Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD)

Water pollutant fingerprinting tracks recent industrial transfer from coastal to inland China: a case study

In recent years, China’s developed regions have transferred industries to undeveloped regions. Large numbers of unlicensed or unregistered enterprises are widespread in these undeveloped regions and they are subject to minimal regulation. Current methods for tracing industrial transfers in these areas, based on enterprise registration information or economic surveys, do not work. The authors have developed an analytical framework combining water fingerprinting and evolutionary analysis to trace the pollution transfer features between water sources. We collected samples in Eastern China (industrial export) and Central China (industrial acceptance) separately from two water systems. Based on the water pollutant fingerprints and evolutionary trees, we traced the pollution transfer associated with industrial transfer between the two areas. The results are consistent with four episodes of industrial transfers over the past decade. The results also show likely types of the transferred industries - electronics, plastics, and biomedicines - that contribute to the water pollution transfer

Stability analysis of token-based wireless networked control systems under deception attacks

Currently, cyber-security has attracted a lot of attention, in particular in wireless industrial control networks (WICNs). In this paper, the stability of wireless networked control systems (WNCSs) under deception, attacks is studied with a token-based protocol applied to the data link layer (DLL) of WICNS. Since deception attacks cause the stability problem of WNCSs by changing the data transmitted over a wireless network, it is important to detect deception attacks, discard the injected false data and compensate for the missing data (i.e., the discarded original data with the injected false data). The main contributions of this paper are: 1) With respect to the character of the token-based protocol, a switched system model is developed. Different from the traditional switched system where the number of subsystems is fixed, in our new model this number will be changed under deception attacks. 2) For this model, a new Kalman filter (KF) is developed for the purpose of attack detection and the missing data reconstruction. 3) For the given linear feedback WNCSs, when the noise level is below a threshold derived in this paper, the maximum allowable duration of deception attacks is obtained to maintain the exponential stability of the system. Finally, a numerical example based on a linearized model of an inverted pendulum is provided to demonstrate the proposed design

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis.

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9-CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9\u27s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis

ApoG2 induces cell cycle arrest of nasopharyngeal carcinoma cells by suppressing the c-Myc signaling pathway

<p>Abstract</p> <p>Background</p> <p>apogossypolone (ApoG2) is a novel derivate of gossypol. We previously have reported that ApoG2 is a promising compound that kills nasopharyngeal carcinoma (NPC) cells by inhibiting the antiapoptotic function of Bcl-2 proteins. However, some researchers demonstrate that the antiproliferative effect of gossypol on breast cancer cells is mediated by induction of cell cycle arrest. So this study was aimed to investigate the effect of ApoG2 on cell cycle proliferation in NPC cells.</p> <p>Results</p> <p>We found that ApoG2 significantly suppressed the expression of c-Myc in NPC cells and induced arrest at the DNA synthesis (S) phase in a large percentage of NPC cells. Immunoblot analysis showed that expression of c-Myc protein was significantly downregulated by ApoG2 and that the expression of c-Myc's downstream molecules cyclin D1 and cyclin E were inhibited whereas p21 was induced. To further identify the cause-effect relationship between the suppression of c-Myc signaling pathway and induction of cell cycle arrest, the expression of c-Myc was interfered by siRNA. The results of cell cycle analysis showed that the downregulation of c-Myc signaling pathway by siRNA interference could cause a significant arrest of NPC cell at S phase of the cell cycle. In CNE-2 xenografts, ApoG2 significantly downregulated the expression of c-Myc and suppressed tumor growth <it>in vivo</it>.</p> <p>Conclusion</p> <p>Our findings indicated that ApoG2 could potently disturb the proliferation of NPC cells by suppressing c-Myc signaling pathway. This data suggested that the inhibitory effect of ApoG2 on NPC cell cycle proliferation might contribute to its use in anticancer therapy.</p

The SMAC Mimetic APG-1387 Sensitizes Immune-Mediated Cell Apoptosis in Hepatocellular Carcinoma

The inhibitor of apoptosis protein (IAP) genes are frequently overexpressed in malignancies. Second mitochondria-derived activator of caspase (SMAC) mimetics, which target IAPs, have potential to trigger cancer cell death and sensitize tumor cells to cytotoxic therapy. The aim of this study was to investigate the anti-tumor potential of a novel bivalent SMAC mimetic, APG-1387, in hepatocellular carcinoma (HCC). The mRNA and protein expressions of IAPs, including cellular IAPs (cIAP1 and cIAP2) and X chromosome-linked IAP (XIAP), were increased in HCC tumors compared with normal liver tissue. APG-1387 treatment alone significantly reduced the protein levels of IAPs, but had only a modest effect on the viability and apoptosis of HCC cells in vitro. However, APG-1387 in combination with tumor necrosis factor-alpha (TNF-α) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) significantly reduced cell viability and proliferation, and induced apoptosis in HepG2 cells, as well as in HCCLM3 cells that harbors cancer stem cell-like properties. These synergistic killing effects were caspase-dependent and partially dependent on RIPK1 kinase activity. Furthermore, APG-1387 also promoted the killing effect of Natural Killer cells on HCC cells in vitro and the combination therapy significantly inhibited tumor growth by inducing cell apoptosis in xenograft mice model. In conclusion, our study clarified that APG-1387 could sensitize HCC cells to cytokines or immune cells mediated cell killing and implied that potential of SMAC mimetic based combination immunotherapy for HCC treatment

Type-2 Fuzzy Hybrid Controller Network for Robotic Systems

Dynamic control, including robotic control, faces both the theoretical challenge of obtaining accurate system models and the practical difficulty of defining uncertain system bounds. To facilitate such challenges, this paper proposes a control system consisting of a novel type of fuzzy neural network and a robust compensator controller. The new fuzzy neural network is implemented by integrating a number of key components embedded in a Type-2 fuzzy cerebellar model articulation controller (CMAC) and a brain emotional learning controller (BELC) network, thereby mimicking an ideal sliding mode controller. The system inputs are fed into the neural network through a Type-2 fuzzy inference system (T2FIS), with the results subsequently piped into sensory and emotional channels which jointly produce the final outputs of the network. That is, the proposed network estimates the nonlinear equations representing the ideal sliding mode controllers using a powerful compensator controller with the support of T2FIS and BELC, guaranteeing robust tracking of the dynamics of the controlled systems. The adaptive dynamic tuning laws of the network are developed by exploiting the popular brain emotional learning rule and the Lyapunov function. The proposed system was applied to a robot manipulator and a mobile robot, demonstrating its efficacy and potential; and a comparative study with alternatives indicates a significant improvement by the proposed system in performing the intelligent dynamic control

Use of human gestures for controlling a mobile robot via adaptive CMAC network and fuzzy logic controller

Mobile robots with manipulators have been more and more commonly applied in extreme and hostile environments to assist or even replace human operators for complex tasks. In addition to autonomous abilities, mobile robots need to facilitate the human–robot interaction control mode that enables human users to easily control or collaborate with robots. This paper proposes a system which uses human gestures to control an autonomous mobile robot integrating a manipulator and a video surveillance platform. A human user can control the mobile robot just as one drives an actual vehicle in the vehicle’s driving cab. The proposed system obtains human’s skeleton joints information using a motion sensing input device, which is then recognized and interpreted into a set of control commands. This is implemented, based on the availability of training data set and requirement of in-time performance, by an adaptive cerebellar model articulation controller neural network, a finite state machine, a fuzzy controller and purposely designed gesture recognition and control command generation systems. These algorithms work together implement the steering and velocity control of the mobile robot in real-time. The experimental results demonstrate that the proposed approach is able to conveniently control a mobile robot using virtual driving method, with smooth manoeuvring trajectories in various speeds