The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

A phytochemical investigation on the aerial parts of a Tibetan medicine Meconopsis horridula, by solvent extraction, repeated chromatographies on silica gel, Sephadex LH-20, and preparative TLC techniques, led to the isolation of 9 compounds. By spectroscopic analysis and comparison of its 1H and 13C-NMR data with those in literatures, their structures were identified as oleracein E(1), N-( trans-p-coumaroyl) tyramine (2), chrysoeriol (3), apigenin (4), hydnocarpin (5), p-coumaric acid glucosyl ester (6), stigmast-5-ene-3beta-ylformate (7), 3beta-hydroxy-7alpha-ethoxy-24beta-ethylcholest-5-ene (8), and beta-sitosterol (9), respectively, among which compounds 6-8 were isolated from the genus for the first time,and 1,3 were isolated from the species for the first time. A MTT method was applied to evaluate the cytotoxic activity of compounds 14 against the human hepatocellular liver carcinoma cell line (HepG2), and compound 1 showed significant cytotoxicity against HepG2,with its inhibitory rate of 52.2% at 10 micromol x L(-1).
Medicine, Tibetan Traditional ; Molecular Structure ; Papaveraceae ; chemistry ; Plant Extracts ; chemistry ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo observe the clinical efficiency of curettage combining circumcision on giant condyloma acuminata(CA) in male external genitalia, the relationship between recurrence and curettage depth, the possibility of HPV infection in PBMC after operation.

METHODSCurettage combining circumcision was carried out on 50 cases with CA. The removed wart and wound surface tissues were examined under light microcope and for HPV-DNA detection by PCR. HPV-DNA was detected in PBMC during < or =1 and > or =2 weeks after operation.

RESULTS(1) 46 cases were cured completely after one treating (once the cure rate is 92%), 4 cases twice(twice the cure rate is 8%); (2) The tissues were proved to be HPV-DNA positive by PCR amplification and CA relapse occurred; (3) HPV-DNA was detected in PBMC only within the week after curettage in the 19 cases.

CONCLUSIONS(1) The clinical efficiency of curettage combining circumcision on giant condyloma acuminata in male external genitalia is sure; (2) Cure rate and relapse rate are related with curettage depth; (3) Transient positive HPV-DNA in PBMC may be detected.

Adolescent ; Adult ; Aged ; Circumcision, Male ; Condylomata Acuminata ; surgery ; Curettage ; methods ; Humans ; Male ; Middle Aged ; Young Adult

Objective To investigate the effects of different concentrations of sodium fluoride on the morphologic characteristics of primarily cultured thyroid cells of SD rats and in order to obtain important proof for approaehing the mechani8m of thyroid gland damage caused by fluoride.Methods Thyroid cells of SD rat were primarily culture for 96 hours,and cell density was adjusted to 5.0×108/L Cell suspension with 5 ml Wills seeded into 6 weII plates,after 12 hours,0(contr01),10.100,1000 μmol/L of sodium fluoride was added into the well, witll each well representing different level of treatment group.Finally the cultured thyroid cells were collected for morph010gic study.Results Under microscope,the transparency of the control thyroid cells Was good,and cells gathered in cluster and adhered to wall.But a lot of cells treated with fluoride suspended,and lost their transparency-under scaning delectron microscope,the control calls showed integrated membrane and tightness to each other,as well as clear boundary between cells normal proliferation.While the thyroid cells treated with 10,100 μmol/L sodium fluoride 0bviouslv shrinked and deformed,and the cells treated with 1000 μmol/L of sodium fluoride were broken-Conclusions nuoride can affect the growth and development of thyroid cell and damage the structure and morphology.Sodium fluoride affects the morphologie characteristics of thyroid cells in a dose-response manner.

Objective To express the plasminogen activator(Pla) of Yersinia pestis and one of its gene fragments,and to detect their immunological reactivity.Methods The pla gene and its specific gene fragment pla-c were amplified by PCR using the EV76 strain as a template.PCR products were then ligated with the plasmid pET32a (+).The recombinant plasmids pET32a (+)-pla and pET32a (+)-pla-c were subsequently trausformed into E.coli BL21 (DE3).The expressed products were purified by HIS affinity chromatography,and their immunological reactivity was detected by Western blotting.Results The recombinant Pla(52.8 × 103) was expressed as inclusion bodies,and the recombinant Pla-c protein (24.0 × 103) was expressed in the soluble form.These two recombinant proteins reacted with anti-Yersinia pestis EV76 rabbit sera.Conclusions The recombinant Pla and its specific fragments have displayed immunological reactivity,and can be served as an alternative diagnosis method for Yersinia pestis.

Objective： The current study was designed to clarify whether hepatopoietin (HPO) stimulates autonomous growth of hepatoma cell by autocrine loop. Methods： The authors conducted experiments in vitro with hepatoma cell lines. RT-PCR, ELISA and Western blot were used to examine HPO expression in hepatoma cells. Blocking effect of HPO by HPO neutralizing antibody was utilized and the changes of cell proliferation was observed. Results： HPO was expressed by hepatoma cells and secreted into the medium. Moreover, the HPO antibody inhibited specifically the autonomous proliferation of hepatoma cell and antagonized the stimulatory effect of concentrated conditioned medium derived from hepatoma cell HepG2. Conclusion： The results strongly suggest that HPO acts as an autocrine factor to maintain the autonomous growth of hepatoma cells.

Objective To investigate the relations between saliva arsenic levels and serum arsenic and urinary arsenic of rats after exposed to different levels of sodium arsenite.Methods Thirty-two SD rats were randomly divided into four groups(8 rats in each group),namely the control group,the low,the medium,and the high doses of sodium arsenite exposure groups.Rats of the control group were given 0.9％ NaCI by gavage,and other three groups were given sodium arsenite of 0.2,2.0,20.0 mg/kg body weight by gavage.All animals were administrated every other day for two weeks,then saliva,blood,urine and tissue organs were collected,organ coefficients were calculated,total arsenic concentrations in blood and urine were detected by Atomic Fluorescence Spectrometry(AFS-230) and total arsenic concentration in saliva was detected by Inductively Coupled Plasma Mass Spectrometer(ICP-MS).Results The weight gain values of rats exposed to sodium arsenite were lower than that of the control group,the difference was statistically significant between the highest dose group[(76.13 ± 17.19)g]and the control group[(103.00 ± 12.31)g,P ＜ 0.05].The liver and kidney organ coefficients in the highest dose group [(3.92 ± 0.54)％,(0.96 ± 0.15)％]were significantly higher than that in the control group[(3.27 ± 0.35)％,(0.76 ± 0.05)％,P ＜ 0.05 or ＜ 0.01].The total arsenic concentrations in saliva[(0.044 ± 0.019),(0.211 ± 0.071),(1.128 ± 0.380)mg/L],blood[(11.832 ± 1.887),(45.032 ± 7.216),(121.839 ± 17.323)mg/L]and urine[(0.138 ± 0.085),(0.874 ± 0.328),(8.843 ± 1.754)mg/L]in the three treatment groups were significantly higher compared with that of the control group [(0.018 ± 0.014),(2.267 ± 0.370),(0.025 ± 0.011)mg/L,all P ＜ 0.05],furthermore,there was a significant difference among the three treatment groups (all P ＜ 0.05).The arsenic contents in saliva were significantly correlated with blood arsenic and urinary arsenic,the correlation coefficient was 0.934 and 0.960,respectively (all P ＜ 0.01).Conclusions High dose of arsenic exposure,with a strong toxicity to liver and kidney,can inhibit the increase of rat body weight.Arsenic dose-response relationship exists in the saliva,and saliva arsenic is significantly correlated with blood arsenic and urinary arsenic,suggesting that salivary arsenic can be used as a new biomarker for assessing human exposure to arsenic.

Imatinib, a breakpoint cluster region (BCR)-Abelson murine leukemia(ABL) tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myelogenous leukemia (CML). However, development of multidrug resistance(MDR) limits the use of imatinib. In the present study, we aimed to investigate the mechanisms of cellular resistance to imatinib in CML. Therefore, we established an imatinib-resistant human CML cell line(K562-imatinib) through a stepwise selection process. While characterizing the phenotype of these cells, we found that K562-imatinib cells were 124.6-fold more resistant to imatinib than parental K562 cells. In addition, these cells were cross-resistant to second- and third-generation BCR-ABL TKIs. Western blot analysis and reverse transcription-polymerase chain reaction(RT-PCR) demonstrated that P-glycoprotein(P-gp) and MDR1 mRNA levels were increased in K562-imatinib cells. In addition, accumulation of [14C]6-mercaptopurine (6-MP) was decreased, whereas the ATP-dependent efflux of [14C]6-MP and [3H]methotrexate transport were increased in K562-imatinib cells. These data suggest that the overexpression of P-gp may play a crucial role in acquired resistance to imatinib in CML K562-imatinib cells.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Benzamides ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; antagonists & inhibitors ; Gene Expression Regulation, Neoplastic ; Humans ; Imatinib Mesylate ; K562 Cells ; Mercaptopurine ; metabolism ; Methotrexate ; metabolism ; Piperazines ; pharmacology ; Protein Kinase Inhibitors ; pharmacology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; RNA, Messenger ; metabolism

This study was aimed to analyze the correlation of JAK2V617F mutation burden with clinical features in patients with polycythemia vera (PV) and essential thrombocythemia (ET), The JAK2V617F mutation ratios in 47 PV samples and 43 ET samples were detected by real-time PCR. The correlation of mutation allele ratio in PV and ET samples with clinical features (hemoglobin, hematocrit, white blood cell count and platelet count) was analyzed. The results showed that the JAK2V617F mutation burden was higher in PV (0.441 +/- 0.270) than that in ET (0.209 +/- 0.192). The JAK2V617F mutation burden was positively correlated with levels of hemoglobin (PV: R = 0.518, p < 0.001; ET: R = 0.528, p = 0.005), hematocrit (PV: R = 0.510, p < 0.001; ET: R = 0.524, p = 0.005) and leukocyte (PV: R = 0.584, p = < 0.001; ET: R = 0.471, p = 0.013) in PV and ET samples. The higher JAK2V617F mutation burden was negatively correlated with levels of platelet count in PV samples (R = -0.354, p = 0.020), but there was no correlation between the JAK2V617F mutation burden and platelet count in ET samples (R = 0.233, p = 0.242). It is concluded that the higher JAK2V617F mutation burden is related with higher hemoglobin, hematocrit and leukocyte count in both PV and ET samples. The higher JAK2V617F mutation burden is correlated with lower platelet count in PV samples, but there is no correlation between JAK2V617F mutation burden and platelet count in ET samples.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Hemoglobins ; Humans ; Janus Kinase 2 ; genetics ; Male ; Middle Aged ; Mutation ; Polycythemia Vera ; genetics ; Polymerase Chain Reaction ; Thrombocythemia, Essential ; genetics ; Young Adult