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Optimization of parameters for preparation of docetaxel-loaded PLGA nanoparticles by nanoprecipitation method

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.SummaryThe purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.

Effects of salivae miltiorrhizae liguspyragine hydrochloride and glucose injection (参芎葡萄糖注射液) on the levels of main platelet thrombin receptors in chronic haemodialysis patients

ObjectiveTo investigate the effects of Salvia Miltiorrhiza Liguspyragine Hydrochloride and Glucose Injection (参芎葡萄糖注射液, SLGI) on the expression of platelet membrane receptors proteinase-activated receptor-1 (PAR1) and proteinase-activated receptor-4 (PAR4) in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD).MethodsEighty-six ESRD patients on HD (treated group) were treated with SLGI, 7 days as one therapeutic course, for two successive courses. The previous therapies were unchanged. Flow cytometry was used to assess the expression of platelet PAR1 and PAR4 in the patients, and turbidity method was used to determine the platelet maximum aggregation rate (MAR). Meanwhile, renal function was measured. The final data were compared with those before treatment and with those in the normal control group (54 healthy subjects).ResultsCompared with the normal control group, the expressions of PAR1 and PAR4 and platelet MAR in ESRD patients on HD was significantly higher before treatment (P=0.001, P=0.006, and P=0.008); after treatment with SLGI, the above indices in patients were remarkably decreased (P=0.036 and P=0.046), except PAR4 (P=0.067), but still higher than those in the normal control group, however, it was not statistically significant.Conclusions(1) The overexpression of PAR1 and PAR4 might lead to increased platelet aggregation and this could be one of the reasons for the thrombotic events in ESRD patients on HD. (2) SLGI was able to down-regulate the expression of PAR1 in ESRD patients on HD, improve platelet function, and regulate platelet activation.

Cardamonin induces ROS-mediated G2/M phase arrest and apoptosis through inhibition of NF- κ B pathway in nasopharyngeal carcinoma

Cardamonin has been demonstrated to have an inhibitory effect in many cancers, but its underlying mechanism remains elusive. Here, we studied, for the first time, the mechanism of cardamonin-induced nasopharyngeal carcinoma cell death both in vitro and in vivo. In our study, we showed that cardamonin inhibited cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis via accumulation of ROS. NF-κB activation was involved in breaking cellular redox homeostasis. Therefore, our results provided new insight into the mechanism of the antitumor effect of cardamonin, supporting cardamonin as a prospective therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox balance.

Famitinib enhances nasopharyngeal cancer cell radiosensitivity by attenuating radiation-induced phosphorylation of platelet-derived growth factor receptor and c-kit and inhibiting microvessel formation.

Purpose: Famitinib is a novel tyrosine kinase inhibitor. We investigated the effects of famitinib on the radiosensitivity of human nasopharyngeal carcinoma (NPC) cell radiosensitivity in vitro and in vivo, and explored its possible mechanisms. Materials and methods: Human nasopharyngeal carcinoma cell line (CNE-2) were treated with famitinib and radiation, and analyzed by3-(4,5-dimethylthaizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic survival assay, and Western blot. A xenograft model using CNE-2 cells was established to analyze the effects of famitinib and radiation on tumor volume and microvessel density (MVD). Results: Famitinib dose-dependently inhibited CNE-2 cells growth and significantly reduced clonogenic survival (p < 0.05), with a sensitivity enhancement ratio (SER) of 1.45. The tumor inhibition rate of the combined treatment group was 91%, which was significantly higher than the radiation group (35%, p < 0.05) and famitinib group (46%, p < 0.05). Famitinib attenuated radiation-induced phosphorylation of the platelet-derived growth factor receptor (PDGFR) and stem cell factor (c-kit) at 0, 30, 60 min after radiation treatment. Furthermore, radiation combined with famitinib decreased tumor MVD (p < 0.05). Conclusions: Famitinib significantly increased CNE-2 cell radiosensitivity in vitro and in vivo by attenuating radiation-induced PDGFR and c-kit phosphorylation and by inhibiting microvessel formation.

Magnetic nanoparticle clusters radiosensitise human nasopharyngeal and lung cancer cells after alternating magnetic field treatment.

Abstract Purpose: Heat generated by magnetic nanoparticle clusters (MNCs) in an alternating magnetic field (AMF) can be used for hyperthermia cancer treatment. Here, we have synthesised polyacrylic acid-coated MNCs according to previous report, with the ability to increase particle stability in suspension. Radiosensitisation effects of the MNCs under an AMF were investigated in vitro and in vivo. Materials and methods: MTT assay, flow cytometry, clone formation assay, Western blotting, and a γ-H2AX experiment were used to explore the biocompatibility and radiosensitisation effect of the MNCs and their putative radiosensitisation mechanism. An NCI-H460 mouse xenograft model was used to investigate the anti-tumour effect under an AMF in vivo. Results: The temperature of MNC fluids at different concentrations (200 μg/mL to 2 mg/mL) increased rapidly. The MNCs were endocytosed by the cells and were found to be biocompatible. Hsp70 and caspase-3 were found to be up-regulated upon MNCs under an AMF, radiation, and combination of both treatments. MNCs under an AMF efficiently radiosensitised both CNE-2 cells and NCI-H460 cells. Finally, the tumour inhibition rate after treatment with MNCs under an AMF and radiation was significantly higher than that after either treatment alone. The mechanism of radiosensitisation putatively involves inhibition of DNA repair and induction of apoptosis. Conclusions: The MNC fluids under an AMF enhanced the radiosensitivity of tumour cells both in vitro and in vivo.

Smilax china L. rhizome extract inhibits nuclear factor-κB and induces apoptosis in ovarian cancer cells

ObjectiveTo study the antitumor effects and associated mechanisms of extract of the Smilax china L. rhizome (SCR) on ovarian cancer cells.MethodsOvarian cancer cells A2780 were treated with different concentrations of SCR extract (SCRE), and compared with controls. Effects on cell growth were evaluated by cell counting kit-8 (CCK-8) assay; proliferation effects by EdU incorporation assay; cell cycle by propidium iodide staining; apoptosis by annexin V-fluorescein isothiocyanate/propidium iodide; cellular distribution of nuclear factor-κB (NF-κB) by immunofluorescence; protein levels of NF-κB, caspase-3, poly-adenosine diphosphate (ADP)-ribose polymerase (PARP), Bcl-2-associated X protein (Bax), cellular inhibitor of apoptosis (cIAP)-1, anti-X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-extra large (Bcl-XL), B-cell lymphoma-2 (Bcl-2) and AKT by Western blotting; and effects of SCRE combined with cisplatin or adriamycin on A2780 cells by CCK-8 assay.ResultsSCRE suppressed A2780 cell proliferation in a dose-dependent manner (P<0.05,P<0.01), arrested cells in G2/M phase and induced apoptosis by activating caspase-3, PARP and Bax. SCRE treatment also correlated with inhibition of NF-κB and downregulation of Bcl-2, Bcl-XL, cIAP-1, XIAP and AKT. SCRE can promote chemosensitivity to cisplatin and adriamycin in A2780 cells (P<0.01).ConclusionSCR effectively inhibits NF-κB, induces apoptosis and reduces chemoresistance to cisplatin and adriamycin in ovarian cancer cells, which might be its molecular basis for treating ovarian cancer.

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on the expression of platelet membrane glycoprotein I b/IX/V complex in patients with chronic renal failure

ObjectiveTo investigate the effect of Xiaoyu Zhixue Tablet (消瘀止血片, XYZXT) on the expression of platelet membrane glycoprotein (GP) Ib/IX/V complex and GP I b α in patients with chronic renal failure (CRF) in early metaphase.MethodsFifty-one patients with CRF in early metaphase (treated group) were treated with XYZXT, 3 months as the course of treatment for 2 courses. The previous therapies remained unchanged. Flow cytometry was used to assess the expression of platelet GP Ib/IX/V complex and GP Ib α in patients with CRF, and turbidity method was used to determine the platelet maximum aggregation rate (MAR), meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group (31 healthy subjects).ResultsCompared with the normal control group, expressions of GP I b/IX/V complex and GP I b α, and platelet MAR in CRF patients were significantly lower (P=0.007, P=0.001, P=0.009) before the treatment; after the treatment with XYZXT, the above indexes in CRF patients were remarkably increased (P=0.033, P=0.026, P=0.045), but still lower than those in the normal control group, however, it was not statistically significant.Conclusion(1) The expression of GP I b/IX/V complex in CRF patients of early metaphase was decreased, which lead to platelet aggregation dysfunction. This might be one of the reasons for the hemorrhagic trend in CRF. (2) XYZXT was able to upgrade expressions of GP I b/IX/V complex and GP I b α in CRF patients, improve platelet function and down-regulate platelet activation in patients with CRF.

Synthesis and characterization of surface-modified Fe3O4 super-paramagnetic nanoparticles

SummaryAqueous dispersion and stability of Fe3O4 nanoparticles remain an issue unresolved since aggregation of naked iron nanoparticles in water. In this study, we successfully synthesized different Fe3O4 super-paramagnetic nanoparticles which were modified by three kinds of materials [DSPE-MPEG2000, TiO2 and poly acrylic acid (PAA)] and further detected their characteristics. Transmission electron microscopy (TEM) clearly showed sizes and morphology of the four kinds of nanoparticles. X-ray diffraction (XRD) proved successfully coating of the three kinds of nanoparticles and their structures were maintained. Vibrating sample magnetometer (VSM) verified that their magnetic properties fitted for the super-paramagnetic function. More importantly, the particle size analysis indicated that Fe3O4@PAA had a better size distribution, biocompatibility, stability and dispersion than the other two kinds of nanoparticles. In addition, using CNE2 cells as a model, we found that all nanoparticles were nontoxic. Taken together, our data suggest that Fe3O4@PAA nanoaparticles are superior in the application of biomedical field among the four kinds of Fe3O4 nanoparticles in the future.Aqueous dispersion and stability of Fe3O4 nanoparticles remain an issue unresolved since aggregation of naked iron nanoparticles in water. In this study, we successfully synthesized different Fe3O4 super-paramagnetic nanoparticles which were modified by three kinds of materials [DSPE-MPEG2000, TiO2 and poly acrylic acid (PAA)] and further detected their characteristics. Transmission electron microscopy (TEM) clearly showed sizes and morphology of the four kinds of nanoparticles. X-ray diffraction (XRD) proved successfully coating of the three kinds of nanoparticles and their structures were maintained. Vibrating sample magnetometer (VSM) verified that their magnetic properties fitted for the super-paramagnetic function. More importantly, the particle size analysis indicated that Fe3O4@PAA had a better size distribution, biocompatibility, stability and dispersion than the other two kinds of nanoparticles. In addition, using CNE2 cells as a model, we found that all nanoparticles were nontoxic. Taken together, our data suggest that Fe3O4@PAA nanoaparticles are superior in the application of biomedical field among the four kinds of Fe3O4 nanoparticles in the future.

Expression of platelet membrane glycoprotein Ib/IX/V complex, a receptor of thrombin, in patients with hemorrhagic thrombopathy

SummaryTo investigate the role of platelet membrane glycoprotein (GP) Ib/IX/V complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/IX/V complex and GP Ibα, defined as mean fluorescence intensity (MFI), were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/IX/V complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP Ib/IX/V complex and GP Ibα between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/IX/V complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.To investigate the role of platelet membrane glycoprotein (GP) Ib/IX/V complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/IX/V complex and GP Ibα, defined as mean fluorescence intensity (MFI), were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/IX/V complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP Ib/IX/V complex and GP Ibα between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/IX/V complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.