MIR-99a and MIR-99b Modulate TGF-β Induced Epithelial to Mesenchymal Plasticity in Normal Murine Mammary Gland Cells

Epithelial to mesenchymal transition (EMT) is a key process during embryonic development and disease development and progression. During EMT, epithelial cells lose epithelial features and express mesenchymal cell markers, which correlate with increased cell migration and invasion. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that induces EMT in multiple cell types. The TGF-β pathway is regulated by microRNAs (miRNAs), which are small non-coding RNAs regulating the translation of specific messenger RNAs

Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin

<p>Abstract</p> <p>Background</p> <p>The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC.</p> <p>Methods</p> <p>Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells.</p> <p>Results</p> <p>MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively).</p> <p>Conclusions</p> <p>The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.</p

Molecular therapy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further

Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution

MicroRNA (miRNA)–mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution

Improved activity of SnO for the photocatalytic oxygen evolution

SnO prepared by soft chemistry exhibits a black color and semiconducting properties. The X-ray diffraction indicates a tetragonal symmetry (SG: P4/nmm) with nano crystallites of an average size of 85 nm. The forbidden band, determined from the diffuse reflectance is found to be 1.46 eV. The electrical conductivity occurs by polaron hopping and follows an Arrhenius type law with activation energy of 0.21 eV, the change in the slope at 526 K is attributed to the oxidation to SnO2. The photo-electrochemical study shows n type conduction with a flat band potential of −0.45 V, close to the photocurrent onset potential (−0.40 V). The electrochemical impedance spectroscopy shows the bulk contribution of SnO (Rb = 1.7 kΩ cm2) and decreases down to 1.89 kΩ cm2 under illumination. The photocatalytic properties have been evaluated for the first time for to the oxygen evolution. The valence band, deriving from Sn2+: 5p orbital with a potential (−0.80 VSCE/5.55 eV), is suitably positioned with respect to O2/H2O level (∼0.6 VSCE), leading to water oxidation under visible light. The best performance occurs at pH ∼ 7 with an oxygen liberation rate of 23 µmol mL h−1 (mg catalyst)−1 and a quantum efficiency of 1.2%. An improvement of ∼13% is observed on the system SnO/clay

Synthesis, physical and semiconducting properties of SnS2 prepared by chemical route

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Effects of cooling rate on the glass formation process and the microstructural evolution of Silver mono-component metallic glass

International audienceIn this study, using molecular dynamics simulations in combination with the embedded-atom approach, we investigate the effect of cooling rate on the microstructural evolution and the glass formation process of Silver monatomic metallic glass. In order to accomplish our investigation, we have utilised a variety of analytical techniques, including the pair distribution function, the bond angle distribution, the Voronoi tessellation analysis, the coordination number, and the five-fold symmetry. The splitting of the second peak in the pair distribution function during the cooling process confirms that glass formation occurs. Via the Went-Abraham parameter, we have found that a faster cooling rate leads to a higher glass transition temperature , and a less relaxed glass has a lower density due to its greater free volume and disordered structure. In the same context, the bond angle distribution revealed that the cooling rate clearly influences the icosahedral short-range order in the quenched system, and the Voronoi tessellation analysis indicated that the percentage of mixed-like and icosahedral-like clusters grows as the cooling rate increases. Furthermore, the coordination number indicated that when the temperature drops throughout the cooling process, the local environment and topological structure of the amorphous Silver change. Lastly, we have also revealed that the five-fold symmetry controls the formation of the amorphous structure and that the highest cooling rate yields the greatest amount of icosahedral-like clusters in the vitreous phase, implying that fast cooling rates subserve the formation of glassy states with icosahedral-like features