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In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.
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Objective To construct a novel thiolated chitosan modified poly(lactide-co-ε-caprolactone)-d-α-tocopheryl polyethylene glycol 1 000 succinate (PLA-PCL-TPGS) nanoparticle,and investigate the feasibility of its use as an oral carrier for lung cancer chemotherapy.Methods The PLA-PCL-TPGS random copolymer was synthesized and characterized.Then three types of nanoparticles from commercial PCL and PLA-PCL-TPGS random copolymer were prepared for oral carrier of paclitaxel,including 5％ thiolated chitosan-modified PCL nanoparticles (CNPs),unmodified PLA-PCL-TPGS nanoparticles (UNPs),and 5％ thiolated chitosan-modified PLA-PCL-TPGS nanoparticles (TNPs).The prepared nanoparticles were characterized in terms of size,Zeta potential,morphology,drug loading and encapsulation efficiency.The in vitro drug release profiles and cellular uptake of the nanoparticles by human lung cancer cell lines A549 cells were investigated,and cytotoxicity against A549 cells was also evaluated.The evened sac method was used for the measurement of transportation of paclitaxel across the intestine barrier.Results The field emission scanning electron microscopy results showed that the three types of paclitaxel-loaded nanoparticles were spherical with a diameter about 200 nm.The surface charge of PLA-PCL-TPGS nanoparticles was reversed from negative to positive charge after thiolated chitosan modification.The UNPs and TNPs achieved higher drug loading,encapsulation efficiency and drug release after 32 d than CNP (all P＜0.05).The TNPs had significantly higher cell uptake efficiency than that of CNPs and UNPs (all P＜0.05).In vitro cell viability studies showed advantages of TNPs over a clinically available paclitaxel injection in terms of cytotoxicity against A549 cells.Ex vivo absorption studies revealed that the TNPs can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein.Conclusion PLA-PCL-TPGS nanoparticles modified by thiolated chitosan can enhance the cellular uptake and cytotoxicity,which reveals a potential application for oral chemotherapy of lung cancer.
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Objective To prepare a redox-responsive doxorubicin-loaded nanoparticle,and to study its in vitro realease behavior and targeting effect on heptoma cells.Methods Cystamine was grafted on the side chains of hyaluronic acid with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide catalyst,and then β-cyclodextrin (β-CD) was conjugated on the amine groups of the cystamine by Schiff's base reaction to prepare β-CD modified hyaluronic acid (HACD).The HACD/DOX nanoparticles were prepared by encapsulating DOX into HACD using dialysis method.The drug loading,encapsulation efficiency,particle size and distribution,zeta potential and other physical and chemical properties,as well as in vitro drug release behavior of the HACD/DOX nanoparticles were characterized.The cytotoxicity of HACD/DOX nanoparticles to HepG2 cells was studied by cell counting kit-8 (CCK-8) method.The targeting effect of HACD/DOX nanoparticles on HepG2 cells was studied using flow cytometry and confocal laser scanning microscopy (CLSM).Results HACD were successfully synthesized,which could carry DOX to form uniform homogeneous nanoparticles.The drug loading of DOX in the nanoparticles was (16.1±0.2)％ and the encapsulation efficiency was (64.2±0.9)％.The transmission electron microscope images indicated that the shape of the HACD/DOX nanoparticles was homogeneous sphere.The results of granularity analysis showed that the average size of the HACD/DOX nanoparticles was (203.1 ±2.5) nm with a narrow size distribution (PDI =0.202).The zeta potential of the HACD/DOX nanoparticles was (-29.1±0.8) mV.The in vitro release behavior of the nanoparticles exhibited obvious redox-sensitivity.The results of in vitro cytotoxicity showed that the blank carrier material HACD had no obvious toxicity to hepatoma cells,and the HACD/DOX nanoparticles could effectively kill hepatoma cells with the 0.38 μg/ml half maximal inhibitory concentration (IC50) value at 48 h.Flow cytometry and CLSM results demonstrated that the HACD/DOX nanoparticles could target hepatoma cells through the mediating effect of hyaluronic acid.Conclusions The prepared HACD/DOX nanoparticles have suitable particle size,high drug loading and encapsulation efficiency,and can release DOX under the stimulation of reducing agent.These nanoparticles have obvious targeting effect on hepatoma cells,which is expected to be applied as the drug delivery system of hepatocellular carcinoma (HCC) therapy.
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Objective To investigate susceptibility and antibacterial activity of cationic porphyfin derivative mediated photodynamic antimicrobial chemotherapy (CPD-PACT) against Pseudomonas aeruginosa,to provide experimental evidence for its high efficiency antibacterial activity.Methods The impacts of culture environments on minimum inhibitory concentration (MIC) were measured by double dilution method.The formation of inhibition zone was determined by diffusion plate method.The postantibiotic effect was analyzed by colony forming units.The viability and morphology of Pseudomonas aeruginosa were observed by confocal laser scanning microscopy (CLSM).Results The inoculum size of bacterial had a certain effect on the MIC.The MIC values increased as the pH of medium rose.When the calf serum content of culture medium increased,the MIC rose in light reaction and dropped in dark reaction.The diameter of inhibition zone mainly depended on the laser energy density,but not the concentration of photosensitizer.Though CPD possessed strong antimicrobial activity and persistent suppression on bacterial growth,the surviving Pseudomonas aeruginosa would soon continue to proliferate after PACT.The fluorescence images captured by CLSM showed that CPD-PACT could destroy the membrane integrity,leak the cytoplasmic component,decrease the bacterial activity and finally lead Pseudomonas aeruginosa to death.Conclusions CPD has strong inhibitory activity and obvious postantibiotic effect on Pseudomonas aeruginosa,which is suitable to be developed as an drug candidate for PACT.
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Objective To investigate the cell compatibility of polystyrene(PS) plate chemically modified with RGD peptides.Methods PS surfaces were carboxylated by permanganate oxidation in diluted sulfuric acid,and carboxyls were activated with water-soluble carbodiimide to graft with gelatin,collagen and RGD peptides.IR,X-ray photo-electronic spectroscopy (XPS) and dynamic contact angle were used to characterize the surface modification of PS surface.Results XPS results confirmed the existence of nitrogen element from protein molecules and the covalently binding of proteins to PS surfaces.Dynamic contact angle measurement indicated hydrophilicity of PS surfaces was improved obviously after grafting modification.The cell culture results showed that the cell adhesion and proliferation was better on modified surfaces than the initial.Conclusion The cell compatibility of PS surface was great improved after modification with RGD peptides,which would provide a potential strategy to improve the culture of purified endothelial progenitor cells isolated by immunomagnetic beads.
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Objective To investigate the effects of different thickness of cell culture dishes on fluorescent image with confocal microscope.Methods The fluorescent staining experiments of live cells and fixed cells were used to determine the differences among three dishes with different thickness coverslips of 0.085～0.13 mm,0.13～0.16 mm and 0.16～0.19 mm,while the cell appearance,fluorescence lightness and mean of fluorescence intensity were studied with confocal microscope.Results Demonstrated by the results of cytoskeleton staining experiments,the dish with 0.13～0.16 mm thickness coverslip was the best choice for confocal microscope,the dish with 0.16～0.19 mm thickness coverslip was the second one,the dish with 0.16～0.19 mmthickness coverslip was the last one.ConclusionThe dish with 0.13～0.16 mm thickness coverslip is the best choice for confocal microscope.On this type of dish,the cytoskeleton is unfolding and clear after staining.The intensity of fluorescence is the strongest,and the imaging effect is the best.
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Objective The aim of this study was to observe the outcome and evaluate the clinical efficacy of pulsed electromagnetic fields (PEMF) on pain management in patients with osteoporosis.MethodsA total of 58 patients with osteoporosis were treated with PEMF stimulation.Pains as main indicators of their symptom were evaluated before and after treatments.The clinical outcomes were assessed by observing the visual analogue scale (VAS).Statistical analysis was carried out to support the data.Results After PEMF treatment,the patients exhibited significant pain relief from mean VAS of 6.97±1.83 to 3.36±1.69(t-test,P＜0.05 ).Of the 58 patients,28 obtained significant symptom alleviation and 18 obtained moderate symptom alleviation,while 8 obtained slight alleviation,indicating the total clinical efficacy of 93%(54/58).Conclusion The current study provides the clinical outcomes indicating that PEMF may help to release the pain from primary osteoporosis and it might be an applicable supplementary treatment method for the osteoporosis related pain.