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The poor reversibility of the zinc (Zn) anodes and the irreversible deposition/dissolution of Mn2+/MnO2 significantly impede the commercialization of Zn-Mn aqueous batteries (ZMABs). In reducing the difference between the desired interfacial reaction environments of the cathode and anode, we found that they face the same problem of interference-the generation of irreversible corrosion products. Herein, we have introduced a novel self-regulatory mechanism. This mechanism involves the addition of sodium dihydrogen phosphate, which shifts from passive protection to active regulation. It effectively captures OH- ions, prevents corrosion product formation, and facilitates the in situ generation of a solid electrolyte interface (SEI) film. This modification also homogenizes Zn ion flow and improves the reversibility of Zn plating and stripping. Furthermore, a stable and slightly acidic environment has been established to stabilize the pH at the cathodic interface, mitigate corrosion product formation, and enhance the reversible deposition and dissolution of Mn2+/MnO2. With the optimal electrolyte, ZnâZn symmetric cells demonstrate stable operation for over 3000 hours at 1 mA cm-2, 1 mA h cm-2. Additionally, the ZnâCu cells maintain high reversibility after 1000 cycles, achieving an average coulombic efficiency (CE) of 99.76%. The assembled ZnâMnO2 full cells exhibit exceptional cycling stability and rate performance. This work adopts the approach of seeking common ground and emphasizing the balance of cathode and anode interfacial requirements, which represents a new and significant insight for design of ZMABs with high reversibility and high cyclability.
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Arsenate [As(V)] reduction is a major cause of arsenic (As) release from soils, which threatens more than 200 million people worldwide. While heterotrophic As(V) reduction has been investigated extensively, the mechanism of chemolithotrophic As(V) reduction is less studied. Since As is frequently found as a sulfidic mineral in the environment, microbial mediated sulfur oxidation coupled to As(V) reduction (SOAsR), a chemolithotrophic process, may be more favorable in sites impacted by oligotrophic mining (e.g. As-contaminated mine tailings). While SOAsR is thermodynamically favorable, knowledge regarding this biogeochemical process is still limited. The current study suggested that SOAsR was a more prevalent process than heterotrophic As(V) reduction in oligotrophic sites, such as mine tailings. The water-soluble reduced sulfur concentration was predicted to be one of the major geochemical parameters that had a substantial impact on SOAsR potentials. A combination of DNA stable isotope probing and metagenome binning revealed members of the genera Sulfuricella, Ramlibacter, and Sulfuritalea as sulfur oxidizing As(V)-reducing bacteria (SOAsRB) in mine tailings. Genome mining further expanded the list of potential SOAsRB to diverse phylogenetic lineages such as members associated with Burkholderiaceae and Rhodocyclaceae. Metagenome analysis using multiple tailing samples across southern China confirmed that the putative SOAsRB were the dominant As(V) reducers in these sites. Together, the current findings expand our knowledge regarding the chemolithotrophic As(V) reduction process, which may be harnessed to facilitate future remediation practices in mine tailings.
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Arseniatos , Minería , Oxidación-Reducción , Filogenia , Microbiología del Suelo , Azufre , Arseniatos/metabolismo , Azufre/metabolismo , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Ecosistema , Metagenoma , ARN Ribosómico 16S/genética , Contaminantes del Suelo/metabolismoRESUMEN
The high efficiency electrocatalytic degradation of late landfill leachate is still not an easy task due to the complexity and variability of organic pollutants. A chemical coating strategy for assembling a boron-doped diamond anode (BDD) towards electrocatalytic degradation of late landfill leachate was adopted and studied. The results shows the high removal rates of organic carbon (TOC) and ammonia nitrogen (NH3-N) after electrochemical oxidation for 5 h can reach 99% and 100%. Further, the organic migration and transformation depends on current density, A/V value, initial pH, electrochemical degradation time, and composition of the stock solution. Specifically, alkaline conditions can increase both TOC and NH3-N removal rates, which is reflected in the NH3-N removal rate of 100% when the pH is 8.5 after only 5 h. The types of organic matter decreased from 63 species to 24 species in 5 h, in which the removal of fulvic acids is superior to that of soluble biometabolites. Amides/olefins and phenolic alcohols are all degraded and converted into other substances or decomposed into CO2 and H2O by BDD, accompanied by the continuous decomposition of alcohol-phenols into alkanes. In all, this study provides a core reference on electrocatalytic degradation of late landfill leachate.
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Background: Cholesterol crystals (CCs) in lesions are the hallmark of advanced atherosclerotic plaque. Previous studies have demonstrated that CCs could activate NLRP3 inflammasome, which played an important role in atherosclerotic lesion progression. However, the relationship between CCs, NLRP3 inflammasome pathway, and plaque vulnerability in patients with ACS is still not elucidated. Methods: Two hundred sixty-nine consecutive acute coronary syndrome (ACS) patients with 269 culprit lesions were included in this study. CCs and other plaque characteristics within the culprit lesion segment were evaluated by optical coherence tomography (OCT) before percutaneous coronary intervention (PCI). The NLRP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and the serum levels of interleukin (IL)-1ß, IL-18, and other biological indices were measured. Results: Cholesterol crystals were observed in 105 (39%) patients with 105 culprit lesions. There were no significant differences in baseline clinical characteristics between the patients with CCs (CCs group, n = 105) and the patients without CCs (non-CCs group, n = 164) within the culprit lesion segment except for lipoprotein(a) [Lp(a)]. The CCs group had a higher level of NLRP3 mRNA expression in PBMCs and higher levels of serum cytokine IL-1ß and IL-18. OCT showed that the CCs group had longer lesion length, more severe diameter stenosis, and less minimum luminal area (MLA) than the non-CCs group (all p < 0.05). The frequency of thin-cap fibroatheroma (TCFA), thrombus, accumulation of macrophages, plaque rupture, micro-channel, calcification, spotty calcification, and layered plaque was higher in the CCs group than in the non-CCs groups (all p < 0.05). Multivariate logistic analysis revealed that the level of NLRP3 expression (OR = 10.204), IL-1ß levels (OR = 3.523), IL-18 levels (OR = 1.006), TCFA (OR = 3.593), layered plaque (OR = 5.287), MLA (OR = 1.475), macrophage accumulation (OR = 2.881), and micro-channel (OR = 3.185) were independently associated with CCs. Conclusion: Acute coronary syndrome patients with CCs in culprit lesions had a higher expression of NLRP3, IL-1ß, and IL-18, and had more vulnerable plaque characteristics than patients without CCs. CCs might have interacted with NLRP3 inflammasome activation in patients with ACS, which could contribute to plaque vulnerability in culprit lesions.
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Ce modified MnO x /SAPO-34 was prepared and investigated for low-temperature selective catalytic reduction of NO x with ammonia (NH3-SCR). The 0.3Ce-Mn/SAPO-34 catalyst had nearly 95% NO conversion at 200-350 °C at a space velocity of 10 000 h-1. Microporous SAPO-34 as the support provided the catalyst with increased hydrothermal stability. XPS and H2-TPR results proved that the Mn4+ and Oα content increased after incorporation of Ce, this promoted the conversion of NO at low temperature via a 'fast SCR' route. NH3-TPD measurements combined oxidation experiments of NO, NH3 indicated the reduction of both the surface acidity and the amount of acid sites, which effectively decreased the NH3 oxditaion to NO or N2O at elevated temperature and promoted the catalytic selectivity for nitrogen. A redox cycle between manganese oxide and Ce was assumed for the active oxygen transfer and facilitated the catalyst durability.
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Previous studies have established that proteinaseâactivated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferasemediated dUTP nick endlabeling staining. Annexin V/propidium iodide staining, and expression of Bcl2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injurysimulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RIassociated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI.
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Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos/patología , Receptor PAR-2/genética , Animales , Apoptosis , Hipoxia de la Célula , Línea Celular , Modelos Animales de Enfermedad , Eliminación de Gen , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Daño por Reperfusión Miocárdica/epidemiología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Factores Protectores , Interferencia de ARN , RatasRESUMEN
BACKGROUND: Myocardial strain is increasingly recognized as an important assessment for myocardial function. In addition, it also improves outcome prediction. However, there is lack of standardization in strain evaluation by cardiovascular magnetic resonance (CMR). In this study we compared strain values using multiple techniques and multiple vendor products. METHODS: Prospectively recruited patients with cardiomyopathy of diverse etiology (N = 77) and healthy controls (N = 10) underwent CMR on a 1.5 T scanner. Tagging, displacement encoding with stimulated echoes (DENSE) and balanced stead state free precession cine imaging were acquired on all subjects. A single matched mid left ventricular (LV) short axis plane was used for the comparisons of peak circumferential (Ecc) and radial strain (Err) and a 4-chamber view for longitudinal strain (Ell). Tagging images were analyzed using harmonic phase (HARP) and displacement encoding with stimulated echoes (DENSE) images using a proprietary program. Feature tracking (FT) was evaluated using 3 commercially available software from Tomtec Imaging Systems, Cardiac Image Modeller (CIM), and Circle Cardiovascular Imaging. Tagging data were used as reference. Statistic analyses were performed using paired t-test, intraclass correlation coefficient (ICC), Bland Altman limits of agreement and coefficient of variations. RESULTS: Average LV ejection fraction was 50% (range 32 to 62%). Regional LV wall motion abnormalities were present in 48% of the analyzed planes. The average Ecc was - 13 ± 4%, - 13 ± 4%, - 16 ± 6%, - 10 ± 3% and - 14 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively, with the best agreement seen in DENSE and Circle with tagging. The Err was highly varied with poor agreement across the techniques, 32 ± 24%, 40 ± 28%, 47 ± 26%, 64 ± 33% and 23 ± 9% for tagging, DENSE, Tomtec, CIM and Circle, respectively. The average Ell was - 14 ± 4%, - 8 ± 3%, - 13 ± 5%, - 11 ± 3% and - 12 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively with the best agreement seen in Tomtec and Circle with tagging. In the intra- and inter-observer agreement analysis the reproducibility of each technique was good except for Err by HARP. CONCLUSIONS: Small but important differences are evident in Ecc and Ell comparisons among vendors while large differences are seen in Err assessment. Our findings suggest that CMR strain values are technique and vendor dependent. Hence, it is essential to develop reference standard from each technique and analytical product for clinical use, and to sequentially compare patient data using the same software.
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Cardiomiopatías/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Cinemagnética/métodos , Contracción Miocárdica , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Fenómenos Biomecánicos , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Estrés MecánicoRESUMEN
Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-ß and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes.
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Angiotensina II/metabolismo , Aorta/citología , Aorta/metabolismo , Fibroblastos/metabolismo , Receptor PAR-1/metabolismo , Receptor PAR-2/metabolismo , Animales , Aorta/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Receptor PAR-1/agonistas , Receptor PAR-1/antagonistas & inhibidores , Receptor PAR-2/agonistas , Receptor PAR-2/antagonistas & inhibidoresRESUMEN
BACKGROUND: Hypertension complicated with left ventricular hypertrophy (LVH) and diastolic dysfunction is one of the most common risks for heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term beta-blocker prescription in these patients. METHODS: This retrospective analysis included eligible patients diagnosed with hypertension, LVH (left ventricular (LV) mass index >125 g/m(2) for men and >110 g/m(2) for women) and suspected diastolic dysfunction (E/E' ratio between 8 and 15) and without clinical signs or symptoms of heart failure in our hospital medical record database (January 2005-December 2009). A total of eligible 1498 patients were enrolled, of whom 803 received beta-blocker prescription and 695 accepted non-beta-blocker therapy. RESULTS: With a median follow-up of 7.2 years, the new-onset symptomatic HFpEF occurred in 48 of 803 patients in the beta-blocker group (6.0%) and 92 of 695 patients in the non-beta-blocker group (13.2%, p < 0.001). Beta-blockers also generated more prominent improvement in diastolic function and LVH. And Cox proportional hazards model revealed that beta-blocker (hazard ratio (HR) 0.327, 95% confidence interval (CI): 0.121-0.540, p = 0.009) or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) exposure (HR 0.422, 95% CI: 0.210-0.699, p = 0.015) was associated with a reduced risk of new onset of symptomatic HFpEF, and the elevation of LVMI (HR 1.210, 95% CI: 1.069-1.362, p = 0.040) or E/E' (HR 1.398, 95% CI: 1.306-1.541, p = 0.032) was associated with a high risk of new onset of symptomatic HFpEF. CONCLUSIONS: Long-term beta-blocker exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and LVH, which might be beneficial for the delay of HFpEF progression.
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Antagonistas Adrenérgicos beta/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Volumen Sistólico/fisiología , Anciano , Progresión de la Enfermedad , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Pronóstico , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Factores de Tiempo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: Paraoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes. MATERIAL/METHODS: Non-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative. RESULTS: Both PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all P<0.001). PON1 paraoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase. CONCLUSIONS: PON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.
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Arildialquilfosfatasa/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus/sangre , Factor de von Willebrand/metabolismo , Anciano , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/enzimología , Estenosis Coronaria/sangre , Estenosis Coronaria/complicaciones , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
Fabrication of nonlinear elastic materials that resemble biological tissues remains a challenge in biomaterials research. Here, a new fabrication protocol to produce elastomeric fibrous scaffolds was established, using the core/shell electrospinning technique. A prepolymer of poly(xylitol sebacate) with a 2:5mol ratio of xylitol:sebacic acid (PXS2:5) was first formulated, then co-electrospun with polyvinyl alcohol (PVA - 95,000Mw). After cross-linking of core polymer PXS2:5, the PVA shells were rinsed off in water, leaving a porous elastomeric network of PXS2:5 fibres. Under aqueous conditions, the PXS2:5 fibrous scaffolds exhibited stable, nonlinear J-shaped stress-strain curves, with large average rupture elongation (76%) and Young׳s modulus (~1.0MPa), which were in the range of muscle tissue. Rupture elongation of PXS2:5 was also much higher when electrospun, compared to 2D solid sheets (45%). In direct contact with cell monolayers under physiological conditions, PXS2:5 scaffolds were as biocompatible as those made of poly-l-lactic acid (PLLA), with improvements over culture medium alone. In conclusion, the newly developed porous PXS2:5 scaffolds show tissue-like mechanical properties and excellent biocompatibility, making them very promising for bioengineering of soft tissues and organs.
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Materiales Biocompatibles , Elastómeros , Ensayo de Materiales , Estrés Mecánico , Resistencia a la Tracción , Andamios del Tejido , Elasticidad , Polímeros , Ingeniería de Tejidos/métodos , XilitolRESUMEN
Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of â¼60 µm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several µm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.
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Huesos/fisiología , Fosfatos de Calcio/farmacología , Quitosano/farmacología , Osteón/fisiología , Cicatrización de Heridas/efectos de los fármacos , Animales , Materiales Biocompatibles/farmacología , Huesos/efectos de los fármacos , Osteón/efectos de los fármacos , Humanos , Implantes Experimentales , Masculino , Ratas Wistar , Cráneo/efectos de los fármacos , Cráneo/cirugía , Cráneo/ultraestructuraRESUMEN
Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising drug-delivery system that can enhance the therapeutic effects of chemotherapy drugs, such as doxorubicin (DOX), with minimized side effects. This work explores the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX triads. Different generations (G3, G5, and G6) of PAMAMs were synthesized and modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DGx where x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated with drug DOX. The loading and releasing efficiencies of DOX increased with the PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87, 93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5, and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as â¼ 15%. Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild toxicity against human cervical adenocarcinoma cell line HeLa at pH 7.4, which indicated that DOX can be fairly benignly carried and sparingly released until PAMAM-Fe3O4-DOX is taken up into the cell.
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Dendrímeros/química , Portadores de Fármacos , Óxido Ferrosoférrico/química , Nanopartículas de Magnetita/química , Polietilenglicoles/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Dendrímeros/síntesis química , Doxorrubicina/química , Doxorrubicina/farmacología , Composición de Medicamentos , Ácido Glutámico/química , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Microscopía Fluorescente , Electricidad EstáticaRESUMEN
Poly(glycerol sebacate) (PGS) and poly(xylitol sebacate) (PXS) are biodegradable elastomers with tremendous potential in soft tissue engineering. This study was aimed at exploring the enzymatic degradation mechanisms of these polyesters, using biochemical conditions similar to those occurring in vivo. To this end, PGS and PXS (crosslinked at 130 for 2 or 7 (PGS)/12 days (PXS)) were incubated in vitro under physiological conditions in tissue culture media supplemented with either a biodegrading enzyme (esterase), an oxidant species (FeSO4/H2O2 with 0.11 molar ratio of Fe(2+/)H2O2), an oxidant generating enzyme (xanthine oxidase and xanthine) or combinations of these (FeSO4/H2O2 and esterase, or (v) xanthine oxidase/xanthine and esterase), based on their independent effects on polymer degradation. Testing was performed over 35 days of continuous incubation, during which mechanical properties, mass loss, biomaterial thickness and pH value of the culture medium were determined. Degradation kinetics of both PGS and PXS samples were primarily determined by the degree of crosslink density. Esterase and FeSO4/H2O2 accelerated the degradation of both polymers, by promoting hydrolysis and free-radical degradation, although this action was not affected by the presence of xanthine oxidase and xanthine. Degradation of PGS and PXS is primarily mediated by the action of esterase, with free-radical oxidation playing a secondary role, suggesting that both could synergistically affect the biodegradability of biomaterial implants, under more complex biological conditions.
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Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Decanoatos/química , Decanoatos/metabolismo , Glicerol/análogos & derivados , Poliésteres/química , Poliésteres/metabolismo , Polímeros/química , Polímeros/metabolismo , Implantes Absorbibles , Animales , Fenómenos Biomecánicos , Elastómeros/química , Elastómeros/metabolismo , Esterasas/metabolismo , Glicerol/química , Glicerol/metabolismo , Concentración de Iones de Hidrógeno , Cinética , Ensayo de Materiales , Ratones , Microscopía Electrónica de Rastreo , Oxidantes/metabolismo , Oxidación-Reducción , Ingeniería de Tejidos , Xantina Oxidasa/metabolismoRESUMEN
Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).
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One of the major challenges in the field of biomaterials engineering is the replication of the non-linear elasticity observed in soft tissues. In the present study, non-linearly elastic biomaterials were successfully fabricated from a chemically cross-linked elastomeric poly(glycerol sebacate) (PGS) and thermoplastic poly(L-lactic acid) (PLLA) using the core/shell electrospinning technique. The spun fibrous materials, containing a PGS core and PLLA shell, demonstrated J-shaped stress-strain curves, and having ultimate tensile strength, rupture elongation, and stiffness constants respectively comparable to muscle tissue properties. In vitro evaluations also showed that PGS/PLLA fibrous biomaterials possess excellent biocompatibility, capable of supporting human stem-cell-derived cardiomyocytes over several weeks in culture. Therefore, the core/shell electrospun elastomeric materials provide a new potential scaffold to support cells in the therapy of a wide range of soft tissues exposed to cyclic deformation, such as tendon, ligament, cardiac or smooth muscle and lung epithelium.
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Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Decanoatos/química , Elastómeros/química , Glicerol/análogos & derivados , Ácido Láctico/química , Fenómenos Mecánicos , Miocitos Cardíacos/citología , Polímeros/química , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Glicerol/química , Humanos , Ensayo de Materiales , Ratones , Miocitos Cardíacos/efectos de los fármacos , Poliésteres , Estrés Mecánico , Resistencia a la Tracción , Andamios del Tejido/químicaRESUMEN
An efficient delivery system is critical for the success of cell therapy. To deliver cells to a dynamic organ, the biomaterial vehicle should mechanically match with the non-linearly elastic host tissue. In this study, non-linearly elastic biomaterials have been fabricated from a chemically crosslinked elastomeric poly(glycerol sebacate) (PGS) and thermoplastic poly(l-lactic acid) (PLLA) using the core/shell electrospinning technique. The spun fibrous materials containing a PGS core and PLLA shell demonstrate J-shaped stress-strain curves, having ultimate tensile strength (UTS), rupture elongation and stiffness constants of 1 ± 0.2 MPa, 25 ± 3% and 12 ± 2, respectively, which are comparable to skin tissue properties reported previously. Our ex vivo and in vivo trials have shown that the elastomeric mesh supports and fosters the growth of enteric neural crest (ENC) progenitor cells, and that the cell-seeded elastomeric fibrous sheet physically remains in intimate contact with guts after grafting, providing the effective delivery of the progenitor cells to an embryonic and post-natal gut environment.
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Materiales Biocompatibles/química , Colon/cirugía , Decanoatos/química , Glicerol/análogos & derivados , Ácido Láctico/química , Cresta Neural/citología , Polímeros/química , Trasplante de Células Madre , Andamios del Tejido/química , Animales , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Colon/citología , Elasticidad , Glicerol/química , Ratones , Ratones Endogámicos C57BL , Poliésteres , Resistencia a la Tracción , Ingeniería de TejidosRESUMEN
In order to develop degradable elastomers with a satisfactory combination of flexibility and enzyme-mediated degradation rate, the mechanical properties, enzymatic degradation kinetics and biocompatibility of poly(xylitol sebcate) (PXS) has been systematically investigated in comparison with poly(glycerol sebacate) (PGS). Under the same level of crosslinked density, the PXS elastomer networks have approximately twice the stretchability (elongation at break) of their PGS counterparts. This observation is attributable to the relatively longer and more orientable xylitol monomers, compared with glycerol molecules. Although xylitol monomers have two more hydroxyl groups, we, surprisingly, found that the hydrophilic side chains did not accelerate the water attack on the ester bonds of the PXS network, compared with their PGS counterpart. This observation was attributed to a steric hindrance effect, i.e. the large-sized hydroxyl groups can shield ester bonds from the attack of water molecules. In conclusion, the use of polyols of more than three -OH groups is an effective approach enhancing flexibility, whilst maintaining the degradation rate of polyester elastomers. Further development could be seen in the copolymerization of PPS with appropriate thermoplastic polyesters, such as poly(lactic acid) and polyhydroxyalkanoate.
Asunto(s)
Materiales Biocompatibles/química , Decanoatos/química , Glicerol/análogos & derivados , Polímeros/química , Xilitol/análogos & derivados , Animales , Fenómenos Biomecánicos , Línea Celular , Proliferación Celular , Elastómeros/química , Esterificación , Fibroblastos/citología , Glicerol/química , Ensayo de Materiales , Ratones , Xilitol/químicaRESUMEN
This study sought to determine if apocynin, a nicotinamide adenine dinucleotide phosphate oxidase inhibitor, would attenuate arterial stiffness in salt-sensitive hypertensive rats via structural and functional changes in conduit arteries. We showed that tail blood pressure was significantly higher in deoxycorticosterone acetate-salt-induced hypertensive (DSH) rats compared with the sham control group (P<0.01). Morphological analysis and biochemical assay showed that large arteries in DSH rats underwent significant remodeling including increased medial thickness in carotid arteries compared with the control rats (194.25±5.66 vs. 120.48±7.93 µm, P<0.05) and increased collagen deposition in thoracic aorta (1.03±0.09 vs. 0.85±0.04 mg cm(-1), P<0.05). These changes were associated with increases in reactive oxygen species (ROS) level and increased thoracic aortic stiffness compared with the control rats (6.21±0.79 m s(-1) vs. 4.64±0.59 m s(-1), P<0.01). Treatment with apocynin significantly prevented ROS increases and collagen deposition (0.84±0.04 vs. 1.03±0.09 mg cm(-1), P<0.05), and reduced arterial stiffness as shown by decreased pulse wave velocity in the thoracic aorta (5.31±0.88 vs. 6.21±0.79 m s(-1), P<0.01). Additionally, apocynin prevented carotid artery wall thickening (58.57±3.40 vs. 78.89±4.10 µm, P<0.05). In conclusion we have shown that increased ROS level is associated with increased aortic stiffness, and deposition of collagen in the aortic arterial wall in DSH rats. Apocynin prevented ROS increases and arterial stiffness in DSH rats. Antioxidant therapy may be a potential treatment of large arterial stiffness in salt-sensitive hypertension.
Asunto(s)
Acetofenonas/farmacología , Antioxidantes/farmacología , Desoxicorticosterona , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Estrés Oxidativo/efectos de los fármacos , Cloruro de Sodio , Rigidez Vascular/efectos de los fármacos , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/metabolismo , Aorta Torácica/patología , Presión Sanguínea/efectos de los fármacos , Arterias Carótidas/química , Arterias Carótidas/metabolismo , Colágeno/metabolismo , Elastina/metabolismo , Hipertensión/inducido químicamente , NADPH Oxidasas/biosíntesis , Análisis de la Onda del Pulso , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Driven by the increasing economic burden associated with bone injury and disease, biomaterial development for bone repair represents the most active research area in the field of tissue engineering. This article provides an update on recent advances in the development of bioactive biomaterials for bone regeneration. Special attention is paid to the recent developments of sintered Na-containing bioactive glasses, borate-based bioactive glasses, those doped with trace elements (such as Cu, Zn, and Sr), and novel elastomeric composites. Although bioactive glasses are not new to bone tissue engineering, their tunable mechanical properties, biodegradation rates, and ability to support bone and vascular tissue regeneration, as well as osteoblast differentiation from stem and progenitor cells, are superior to other bioceramics. Recent progresses on the development of borate bioactive glasses and trace element-doped bioactive glasses expand the repertoire of bioactive glasses. Although boride and other trace elements have beneficial effects on bone remodeling and/or associated angiogenesis, the risk of toxicity at high levels must be highly regarded in the design of new composition of bioactive biomaterials so that the release of these elements must be satisfactorily lower than their biologically safe levels. Elastomeric composites are superior to the more commonly used thermoplastic-matrix composites, owing to the well-defined elastic properties of elastomers which are ideal for the replacement of collagen, a key elastic protein within the bone tissue. Artificial bone matrix made from elastomeric composites can, therefore, offer both sound mechanical integrity and flexibility in the dynamic environment of injured bone.