Co-delivery of paclitaxel and doxorubicin using polypeptide-engineered nanogels for combination therapy of tumor.

Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt%, 70 wt%, and 8.55 wt%, 83 wt%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. Thein vitroandin vivoantitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.

Effects of heating or ultrasound treatment on the enzymolysis and the structure characterization of hempseed protein isolates.

The effects of heating (90 °C/30 min) or ultrasound (200/400/600 W) treatment on antioxidant and angiotensin-converting enzyme inhibitory (ACEI) activity of hydrolysates from hempseed protein isolates (HPI) were studied. The secondary structure, surface hydrophobicity, intrinsic fluorescence, scanning electron microscopy (SEM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of HPI treated by heating or ultrasound were measured. The results showed that hydrolysate from HPI treated with ultrasound at 200 W showed higher hydrolysis degree, proportion of lower molecular mass components (1.0-3.0 kDa), antioxidant and ACEI activity than those from heating or high-power treated. The changes in secondary structure, surface hydrophobicity and intrinsic fluorescence indicated the unfolding of HPI after ultrasound. The SEM results showed that HPI treated with ultrasound at 200 W exhibited decrease in particle size and deformation and further increased in power caused the aggregates of HPI. In conclusion, the ultrasound treatment at low-power was superior to 90 °C/30 min treatment in facilitating enzymatic release of antioxidant and ACEI peptides from HPI.

Effects of high-intensity ultrasound treatment on functional properties of plum (Pruni domesticae semen) seed protein isolate.

BACKGROUND: In order to improve the functional properties of plum seed protein isolate (PSPI), the effects of high-intensity ultrasound (20 kHz) at different levels of power output (200, 400 and 600 W) on the water/oil holding, solubility, emulsifying, foaming, gel, film formation capacity and hydrolysis degrees of PSPI were investigated. RESULTS: Compared with untreated PSPI, ultrasound treatment improved water holding capacity, solubility, emulsifying properties, foaming capacity of PSPI. The gel prepared from ultrasound treated PSPI showed the higher gel strength compared with untreated protein. The film prepared from ultrasound treated PSPI showed higher tensile strength, lower elongation and permeability, denser and more compact microstructure compared with untreated protein. Ultrasonic treatment also improved the accessibility of PSPI to the protease (Alcalase, Trypsin, Neutrase, Protamex, Papain and Flavourzyme). Furthermore, the ultrasonic treatment could induce a decrease in particle size and relative fluorescence intensity, an increase in surface hydrophobicity, and changes in secondary structure and microstructure of PSPI. CONCLUSION: The changes in structure analysis of PSPI indicated that ultrasound treatment could induce molecular unfolding of protein, which might be helpful for improving the functional properties and efficiency of enzymatic hydrolysis. © 2018 Society of Chemical Industry.

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

BACKGROUND: Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. METHODS: In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. RESULTS: Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. CONCLUSION: These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

[Early intravenous thrombolysis with recombinant tissue plasminogen activator for acute cerebral infarction].

OBJECTIVE: To evaluate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) and to explore the most suitable dosage of rt-PA in the early treatment of the Chinese patients with acute cerebral infarction (ACI). METHODS: The patients who suited for the standard were divided into three groups. Group A received rt-PA at 0.9 mg/kg, group B received rt-PA at 0.7 mg/kg, and group C did not receive any thrombolytic therapy. In thrombolytic groups, rt-PA at 8 mg was injected intravenously in a bolus at first and then the rest was given over 60 minutes. The maximal dosage was 90 mg. The Chinese stroke scale (CSS) and Barthel Index (BI) were used to evaluate the recovery of neurological functions after rt-PA treatment for 24 hours and 90 days. The hemorrhagic rate and 30 days mortality rate were also analysed. RESULTS: In group A the CSS significant effective rate was 41.18 percent at 24 hours and 76.47 percent at 90 days after thrombolysis. At 90 days BI significant effective rate was 58.82 percent. At 30 days hemorrhagic rate was 8.82 percent and mortality rate was 5.88 percent. In group B, the CSS significant effective rate was 39.39 percent at 24 hours and 69.70 percent at 90 days. At 90 days, BI significant effective rate was 54.55 percent, and at 30 days, hemorrhagic rate was 9.09 percent and mortality rate was 9.09 percent. In group C, the CSS significant effective rate was 21.21 percent, at 24 hours and 30.30 percent at 90 days (P>0.05). At 90 days, BI was 21.21 percent the mortality rate was 9.09 percent. At 30 days the mortality rate was no significant difference within three groups At 90 days, significant effective rate was 73.13 percent vs. 30.30 percent in thrombolytic and control groups (P=0.001 7). The significant disability rate was 13.43 percent vs. 24.24 percent. CONCLUSION: For Chinese individuals, with ACI, rt-PA thrombolysis was effective and safe. The dosage of 0.9 mg/kg for foreign people also fitted for Chinese individuals.

[Morphological and histological study on Pteris multifida].

The thesis studies on the pharmacognostical characteristics of Pteris multifida were carried out in this paper. The blade has special vein-like cell. The stomas in dorsal epidermis are regular. The petiol has V-shaped amphicribral bundles. The rhizome has 6-8 meristeles. The triangle-form spore has tumor-shaped or pellet-shaped decorations on its surface.