ABCG2 is associated with HER-2 Expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>ABCG2 is an ABC transporter. It has been demonstrated that endogenous ABCG2 expression in certain cancers is a possible reflection of the differentiated phenotype of the cell of origin and likely contributes to intrinsic drug resistance. But little is known about the contribution of ABCG2 to the drug resistance and the clinicopathological characteristics in breast cancer. In the present study, we investigated the expression of ABCG2 and the correlations between ABCG2 expression and patients' clinicopathological and biological characteristics.</p> <p>Methods</p> <p>Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 breast cancer patients with clinicopathological data.</p> <p>Results</p> <p>The results showed that ABCG2 was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive stain for ABCG2 was defined as a brown stain observed in the cytoplasm and cytomembrane. A statistically significant correlation was demonstrated between ABCG2 expression and HER-2 expression (p = 0.001), lymph node metastasis (p = 0.049), and clinical stage (p = 0.015) respectively.</p> <p>Conclusion</p> <p>ABCG2 correlated with Her-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. It could be a novel potential bio-marker which can predict biological behavior, clinical progression, prognosis and chemotherapy effectiveness.</p

High Performance Composite Polymer Electrolytes Doped With Spherical-Like and Honeycomb Structural Li0.1Ca0.9TiO3 Particles

The spherical-like and honeycomb structural Li0.1Ca0.9TiO3 particles are prepared by spray drying combined with following calcination confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS). The poly (vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP))-based composite polymer electrolytes (CPEs) modified with the particles are fabricated by phase inversion and activation processes. The characterization results show that the as-prepared CPE membranes possess the smoothest surface and most abundant micropores with the lowest crystallinity with adding the particles into the polymer matrix, which results in high ionic conductivity (3.947 mS cm−1) and lithium ion transference number (0.4962) at ambient temperature. The interfacial resistance can be quickly stabilized at 508 Ω after 5 days storage and the electrochemical working window is up to 5.2 V. Moreover, the mechanical strength of the membranes gains significant improvement without lowering the ionic conductivity. Furthermore, the assembled coin cell can also deliver high discharge specific capacity and preserve steady cycle performance at different current densities. Those outstanding properties may be ascribed to the distinctive structure of the tailored spherical-like and honeycomb structural Li0.1Ca0.9TiO3 particles, which can guarantee the desirable CPEs as a new promising candidate for the polymer electrolyte

Effects of treatment with Astragalus Membranaceus on function of rat leydig cells

Background Astragalus membranaceus (AM) is a Chinese traditional herb which has been reported to have broad positive effects on many diseases, including hepatitis, heart disease, diabetes and skin disease. AM can promote cell proliferation, increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and inhibit apoptosis by regulating the transcription of proto-oncogenes controlling cell death. While AM is included in some commercially available “testosterone boosting supplements”, studies directly testing ability of AM to modulate testosterone production are lacking. In the present study, we examined the effects of AM on Leydig cell function in vitro. Methods Rat Leydig cells were purified and treated with AM at different concentrations (0 μg/mL, 10 μg/mL, 20 μg/mL, 50 μg/mL, 100 μg/mL and 150 μg/mL) and cell counting-8 (CCK-8) assay, Enzyme-linked immunosorbent assay, quantitative real time PCR and analysis of activities of SOD and GPx were done respectively. Results Treatment with 100 μg/mL (P \u3c 0.05) and 150 μg/mL AM (P \u3c 0.01) significantly increased Leydig cell numbers. Treatment with AM (20 μg/mL, 50 μg/mL and 100 μg/mL) significantly increased testosterone production (P \u3c 0.01). In addition, increased Leydig cell SOD and GPx activities were observed in response to 20 μg/mL and 50 μg/mL AM treatment (P \u3c 0.01). Furthermore, expression of Bax mRNA was significantly decreased (P \u3c 0.01), and the ratio of Bcl-2/Bax mRNA was significantly increased in response to 20 μg/mL AM in the culture medium (P \u3c 0.05). Conclusions Results supported a beneficial effect of AM on multiple aspects of rat Leydig cell function in vitro including testosterone production

Imputation-Based Whole-Genome Sequence Association Study Reveals Constant and Novel Loci for Hematological Traits in a Large-Scale Swine F2 Resource Population

The whole-genome sequences of progenies with low-density single-nucleotide polymorphism (SNP) genotypes can be imputed with high accuracy based on the deep-coverage sequences of key ancestors. With this imputation technology, a more powerful genome-wide association study (GWAS) can be carried out using imputed whole-genome variants and the phenotypes of interest to overcome the shortcomings of low-power detection and the large confidence interval derived from low-density SNP markers in classic association studies. In this study, 19 ancestors of a large-scale swine F2 White Duroc × Erhualian population were deeply sequenced for their genome with an average coverage of 25×. Considering 98 pigs from 10 different breeds with high-quality deep sequenced genomes, we imputed the whole genomic variants of 1020 F2 pigs genotyped by the PorcineSNP60 BeadChip with high accuracy and obtained 14,851,440 sequence variants after quality control. Based on this, 87 novel quantitative traits loci (QTLs) for 18 hematological traits at three different physiological stages of the F2 pigs were identified, among which most of the novel QTLs have been repeated in two of the three stages. Literature mining pinpointed that the FGF14 and LCLAT1 genes at SSC11 and SSC3 may affect the MCH at day 240 and MCV at day 18, respectively. The present study shows that combining high-quality imputed genomic variants and correlated phenomic traits into GWAS can improve the capability to detect QTL considerably. The large number of different QTLs for hematological traits identified at multiple growth stages implies the complexity and time specificity of these traits

Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

<p>Abstract</p> <p>Background</p> <p>Celastrol is an active ingredient of the traditional Chinese medicinal plant <it>Tripterygium Wilfordii</it>, which exhibits significant antitumor activity in different cancer models <it>in vitro </it>and <it>in vivo</it>; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity.</p> <p>Methods</p> <p>The downregulation of heat shock protein 90 (HSP90) client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK), and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS) was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP) and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC) complexes.</p> <p>Results</p> <p>Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC), an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP). Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC. Moreover, the inhibition of MRC complex I activity preceded ROS accumulation in H1299 cells after celastrol treatment.</p> <p>Conclusion</p> <p>We identified ROS as the key intermediate for celastrol-induced cytotoxicity. JNK was activated by celastrol-induced ROS accumulation and then initiated mitochondrial-mediated apoptosis. Celastrol induced the downregulation of HSP90 client proteins through ROS accumulation and facilitated ROS accumulation by inhibiting MRC complex I activity. These results identify a novel target for celastrol-induced anticancer activity and define its mode of action.</p

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO