Thieno [2, 3-d] pyrimidine inhibits gastric cancer cell proliferation via the down-regulation of bcl-2 and survivin expressions

Purpose: To investigate the effect of thieno [2, 3-d] pyrimidine on gastric cancer (GC) cell proliferation, and elucidate the mechanism of action involved. Methods: Human GC cells (MKN1, MKN28 and SGC 7901) were cultured in RPMI-1640 medium supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/ streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. After attaining 60 - 70 % confluency, the cells were treated with serum-free medium and graded concentrations of thieno [2, 3-d] pyrimidine (0 – 12 µM) for 24 h. Normal cell culture without thieno [2, 3-d] pyrimidine served as control group. The cells were used in logarithmic growth phase. Cell viability and apoptosis were assessed using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The levels of expression of ZNF139, B cell lymphoma 2 (bcl-2) and survivin in MKN1 cells and orthotopically transplanted mice were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment of MKN1, MKN28 and SGC 7901 cells with thieno [2, 3-d] pyrimidine for 72 h led to significant and dose-dependent reductions in their viabilities, as well as significant and dose-dependent increases in the number of apoptotic cells (p < 0.05). The results of qRT-PCR and Western blotting showed that ZNF139 mRNA and protein expressions in MKN1 cells were significantly down-regulated by thieno [2, 3-d] pyrimidine treatment (p < 0.05). Thieno [2, 3-d] pyrimidine treatment significantly and dose-dependently down-regulated the expressions of bcl 2 and survivin proteins in MKN1 cells and orthotopically transplanted mice (p < 0.05). It also significantly and dose-dependently inhibited the proliferation of GC cells in orthotopic mouse model of GC after 31 days of treatment (p < 0.05). Conclusion: These results suggest that thieno [2, 3-d] pyrimidine suppresses the proliferation of GC cells via down-regulation of the expressions of ZNF139, bcl 2 and sur¬vivin. Thus, it has potentials for development for the management of gastric cancer

A Cocktail Method for Promoting Cardiomyocyte Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

A growing body of evidence supports the argument that bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into cardiomyocyte-like cells in an appropriate cellular environment, but the differentiation rate is low. A cocktail method was designed: we investigated the role of 5-azacytidine (5-aza), salvianolic acid B (SalB), and cardiomyocyte lysis medium (CLM) in inducing MSCs to acquire the phenotypical characteristics of cardiomyocytes. The fourth-passage MSCs were treated with 5-aza, SalB, CLM, 5-aza+salB, 5-aza+CLM, SalB+CLM, and 5-aza+SalB+CLM for 2 weeks. Immunofluorescence results showed that cTnT expression in the 5-aza+salB+CLM group was stronger than other groups. Real-time qPCR and Western blotting analyses showed that cTnT, alpha-cardiac actin, mef-2c, Cx43, and GSK-3beta expression increased while beta-catenin expression decreased. The salB+5-aza+CLM group had the most evident effects. SalB combined with 5-aza and CLM improved cardiomyocyte differentiation from MSCs. In the MSCs differentiation process, the Wnt/beta-catenin signaling pathway had been inhibited

Fluorescent gold nanoparticles-based fluorescence sensor for Cu2+ ions

A new fluorescence sensor for the highly selective detection of Cu2+ ion with a detection limit of 3.6 nM based on the aggregation-induced fluorescence quenching of the highly fluorescent glutathione-capped gold nanoparticles is reported.National Natural Science Foundation of China [20675068, 20835005

Simvastatin Blocks Blood-Brain Barrier Disruptions Induced by Elevated Cholesterol Both In Vivo and In Vitro

Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia

Socially-aware Dynamic Computation Offloading Scheme for Fog Computing System with Energy Harvesting Devices

Fog computing is considered as a promising technology to meet the ever-increasing computation requests from a wide variety of mobile applications. By offloading the computation-intensive requests to the fog node or the central cloud, the performance of the applications, such as energy consumption and delay, are able to be significantly enhanced. Meanwhile, utilizing the recent advances of social network and energy harvesting (EH) techniques, the system performance could be further improved. In this paper, we take the social relationships of the EH mobile devices (MDs) into the design of computational offloading scheme in fog computing. With the objective to minimize the social group execution cost, we advocate game theoretic approach and propose a dynamic computation offloading scheme designing the offloading process in fog computing system with EH MDs. Different queue models are applied to model the energy cost and delay performance. It can be seen that the proposed problem can be formulated as a generalized Nash equilibrium problem (GNEP) and we can use exponential penalty function method to transform the original GNEP into a classical Nash equilibrium problem and address it with semi-smooth Newton method with Armijo line search. The simulation results demonstrate the effectiveness of the proposed scheme.peerReviewe

Resource Allocation and Computation Offloading for Wireless Powered Mobile Edge Computing

In this paper, we investigate a resource allocation and computation offloading problem in a heterogeneous mobile edge computing (MEC) system. In the considered system, a wireless power transfer (WPT) base station (BS) with an MEC sever is able to deliver wireless energy to the mobile devices (MDs), and the MDs can utilize the harvested energy for local computing or task offloading to the WPT BS or a Macro BS (MBS) with a stronger computing server. In particular, we consider that the WPT BS can utilize full- or half-duplex wireless energy transmission mode to empower the MDs. The aim of this work focuses on optimizing the offloading decision, full/half-duplex energy harvesting mode and energy harvesting (EH) time allocation with the objective of minimizing the energy consumption of the MDs. As the formulate problem has a non-convex mixed integer programming structure, we use the quadratically constrained quadratic program (QCQP) and semi-definite relaxation (SDR) methods to solve it. The simulation results demonstrate the effectiveness of the proposed scheme.peerReviewe

Energy-efficient resource allocation for OFDMA two-way relay networks with imperfect CSI

Most of the existed works on the radio resource allocation (RRA) problem commonly assume the channel-state information (CSI) can be perfectly obtained by the transmission source. However, such assumption is not practical in the realistic wireless systems. In this work, we consider the practical implementation issues of resource allocation in orthogonal frequency division multiple access (OFDMA) two-way relay networks: the inaccuracy of channel-state information (CSI) available to the source. Instead, only the estimated channel status is known by the source. In this context, a joint optimization of subcarrier pairing and allocation, relay selection, and transmit power allocation is formulated in OFDMA two-way amplify-and-forward relay networks. Moreover, the objective of this work is to minimize the energy consumption of the overall system. Further, to ensure the quality of service (QoS) or data rate requirement, the energy consumption must be minimized without compromising the QoS. Therefore, by applying convex optimization techniques, energy-efficient algorithms are developed with the objective to minimize the total transmit power with guaranteeing the required data rates. Through simulation studies, energy consumption performance of the systems under the proposed schemes is investigated. It can be observed that our proposed scheme can improve the energy consumption performance of the considered system.peerReviewe