Table of Content

Volume 16 Issue 6
26 June 2011

Previous Issue    Next Issue

Impact of cardiovascular drug Quick-Acting Heart Reliever and Tongxinluo capsules on CYP450s in rats after successive administration

BU Ming-hua, ZHENG Yong-qiu, ZHANG Ying, LI Li-qun, LIU Jian-xun, LIU Dong-chun

2011, 16(6):  601-605. 

Asbtract ( 540 )   PDF (331KB) ( 436 )  

References | Related Articles | Metrics

AIM: To investigate the influence of Quick-Acting Heart Reliever and Tongxinluo capsules on drug metablic enzyme cytochrome P450(CYP450) system in rats. METHODS: Rat liver and intestine microsome were prepared after a ten-day continuous administration of Quick-Acting Heart Reliever and Tongxinluo capsules. The content of total CYP450s in rat liver microsome was measured by UV-visible absorption spectrometry. Meanwhile, the protein expression of CYP1A2, CYP2C11, CYP2E1 and CYP3A in the liver microsome and CYP3A in the small intestine microsome was detected by western blotting assay. RESULTS: No significant difference of total CYP450 content was observed between each treatment group and control group(P>0.05). Western blot analysis showed that Quick-Acting Heart Reliever induced the CYP1A2 in liver microsome, but inhibited the liver CYP2C11 and CYP3A in intestine microsome; Tongxinluo capsules induced the expression of CYP1A2 and CYP2E1 in liver microsome. CONCLUSION: Quick-Acting Heart Reliever and Tongxinluo capsules exhibit induction/inhibition on the expression of CYP450 isoforms. The results suggest that the related possible side effects of drug-drug interaction could not be neglected in the period of clinical therapy.

Baicalin downregulates expression of TLR2 and TLR4 gene in chlamydia trachomatis-infected mice

HUANG Hao, FU Lei, YI Yan-dong

2011, 16(6):  606-610. 

Asbtract ( 398 )   PDF (333KB) ( 400 )  

References | Related Articles | Metrics

AIM: To investigate the effects of baicalin on TLR2 and TLR4 expression in cervical tissue of gential tract Chlamydia trachomatis(Ct) infected mice. METHODS: Female C57BL/ 6 mice aged 6-8 weeks were divided into azithromycin group, model group, high concentrations of baicalin group, the concentration of baicalin group and low concentrations of baicalin group. Seven days before inoculation with Ct through vagina, progesterone was administered to all the experimental mice by subcutaneous injection. The numbers of Ct shedding from genital tract were evaluated between the five groups. Twenty seven days after infection, cervical tissue were taken and expression of TLR2 and TLR4 were determined by RT-PCR or Western blot. RESULTS: On the 3rd and 6th day after infection, the amount of Ct in vaginal tract in model group was higher than those in the other groups. After baicalin treatment, the amount of Ct in vaginal tract in the drug groups was lower than that in the model group. The amount of Ct in vaginal tract in the azithromycin group and high concentrations of baicalin group were significantly decreased. Meanwhile, baicalin also reduced the expression of TLR2 and TLR4 in cervical tissue. CONCLUSION: Baicalin effectively blocks high expression of TLR2 and TLR4 in cervical tissue of gential tract chlamydia-infected mice. This is probably the mechanism of baicalin in ameliorating Chlamydia trachomatis-infected mice.

Effect and mechanism of radix astragali injection on production of inflammatory factors induced by lipopolysaccharide in human umbilical vein endothelial cells

LIANG Rong-shou, LI Jian-zhe

2011, 16(6):  611-616. 

Asbtract ( 370 )   PDF (395KB) ( 296 )  

References | Related Articles | Metrics

AIM: To observe the effect of radix astragali injection on the production of inflammatory factors induced by lipopolysaccharide (LPS) and investigate the anti-inflammation mechanism of radix astragali injection. METHODS: The human umbilical vein endothelial cells (HUVECs) were treated with LPS (1 mg/L) for 24 h following pretreatment with various concentrations of radix astragali injection (10, 20 or 40 mg/L) for 2 h. Cell viability was detected by MTT; The mRNA expression and levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were determinded by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) respectively; The mRNA expression of Toll-like receptor 4 (TLR4) was measured by real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR) and the activity of nuclear factor kappa B (NF-κB) was assayed by electrotracellular mobility shift assay (EMSA). RESULTS: LPS could significantly decrease the cell viability, increase the mRNA expression and levels of ICAM-1, IL-8 and TNF-α, upregulate the expression of TLR4 mRNA and NF-κB acitivity. However, the aboving effects of LPS were markedly inhibited by pretreatment with radix astragali injection. CONCLUSION: Radix astragali injection inhibits the production of inflammatory factors may be associated with depressing the TLR4/ NF-κB signaling pathway.

Protective effects studing of total flavonoids of sowthistle-leafixeris seedling on cerebral ischemia injury in rats

JIA De-wu, LUO Sheng-yong, YE Shou-shan, JIA De-yun, LI Xin-wei, MA Zheng, LI Rui

2011, 16(6):  616-620. 

Asbtract ( 437 )   PDF (289KB) ( 378 )  

References | Related Articles | Metrics

AIM: To investigate the protective effects of total flavonoids of sowthistle-leafixeris seedling (TFS) against acute cerebral ischemia in mice and focal cerebral ischemia in rats. METHODS: The occlusion of bilateral common carotid arteries with vagus in mice was used for make the acute cerebral ischemia models.The survival time and the death rate were observed.The permanent occlusion of the proximal of the right middle cerebral artery (MCA)was used for make the focal cerebral ischemia models.The extent of neurological deficits was observed,and the infarct area was measured by NBT staining technique, investigating the influence of TFS on the contents of NOS and iNOS. RESULTS: Compared with model group,TFS of 16,8 mg/kg prolonged the survival time and decreased the death rate of mice with acute cerebral ischemia injury(P＜0.05,P＜0.01).TFS of 16, 8, 4 mg/kg ameliorated neurologic deficits score and the infarct size of rats with MCAO, reduced the contents of NOS, iNOS(P＜0.05). CONCLUSION: TFS has profective effects on cerebral ischemia injury,the mechanism may relate to the inhibiton of NOS and iNOS .

Combined treatment of vitamin K₂ and benazepril induces apoptosis and inhibits angiogenesis on gastric cancer in vitro experiments

CHEN Hua, YING Wei-xing, LI Rong-zhou

2011, 16(6):  621-626. 

Asbtract ( 838 )   PDF (412KB) ( 517 )  

References | Related Articles | Metrics

AIM: To investigate the effect of vitamin K₂ combined with benazepril on human gastric carcinoma SGC-7901 cells in vitro. METHODS: SGC-7901 cells at logarithmic growth phase were obtained and were divided into 5 groups: negative control group, blank control group, vitamin K₂ therapy group, benazepril therapy group and combination therapy group(vitamin K₂+benazepril). SGC-7901 cells were cultured with drugs of different concentrations (vitamin K₂: 5, 10, 20, 40, 80 μmol/L)or benazepril (benazepril: 0.625, 1.25, 2.5, 5, 10 μg/mL) or vitamin K₂+benazepril for 24, 48 and 72 h in drugs group. Cells cultured without drugs were served as negative control and blank control group without cells. The inhibition rates of SGC-7901 cells were detected by MTT assay, apoptosis rate of SGC-7901 cells was determined by Annexin V/PI double staining flow cytometry and DNA ladder, cell cycles of SGC-7901 cells were analysed by flow cytometry and VEGF expression of SGC-7901 cells were detected with RT-PCR. RESULTS: Vitamin K₂ or benazepril had significant inhibitory effect on SGC-7901 cells growth, but combination group was more effective than the drug group alone on SGC-7901 cells proliferation, apoptosis and VEGF expression. CONCLUSION: Vitamin K₂ combined with benazepril have obvious coordination therapeutic effect. The proliferation of SGC-7901 cells could be inhibited by inducing apoptosis and inhibiting VEGF expression.

Meta-analysis of lactobacillus for children acute diarrhoea

ZHOU Dong-ping

2011, 16(6):  627-631. 

Asbtract ( 380 )   PDF (270KB) ( 327 )  

References | Related Articles | Metrics

AIM: To evaluate the effect of lactobacillus in treating children acute diarrhoea. METHODS: By searching CENTRAL(the Cochrane central register of controlledtrials),Medline, EMBSE,CBM,CNKI and WANFANG et al, we collected both domestic and overseas published randomized controled trials about the effect of lactobacillus in treating children acute diarrhoea. The study subjects were children suffering from acute diarrhoea; the intervention was the lactobacillus; the control was placebo;and the outcome was the duration of acute diarrhoea, measured by sandard mean differece(SMD) and its 95% confidence interval (CI). The statistical heterogeneity was tested by cochran's chi-square test (Q test). The Egger test was used to test the publication bias. The data was analyzed by using statistic software Stata11.0. RESULTS: 7 trials that included a total of 945 patients were analyzed in the meta-analysi.479 children were in the lactobacillus group and 466 were in the placebo group.The pooled sandard mean differece for treating acute diarrhoea was -1.24[SMD=-1.24, 95%CI=(-2.21,-0.28),Z=2.54,P=0.01] in the lactobacillus group as compared with the control group. CONCLUSION: The lactobacillus has clinical effectiveness for treating children acute diarrhoea.

An experimental study on inhibition effect of thymoquinone on human colon cancer

WU Yu-hai, XIE Li-wei

2011, 16(6):  632-636. 

Asbtract ( 590 )   PDF (371KB) ( 342 )  

References | Related Articles | Metrics

AIM: To investigate the effect and the mechanism of thymoquinone in the growth inhibition of human colon cancer in vitro and in vivo. METHODS: After human colon cancer SW480 cells were treated with different concentrations of thymoquinone, the cellular proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. The flow cytometry (FCM) was used to determine apoptosis in SW480 cells. Western blotting was used to detect the protein expression of NF- B, Bcl-2 and Survivin. SW480 cells were injected subcutaneously into nude mice to establish xenograft model, and the mice were randomized into two groups (n= 10): Control group, feed with 1% ethanol; Test group, thymoquinone (3 mg/mouse) was given by intragastric intubation. All treatment lasted for two weeks, thrice per week. Eight weeks after implantation, tumor weight and inhibition rate were evaluated respectively after the mice were sacrificed. Immunohistochemistry was used to detect the positive expression of NF- B, Bcl-2 and Survivin in the tumors. RESULTS: Thymoquinone induced a higher percentage of growth inhibition and apoptosis in SW480 cell when compared with the control. The expression of NF- B, Bcl-2 and Survivin were down-regulated in human colon cell line SW480 after treatment of thymoquinone. The treatment of thymoquinone showed significant decrease (P<0.05) in tumor weight relative to untreated control, and the positive expression of NF- B, Bcl-2 and Survivin in the tumors of test group was significantly lower than those in control group. CONCLUSION: Thymoquinone has the antitumor effect to the human colon cancer both in vitro and in vivo, and the effect may be related to the down-regulation of NF-κB and its regulated molecules such as Bcl-2 and Survivin proteins.

Expressions of nucleotide-binding oligomerization domain 2 and Toll-like receptor 1 in rat asthma model and the regulation of budesonide

ZHANG Zhi-gang, YE Bin, TONG Xia-sheng, KANG Xiao-dong, YE Hui, WANG En-zhi, CHEN Hao, CHEN Qi

2011, 16(6):  637-642. 

Asbtract ( 320 )   PDF (459KB) ( 286 )  

References | Related Articles | Metrics

AIM: To investigate the potential roles of pattern recognition receptor in pathogenesis of asthma inflammation, the expressions of nucleotide-binding oligomerization domain 2(NOD2) and Toll-like receptor 1(TLR1) which affected by budesonide were determined in rat asthma model. METHODS: Rat models of asthma were randomly divided into three groups on average, including asthma group, control group and budesonide treated group. The expressions of NOD2 proteins were detected by immunohistochemical method, and levels of TLR1 were also measured by flow cytometry at blood neutrophil. RESULTS: The expressions of NOD2 proteins in asthma group (0.148±0.009,optical density)at lung tissure were significantly lower than those in control group(0.157±0.006, optical density)(P<0.05), but there were nonsignificance difference of NOD2 protein expressions neither between in budesonide treated group(0.149±0.008 optical density) and asthma group, nor between in budesonide treated group and control group(all P>0.05). Dramaticly, levels of TLR1 in asthma group and in budesonide treated group(74.07±6.26 and 78.54±4.65, optical density, respectively) were significantly lower than those in control group(84.37±4.96, optical density)at blood neutrophil either(P<0.01 or P<0.05, respectively).Moreover, there were a strong positive correlation between levels of NOD2 and TLR1 (n=26, r=0.780, P<0.01 ). CONCLUSION: Levels of NOD2 and TLR1 were decreased in asthmatic rats, the pattern recognition receptor may be a potential role in pathogenesis of asthma inflammation. Perhaps there is a mild effect on up-regulating NOD2 and TLR1 levels by budesonide.

Effects of genistein on cytochrome P450 3A activity in healthy volunteers

XIAO Chang-qiong, ZHOU Hong-hao

2011, 16(6):  643-646. 

Asbtract ( 336 )   PDF (192KB) ( 279 )  

References | Related Articles | Metrics

AIM: To examine the potential effects of genistein on CYP3A activity. METHODS: The experiment was conducted in an open, randomized, 2-period crossover study. The probe drug midazolam was used as an indicator of CYP3A function. Every volunteer was administered orally, once a day for 14 days, genistein 1000 mg or placebo(control).On 15th day, a 7.5 mg midazolam was administrated orally. The plasma concentration of midazolam, 1-OH midazolam was determined over 36 h. RESULTS: Coadministration of genistein obviously decreased the area under the curve AUC_0-36 of midazolam [(144±55) ng·mL^-1·h vs (126±40) ng·mL^-1·h,P<0.05] , and significantly decreased AUC_0-∝ of midazolam[(209±57) vs (181±43) ng·mL^-1·h,P<0.05] ,and also decreased C_max of midazolam[(49±20) vs (36±14),P<0.05] . CONCLUSION: Genistein, a principal isoflavone in soybean, in regular doses may induce CYP3A activity in vivo, and it should be aware of potential drug-food interactions.

Development of pyrosequencing method for detection of LAMA5 rs944895

JIA Zheng-jun, WANG Hua, PENG Xiang-jing, HUANG Ding-mei, WANG Guo

2011, 16(6):  647-651. 

Asbtract ( 505 )   PDF (314KB) ( 273 )  

References | Related Articles | Metrics

AIM: To establish a pyrosequencing based method for detection LAMA5 rs944895 polymorphism and to determine the frequency of this polymorphism in healthy Chinese. METHODS: After preparation of gDNA from blood of 201 subjects, LAMA5 rs944895 target fragments were amplified by PCR, LAMA5 rs944895 polymorphism was detected on PyroMark ID by pyrosequencing technology. The reliability of pyrosequencing method was validated by repeat tests and Sanger sequencing. RESULTS: We established a new pyrosequencing method to detect the LAMA5 rs944895 polymorphism in healthy Chinese. The detection rate and repetition rate were both 100%. The frequencies of A allele and G allele were 72.4% and 27.6%, respectively. And the frequencies of AA, AG and GG genotype were 53.2%, 38.3% and 8.5%, respectively. The genotype frequencies match the Hardy-Weinberg equilibrium (P=0.55). CONCLUSION: This pyrosequencing assay to detect the LAMA5 rs944895 polymorphism is proved to be a rapid, accurate and high-throughput alternative to conventional methods, and it can be a preferred option in research and clinical application.

Comparison of prednisone versus hydroxyethylstarch for prevention of moderate and severe ovarian hyperstimulation syndrome

YANG Hai-yan, ZHAO Jun-zhao, LIN Wen-qin, LIN Jin-ju, RU Rong

2011, 16(6):  652-656. 

Asbtract ( 753 )   PDF (198KB) ( 374 )  

References | Related Articles | Metrics

AIM: To compare the efficiency of prednisone and 6% hydroxyethylstarch in the prevention of moderate and severe ovarian hyperstimulation syndrome (OHSS). METHODS: A total of 207 OHSS high-risk patients and 207 cycles of in vitro fertilization and embryo transfer (IVF-ET) programme with estradiol serum concentration≥4000 pg/mL on the day of hCG injection and/or≥15 oocyte collection were prospective and randomized divided into A, B and C three groups. The patients in group A (66 cycles) orally took prednisone 5 mg tid on the day of hCG injection for 2 d, and then changed to 5 mg qd for 5 d; the patients in group B (75 cycles) were infused with 500 mL 6% hydroxyethylstarch on the day of oocyte collection for 3d; the patients in group C (66 cycles) were treated with prednisone and hydroxyethylstarch. The incidence of moderate and severe OHSS and the other corresponding indexes among the three groups were analyzed. RESULTS: There have 60 cycles were transferred in group A, clinical pregnancy rate was 50% and the incidence of moderate and severe OHSS was 3.03%; 65 cycles were transferred in group B, clinical pregnancy rate was 44.6%, and the incidence of moderate and severe OHSS was 13.33%; 59 cycles were transferred in group C, clinical pregnancy rate was 42.4% and the incidence of moderate and severe OHSS was 3.03% .There was no significant difference in pregnancy outcome among the three groups (P>0.05), but the incidence of moderate and severe OHSS in group B was higher than those in group A and group C (P<0.05). CONCLUSION: Oral administration of prednisone have no effect on pregnant rate of IVF and it is a cheaper, more convenient and effective alternative to 6% hydroxyethylstarch in moderate and severe OHSS prevention.

Analysis of risk factors with refractory Kawasaki disease to gamma-globulin therapy

ZHANG Song-yue, ZHANG Yuan-hai, RONG Xing, REN Yue, CHEN Qi, XIANG Ru-lian

2011, 16(6):  657-660. 

Asbtract ( 428 )   PDF (162KB) ( 308 )  

References | Related Articles | Metrics

AIM: To investigate the incidence and risk factors of children with refractory Kawasaki disease (KD). METHODS: Clinical data of KD patients hospitalized in the Second Affiliated Hospital of Wenzhou Medical College from January 2005 to December 2010 were summarized.Refractory KD was defined as those who remained febrile with a temperature of > 38.5 ℃ for 36 hours after initial intravenous immunoglobulin treatment. All KD patients were divided into two groups, responsiveness group and non-responsiveness group,based on their response to the first high dose IVIG therapy. RESULTS: Total 515 KD patients treated with high dose IVIG were included.The incidence of non-responsiveness to IVIG therapy is 7.57% (39/515). Logistic regression revealed that white blood cell(WBC), hemoglobin,C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), alanine aminotransferase (ALT), serum albumin and IVIG dosage were independent risk factors for refractory KD(P<0.05). CONCLUSION: The incidence of refractory KD is 7.57%. WBC, hemoglobin, CRP, ESR,ALT, serum albumin and IVIG dosage can predict the occurrence of refractory KD.

Comparison of entecavir and adefovir dipivoxil on suppressing for the function of regulatory T cells for patients with chronic hepatitis B

ZOU Ming-zhi

2011, 16(6):  661-665. 

Asbtract ( 341 )   PDF (299KB) ( 287 )  

References | Related Articles | Metrics

AIM: To observe the effect of entecavir (ETV) and adefovir dipivoxil (ADV)on suppressing for the function of regulatory T cells (Treg) for patients with chronic hepatitis B(CHB). METHODS: Thirty six CHB patients were randomly divided into the ETV and ADV groups. Patients in ETV group were administrated ETV 0.5 mg q.d., whereas the ones in the ADV group were dosed with ADV 10 mg q.d.. All the subjects were treated for 48 weeks and were followed at the end of the 12th, 24th, 36th and 48th week to collect the peripheral blood for test. Flow cytometry was applied to test the percentage of Treg, whose cytokines including IL-10 and TGF-β₁ were detected by ELISA. Real time PCR was used to test the quantities of HBV DNA as well as the Foxp3 mRNA. Besides, the liver function including ALT and T-Bil were also examined for all the CHB patients. RESULTS: There was no statistical difference between the two groups before therapy. The percentages of Treg in ETV group were significantly lower than those of ADV group at the end of the 24th, 36th and 48th week. The levels of Treg's functional factors, the Foxp3, IL-10 and TGF-β₁, were also totally lower in the ETV group when compared with the ADV group (P<0.05). For the function of anti-HBV, the HBV DNA copies in ETV group were significantly lower than those in ADV group at the end of the 12th and 36th week (P<0.05). The level of ALT was also significantly lower in ETV group at the end of the 12th week when compared with the ADV group (P<0.05). But there was no statistical difference of T-Bil level between any point times of follow-up. Pearson analysis showed that percentages of Treg correlated the copies of HBV-DNA positively(r=0.785 and P=0.016). CONCLUSION: Entecavir is proven to be more effective on suppressing for the function of regulatory T cells for patients with CHB when compared with adefovir dipivoxil.

Analysis of the relationship between expression of β-tubulinⅢ, survivin and response to docetaxel in metastatic breast cancer

YUAN Shao-fei, ZHU Lin-jia, ZHENG Wei-e, CHEN Wen-jun, CHEN Hua, ZHANG Wu

2011, 16(6):  666-671. 

Asbtract ( 368 )   PDF (357KB) ( 246 )  

References | Related Articles | Metrics

AIM: To investigate the expression of β-tubulinⅢ, survivin protein and chemoresistance to docetaxel in advanced gastric cancer. METHODS: Seventy-four patients of advanced gastric cancer treated with docetaxel were enrolled in this study and their tumor samples were collected retrospectively for analysis. The expression of β-tubulinⅢ, survivin protein in tumor samples was detected by the immuno- histochemical methods. The data of therapeutical effect and toxicity were collected and analyzed. RESULTS: β-tubulinⅢ positive staining accounted for 38.1％(32/84). Survivin positive staining accounted for 76.2％(64/84). There was no correlation between β-tubulinⅢ, survivin positive expression and age, gender, pathological type. The response rate(CR+PR)was 52.38％. Patients with overexpression β-tubulinⅢ were less response rate (37.50％vs 61.54％) to docetaxel (P<0.05). Patients with overexpression survivin were less response rate (48.40％vs 65.50％) to docetaxel (P<0.05). Patients with overexpression β-tubulinⅢ and survivin were also lower response rate (25.0％vs 73.91％, P<0.05). Patients with over expression β-tubulinⅢ and survivin have also lower the median time to progress and 1- and 2-year survival rates (3.9m vs 7.7m, 34.5% vs 61.6%, 15.1% vs 31.4%, P<0.05). The main side-effects were myelosuppression and digestive apparatus toxicity. CONCLUSION: The expression of β-tubulinⅢ and survivin is associated with clinical response to docetaxel chemotherapy in metastatic breast cancer and can be used as method of detection of sensitivity.

Endogenous sleep-promoting substances

YUE Xiao-fang, QIU Mei-hong, QU Wei-min, HUANG Zhi-li

2011, 16(6):  672-678. 

Asbtract ( 505 )   PDF (341KB) ( 444 )  

References | Related Articles | Metrics

Sleep-wake cycle is regulated by humoral and neuronal mechanism, as well as circadian rhythm. Kuniomi Ishimori and Henri Piéron provided the first experimental evidence for chemical factors that presumably accumulate in the cerebrospinal fluid in dogs after sleep deprivation, and eventually induce sleep. These substances are named hypnotoxin. Accumulated findings show that these endogenous substances include prostanoids, nucleotides, cytokines, neuropeptides, hormones, amine derivatives, nitrogen oxide and so on. This paper presents an overview of current knowledge about the roles of endogenous sleep-promoting substances in the sleep-wake regulation with a focus on prostaglandin D₂, adenosine, interleukin-1, and tumor necrosis factor.

Progresses of AEG-1 on cancer research

HAO Gang, ZHOU Fang, WU Xiao-lan, WANG Guang-ji

2011, 16(6):  679-687. 

Asbtract ( 750 )   PDF (399KB) ( 495 )  

References | Related Articles | Metrics

Astrocyte-elevated gene-1 (AEG-1), a novel oncogene, has been implicated in several crucial aspects of tumor progression, including oncogenic transformation, evasion of apoptosis, proliferation, invasion, metastasis, angiogenesis, chemoresistance and protective autophagy. Human AEG-1 gene is located in chromosome 8q22, which is known to be a hot spot for genomic alterations in several cancer cells. AEG-1 is regulated by Ras/PI3K/Akt/c-Myc pathway and exerts its effects by activating various pathways such as PI3K/Akt, NF-κB, Wnt/β-catenin, MAPK and so on. Since its clinical significance and biological role in human cancers, AEG-1 provides a novel target for intervening in the cancer phenotype. This article reviewed the current progress in the research field of AEG-1 in human tumor.

Advantages, disadvantages and applications of in vitro hepatic metabolic models

LI Dan, HAN Yong-long, YU Tao, MENG Xiang-le, YU Qi, WANG Jun, GUO Cheng

2011, 16(6):  688-694. 

Asbtract ( 554 )   PDF (254KB) ( 1232 )  

References | Related Articles | Metrics

The liver is the predominant organ participating metabolism of xenobiotics.Generally, drugs will be mainly eliminated from the body by the way of metabolism.Drug biotransformation is one of the most important events that affect the overall pharmacologic and toxic profile and the subsequent therapeutic and safety index.Hence, hepatic metabolism research is a key step in the preclinical drug discovery and development process.For this purpose, in vitro approaches using various hepatic metabolism models, with the merits of rapidness, accuracy, high throughput have been gaining increasing popularity in the academic and pharmaceutical fields.The presently used in vitro models includes recombinant enzymes, microsomes, cytosol, S9 fraction, cell lines, transgenic cell lines, primary hepatocytes, stem cell derived hepatic cell, precise liver slices and perfused liver.This review will describe the advantages, disadvantages and the applications of these in vitro models with the purpose of facilitating researchers to choose appropriate models to make reasonable evaluation of in vitro metablism and study the possible drug biotransformation model in liver,and finally to predict drug elimination mode in vivo scientifically.

Effect of Nrf₂-ARE pathway in the heart ischemic injury

XU Yuan-qing, HE Hai-bo, ZHANG Chang-cheng, WANG Hong-wu, YUAN Ding

2011, 16(6):  695-698. 

Asbtract ( 363 )   PDF (162KB) ( 245 )  

References | Related Articles | Metrics

Nrf₂-ARE pathway is particularly important as an anti-oxidative stress pathway in recent years, the mechanism of signal pathway is intricate and general. More research suggests that it plays an important role in the pathogenesis of heart ischemic injury, and it will be an important potential target for treatment of heart ischemic injury. In summary, the physiological and pathophysiological function of Nrf₂-ARE pathway and relation with heart ischemic injury has been reviewed.

Prediction of key pharmacokinetic parameters in human

ZHU Jian-ping, SUN Jian-guo, PENG Ying, WANG Guang-ji

2011, 16(6):  699-709. 

Asbtract ( 819 )   PDF (343KB) ( 2207 )  

References | Related Articles | Metrics

Volume of distribution, clearance, half of life and bioavailability are crucial pharmacokinetic parameters determining the extent and sustained time of drugs exposed in vivo. Thus, in the stage of drug discovery and development, it is of particular interest to estimate the pharmacokinetic parameters of drug candidates in human as early as possible to select the most promising compounds for further development. This paper reviews recent developments in prediction of human key pharmacokinetic parameters based upon preclinical animal pharmacokinetic data, absorption and metabolism data in vitro, physico-chemical property and in silico prediction.

Pharmacogenomics and personalized medicine of tacrolimus

ZHU Lin, HUA Zhi-hui, SONG Hong-tao

2011, 16(6):  710-715. 

Asbtract ( 505 )   PDF (213KB) ( 277 )  

References | Related Articles | Metrics

Tacrolimus (FK506), a widely used immunosuppressant, exerts a key effect in patients with organ transplantation. The drug requires therapeutic monitoring due to its narrow therapeutic index and great inter-individual variability. FK506 is known to be a substrate of CYP3A and P-glycoprotein (P-gp) . FK506 is metabolized by CYP3A and transported by P-gp. The difference in expression level and the bioactivity of these proteins may explain individual variations of FK506 pharmacokinetics.The differences in bioactivities of CYP3A and P-gp are believed to be due to CYP3A and MDR1 geneticmutation. Therefore, genetic variations of CYP3A and MDR1 may play an important role in the inter-individual variability of FK506. In this article, we reviewed the effect of CYP3A and MDR1 gene polymorphisms on pharmacokinetics of FK506 in patients with organ transplantation. This article presents an overview of the current research progress of pharmacogenomics of tacrolimus.

Clinical research advancement of nanoparticle albumin-bound paclitaxel in anti-cancer treatment

CAI Xin-jun, XU Ying-ying, NI Jian-jun

2011, 16(6):  716-720. 

Asbtract ( 871 )   PDF (181KB) ( 558 )  

References | Related Articles | Metrics

Albumin is a vital drug carrier for nanoparticle paclitaxel in the anti-cancer treatment.This paper reviewed the pharmacokinetics and mechanism of nanoparticle transport of nanoparticle albumin-bound paclitaxel,and summarized the recent clinical trials of nanoparticle albumin-bound paclitaxel in breast cancer,non-small cell lung cancer,and other malignant treatment which could be a reference for its clinical use.