ABSTRACT
Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
ABSTRACT
Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors and . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
ABSTRACT
Objective To investigate the linear relationship and standard curve equation between acidic concentrated solution added KCl and the changes of K+ concentration in dialysate,and to apply it in personalized dialysis.Methods The speed of concentrated liquid pump of Fresenius 4008S hemodialysis machine was calibrated,the ratio of the concentration solution to the reverse osmosis water was determined,KCl was added to the concentrated A solution by an equal increment method to detect K+ concentration in the corresponding dialysate,and the K+ concentration standard curve of dialysate was mapped.This study is based on blood K+ concentration of adams-stokes syndrome patients before dialysis,referring to the standard curve,the most suitable dialysate K+ concentration was selected to personalized dialysis,the blood K+ concentration of the patients was measured after dialysis,and ECG monitoring and clinical symptoms observation were carried out.Results There was a linear relationship between acidic concentrated solution added KCl and the changes of K+ concentration in dialysate,the curve equation was y =0.384 lx + 0.002 3,R2 =0.999 4.There was no obvious change in the concentration of other electrolyte ions in the dialysate.Referring to the standard curve,the concentration of dialysate K+ could be adjusted accurately.The blood K+ concentration of adams-stokes syndrome patients could be corrected in time after several times of K+ concentration of personalized dialysis,and ECG recovered eventually,and arrhythmia,syncope,chest tightness and other symptoms disappeared.Conclusion There is a linear relationship between the concentration of dialysate K + and the concentration of KCl added in acidic concentrated solution in the Fresenius 4008S hemodialysis machine.Personalized dialysis is performed by the standard curve with obvious clinical application value,and references are provided for precise regulation of dialysate ion concentration.
ABSTRACT
Objective To investigate the linear relationship and standard curve equation between acidic concentrated solution added KCl and the changes of K+ concentration in dialysate,and to apply it in personalized dialysis.Methods The speed of concentrated liquid pump of Fresenius 4008S hemodialysis machine was calibrated,the ratio of the concentration solution to the reverse osmosis water was determined,KCl was added to the concentrated A solution by an equal increment method to detect K+ concentration in the corresponding dialysate,and the K+ concentration standard curve of dialysate was mapped.This study is based on blood K+ concentration of adams-stokes syndrome patients before dialysis,referring to the standard curve,the most suitable dialysate K+ concentration was selected to personalized dialysis,the blood K+ concentration of the patients was measured after dialysis,and ECG monitoring and clinical symptoms observation were carried out.Results There was a linear relationship between acidic concentrated solution added KCl and the changes of K+ concentration in dialysate,the curve equation was y =0.384 lx + 0.002 3,R2 =0.999 4.There was no obvious change in the concentration of other electrolyte ions in the dialysate.Referring to the standard curve,the concentration of dialysate K+ could be adjusted accurately.The blood K+ concentration of adams-stokes syndrome patients could be corrected in time after several times of K+ concentration of personalized dialysis,and ECG recovered eventually,and arrhythmia,syncope,chest tightness and other symptoms disappeared.Conclusion There is a linear relationship between the concentration of dialysate K + and the concentration of KCl added in acidic concentrated solution in the Fresenius 4008S hemodialysis machine.Personalized dialysis is performed by the standard curve with obvious clinical application value,and references are provided for precise regulation of dialysate ion concentration.
ABSTRACT
<p><b>OBJECTIVE</b>To study correlation of brain hypoxia of different degrees with brain function and damage.</p><p><b>METHODS</b>The brain regional oxygen saturation (rSO2) was determined by using a non-invasive near infrared spectroscopy (NIRS) technique in 15 piglets; the piglets were subjected to inhale 3% - 11% oxygen-nitrogen mixed gas through mechanical ventilation for 30 min. The piglets were divided into groups according to the level of brain rSO2 (i.e. < 30%, 30% - 35%, 35% - 40%, and 40% - 50%), and the data were compared with those of the control group (rSO2 > 60%). Changes of brain function were detected through amplitude and frequency of EEG waves and signal complexity. The piglets were sacrificed via decapitation 72 h after brain damage, and then histopathological and ultrastructural examinations were performed on cerebral cortex and hippocampal CA1 area.</p><p><b>RESULTS</b>In the group with rSO2 > 40%, the mean arterial pressure (MAP) after hypoxia was (56 +/- 0.00) mm Hg (1 mm Hg = 0.133 kPa), the blood lactic acid (LA) was (2.3 +/- 1.2) mmol/L, the EEG findings were within normal range, and there was no change in brain tissue ultrastructure. In the group with brain rSO2 = 30% approximately 40%, the MAP was (73 +/- 8) mm Hg, the LA was (8.2 +/- 3.9) mmol/L, the EEG waves showed decreased amplitude, frequency and complexity, but restored to some extent after hypoxia. The brain tissue ultrastructure showed damages to the cerebral cortex and neuron mitochondria at hippocampal CA1 area. In the group with brain rSO2 < 30%, the MAP was (35 +/- 0) mm Hg, the LA was (12 +/- 2) mmol/L, the EEG showed decreased amplitude, frequency, and complexity of signals compared with those of the normal control group, and was difficult to restore after hypoxia in some of the piglets; the brain tissue ultrastructure appeared to be similar to the changes seen with high-degree swollen cerebral cortex and neuron mitochondria at hippocampal CA1 area.</p><p><b>CONCLUSION</b>Different degrees of hypoxia had different influence on brain function and brain damage. The lower the brain rSO2, the more severe the damages to the brain and its function. The rSO2 of brain tissues detected with noninvasive NIRS can reflect brain injury and its severity during cerebral anoxia.</p>