Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis

<p>Abstract</p> <p>Background</p> <p>In addition to its essential role in ribonucleotide reduction, ribonucleotide reductase (RNR) small subunit, RRM2, has been known to play a critical role in determining tumor malignancy. Overexpression of RRM2 significantly enhances the invasive and metastatic potential of tumor. Angiogenesis is critical to tumor malignancy; it plays an essential role in tumor growth and metastasis. It is important to investigate whether the angiogenic potential of tumor is affected by RRM2.</p> <p>Results</p> <p>We examined the expression of antiangiogenic thrombospondin-1 (TSP-1) and proangiogenic vascular endothelial growth factor (VEGF) in two RRM2-overexpressing KB cells: KB-M2-D and KB-HURs. We found that TSP-1 was significantly decreased in both KB-M2-D and KB-HURs cells compared to the parental KB and mock transfected KB-V. Simultaneously, RRM2-overexpressing KB cells showed increased production of VEGF mRNA and protein. In contrast, attenuating RRM2 expression via siRNA resulted in a significant increased TSP-1 expression in both KB and LNCaP cells; while the expression of VEGF by the two cells was significantly decreased under both normoxia and hypoxia. In comparison with KB-V, overexpression of RRM2 had no significant effect on proliferation in vitro, but it dramatically accelerated in vivo subcutaneous growth of KB-M2-D. KB-M2-D possessed more angiogenic potential than KB-V, as shown in vitro by its increased chemotaxis for endothelial cells and in vivo by the generation of more vascularized tumor xenografts.</p> <p>Conclusion</p> <p>These findings suggest a positive role of RRM2 in tumor angiogenesis and growth through regulation of the expression of TSP-1 and VEGF.</p

Analysis on the technical detection capacity of radioactive substances in food in China

To analyze the detection capacity of radioactive substances in food in China， and improve the radioactive contamination monitoring system. By studying the distribution of certified institutions and testing items and the results of proficiency assessment， the current situation and deficiencies of the detection capacities were analyzed， and corresponding countermeasures were put forward. The capacity of radioactive material detection in China can better support the operation of the monitoring system， however， the effectiveness and sustainability of testing capacity， the layout of capacity network and the construction of food radioactive pollution monitoring system need to be further improved and strengthened， so as to meet the needs of normal circumstances and rapid response in case of nuclear or radiological emergencies in China

Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells.

Autophagy is the principal catabolic response to nutrient starvation and is necessary to clear dysfunctional or damaged organelles, but excessive autophagy can be cytotoxic or cytostatic and contributes to cell death. Depending on the abundance of enzymes involved in molecule biosynthesis, cells can be dependent on uptake of exogenous nutrients to provide these molecules. Argininosuccinate synthetase 1 (ASS1) is a key enzyme in arginine biosynthesis, and its abundance is reduced in many solid tumors, making them sensitive to external arginine depletion. We demonstrated that prolonged arginine starvation by exposure to ADI-PEG20 (pegylated arginine deiminase) induced autophagy-dependent death of ASS1-deficient breast cancer cells, because these cells are arginine auxotrophs (dependent on uptake of extracellular arginine). Indeed, these breast cancer cells died in culture when exposed to ADI-PEG20 or cultured in the absence of arginine. Arginine starvation induced mitochondrial oxidative stress, which impaired mitochondrial bioenergetics and integrity. Furthermore, arginine starvation killed breast cancer cells in vivo and in vitro only if they were autophagy-competent. Thus, a key mechanism underlying the lethality induced by prolonged arginine starvation was the cytotoxic autophagy that occurred in response to mitochondrial damage. Last, ASS1 was either low in abundance or absent in more than 60% of 149 random breast cancer biosamples, suggesting that patients with such tumors could be candidates for arginine starvation therapy

Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease

Coronary heart disease (CHD) is top risk factor for health in modern society, causing high mortality rate each year. However, there is no reliable way for early diagnosis and prevention of CHD so far. So study the mechanism of CHD and development of novel biomarkers is urgently needed. In this study, metabolomics and metagenomics technology are applied to discover new biomarkers from plasma and urine of 59 CHD patients and 43 healthy controls and trace their origin. We identify GlcNAc-6-P which has good diagnostic capability and can be used as potential biomarkers for CHD, together with mannitol and 15 plasma cholines. These identified metabolites show significant correlations with clinical biochemical indexes. Meanwhile, GlcNAc-6-P and mannitol are potential metabolites originated from intestinal microbiota. Association analysis on species and function levels between intestinal microbes and metabolites suggest a close correlation between Clostridium sp. HGF2 and GlcNAc-6-P, Clostridium sp. HGF2, Streptococcus sp. M143, Streptococcus sp. M334 and mannitol. These suggest the metabolic abnormality is significant and gut microbiota dysbiosis happens in CHD patients

Lymph node dissection effectively shortens the course of anti-tuberculosis treatment

Objective: To evaluate the clinical efficacy of postoperative ultra-short-course chemotherapy in treating cervical lymph node tuberculosis in the Wuhan region. Methods: Follow-up of patients in the surgery and non-surgery group after discharge, evaluating the number of cervical lymph nodes during the administration of antituberculosis drugs. Results: The age of the patients in the surgical therapy group ranged from 6 to 83 years old with an average age of 45 and a standard deviation of 20. The number of cervical lymph nodes in the patients ranged from 1.61 to 8.15. The average antituberculosis treatment duration before surgery for patients in the surgical group was 98.02 days, while for patients in the non-surgical group it was 96.13 days. The average length of hospital stay for patients receiving surgical treatment was 12.76 days, while for patients receiving non-surgical treatment it was 8.74 days. The average antituberculosis treatment duration after discharge for patients in the surgical group was 205 days, with a standard deviation of 42.39, while for patients in the non-surgical group it was 372 days, with a standard deviation of 71.54. The T-test results for antituberculosis treatment during hospitalization and after discharge were 98.3x10-10 and 5.02x10-67, respectively. Conclusion: After surgical treatment of cervical lymph node tuberculosis, the effectiveness of a 4–6 month short-course chemotherapy in Wuhan region is not weaker than the effectiveness of a conventional 6–9 month drug treatment

Mechanism of surface texture evolution in pure copper strips subjected to double rolling

Developing ultra-thin copper foils with different surface roughness and microstructure has important significance for improving the service performance and reducing the production cost of high-end circuit boards. In this paper, pure copper strips with initial cube texture were subjected to a double rolling process (deformation amount ranges from 50% to 95%), and the surface textures evolution law and mechanism of double-rolled strips were studied by an X-ray diffraction technique. The results show that when a deformation amount increased from 50% to 70%, the grains of two surfaces rotate away from the cube orientation, and the formed textures of two surfaces mainly consisted of C, S and B orientation components. The orientation density values for these three components on bright surface only had slight difference; the orientation density values for C and S components were much larger than that for B components on a matt surface. When the deformation amount increased to 90%, the increase extents of orientation density values for C and S components were obviously larger than that for B components on a bright surface; the increase extents of orientation density values for these three components were almost the same on the matt surface. It has been found that when deformation amount reaches 95%, the grains orientation of bright surface were relatively concentrated, and the orientation density value for C texture obviously increased to 11.68 and that for B texture was only 3.15; the grains orientation of matt surface were relatively dispersed, and the orientation density value for C texture increased to 9.26 and that for B texture obviously increased to 6.35, and the density values of these two textures had less difference. For the condition of strong compressive and shear stress on the bright surface, grains were mainly rotating to C texture orientation; compared with the bright surface, “semi-free” deformation condition on the matt surface is beneficial to promote much more grains to rotate to the B texture orientation

Directional Blasting Technology of Slit Charge for Geological Disposal of High-Level Radioactive Waste

Based on the slit charge technology, the blasting progress and the blasting theory have been studied in detail. Combined with the high-level radioactive waste geological disposal, in which the excavation damaged zone of the surrounding rock is required as small as possible, the testing of the Beishan exploration tunnel (BET) has been studied, and the blasting parameters have been designed using the slit charge technology. Theoretically, the rock failure criterion has been proposed, which adopted the dynamic mechanical parameters, such as the dynamic compress strength, dynamic tensile strength, dynamic modulus, dynamic passion ratio, dynamic fracture toughness, and dynamic stress intensity factor. Furthermore, the blasting test has been carried out under the same tunnel face with left and right sides simultaneously, and it can be found that the blasting effect with the slit charge technology is better than another side, which verified the useful and scientific meaning of this technology. It should be noticed that the blasting method includes numerous blasting parameters, which interact with each other. Those blasting parameters obtained just limited the slit charge, and the result and the theoretical knowledge could be applied to the blasting and excavation of the deep geoengineering and HLW geodisposal

Blasting Energy Analysis of the Different Cutting Methods

Based on the smooth blasting method, the blasting parameters of the Beishan exploration tunnel have been designed. According to the principle of blasting parameters design, three kinds of cutting methods have been laid out, which are straight parallel hole cutting, single-wedge cutting, and double-wedge cutting. The other parameters such as the borehole number, the detonator segment, and the charge amount of each hole are also designed. Then, the blasting tests under different cutting methods were carried out in the field. The results show that all the three cutting methods can achieve good utilization ratio of blasting holes. The blasting effect of straight parallel hole cutting is good. The rock slag size of single-wedge and double-wedge cutting is uniform, which is beneficial to slag extraction. Moreover, the blasting vibration velocity and blasting energy have been analyzed. It is found that the energy distribution of single-wedge and double-wedge cutting is more uniform, mainly concentrated in the high-frequency part, while the energy of straight parallel hole cutting is more concentrated in the low-frequency part. Among many factors affecting blasting vibration velocity, besides the explosive quantity, it would also be easily influenced by the cutting way. It should be noticed that the blasting method includes numerous blasting parameters, which interact with each other. Those blasting parameters obtained were just limited to the cutting method, and the result and the theoretical knowledge could be applied to the blasting and excavation of the deep geoengineering and the HLW geo-disposal