Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.

Hamartoma ; congenital ; pathology ; Humans ; Mesoderm ; Mouth ; Mouth Diseases ; congenital ; pathology

Objective To investigate the effect of rocuronium on spectral entropy during induction of general anesthesia in patients of Uygur nstionality. Methods Forty ASA Ⅰ or Ⅱ patients (Uygur nationality) of both sexes, aged 20-50 yr, weighing 45-70 kg, undergoing elective surgery under general anesthesia, were divided into 2 groups ( n = 20 each): normal saline (NS) group and rocuronium group (group R). Anesthesia was induced with target-controlled infusion of propofol. The initial target plasma concentration wan net at 2 μg/ml. The concentration wan then increased by 0.5 μg/ml every 4 min until response entropy (RE) was decreased to 45 and maintained for 4 min. When the plasma concentration was equal to the effect-site concentration, iv rocuronium 0.6 mg/kg was injected in group R, while group NS received the equal volume of NS instead. Fentanyl 3 μg/kg was injected intravenously at 3 min after recuronium administration. The patients were tracheal intubated and mechanically ventilated. State entropy (SE) and RE were recorded immediately before induction (baseline, To), before rocuronium administration (T1), 2 main after rocuronium administration (T2) and at 0, 1, 2 and 3 min after intubation (T3-6). The difference between RE and SE wan calculated. Results The RE value at T3 and T4 and the difference between RE and SE at T2.5 were significantly lower in group R than in group NS ( P ＜ 0.05). Conclusion Rocuronium can decrease the RE value and degree of increase in the difference between RE and SE during induction of general anesthesia in patients of Uygur nationality, which may affect the accuracy of spectral entropy in monitoring the depth of anesthesia.

Objective To summarize the analytical results of radioactivity in the food and drinking water nationwide following the Fukushima nuclear accident,and to evaluate its possible contamination to the public health in China.Methods According to the national standard methods and IAEA,FDA correlative references,the scheme was established on sampling and measurements in food and drinking water after the breakout of the accident.The quality control was requested on the sampling,analyses and data report.Results Trace artificial radioactive isotope of 131I was measured in spinach samples on 2 April 2011 in Beijing. Subsequently 131I was found in 10 kinds of growing leaves vegetables (open field)nationwide.The maximum detectable activity of 131I in vegetables was about 3.1 Bq/kg.Since 3 May 2011,the concentration of 131I has been below the detection limits.No artificial radionulide was detectable in all of milk,drinking water and marine products samples during March to December,2011.Conclusions The food and drinking water measurements in China following the Fukushima nuclear accident denoted that the minor amounts of 131I in vegetables might result in very low absorbed dose and induce no impact on human health.The maximum detectable activity of 131I in vegetables was close to that reported in European countries,and much less than that measured in China immediately after the Chernobyl accident in 1986.

OBJECTIVETo investigate the regulation of Cha Gan Beng Ga on the activity of biomarker PGC-1α in vivo and in vitro, and lay the foundation for studying the efficacy result of Cha Gan Beng Ga on xenograft tumor model and extracting active constituents.

METHOD(1) The coarse powder of Cha Gan Beng Ga was extracted with 70% ethanol solution through heating and refluxing, and finally was used to freeze dry powder. (2) 50 mg x kg(-1) of freeze-dried power was orally administrated to KM and C57BL/6J mice once daily, lasting for 5 consecutive days; different concentrations of extracted materials was given to non-small cell lung cells A549. (3) The expression level of PGC-1α mRNA was quantitatively determined in lung tissue of mice and non-small cell lung cells A549.

RESULTThe expression levels of PGC-1α in lung tissue of different mice strains had an increasing tendency. Furthermore, the expression levels of PGC-1α in non-small cell lung cells A549 also had an increasing tendency, showing dose and time-dependent relationships.

CONCLUSIONMongolian Medicine Cha Gan Beng Ga could induce the over-expression of PGC-1α mRNA in lung tissue of mice and in non-small cell lung cells A549. The present results will lay foundation for studying the efficacy result of antitumor and active constitutes in future.

Aconitum ; chemistry ; Animals ; Biomarkers, Tumor ; genetics ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Lung ; drug effects ; metabolism ; Lung Neoplasms ; genetics ; pathology ; Male ; Medicine, Mongolian Traditional ; Mice, Inbred C57BL ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Plant Extracts ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Transcription Factors ; genetics

Objective:To evaluate the safety and efficacy of antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary in-tervention. Methods:In the study, 96 patients suffering from acute ST segment elevation myocardial infarction onset within 12 h undergoing primary percutaneous coronary intervention from May to October in 2013 were randomly divided into ticagrelor group (n=48) and clopidogrel group (n=48) by using the method of random number table. Ticagrelor and clopidogrel antiplatelet treatment were used before and after operation. Their baseline data, coronary artery disease characteristics, platelet count, adenosine diphosphate(ADP)-induced platelet inhibition rate by thrombelastograph after 5 days of treatment, the major adverse cardiovascular events of the follow up for 6 months and bleeding complications were observed and compared in the two groups. Re-sults:The differences between the two groups of patients with their baseline data, the features of coronary ar-tery lesions, platelet count before and after 5 days of treatment had no statistical significance (P>0. 05). ADP induced platelet inhibition rate [(80. 2 ± 10. 7)%] after 5 days of treatment in ticagrelor group was sig-nificantly higher than that in clopidogrel group [(75. 3 ± 12. 1)%, P<0. 05]. The two groups of patients were followed up for 6 months, 8 cases of major adverse cardiovascular events occurred in clopidogrel group, 2 ca-ses of major adverse cardiovascular events occurred in ticagrelor group, and there was significant difference between the two groups (P<0. 05). The two groups (7 cases of 48 patients in ticagrelor group vs. 3 cases of 48 patients in clopidogrel group ) had no statistically significant difference in bleeding complications ( P>0. 05). Conclusion: Antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing emergency PCI has good efficacy and safety.

Brain ; abnormalities ; Cerebral Cortex ; abnormalities ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Nervous System Malformations ; diagnosis ; Prognosis

Objective To establish an effective and reliable method for analysis of uhratrace uranium in multi-stage atmospheric particles providing the monitoring and evaluation of the content of radioactive uranium in the atmosphere.Methods A large volume six-stage-impactor sampler of atmosphere particles was used to collect aerosol samples,and uhratrace uranium in particles was digested using microwave and measured by inductively coupled plasma mass spectrometry.The filter material,digestion conditions and microwave digestion system had been optimized.Results The background of uranium level on the cellulose filter was the lowest,and the samples were digested by using HNO3-HCI (aqua regia)-H2O2 solution.Reference material SRM2783 was used to validate the accuracy of the method,and the relative error of the 238U was 7％,The detection limit of the method was 2 × 10-4ng/m3.The aerosol actual samples were analyzed using the established method.The mass concentrations of uranium in PM2.5 was in the range of 0.023-0.065 ng/m3.Conclusions The established method was effective and reliable to monitor the concentration level of ultratrace uranium in multi-stage atmospheric particles.

Background and purpose:Suppression of apoptotic signaling pathways is an important factor in tumor cell resistance. Research on cell apoptosis will open up a new way of reversing drug resistance and tumor treatment. This study examined the effects of a novel naphthalimide derivative 8c on multidrug resistant colon cancer HCT116/L-OHP cells and explored the molecular mechanisms underlying the apoptosis induction. Methods: The anti-proliferative effects of 8c were detected by CCK-8 assays and the effects on apoptosis induction were examined by lfow cytometry. The mRNA expression levels of p53, Bax and Bcl-2 were measured by real-time PCR;The protein expressions of p-p53, Bax, Bcl-2 and Cyt-c were detected by Western blot. Results:8c (IC50=8.16 μmol/L) seemed to be more potent than amonaifde (IC50=28.37 μmol/L) against HCT116/L-OHP cells. 8c induced apoptosis on HCT116/L-OHP cell lines through intrinsic or mitochondria dependent pathway. The protein expression of phosphorylation of p53 at Ser-15 was increased, but the mRNA level of p53 did not increase in HCT116/L-OHP cells. Bax protein and mRNA levels were signiifcantly increased, and Bcl-2 protein and mRNA levels were decreased, suggesting an increase of Bax/Bcl-2 ratios. Meanwhile, 8c induced a substantial release of cytochrome c from the mitochondria into the cytosol in HCT116/L-OHP cells. Conclusion: 8c induced cell death signal by inducing the activation p53 phosphorylation which subsequently activated related protein expressions of apoptotic pathway, which may be an important mechanism of 8c on inhibiting proliferation of HCT116/L-OHP resistant cells. All the results suggested that 8c was a potent compound to be developed as an anti-tumor and anti-resistance agent for clinic application in the future.

Phthaloyl dichloride (1)was reacted with LiAlSeH2 to give benzo[c]selenophene-1;3-dione (2);which was treated with the Grignard reagents to generate hydroxyl compounds 3a-3h.These compounds were finally converted to target products 4a-4h by treatment with hydriodic acid.The structures of 4a-4h were confirmed by MS and 1 H NMR.Their inhibitory activity against adenosine diphosphate (ADP)-induced platelet aggregation was evaluated by Born′s turbidimetric assay;free radical scavenging activity was assayed by xanthine oxidasemethod and 1;10-phenanthroline spectrophotometric method.It was found that compound 4 f displayed more potent inhibi-tory effect on platelet aggregation than 3-n-butylphthalide and comparable hydroxyl free radical scavenging activity in vitro to that of edaravone.Therefore;compound 4 f might be the candidate for further investigation.