The effects of quercetin and kaempferol on multidrug resistance and the expression of related genes in human erythroleukemic K562/A cells

Leukemia chemotherapy is believed to be impeded by multidrug resistance (MDR). Some compounds of flavonoid molecules were previously shown to inhibit drug transporter Pgp or induce apoptosis to sensitize MDR tumors. In this study, we attempted to investigate the possibility and mechanism of quercetin and kaempferol, flavonoid molecules, in reversing MDR. K562/A cells were cultured in vitro with the flavonoids as single and in combination respectively. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 -diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was examined by Annexin V/PI staining method. Moreover, the expression of related genes for drug transporters and apoptosis was also tested after incubation with resveratrol for the first time. Results show a dose dependent manner and synergistic effect of the two compounds on K562/A. Furthermore, some of the genes in drug transporter families such as ATP-binding cassette (ABC) and solute carrier (SLC) and apoptosis related genes such as Bcl-2、tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) families were regulated. The experiment indicates that quercetin and kaempferol may be used as reveratrol in leukemia chemotherapy, but their interaction and difference should be noticed.Key words: Flavonoids, leukemia, multidrug resistance, polymerase chain reaction (PCR) array

Attributing variations of temporal and spatial groundwater recharge: a statistical analysis of climatic and non-climatic factors

This paper demonstrated the benefits of statistical methods when investigating the climatic and non-climatic drivers responsible for variations in groundwater recharge with a series of up to 43 years of annual recharge for 426 bores in South-East South Australia. We identified the factors influencing groundwater recharge based on 71 climatic metrics and 13 non-climatic metrics (including groundwater abstraction). The results showed: 1) Rainfall during April to October was the most important variable influencing recharge temporal variation, with its decline identified as the most significant factor related to recharge reduction; 2) In contrast, a negative correlation between rainfall during December to February (DJF) and annual groundwater recharge was found. This suggests that a seasonal shift in rainfall (such as decreasing rainfall during April to October and an increase during DJF) can result in a decline in recharge even when the annual rainfall remains unchanged; 3) The length of wet spells (consecutive rain days) and increasing PET were additional significant predictors for recharge temporal variation. It demonstrated that a simple empirical relationship (such as recharge as a fixed percentage of rainfall) is not a reliable estimation of renewable groundwater resources under changing climatic conditions; 4) There is a statistically significant spatial correlation between mean groundwater depth and recharge, and this implies that a reduction in rainfall can lead to a positive feedback loop of declining recharge and water level; 5) Spatially the most statistically significant factors influencing groundwater recharge were soil types and land attributes. The findings of this study can identify which stressors should be included when investigating the impact of climate change on groundwater recharge

Threats to the Soil Resource Base of Food Security in China and Europe. A report from the Sino-EU Panel on Land and Soil

To secure adequate food supply is the major challenge for humanity in the 21st century. Growing world population and its urbanization put pressure on this basic need, which is further threatened by the constant loss of fertile land. The assessment of sustainability of food supply under increasing pressure on land resources has been selected as one of the most important priority topics of the activities of Sino-EU Panel on Land and Soil (SEPLS). The Panel has performed a number of related researches and discussed the results on a scientific seminar in January 2012 in Nanjing, China. This report is an output of this seminar with a summary of the structured discussions on the below issues. 1. Urban and peri-urban development (soil sealing and loss of land functions) Urbanization and the linked spread of infrastructural development mean sealing of soil surfaces. Soil sealing is the most rapidly growing limitation for soil functions (including biomass production function) both in China and Europe. Soil sealing in China has been taking dramatic degree in the last two decades and the process is estimated to continue in the coming period as well. While urban and peri-urban development is looked as a necessity for social development, its negative effect on natural resources are inevitable. 2. Land degradation Despite the widely recognized importance of land degradation in the unsustainability of economic development and implementation of various policies to halt degradation (e.g. green for grain programme in China; cross-compliance measures in the EU), loss of land productivity by degradation is an ongoing process both in China and the EU. Major forms of soil degradation (erosion, desertification, landslides etc.) are similar in both regions. Assessment of the causes and consequences of soil degradation processes in relation to policy actions is highlighted among the priorities of the SEPLS. 3. Intensive agriculture and multi-function management of land resources Intensification and extensification in agriculture can be considered as the main changes in land use in rural areas in both EU and China. While agricultural intensification is one of the greatest threats to the soil and environment and then hampers the sustainable development of agriculture and food security. To meet this challenge, sustainable management of multi-functionality of land resources is undoubtedly an effective strategy, in which the EU has a good expertise. Bilateral exchange of the experience and knowledge benefits the sustainable management of land resources.JRC.H.5-Land Resources Managemen

High-voltage-compatible, fully depleted CCDs

We describe charge-coupled device (CCD) developmentactivities at the Lawrence Berkeley National Laboratory (LBNL).Back-illuminated CCDs fabricated on 200-300 mu m thick, fully depleted,high-resistivity silicon substrates are produced in partnership with acommercial CCD foundry.The CCDs are fully depleted by the application ofa substrate bias voltage. Spatial resolution considerations requireoperation of thick, fully depleted CCDs at high substrate bias voltages.We have developed CCDs that are compatible with substrate bias voltagesof at least 200V. This improves spatial resolution for a given thickness,and allows for full depletion of thicker CCDs than previously considered.We have demonstrated full depletion of 650-675 mu m thick CCDs, withpotential applications in direct x-ray detection. In this work we discussthe issues related to high-voltage operation of fully depleted CCDs, aswell as experimental results on high-voltage-compatible CCDs

Down-Regulation of AP-4 Inhibits Proliferation, Induces Cell Cycle Arrest and Promotes Apoptosis in Human Gastric Cancer Cells

BACKGROUND: AP-4 belongs to the basic helix-loop-helix leucine-zipper subgroup; it controls target gene expression, regulates growth, development and cell apoptosis and has been implicated in tumorigenesis. Our previous studies indicated that AP-4 was frequently overexpressed in gastric cancers and may be associated with the poor prognosis. The purpose of this study is to examine whether silencing of AP-4 can alter biological characteristics of gastric cancer cells. METHODS: Two specific siRNAs targeting AP-4 were designed, synthesized, and transfected into gastric cancer cell lines and human normal mucosa cells. AP-4 expression was measured with real-time quantitative PCR and Western blot. Cell proliferation and chemo-sensitivity were detected by CCK-8 assay. Cell cycle assay and apoptosis assay were performed by flow cytometer, and relative expression of cell cycle regulators were detected by real-time quantitative PCR and Western blot, expression of the factors involved in the apoptosis pathway were examined in mRNA and protein level. RESULTS: The expression of AP-4 was silenced by the siRNAs transfection and the effects of AP-4 knockdown lasted 24 to 96 hrs. The siRNA-mediated silencing of AP-4 suppressed the cellular proliferation, induced apoptosis and sensitized cancer cells to anticancer drugs. In addition, the expression level of p21, p53 and Caspase-9 were increased when AP-4 was knockdown, but the expression of cyclin D1, Bcl-2 and Bcl-x(L) was inhibited. It didn't induce cell cycle arrest when AP-4 was knockdown in p53 defect gastric cancer cell line Kato-III. CONCLUSIONS: These results illustrated that gene silencing of AP-4 can efficiently inhibited cell proliferation, triggered apoptosis and sensitized cancer cells to anticancer drugs in vitro, suggesting that AP-4 siRNAs mediated silencing has a potential value in the treatment of human gastric cancer

Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host

Since 2003, H5N1 influenza viruses have caused over 400 known cases of human infection with a mortality rate greater than 60%. Most of these cases resulted from direct contact with virus-contaminated poultry or poultry products. Although only limited human-to-human transmission has been reported to date, it is feared that efficient human-to-human transmission of H5N1 viruses has the potential to cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral transmission among humans is largely unknown. In this study, we used guinea pigs as a mammalian model to study the transmission of six different H5N1 avian influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35) and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated animals to naïve contact animals. Our mutagenesis analysis revealed that the amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at 158–160, was responsible for HA binding to sialylated glycans and was critical for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates