USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance.

Background: Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed.

Methods: We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM.

Expression of synaptopodin in endothelial cells exposed to laminar shear stress and its role in endothelial wound healing.

We examined the hypothesis that certain actin binding proteins might be upregulated by laminar shear stress (LSS) and could contribute to endothelial wound healing. Analysis of mRNA expression profiles of human umbilical vein endothelial cells under static and LSS-exposed conditions provided a list of LSS-induced actin binding proteins including synaptopodin (SYNPO) whose endothelial expression has not been previously reported. Additional studies demonstrated that SYNPO is a key mediator of endothelial wound healing because small interfering RNA-mediated suppression of SYNPO attenuated wound closure under LSS whereas overexpression of exogenous SYNPO enhanced endothelial wound closure in the absence of LSS.

Laminar shear stress induces the expression of aquaporin 1 in endothelial cells involved in wound healing.

Laminar shear stress (LSS) due to blood flow contributes to the maintenance of endothelial health by multiple mechanisms including promotion of wound healing. The present study examined the hypothesis that the induction of water channel aquaporin 1 (AQP1) expression by LSS might be functionally associated with endothelial wound healing. When human umbilical vein endothelial cells were exposed to LSS at 12 dyn cm(-2) for 24h, significant increases in AQP1 expression were observed at the mRNA and protein levels as compared with static control.

Analysis of serum cytokine/chemokine profiles affected by aging and exercise in mice.

Aging could be the cause of inflammation involved in the progression of many degenerative diseases while physical exercise might reduce the inflammation. This study examined the effects of aging versus exercise on serum profiles of cytokines and chemokines in mice models. Male C57BL/6N mice with different ages (2 and 20 months old) were subjected to treadmill exercise for 4 weeks.

A regulatory role of Kruppel-like factor 4 in endothelial argininosuccinate synthetase 1 expression in response to laminar shear stress.

Endothelial argininosuccinate synthetase 1 (ASS1) regulates the provision of l-arginine to nitric oxide synthase 3 (NOS3). Previous studies demonstrated that endothelial ASS1 expression was induced by laminar shear stress (LSS) and that this enzyme plays a role in maintaining anti-inflammatory microenvironments through enhancing NO production. However, differently from the case of NOS3, the regulatory mechanism for the endothelial ASS1 expression in response to LSS is not well understood.

Detection of low levels of nitric oxide using an electrochemical sensor.

Nitric oxide produced from nitric oxide synthases mediates various physiological and pathological events in biological systems. However, quantitative assessment of nitric oxide from biological sources remains a difficult task. Here we describe a procedure for the quantification of low levels of nitric oxide using a nitric oxide - selective electrochemical sensor.

Endothelial argininosuccinate synthetase 1 regulates nitric oxide production and monocyte adhesion under static and laminar shear stress conditions.

Laminar shear stress (LSS) is known to increase endothelial nitric oxide (NO) production, which is essential for vascular health, through expression and activation of nitric oxide synthase 3 (NOS3). Recent studies demonstrated that LSS also increases the expression of argininosuccinate synthetase 1 (ASS1) that regulates the provision of L-arginine, the substrate of NOS3. It was thus hypothesized that ASS1 might contribute to vascular health by enhancing NO production in response to LSS.

Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells.

The mechanism that is responsible for progression of atherosclerosis seen with increasing age remains controversial. This issue was addressed in the present study, by searching for genes that are uniquely expressed in senescent endothelial cells and functionally involved in inflammatory leukocyte adhesion recognized as a critical step in the initiation of atherogenesis. Senescent human umbilical vein endothelial cells (HUVECs) prepared by continuous subculturing in vitro showed higher binding affinity for monocytes (THP-1 cells, human acute monocytic leukemia cell line) compared with young cells.

Evidence for the association of peroxidases with the antioxidant effect of p-coumaric acid in endothelial cells exposed to high glucose plus arachidonic acid.

Although many plant-derived phenolic compounds display antioxidant effects in biological systems, their mechanism of action remains controversial. In this study, the mechanism by which p-coumaric acid (p-CA) performs its antioxidant action was investigated in bovine aortic endothelial cells under oxidative stress due to high levels of glucose (HG) and arachidonic acid (AA), a free fatty acid. p-CA prevented lipid peroxidation and cell death due to HG+AA without affecting the production of reactive oxygen species.

Differential gene expression in young and senescent endothelial cells under static and laminar shear stress conditions.

Laminar shear stress (LSS) caused by blood flow is known to regulate endothelial function and to contribute to vascular health. By way of contrast, endothelial cell senescence seems to increase the incidence of vascular disorders. In an attempt to identify genes associated with vascular health/disease states, this study assessed the differential gene expression of young and senescent human umbilical vein endothelial cells (HUVECs) under static and LSS conditions.

Laminar shear stress inhibits lipid peroxidation induced by high glucose plus arachidonic acid in endothelial cells.

Elevated blood glucose and free fatty acids induce oxidative stress associated with the incidence of cardiovascular disease. In contrast, laminar shear stress (LSS) plays a critical role in maintaining vascular health. The present study examined the mechanism for the antioxidant effect of LSS attenuating the oxidative stress induced by high glucose (HG) and arachidonic acid (AA) in human umbilical vein endothelial cells.