Enterovirus 71 is an enterovirus of the family Picornaviridae. The 2C protein of poliovirus, a relative of enterovirus 71, is essential for viral replication. The poliovirus 2C protein is associated with host membrane vesicles, which form viral replication complexes where viral RNA synthesis takes place. We have now identified a host-encoded 2C binding protein called reticulon 3, which we found to be associated with the replication complex through direct interaction with the enterovirus 71-encoded 2C protein. We observed that the N terminus of the 2C protein, which has both RNA-and membrane-binding activity, interacted with reticulon 3. This region of interaction was mapped to its reticulon homology domain, whereas that of 2C was encoded by the 25th amino acid, isoleucine. Reticulon 3 could also interact with the 2C proteins encoded by other enteroviruses, such as poliovirus and coxsackievirus A16, implying that it is a common factor for such viral replication. Reduced production of reticulon 3 by RNA interference markedly reduced the synthesis of enterovirus 71-encoded viral proteins and replicative doublestranded RNA, reducing plaque formation and apoptosis. Furthermore, reintroduction of nondegradable reticulon 3 into these knockdown cells rescued enterovirus 71 infectivity, and viral protein and double-stranded RNA synthesis. Thus, reticulon 3 is an important component of enterovirus 71 replication, through its potential role in modulation of the sequential interactions between enterovirus 71 viral RNA and the replication complex.

Astrocyte elevated gene-1 (AEG-1), upregulated in various types of malignancies including colorectal cancer (CRC), has been reported to be associated with the carcinogenesis. MicroRNAs (miRNAs) are widely involved in the initiation and progression of cancer. However, the functional significance of AEG-1 and the relationship between AEG-1 and microRNAs in human CRC remains unclear. The aim of this study was to investigate whether AEG-1 could serve as a potential therapeutic target of human CRC and its possible mechanism. We adopted a strategy of ectopic overexpression or RNA interference to upregulate or downregulate expression of AEG-1 in CRC models. Their phenotypic changes were analyzed by Western blot, MTT and transwell matrix penetration assays. MicroRNAs expression profiles were performed using microarray analysis followed by validation using qRT-PCR. Knockdown of AEG-1 could significantly inhibit colon cancer cell proliferation, colony formation, invasion and promotes apoptosis. Conversely, upregulation of AEG-1 could significantly enhance cell proliferation, invasion and reduced apoptisis. AEG-1 directly contributes to resistance to chemotherapeutic drug. Targeted downregulation of AEG-1 might improve the expression of miR-181a-2(∗), -193b and -193a, and inversely inhibit miR-31 and -9(∗). Targeted inhibition of AEG-1 can lead to modification of key elemental characteristics, such as miRNAs, which may become a potential effective therapeutic strategy for CRC.

In this study, the antiviral activities of seven different extracts of Salvia miltiorrhiza (danshen) were determined. The first two extracts, SA1 and SA2, isolated at room temperature by ethyl acetate and water extraction, respectively, neutralized the enterovirus 71-induced cytopathic effect in Vero, rhabdomyosarcoma and MRC-5 cells. The other five crude extracts, extracted with warm water (60-70 degrees C) or organic solvents, did not have any protective activity. The 50% inhibitory concentrations for neutralizing the enterovirus 71-induced cytopathic effect were 0.742 +/- 0.042 mg/ml for SA1 and 0.585 +/- 0.018 mg/ml for SA2 in Vero cells. No antiviral activity was observed in the other viruses tested. Antiviral activity was more efficient in cultures treated with SA1 or SA2 during viral infection compared to the cultures treated before or after infection, suggesting that these danshen extracts could interfere with viral entry. SA1 and SA2 were able to inhibit viral RNA synthesis in the infected cells and to abate the apoptotic process in enterovirus 71-infected Vero cells. We conclude that danshen extracts possess antiviral activity and have potential for the development as an anti-enterovirus 71 agent.

Due to unique characteristics, umami substances have gained much attention in the food industry during the past decade as potential replacers to sodium or fat to increase food palatability. Umami is not only known to increase appetite, but also to increase satiety, and hence could be used to control food intake. Therefore, it is important to understand the mechanism(s) involved in umami taste perception. This review discusses current knowledge of the mechanism(s) of umami perception from receptor level to human brain imaging. New findings regarding the molecular mechanisms for detecting umami tastes and their pathway(s), and the peripheral and central coding to umami taste are reviewed. The representation of umami in the human brain and the individual variation in detecting umami taste and associations with genotype are discussed. The presence of umami taste receptors in the gastrointestinal tract, and the interactions between the brain and gut are highlighted. The review concludes that more research is required into umami taste perception to include not only oral umami taste perception, but also the wider "whole body" signaling mechanisms, to explore the interaction between the brain and gut in response to umami perception and ingestion.