Doublecortin-like kinase 1 activates NF-κB to induce inflammatory responses by binding directly to IKKβ.

Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis, and its levels are elevated in various human cancers. Recent studies suggest that DCLK1 may relate to inflammatory responses in the mouse model of colitis. However, cellular pathways engaged by DCLK1, and potential substrates of the kinase remain undefined.

Investigation of the Molecular Profile of Granular Cell Tumours and Schwannomas of the Oral Cavity.

Granular cell tumours (GCTs) are rare submucosal lesions, thought to develop from Schwann cells, characterised by large polygonal cells with abundant lysosomes. The objectives of this study are to investigate whether GCTs have an antigen-presenting cell (APC) phenotype or a neural crest phenotype using immunohistochemistry and to compare expression profiles with Schwannomas. Immunoreactivity to CD68, HLA-DR, CD163, CD40 and CD11c (APC phenotype) and markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43 in 23 cases of GCTs and 10 cases of Schwannomas were evaluated.

2-amino-phenoxazine-3-one attenuates glucose-induced augmentation of embryonic form of myosin heavy chain, endothelin-1 and plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.

The aim of this study was to investigate the changes in mRNA level of embryonic form of myosin heavy chain (SMemb), endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1), which are considered to be involved in the angiogenesis and atherosclerosis in diabetic blood vessels, in human umbilical vein endothelial cells (HUVECs) caused by high ambient glucose, and the effects of 2-aminophenoxazine-3-one (Phx-3), which was produced by the reaction of bovine hemoglobin with o-aminophenol, on them. The mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were extensively upregulated in HUVECs treated with high concentration of glucose (15 mM), compared with those in the cells with normal concentration of glucose (5 mM). The migration activity of HUVECs evaluated by the cell migration assay was accelerated by 15 mM glucose.

C-peptide and retinal microangiopathy in diabetes.

Increased extracellular matrix (ECM) protein deposition and capillary basement membrane (BM) thickening are characteristic features of diabetic retinal microangiopathy. Recent observations in the authors' laboratories suggest that high glucose in endothelial cells as well as diabetes causes up-regulation of total fibronectin (FN), as well as extradomain-B (EDB) containing the spliced variant of FN, oncofetal FN, in the retina. This splice variant is normally absent in mature adult tissues and is believed to be involved in angiogenesis.

The role of the sodium hydrogen exchanger-1 in mediating diabetes-induced changes in the retina.

Background: The sodium hydrogen exchanger (NHE) is a transmembrane protein responsible for alkalinization and control of intracellular acidosis by the removal of hydrogen and the subsequent influx of sodium. Our investigation attempts to determine the role of NHE-1 in the pathogenesis of early retinal microangiopathy due to diabetes.

Methods: Diabetes was induced in male Sprague-Dawley rats with a single intravenous streptozotocin injection (65 mg/kg).

Growth factors in proliferative diabetic retinopathy.

Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia.

Endothelins in chronic diabetic complications.

Endothelins are widely distributed in the body and perform several vascular and nonvascular functions. Experimental data indicate abnormalities of the endothelin system in several organs affected in chronic diabetic complications. In support of this notion, it has been shown that endothelin-receptor antagonists prevent structural and functional abnormalities in target organs of diabetic complications in animal models.

Differential activation of NF-kappa B and AP-1 in increased fibronectin synthesis in target organs of diabetic complications.

Increased extracellular matrix protein production leading to structural abnormalities is a characteristic feature of chronic diabetic complications. We previously showed that high glucose in endothelial cell culture leads to the upregulation of basement membrane protein fibronectin (FN) via an endothelin (ET)-dependent pathway involving activation of NF-kappaB and activating protein-1 (AP-1). To delineate the mechanisms of basement membrane thickening, we used an animal model of chronic diabetes and evaluated ET-dependent activation of NF-kappaB and AP-1 and subsequent upregulation of FN in three target organs of chronic diabetic complications.

Alteration of endothelins: a common pathogenetic mechanism in chronic diabetic complications.

Endothelin (ET) peptides perform several physiological, vascular, and nonvascular functions and are widely distributed in a number of tissues. They are altered in several disease processes including diabetes. Alteration of ETs have been demonstrated in organs of chronic diabetic complications in both experimental and clinical studies.