Objective To observe whether sodium arsenite(NaAsO2)can activate the expressions of hemeoxygenase-1(HO-1)of normal human liver cell line named Chang liver.Methods Chang liver cells were exposed to NaAsO2 at 10 μmoL/L,0(contml),2,6,12,24 h and at 0(control),5,10,25,50 μmol/L in 12 h, followed by the measuring of the expressions of HO-1 protein in ceUs with western blot.Results In 10 μmol/L groups Chang liver cells exposed for 6,12,24 h cultured in vitro,the expressions of HO-l protein(3.97±0.72, 12.92±2.98,23.29±3.82)was significantly higher than that of control(1.00±0.00),and compared with the control, the difference being statistically significant(F=85.83,P＜0.01;t=-9.42,-8.95,-13.83,respectively,P＜ 0.05 or＜0.01).In 12 h,5,10,25 and 50 μmol/L groups cultured in vitro,the expressions of HO-1(16.34±0.25, 7.75±0.39,7.93±0.14,12.48±0.35)was significantly higher than that of control(1.00±0.00).and compared with the control,the difference being statistically significant(F=85.83,P＜0.01;t=-36.25,-30.19,-86.40, -56.40,respectively,all P＜0.01).Conclusion Inorganic arsenic call induce the activation of HO-1,promote the expression of protein in a time-and dose-dependent manner.

Objective To evaluate effects of chronic arsenic exposure and arsenic exposure time on oxidative DNA lesions in humans. Methods A cross-sectional study was conducted in 108 subjects exposed to high concentrations of arsenic in drinking water and 75 control subjects. A cohort study was conducted in 64 subjects exposed to high levels of arsenic in drinking water for 7 or 9 years. Urinary 8-oxo-7,8-dihydredeoxygnanine(8-OHdG) levels were analyzed by the enzyme-linked immunosorbent assay kit(ELISA). Urinary arsenic concentration was detected with hydride generation atomic absorption spectroscopy. Results In the cross-sectional study, the median of urinary arsenic concentration was 484.17 mg/kg Cr for the arsenic-exposed group, and 13.80 mg/kg Cr for the control group, and the difference between the two groups was statistically significant (t=32.57, P<0.01). The median of urinary 8-OHdG levels was 16.60 and 21.88 mg/kg Cr for arsenic-exposed children and adults respectively, much higher than control children(10.50 mg/kg Cr) and adults (9.11 mg/kg Cr), and the difference was statistically significant (t=5.049, 6913, all P<0.01). Urinary 8-OHdG levels were signifieandy lower for children than adults in the exposed group(t=-1.997, P<0.05). In the cohort study, the median of urinary arsenic concentration was 461.3 mg/kg Cr for the 7-year-exposed subjects and 422.90 mg/kg Cr for the 9-year-expesed subjects, and no significant difference was observed(t=-0.250, P 0.05). The median of urinary 8- OHdG levels for 9-year-exposed children and adults were 23.46 and 24.30 mg/kg Cr respectively, significantly increased compared with those of 7-year-exposed(14.29 and 18.38 mg/kg Cr), and the difference had statical signhqcanees (t= -2.949,-3.055, all P<0.01). Conclusions Chronic arsenic exposure can lead to oxidative DNA lesions in humans. The arsenic-induced DNA lesions may aggravate with the exposure time in a certain period.

Osteosarcoma, originated from mesenchymal tissue, is one of the highest incidence of primary malignant bone tumors which were characteristic double peak distribution both in adolescents and elderly. Immune-targeted therapy could block the tumor cell signaling pathway and promote cancer cell death by apoptosis. Immune-targeted therapy is an effective treatment of anti-osteosarcoma after surgery and chemotherapy in recent years. The paper reviews the advances in latest research on the related mechanisms of the immune-targeted therapy on osteosarcoma, and hope to provide a theoretical basis for clinical treatment.

OBJECTIVETo assess the risk factors for vulvar dystrophy.

METHODSAn epidemiological study was carried out. Data on 100 cases with vulvar dystrophy was reviewed and face to face interviewed with a uniform questionnaire including the manner of work, environmental temperature, habit of eating, mood, underwear wearing, autoimmune diseases, marriage, menstrual age, the quantity of menses, orders of pregnancy, and labor trauma of vulvar during delivery, vulvitis and urethritis ect. Univariable analysis and multivariate logistic regression analysis were carried out with 1:1 case-control methodology.

RESULTSMultiple conditional logistic regression analysis showed that vulvar dystrophy was positively associated with hot food (OR = 2.55, 95% CI: 1.24 - 5.25), mood (OR = 4.27, 95% CI: 1.96 - 9.29), order of pregnancy (OR = 3.37, 95% CI: 2.11 - 5.40), vulvitis (OR = 6.74, 95% CI: 2.66 - 17.09) and urethritis (OR = 11.02, 95% CI: 1.01 - 120.19). Vulviitis or urethritis increased 6.74 or 11.02 times the incidence of vulva dystrophy. Anger or nervous state contributed to the incidence of vulva dystrophy (OR = 4.27). Addict to hot food and order of labor also increased risk ratio for 2.55 and 3.37 times, respectively.

CONCLUSIONThe risk factors of vulvar dystrophy were: addict to hot food, often holding a angry or nervous state, increase of labors, having vulvitis and urethritis.

Diet ; Emotions ; Female ; Humans ; Multivariate Analysis ; Parity ; Risk Factors ; Vulvar Lichen Sclerosus ; etiology

Objective To investigate the distribution of water fluoride and the present status of water- improving delluoridation projects in the endemic fluorosis areas in Gansu Province. Methods According to "The National Technical Scheme for Endemic Disease Control in 2004" for the water improving projects, water fluoride content was determined from fluorosis villages in 34 counties of 11 cities in Gansu Province. The fluoride content in drinking water was assessed by F-ion selective electrode. Results Water fluoride content was determined in 1576 fluorosis villages of 34 counties. Water fluoride content of 7829 water samples was determined, and the fluoride content of 1891 samples was over standard. Water fluoride content was ≤ 1.00 mg/L(accounting for 75.19%) in 1185 villages and 1.00 mg/L(accounting for 24.81%) in 391 villages; the highest water fluoride content was 6.78 mg/L Nine hundred and ninety three water-improving and defluoridation projects were determined. Water fluoride content of 867 water-improving and defluoridation projects was determined; 768 projects had water fluoride content ≤1.00 mg/L(accounting for 87.67%) and water fluoride content of 108 projects was 1.00 mg/L(accounting for 12.33%),with the highest water fluoride content being 5.27 mg/L. Water-improving and delluoridation projects mostly relied on drilling a well to obtain under-grand water. Abandoned projects accounted for 30%. Conclusions In 34 counties of 11 cites(prefecture), nearly 30% of the villages had water fluoride content exceeding the standard. The situation of endemic fluorosis control is still serious in Gausu Province, countermeasures for endemic fluorosis must be carried out as soon as possible and surveillance of water-improving and defluoridation projects must be strengthened.

OBJECTIVETo investigate whether Ca2+ contribute to cardiomyocyte hypertrophy induced by tumor necrosis factor-alpha (TNF-alpha) through PI3-kinase pathway.

METHODSThe protein content was assayed with Lowry's method. The cardiomyocytes volumes were measured by computer photograph analysis system. The protein synthesis was assayed with [3H]-leucine incorporation method. [Ca2+]i transient was measured by Till image system by cell-loading Fura-2/AM.

RESULTS(1) TNF-alpha significantly induced the increase of protein content, [3H]-leucine incorporation and cell size. These responses were significantly suppressed by LY294002, a selective PI3-kinase inhibitor. Verapamil, L-type calcium channels antagonist, slightly attenuated TNF-alpha-induced these responses. (2) TNF-alpha increased the amplitude of the spontaneous Ca2+ transients in cultured ventricular myocytes from the neonatal rat; PI3-kinase inhibitor LY294002 could suppress the elevation induced by TNF-alpha, but calcium antagonist verapamil took the minor effects of TNF-alpha on [Ca2+]i metabolism.

CONCLUSIONIncreasing the intercellular free Ca2+ level may play an essential role in TNF-alpha-induced cardiomyocyte hypertrophy through PI3-kinase pathway in rats, while L-type calcium channel takes the minor effects on it.

Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; metabolism ; Chromones ; pharmacology ; Female ; Hypertrophy ; Male ; Morpholines ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; pathology ; Phosphatidylinositol 3-Kinases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha ; pharmacology

BACKGROUNDIt is generally accepted that gliomas are the most common primary brain tumors with poor prognosis. We aimed to explore the relationship of the immunity of the central nervous system and the genesis and development of glioma.

METHODSG422 glioma was implanted in the brain of BALB/c mice (immuno-competent mice), nude mice (T cell related immuno-deficient) and complement C3 knock-out mice (complement C3 related immunodeficient). The survival time of the host, growth and histopathology of the tumor, and concentrations of tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ) in tumor tissues were assessed.

RESULTSTumor spheres were formed in all mice after injection, and glial fibrillary acidic protein (GFAP) positive staining of the cells declared their glioma origin. The longest median survival time of (44.3 ± 6.0) days was found in BALB/c mice, followed by (24.8 ± 5.2) days in nude mice and the shortest (18.6 ± 5.8) days in complement C3 knock-out mice. Accordingly, the growth of the tumor was fastest in complement C3 knock-out mice, followed by the nude mice and slowest in the BALB/c mice. Although the proportions of infiltrating CD68(+) lymphocytes in tumor tissues showed no significant difference (P > 0.05), TNF-α level in the nude and C3 knock-out mice, (28.11 ± 4.86) µmol/L and (22.87 ± 6.36) µmol/L respectively, were significantly lower (P < 0.01) than that in the BALB/c mice, which was (230.21 ± 39.17) µmol/L. The INF-γ level was highest in the BALB/c mice ((180.76 ± 29.19) µmol/L), followed by the nude mice ((113.46 ± 23.76) µmol/L) and then the C3 knock-out mice ((16.84 ± 4.45) µmol/L).

CONCLUSIONSThe G422 glioma implanted in the brains of mice with different immune ability would be a useful model for studying the relationship of the immune system and tumor in the central nervous system. Furthermore, the T cells and complement C3 compartments of the immune response may affect the growth of implanted tumors and inflammatory factors such as TNF-α and INF-γ.

Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; Complement C3 ; genetics ; metabolism ; Glioma ; metabolism ; pathology ; Interferon-gamma ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Mice, Nude ; Tumor Necrosis Factor-alpha ; metabolism

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-gamma as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-kappaB, iNOS, and COX-2, and upregulating IkappaB-alpha . These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.
Animals ; Blotting, Western ; Inflammation ; Mice ; Mice, Inbred ICR* ; NF-kappa B ; Ranitidine ; Reserpine* ; Stomach Ulcer* ; Ulcer ; Urinary Bladder*

Objective To investigate the role of aquapofin 1(AQP1)in he migration of eosinophils (EOS)and to determine if AQP-1 can be viewed as the chemotactic activity marker of EOS.Methods Asthma model of guinea pigs were developed and EOS were purified from both peripheral blood and bronchoalveolar lavage fluid(BALF).The smears of EOS were studied by in situ hybridization for determining AQP1 mRNA and immunofluorescence under laser scanning confocal microscope for determining AQP1 protein.Results AQP1 was found expressed in EOS both from peripheral blood and from BALF.Compared with the expression of AQP1 mRNA(mean grey value 109.200+-5.756,-x±s)and protein (average fluorescence intensity 279.926+-11.293)in EOS from BALF,there was stronger expression of AQP1 mRNA(92.904±3.290)and protein(425.081±17.474)in EOS from peripheral blood.The difference both of AQP1 mRNA(t=9.519,P<0.05)and protein(t=27.020,P<0.05)were considered statistically significant respectively.Conclusions AQP1 plays a crucial role in EOS movement.It is possible that EOS produce more AQP1 protein to accelerate its migration to inflammatory tiusse under allergic disease and EOS with AQP1 highly expressed are activated.AQP1 can be viewed as the chemotactic activity marker of EOS.

OBJECTIVEMultiple genetic and environmental factors contribute to the onset of many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an important polymorphism gene which transmembrane transports unconjugated bilirubin(UCB). Genetic polymorphisms that affect the functionality of the protein may potentially lead to altered transport characteristics. The T521C/A388G polymorphism of this gene has been reported to considerably reduce the transporting property of drugs like pravastatin, and may be involved in the membrane translocation of bilirubin. Some studies have shown that OATP 1B1 mediates bilirubin uptake from blood into the liver, and the OATP 1B1 polymorphism is a likely mechanism explaining the differences of bilirubin level in peripheral blood. The aim of this study was to evaluate the relationship between OATP 1B1 polymorphisms and neonatal hyperbilirubinemia.

METHODSA total of 220 newborn infants with hyperbilirubinemia were recruited from Hunan Children Hospital from November 2008 to December 2009 according to the diagnostic criteria. Age and sex matched control subjects comprised of 200 unrelated, hyperbilirubinemia-free newborns. Biochemical and clinical data were collected from the case history. One ml venous blood samples in EDTA vials were taken from each subject and DNA was isolated from peripheral leukocytes by standard methods, preserved in 4°C. 1 - 2 ml venous blood samples were also taken for detecting the serum total bilirubin and direct bilirubin level by chemical oxidation method. OATP 1B1 T521C/A388G polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were compared between patients and control. The gene polymorphism and risk of disease were also analyzed. Serum total bilirubin, conjugated bilirubin and unconjugated bilirubin levels were compared between different OATP 1B1 T521C/A388G genotypes.

RESULTSAllele frequencies in patients and control population were in Hardy-Weinberg equilibrium (P > 0.05). Allele and genotype frequencies of the OATP 1B1 T521C polymorphism in patients were significantly different from the controls. The OATP 1B1 521C allele frequency was only 8.2% in patients, while reached 14.0% in the control group which was very close to the frequency of common Chinese people. However, the proportion of wild type genotypes was significantly higher than those of the controls, reached 84.1%. The 521 C allele and genotypes carrying 521 C allele illustrated low risk for neonatal hyperbilirubinemia (OR = 0.530, 95%CI = 0.328 - 0.857; OR = 0.541, 95%CI = 0.344 - 0.851). However, the frequencies of alleles and genotypes of SLCO1B1 A388G did not differ significantly from those of the controls, and this polymorphism did not influence susceptibility to such disease. Among the three OATP 1B1 A388G genotypes, the level of total serum bilirubin (TSB), direct bilirubin (DB) and unconjugated bilirubin (UCB) were significantly different. Values of TSB, DB and UCB were the highest in wild type subjects, lower in heterozygotes, and the lowest in mutant homozygotes. TSB and UCB in patients with wild type genotypes reached 602.5 µmol/L and 585.0 µmol/L respectively, nearly twice the average value of homozygous patients. While the TSB and UCB in homozygotes were below the average value of all patients, only 351.7 µmol/L and 338.8 µmol/L respectively.

CONCLUSIONSOur findings indicated that OATP 1B1 A388G polymorphism has a notable influence on the serum bilirubin level in neonatal hyperbilirubinemia patients. The OATP 1B1 521T allele may be a potential risk factor of such disease. OATP 1B1 T521C/A388G was an important polymorphism gene which related with neonatal hyperbilirubinemia. Future study should involve other polymorphisms of OATP 1B1, more candidate genes and environmental risk factors. It is also necessary to investigate their association with the severity and prognosis of this disease in order to elucidate the genetic pathogenesis of neonatal hyperbilirubinemia as a complex disease. This study should be repeated in a larger population and different ethnic groups.

Bilirubin ; blood ; Case-Control Studies ; Female ; Humans ; Hyperbilirubinemia, Neonatal ; genetics ; Infant, Newborn ; Male ; Organic Anion Transporters ; genetics ; Polymorphism, Restriction Fragment Length ; Solute Carrier Organic Anion Transporter Family Member 1b1