblast growth factor-21 (FGF-21) as a therapeutic biomaterial in a scald-wound model of type-2 diabetes in Goto-Kakizaki (GK) rats.Research design and methodsIn this study, a poloxamer 407 thermosensitive hydrogel loaded with KGF-2 and/or FGF-21 was prepared and its physical and biological properties were characterized. The repairing effects of this hydrogel were investigated in a scald-wound model of type-2 diabetes in GK rats. The wound healing rate, epithelialization, and formation of granulation tissue were examined, and biomarkers reflecting regulation of proliferation and inflammation were quantified by immunostaining and Western blotting. T tests and analyses of variance were used for statistical analysis via Graphpad Prism V.6.0.ResultsA 17.0% (w/w) poloxamer 407 combined with 1.0% (w/w) glycerol exhibited controlled release characteristics and a three-dimensional structure. A KGF-2/FGF-21 poloxamer hydrogel promoted cellular migration without apoptosis. This KGF-2/FGF-21 poloxamer hydrogel also accelerated wound healing of scalded skin in GK rats better than that of a KGF-2 or FGF-21 hydrogel alone due to accelerated epithelialization, formation of granulation tissue, collagen synthesis, and angiogenesis via inhibition of inflammatory responses and increased expression of alpha-smooth muscle actin (α-SMA), collagen III, pan-keratin, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and CD31.ConclusionsA KGF-2/FGF-21 poloxamer hydrogel accelerated wound healing of scalded skin in GK rats, which was attributed to a synergistic effect of KGF-2-mediated cellular proliferation and FGF-21-mediated inhibition of inflammatory responses. Taken together, our findings provide a novel and potentially important insight into improving wound healing in patients with diabetic ulcers.
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