Systematic Comparison of Structural Characterization of Polysaccharides from Ziziphus Jujuba cv. Muzao.

To investigate the structural information differences of Ziziphus Jujuba cv. Muzao polysaccharides, ten samples were successfully extracted from aqueous and alkaline solutions, prepared via DEAE-Sepharose Fast Flow through different eluents and Sephacryl S-300 columns, and systematically analyzed. Their characteristics were studied and then compared using chemical testing, high-performance gel permeation chromatography (HPGPC), gas chromatography (GC), methylation analysis, and NMR spectroscopy. The data achieved demonstrated that different jujube polysaccharide fractions possessed different structural characteristics, and most of them belonged to pectic polysaccharides. Overall, the structural information difference of jujube polysaccharides was preliminarily illuminated, which could not only promote the potential application of Z. Jujuba cv. Muzao polysaccharides but also provide an effective way to analyze the structures of polysaccharides from other genera jujube fruit.

Preparation and related properties of melanin iron supplement.

In this study, BM-Fe (black sesame melanin-iron complex) was prepared and characterized. The results showed that the carboxyl hydroxyl group of BSM (black sesame melanin) participated in the chelation of iron ions. EDS (energy dispersive spectroscopy) and XPS (X-ray photoelectron spectroscopy) results confirmed the presence of iron ions in BM-Fe. The results of DLS (dynamic light scattering) showed that the average particle sizes of BSM and BM-Fe were 844.9 nm and 294.3 nm, respectively, indicating that the structure of BM-Fe with a smaller particle size was formed after the binding of iron ions with the active group on BSM. Finally, the in vitro iron dissolution, iron ion identification, in vitro iron ion reduction, antioxidant activity, cytotoxicity and moisture resistance properties of BM-Fe and FST (ferrous sulfate tablets, a commonly used iron supplement) were comprehensively compared. The results showed that BSM combined with iron instead of physically mixing, and BM-Fe was easily reduced in the gastrointestinal environment. BM-Fe had good bioavailability and retained the excellent characteristics (such as oxidation resistance and biocompatibility) of BSM, and had the potential to be applied in the treatment of iron-deficiency-related diseases. In summary, BM-Fe prepared in this study not only retained the excellent characteristics of BSM but also had a good effect on iron supplementation, high bioavailability and low side effects. Comprehensive analysis showed that the performance of BM-Fe prepared in this study was similar to or even better than that of the control (FST). Thus, BM-Fe is expected to become a new comprehensive multi-functional iron supplement and has a broad developmental prospect.

Development of a novel capillary electrophoresis-based approach for detection of anti-drug antibody responses.

Peggy Sue is a capillary-based western/immunoassay platform that can separate and characterize proteins by size or charge. A quick and automated immunogenicity assay was developed on Peggy Sue based on charge separation and compared with a traditional bridging method using preclinical samples from non-human primate studies. The results generated with the Peggy Sue assay were comparable to those of the bridging assays. The Peggy Sue platform has several advantages, including time efficiency, low sample consumption, and easy automation. The platform is especially ideal for further characterization of anti-drug antibody (ADA) specificity against complex biologics such as bispecific or multi-specific biotherapeutics as it is easy to conduct domain specificity assessment of observed ADA responses. Our evaluation suggests that the Peggy Sue platform is a promising tool for preclinical ADA analysis.

A study on the paraspinal muscle surface electromyography in acute nonspecific lower back pain.

Aim of this study was to determine if surface electromyography (sEMG) could provide objective data in monitoring the alteration of signal amplitude of myoelectric activity of the paraspinal muscles in the patients with acute nonspecific lower back pain (ANLBP), and to explore the correlation between sEMG data and symptom relief in the ANLBP patients before and after massage therapy.Forty-five ANLBP patients and 20 healthy subjects were enrolled into this study. Patients were given massage therapy for 1 week. The average electromyography (AEMG), visual analogue scale (VAS), and distance of finger to floor (DFTF) were measured before and after treatment.AEMG at flexion and maintained flexion positions were significantly higher in the ANLBP group compared to that in the control group. At extension position, in contrast, AEMG was significantly lower in the ANLBP patients than that of control group, and there was no significant difference between the 2 groups at upright position. After massage therapy for the ANLBP patients, AEMG was significantly reduced at flexion and maintained flexion positions, but significantly increased at extension position than that before treatment. VAS and DFTF were also significantly reduced after treatment. In addition, AEMG alteration at maintained flexion position was significantly correlated with improvement of VAS or DFTF.Myoelectric activity of the paraspinal muscles in the ANLBP patients was different from that of healthy subjects. Massage therapy not only relived patients' symptoms, but also normalized myoelectric activity of the paraspinal muscles in the ANLBP patients.

Pharmacokinetic Properties of Humanized IgG1 and IgG4 Antibodies in Preclinical Species: Translational Evaluation.

Assessment of the factors that regulate antibody exposure-response relationships in the relevant animal models is critical for the design of successful translational strategies from discovery to the clinic. Depending on the specific clinical indication, preclinical development paradigms may require that the efficacy or dosing-related attributes for the existing antibody be assessed in various species when cross-reactivity of the lead antibody to the intended species is justified. Additionally, with the success of monoclonal antibodies for management of various human conditions, a parallel interest in therapeutic use of these novel modalities in various veterinary species has followed. The protective role of neonatal Fc receptor (FcRn) in regulation of IgG homeostasis and clearance is now well recognized and the "nonspecific clearance" of antibodies through bone marrow-derived phagocytic and vascular endothelial cells (via lysosomal processes) is modulated by interactions with FcRn receptors. In this study, we have attempted to examine the PK properties of human IgG antibodies in dog and monkey. These studies establish a translational framework for evaluation of IgG antibody PK properties across species.

Lipidomics to investigate the pharmacologic mechanisms of ginkgo folium in the hyperuricemic rat model.

Hyperuricemia caused by purine metabolic abnormalities is reported to have close correlation with lipid metabolic disorders. Ginkgo folium, a frequently-used lipid-lowering medicine, has significant anti-hyperuricemia effects. However, it is poorly known about the interaction between lowering uric acid and regulation of lipid metabolic disorders. In this study, hyperuricemic rat model was induced by orally administration with fructose. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with pattern recognition approaches were used to determine different lipid metabolites in serum of control group, model group, and different doses of ginkgo folium groups. Principal component analysis (PCA) was applied to analyze the MS data to assess the establishment of model, partial least squares-discriminate analysis (PLS-DA) and independent samples T-test were performed to indicate the differences between different groups of rats and to find biomarkers. Metabolomics pathway analysis (MetPA) was introduced to reveal the pharmacologic mechanisms of ginkgo folium. 19 potential biomarkers associated with hyperuricemia were found. After intervened by ginkgo folium, these biomarkers were returning to normal level. Among these biomarkers, 13 lipid biomarkers were significantly reversed. Ginkgo filum can lower uric acid via adjusting back the level of PCs and LPCs, which suggested that its treatment mechanisms may be related to reducing the activity of PLA2. In sum, the lipidomics analysis in the system level have enhanced our understanding to pathogenesis of hyperuricemia and the results suggested that ginkgo folium could alleviate the abnormal metabolic status of hyperuricemia. These results demonstrated a new mechanism for lowering uric acid, which was helpful to the early treatment for hyperuricemia.

[Lipid metabolomics in serum of hyperuricemic rats induced by fructose based on UPC²-Q/TOF-MS].

To explore the differences in lipid metabolites in serum of hyperuricemic rats induced by fructose and normal rats by using lipid metabolomics technology, and screen the potential biomarkers related to hyperuricemia. The metabolic fingerprint spectrum of the serum in hyperuricemic rats(model group) and normal rats(control group) was obtained and analyzed by using ultra performance convergence chromatography-tandem-Q-time of flight mass spectrometry(UPC ² -Q/TOF-MS) method and the differences of metabolic spectra between two groups were compared via the multivariate statistical methods to screen differential metabolites. The results indicated that there was significant difference in metabolic spectra between model group and control group, and 11 differential metabolites were screened. Then eight potential biomarkers such as arachidonic acid, palmitic acid, oleic acid and linoleic acid were tentatively identified by using the exact mass number and secondary mass spectrometry(MS/MS spectrum). Therefore, a new research method for lipid metabolomics in serum of hyperuricemic rats induced by fructose was established successfully based on UPC ² -Q/TOF-MS. What's more, it was speculated that the abnormal metabolism of fatty acid might be associated with the pathogenesis of hyperuricemia, which would provide scientific basis for early detection and prevention of hyperuricemia.

[Establishment of culture system of Silybum marianum hairy roots and determination of silybin].

This research uses six Agrobacterium rhizogenes R1601, R15384, R1000, A4, R1025 and R1 to infect silymarin explants to induce hairy roots and silibin. All of the six A. rhizogenes can induce Silybum marianum to generate hairy roots and the A. rhizogene A4 shows comparatively high infection on the plant. This research determines the condition to induce silymarin hairy roots by the factors of infection time, pre-culturing, co-culturing and pH value. The fact that MS liquid medium fits the proliferation of silymarin hairy roots is determined. Through PCR molecular identification, it can be seen that the DNA plasmids in the A. rhizogenes are successfully integrated into the genome of transformed roots. Using liquid chromatography, it is determined that the silibin content in silymarin hairy roots is 2.5 times that in the plant In this research, the silymarin hairy roots culturing system is established, which lays a foundation for the study of culturing silymarin hairy roots and producing silibin.