Sorafenib-Loaded Long-Circulating Nanoliposomes for Liver Cancer Therapy.

A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo. The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8 ± 4.2 nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy.

Engineering natural matrices with black phosphorus nanosheets to generate multi-functional therapeutic nanocomposite hydrogels.

Natural polysaccharides and proteins have been widely explored for the preparation of hydrogel matrices due to their promising biocompatibility and biodegradability. However, it is challenging to achieve multiple functions of the hydrophilic matrix through convenient functionalization strategies. Herein we report the facile engineering of a natural matrix with black phosphorus (BP) nanosheets as building blocks to generate a therapeutic nanocomposite hydrogel (BP/Gel) with an array of promising features. BP nanosheets could reinforce the crosslinking networks and significantly promote their capabilities of mineralization. The BP/Gel nanocomposite hydrogel exhibits excellent near infrared (NIR) photothermal performance and good biocompatibility in vitro and in vivo. Upon NIR irradiation, the nanocomposite hydrogel demonstrates efficient photothermal antibacterial features. More remarkably, the BP nanosheet engineered hydrogel matrix is capable of promoting in vitro osteogenesis in the absence of osteoinductive factors, and in the meantime demonstrates significant newborn cranial bone tissue formation in a Sprague-Dawley rat model. These results demonstrate that BP nanosheets could endow the natural matrix with multiple functions including reinforced networks, photothermal performance, enhanced mineralization and bone regeneration, which provides a facile and highly efficient therapeutic strategy for bone tissue engineering.

Design and Synthesis of Soluble and Cell-Permeable PI3Kδ Inhibitors for Long-Acting Inhaled Administration.

PI3Kδ is a lipid kinase that is believed to be important in the migration and activation of cells of the immune system. Inhibition is hypothesized to provide a powerful yet selective immunomodulatory effect that may be beneficial for the treatment of conditions such as asthma or rheumatoid arthritis. In this work, we describe the identification of inhibitors based on a thiazolopyridone core structure and their subsequent optimization for inhalation. The initially identified compound (13) had good potency and isoform selectivity but was not suitable for inhalation. Addition of basic substituents to a region of the molecule pointing to solvent was tolerated (enzyme inhibition pIC50 > 9), and by careful manipulation of the pKa and lipophilicity, we were able to discover compounds (20b, 20f) with good lung retention and cell potency that could be taken forward to in vivo studies where significant target engagement could be demonstrated.

Hybrid facial image feature extraction and recognition for non-invasive chronic fatigue syndrome diagnosis.

Due to an absence of reliable biochemical markers, the diagnosis of chronic fatigue syndrome (CFS) mainly relies on the clinical symptoms, and the experience and skill of the doctors currently. To improve objectivity and reduce work intensity, a hybrid facial feature is proposed. First, several kinds of appearance features are identified in different facial regions according to clinical observations of traditional Chinese medicine experts, including vertical striped wrinkles on the forehead, puffiness of the lower eyelid, the skin colour of the cheeks, nose and lips, and the shape of the mouth corner. Afterwards, such features are extracted and systematically combined to form a hybrid feature. We divide the face into several regions based on twelve active appearance model (AAM) feature points, and ten straight lines across them. Then, Gabor wavelet filtering, CIELab color components, threshold-based segmentation and curve fitting are applied to extract features, and Gabor features are reduced by a manifold preserving projection method. Finally, an AdaBoost based score level fusion of multi-modal features is performed after classification of each feature. Despite that the subjects involved in this trial are exclusively Chinese, the method achieves an average accuracy of 89.04% on the training set and 88.32% on the testing set based on the K-fold cross-validation. In addition, the method also possesses desirable sensitivity and specificity on CFS prediction.

[Determination of aromadendrin in Euonymus alatus by HPLC].

OBJECTIVE: To establish a HPLC method to determine the content of aromadendrin in Euonymus alatus. METHOD: Kromasil 100-5C18 column was used with a mobile phase composed of acetonitrile-0.3% glacial acetic acid (24:76) at a flow rate of 1.0 mL x min(-1). The detection wavelength was 292 nm and the temperature of column was 30 degrees C. RESULT: The calibration curve was linear in the range of 0.051-2.04 microg for aromadendrin. The correlation coefficient of the calibration curve was 0.999 9. Twenty batches of the crude E. alatus purchased from different areas were determined and the contents of aromadendrin in the twigs of E. alatus were fluctuated from 0.001 57% to 0.041 6%. CONCLUSION: This method is simple, repeatable and can be used for determination of aromadendrin.

[Effect of Xuesaitong drop pills on experimerntal thrombosis and thrombolysis in rats].

OBJECTIVE: To study the effect and the mechanism of Xuesaitong drop pills (total saponins in Radix Notoginseng; XDP) on experimental thrombosis, thrombolysis and blood theology. METHOD: First, the rats were randomly divided into five groups: control, XDP (90, 30, 10 mg x kg(-1)), Xuesaitong tablet (XP) 30 mg x kg(-1). Then the effect of the drugs on thrombus and thrombosis was studied after the ratsthrombosis was induced by the arteriovenous shunt. Second, the rats were randomly divided into seven groups: model, XDP (90, 30, 10 mg x kg(-1)), XT (90, 30 mg x kg(-1)), lumbrukinase capsule. Then the effect of the drugs on thrombus and thrombosis was studied after the rats'thrombosis was induced by the electrical stimulation of common carotid artery. Third, the rats were randomly divided into six groups: control, model, XDP (80, 40 mg x kg(-1)), XT (40, 20 mg x kg(-1)). Then the effect of the drugs on blood circulation promoting was observed after the rats'acute blood stasis induced by adrenalin and icy water. RESULT: XDP 90, 30 mg x kg(-1) could notably lighten the wet-weight and dry-weight of thrombus in the arteriovenous shunt model in rats in a dose-dependent manner (P < 0.01). XDP 90 mg x kg(-1) with intragastric administration for 3 days had the satisfactory effect on thrombolysis after the rat's thrombosis was induced by the electrical stimulation of common carotid artery (P < 0.01). XDP 80, 40 , 20 mg x kg(-1) reduced significantly erythrocyte aggregation (P < 0.01) and decreased the whole blood viscosity at low shear rate (P < 0.05). XDP 80, 40 mg x kg(-1) reduced the whole blood viscosity at high shear rate and plasma viscosity (P < 0.05). XDP 80 mg x kg(-1) decreased the whole blood viscosity at high shear rate (P < 0.05). CONCLUSION: XDP can significantly inhibit the thrombosis and has the satisfactory effect on thrombolysis. One kind of the mechanism is related to the effect on blood rheology.