Reprogramming of Glucose Metabolism Pathways in Triple-negative Breast Cancer Cells under Hypoxia / 中国生物化学与分子生物学报

Metabolic changes are recognized as one of the hallmarks of cancer cells. Previous studies have shown that hypoxia can change the glucose metabolism of cancer cells. However, the mechanisms still need to be studied in detail. In this study, by using RNA-Sequencing (RNA-seq) and bioinformatics analysis, we found that there is a significant change in the expression of 334 genes in BT549 cells and 215 genes in MDA-MB-231 cells induced by hypoxia at the mRNA level. Most of these genes were associated with glucose metabolism. RNA-seq data, Western blot, enzyme activity assays, and metabolite quantification experiments showed that the glucose uptake increased by elevating the expression of glucose transporter protein 1 (GLUT1) in BT549 cells and GLUT1 and GLUT3 in MDA-MB-231 cells induced by hypoxia. Hypoxia promotes glycolysis by increasing the expression of at least one isozyme or enzyme protein subunit of the enzymes that catalyze the each reaction in the glycolysis pathway, as well as the regulatory enzymes 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) and 4 (PFKFB4) isozymes. Hypoxia increases the expression of pyruvate dehydrogenase kinase 1 (PDK1) and PDK3 and reduces the expression of isocitrate dehydrogenase 3(IDH3), succinate dehydrogenase subunit B(SDHB) and D(SDHD) to reduce the aerobic oxidation pathway. The expression of glucose-6-phosphate dehydrogenase (G6PD) and glycogen synthase was significantly increased to promote the pentose phosphate pathway and glycogen synthesis pathway. The mRNA levels of enzyme genes had no significant difference in gluconeogenesis and glycogenolysis. The breast cancer database suggests that the mRNA levels of the glucose metabolism enzymes were consistent in vivo and in vitro. Hypoxia regulates the reprogramming of glucose metabolism by altering the gene expression of isozymes or subunits of these enzymes. The study comprehensively analyzed the effects of hypoxia on the expression of all enzyme genes and major regulatory enzymes in six glucose metabolism pathways and provides an understanding of glucose metabolism in cancer cells under a hypoxia environment.

Carnosic acid alleviates brain injury through NF­κB­regulated inflammation and Caspase­3­associated apoptosis in high fat­induced mouse models.

High fat diet (HFD) is a risk factor for various diseases in humans and animals. Metabolic disease­induced brain injury is becoming an increasingly popular research topic. Carnosic acid (CA) is a phenolic diterpene synthesized by plants belonging to the Lamiaceae family, which exhibits multiple biological activities. In the present study, a mouse model of HFD­induced metabolic syndrome was generated. The body weight, liver weight, daily food intake, daily caloric intake, serum TG, serum TC, serum insulin and serum glucose of animals treated with CA were recorded. Additionally, the gene and protein expression levels of inflammatory cytokines, NF­κB signaling componnts, and caspase­3 were evaluated in the various CA treatment groups via immunohistochemical analysis, western blotting, reverse transcription­quantitative PCR. CA treatment significantly decreased HFD­induced metabolic syndrome by decreasing the serum levels of triglycerides, total cholesterol, insulin and glucose. Furthermore, CA served a protective role against brain injury by inhibiting the inflammatory response. CA significantly decreased the protein expression levels of various pro­inflammatory cytokines in serum and brain tissues, including interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α, regulated by the NF­κB signaling pathway. In addition, CA was revealed to promote the expression levels of anti­apoptotic Bcl­2, and to decrease the expression levels of pro­apoptotic Bax and matrix metallopeptidase 9. The present results suggested that CA was able to alleviate brain injury by modulating the inflammatory response and the apoptotic pathway. Administration of CA may represent a novel therapeutic strategy to treat metabolic disease­induced brain injury in the future.

Field and long-term demonstration of a wide area quantum key distribution network.

A wide area quantum key distribution (QKD) network deployed on communication infrastructures provided by China Mobile Ltd. is demonstrated. Three cities and two metropolitan area QKD networks were linked up to form the Hefei-Chaohu-Wuhu wide area QKD network with over 150 kilometers coverage area, in which Hefei metropolitan area QKD network was a typical full-mesh core network to offer all-to-all interconnections, and Wuhu metropolitan area QKD network was a representative quantum access network with point-to-multipoint configuration. The whole wide area QKD network ran for more than 5000 hours, from 21 December 2011 to 19 July 2012, and part of the network stopped until last December. To adapt to the complex and volatile field environment, the Faraday-Michelson QKD system with several stability measures was adopted when we designed QKD devices. Through standardized design of QKD devices, resolution of symmetry problem of QKD devices, and seamless switching in dynamic QKD network, we realized the effective integration between point-to-point QKD techniques and networking schemes.

Experimental generation of an eight-photon Greenberger-Horne-Zeilinger state.

Multi-partite entangled states are important for developing studies of quantum networking and quantum computation. To date, the largest number of particles that have been successfully manipulated is 14 trapped ions. Yet in quantum information science, photons have particular advantages over other systems. In particular, they are more easily transportable qubits and are more robust against decoherence. Thus far, the largest number of photons to have been successfully manipulated in an experiment is six. Here we demonstrate, for the first time, an eight-photon Greenberger-Horne-Zeilinger state with a measured fidelity of 0.59±0.02, which proved the presence of genuine eight-partite entanglement. This is achieved by improving the photon detection efficiency to 25% with a 300-mW pump laser. With this state, we also demonstrate an eight-party quantum communication complexity scenario. This eight-photon entangled-state source may be useful in one-way quantum computation, quantum networks and other quantum information processing tasks.