The grading quality markers identification of Panax notoginseng under the guidance of traditional experience using untargeted metabolomics and anti-myocardial ischemia evaluation of zebrafish.

BACKGROUND: Panax notoginseng (PN) was an edible Chinese herbal medicine. PN's current quality control standard cannot precisely match the traditional grading experience. PURPOSE: In this study, under the guidance of the traditional grading experience, the combined metabolomics and biological effect evaluation were used to reveal the distinct chemical quality of PN. METHODS: The quality of PN was evaluated by traditional experience and characterized by the electronic tongue. A zebrafish myocardial ischemia model was developed to verify the grading experience. The untargeted metabolomics method was used to identify and validate the grading markers of PN. RESULTS: The taste was the critical indicator for classifying the quality. Based on the experience sensory scores (ranged from 47.0 to 87.8), PNs could be divided into two grades. The experience scores were significantly associated with umami and richness of the electronic tongue(p<0.01). Besides, superior PN showed substantially stronger anti-myocardial ischemia activity(p<0.001). Thirty-nine differential components were found using UHPLC-LTQ-Orbitrap MS, of which 22 were identified. A new kind of grading quality markers alkynols in PN-associated efficacy was identified, which revealed stronger anti-myocardial ischemia activities than saponin. CONCLUSION: This study evaluated PN through untargeted metabolomics and anti-myocardial ischemia evaluation of zebrafish and proposed the critical role of alkynols in PN's quality classification.

Preparation of carboxylic graphene oxide-composited polypyrrole conduits and their effect on sciatic nerve repair under electrical stimulation.

Carboxylic graphene oxide-composited polypyrrole/poly-l-lactic acid (C-GO/PPy/PLLA) films were fabricated by electrochemical deposition of C-GO-composited PPy on PLLA fibers-film, and their conductivity and tensile strength (∼4.6 S/cm and 26.4 MPa, respectively) were stably remained after the immersion of 4 weeks, due to the hydrogen bond interaction between graphene oxide's carboxylic groups and pyrrole's imino groups. Their specific surface areas of ∼57.5 m2 /g and pore volume of ∼0.02 cm3 /g were significantly larger than those of PPy/PLLA films, due to the addition of C-GO nanosheets. Then, C-GO/PPy/PLLA conducting conduit with 2 mm inner diameter was prepared to bridge 10 mm sciatic nerve defect of rats, and the direction of fiber-axis in the conduit was the same as the conduit central axis. Electrical stimulation (ES) of 1 V and 20 Hz through the conducting conduit was exerted on the defect site. The results of in vivo electrophysiological and histological evaluation indicated that, the sciatic nerve defect could be repaired in C-GO/PPy/PLLA conduit, moreover the re-innervated gastrocnemius muscle and nerve conduction in C-GO/PPy/PLLA conduit & ES group were obviously better than the conduit without ES group. The results of transmission electron microscope analysis also demonstrated that the mean thickness of myelin sheath and diameter of axon in C-GO/PPy/PLLA conduit & ES group were significantly larger than those without ES, suggesting that the repair efficiency of ES & conduit group was closer to that of autograft group. These results indicated the great potential of C-GO/PPy/PLLA with the in vivo ES in the application of sciatic nerve repair.

HAp@GO drug delivery vehicle with dual-stimuli-triggered drug release property and efficient synergistic therapy function against cancer.

Nanoscale hydroxyapatite (HAp) is an optimal candidate material in biomedical area for its good biocompatibility and bioactivity. In this study, HAp nanorods are prepared via hydrothermal method and combined with monolayered graphene oxide (GO). The obtained HAp@GO with excellent biocompatibility is revealed to have high drug loading capacity (698.7 µg/mg) for anticancer drug doxorubicin (DOX) and efficient photothermal conversion property. And the drug release property of DOX loaded HAp@GO (HAp@GO-DOX) is demonstrated to be controlled by pH and near-infrared light, which is favorable for cancer therapy. in vitro studies on cancer therapy demonstrate that the combined treatment, compared with either chemotherapy or photothermal therapy alone, has better synergistic therapeutic effect. These findings prove the great potential application of the nanocomposites for cancer therapy.

Cobalt nanowire-based multifunctional platform for targeted chemo-photothermal synergistic cancer therapy.

Cobalt nanowires (CoNWs) simultaneously possessing advantages in photothermal effect, targeting drug delivery and photoacoustic imaging property are hopefully promising strategies to further improve the treatment efficiency and reduce the side effects of cancer chemotherapy. Herein, a unique cobalt-based structure decorated with graphene oxide (GO) and polyethylene glycol (PEG) is fabricated through a facile approach. The resultant nanohybrids show relatively low cytotoxicity, favorable biocompatibility as well as inherit the outstanding properties of cobalt. Moreover, CoNWs decorated with GO and PEG (CoNWs-GO-PEG) can load therapeutic drug molecules (e.g., doxorubicin, DOX) with a high drug loading capacity (992.91 mg/g), and simultaneously they are responsive to pH, NIR (near-infrared) irradiation and magnetism stimulation. Accordingly, CoNWs-GO-PEG-DOX shows the satisfactory effect of eliminating cancer cells with synergistic chemo-photothermal therapy in vitro. Current work provides a solid demonstration of the potential of CoNWs-GO-PEG for serving as a targeted antitumor agent in synergistic chemo-photothermal therapy.

Biomimetic Mineralization of Magnetic Iron Oxide Nanoparticles Mediated by Bi-Functional Copolypeptides.

Magnetite (Fe3O4) nanoparticles are widely used in multiple biomedical applications due to their magnetic properties depending on the size, shape and organization of the crystals. However, the crystal growth and morphology of Fe3O4 nanoparticles remain difficult to control without using organic solvent or a high temperature. Inspired by the natural biomineralization process, a 14-mer bi-functional copolypeptide, leveraging the affinity of binding Fe3O4 together with targeting ovarian cancer cell A2780, was used as a template in the biomimetic mineralization of magnetite. Alongside this, a ginger extract was applied as an antioxidant and a size-conditioning agent of Fe3O4 crystals. As a result of the cooperative effects of the peptide and the ginger extract, the size and dispersibility of Fe3O4 were controlled based on the interaction of the amino acid and the ginger extract. Our study also demonstrated that the obtained particles with superparamagnetism could selectively be taken up by A2780 cells. In summary, the Fe3O4-QY-G nanoparticles may have potential applications in targeting tumor therapy or angiography.

Chitosan-based asymmetric topological membranes with cell-like features for healthcare applications.

Chitosan-based guided tissue regeneration (GTR) membranes are extensively used in orthopedic/stomatological regenerative medicine since chitosan shares many chemical and structural similarities with glycosaminoglycans (GAGs) in the extracellular matrix. However, the available chitosan-based GTR membranes mostly lack topological features of natural tissues, resulting in unsatisfactory biocompatibility. To address this limitation, we developed a novel biologically-inspired asymmetric topological chitosan (ATCS) membrane supported by a nanoporous anodic aluminum oxide (AAO) template. We, thereafter, investigated the mechanical properties, degradation, and cytocompatibility of the ATCS membranes and compared them with those of the symmetric chitosan (SyCS) membranes, produced with a smooth Al template. The asymmetric topological structure significantly increased the tensile strength but decreased the extent of degradation of the ATCS membranes compared to those of SyCS. In the in vitro studies, the ATCS membranes outperformed the SyCS membranes in cytocompatibility due to their cell-like features. In addition to the ATCS membranes, the ethylene vinyl acetate (EVA) membranes with a similar cell-like structure were successfully fabricated using the AAO template to verify the universality of the AAO template-assisted technique. Accordingly, the AAO template-assisted strategy, defined in this study, is an innovative, universal, and facile way to fabricate polymeric asymmetric membranes with cell-like features. The bioengineered ATCS membranes with tunable degradability, prominent mechanical properties and biocompatibility are promising candidates for orthopedic healthcare applications.

Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.

BACKGROUND: Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF). METHODS: This study will be an 8-week double-blinded, randomized, placebo-controlled clinical trial conducted at Guang'anmen Hospital in Beijing, China, and 168 patients with moderately active RA will be randomly assigned with a 1:1 ratio to apply a topical gel preparation containing TwHF or placebo. The primary outcome variable will be the proportion of subjects, by study group, to achieve a 20% improvement in the American College of Rheumatology criteria (ACR20) by week 8. Secondary outcome measures to be assessed at weeks 4 or 8 will include: measurement of ACR20 response rate at week 4, ACR50 response rate, the changes in DAS28 score, and joint synovitis classification assessment monitored by musculoskeletal ultrasound. Safety evaluations conducted at weeks 4, 8 and 12 will be based on spontaneous complaints by the study subjects, but special emphasis will be focused on cutaneous allergy and alterations of menstruation in premenopausal female participants. Statistical analyses will be performed using the intention to treat analysis data set. DISCUSSION: This proposed clinical trail is designed to evaluate the efficacy and safety of CET based on a single topically-applied agent in a relatively large patient population with RA. This study protocol gives a detailed description of the usage and dosage of the topical compound TwHF gel and the methodology of this study. In addition, it is hoped that the outcomes of this study will be viewed as supporting the generalizability of CET in the setting of inflammatory rheumatic diseases. The results of this study are expected to have important public health implications for Asian RA patients that currently utilize CET as a complimentary treatment. TRIAL REGISTRATION: Clinical trial gov Identifier: NCT02818361 . Registrated on Jun. 15, 2016.

Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts.

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.

Fabrication of conductive NGF-conjugated polypyrrole-poly(l-lactic acid) fibers and their effect on neurite outgrowth.

In order to fabricate a tissue scaffold with the neurotrophic and electrical activities, conductive nerve growth factor (NGF)-conjugated polypyrrole-poly(l-lactic acid) (PPy-PLLA) composite fibers were prepared by oxidation polymerization and EDC chemistry with poly-l-lysine. PPy nanoparticles (∼70nm diameter) accumulated on PLLA fiber surface to form a rough thick shell (∼200nm thickness). These NGF-conjugated PPy-PLLA fibers could support PC12 neurite outgrowth and extension. Especially, 40% and 74% increase in PC12 neurite outgrowth and extension, respectively, could be obtained under electrical stimulation of 100mV/cm voltages through the composite fibers. A mechanism for the interaction between neurite extension and the NGF-conjugated PPy-PLLA fibers under electro-stimulation was proposed, to explain the synergistic effect of the rough PPy shell, conjugated NGF and electricity on neurite outgrowth and elongation.

[Study on purification process of depsides in Salvia miltiorrhiza with macroporous resin].

OBJECTIVE: To study the technological parameters of the purification process of Depsides in Salvia miltiorrhiza with macroporous resin. METHOD: The adsorptive characteristics and eluting parameters of the process were studied by taking the content of depsides as index. RESULT: 85 mL of extractive of depsides (1.25 g x mL(-1)) was purified with a column of macroreticular resin ( Phi30 mm,127 mL) and washed with 4 BV of distilled water, the eluted with 4 BV of 80% ethanol (1% ammonia). CONCLUSION: This process of applying macroporous resin to adsorb and purify depsides in S. miltiorrhiza is feasible.

[Effect of the sustained release excipients on the release rate of ginsenoside Rg1 and ginsenoside Rb1 in sustained-release tablet of Panax notoginsenosides].

OBJECTIVE: To study the influence of the sustained release excipient on the release rate of ginsenoside Rg1 and ginsenoside Rb1 in sustained-release tablet of Panax Notoginsenosides. METHOD: The release rate of ginsenoside Rg1 and ginsenoside Rb1 in different matrix tablets with different excipient (HPMC, EC), different viscosity of EC (RT-50, RT-100), different ratio of EC in matrix tablet were detected. RESULT: All above different factors influence the release rate of ginsenoside Rg1 and ginsenoside Rb1 and brought them different release curve. CONCLUSION: Emphasis should be laid on the different release characteristic of different active compounds in active fraction.