Expression profile analysis to identify potential gene changes induced by dexamethasone in the trabecular meshwork

AIM: To investigate potential gene changes in trabecular meshwork (TM) induced by dexamethasone (DEX) in steroid-induced glaucoma (SIG). METHODS: The expression data of 24 cases from a public functional genomics data were sorted to identify the mechanisms of action of DEX on the TM. The relationships of the differentially expressed genes (DEGs) were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the hub genes were screened by the Search Tool for the Retrieval of Interacting Genes Database (STRING) and Cytoscape tools. Finally, human TM cells (HTMCs) were treated with DEX to preliminarily explore the function of hub genes. RESULTS: Totally 47 DEGs, including 21 downregulated and 26 upregulated genes were identified. The primary enriched results of the DEGs consisted of inflammatory response, extracellular matrix (ECM), negative regulation of cell proliferation, TNF signalling pathway and the regulation of tryptophan channels by inflammatory mediators. Subsequently, pro-melanin-enriched hormone (PMCH) and Bradykinin B1 receptor (BDKRB1) were screened as hub genes. It is verified in GSE37474 data set. Western blot and quantitative real-time polymerase chain reaction (qPCR) results showed that protein and RNA expression levels of BDKRB1 were significantly decreased after DEX treatment, while PMCH was not significantly changed. CONCLUSION: BDKRB1 may be a key gene involved in SIG onset, providing a suitable therapeutic target for improving the prognosis of SIG patients

HiTrust: building cross-organizational trust relationship based on a hybrid negotiation tree

Small-world phenomena have been observed in existing peer-to-peer (P2P) networks which has proved useful in the design of P2P file-sharing systems. Most studies of constructing small world behaviours on P2P are based on the concept of clustering peer nodes into groups, communities, or clusters. However, managing additional multilayer topology increases maintenance overhead, especially in highly dynamic environments. In this paper, we present Social-like P2P systems (Social-P2Ps) for object discovery by self-managing P2P topology with human tactics in social networks. In Social-P2Ps, queries are routed intelligently even with limited cached knowledge and node connections. Unlike community-based P2P file-sharing systems, we do not intend to create and maintain peer groups or communities consciously. In contrast, each node connects to other peer nodes with the same interests spontaneously by the result of daily searches

An Integrated Edge and Fog System for Future Communication Networks

Put together, the edge and fog form a large diverse pool of computing and networking resources from different owners that can be leveraged towards low latency applications as well as for alleviating high traffic volume in future networks including 5G and beyond. This paper sets out a framework for the integration of edge and fog computing and networking leveraging on ongoing specifications by ETSI MEC ISG and the OpenFog Consortium. It also presents the technological gaps that need to be addressed before such an integrated solution can be developed. These noticeably include challenges relating to the volatility of resources, heterogeneity of underlying technologies, virtualization of devices, and security issues. The framework presented is a Launchpad for a complete solution under development by the 5G-CORAL consortium.This work has been partially funded by the H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant num. 761586

Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, = 20) and control (normal saline, = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group ( < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without Lglutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level

Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma

Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22phox, which is upregulated following Kras activation. Both alterations are also detectable in PDAC cell lines and patient specimens. Furthermore, we show that elevated NOX4 activity accelerates oxidation of NADH and supports increased glycolysis by generating NAD+, a substrate for GAPDH-mediated glycolytic reaction, promoting PDAC cell growth. Mechanistically, NOX4 was induced through p16-Rb-regulated E2F and p22phox was induced by KrasG12V-activated NF-κB. In conclusion, we provide a biochemical explanation for the cooperation between p16 inactivation and Kras activation in PDAC development and suggest that NOX4 is a potential therapeutic target for PDAC