The Mechanisms of Chondroitin Sulphate Lyases Treatment in Promotion of Axonal Growth

Poster PresentationIn Injured nerves, chondroitin sulphate (CS) is upregulated forming barriers with astrocytes/fibroblasts and other extracellular matrix molecules, and thereby hampering nerve regeneration. Cleavage of CS using chondroitin sulphate lyases (Proteus vulgaris) promises axon regrowth through the barrier but the enzymatic efficacy remains to be improved. Two subtypes, endolyase and exolyase, have been found coexisting in the original host but only the former has been exploited for treatment of injured nerve tracts. We hypothesise that the two subtypes are necessary for enzymatic efficacy on CSs. We therefore prepared recombinant enzymes of both subtypes. Enzyme kinetics study revealed feedback inhibition by limit digestion products: that of the endolyase by tetrasaccharides and that of the exolyase by the disaccharides. When the two subtypes were used in combination, the digestion efficiency increased. We then used TGF beta-1 to induce CS production by astrocytes in culture, mimicking reactive glia in injured nerves. In co-cultures of such astrocytes with cortical neurons, treatment with combinations of the two subtypes resulted in increased neurite lengths as compared to co-cultures treated with one of the subtypes. The limit digestion products of CS were further tested for their effects on neurite extension on astrocytes that had been treated with TGF beta-1. The CS disaccharides, both 4- and 6-sulphated but not the tetrasaccharides, promoted neurite extension significantly. Taken together, the combinatorial use of the ChABC subtypes not only improved efficacy of enzyme activity on the axon-restrictive CS moiety, but also increased the yield of CS disaccharides which contributed to axonal growth.published_or_final_versio

Isolation of leptin-binding peptides from a random peptide phage library

Leptin plays a role in regulating the body weight in mice. Injection of recombinant mouse leptin expressed in Escherichia coli reduced the food intake and body weight in normal, ob/ob and diet-induced obesity mice. Hyperglycemia, hyperinsulinemia and hypothermia can also be corrected in ob/ob mice after leptin injection. Leptin is a 16-kDa secretory protein comprising 167 amino acids produced in adipose tissue and is secreted to blood stream. In this study, a recombinant mouse leptin was generated and purified from a baculovirus expression system. This protein was used to identify putative ligands using a phage library of random peptides. Three leptin-binding phage clones were found, which were characterized by DNA sequencing and ELISA methods. The amino acid sequences of the reactive peptides are: LAYCSDPVRCLVWWY, MFWlSAVSFVDHALV and LVLVLSAFLCCGVG. All three clones bound to recombinant human and mouse leptins. These peptides may be useful tools to study leptin-receptor interaction, food intake and body weight regulation.postprin

NiOZnO light emitting diodes by solution-based growth

Heterojunction NiOZnO light emitting diodes have been fabricated using low temperature solution-based growth methods. While negligible light emission has been obtained for the as-grown NiO film, devices with annealed NiO film exhibit room-temperature electroluminescence (EL), which was attributed to the detrimental effects of nickel oxide hydroxide in as-grown NiO layers. The device performance can be further modified by insertion of the organic layers between NiO and ZnO and the EL spectra exhibited dependence on the bias voltage. For higher bias voltages, strong UV-violet emission peak can be obtained in spite of the dominance of defect emission in the photoluminescence spectra. © 2008 American Institute of Physics.published_or_final_versio

Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

A γA-Crystallin Mouse Mutant Secc with Small Eye, Cataract and Closed Eyelid

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Change of the emission spectra in organic light-emitting diodes by layer thickness modification

The electroluminescence (EL) and photoluminescence properties of organic light-emitting diodes (LED) were analyzed using layer thickness modification. Investigations show that the EL spectra exhibited significant variation with the increase of the viewing angle. It was found that multiple peak emission could be achieved for a certain range of thickness values. It was concluded that near white emission with CIE coordinates (0.32, 0.43) could be obtained for optimized device thickness.published_or_final_versio

Effect of annealing on the performance of CrO3/ZnO light emitting diodes

Heterojunction CrO3/ZnO light emitting diodes have been fabricated. Their performance was investigated for different annealing temperature for ZnO nanorods. Annealing in oxygen atmosphere had significant influence on carrier concentration in the nanorods, as well as on the emission spectra of the nanorods. Surprisingly, annealing conditions, which yield the lowest band edge-to-defect emission ratio in the photoluminescence spectra, result in the highest band edge-to-defect emission ratio in the electroluminescence spectra. The influence of the native defects on ZnO light emitting diode performance is discussed. © 2009 American Institute of Physics.published_or_final_versio

Solution-based growth of ZnO nanorods for light-emitting devices: Hydrothermal vs. electrodeposition

ZnO nanorods have been grown by two inexpensive, solution-based, low-temperature methods: hydrothermal growth and electrodeposition. Heterojunction n-ZnO nanorods/p-GaN light-emitting diodes have been studied for different nanorod growth methods and different preparation of the seed layer. We demonstrate that both the nanorod properties and the device performance are strongly dependent on the growth method and seed layer. All the devices exhibit light emission under both forward and reverse bias, and the emission spectra can be tuned by ZnO nanorod deposition conditions. Electrodeposition of rods or a seed layer results in yellow emission, while conventional hydrothermal growth results in violet emission. © The Author(s) 2010. This article is published with open access at Springerlink.com.published_or_final_versionSpringer Open Choice, 01 Dec 201

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance. Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1–E2F1–IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes. Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types. Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1–E2F1–IGF2 regulatory axis has important implications for cancer prognosis and treatment. ©2015 AACR.postprin

Chemotherapy of tuberculosis in Hong Kong: a consensus statement

This consensus statement is prepared primarily as a concise reference for tuberculosis chemotherapy in Hong Kong. Treatment should be tailored to patients individually, expert advice should be sought when necessary, and 'directly observed treatment' should be used where possible. A 6-month regimen is recommended as the initial treatment of uncomplicated pulmonary tuberculosis and a 9-month regimen is recommended for retreatment. Patients with disease that is resistant to isoniazid or rifampicin may require modified regimens. Multidrug-resistant tuberculosis should be managed in specialised centres, using multiple drugs as guided by in vitro susceptibility tests. Recommended regimens to treat extrapulmonary tuberculosis are based on limited current evidence, although shorter regimens may be acceptable when better evidence emerges. A longer duration of treatment is required for diabetic, immuno-compromised, or silicotic patients. During pregnancy, streptomycin should be avoided; the safety profiles of second-line drugs have not yet been ascertained. Hepatotoxic drugs should be used with caution in patients with liver dysfunction, and extra caution and dosage reductions are required if streptomycin and ethambutol are used in patients with renal impairment.published_or_final_versio