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Objective: To prepare plumbagin transfersomal (PBG-T) gel and investigate its transdermal penetration characteristics in vitro. Methods: Plumbagin transfersomes were prepared by film-ultrasonic dispersion method. The optimal prescription condition of PBG-T was selected by central composite design and response surface method. The formula of PBG-T gel was optimized by orthogonal test. The Franz diffusion cell was used to investigate transdermal penetration characteristics of PBG-T gel in vitro. Results: The optimal prescription condition of transfersomes was determined as drug 10.0 mg, phospholipids 700.0 mg, Tween-80 91.5 mg, ultrasonication time 13 min. The optimal prescription condition of transfersomal gel was 1% carbomer 940 as gel matrix, and 5% glycerol as the humectant. According to the optimized prescription, the entrapment efficiency, the mean particle size, and Zeta potential of PBG-T were (79.88 ± 2.26)%, (125.64 ± 4.54) nm, and (-30.97 ± 1.13) mV. The cumulative penetration rate of PBG-T gel was 70.0% at 12 h. Conclusion: The optimal preparation technique is stable and feasible. Transfersomal gel features a sustained release in vitro, the transfersomal gel can increase penetration rate of plumbagin through the skin of rats.
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BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are a group of cells that have self-renewal, highly proliferative and multidrug differentiation potential. The properties of UC-MSCs and their tumor tropism make them an ideal tool for glioma cell therapy. These cells can act by paracrine or as a delivery system for genes and drugs. It has been demonstrated that UC-MSCs can inhibit the growth of glioma and improve the survival after transplantation into the brain. OBJECTIVE: To summarize the molecular mechanisms and safety of UC-MSCs in the treatment of glioma and to provide a useful reference for further research. METHODS: We searched the PubMed and CNKI databases from 2000 to 2017 with the English terms of "glioma; umbilical cord mesenchymal stem cells" and the Chinese terms of "glioma; umbilical cord mesenchymal stem cells; safety; molecular mechanism". Based on the inclusion and exclusion criteria, 55 articles were finally reserved for review. RESULTS AND CONCLUSION: UC-MSCs have obvious effect on treating glioma. These cells can treat glioma through homing mechanism and paracrine mechanism as gene carrier and co-culture. Moreover, UC-MSCs have certain safety in the treatment of glioma.
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Objective To knockout the exon51 of DMD gene in HEK293T cells using the CRISPR/Cas9 system. Methods Design the target sequences of sgRNA and clone them into plasmid PX459 respectively; transfer these plasmids into HEK293T cell and extract the total genome DNA; test the activity of sgRNAs with surveyor assay, choose the most efficient one in each end;construct plasmid PX459-2sgRNA and transfer it into HEK293T cells;check whether the exon51 has been knocked known with PCR and T vector sequencing. Results 50% of HEK293T cells' DMD gene exon51 were knocked out,showing a high gene editing efficiency. Conclusions We successfully establish a platform to target knockout the exon51 of DMD gene and provide an important experimental basis for the treatment of DMD and other genetic diseases.
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Objective To evaluate the pharmacokinetics, drug concentration and effect relationship of PEGylated IL-11 mutein (PEG-mIL11) in cynomolgus monkeys through the validated anti-PEG-ELISA method. Methods PEG-mIL11 at 350 μg/kg was subcutaneously injected in cynomolgus monkeys, and the blood samples were collected at various time points. An anti-PEG-ELISA method was validated and used to investigate the concentration of PEG-mIL11, and platelet counts were measured to explore the relationship of drug concentration and effect. Results Results of the validation test demonstrated that PEG-mIL11 in monkey blood could be quantitated by anti-PEG-ELISA. Its linear range was (26.34-200) ng/ml. The specificity, accuracy and precision of the method met the present criteria. The terminal elimination half-life (T1/2) of PEG-mIL11 was (13.4 ± 2.4) h, the peak time (Tmax) was (6.7 ± 2.3) h, the peak concentration (Cmax) was (2.4 ± 0.5) μg/ml, the area under curve (AUC)(0-t) was (77.7 ± 15.6) μg∙h/ml, and the clearance (CL) was (4.6 ± 0.8) ml/ (h·kg). The thrombopoietic effect did not relate directly with the concentration of PEG-mIL11 in serum. Conclusion Anti-PEG-ELISA, used in this study to measure the concentration of PEG-mIL11, is a steady, reliable and specific method for PEGmIL11 pharmacokinetic study, and its chemical modification by PEG possesses long circulating half-lives, thereby suggesting less frequency of administration.
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<p><b>OBJECTIVE</b>To evaluate the effect of PEGylated IL-11 mutein (PEG-mIL 11) with different dose or injection frequency on thrombocytopenia in myelosuppressed mice and to compare its effect with mIL-11, so as to provide reference data for clinical use.</p><p><b>METHODS</b>Myelosuppressive model with thrombocyopenia was produced in BALB/c mice by whole bodyCo γ-ray irradiation in dose of administration 2.5 Gy followed by i.p. injections of carboplatin at 50 mg/kg. In study of injection frequency, 30 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1, 4, 7), mIL-11 group [200 µg/(kg·d)×9 d], PEG-mIL 11 A group [111800 µg/(kg·d)×1 d (d 1)], PEG-mIL 11 B group 900 µg/(kg·d)×2 d (d 1,5), and PEG-mIL 11 C group [600 µg/(kg·d)×3 d (d 1,4,7)]. The route of administration is subcutaneous injection. The platelet counts were monitored in the subsequant 5 weeks. In study of dose administration, 100 thrombocytopenic BALB/c mice were randomly divided into 5 groups: vehicle control group (once daily on d1 and 5), mIL-11 group 200 µg/(kg·d)×9 d, and PEG-mIL 11 low-, mid-, and high-dose groups (200, 420 and 900 µg/(kg·d)×2 d, once a day on d1 and 5). The route of administration is subcutaneous injection. The platelet counts were monitored every 2-3 days in the subsequant 5 weeks, and CFU-Meg was determined on d 8 of the bone marrow cells collection.</p><p><b>RESULTS</b>AfterCo irradition and carboplatin injection, Plt level decreased with time, and a >80% reduction was noted at nadir when comparing with baseline. In frequency of administration study, the platelet nadir of the 3 PEG-mIL 11 groups were significantly higher than that of vehicle control and mIL-11 groups (P<0.05), while no significant difference was noted among the 3 groups of different administration frequences; In dose level study, the reduction of Plt count at the nadir in the 3 PEG-mIL 11 groups was significantly less than that of vehicle control and mIL-11 groups (P<0.05). And a rapid recovery of Plt count was found in the PEG-mIL 11 groups with a dose-dependent increase of Plt count on d 10. A lower reduction and a rapider recovery of RBC was also found in the PEG-mIL 11 groups. No significant effect on WBC was found for all the treatment groups. An increase in CFU-Meg was observed in PEG-mIL 11 and mIL-11 groups, with higher CFU-Meg in PEG-mIL 11 groups.</p><p><b>CONCLUSION</b>A preventive effect of PEG-mIL 11 on thrombocytopenia in myelosuppressed mice has been confirmed. In comparison with mIL-11, a better effect of PEG-mIL 11 is obtained under lower dose frequency, indicating a better compliance of the treatment regimen, and providing a foundation for developing a long-acting preparation of rhIL-11.</p>
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<p><b>OBJECTIVE</b>To investigate the effect of Sarcandra glabra in scavenging reactive oxygen species (ROS) produced by γ-ray irradiation in the parotid gland of miniature pigs.</p><p><b>METHODS</b>Forty-five male miniature pigs were randomly divided into control group, radiation group and radiation plus medication group, and each group contained 3 parallel groups (subgroups a, b and c). From 1 week before exposure of the parotid gland region to 15 Gy γ-ray irradiation (which was not administered in the control group), the miniature pigs in radiation plus medication group were given Sarcandra glabra powder, while those in the other groups received an equal amount of saline. Bilateral parotid glands were taken and weighed on the days 10, 40 and 90 following the exposure in subgroups a, b, and c, respectively, and ROS content in the parotid glands were determined by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The content of ROS was significantly lower in radiation plus medication group than in the radiation group (P<0.01). In the radiation plus medication group, the ROS content showed no significant difference between subgroups a and b or between subgroups a and c (P>0.01), but differed significantly between subgroups b and c (P<0.01). Sarcandra glabra showed a strong ROS-scavenging effect 10 days after the irradiation, and the ROS content was similar with that in the control group (P>0.01); at 40 and 90 days, the ROS-scavenging effect of Sarcandra glabra was still observable, but the ROS content was significantly higher in the irradiation plus medication group than in the control group (P<0.01).</p><p><b>CONCLUSION</b>Sarcandra glabra displays a ROS-scavenging effect in the parotid gland of miniature pigs against irradiation, especially at 10 days following the exposure, which may serve as the main mechanism for the protective effect of Sarcandra glabra against radiation injury in the parotid gland.</p>