Daidzin decreases blood glucose and lipid in streptozotocin-induced diabetic mice

Purpose: To investigate the ameliorative effect of daidzin (DZ) on diabetes in streptozotocin (STZ)- induced diabetic Institute of Cancer Research (ICR) mice, with a view to determining its usefulness in the treatment of diabetes.Methods: The effect of DZ (100, 200 and 400 mg/kg) on blood glucose was investigated in both normal and STZ-induced diabetic mice with glibenclamide (3 mg/kg) and metformin (400 mg/kg) as positive control, respectively. Serum or hepatic levels of lipid, proinflammatory factors, malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Glucosidase activity assay and glucose uptake by C2C12 myotubes were performed in vitro and the expression of glucose transporter 4 (GLUT4) in C2C12 cells was determined by western blot.Results: DZ (200 and 400 mg/kg) did not decrease fasting blood glucose in normal mice but inhibited starch-induced postprandial glycemia. Oral administration of 400 mg/kg of DZ for 14 days significantly decreased mouse blood glucose (p < 0.01), as well as serum total cholesterol (TC, p < 0.01), triglycerides (TG, p < 0.01), low-density lipoprotein cholesterol (LDL-c, p < 0.01) levels in STZ-induced hyperglycemic mice and improved oral glucose tolerance. The serum and hepatic activity of SOD was enhanced (p < 0.01 and p < 0.001, respectively) while MDA level decreased (p < 0.001). Blood concentrations of interleukin-6 (IL-6, p < 0.001), tumor necrosis factor α (TNF-α, p < 0.01), monocyte chemotactic protein 1 (MCP-1, p < 0.01) were also significantly reduced. In vitro glucosidase activity results showed that DZ inhibited α-glucosidase with IC50 values of 82, 98 and 389 μg/mL for α- glucosidase from S. cerevisiae, Rhizopus sp. and rat intestines, respectively. It also stimulated glucose uptake and GLUT4 membrane translocation in C2C12 myotubes at 20 μM (p < 0.05).Conclusion: Oral administration of DZ is effective in alleviating diabetic hyperglycemia, dyslipidemia and inflammation. Inhibition of α-glucosidase and stimulation of glucose consumption by muscles may account for its inhibitory effect on blood glucose.Keywords: Daidzin, Diabetes, Inflammation, Superoxide dismutase (SOD), Malondialdehyde (MDA), Glucosidase, C2C12 myotubes, Glucose transporte

Fault localisation for WS-BPEL programs based on predicate switching and program slicing

Service-Oriented Architecture (SOA) enables the coordination of multiple loosely coupled services. This allows users to choose any service provided by the SOA without knowing implementation details, thus making coding easier and more flexible. Web services are basic units of SOA. However, the functionality of a single Web service is limited, and usually cannot completely satisfy the actual demand. Hence, it is necessary to coordinate multiple independent Web services to achieve complex business processes. Business Process Execution Language for Web Services (WS-BPEL) makes the coordination possible, by helping the integration of multiple Web services and providing an interface for users to invoke. When coordinating these services, however, illegal or faulty operations may be encountered, but current tools are not yet powerful enough to support the localisation and removal of these problems. In this paper, we propose a fault localisation technique for WS-BPEL programs based on predicate switching and program slicing, allowing developers to more precisely locate the suspicious faulty code. Case studies were conducted to investigate the effectiveness of the proposed technique, which was compared with predicate switching only, slicing only, and one existing fault localisation technique, namely Tarantula. The experimental results show that the proposed technique has a higher fault localisation effectiveness and precision than the baseline techniques

Systems Biology Analysis of the Effect and Mechanism of Qi-Jing-Sheng-Bai Granule on Leucopenia in Mice

Qi-Jing-Sheng-Bai granule (QJSB) is a newly developed traditional Chinese medicine (TCM) formula. Clinically, it has been used for the treatment of leucopenia. However, its pharmacological mechanism needs more investigation. In this study, we firstly tested the effects of QJSB on leucopenia using mice induced by cyclophosphamide. Our results suggested that QJSB significantly raised the number of peripheral white blood cells, platelets and nucleated bone marrow cells. Additionally, it markedly enhanced the cell viability and promoted the colony formation of bone marrow mononuclear cells. Furthermore, it reversed the serum cytokines IL-6 and G-CSF disorders. Then, using transcriptomics datasets and metabonomic datasets, we integrated transcriptomics-based network pharmacology and metabolomics technologies to investigate the mechanism of action of QJSB. We found that QJSB regulated a series of biological processes such as hematopoietic cell lineage, homeostasis of number of cells, lymphocyte differentiation, metabolic processes (including lipid, amino acid, and nucleotide metabolism), B cell receptor signaling pathway, T cell activation and NOD-like receptor signaling pathway. In a summary, QJSB has protective effects to leucopenia in mice probably through accelerating cell proliferation and differentiation, regulating metabolism response pathways and modulating immunologic function at a system level

Elevated Plasma Levels of Drebrin in Glaucoma Patients With Neurodegeneration

Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs). Aberrations in several cytoskeletal proteins, such as tau have been implicated in the pathogenesis of neurodegenerative diseases, could be initiating factors in glaucoma progression and occurring prior to axon degeneration. Developmentally regulated brain protein (Drebrin or DBN1) is an evolutionarily conserved actin-binding protein playing a prominent role in neurons and is implicated in neurodegenerative diseases. However, the relationship between circulating DBN1 levels and RGC degeneration in glaucoma patients remains unclear. In our preliminary study, we detected drebrin protein in the plasma of glaucoma patients using proteomic analysis. Subsequently, we recruited a total of 232 patients including primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and Posner-Schlossman syndrome (PS) and measured its DBN1 plasma levels. We observed elevated DBN1 plasma levels in patients with primary glaucoma but not in patients with PS compared to nonaxonopathic controls. Interestingly, in contrast to tau plasma levels increased in all groups of patients, elevated drebrin plasma levels correlated with retinal nerve fiber layer defect (RNFLD) in glaucoma patients. To further explore the expression of DBN1 in neurodegeneration, we conducted experiment of optic nerve crush (ONC) models, and observed increased expression of DBN1 in the serum as well as in the retina and then decreased after ONC. This result reinforces the potentiality of circulating DBN1 levels are increased in glaucoma patients with neurodegeneration. Taken together, our findings suggest that circulating DBN1 levels correlated with RNFLD and may reflect the severity of RGCs injury in glaucoma patients. Combining measurement of circulating drebrin and tau levels may be a useful indicator for monitoring progression of neurodegenerative diseases

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13