Cobalt chloride, a chemical hypoxia-mimicking agent, suppresses myoblast differentiation by downregulating myogenin expression.

Cobalt chloride can create hypoxia-like state in vitro (referred to as chemical hypoxia). Several studies have suggested that chemical hypoxia may cause deleterious effects on myogenesis. The intrinsic underlying mechanisms of myoblast differentiation, however, are not fully understood.

1α, 25(OH)D regulates agrin-induced acetylcholine receptor clustering through upregulation of rapsyn expression in C2C12 myotubes.

The active form of vitamin D (1α, 25-dihydroxyvitamin D [1α, 25(OH)D], referred to as 1,25D) has been suggested to play a pivotal role in skeletal muscle function and metabolism. However, the mechanisms through which 1,25D functions in this tissue remain to be elucidated. Recent studies have shown that vitamin D signaling regulates neuromuscular maintenance and improves locomotion in mice.

A new biomarker candidate for spinal muscular atrophy: Identification of a peripheral blood cell population capable of monitoring the level of survival motor neuron protein.

Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by insufficiency of functional survival motor neuron (SMN) protein. Several clinical trials have been conducted with the aim of upregulating the expression of the SMN protein in SMA patients. In order to evaluate the efficiency of these SMN-targeted approaches, it has become necessary to verify SMN protein levels in the cells of SMA patients.

Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy.

Background: Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose.

A novel evaluation method of survival motor neuron protein as a biomarker of spinal muscular atrophy by imaging flow cytometry.

Spinal muscular atrophy (SMA) is caused by mutations within the survival motor neuron 1 (SMN1) gene. These mutations result in the reduction of survival motor neuron (SMN) protein expression and SMN complex in spinal motor neurons and other tissues. SMN protein has been used as a therapeutic biomarker in recent SMA clinical studies using enzyme-linked immunosorbent assay (ELISA).

Efficacy of liraglutide as a follow-up therapy after resolution of glucotoxicity with intensive insulin therapy.

Objective: To assess the utility of liraglutide, a GLP-1 receptor agonist, as additional therapy following resolution of glucotoxicity with insulin therapy.

Methods: The subjects were 13 Japanese patients with short-duration type 2 diabetes mellitus (2.0 ± 2.

The Effect of Lactic Acid Bacteria-fermented Soybean Milk Products on Carrageenan-induced Tail Thrombosis in Rats.

Thrombosis is characterized by congenital and acquired procatarxis. Lactic acid bacteria-fermented soybean milk products (FS-LAB) inhibit hepatic lipid accumulation and prevent atherosclerotic plaque formation. However, the therapeutic efficacy of FS-LAB against thrombosis has yet to be investigated.

Inactivation of Escherichia coli by sonoelectrocatalytic disinfection using TiO2 as electrode.

This is the first study to demonstrate sonoelectrocatalytic disinfection using titanium dioxide (TiO(2)) as an anode for effective inactivation of Escherichia coli. In brief, a non-woven TiO(2) fabric used as an anode and a platinum cathode were immersed in an E. coli suspension in which a positive potential was applied to TiO(2) concomitant with ultrasound (US) irradiation.

Amycolamicin: a novel broad-spectrum antibiotic inhibiting bacterial topoisomerase.

The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution of multidrug resistance in many pathogens. Our efforts to discover novel classes of antibiotics to combat these pathogens resulted in the discovery of amycolamicin (AMM). The absolute structure of AMM was determined by NMR spectroscopy, X-ray analysis, chemical degradation, and modification of its functional groups.

Human first-trimester chorionic villi have a myogenic potential.

First-trimester chorionic-villi-derived cells (FTCVs) are the earliest fetal material that can be obtained for prenatal diagnosis of fetal disorders such as Duchenne muscular dystrophy (DMD). DMD is a devastating X-linked disorder characterized by the absence of dystrophin at the sarcolemma of muscle fibers. Currently, a limited number of treatment options are available for DMD, although cell therapy is a promising treatment strategy for muscle degeneration in DMD patients.

Influence of fruit juice on fingertips and patient behavior on self-monitoring of blood glucose.

We examined the influence of fruit juice on fingertips on self-monitoring of blood glucose (SMBG) results and patient behavior regarding SMBG. We found hand washing with tap water after touching the flesh of fruit, rather than using alcohol swabs, to be very important for accurate SMBG.

IRS-2 deficiency in macrophages promotes their accumulation in the vascular wall.

The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2(-/-) bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages in the vascular wall. Experiments using cultured peritoneal macrophages showed that IRS-2-mediated signal pathway stimulated by physiological concentrations of insulin, not by IL-4, contributed to the suppression of monocyte chemoattractant protein-1 expression induced by lipopolysaccharide.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury.

Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury.

In vivo evaluation method of the effect of nattokinase on carrageenan-induced tail thrombosis in a rat model.

Thrombosis is characterized by congenital and acquired procatarxis. Nattokinase inhibits thrombus formation in vitro. However, in vivo evaluation of the therapeutic efficacy of nattokinase against thrombosis remains to be conducted.

Transcutaneous immunization by a solid-in-oil nanodispersion.

We have successfully achieved transcutaneous immunization without the use of any skin pre-treatment or immune-stimulant adjuvant by applying a solid-in-oil (S/O) nanodispersion: an oil-based nanodispersion of antigens coated with hydrophobic surfactant molecules. This finding indicates that the S/O nanodispersion has great promise for effective transcutaneous vaccination.

Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4.

Objective: Exogenous administration of glucagon-like peptide-1 (GLP-1) or GLP-1 receptor agonists such as an exendin-4 has direct beneficial effects on the cardiovascular system. However, their effects on atherosclerogenesis have not been elucidated. The aim of this study was to investigate the effects of GLP-1 on accumulation of monocytes/macrophages on the vascular wall, one of the earliest steps in atherosclerogenesis.

Physical properties of griseofulvin-lipid nanoparticles in suspension and their novel interaction mechanism with saccharide during freeze-drying.

Size reduction of drug particles to the nanoscale is important in improving the dissolution rate of poorly water-soluble drugs. The aim of this study was to investigate the physicochemical properties of griseofulvin (GF)-lipid nanoparticles and the interactions between GF-lipid nanoparticles and various saccharides during freeze-drying. The phase transition temperature of the GF-lipid nanoparticle suspension was 56.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents.

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions.

Preparation of griseofulvin nanoparticle suspension by high-pressure homogenization and preservation of the suspension with saccharides and sugar alcohols.

Aim: We have attempted to micronize drug particles with a particle size of less than 100 nm and maintain the particle size of their suspension to improve the solubility and bioavailability of poorly water-soluble drugs. Furthermore, the method of freeze-drying nanoparticles was applied to maintain particulate nature of nanoparticles containing various saccharides and sugar alcohols for a long time.

Method: Griseofulvin (GF)-lipid nanoparticle suspension is prepared using GF and a lipid by high-pressure homogenization.

Improving frequency of thrombosis by altering blood flow in the carrageenan-induced rat tail thrombosis model.

The carrageenan-induced tail thrombosis model in rats and mouse is useful for evaluating compounds having antithrombotic effects in drug discovery projects as an in vivo model. However, the frequency of thrombosis is low, and the signs of thrombosis are not constant under the standard conditions. In this study, we modified this model on the basis of hypercoagulability, endothelial injury, and alteration in the normal blood flow.

The relationship between the efficacy of epidural anesthesia and the concentration of lidocaine in cerebrospinal fluid.

Background: Addition of bicarbonate to local anesthetics improves the efficacy of epidural anesthesia. We evaluated whether the addition of bicarbonate to lidocaine enhanced pain threshold in cesarean section. We speculated that bicarbonate would increase the concentration of lidocaine in cerebrospinal fluid (CSF).

Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet.

Autophagy is an evolutionarily conserved machinery for bulk degradation of cytoplasmic components. Here, we report upregulation of autophagosome formation in pancreatic beta cells in diabetic db/db and in nondiabetic high-fat-fed C57BL/6 mice. Free fatty acids (FFAs), which can cause peripheral insulin resistance associated with diabetes, induced autophagy in beta cells.

A new terrein glucoside, a novel inhibitor of angiogenin secretion in tumor angiogenesis.

Angiogenesis is a critical step for the tumor therapy. Many angiogenic factors are involved in the tumor angiogenesis. In the course of our screening for inhibitors of angiogenin secretion, one of angiogenic factors, we have isolated a new terrein glucoside (1) and terrein (2) from the fermentation broth of fungal strain Aspergillus sp.

Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects.

Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors. Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion.