OBJECTIVE: To investigate the anti-oxidant mechanism of andrographolide on HaCaT cells via Nrf2/ARE signal pathway. METHODS: The effect of andrographolide on the viability of HaCaT cells and the effect of H2O2-induced cell viability were measured by CCK-8. HaCaT cells were pretreated with andrographolide of different concentration for 24 h. The protein and mRNA expression levels of Nrf2, HO-1, AKR1C1 and NQO1 in HaCaT cells were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2 protein in the nucleus was analyzed by nuclear cytoplasmic separation and immunofluorescence. RESULTS: Andrographolide had no significant effect on cell viability and dose-dependently decreased H2O2-induced cell death, the difference was statistically significant. Andrographolide significantly enhanced the expression of protein and mRNA of antioxidant enzymes Nrf2, HO-1, AKR1C1, NQO1, increased the distribution of Nrf2 in the nucleus, and up-regulated the expression of ARE. Besides, andrographolide upregulated the phosphorylation level of the upstream protein kinase AMPKα (p-AMPKα). CONCLUSION: Andrographolide could decrease H2O2-induced cell death, and its mechanism may be through the activation of Nrf2/ARE signaling pathway, thereby regulating the expression levels of HO-1, AKR1C1, and NQO1.

Melittin exhibits high antibacterial potency against drug-resistant bacteria. However, the clinical utility of melittin is limited by its serious hemolytic activity. Thus, the need for developing novel melittin analogues with high antimicrobial activity and low hemolytic activity has grown. We designed, synthesized, and evaluated 20 novel melittin analogues with varying hydrophobic, polar or positively charged amino acids. The results showed that 8 compounds had antimicrobial activity (MIC: 1-4 μg·mL^-1) against gram-positive pathogens equal to or better than that of melittin, and 16 compounds had low hemolytic activity (HC₅₀ ≥ 11.9 μg·mL^-1). Compounds 13 (MIC: 2-4 μg·mL^-1) and 15 (MIC: 1-2 μg·mL^-1) showed equal or better antimicrobial activity against both susceptible and resistant strains of Staphylococcus aureus and Enterococcus faecium compared to melittin (MIC: 4 μg·mL^-1). Compound 13 (HC₅₀: 24.0 ± 4.3 μg·mL^-1) displayed noticeably decreased hemolytic activity compared to melittin (HC₅₀: 5.3 ± 0.4 μg·mL^-1). This work established a base for further study on the structure-activity relationships and structure-toxicity relationships of melittin.

OBJECTIVETo evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes.

METHODSTo test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA+N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1β were detected in the hepatocytes.

RESULTSCompared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09±2.72 vs 6691.23±2.45, P=0.00) and mitochondrial ROS (64.98±0.94 vs 45.04±0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1β (1603.52±1.32 vs 2629.33±2.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.15±2.87 vs 5445.6±1.17, P=0.00) and suppressed the expressions of NLRP3, ASC and caspase-1.

CONCLUSIONPA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1β.

Acetylcysteine ; pharmacology ; Animals ; Carrier Proteins ; metabolism ; Caspase 1 ; metabolism ; Cells, Cultured ; Hepatocytes ; drug effects ; metabolism ; Inflammasomes ; drug effects ; metabolism ; Interleukin-1beta ; metabolism ; Mice ; Mitochondria ; drug effects ; NADPH Oxidase 4 ; NADPH Oxidases ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxidative Stress ; Palmitic Acid ; pharmacology ; Reactive Oxygen Species ; metabolism

OBJECTIVETo understand the sero-prevalence of hepatitis E virus (HEV) infection among different populations and animals in Fujian province.

METHODSOne thousand one hundred and fifty-one serum samples were collected from 5 species of animals including swine, dog, cow, sheep and rat. A total of 2209 and 1722 serum samples from the general population and from the exposed population were collected. Anti-HEV IgG was detected by ELISA. The general population was composed of healthy blood donors and the individuals who had attended physical examination including farmers, handlers, veterinarians, cooks who worked with pigs or chickens while the poultry wholesale suppliers made up the exposure population.

RESULTSThe infection rates of HEV in animals were different between species (chi2 = 406.25, P < 0.01) with the highest seen in the pig group. With pigs being kept at home, the rates were between 70.00% and 94.12% but the rate was 39.77% for those families that keeping the pigs at farms. The infection rate of HEV was 23.3% in the general population and 33.3% in the exposed populations, respectively. A significantly higher infection rate for anti-HEV was found in the exposed population when comparing with general population. The positive rate of anti-HEV IgG was significantly higher in the exposed population that closely having had contact with chickens than those who had contact with pigs. The increasing trend of HEV infection rate with age had been found but there was no significant difference between males and females in the general population. In the exposed population, the infection rate in males was significantly higher than that in females.

CONCLUSIONThe infection ratse of HEV in pigs and in the exposure population were much higher, especially for those persons in close contact with chickens or pigs, suggesting that the sub-clinical infection for HEV might exist. These data further supported the hypothesis that HEV might have been an zoonotic disease.

Animals ; Animals, Domestic ; Antibodies, Viral ; analysis ; China ; epidemiology ; Female ; Hepatitis E ; epidemiology ; veterinary ; Hepatitis E virus ; immunology ; Humans ; Immunoglobulin G ; analysis ; Male ; Rats ; Seroepidemiologic Studies ; Zoonoses

OBJECTIVECancer is one of the leading causes of death in China. The study aimed to examine the temporal trend of cancer mortality rate during 1989-2008 in urban and rural areas of China.

METHODSThe mortality data of all cancers from 1989 to 2008 from National Cancer Registry database were sorted and checked. Age standardized mortality rates were calculated by the direct methods using the China population of 1982 and World Segi's population. Joinpoint regression was performed to obtain the annual percentage changes (APC) in mortality rates. The top ten cancer sites were calculated and analyzed. The mortality rates were compared with statistics of the United States.

RESULTSFrom 1989 to 2008, the trend of crude cancer mortality increased with an annual percentage change (APC) of 1.0%. After age standardization, the mortality rate was significantly decreased, with an APC of -1.2%. In urban areas, lung cancer was the most common cancer of death, whereas in rural areas, stomach cancer and esophageal cancer remained top cancers of death. Especially, in both urban and rural areas, the mortality of lung cancer was on increase. The mortality rates of stomach and esophageal cancers showed a decrease in urban areas. Compared with the cancer mortality rates of the United States, the Chinese cancer mortality rate in males remained highest. The decreasing trend of cancer mortality in females of China was less obvious than that of the United States.

CONCLUSIONSThe crude mortality rates of cancer in China show an increase whereas the age standardized mortality raters has declined between 1989 and 2008. Cancer is still a major public health issue threatening people's life in China. Effective intervention for cancer control and prevention is needed in the future.

China ; epidemiology ; Esophageal Neoplasms ; mortality ; Female ; Humans ; Lung Neoplasms ; mortality ; Male ; Mortality ; trends ; Neoplasms ; mortality ; Registries ; Rural Population ; Sex Factors ; Stomach Neoplasms ; mortality ; United States ; epidemiology ; Urban Population

OBJECTIVENationwide cancer incidence data were used to analyze the trends of cancer incidence in China in order to provide basic information for making cancer control strategy.

METHODSWe retrieved and re-sorted valid cancer incidence data from the National Central Cancer Registry Database over the 20 year-period 1989-2008. Crude incidence rate and age-standardized incidence rate were calculated for analysis. Annual percent changes in incidence for all cancers combined were estimated using Joinpoint software.

RESULTSThe cancer incidence rate in cancer registration areas was increased from 184.81/10(5) in 1989 to 286.69/10(5) in 2008 (from 209.33/10(5) to 307.04/10(5) in urban and from 176.10/10(5) to 269.57/10(5) in rural areas). Uptrends of crude cancer incidence were shown in both male and female in urban and rural areas over the 20 year-period. After standardized by age, overall incidence rate kept stable with 0.5% annual increase in urban and no change in rural areas. Since 2000, the cancer incidences in both sexes and areas were significantly increased. The incidence increased for most major cancers, especially lung cancer, colorectal cancer, female breast cancer and cervical cancer.

CONCLUSIONSOver the 20 year-period 1989-2008, cancer incidence of most cancers has been increasing by time. The incidences of gastric cancer, liver cancer and esophageal cancer still keep gradually increasing. The incidences of lung cancer, female breast cancer, colorectal cancer and cervical cancer are markedly going up, so that cancer prevention and control should be enhanced. Cancer registration will play an important role on cancer control in China along with the number of registries increasing and data quality improving.

Breast Neoplasms ; epidemiology ; China ; epidemiology ; Colorectal Neoplasms ; epidemiology ; Esophageal Neoplasms ; epidemiology ; Female ; Humans ; Incidence ; Liver Neoplasms ; epidemiology ; Lung Neoplasms ; epidemiology ; Male ; Neoplasms ; epidemiology ; Registries ; Rural Population ; Stomach Neoplasms ; epidemiology ; Urban Population ; Uterine Cervical Neoplasms ; epidemiology

Objective To observe the effects of Class 5 and 6 chemical indicative cards used for monitoring pressure steam sterilization to standardize the procedure for selecting the monitoring substance of pressure steam sterilization. Methods Several pieces of Class 5 and 6 cards were placed at the four corners and center of the clave to undergo sterilization with the conventional parameters of 134 ℃, 240 s and 220 kPa as well as the simulation critical parameters of 134 ℃, 120 s and 220 kPa.The two kinds of cards had their qualification rates compared with two sets of parameters.SPSS 19.0 software was used for data analysis and Chi-square test was applied to comparison.Results The two kinds of cards had the qualification rates being 100% with the conventional parameters;with the simulation critical parameters,Class 5 card had the qualification rate being 100%,while Class 6 card had the rate of 66.67%,and there were significant difference between the qualification rates of the two cards(P<0.05).Conclusion Class 6 chemical indicative card has higher resistance and efficiency with the same conditions when compared with Class 5 card,which can be combined with the tube cavity challenger to execute mass monitoring with unstable parameters.

Humans ; Islets of Langerhans Transplantation

Whole-cell patch clamp and cell volume measurement techniques were used to investigate the ATP-activated chloride current and the ATP effect on cell volume in nasopharyngeal carcinoma cells. Extracellular application of ATP in micromolar concentrations activated a current with the properties of modest outward rectification and negligible time-dependent inactivation in a dose-dependent manner. The current reversed at a potential [(-0.05+/-0.03) mV] close to the Cl- equilibrium potential (-0.9 mV). Substitution of Cl- with gluconate in the extracellular solution decreased the ATP-activated current and shifted the reversal potential positively. NPPB, one of the chloride channel blockers, inhibited the current by (81.03+/-9.36)%. The current was also depressed by the P2Y purinoceptor antagonist, reactive blue 2, by (67.39+/-5.06)%. ATP (50 micromol/L) decreased the cell volume under the isotonic condition. Depletion of extracellular and intracellular Cl- abolished the ATP effect on cell volume. The results suggest that extracellular ATP of micromolar scales can induce a chloride current associated with cell volume regulation by activation of chloride channel through binding to purinoceptor P2Y.
Adenosine Triphosphate ; physiology ; Cell Size ; drug effects ; Chloride Channels ; antagonists & inhibitors ; metabolism ; physiology ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Nitrobenzoates ; pharmacology ; Patch-Clamp Techniques ; Tumor Cells, Cultured