A5053244083- Pancreatic function and diabetes
- Muscle Physiology and Disorders
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Diet, Metabolism, and Disease
- Lipid metabolism and biosynthesis
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cholesterol and Lipid Metabolism
- Thyroid Disorders and Treatments
- Lung Cancer Treatments and Mutations
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Lipid metabolism and disorders
- Telomeres, Telomerase, and Senescence
- Parathyroid Disorders and Treatments
- NF-κB Signaling Pathways
- Glycogen Storage Diseases and Myoclonus
- RNA Research and Splicing
- Renal and related cancers
- Hormonal Regulation and Hypertension
- Platelet Disorders and Treatments
Daiichi-Sankyo (Japan)
2003-2024
Daiichi Sankyo (Germany)
2010
The University of Texas Southwestern Medical Center
2003-2004
Abstract Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report development of an exon-skipping therapy using antisense-oligonucleotide (ASO) severe male X-linked syndrome (XLAS). We targeted truncating variants in exon 21 COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, vitro vivo treatment efficacy evaluation. show that skipping enabled trimer formation, leading to...
We have examined gene expression in the fat tissue of normal mice at onset diet-induced obesity. Insulin-induced 1 (insig-1) mRNA rose progressively with a high-fat diet and declined on restricted diet. Because insig-1 binds sterol regulatory element-binding protein cleavage-activating endoplasmic reticulum, thereby blocking proteolytic processing required for activation, we tested its influence lipogenesis. In differentiating 3T3-L1 cells, -2 parallel aP 2 during differentiation. The...
To determine whether the antilipogenic actions of insulin-induced gene 1 (insig-1) demonstrated in cultured preadipocytes also occur vivo, we infected Zucker diabetic fatty (ZDF) (fa/fa) rats, with recombinant adenovirus containing insig-1 or -2 cDNA. An increase both proteins appeared their livers. In control ZDF rats beta-galactosidase (beta-gal) cDNA, triacylglycerols liver and plasma rose steeply whereas insig-infected exhibited substantial attenuation hepatic steatosis hyperlipidemia....
Rat cytokine-induced neutrophil chemoattractant (CINC), which is a counterpart of human gro and belongs to the interleukin-8 family, has been quantified by new sandwich enzyme-linked immunosorbent assay. Administration lipopolysaccharide (LPS) into an air pouch performed subcutaneous injection caused inflammation severe infiltration. After LPS injection, changes in concentration CINC/gro, chemotactic activity, number neutrophils exudate were determined. The activity was augmented before...
Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration preparative reverse-phase high-pressure liquid rechromatography on HPLC. Two factors were their N-terminal amino acid sequences determined. One factor protein...
Abstract Mutations in activin receptor-like kinase 2 (ALK2) can cause the pathological osteogenic signaling seen some patients with fibrodysplasia ossificans progressiva and other conditions such as diffuse intrinsic pontine glioma. Here, we report that intracellular domain of wild-type ALK2 readily dimerizes response to BMP7 binding drive signaling. This is pathologically triggered by heterotetramers type II receptor kinases mutant forms, which form dimers A binding. We develop a blocking...
An obesity-induced diabetes model using genetically normal mouse strains would be invaluable but remains to established. One reason is that several are resistant high-fat diet-induced obesity. In the present study, we show effectiveness of gold thioglucose (GTG) in inducing hyperphagia and severe obesity mice, demonstrate development strains. GTG treated DBA/2, C57BLKs, BDF1 mice gained weight rapidly exhibited significant increases nonfasting plasma glucose levels 8-12 weeks after...
The pharmacokinetics and tissue distribution of renadirsen sodium, a dystrophin exon-skipping phosphorothioate-modified antisense oligonucleotide with 2'-
Cytokine-induced neutrophil chemoattractant (CINC)-1, a counterpart of the human growth-regulated gene product (GRO) interleukin-8 family, has been suggested to play critical roles as mediator inflammatory reactions with infiltration in rats. NF-kappaB speculated be involved production CINC-1, since NF-kappaB-binding domain is important for CINC-1 promoter activity several our reporter assays. In present study, we examined effects an overexpression IkappaBalpha, specific natural inhibitor...
Glycogen storage disease type 1a (GSD1a) is caused by a congenital deficiency of glucose-6-phosphatase-alpha (G6Pase-α, encoded G6PC), primarily associated with life-threatening hypoglycemia. Although strict dietary management substantially improves the life expectancy, patients still suffer from intermittent hypoglycemia and develop hepatic complications. Emerging therapies utilizing new modalities such as adeno-associated virus mRNA lipid nanoparticles are under development for GSD1a, but...