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@#Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor(VEGF)family members. VEGF-A, VEGF-B and placental growth factor(PLGF)were included in VEGF family that could inhibit downstream signalling mediated by these ligands. Aflibercept binds to all isoforms of VEGF-A with high affinity, and presented a markedly higher affinity compared with ranibizumab or bevacizumab. Intravitreal injection aflibercept has been approved for the treatment of patients with age-related macular degeneration(ARMD). Numerous studies showed it could improve best corrected visual acuity(BCVA), reduce macular edema and with fewer complications that has been another choice for ARMD patients. However, studies of participation time with large sample are lacking, and relevant studies are limited in China. Contribution in clinical efficacy, advancement in selection and use of medicines, safety and limitations with aflibercept will be here summarized.
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Objective To establish a mouse model for short-term exposure to ambient PM and to investigate the impact on the Cytochrome P450 1A1(CYP1A1)and O6-methylguanine-DNA methyltransferase(MGMT)mRNA expression. Methods Twenty 6-week-old BALB/c mice were randomly assigned to one of two groups, each consisting of 5 male and 5 female animals. These mice were then housed in situ concurrently for 2 weeks in our lab located in urban area of Hangzhou. The first group was kept inside an individual ventilated caging(IVC)system equipped with a high-efficiency particulate-air(HEPA)filter, whereas the second was housed inside a IVC with HEPA filter removed. Then it's allowed flow-through of ambient air freely via a pipeline outside. Mice inside the HEPA filtration chamber were therefore protected from exposure to all airborne particulate. The other was in fact exposed to ambient air directly. After the exposure, the bronchoalveolar lavage(BAL)fiuid was collected for each animal and the differentials and percentages of BAL cells were determined. Paraffin sections of lungs of the mice were made and were examined for any inflammation changes. CYP1A1 and MGMT mRNA levels in the lungs were then detected by RT-qPCR. Results The mean concentration of PM2.5was(99.7±51.6)μg/m3in the exposure group. Weight increases were similar between the two groups(P>0.05). The number of total cells and macrophages in BALF from exposure mice was significantly greater than control.A mild inflammation was observed from light photomicrographs of the lung after PM exposure. CYP1A1 and MGMT mRNA levels were significantly up-regulated in the lung from the exposure group. Conclusion A mouse model for short-term exposure to ambient PM was established. CYP1A1 and MGMT may mediate the toxic effect of PM exposure.
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Objective To study maternal toxicity, embryotoxicity and teratogenecity of Chimonanthus salicifolius S. Y. Hu in SD rats.Methods A total of 64 successfully mated female SD rats were randomly divided in to 4 groups (16 per group), in which 3 experimental groups were daily treated with 3.75, 7.5 and 15.0 g/kg. bw test substance by lavage from 7th to 16th day during gestation respectively. Body weight and general conditions of the pregnant rats were recorded during the study. On the 20th day in pregnancy, the rats were anatomized and examined grossly, the fetuses were removed and counted, weight, length, visceral and skeletal changes were then examined. Results There was no significant difference in the conception rate, total weight gain during the pregnancy and the number of living, dead and resorbed fetuses between each dosage groups and the control group (P>0.05) . The number of the rib, sternum, the fifth sternum punctated and the parietal bone which were ossified defectively all showed no difference among the four groups (P>0.05) . Conclusion Chimonanthus salicifolius S. Y. Hu extract had no obvious maternal toxicity, embryotoxicity and teratogenecity in SD rats under this experiment condition.
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Objective To evaluate the safety of the Eucommia folium and to provide the basis of the rational use ofEucommia folium resource.Methods According to < Technical Standards for Testing & Assessment of Health Food>,version 2003, acute safety test/micronucleus test of born marrow in mice/sperm shape abnormality test in mice/Ames test andthirty-day feeding test were all performed after water extract concentrations of Eucommia folium treatment (1 mLconcentrations equal to 1.5 g Eucommia folium) . Results On the acute toxicity test, the MTD of rats and mice were both40.0 mL/kgbw. The results of genetic toxicity test were all negative in the dosage of 10 g/kg bw(according to the dosage ofEucommia folium) .The results of thirty-day feeding test indicated that there have no significant differences in body weight,blood cytology indexes, blood biochemical indexes, organ/body ratio and pathematology examination in the rats in all thegroups (0.83, 1.67, 3.30 mL/kg) as compared to the control group(P>0.05) . Conclusion Under this experimentalcondition, no obvious abnormity and toxic reaction were observed.
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Objective To explore the influence of 30 day feeding test of health food containing caffeine on the physiological state of SD rat.Methods SD rats were randomly divided into five groups according weight :three health food containing caffeine(1.64,3.28,6.57 g/kg),one health food containing reduced caffeine (6.48 g/kg)and the control group. Haematological and biochemical parameters were measured at the end of experiment,and main organ tissue analysis was also performed.Results Weight at the end of 4 week,weight after absolute diet,total weight increased,and total food consumption and food consumption at the end of 4 week in 6.57 g/kg groups of male rats were decreased compared with the control group (P <0.05 ).Conclusion In comparison with 6.48 g/kg group,all those changes may be caused by overhigh caffeine in 6.48 g/kg group.
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Objective Toevaluatetheeffectsofwholecranberrypowder(Pacranpowder)onimmunefunctionsofICR miceinvivo.Methods FemaleICRmice(18-22g)wererandomlydividedintocontrolgroupandlow,mediumandhigh dose groups of whole cranberry powder (83,1 66,and 332 mg/kgbw).Whole cranberry powder was treated with by gavage for 30 days continuously.Control mice were treated with distilled water only.Their immune functions were analyzed, including serum hemolysin analysis, antibody -producing cells (APCs ), conA -induced splenic lymphocyte transformation,SRBC-induced delayed type hypersensitivity,natural killer cell activity assay,peritoneal macrophages phagocytosed chicken red blood cells (CRBC),carbon clearance test and thymus or spleen /body weight ratio.Results Ascomparedwiththecontrols,wholecranberrypowdertreatmentincreasedthenumberofplagueformingcells(PFCs)at 83 mg/kgbw group(P<0.05 ).There were no statistical difference in the total production of antibodies,the activity of conA-induced splenic lymphocyte transformation,the left-hind voix pedis thickness,NK cytoactivity,the phagocytosis index and ratio of peritoneal macrophages, the carbon clearance ability between the groups treated with different concentrationsofwholecranberrypowderandthecontrolgroup(P>0.05).Conclusion Wholecranberrypowdercan enhance mouse the number of plague forming cells (PFCs).
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Objective Toinvestigatethecytotoxicityandoxidativestressofambientfineparticulatematter(PM2.5)and water-solublefractionofPM2.5onhumanbronchialepithelialcells(HBE).Methods PM2.5sampleswerecollected in the urban area of Hangzhou.Then the water-soluble fraction was extracted from PM2.5.After HBE cells were exposed to PM2.5 and its water-soluble fraction at the doses of 0,100,250,500,1 000,1 500 and 2 000 μg/mL for 24 h, CCK-8 (cell counting kit-8 )assay was conducted to examine the cytotoxicity of the PM2.5 and its water-soluble fraction.The oxidative damage induced by PM2.5 and its water-soluble fraction on HBE cells was then evaluated with lipid peroxidation,the superoxide dismutase (SOD ) activity,and the levels of glutathione peroxidase (GSH -Px ). Results ThePM2.5anditswater-solublefractionreducedtheviabilityofHBEcellsinadose-dependentmanner. When the PM concentrations were 200,400 and 800 μg/mL,the SOD activity of the HBE cells decreased significantly,as compared with the control group (P<0.05 ).Also,the malondialdehyde (MDA)levels of the HBE cells significantly increased at the doses of 200,400 and 800 μg/mL (P<0.05).However,there were no significant differences of GSH-Pxactivityamongthegroups.Conclusion ThePM2.5anditswater-solublefractioncouldinducecytotoxicand oxidative damage effects on the HBE cells.
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Objective To explore the effects of dichloromethane(DCM)exposure on serum biochemical indexes among furniture manufacturing workers. Methods A total of 65 workers who engaged in adhesive operations in furniture manufactory and 56 workers who would be recruited into another factory as new employees were investigated. Twenty two pairs of workers were selected as occupationally exposure group and control group,respectively. The concentration of DCM in workplace of adhesive operations in furniture manufactory was determined. Serum levels of TP,ALB,GloB,A/ G, ALT,AST,GGT,AFU,GPDA,ADA,ALP,CHE,CHOL,TG,TBA,TBIL,DBIL and IBIL were tested by automatic biochemical analyzer in all groups. Results The mean levels of serum TP,ALB,GloB in exposure group( the concentrations of DCM in workplace were 1 300 - 7 760 mg/ m3 )were 73. 7 ± 3. 6,47. 5 ± 2. 3 and 26. 2 ± 2. 8 g/ L,which were significantly lower than that of control group(P < 0. 05). Compared to the control group,the mean levels of CHE, ADA,AST and ALT activity in exposure group(7 477. 8 ± 1 240. 8,7. 3 ± 1. 7,21. 6 ± 5. 6 and 13. 0 ± 5. 6 U/ L)were significantly lower(P < 0. 05). The mean levels of TBIL,DBIL and IBIL were 13. 9 ± 7. 6,6. 4 ± 4. 3 and 7. 5 ± 3. 4μmol/ L,respectively,which were significantly higher than that of control group(P < 0. 05). No significant difference in the mean levels of the other biochemical indexes in serum was observed between exposure and control group. However,no correlation was found between the levels of ALB and TBIL,ALB and DBIL,or ALB and IBIL. Conclusion Occupational exposure to DCM is associated with the decrease of TP,ALB,GloB and CHE levels in serum. Meanwhile,DCM occupational exposure is correlated with the increase of TBIL,DBIL and IBIL levels in serum. Our data suggest that occupational exposure to DCM may be related to inhibition of synthetic function in live,damage of blood cells and declined metabolism of bilirubin.
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Objective To know the effect of nanometer titanium dioxide (nano -TiO2 )on the oxidative stress in zebrafish. Methods A total of 64 zebrafishes were randomly divided into 4 groups with different concentrations of nano -TiO2 exposure,which including control group,low dose group (2 mg/L),moderate dose group (8 mg/L)and high dose group (32 mg/L).The content of MDA,the activities of SOD and ATPase in gill,liver and muscle were measured in 1 0 zebrafishes in each group after 30 d exposure.Histopathological changes of gill,liver and muscle in the remainder fishes were observed.Results The content of Malondialdehyde (MDA)in the fish gill of the moderate and high dose group were significantly higher than that of the control group (P <0.05).The activity of Superoxide dismutase (SOD)in the fish gill of the high dose group was significantly increased compared with the control group (P <0.05).The activities of Adenosine triphosphatase(ATPase)in the fish gill of the moderate and high dose group were significantly decreased compared with the control group (P <0.05).The changes on the content of MDA and the activities of SOD in the fish liver were similar with that in the fish gill after nano -TiO2 exposure,while there was no significant change in the activity of ATPase of the fish liver.And no significant changes were observed in the content of MDA,the activities of SOD and ATPase in the fish muscle (P >0.05 ). Histopathological observation showed infiltration by inflammatory cells, swelling and degeneration, vacuolation and necrosis in zebrafish gill and liver with different degrees.Conclusion Nano -TiO2 exposure could induce the oxidative stress in zebrafish,causing pathological changes in the fish gill and liver.
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<p><b>OBJECTIVE</b>To evaluate the antimutagenicity of propolis in vivo and in vitro.</p><p><b>METHODS</b>Salmonella typhimurium strains TA98 and TA100 were used as a test model in vitro against a direct mutagen DMC and an indirect mutagen 2AF with or without S9 mix, and MN formation of mice bone marrow cell and CAs induction of mice testicle cell were applied as a test model in vivo against two mutagens CP and MMC.</p><p><b>RESULTS</b>The present study clearly demonstrated that propolis could inhibit mutagenicity of both DMC and 2AF directly in a dose-dependent manner, and significant antimutagenic effects (P < 0.05) were obtained in TA98 strain at 2000 and 3000 microg/plate. It also could inhibit mutagenicity of both DMC and 2AF to TA98 strain in a dose-dependent manner, with significant antimutagenic effects (P < 0.05) appeared at 1000, 2000, and 3000 microg/plate. The results of antimutagenicity test in vivo revealed that propolis could inhibit MN formation significantly (P < 0.05) at the doses of 45.0 and 135.0 mg/kg b. w., and decrease the frequency of chromosome aberrants and chromosome aberrant cells significantly (P < 0.05) only at the dose of 135.0 mg/kg b. w.</p><p><b>CONCLUSION</b>The propolis is a good inhibitor for mutagencity of DMC and 2AF in vitro, as well as for CP and MMC in vivo.</p>