RESUMO
IMPORTANCE: The phenomenon of reversible clustering is expected to further nuance HIV immune stealth because virus surfaces can escape interaction with antibodies (Abs) by hiding temporarily within clusters. It is well known that mucin reduces HIV virulence, and the current perspective is that mucin aggregates HIV-1 to reduce infections. Our findings, however, suggest that mucin is dispersing HIV clusters. The study proposes a new paradigm for how HIV-1 may broadly evade Ab recognition with reversible clustering and why mucin effectively neutralizes HIV-1.
Assuntos
HIV-1 , Mucinas , Humanos , Anticorpos Neutralizantes , Glicosilação , Anticorpos Anti-HIV , Proteína gp120 do Envelope de HIV , Infecções por HIV/imunologia , Infecções por HIV/virologia , Soropositividade para HIV , HIV-1/fisiologia , Mucinas/metabolismoRESUMO
The surface-supported silver nanoparticles have been studied and applied in various applications. Many unique nanostructures have been introduced into this field to improve the functionalities of the surfaces depending on application purposes. We created featured silver nano-array surfaces by utilizing the solvent-mediated phase transition on the surface grafted with poly (acrylic) acids polymer chains and taking advantage of the low temperature of argon gas discharged plasma as a reducing agent. The applied solvents and grafted polymer chain densities affected the phase transition and thus determined the outcome of surface nano-array patterns. However, the total loaded silver ions on the surface affected silver nano-array structures at the sub-micron levels. The featured silver patterned surfaces made in the optimal conditions present a favorable surface-enhanced Raman spectroscopy enhancement as well as recyclability for detection re-usage. This novel method prepares tunable silver nanopatterned surfaces and provides a new approach to various potential applications.
RESUMO
Orlistat, an FDA-approved antiobesity drug, has recently been shown to have anticancer effects. However, orlistat is extremely hydrophobic with low absorption. Therefore, new approaches are needed to effectively deliver orlistat for cancer therapy. Herein, we developed a fast and simple method to use polydopamine-coated hollow capsule (PHC) as a drug nanocarrier for enhancing the therapeutic effects of orlistat. Orlistat-loaded PHC had an average size of 200 nm, which was characterized by using dynamic light scattering and scanning electron microscope. Furthermore, the polydopamine layer provided an excellent control of orlistat release because it was extremely sensitive to pH values. The cellular uptake and cytotoxicity experiments were performed to show that orlistat packaged in PHC could be endocytosed into cells and then significantly improved the cytotoxic activity against cancer cell lines in a short time compared with free orlistat. Moreover, dynamic study of cell membrane lysis was performed by staining with the LIVE/DEAD kit to demonstrate the cancer-killing mechanism. The size of the cell surface area has also been proven to be a key parameter which affected drug efficacy. Taken all together, these results present that orlistat-loaded PHC is a very promising formula for cancer treatments.
Assuntos
Antineoplásicos/química , Cápsulas/química , Indóis/química , Orlistate/química , Polímeros/química , Células A549 , Linhagem Celular Tumoral , Emulsões/química , Células HeLa , Humanos , Células MCF-7 , Microscopia Eletrônica de Varredura , Nanopartículas/químicaRESUMO
BACKGROUND: Left ventricular (LV) dyssynchrony is associated with increased risk of all-cause mortality in patients with end-stage renal disease. Our aim was to determine the associations of LV dynamic dyssynchrony with peritoneal solute clearance in continuous ambulatory peritoneal dialysis (CAPD) patients. Our primary objective was to determine the association between dynamic LV dyssynchrony and CAPD clearance at 2 years. Secondary objectives were to identify the factors influencing dynamic dyssynchrony, and to examine the association between dialysis adequacy and echocardiography-assessed LV outcomes. METHODS: Fifty CAPD patients and 13 healthy volunteers underwent three-dimensional (3D) dobutamine stress echocardiography (DSE). The main endpoint was systolic dyssynchrony index (SDI). Secondary endpoints, including NT-proBNP, troponin I, Kt/V, and biochemical parameters, were measured before stress echocardiography, and Kt/V was measured again 2 years later. All values are expressed as medians and interquartile ranges (IQR). RESULTS: NT-proBNP (3872 [808-11779] vs. 4.99 [4.99-36.83] pg/mL, P < 0.001), and log NT-proBNP (3.587 [2.896-4.071] vs. 0.698 [0.698-1.540], P < 0.001) levels were significantly higher in the CAPD group than in the control group. Real-time 3D DSE showed that the systolic dyssynchrony index was significantly different between the two groups at the peak dobutamine stage (1.11% [0.76-1.64%] vs. 0.66% [0.50-1.02%], P = 0.004), but not at resting (1.30% [0.89-1.74%] vs. 1.22 % [0.72-1.68%], P = 0.358).The subgroup of patients in the CAPD group with greater improvements in dialysis adequacy had lower baseline dynamic SDI and more favorable echocardiographic findings at 2 years. Dialysis adequacy decreased significantly at 2 year in patients with higher, but not in those with lower dynamic SDI at baseline. In multivariate linear regression analysis, log NT-proBNP and SDI at the peak dobutamine dose were significantly associated with Kt/V and weekly creatinine clearance at 2 years, while log NT-proBNP was significant associated with SDI at the peak dobutamine stage. Female CAPD patients group had more pronounced dynamic LV dyssynchrony compared with male patients. CONCLUSIONS: Dynamic systolic dyssynchrony was strongly associated with future dialysis adequacy in CAPD patients. Log NT-proBNP was the important predictor of dynamic dyssynchrony. Our study confirmed the concept that cardiac dysfunction has an impact on dialysis adequacy.
Assuntos
Diálise Peritoneal Ambulatorial Contínua/tendências , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Ecocardiografia sob Estresse/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/métodosRESUMO
Poly(vinyl alcohol) (PVA) hydrogels have been extensively studied as drug delivery systems. However, due to the high hydrophilicity of PVA, these hydrogels have weak abilities to efficiently load drugs and control the initial burst release. In this study, we present a one-step simple and rapid single needle electrospraying (SNESy) method that combines PVA hydrogels with another biocompatible polymer polycaprolactone (PCL). A distinct core-shell structure was obtained with the PVA hydrogel core and PCL shell after the system was properly set up. The results revealed that the volume ratio between PVA hydrogel and PCL played an important role in determining the particle size and the formation of a spherical structure. The double-walled structure of the microsphere was confirmed by taking the fluorescent images and conducting the ATR-FTIR method. Furthermore, doxorubicin hydrochloride was used as a model drug to evaluate the drug loading capacity and the in vitro release behavior of this PVA hydrogel/PCL microsphere. The results indicated that coating a layer of PCL polymer significantly enhanced the drug loading capacity and reduced the drug initial burst release compared to the single-layer PVA hydrogel nanoparticles, demonstrating these biocompatible double-walled microspheres can be applied as excellent drug delivery carriers.
Assuntos
Preparações de Ação Retardada/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Microesferas , Agulhas , Poliésteres/química , Álcool de Polivinil/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fluorescência , Humanos , Concentração Inibidora 50 , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da PartículaRESUMO
Highly sensitive long-period fiber gratings (LPFG) was developed for label-free and rapid detection of Staphylococcus aureus (S. aureus). Specifically, the LPFG was functionalized with antibody and nanopitted polyelectrolyte coatings to facilitate bacterial adhesion and thus enhance the sensitivity of bacteria detection. The kinetics of S. aureus adhesion on functional coatings were tracked by surface morphology evolution and time-resolved resonance wavelength shift of the coated LPFG at a flow rate of 30⯵l/ml and 37⯰C in the concentration range of 104-108 colony forming unit (CFU)/ml. S. aureus detection at concentrations as low as 224â¯CFU/ml can be achieved within a short time span of 30â¯min. The LPFG-based biosensor can be readily adapted to a variety of biophotonic platforms, for applications such as food safety inspection, environmental monitoring, clinical diagnostics, and medical applications.
Assuntos
Técnicas Biossensoriais , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/química , Staphylococcus aureus/isolamento & purificação , Anticorpos/química , Humanos , Nanocompostos/química , Polieletrólitos/química , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidadeRESUMO
The mussel inspired chemistry of dopamine oxidation to form polydopamine (PDA) and in situ reduction of metal ions in solution to form metal nanoparticles have widely opened the application of metal nanoparticles surface modification technology. This article contains the dataset of the scanning electron microscope (SEM) images of silver nanoparticles coated on polyethylene terephthalate (PET) films utilizing dopamine chemistry alone or combined with polyvinylpyrrolidone or glucose. The Ag NPs formed in various environments present round, cubic, or triangle shape. Mendeley Data, http://dx.doi.org/10.17632/bjjrt2dwbn.1.
RESUMO
The emergence of multidrug resistant cancer phenotypes dramatically attenuates the efficiency of a variety of anti-cancer drugs. Silver nanoparticles (AgNPs) display excellent anti-cancer activity and dramatic inhibitory effect on drug resistance related proteins like P-glycoprotein (Pgp). Here we developed a novel drug nanocrystal formulation of Camptothecin (CPT), a broad spectrum anti-cancer agent, decorated by AgNPs. The resulting combinational formulation of CPT and AgNPs, named as CPT/Ag nanocrystals, demonstrated excellent dispersion properties and an improved dissolution rate, drug stability and cellular uptake rate. Because CPT nanocrystals are able to bypass Pgp recognition and AgNPs inhibit both Pgp expression and activity, CPT/Ag nanocrystals showed extreme and indiscriminate cytotoxicity against a variety of both drug sensitive and drug resistant cancer cells. Moreover, the quickly and plenty of released CPT from the CPT/Ag nanocrystals triggered by the tumor microenvironment led to a relaxed and cleavable chromatin structure, facilitating DNA damage and apoptotic potential of AgNPs that were subsequently released.
Assuntos
Ligas/síntese química , Ligas/farmacologia , Anti-Infecciosos/farmacologia , Cobre/farmacologia , Indóis/química , Indóis/farmacologia , Nanopartículas/química , Polímeros/química , Polímeros/farmacologia , Prata/farmacologia , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Polietilenotereftalatos/química , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios XRESUMO
Statin therapy may improve responsiveness to erythropoietin-stimulating agents in patients with end-stage renal disease. Although statins increase hepatic iron uptake and storage capacity in cholestatic rats, the underlying mechanisms are unclear. Therefore, we examined the effects of a statin (simvastatin) on the expression of hepcidin, erythropoietin receptor (EPOR) and erythropoietin (EPO) in cultured HepG2 cells. HepG2 cells (6-6.5 × 10(5) cells) were seeded in 6-cm dishes and incubated overnight. The cells were then treated with 0, 0.5, 1, 3, 5, or 10 µM simvastatin, and the mRNA expression of hepcidin, EPOR, and EPO was determined. Data were collected from three independent experiments. The cDNA extracted from the cells was used as a template for real-time polymerase chain reaction, and each sample was tested in duplicate. Significant differences (P < 0.05) among groups were determined using one-way analysis of variance with Fisher's least significant difference post hoc test. Data were adjusted using Bonferroni's method. The relative mRNA expression of hepcidin in HepG2 cells treated with 0.5, 1, 3, 5, and 10 µM simvastatin, relative to the control group, was 0.7273, 0.3303, 0.2418, 0.4131, and 0.4064, respectively. The relative mRNA expression of EPOR was 0.5196, 0.2319, 0.2398, 0.4253, and 0.1245, respectively, while that of EPO was 0.9751, 0.4712, 0.4613, 0.4875, and 0.1654. There was a reverse dose-dependent effect of simvastatin. These results suggest that statins increase erythropoiesis by targeting hepcidin and iron regulatory pathways, independent of erythropoietin.