Glucan dendrimer for carbohydrate drugs

Dendrimers are highly branched and star-shaped polymers with nanometer-scale dimensions. The nanostructured macromolecules are known for their defined structures, versatility in drug delivery, and high functional properties similar to biomoleclules. We developed a new way to synthesize glucan dendrimer like glycogen by using branching enzyme (EC 2.4.1.18) and glucan phosphorylase (EC 2.4.1.1) by using glucose-1-phosphate as a substrate. This way enables us to produce glucan dendrimers with strictly controlled molecular size and branching structure. In this context, we developed specific glycosylation technology to substitute glucose residues at non-reducing ends with galactose, mannose, glucosamine, glucuronic acid, or N-acetylglucosamine residues. Glucose dendrimers having glucosamine and/or glucuronic acid residues are successfully used for conjugation of other functional molecules. The nano-particle conjugated glucan dendrimers with peptide antigen and nucleotide adjuvant is a potential platform for vaccine. We investigated the glucan dendrimers function as a drug carrier. The uptake of several glucose dendrimers into antigen-presenting cells (APCs), such as dendritic cell and macrophage, were examined. Glucose dendrimers were incorporated into APCs, and introducing various sugar moieties into glucan dendrimers enhance the uptake them by APCs. When glucan dendrimer-peptide conjugates were added to the cultured APCs, the peptides were effectively presented on the surface of APCs. FITC-labeled glucan dendrimers injected subcutaneously in mice accumulated into inguinal lymph nodes, which play important role to introduce acquired immune respons

Magnetic properties of epitaxial Fe3_3O4_4 films with various crystal orientations and TMR effect in room temperature

Fe$_3$O$_4$ is a ferrimagnetic spinel ferrite that exhibits electric conductivity at room temperature (RT). Although the material has been predicted to be a half metal according to ab-initio calculations, magnetic tunnel junctions (MTJs) with Fe$_3$O$_4$ electrodes have demonstrated a small tunnel magnetoresistance effect. Not even the sign of the TMR ratio has been experimentally established. Here, we report on the magnetic properties of epitaxial Fe$_3$O$_4$ films with various crystal orientations. The films exhibited apparent crystal orientation dependence on hysteresis curves. In particular, Fe$_3$O$_4$(110) films exhibited in-plane uniaxial magnetic anisotropy. With respect to the squareness of hysteresis, Fe$_3$O$_4$ (111) demonstrated the largest squareness. Furthermore, we fabricated MTJs with Fe$_3$O$_4$(110) electrodes, and obtained an TMR effect of -12\% at RT. The negative TMR ratio corresponded to the negative spin polarization of Fe$_3$O$_4$ predicted from band calculations

Enzymatic synthesis of glucan dendrimer for pharmaceutical applications

Bio-macromolecules (e.g. protein, peptide, antibody DNA or RNA) present in our bodies are now widely utilized in pharmaceuticals. Carbohydrates, on the other hand, have been receiving increasing attention as drug candidates, but the pharmaceutical usage of carbohydrates is limited to few glycosaminoglycans (e.g. heparin, hyaluronan or chondroitin sulfate), which are all endogenous polysaccharides. Glycogen is another polysaccharide present in our bodies as energy reserves, and its application for pharmaceuticals is not evident either. Glycogen is a highly branched polysaccharide of glucose with a very attractive structure and characteristics. It is a single molecular nano-sized spherical particle with dendritic architecture where numerous non-reducing ends constitute the surface of the molecule. Dendrimers and nano-sized particles have received interest as carriers for drug delivery system because such carriers can enhance the performance and efficacy of drug molecules. From this context, we consider glycogen as potentially a promising polysaccharide as drug carriers; therefore we are currently attempting to develop synthetic glucan dendrimers suitable for drug carriers. Such attempts have been scarce in the recent research of drug candidates. We have developed an enzymatic system to produce glucan dendrimer (GD) from sucrose by combined action of sucrose phosphorylase (EC: 2.4.1.7), glucan phosphorylase (EC: 2.4.1.1) and branching enzyme (EC: 2.4.1.18). This system enables us to produce GDs with strictly controlled molecular size (Mw/Mn value less than 1.1) and particle size ranging from 10 nm to 40 nm. Furthermore, we have developed non-reducing end specific glycosylation technology of GD by using glucan phosphorylase and its substrate analogs. Glucan phosphorylase from Aquifex aeolicus can use not only its original substrate, glucose 1-phosphate, but also other hexose 1-phosphates as substrate and transfer these hexoses moieties (glucuronic acid, glucosamine, N-acetyl glucosamine, galactose and mannose) to the non-reducing end of glucan. Using this enzymatic reaction, we can produce GDs whose surface is modified with these hexose residues. GDs having glucuronic acid and/or glucosamine residues are especially useful since they can be covalently conjugated with functional substances such as sugar chains, peptides, nucleotides and others. It is possible to control the conjugate ratio of the functional substance on the surface of GD. Surface engineered GD is a novel and versatile platform for carbohydrate drugs and drug carriers, and its application will be described

The efficacy of incretin therapy in patients with type 2 diabetes undergoing hemodialysis

BACKGROUND: Although incretin therapy is clinically available in patients with type 2 diabetes undergoing hemodialysis, no study has yet examined whether incretin therapy is capable of maintaining glycemic control in this group of patients when switched from insulin therapy. In this study, we examined the efficacy of incretin therapy in patients with insulin-treated type 2 diabetes undergoing hemodialysis. METHODS: Ten type 2 diabetic patients undergoing hemodialysis received daily 0.3 mg liraglutide, 50 mg vildagliptin, and 6.25 mg alogliptin switched from insulin therapy on both the day of hemodialysis and the non-hemodialysis day. Blood glucose level was monitored by continuous glucose monitoring. After blood glucose control by insulin, patients were treated with three types of incretin therapy in a randomized crossover manner, with continuous glucose monitoring performed for each treatment. RESULTS: During treatment with incretin therapies, severe hyperglycemia and ketosis were not observed in any patients. Maximum blood glucose and mean blood glucose on the day of hemodialysis were significantly lower after treatment with liraglutide compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. The standard deviation value, a marker of glucose fluctuation, on the non-hemodialysis day was significantly lower after treatment with liraglutide compared with treatment with insulin and alogliptin (p < 0.05), but not with vildagliptin. Furthermore, the duration of hyperglycemia was significantly shorter after treatment with liraglutide on both the hemodialysis and non-hemodialysis days compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. CONCLUSIONS: The data presented here suggest that patients with type 2 diabetes undergoing hemodialysis and insulin therapy could be treated with incretin therapy in some cases

異教科で協働できる教員を育成するための実践的研究（1） : 教科教育学専攻の共通科目の始動を通じて

本研究は，平成28 年度より始まった「教科教育学専攻」における新しい共通科目（「教科教育学研究方法論」，「教科教育学融合プロジェクト」，「教科教育学の実践的展開」，「教科教育学の実践的検証」）が始動する際に得られた知見を分析・考察し報告するもので，その全容は平成29 年３月に公開予定のホームページで公表される。本報告書は，その研究の要旨を，(1)　経緯について，(2)　各教科について，(3)　実践からの考察，(4)　理論からの考察，(5)　学生の振り返りからの考察の五点から述べる