The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury.

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine.

Topical Application of Human Wharton's Jelly Mesenchymal Stem Cells Accelerates Mouse Sciatic Nerve Recovery and is Associated with Upregulated Neurotrophic Factor Expression.

Peripheral nerve regeneration following injury is often slow and impaired, which results in weakened and denervated muscle with subsequent atrophy. Human Wharton's jelly mesenchymal stem cells (hWJ-MSC) have potential regenerative properties which, however, remain unknown in mouse nerve recovery. This study investigated the effect of the topical application of hWJ-MSC onto repairing transected sciatic nerves in a mouse model.

Modulation of Neural Differentiation through Submicron-Grooved Topography Surface with Modified Polydopamine.

Surface topography and bioactive molecules can generate physicochemical cues that control proliferation and differentiation of neural cells. In this study, polystyrene (PS) submicron-patterns with different widths (400 and 800 nm) and depths (100 and 400 nm) were prepared and subsequently modified with polydopamine (PDA) by a coating method. We examined neurites of PC12 cells and human adipose-derived stem cells (hADSCs) incubated in neuronal induction medium containing nerve growth factor (NGF) and basic fibroblast growth factor (bFGF), respectively.

A systematic study of 50S ribosomal subunit purification enabling robust crystallization.

A systematic analysis was undertaken to seek correlations between the integrity, purity and activity of 50S ribosomal subunit preparations from Deinococcus radiodurans and their ability to crystallize. Conditions of fermentation, purification and crystallization were varied in a search for crystals that could reliably supply an industrial X-ray crystallography program for the structure-based design of ribosomal antibiotics. A robust protocol was obtained to routinely obtain crystals that gave diffraction patterns extending to 2.

Assessment of cholesteryl ester transfer protein inhibitors for interaction with proteins involved in the immune response to infection.

The CETP inhibitor, torcetrapib, was prematurely terminated from phase 3 clinical trials due to an increase in cardiovascular and noncardiovascular mortality. Because nearly half of the latter deaths involved patients with infection, we have tested torcetrapib and other CETPIs to see if they interfere with lipopolysaccharide binding protein (LBP) or bactericidal/permeability increasing protein (BPI). No effect of these potent CETPIs on LPS binding to either protein was detected.

Purification of the large ribosomal subunit via its association with the small subunit.

We have developed an affinity purification of the large ribosomal subunit from Deinococcus radiodurans that exploits its association with FLAG-tagged 30S subunits. Thus, capture is indirect so that no modification of the 50S is required and elution is achieved under mild conditions (low magnesium) that disrupt the association, avoiding the addition of competitor ligands or coelution of common contaminants. Efficient purification of highly pure 50S is achieved, and the chromatography simultaneously sorts the 50S into three classes according to their association status (unassociated, loosely associated, or tightly associated), improving homogeneity.

Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals.

Sterol regulatory element-binding proteins (SREBPs) are major transcriptional regulators of cholesterol, fatty acid, and glucose metabolism. Genetic disruption of SREBP activity reduces plasma and liver levels of cholesterol and triglycerides and insulin-stimulated lipogenesis, suggesting that SREBP is a viable target for pharmacological intervention. The proprotein convertase SREBP site 1 protease (S1P) is an important posttranscriptional regulator of SREBP activation.

Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules.

Cholesteryl ester transfer protein (CETP) shuttles various lipids between lipoproteins, resulting in the net transfer of cholesteryl esters from atheroprotective, high-density lipoproteins (HDL) to atherogenic, lower-density species. Inhibition of CETP raises HDL cholesterol and may potentially be used to treat cardiovascular disease. Here we describe the structure of CETP at 2.

Expression and protein chemistry yielding crystallization of the catalytic domain of ADAM17 complexed with a hydroxamate inhibitor.

The membrane-anchored metalloproteinase ADAM17 (TNF-alpha converting enzyme; TACE; EC 3.4.24.

Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2).

Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 A resolution.

A novel control scheme for inducing angiostatin-human IgG fusion protein production using recombinant CHO cells in a oscillating bioreactor.

In this study, a novel control scheme for inducing protein production using a recombinant CHO cell line in a BelloCell bioreactor was developed. This control scheme was applied in a simple regular semi-batch process. Production of angiostatin-human IgG fusion protein in a suspension recombinant CHO cell culture and a protein-free medium was used for this study.

3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.

3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.

Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography.

The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures.