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Although anticancer effect of gambogic acid (GA) and its potential mechanisms were well documented in past decades, limited information is available on the anticancer effect of gambogenic acid (GNA), another major active component of Gamboge. Here we performed a study to determine whether GNA possesses anticancer effect and find its potential mechanisms. The results suggested that GNA significantly inhibited the proliferation of several tumor cell lines in vitro and in vivo. Treatment with GNA dose and time dependently induced A549 cells apoptosis, arrested the cells to G0/G1 phase in vitro and down-regulated the expression of cyclin D1 and cyclooxygenase (COX)-2 in mRNA level. In addition, anticancer effect was further demonstrated by applying xenografts in nude mice coupled with the characteristic of apoptosis in the GNA treated group. Taken together, these observations might suggest that GNA inhibits tumor cell proliferation via apoptosis-induction and cell cycle arrest.

The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4EGFPCre-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells. Moreover, Wnt4 is required for the initiation of MD-forming cell migration. Application of anti-Wnt4 function-blocking antibodies after the initiation of MD elongation indicated that Wnt4 is necessary for the elongation as well, and consistent with this, cell culture wound-healing assays with NIH3T3 cells overexpressing Wnt4 promoted cell migration by comparison with controls. In contrast to the Wnt4 null embryos, some Wnt4monomeric cherry/monomeric cherry (Wnt4mCh/mCh) hypomorphic mice survived to adulthood and formed MD in ∼45% of cases. Nevertheless, the MD of the Wnt4mCh/mCh females had altered cell polarization and basement membrane deposition relative to the controls. Examination of the reproductive tract of the Wnt4mCh/mCh females indicated a poorly coiled oviduct, absence of the endometrial glands and an undifferentiated myometrium, and these mice were prone to develop a hydro-uterus. In conclusion, the results suggest that the Wnt4 gene encodes signals that are important for various aspects of female reproductive tract development.

In situ detecting and monitoring intracellular telomerase activity is significant for cancer diagnosis. In this work, we report a facile and fast-responsive bioprobe for in situ detection and imaging of intracellular telomerase activity with superior photostability. After transfected into living cells, quencher group labeled TS primer (QP) can be extended in the presence of intracellular telomerase. Positive charged TPE-Py molecules (AIE dye) will bind to the primer as well as extension repeated units, producing a telomerase activity-related turn-on fluorescence signal. By incorporating positive charged AIE dye and substrate oligonucleotides, in situ light-up imaging and detection of intracellular telomerase activity were achieved. This strategy exhibits good performance for sensitive in situ tracking of telomerase activity in living cells. The practicality of this facile and fast-responsive telomerase detection method was demonstrated by using it to distinguish tumor cells from normal cells and to monitor the change of telomerase activity during treatment with antitumor drugs, which shows its potential in clinical diagnostic and therapeutic monitoring.

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Fluorescent bioprobes, as one of the most important tools, hold high promise for real-time analytical sensing of biological molecules and processes in live cells and organisms. Although several excellent bioprobes employ turn-on fluorescence intensity, such a sole responsive signal is readily perturbed by various experimental conditions. Herein, to improve the reproducibility and robustness, a ratiometric fluorescent bioprobe for telomerase activity detection has been developed. The ratiometric fluorescent bioprobe is designed on the use of two fluorescence dyes in parallel. One is red emissive aggregation-caused quenching (ACQ) dye, Cy5, as a control, molecularly labeled on the 5′-end of telomerase substrate oligonucleotides (TS primer). The other is water-soluble aggregation-induced emission (AIE) dye, Silole-R, as reporter of telomerase activity, nonemissive in buffer. In the presence of telomerase, the blue emission is enhanced by the added negatively charged sites for Silole-R to bind and aggregate, while the red emission is almost unchanged as stable internal reference. With the addition of incremental amounts of telomerase, the ratiometric emission intensity ratios (I 478/I 665) of this bioprobe gradually increase. Furthermore, the distinguishing of telomerase extracts from 20 bladder cancer bloody and 10 normal urine specimens confirms the practicality of this bioprobe. In contrast to previous turn-on bioprobes, these advanced experiments obtain higher reproducibility and positive result rate (100%) toward bladder cancer bloody urine specimens.

The macrophage-tropic retrovirus equine infectious anaemia virus (EIAV) causes persistent infections of equids. Infected horses present with an acute febrile illness characterized by fever, thrombocytopenia and viraemia. The acute disease episode may be followed, weeks or months later, by additional febrile episodes (Montelaro et al., 1993). The Wyoming strain of EIAV is a highly virulent field strain that replicates efficiently in vitro only in primary equine monocyte-