Mutagenicity and Induction of Drug—metabolizing Enzyme Activity by LPG Combustion Particulates in Rats

Methylene chloride extracts of particulates from liquefied petroleum gas(LPG)combustion appliance were studied by using Ames test,micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase(AHH)and glutathione S-transferase(GST)in rats.The extracts showed mutagenicity for Salmonella typhimurium strain TA98 and its derivatives TA98NR and TA98/1,8-DNP6 with or without S9 mix.The revertants in strains TA98NR and TA98/1,8-DNP6 were less than 40%and 50% of than in strain TA98 without S9 mix,respectively.Positive results were obtained in mouse bone marrow micronucleus assay.Intratracheal instillation of the extracts led to increase in pulmonary(but not hepatic)AHH and GST activities in rats.In was seen that AHH was more sensitive than GST to induction by the extracts.     

Study on the Mutagenicity of Diesel Exhaust Particles

The mutagenicity of diesel exhaust particles(DEP)was studied by using Salmonella typhimurium strains TA98 and TA100 in vitro and mice micronucleus in vivo test.DEP from six kinds of medium and heavy-duty diesel vehicles,which were made in China and imported,were tested.The vehicles wer eoperated under free accelerating condition.The results showed that the EP contained mutagenic activity.An increase in the number of the Salmonella TA98 was observed in the presence and especially in the absence of S9 Mmix.Positive results were also obtained from mice micronucleus assay.The frequency of mice bone marrow micronucleated polychromatic erythrocytes(M PCE)was increased and it showed a definite dose-response relationship.Comparing the different types of the vehicles,we found that the mutagenicity of DEP from domestic made vehicles was stronger than that from the imported ones.     

Experimental St■■■es on the Mutagenicity of Hydroxypiperaquine Phosphate

The mutagenicity of hydroxypiperaquine phosphate (HPQP) was detected by a battery of assays including Amestest, chromosomal aberration test in vitro, micronucleus testand dominant lethal test The results obtained have shownthe absence of mutagenicity of HPQP up to the inhibitoryconcentration to Salmonella typhimurium TA97a. TA98.TA100 and TA102 with or without S-9 mix. The incidence     

Evaluation of Protective Effects of Bioactive Phytochemicals Against Methotrexate in Salmonella typhimurium TA1535/pSK1002 Coupled with MicronucleusAssay

正We evaluated the antimutagenic effects of 10kinds of bioactive phytochemicals and some phytochemical combinations against methotrexate(MTX)-induced genotoxicity by the umu test in Salmonella typhimurium TA1535/pS K1002combined with a micronucleus assay.We observed     

Antioxidant Potential of Four Species of Natural Product and Therapeutic Strategies for Cancer through Suppression of Viability in the Human Multiple Myeloma Cell Line U266

Objective This research aimed to evaluate the protective effects of bioactive compounds such as phenolic acids, flavonoids, and tannins present in four species extracted with methanol. Methods The total phenolic content of the methanolic extracts was measured spectrophotometrically. The effect of the extracts on cell viability in U266 cells was measured. The effects of extracts on free radical scavenging were assessed by the DPPH test and FRAP assay. Antibacterial effects of the natural products in this report were investigated by using the disc diffusion method. Results Our results clearly demonstrated that the methanolic extracts were characterized by a high amount of phenolic compounds. It has been speculated that ME-TA and ME-TAl exhibit a significant(P < 0.05) and dose-dependent antiradical potential. The exposure of cells to high doses of extracts almost completely suppressed cell growth in vitro. ME-TA and ME-TAl showed significant cytotoxic effects at a concentration of 100 μg/mL in the U266 cell line. ME-TAl and ME-CF inhibited the growth of B. subtilis and S. aureus, respectively, to the same extent as 10 μg/μL of chloramphenicol at a concentration of 1 mg/mL. Conclusion Overall, these results suggest that plants used in traditional medicine have a novel application as free radical scavengers, bacterial inhibitors and tumor suppressors.     

Antioxidant activities and total phenol content of Inula viscosa extracts selected from three regions of Morocco

Objective:To investigate antioxidant activity,total phenolic and flavonoid content of ethanol(E) and ethyl acetate(A) extracts of Inula viscosa aerial parts selected from three regions of Morocco(Imouzzer.Sefrou and Taounate).Methods:Antioxidants properties were measured by three different test systems of assay namely free radical scavenging activities against 2,2-diphenyI-1-picrylhydrazyl,total antioxidant capacity and iron-reducing capacity.Total phenolic content was measured by FolinCiocalteu reagent.Results:All the extracts showed significant antioxidant activities and contained important levels of phenols.The ethanol extract(0.3 mg/mL) from Sefrou showed the greatest antioxidant capacity in the three systems of assay,which was probably due to its high content of polyphenols(274.39±6.94) mg gallic acid equivalent/g dry extract.Total flavonoid content was found equal for all extracts.Conclusions:Our results of antioxidant assays were justified and partially supported the popular usage of the tested plants.The high antioxidant activity found in the plant from Sefrou and its great biomass in this region suggested that Inula viscosa is a good source of natural antioxidants compounds which might have benefits for health.     

Mutagenicities of 22 Kinds of Foods After Nitrite Treatment

The mutagenicities of 22 kinds of foods,including soy sauce,fish sauce,shrimp paste,sausages,sundried fishes,rice cracker,deep fried pork skin,salted vegetable and spices after nitrite treatment,were detected by meansof Ames test with preincubation.Mutagenicity assay was employed on Sal-monella typhimurium TA100,and meanwhile,the validity of each experi-ment was checked by using the known mutagen,AF-2,as the positivecontrol.16 kinds of foods showed marked direct-acting mutagenicity towardSalmonella typhimurium TA100 after nitrite treatment.Shrimp paste prod-uced in Bankok was the strongest one among these samples.Its specificmutagenicity was 37000 revertants/g.The amount of precursor,tyramine,in shrimp paste was estimated fromthe area of tyramine peak on HPLC by using the authentic tyramine as thestandard.Results showed that one gram shrimp paste contained 439μgtyramine.The mutagenicities of foods suggested that nitrosatable precursors,suchas amine or amide,were present in foods,and they could be converted intoendogenous carcinogen,nitrosamine,in vivo.Therefore,detection of muta-genicities of foods has significance in preventing cancer.     

Anti-angiogenesis Effect on Glioma of Attenuated Salmonella Typhimurium Vaccine Strain with flk-1 Gene

To investigate the anti-vasculature effects and the anti-glioma effects of attenuated Salmonella typhimurium vaccine strain expressing VEGFR2 (flk-1) gene, plasmid pcDNA3, 1-flk1 was constructed and electro-transfected into live attenuated Salmonella typhimurium strain SL7207. Mouse models of intracranial G1261 glioblastoma were treated with an orally administered attenuated Salmonella typhimurium expressing flk-1 gene. The survival period was recorded and vessel density was observed by immunofluorescence. CTLs activity was measured by MTT assay. Our results showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could significantly inhibit glioblastoma growth, reduce vessel density, prolong the survival period and improve the survival rate in these mice. The flk-1 specific CTLs activity was increased obviously after the vaccination. Our study showed that attenuated Salmonella typhlmurium vaccine strain expressing flk-1 gene could break peripheral immune tolerance a in glioma gainst this self-antigen and kill endothelial cells by the orally administered vaccine and can be used for both prophylactic and therapeutic purposes.     

Mutagenicity of Urine From Individuals Exposed to LPG Combustion Products

The mutagenicity of urine from individuals exposed to the combustion products of liquefied petroleum gas(LPG)was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021(nitroreductase overproducing)and YG1024(O-acetyltransferase overproducing).The detection showed significantly increased mutagenicity for two YG strains and increased positive rates for all three strains in the presence of both rat liver S9 and β－glucuronidase.Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significatly higher mutagenic potency(revertants/10μl urine concentrate)than their corresponding controls.These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking.The mutagenic potency of urine samples of all exposed individuals tested with YG 1024 was found to be about 7 times higher than with TA98.The difference in mutagenic potency was smaller for the same samples when comparison was made betweenTG1021 and TA98.This suggests that the mutagenic compounds present in the urine samples contain mainly armatic compounds as glucuronide conjugates.Our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples.In addition ,no significant difference in the mutagenic potency between the‘pure’ exposed(non-smokers‘) and the ‘pure’ smokers’(unexposed) samples was found in all three tester strains.This might mean that the exposure extent of mutagens/carcinogens in LPG combustion products for exposed individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day.Furthermore,the results also suggest that synergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.     

Effects and potential mechanisms of Danzhi Xiaoyao Pill (丹栀逍遥丸) on proliferation of MCF-7 human breast cancer cells in vitro

Objective： To investigate the effects of 50% ethyl alcohol （EtOH） extracts from Danzhi Xiaoyao Pill （丹栀逍遥丸, DXP） on the proliferation of MCF-7 human breast cancer cells and potential mechanisms. Methods： ATP-Lite assay was performed to test the proliferation of the MCF-7 breast cancer cell line; and antioxidant activity was measured by the oxygen radical absorbance capacity （ORAC）. The effects of DXP on nitric oxide （NO） production were tested by lipopolysaccharide （LPS）- stimulated RAW 264.7 murine macrophages using the Griess reaction. Results： The 50% EtOH DXP extracts displayed a cytotoxic response on MCF-7 cells at 0.10, 0.25 and 0.50 mg/mL dosedependently with the proliferation inhibited by more than 85%. The ORAC value of the DXP was 820μ moL Trolox equivalent/g, about 40% of the vitamin C value. DXP extracts had significant inhibitory effect on NO production at the concentration from 0.0625 mg/mL to 0.5 mg/mL （P〈0.05, P〈0.01）. Conclusion： The extracts of DXP could significantly inhibit the proliferation of MCF-7 cells, with the effect possibly related to its antioxidant activity and the inhibition of NO production.     

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy

Background The preclinical experiments and several clinical studies showed icotinib,an oral epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor,in Chinese patients with advanced non-small cell lung cancer （NSCLC） who failed previous chemotherapy.We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients.Methods The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1,2011 to July 31,2012 were retrospectively analyzed.All patients were given icotinib treatment after the failure of previous chemotherapy.Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model.Results The objective response rate was 33/149 and disease control rate was 105/149.No complete response occurred.Median progression free survival （PFS） with icotinib treatment was 5.03 months （95％ CI：3.51 to 6.55）.Median overall survival was 12.3 months （95％ CI：10.68 to 13.92）.Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS.At least one drug related adverse event was observed in 65.8％ （98/149） of patients,but mostly grade 1 or 2 and reversible and none grade 4 toxicity.Conclusions lcotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy.It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.     

Concurrent chemoradiotherapy comparison of taxanes and platinum versus 5-fluorouracil and platinum in nasopharyngeal carcinoma treatment

Background Nasopharyngeal carcinoma （NPC） is a squamous-cell carcinoma especially prevailing among the natives of southern China.The regimen of concurrent chemoradiotherapy （CCRT） that include platinum and 5-fluorouracil （5-FU）is considered to be the standard treatment for NPC.However,its clinical use is limited by its toxicity.Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.Methods Medline,the Cochrane library,and the Chinese medical literature database were searched for eligible studies.Meta-analysis was performed using Review Manager （Version 5.2）.Results Six random controlled trials （RCTs） including 514 patients met our criteria.Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission （CR） and less incidence rate in adverse reactions such as gastrointestinal impairment grades Ⅲll-Ⅳ,liver and kidney impairment grades Ⅰ-Ⅱ,and radiodermatitis grades Ⅲ-Ⅳ versus the conventional regimen of CCRT with 5-FU and platinum,while the long-term effectiveness rate of overall survival,Iocoregional failure-free survival,or distant metastasis failure-free survival between the two groups was therapeutic equivalence.Conclusions The regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT.However,we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare,analyze,and confirm the findings.     

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis： study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.     

Construction of self-assembled cartilage tissue from bone marrow mesenchymal stem cells induced by hypoxia combined with GDF-5

It is widely known that hypoxia can promote chondrogenesis of human bone marrow de- rived mesenchymal stem cells （hMSCs） in monolayer cultures. However, the direct impact of oxygen tension on hMSC differentiation in three-dimensional cultures is still unknown. This research was de- signed to observe the direct impact of oxygen tension on the ability of hMSCs to ＂self assemble＂ into tissue-engineered cartilage constructs, hMSCs were cultured in chondrogenic medium （CM） containing 100 ng/mL growth differentiation factor 5 （GDF-5） at 5% （hypoxia） and 21% （normoxia） 02 levels in monolayer cultures for 3 weeks. After differentiation, the cells were digested and employed in a self- assembly process to produce tissue-engineered constructs under hypoxic and normoxic conditions in vi- tro. The aggrecan and type ]I collagen expression, and type X collagen in the self-assembled con- structs were assessed by using immunofluorescent and immunochemical staining respectively. The methods of dimethylmethylene blue （DMMB）, hydroxyproline and PicoGreen were used to measure the total collagen content, glycosaminoglycan （GAG） content and the number of viable cells in each con- struct, respectively. The expression of type II collagen and aggrecan under hypoxic conditions was in- creased significantly as compared with that under normoxic conditions. In contrast, type X collagen expression was down-regulated in the hypoxic group. Moreover, the constructs in hypoxic group showed more significantly increased total collagen and GAG than in normoxic group, which were more close to those of the natural cartilage. These findings demonstrated that hypoxia enhanced chondro- genesis of in vitro, scaffold-free, tissue-engineered constructs generated using hMSCs induced by GDF-5. In hypoxic environments, the self-assembled constructs have a Thistological appearance and biochemical parameters similar to those of the natural cartilage.     

Cbl-b and PI3K/Akt pathway are differently involved in oxygen-glucose deprivation preconditioning in PC12 cells

Background Transient sublethal ischemia is known as ischemic preconditioning, which enables cells and tissues to survive subsequent prolonged lethal ischemic injury. Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase （PI3K）/Akt pathway. Cbl-b belongs to the Casitas B-lineage lymphoma （Cbl） family, and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioninq （OGDPC） in PC12 cells were investiaated in the ore.~e.nt study     

Efficacy of Different Iron Controlling Fortificants in Wheat Flour in Iron Deficiency

Objective To observe the different impacts of electrolytic iron, FeSO4, and NaFeEDTA on body iron store of anemic school students. Methods Four hundreds anemic students at the age of 11-18 years were divided into four groups. Of which, three consumed different iron fortificants from wheat flour as food vehicle for six months and one consumed non-fortified flour （control）. The fortification level of electrolytic iron, FeSO4, and NaFeEDTA was 60 mg Fe/kg, 30 mg Fe/kg, and 20 mg Fe/kg, respectively. Blood samples were collected at 0, 2, 4, and 6 months and hemoglobin （Hb）, serum ferritin （SF）, and transferrin receptor （TfR） were measured. Results The hemoglobin levels in three intervention groups increased, the increments of Hb in the NaFeEDTA group were significantly higher than that in the other groups. SF and TfR levels increased in the tested groups and body iron store in the NaFeEDTA group was higher than that in the other groups. These parameters did not show any significant changes in the control group. Conclusion NaFeEDTA and FeSO4 tortified wheat flour has positive impacts on iron status in anemic students and NaFeEDTA is more effective than FeSO4, while electrolytic iron is less effective in improving iron store in anemic students.     

A （H1N1） Influenza Pneumonia with Acute Disseminated Encephalomyelitis： A Case Report

INTRODUCTION
A 56-year-old Chinese female patient with A （H1N1） influenza pneumonia accompanied by acute disseminated encephalomyelitis （ADEM） of the Central Nervous System （CNS） is described in this article. The patient had typical clinical manifestation, and the diagnosis was reached after MRI and other examinations. From this case, we can conclude that the virus of A （H1N1） influenza can infect CNS, and we should pay more attention to patients of A （H1N1） influenza pneumonia with neurological complications.     

Effects of radiation-induced suicide gene therapy under radiation of radionuclide 125I on human hepatocarcinoma cells in vitro

There are few efficient therapeutic approaches to hepatocarcinoma.Chen et al1 developed iodine （131I） metuximab injection （Licartin）,a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab＇2 fragment.HAb18G/CD147 is a hepatocellular carcinoma-associated antigen.But their results have no obvious improvements in survival rate of patients with hepatocarcinoma.Keywords：radiation effects; promoter regions, genetic lentivirus; cytosine deaminase; fluorocytosine; HepG2 cells     

吉非替尼与标准化疗对EGFR突变的晚期非小细胞肺癌患者疗效和安全性的比较

1文献来源 Makoto M, Akira I, Kunihiko K, et al. Gefitinib or chemotherapy for non-small cell lung cancerwith mutated EGFR [J]. N Engl J Med, 2010, 362（25） ： 2380-2388.