Transcriptional factor nuclear factor-kappaB (NF-κB) plays a crucial role in human breast cancer cell invasion and metastasis. The carboxyl terminus of Hsc70-interacting protein (CHIP) is a U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins. In this study, we investigated the role of CHIP in the NF-κB pathway in the invasion of MDA-MB-231 cells, a highly aggressive breast cancer cell line. We showed that overexpression of CHIP significantly inhibits the invasion of the MDA-MB-231 cells. The overexpression of CHIP suppressed expression of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 cells. Moreover, CHIP strongly inhibited the nuclear localization and the transcriptional activity of NF-κB. The activation of the IkappaB kinase complex (IKK) was also blocked by CHIP overexpression. Importantly, CHIP overexpression resulted in a significant decrease in the level of TNF receptor-associated factor 2 (TRAF2), an upstream key player in the NF-κB pathway. However, the level of TRAF2 was restored after treatment with a proteasome inhibitor, MG-132. Moreover, CHIP overexpression promoted the ubiquitination of TRAF2. We also found cell invasion significantly decreased in cells transfected with TRAF2 small interfering RNA (siRNA). In contrast, when CHIP expression was suppressed by siRNA in poorly invasive MCF-7 cells, cell invasion significantly increased in conjunction with enhanced NF-κB activation and TRAF2 levels. Taken together, these results suggest that CHIP regulates NF-κB-mediated cell invasion via the down-regulation of TRAF2.

Far-infrared radiation (FIR) has been shown to exert positive effects on the cardiovascular system. However, the biological effects of FIR on bone marrow-derived stem cells (BMSCs) are not understood. In the present study, BMSCs were isolated from rat femur bone marrow and cultured in vitro. To investigate the effects of an FIR generator with an energy flux of 0.13 mW/cm2 on rat BMSCs, survival of BMSCs was measured by crystal violet staining, and cell proliferation was additionally measured using Ez-Cytox cell viability, EdU, and Brd U assays. FIR preconditioning was found to significantly increase BMSC proliferation and survival against H2O2. The scratch and transwell migration assays showed that FIR preconditioning resulted in an increase in BMSC migration. qRT-PCR and Western blot analyses demonstrated that FIR upregulated Nanog, Sox2, c-Kit, Nkx2.5, and CXCR4 at both the mRNA and protein levels. Consistent with these observations, PD98059 (an ERK inhibitor) and AMD3100 (a CXCR4 inhibitor) prevented the activation of CXCR4/ERK and blocked the cell proliferation and migration induced by FIR. Overall, these findings provide the first evidence that FIR confers a real and significant benefit on the preconditioning of BMSCs, and might lead to novel strategies for improving BMSC therapy for cardiac ischemia.

A ging is a physiological process associated with an increase in cardiovascular morbidity and mortality even in the absence of known cardiovascular risk factors. 1 The main feature of arterial aging is the thickening, dilation, and stiffening of the artery, 2,3 which is described as senile arteriosclerosis. 4 The repeated cycles of distension and elastic recoil of the arterial wall accelerate the fragmentation and depletion of elastin, leading to a substantial increase in the inner diameter and the deposition of collagen with increasing stiffness.5 As a result, the stiffening of the proximal aorta and early wave reflection give rise to the development of isolated systolic hypertension, left ventricular hypertrophy, and heart failure with a basis on a ventricular-vascular coupling mechanism; all of these factors lead to an increase of cardiovascular mortality with aging. 5,6 Thus, the assessment of mechanical properties of the artery in humans using noninvasive techniques is of growing importance. For quantification of aortic elastic properties, there are many noninvasive measures, including pulse wave velocity and echocardiographic techniques presented as distensibility, strain, and pressure-strain elastic moduli.7-11 However, these methods represent a global estimation of arterial elasticity and, therefore, have limitations because arterial changes usually begin as regional changes. With the availability of more advanced ultrasound techniques, a novel automated speckletracking method using velocity-vector imaging (VVI) software has facilitated the assessment for angle-independent and instantaneous quantification of arterial elastic properties by providing the 2-dimensional-derived tissue radial velocity (RV), circumferential strain, and strain rate in both regional and segmental aspects. 12-15We previously showed that arterial assessment using VVI represents a new method for quantifying vascular alteration not only in the clinical conditions of vasculitis 12,13 but also in other disorders associated with aging.16 Despite these investigations, further histological validation will facilitate the clinical application of VVI. Therefore, the purpose of this study was to compare the parameters of VVI between young and senescent dogs and to assess the correlations between the VVI parameters and histological changes. Objective-Velocity-vector imaging (VVI) represents a valuable new method for noninvasive quantification of vascular properties associated with aging. The purpose of this study was to assess the correlations between VVI parameters and histological changes with aging. Approach and Results-Fourteen mongrel dogs were classified as either young (n=7; age, 1-2 years; female; weighing 22-29 kg) or senescent (n=7; age, 8-12 years; female; weighing 36-45 kg). The short-axis image of the descending thoracic aorta was obtained for VVI analysis with transesophageal echocardiography. The location of the image was identified using fluoroscopic guidance, and the aortic tissue was extracted. After dividing the aortic wa...

Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models.