In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells

AIM: To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro. METHODS: Rat pancreatic tissue was submitted to digestion by collegenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XlHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulin- producing cells were detected by dithizone-staining. RESULTS: XlHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were signifi cantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 ± 0.43 vs 3.48 ± 0.81, P < 0.01 at 5.6 mmol/L; 4.86 ± 1.15 vs 10.25 ± 1.32, P < 0.01 at 16.7 mmol/L). CONCLUSION: PDX-1 can differentiate rat pancreaticductal epithelial cells into insulin-producing cells in vitro. In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells.

BRCA1 affects global DNA methylation through regulation of DNMT1

Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the promoter of the DNMT1 gene through a potential OCT1 site and the binding is required for maintaining a transcriptional active configuration of the promoter in both mouse and human cells. We further demonstrated that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration in several types of tissues examined in a BRCA1 mutant mouse model at premaligant stages. BRCA1 deficiency is also associated with significantly increased expression levels of several protooncogenes, including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while premalignant mammary epithelial cells displayed an intermediate state between tumors and controls. In human clinical samples, reduced expression of BRCA1 correlates with decreased levels of DNMT1, and reduced methylation of CpG islands. Thus, BRCA1 prevents global DNA hypomethylation through positively regulating DNMT1 expression, and this provides one of mechanisms for BRCAl-associated breast cancer formation.

Biomarker Records of Phytoplankton Productivity and Community Structure Changes During the Last 14000 Years in the Mud Area Southwest off Cheju Island, East China Sea

The ecological environment in the East China Sea(ECS)and the Yellow Sea(YS)has changed significantly due to sea-level rising and the Kuroshio incursion since the last deglaciation.In this study,biomarker records of core F10B from the mud area southwest off Cheju Island(MSWCI)were generated to evaluate phytoplankton productivity and community structure changes in response to environmental evolution during the last 14 kyr.The contents of diatom,dinoflagellate and haptophyte biomarkers(brassicasterol,dinosterol and C37alkenones)display similar trends,with increasing phytoplankton productivity during the last 14kyr due to the increased influences of the Kuroshio,and especially due to the eddy-induced upwelling during the late Holocene.On the other hand,the contents of terrestrial biomarkers(C28+C30+C32n-alkanols)and terrestrial organic matter(TOM)proxies(TMBR′and BIT)all reveal decreasing TOM input into the area around the sampling site for the 14 kyr,mostly due to sea-level ris-ing.Phytoplankton biomarker ratios reveal a shift from a haptophyte-dominated community at 6.2 2.5 kyr BP to a diatom-dominated community at 2.5 1.45 kyr BP,likely caused by a stronger cold eddy circulation system at 2.5 1.45 kyr BP in the MSWCI.

A Brief Analysis of the Applicability of the Archipelago Waters System in China

The archipelagic waters system is stipulated in the United Nations Convention on the Law of the Sea. It is closely related to China＇s marine legislation and maritime law enforcement. It is not only related to the integrity of our country＇s national sovereignty, but also to the maintenance of our maritime rights and interests. However, there is no comprehensive fundamental law governing the overall situation of marine development in our country, also no relevant legal code on the archipelagic waters system. Therefore, we should learn from the world＇s marine legislation and practice which the archipelagic waters system was written into China＇s marine legislation.

Numerieal Prediction of Storm Surge in the Qingdao Area Under the Impact of Climate Change

A typhoon-induced storm surge simulation system was developed for the Qingdao area, including a typhoon diagnostic model for the generation of wind and pressure fields and a 2D Advanced Circulation(ADCIRC) model for simulating the associated storm surge with a 200 m resolution along the Qingdao coastline. The system was validated by an extreme surge event Typhoon Mamie(8509) and the parameters of Typhoon Mamie were used to investigate the sensitivity of typhoon paths to Qingdao storm surges with four selected paths: the paths of Typhoons Mamie(8509), Opal, 3921 and 2413, the selection being made according to their relative position to Qingdao. Experiments based on the Typhoon Mamie(8509) storm surge were also conducted to study the possible influences of future climate changes, including the sea level rise and sea surface temperature(SST) rise, on storm surges along the Qingdao coast. Storm surge conditions under both present day and future(the end of the 21 st century) climate scenarios associated with the four selected paths were simulated. The results show that with the same intensity, when typhoons follow the paths of 3921 and 2413, they would lead to the most serious disasters in different areas of Qingdao. Sea level and SST affect storm surges in different ways: sea level rise affects storm surge mainly through its influence on the tide amplitude, while the increased SST has direct impact on the intensity of the surges. The possible maximum risk of storm surges in 2100 in the Qingdao area caused by typhoons like Mamie(8509) was also estimated in this study.

Effect of Xylazine-Ketamine Anesthesia on Blood ACTH, Cortisol, Adrenaline, Insulin and Glucose in Ovariohysterectomized Cats

A study has been carried out with fourteen healthy mature cats in order to determine the effect of a xylazine-ketamine anesthetic protocol （group X/K） on blood concentrations of adrenaline, ACTH （adrenocorticotropic hormone）, cortisol, insulin and glucose in comparison with a control group （group K--no anesthesia and surgery）. The animals were randomly allocated in two groups （n = 7）. The premeditation in the experimental group was made with xylazine 2 mg/kg intramuscularly. Induction and maintenance of anesthesia were made with ketamine 10 mg/kg intramuscularly. Ovariohysterectomy was performed upon occurrence of deep anesthesia. Blood specimens were obtained at 0, 30, 60, 120 min and 24 h from the two groups. Pronounced decrease in blood ACTH, cortisol, and adrenaline in group X/K was determined by the 30 min. Significant hyperglycemia together with hyperinsulinemia in the X/K group was established at the 120 min from the beginning of the anesthesia. Anesthesia with xylazine and ketamine led to reduction of the blood levels of stress hormones immediately after the beginning of anesthesia and caused a remarkable hyperglycemia with hyperinsulinemia.

Mean Sea Level Changes near Weizhou Island from 1969 to 2010

Tidal data from Weizhou, Zhapo, and Shanwei stations between 1969 and 2010 and from five gauging stations in the western Pacific Ocean provided by PSMSL, and the global mean sea level data recorded between December 1992 and December 2010 by TOPEX and Jason satellites were compiled and analyzed. The results show that the perennial mean sea level near Weizhou Island is 211.7 cm(relative to the water gauge zero), and the relative mean sea level rising rate is 2.2 mm yr-1 from 1969 to 2010, which is consistent with the relative mean sea level rising rate recorded at other gauging stations in the western Pacific regions and with the global mean sea level rising rate. The absolute mean sea level rising rate at Weizhou Island is 3.0 mm yr-1 from 1993 to 2010, also conforming with the global mean sea level rising rate(3.1±0.4 mm yr-1) during the same time period. The highest annual tide level at Weizhou Island has a rising rate of 4.6 mm yr-1 and shows a 20-year quasi-periodic variation from 1966 to 2010. The primary cause of the mean sea level rising is global warming.

Syringaresinol-4-O-β-D-glucoside alters lipid and glucose metabolism in HepG2 cells and C2C12 myotubes

Syringaresinol-4-O-β-D-glucoside(SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder,especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in Hep G2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in Hep G2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1–10 μmol/L. SSG also increased glucose consumption by Hep G2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c,-2(SREBP-1c,-2), fatty acid synthase(FAS), acetyl CoA carboxylase(ACC) and hydroxyl methylglutaryl CoA reductase(HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma(PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγtested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.

Addressing Global Warming

China and the United States join hands to combat climate change As global temperatures rise,wetland areas are shrinking,droughts descend frequently on what used to be fertile farmland,and some small islands are becoming completely submerged.