Improved efficacy of a next-generation ERT in murine Pompe disease.

Pompe disease is a rare inherited disorder of lysosomal glycogen metabolism due to acid α-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) using alglucosidase alfa, a recombinant human GAA (rhGAA), is the only approved treatment for Pompe disease. Although alglucosidase alfa has provided clinical benefits, its poor targeting to key disease-relevant skeletal muscles results in suboptimal efficacy.

Morphology, cytoskeletal organization, and myosin dynamics of mouse embryonic fibroblasts cultured on nanofibrillar surfaces.

Growth of cells in tissue culture is generally performed on two-dimensional (2D) surfaces composed of polystyrene or glass. Recent work, however, has shown that such 2D cultures are incomplete and do not adequately represent the physical characteristics of native extracellular matrix (ECM)/basement membrane (BM), namely dimensionality, compliance, fibrillarity, and porosity. In the current study, a three-dimensional (3D) nanofibrillar surface composed of electrospun polyamide nanofibers was utilized to mimic the topology and physical structure of ECM/BM.

Living in three dimensions: 3D nanostructured environments for cell culture and regenerative medicine.

Research focused on deciphering the biochemical mechanisms that regulate cell proliferation and function has largely depended on the use of tissue culture methods in which cells are grown on two-dimensional (2D) plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the more complex three-dimensional (3D) architecture of the extracellular matrix (ECM) and the basement membrane (BM), a structurally compact form of the ECM. Recent work has provided strong evidence that the highly porous nanotopography that results from the 3D associations of ECM and BM nanofibrils is essential for the reproduction of physiological patterns of cell adherence, cytoskeletal organization, migration, signal transduction, morphogenesis, and differentiation in cell culture.

Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro.

Current methods to promote growth of cultured neurons use two-dimensional (2D) glass or polystyrene surfaces coated with a charged molecule (e.g. poly-L-lysine (PLL)) or an isolated extracellular matrix (ECM) protein (e.

Retinoic acid stimulates the dynamics of mouse gastric epithelial progenitors.

The gastric epithelial progenitors proliferate and undergo bipolar migration associated with their differentiation into pit, parietal, and zymogenic cell lineages. Retinoids have long been known to modulate proliferation and differentiation of various renewing epithelia, and the expression of their receptors has been demonstrated in the gastric mucosa. The aim of this study was to examine the effects of retinoic acid on progenitor cell proliferation and cell lineage formation in the mouse stomach.

Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats.

Objective: To examine the effect of ipamorelin (IPA), a novel pentapeptide with a strong growth hormone releasing potency, on insulin secretion from pancreatic tissue fragments of normal and diabetic rats.

Materials And Methods: Diabetes mellitus was induced by streptozotocin (60 mg kg(-1)). Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were removed and incubated with different concentrations (10(-12) - 10(-6) M) of IPA.

Cytokine expression by attenuated intracellular bacteria regulates the immune response to infection: the Salmonella model.

Attenuated Salmonella strains have shown excellent efficacy as mucosal vaccine delivery systems. In the present report, several recombinant strains of Salmonella enterica serovar Typhimurium, engineered to express defined murine cytokines, were used to study their potential immunoregulatory capacity in the mouse model of typhoid fever. Specifically, recombinant strains expressing IL-2 (known as GIDIL2) or TNF-alpha (GIDTNF) were compared with the parental, non-cytokine-secreting, strain (BRD509) for their ability to induce a variety of immune responses in susceptible BALB/c mice.

Distribution of serotonin and its effect on insulin and glucagon secretion in normal and diabetic pancreatic tissues in rat.

OBJECTIVES: The distribution of serotonin (5-HT) and its effect on insulin and glucagon secretion were investigated to examine whether there are changes in the pattern of distribution and effect of 5-HT after the onset of experimental diabetes. METHODS: The pattern of 5-HT and its effect of insulin and glucagon secretion was examined using immunohistochemical and radioimmunoassay techniques, respectively. RESULTS: 5-HT was demonstrated mainly in the neural elements of the pancreas.