New treatments are needed for cholangiocarcinoma, an aggressive cancer with a poor prognosis. Combination of statins and bisphosphonates may be useful in treating through influencing the mevalonate pathway. We studied synergistic effects simvastatin alendronate against cholangiocarcinoma cells, looking first at cytotoxic, apoptotic anti-migratory effects, then possible mechanisms action. Indivi...

background: considering the role of matrix metalloproteinase-3 (mmp-3) and tissue inhibitor of matrix metalloproteinase-1 (timp-1) in the pathogenesis of periodontitis, the present study is to estimate the levels of mmp-3 and timp-1 in gingival crevicular fluid (gcf) in periodontal health, disease and to evaluate the effect of periodontal therapy on mmp-3 and timp-1 concentrations in gcf. mater...

Angiogenesis is a prominent feature of numerous diseases, including cancer and arthritis, and appears to play an important role in kidney disease and hypertension. The matrix metalloproteinases, especially matrix metalloproteinase-2, play a vital role during angiogenesis by degrading the surrounding extracellular matrix and allowing endothelial cell invasion. Membrane type 1 matrix metalloprote...

Inflammatory cytokines play critical roles in the pathogenesis of osteoarthritis. Recent studies have demonstrated that natural active substances can serve as alternative therapeutic agents for the prevention and treatment of osteoarthritis. Sanguinarine, an alkaloid isolated from the roots of Sanguinaria canadensis, is known to have anti-inflammatory properties. The aim of the present study wa...

Nerve growth factor (NGF) plays an important role in regulating mammalian neuronal/embryonic development, angiogenesis, and other physiological processes and has recently been investigated as a potential treatment for the neurodegenerative disorder, Alzheimer disease. In this study, we provide evidence that human NGF may also function as a metalloproteinase inhibitor, based on studies of NGF fr...

The sarafotoxins and endothelins are approximately 25-residue peptides that spontaneously fold into a defined tertiary structure with specific pairing of four cysteines into two disulfide bonds. Their structures show an interesting topological similarity to the core of the metalloproteinase interaction sites of the tissue inhibitors of metalloproteinases. Previous work indicates that sarafotoxi...

PURPOSE To test the hypothesis that extracellular matrix turnover, mediated by the matrix metalloproteinases, modulates aqueous humor outflow facility in a human outflow model. METHODS Matrix metalloproteinase activity was manipulated and outflow facility evaluated using perfused human anterior segment organ culture. Purified matrix metalloproteinases, tissue inhibitors of metalloproteinases ...

Pulmonary arterial hypertension (PAH) results from persistent vasoconstriction, smooth muscle growth and extracellular matrix (ECM) remodelling of pulmonary arteries (PAs). Matrix metalloproteinases (MMPs) are matrix-degrading enzymes involved in ECM turnover, and in smooth muscle cell (SMC) and endothelial cell migration and proliferation. MMP expression and activity are increased in experimen...