Targeting long non-coding RNA-TUG1 inhibits tumor growth and angiogenesis in hepatoblastoma.

Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma.

Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.

Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viability and improve bone metabolism. However, little is known about the effects of EPA on dexamethasome (Dex)-induced cell apoptosis. In this study, we showed that EPA-induced autophagy of murine bone marrow-derived mesenchymal stem cells (mBMMSCs). Meanwhile, EPA, but not arachidonic acid (AA), markedly inhibited Dex-induced apoptosis and promoted the viability of mBMMSCs. We also observed that EPA-induced autophagy was modulated by GPR120, but not GPR40. Further experiments showed that the mechanism of EPA-induced autophagy associated with GPR120 modulation involved an increase in the active form of AMP-activated protein kinase and a decrease in the activity of mammalian target of RAPA. The protective effect of EPA on Dex-induced apoptosis via GPR120-meditated induction of adaptive autophagy was supported by in vivo experiments. In summary, our findings may have important implications in developing future strategies to use EPA in the prevention and therapy of the side effects induced by long-term Dex-abuse.

Regulation of p21 by TWIST2 contributes to its tumor-suppressor function in human acute myeloid leukemia.

TWIST2 has a dual function in tumors. Its implication in the initiation and metastasis of various solid tumors is well established, and its tumor-suppressor role in murine osteosarcoma cells has been reported recently. However, the function of TWIST2 and its underlying mechanisms in human normal and malignant hematopoiesis remain unclear. In the present study, we found that TWIST2 directly regulated p21 in human hematopoietic cells and whose silence promoted cell proliferation and cell cycle progression. Hypermethylation of TWIST2 occurred to 23 out of the 75 adult acute myeloid leukemia (AML) patients and resulted in the impaired expression of both TWIST2 and p21. Conversely, TWIST2 overexpression inhibited the growth of AML cells partially through its direct activation of p21 with intact HLH (helix-loop-helix) domain. The microarray data and gene expression validation showed that TWIST2 was sufficient to activate known tumor-suppressor genes, whereas suppress known oncogenes, which further supported its inhibitory effect against AML cells. Taken together, our data have identified a novel TWIST2-p21 axis that modulates the cell cycle of both normal and leukemic cells and demonstrated that the direct regulation of p21 by TWIST2 has a role in its tumor-suppressor function in AML.

Genistein prevents cadmium-induced neurotoxic effects through its antioxidant mechanisms.

INTRODUCTION: Cadmium-induced neurotoxic effects are mediated through adverse oxidative stress and calcium signaling. Genistein, a phytoestrogen is a potent antioxidant and exhibits property to cross blood-brain barrier. METHODS: Experimental model of cadmium-induced neurotoxic effects were induced by treatment with cadmium (5 mg/kg) for 28 days in wistar rats. For determining the protective effect, genistein was administered at a dose of (10 mg/kg) for 7 days followed by cadmium treatment for 28 days. Serum and tissues were analyzed for various oxidative stress markers such as total antioxidant capacity, total oxidant levels, non-enzymic antioxidants, enzymic antioxidants, lipid peroxide levels and protein carbonyl content. RESULTS: The results showed significant increase in the oxidative stress markers during cadmium treatment was attenuated in rats treated with genistein followed by cadmium treatment. In addition, cadmium induced alterations and activities of ATPase were significantly restored by genistein treatment. CONCLUSION: The present study observations show promising results of genistein against cadmium-induced neurotoxic effects in wistar rats. Thus its potent antioxidant and cytoprotective effects could act as potent therapeutic agent against various neuro-degenerative diseases involving oxidative stress as primary mechanism.

Locality and universality of quantum memory effects.

The modeling and analysis of the dynamics of complex systems often requires to employ non-Markovian stochastic processes. While there is a clear and well-established mathematical definition for non-Markovianity in the case of classical systems, the extension to the quantum regime recently caused a vivid debate, leading to many different proposals for the characterization and quantification of memory effects in the dynamics of open quantum systems. Here, we derive a mathematical representation for the non-Markovianity measure based on the exchange of information between the open system and its environment, which reveals the locality and universality of non-Markovianity in the quantum state space and substantially simplifies its numerical and experimental determination. We further illustrate the application of this representation by means of an all-optical experiment which allows the measurement of the degree of memory effects in a photonic quantum process with high accuracy.

Targeting central serotonergic neurons with lentiviral vectors based on a transcriptional amplification strategy.

Numerous pathological processes have been linked to disorders of the central 5-hydroxytryptamine (5HT) system but the possibility of gene therapy through modulation of 5HT system remained unexplored due to the lack of the specific targeting vectors. We explored the sequences upstream of the tryptophan hydroxylase-2 (TPH-2) gene, the key enzyme in neuronal 5HT synthesis and generated lentiviral vectors, which were then tested in vivo using microinjections into the rat raphe. All fragments longer than 1 kb (called 2TPH, 3.6TPH and 6.7TPH) drove highly specific expression in 5HT neurons which was, however too weak to be detectable without immunostaining. To enhance the level of expression, a two-step transcriptional amplification strategy was employed whereby the activity of a TPH-2 promoter fragment was potentiated by a chimeric enhancer GAL4/p65. Surprisingly, previously published implementations of this strategy compromised the specificity of expression. We therefore used a new approach where both, the transgene and GAL4/p65 are co-expressed using an internal ribosomal entry site and GAL4/p65 operates in a positive feedback manner to amplify the expression. Thus, we have generated new vectors, which are both, highly specific for 5HT neurons and sufficiently powerful. They open a range of new opportunities for enquiries into genetic correction of 5HT-related disorders.

Role of reynolds stress-induced poloidal flow in triggering the transition to improved ohmic confinement on the HT-6M tokamak

Time and space resolved measurements of electrostatic Reynolds stress, radial electric field E(r), and plasma rotations have been performed across the transition to improved Ohmic confinement in the Hefei Tokamak-6M (HT-6M). The first experimental evidence of the correlation between the enhanced Reynolds stress gradient and the poloidal flow acceleration in the edge plasma is presented. The results indicate that the turbulence-induced Reynolds stress might be the dominant mechanism to create the sheared poloidal flow and E(r), which may further trigger the transition.