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Bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for cardiovascular disease. However, there is no evidence so far that BMSCs can heal pathological myocardial hypertrophy. In this study, BMSCs were indirectly cocultured with neonatal rat ventricular cardiomyocytes (NRVCs) in vitro or intramyocardially transplanted into hypertrophic hearts in vivo. The results showed that isoproterenol (ISO)-induced typical hypertrophic characteristics of cardiomyocytes were prevented by BMSCs in the coculture model in vitro and after BMSC transplantation in vivo. Furthermore, activation of the Ca2+/calcineurin/nuclear factor of activated T cells cytoplasmic 3 (NFATc3) hypertrophic pathway in NRVCs was abrogated in the presence of BMSCs both in vitro and in vivo. Interestingly, inhibition of vascular endothelial growth factor (VEGF) release from BMSCs, but not basic fibroblast growth factor and insulin-like growth factor 1, abolished the protective effects of BMSCs on cardiomyocyte hypertrophy. Consistently, VEGF administration attenuated ISO-induced enlargement of cellular size; the upregulation of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain expression; and the activation of Ca2+/calcineurin/NFATc3 hypertrophic pathways, and these pathways can be abrogated by blocking VEGFR-1 in cardiomyocytes, indicating that VEGF receptor 1 is involved in the antihypertrophic role of VEGF. We further found that the ample VEGF secretion contributing to the antihypertrophic effects of BMSCs originates from the crosstalk of BMSCs and cardiac cells but not BMSCs or cardiomyocytes alone. Interplay of mesenchymal stem cells with cardiomyocytes produced synergistic effects on VEGF release. In summary, crosstalk between mesenchymal stem cells and cardiomyocytes contributes to the inhibition of myocardial hypertrophy via inhibiting Ca2+/calcineurin/NFATc3 hypertrophic pathways in cardiac cells. These results provide the first evidence for the treatment of myocardial hypertrophy using BMSCs. Significance This study found that mesenchymal stem cells may crosstalk with cardiomyocytes, which causes a synergistic vascular endothelial growth factor (VEGF) release from both kinds of cells and then inhibits pathological cardiac remodeling following hypertrophic stimulation in cardiomyocytes in vitro and in vivo. Blockage of VEGF release from bone marrow-derived mesenchymal stem cells (BMSCs) abolishes the antihypertrophic actions of BMSCs in vitro and in vivo. On the contrary, VEGF administration attenuates hypertrophic signaling of calcineurin/ nuclear factor of activated T cell cytoplasmic 3 signal pathways. This study provides the first evidence for the treatment of myocardial hypertrophy using BMSCs.

Beta-adrenoceptor (β-AR) exerts critical regulation of cardiac function. MicroRNAs (miRNAs) are potentially involved in a variety of biological and pathological processes. This study aimed to investigate the role of miRNA let-7e in the up-regulation of β(1) -AR and arrhythmogenesis in acute myocardial infarction (AMI) in rats. β(1) -AR expression was significantly up-regulated and let-7a, c, d, e and i were markedly down-regulated in the infarcted heart after 6 and 24 hrs myocardial infarction. Forced expression of let-7e suppressed β(1) -AR expression at the protein level, without affecting β(1) -AR mRNA level, in neonatal rat ventricular cells (NRVCs). Silencing of let-7e by let-7e antisense inhibitor (AMO-let-7e) enhanced β(1) -AR expression at the protein level in NRVCs. Administration of the lentivirus vector containing precursor let-7e (len-pre-let-7e) significantly inhibited β(1) -AR expression in rats, whereas len-AMO-let-7e up-regulated β(1) -AR relative to the baseline control level, presumably as a result of depression of tonic inhibition of β(1) -AR by endogenous let-7e. Len-negative control (len-NC) did not produce significant influence on β(1) -AR expression. Len-pre-let-7e also profoundly reduced the up-regulation of β(1) -AR induced by AMI and this effect was abolished by len-AMO-let-7e. Importantly, len-pre-let-7e application significantly reduced arrhythmia incidence after AMI in rats and its anti-arrhythmic effect was cancelled by len-AMO-let-7e. Notably, anti-arrhythmic efficacy of len-pre-let-7e was similar to propranolol, a non-selective β-AR blocker and metoprolol, a selective β(1) -AR blocker. Down-regulation of let-7e contributes to the adverse increase in β(1) -AR expression in AMI and let-7e supplement may be a new therapeutic approach for preventing adverse β(1) -AR up-regulation and treating AMI-induced arrhythmia.

In this paper, we present an unsupervised method to find the covert properties of the product on E-commerce web sites. Our method is generic because we do not have to depend on web site restricted pattern. The method works by 3 algorithms which are Page Type Recognition, List Page Clustering and Query Relationship Discovery. Experimental results show that it can acquire accurate rate of 96% and recall rate of 94%.

Early hardware limitations of GPU (lack of synchronization primitives and limited memory caching mechanisms) can make GPU-based computation inefficient. Now Bio-technologies bring more chances to Bioinformatics and Biological Engineering. Our paper introduces a way to solve the longest overlap region of non-coding DNA sequences on using the Compute Unified Device Architecture (CUDA) platform Intel(R) Core(TM) i3- 3110m quad-core. Compared to standard CPU implementation, CUDA performance proves the method of the longest overlap region recognition of noncoding DNA is an efficient approach to high-performance bioinformatics applications. Studies show the fact that efficiency of GPU performance is more than 20 times speedup than that of CPU serial implementation. We believe our method gives a cost-efficient solution to the bioinformatics community for solving longest overlap region recognition problem and other related fields., 6 pages, 6 figures

Node localization is essential in wireless sensor networks (WSNs). However, due to limited node energy and overhead network, node localization faces many challenges in WSNs. In addition, it is difficult to meet the requirement of localization accuracy and energy consumption at the same time in existing algorithms. In this paper, we proposed a novel eliminating algorithm called NPLA which achieves high localization accuracy and reduces energy consumption effectively. It makes full use of multiple-hop neighbor nodes of unknown node to eliminate the possible location area (PLA) of the unknown node. Simulations show that the localization error of algorithm NPLA can be controlled within 20%.

Bone marrow mesenchymal stem cells (BMSCs) are capable of homing to and repair damaged myocardial tissues. Apoptosis of BMSCs in response to various pathological stimuli leads to the attenuation of healing ability of BMSCs. Plenty of evidence has shown that elevated homocysteine level is a novel independent risk factor of cardiovascular diseases. The present study was aimed to investigate whether homocysteine may induce apoptosis of BMSCs and its underlying mechanisms. Here we uncovered that homocysteine significantly inhibited the cellular viability of BMSCs. Furthermore, TUNEL, AO/EB, Hoechst 333342 and Live/Death staining demonstrated the apoptotic morphological appearance of BMSCs after homocysteine treatment. A distinct increase of ROS level was also observed in homocysteine-treated BMSCs. The blockage of ROS by DMTU and NAC prevented the apoptosis of BMSCs induced by homocysteine, indicating ROS was involved in the apoptosis of BMSCs. Moreover, homocysteine also caused the depolarization of mitochondrial membrane potential of BMSCs. Furthermore, apoptotic appearance and mitochondrial membrane potential depolarization in homocysteine-treated BMSCs was significantly reversed by JNK inhibitor but not p38 MAPK and ERK inhibitors. Western blot also confirmed that p-JNK was significantly activated after exposing BMSCs to homocysteine. Homocysteine treatment caused a significant reduction of BMSCs-secreted VEGF and IGF-1 in the culture medium. Collectively, elevated homocysteine induced the apoptosis of BMSCs via ROS-induced the activation of JNK signal, which provides more insight into the molecular mechanisms of hyperhomocysteinemia-related cardiovascular diseases.

The objective of this study was to evaluate an ergonomically designed handle of a mason's trowel in comparison with two standard types, both with a round cross-section of the handle and either a straight neck or a swan's neck. All the tools were equipped with the same blade. Job-specific dynamic and static working elements were performed by 10 subjects in a laboratory. Under well-controlled conditions, physiological cost associated with mixing and throwing of mortar onto a vertical wall, translatory carrying and depositing of sand on a horizontal wall, rotatory scooping movements (supination and pronation of the forearm) with and without an external load of the trowel, and static holding of the tool in different working postures were measured. Electromyographic activity (EA) of the biceps brachii, pronator teres, flexor digitorum, and extensor carpi ulnaris was registered continuously and summed up during all of the test sessions lasting 30 or 45 s, each. All data were standardized by means of maximum EA resulting from preceding job-specific maximum voluntary contractions. Before and after the working sessions, which lasted about 4 h for each subject, the ergonomic quality of the handles had to be rated by means of a questionnaire with 9 items on a bipolar 4-step scale. In accordance with the hypothesis that the ergonomically designed handle should enable a specific relief of the strain in the grip musculature and the ulnar deviation muscles, significantly lower EA values were measured with this model during most of the test phases. But the effect was much less in scale than was expected from the subjective assessment before the tests. Also, subjective rating data after the working sessions differed clearly between the 3 handles mostly corresponding with the pretest assessment.