Marsdenia tenacissima extract alters crucial metabolites in cancer, determined by 1H NMR based metabolomics approach

Altered metabolites level in the biosystems, is the potential cause of cancer, the primary reason of alteration of metabolism is change in nutrient consumption and waste excretion, as a result genetic mutation leads to cancer initiation and progression. Aberration of specific metabolites such as fumarate, succinate, 2-hydroxyglutarate may alter cell signaling. We collected liver and kidney samples and prepared for 1 H NMR analysis, then executed NMR spectroscopy. We used a set of domestic R scripts to perform an unsupervised principal component analysis (PCA) and a supervised orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA). It signifies class discrimination for getting a clear separation, whereas PCA scores plot signifies the model group kept further away from the control group than drug group on the horizontal axis. In another PCA scores plots, most parts of the control group was overlapping with the drug group but was distant from the model group. Marsdenia tenacissima extract (MTE) (Chines name: Xiao-Ai-Ping, XAP) modulates level of crucial metabolites such as fumarate, lactate, succinate, determined by 1 H NMR spectroscopy and their altered level contributes major role in cancer

BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The role of B Lymphocyte Stimulator (BLyS) in the survival of malignant B cells and the maintenance of normal B cell development and homeostasis has been intensively studied in the literature. However, the influence of BLyS on breast cancer progression remains unclear. The study aimed to investigate the effect of hypoxia on BLyS regulation, cell migratory response to BLyS and the possible molecular mechanisms.</p> <p>Methods</p> <p>In this study, we examined the role of BLyS in the migration of human breast cancer cells by transwell assay. We also explored whether BLyS and its receptors expressed in human breast cancer cell lines by immunofluorescence and Western Blotting. Then we detected the expression level of BLyS in both normoxic and hypoxic conditions by real time-PCR and Western Blotting. Pathways involved were confirmed by Western Blotting, immunofluorescence, transwell assay and luciferase assay.</p> <p>Results</p> <p>According to our study, the expression level of BlyS was increased in human breast cancer cell lines in hypoxic conditions. Up-regulation of this protein led to activation and nuclear translocation of NF-kappa B p65. We also found that the number of migrated cells was increased in the presence of BLyS and inhibition of phosphorylation of Akt attenuated the enhanced migratory response.</p> <p>Conclusions</p> <p>It suggested that better understanding of BLyS, an immunopotentiator, may offer a potential therapeutic target for the treatment of human breast cancers. In addition, BLyS promoted breast cancer cells migration, underscoring the necessity of appropriate applications of immunopotentiators to cancer treatment.</p

Electronic band reconstruction across the insulator-metal transition in colossal magnetoresistive EuCd2P2

While colossal magnetoresistance (CMR) in Eu-based compounds is often associated with strong spin-carrier interactions, the underlying reconstruction of the electronic bands is much less understood from spectroscopic experiments. Here using angle-resolved photoemission, we directly observe an electronic band reconstruction across the insulator-metal (and magnetic) transition in the recently discovered CMR compound EuCd2P2. This transition is manifested by a large magnetic band splitting associated with the magnetic order, as well as unusual energy shifts of the valence bands: both the large ordered moment of Eu and carrier localization in the paramagnetic phase are crucial. Our results provide spectroscopic evidence for an electronic structure reconstruction underlying the enormous CMR observed in EuCd2P2, which could be important for understanding Eu-based CMR materials, as well as designing CMR materials based on large-moment rare-earth magnets.Comment: 6 pages, 4 figure

Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients

Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped. Dose-adjusted trough blood concentrations (C/D ratio, mg/kg body weight) in lung transplant patients during the first 4 postoperative weeks were calculated. Results. IL-18 rs5744247 allele C and rs1946518 allele A were associated with fast tacrolimus metabolism. Combined analysis showed that the numbers of low IL-18 mRNA expression alleles had positive correlation with tacrolimus C/D ratios in lung transplant recipients. The influence of IL-18 polymorphisms on tacrolimus C/D ratios was observed in CYP3A5 expresser recipients, but not in CYP3A5 nonexpresser recipients. No clinical significance of tacrolimus C/D ratios difference of IL-10 polymorphisms was found in our data. Conclusions. IL-18 polymorphisms may influence tacrolimus elimination in lung transplantation patients

Genome-Wide Transcriptome and Antioxidant Analyses on Gamma-Irradiated Phases of Deinococcus radiodurans R1

Adaptation of D. radiodurans cells to extreme irradiation environments requires dynamic interactions between gene expression and metabolic regulatory networks, but studies typically address only a single layer of regulation during the recovery period after irradiation. Dynamic transcriptome analysis of D. radiodurans cells using strand-specific RNA sequencing (ssRNA-seq), combined with LC-MS based metabolite analysis, allowed an estimate of the immediate expression pattern of genes and antioxidants in response to irradiation. Transcriptome dynamics were examined in cells by ssRNA-seq covering its predicted genes. Of the 144 non-coding RNAs that were annotated, 49 of these were transfer RNAs and 95 were putative novel antisense RNAs. Genes differentially expressed during irradiation and recovery included those involved in DNA repair, degradation of damaged proteins and tricarboxylic acid (TCA) cycle metabolism. The knockout mutant crtB (phytoene synthase gene) was unable to produce carotenoids, and exhibited a decreased survival rate after irradiation, suggesting a role for these pigments in radiation resistance. Network components identified in this study, including repair and metabolic genes and antioxidants, provided new insights into the complex mechanism of radiation resistance in D. radiodurans

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage

Influence of Temperature Field Distribution on the Growth of Aluminum Nitride Crystal by Simulation Technology

During the crystal growth process, the temperature distribution in the reactor plays a decisive role in crystal growth and directly affects the crystal growth rate. In this study, a numerical simulation method was used to model and study the temperature distribution in the PVT AlN crystal reactor. By adjusting the relative position of the heater and the crucible, different temperature field structures are obtained. The effect of different temperature gradients on the decisiveness of the crystal growth and the growth rate is explored and analyzed, and the best scheme is selected. With the help of simulation technology, a 52 mm diameter AlN crystal is successfully prepared with a certain thickness. The results prove the feasibility of the simulation scheme, which is supported by the existing experimental data

Influence of Temperature Field Distribution on the Growth of Aluminum Nitride Crystal by Simulation Technology

During the crystal growth process, the temperature distribution in the reactor plays a decisive role in crystal growth and directly affects the crystal growth rate. In this study, a numerical simulation method was used to model and study the temperature distribution in the PVT AlN crystal reactor. By adjusting the relative position of the heater and the crucible, different temperature field structures are obtained. The effect of different temperature gradients on the decisiveness of the crystal growth and the growth rate is explored and analyzed, and the best scheme is selected. With the help of simulation technology, a 52 mm diameter AlN crystal is successfully prepared with a certain thickness. The results prove the feasibility of the simulation scheme, which is supported by the existing experimental data