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Inhibition Mechanism of Novel Pyrazolo1,5-apyrazin-4(5H)-one Derivatives Against Proliferation of A549 and H322 Cancer Cells.

Jin-hui SHAO ; Gui-hua FENG

Chinese Medical Sciences Journal.2015;30(4):260-265.

OBJECTIVETo explore the inhibition mechanism and safety of pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives against proliferation of human lung cancer A549 cells, H322 cells, and human umbilical vein endothelial cell (HUVEC).

METHODSCells were treated with 40 Μmol/L of the ppo3a, ppo3b, ppo3i, and 0.1% DMSO (control) for 48 hours, respectively. Apoptosis was determined by Hoechst 33258 staining assay in H322 and A549 cells. Cell cycle distribution was determined by flow cytometry analysis in A549 cell. LC3-II, p53, and heat shock protein (HSP) 70 protein levels were detected by Western blotting in A549 cells treated with ppo3b for 48 hours. The morphology and viability of HUVEC were observed by inverted microscope and sulforhodamine B (SRB) assay.

RESULTSPpo3a, ppo3b, and ppo3i significantly induced apoptosis in H322 and A549 cells. A strong G1-phase arrest was concomitant with the growth inhibitory effect on A549 cells. Ppo3b effectively elevated the p53 protein level, but significantly reduced the HSP70 protein level. There were no significantly inhibitory effect on the morphology and viability of HUVEC when treated with ppo3a, ppo3b, and ppo3i.

CONCLUSIONSppo3a, ppo3b, and ppo3i could inhibit H322 proliferation through apoptosis and inhibit A549 through apoptosis and G1-phase arrest. The protein p53 and HSP70 might involve in the inhibition effects. These derivatives might be a clue to find effective and safe drug for lung cancers.

Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; HSP70 Heat-Shock Proteins ; analysis ; physiology ; Humans ; Pyrazoles ; pharmacology ; Tumor Suppressor Protein p53 ; analysis ; physiology

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Influence of Photodynamic Therapy on Apoptosis and Invasion of Human Cholangiocarcinoma QBC939 Cell Line.

Yun-jie CHEN ; Hai-tao JIANG ; Jing-yu CAO

Chinese Medical Sciences Journal.2015;30(4):252-259.

OBJECTIVETo investigate the effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on apoptosis and invasion of cholangiocarcinoma QBC939 cell lines.

METHODSIn vitro cultured cholangiocarcinoma QBC939 cell line was exposed to 2, 4, 6, 8, 10, 12, and 14 μg/ml HPD with 5, 10, and 15 J/cm2 light intensity, respectively. The optical density at 450 nm of the QBC939 cells was measured by CCK8 assay and its growth inhibition ratio was calculated. Flow cytometry and transwell migration assay were applied to detect cell apoptosis and invasion respectively. RT-PCR and immunocytochemistry analyses were used to detect expressions of vascular endothelial growth factor-C (VEGF-C), cyclooxygenase-2 (COX-2), and proliferating cell nuclear antigen (PCNA). Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the secretion of VEGF-C and COX-2 in QBC939 cells.

RESULTSExposure to HPD-PDT can significantly suppress the growth of QBC939 cells (all P<0.05). HPD-PDT can promote apoptosis of QBC939 cells at the early stage. When the concentration of HPD was 2 μg/ml and light irradiation was 5 J/cm2, HPD-PDT had no obvious inhibitory effect on QBC939 cell growth, but can obviously inhibit cell invasion, and significant difference was observed between the HPD-PDT and control groups (P<0.01). The HPD-PDT can reduce the mRNA and protein expressions of VEGF-C, COX-2, and PCNA, and decrease the secretion of VEGF-C and COX-2 in QBC939 cells.

CONCLUSIONPDT could promote apoptosis and inhibit growth and invasion of cholangiocarcinoma cells QBC939 in vitro.

Apoptosis ; drug effects ; Bile Duct Neoplasms ; drug therapy ; pathology ; Bile Ducts, Intrahepatic ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cholangiocarcinoma ; drug therapy ; pathology ; Humans ; Neoplasm Invasiveness ; Photochemotherapy ; Proliferating Cell Nuclear Antigen ; analysis

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Effect of Atorvastatin on Expression of Peroxisome Proliferator-activated Receptor Beta/delta in Angiotensin II-induced Hypertrophic Myocardial Cells In Vitro.

Li SHENG ; Xu YANG ; Ping YE ; Yong-xue LIU ; Chun-guang HAN

Chinese Medical Sciences Journal.2015;30(4):245-251.

OBJECTIVETo explore the effect of atorvastatin on cardiac hypertrophy and to determine the potential mechanism involved.

METHODSAn in vitro cardiomyocyte hypertrophy from neonatal rats was induced with angiotensin II (Ang II) stimulation. Before Ang II stimulation, the cultured rat cardiac myocytes were pretreated with atorvastatin at different concentrations (0.1, 1, and 10 μmol/L). The following parameters were evaluated: the myocyte surface area, 3H-leucine incorporation into myocytes, mRNA expressions of atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase 9, matrix metalloproteinase 2, and interleukin-1β, mRNA and protein expressions of the δ/β peroxisome proliferator-activated receptor (PPAR) subtypes.

RESULTSIt was shown that atorvastatin could ameliorate Ang II-induced neonatal cardiomyocyte hypertrophy in the area of cardiomyocytes, 3H-leucine incorporation, and the expression of atrial natriuretic peptide and brain natriuretic peptide markedly. Meanwhile, atorvastatin also inhibited the augmented mRNA level of several cytokines in hypertrophic myocytes. Furthermore, the down-regulated expression of PPAR- δ/β at both the mRNA and protein levels in hypertrophic myocytes could be significantly reversed by atorvastatin treatment.

CONCLUSIONSAtorvastatin could improve Ang II-induced cardiac hypertrophy and inhibit the expression of cytokines. Such effect might be partly achieved through activation of the PPAR-δ/β pathway.

Angiotensin II ; pharmacology ; Animals ; Atorvastatin Calcium ; pharmacology ; therapeutic use ; Cardiomegaly ; metabolism ; pathology ; prevention & control ; Cells, Cultured ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; PPAR delta ; genetics ; PPAR-beta ; genetics ; Rats ; Rats, Wistar

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Retroperitoneal Versus Transperitoneal Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-analysis.

Jing FU ; Shan YE ; Hua-jian YE

Chinese Medical Sciences Journal.2015;30(4):239-244.

OBJECTIVETo review published literatures comparing the safety and effectiveness of retroperitoneal laparoscopic partial nephrectomy (RLPN) with transperitoneal laparoscopic partial nephrectomy (TLPN) and provide reference for clinical work.

METHODSThe search strategy was performed to identify relevant papers from the Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, Google Scholar, China Hospital Knowledge Database, Wangfang Chinese Periodical Database, and VIP Chinese Periodical Database. All papers comparing RLPN with TLPN were included from 2000 to 2015. Two to three reviewers independently screened, evaluated, and extracted the included papers. A Meta-analysis was executed by using Review Manager 5.3 software. The interesting outcomes were tumor size, operating time, estimated blood loss, warm ischaemia time, length of hospital stay, positive margin rate, open conversion rate, overall complication rate, and recurrence rate.

RESULTSThe literature search obtained 378 papers, then 10 of them were ultimately met the inclusion criteria and included in the systematic review. Finally, 6 of the 10 papers were included in the Meta-analysis. RLPN had significantly less operating time [P = 0.01, mean difference (MD)=-33.68, 95% confidence interval (CI) within (-60.35, -7.01)] and shorter length of hospital stay [P < 0.0001, MD=-1.47, 95% CI within (-2.18, -0.76)] than TLPN. Significant differences were not found between RLPN and TLPN in other outcomes.

CONCLUSIONSRLPN may be equally safe and be faster than TLPN. Each center can choose a modality according to your own operating habits and experience.

Humans ; Laparoscopy ; methods ; Nephrectomy ; methods ; Peritoneum ; Publication Bias ; Retroperitoneal Space

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Gender Differences in Ventricular-vascular Coupling Following Exercise.

Zhao-jun LI ; Lian-fang DU ; Xiang-hong LUO

Chinese Medical Sciences Journal.2015;30(4):231-238.

OBJECTIVETo study the differences of cardiovascular system between men and women in response to exercise stress.

METHODSForty healthy youth were tested according to Bruce protocol of exercise stress. They were detected by ultrasonography during the rest, peak exercise, and recovery stages, respectively. The left ventricular diastolic elastance (Ed), effective arterial elastance (Ea), left ventricular end-systolic elatance (Ees), ventricular-vascular coupling index (VVI), and total stiffness index (TSI) were measured and calculated according to the formulas. The results of all stages were compared according to genders.

RESULTSAll stages, the Ed, TSI, and VVI of women were higher than those of men, but the Ees was lower than that of men (all P<0.05); there was no significant difference in Ea between men and women. The Ed, Ees, Ea, and TSI were closely related with left ventricular oxygen consumption and heart function, and women showed more closely. Before and after exercise, the changes were different in Ed, Ees, Ea, TSI, and VVI (all P<0.05), and VVI changed least.

CONCLUSIONSBefore and after exercise, the ventricular stiffness matched well with arterial stiffness and maintained within a narrow range. For women, the tolerance of exercise was lower than that of men.

Adult ; Diastole ; physiology ; Exercise ; physiology ; Female ; Humans ; Male ; Sex Characteristics ; Vascular Resistance ; physiology ; Vascular Stiffness ; physiology ; Ventricular Function, Left ; physiology

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Management of Cesarean Scar Pregnancy: A Case Series.

Min-hui GUO ; Mei-fen WANG ; Man-man LIU ; Feng QI ; Fan QU ; Jian-hong ZHOU

Chinese Medical Sciences Journal.2015;30(4):226-230.

OBJECTIVETo survey effective treatment strategies for cesarean scar pregnancy (CSP).

METHODSThe clinical data of 78 patients diagnosed with CSP from January 2010 to December 2013 were reviewed.

RESULTSAmong these patients, 17 patients were first treated at our hospital; of them, 2 were misdiagnosed. The other 61 patients were referred from other hospitals; of them, 21 were initially misdiagnosed. There were 9 patients who were treated with laparotomy, 50 patients with curettage after uterine artery embolization (UAE) with or without local methotrexate (MTX) infusion, 10 patients with dilatation and curettage, 6 patients with transvaginal sonographic guided local intragestational MTX injection, and 3 patients with systemic MTX injection. All patients finally recovered. Patients with excessive vaginal hemorrhage underwent either emergency UAE treatment or laparotomy. These two treatments had similar success rates (81.82% vs. 100%, χ2 =0.289, P>0.05).

CONCLUSIONSThe accurate diagnosis of CSP is important. Curettage after UAE with or without local MTX infusion is a safe and effective method.

Adult ; Cesarean Section ; Cicatrix ; complications ; Curettage ; Female ; Humans ; Methotrexate ; administration & dosage ; Pregnancy ; Pregnancy, Ectopic ; diagnosis ; etiology ; therapy ; Retrospective Studies ; Uterine Artery Embolization

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Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro.

Jin-hua WEN ; Xiao-hua WEI ; Xiang-yuan SHENG ; De-qing ZHOU ; Hong-wei PENG ; Yan-ni LU ; Jian ZHOU

Chinese Medical Sciences Journal.2015;30(4):218-225.

OBJECTIVETo evaluate whether ursolic acid can inhibit breast cancer resistance protein (BCRP)-mediated transport of rosuvastatin in vivo and in vitro.

METHODSFirstly, we explored the pharmacokinetics of 5-fluorouracil (5-FU, a substrate of BCRP) in rats in the presence or absence of ursolic acid. Secondly, we studied the pharmacokinetics of rosuvastatin in rats in the presence or absence of ursolic acid or Ko143 (inhibitor of BCRP). Finially, the concentration-dependent transport of rosuvastatin and the inhibitory effects of ursolic acid and Ko143 were examined in Madin-Darby Canine Kidney (MDCK) 2-BCRP421CC (wild type) cells and MDCK2-BCRP421AA (mutant type) cells.

RESULTSAs a result, significant changes in pharmacokinetics parameters of 5-FU were observed in rats following pretreatment with ursolic acid. Both ursolic acid and Ko143 could significantly affect the pharmacokinetics of rosuvastatin. The rosuvastatin transport in the BCRP overexpressing system was increased in a concentration-dependent manner. However, there was no statistical difference in BCRP-mediated transport of rosuvastatin betweent the wild type cells and mutant cells. The same as Ko143, ursolic acid inhibited BCRP-mediated transport of rosuvastatin in vitro.

CONCLUSIONUrsolic acid appears to be a potent modulator of BCRP that affects the pharmacokinetic of rosuvastatin in vivo and inhibits the transport of rosuvastatin in vitro.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; physiology ; Adenosine ; analogs & derivatives ; pharmacology ; Animals ; Biological Transport ; drug effects ; Diketopiperazines ; Heterocyclic Compounds, 4 or More Rings ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rosuvastatin Calcium ; pharmacokinetics ; Triterpenes ; pharmacology

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Efficacy of Topical Tacrolimus for Erosive Oral Lichen Planus: A Meta-analysis.

Chun-lan GUO ; Ji-zhi ZHAO ; Jie ZHANG ; Hai-tao DONG

Chinese Medical Sciences Journal.2015;30(4):210-217.

OBJECTIVETo assess the efficacy and safety of topical tacrolimus for erosive oral lichen planus (EOLP).

METHODSLiteratures published up to December 2013 were searched from PubMed, Embase, CENTRAL, Chinese BioMedical Literature Database (CBM), and System for Information on Grey Literature in Europe (SIGLE). All randomized controlled trials (RCTs) of topical tacrolimus for EOLP which compared with other interventions or a placebo were considered in this Meta-analysis. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane Handbook and the materials were analyzed with the software Revman 5.2.5. The primary outcome measures were the symptoms (e.g. pain, discomfort) complained by patients. The secondary outcome measures included the improvement rate of clinical signs assessed by the investigators and the incidence of adverse effects (e.g. clinical candidiasis).

RESULTSA total of 9 RCTs involving 476 patients were finally included. The pooled odds ratio (OR) of clinical improvement for topical tacrolimus vs. topical corticosteroids was 1.19 [95% confidence interval (CI): 0.64-2.22, I2: 44%]. Regarding to 0.1% tacrolimus and 0.03% tacrolimus, the pooled OR were 1.87 (95% CI: 0.60-5.82) and 1.47 (95% CI: 0.14-16.04) respectively in subgroup analysis. No serious adverse events were reported in topical tacrolimus group.

CONCLUSIONSThere was no evidence to support that topical tacrolimus for EOLP was more effective and safer than topical corticosteroids in this Meta-analysis. Clinical assessment criteria should be established and accepted by clinicians and researchers before further RCTs are undertaken.

Administration, Topical ; Humans ; Immunosuppressive Agents ; administration & dosage ; Lichen Planus, Oral ; drug therapy ; Randomized Controlled Trials as Topic ; Tacrolimus ; administration & dosage ; adverse effects

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"Identification Card": Sites on Histone Modification of Cancer Cell.

Chao HUANG ; Bin WEN

Chinese Medical Sciences Journal.2015;30(4):203-209.

Formation of malignant tumor originating from normal healthy cell is a multistep process including genetic and epigenetic lesions. Previous studies of cell line model systems displayed that early important epigenetic events happened in stepwise fashion prior to cell immortalization. Once these epigenetic alterations are integrated into chromatin, they will perform vertical propagation through cell subculture. Hence, status of epigenetics is dramatically important in maintaining of cell identity. Histone modification is another factor of epigenetic alterations during human oncogenesis. Histones, one of main components of chromatin, can be modified post-translationally. Histone tail modifications are regulated by corresponding modification enzymes. This review focuses on the description of relationship between the main sites of histone modification and oncogenesis.
Acetylation ; Carcinogenesis ; Epigenesis, Genetic ; Histones ; metabolism ; Humans ; Methylation ; Phosphorylation

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Serum Myeloperoxidase Level in Systemic Lupus Erythematosus.

Ming-jian BAI ; Jing FENG ; Feng YU ; Cun-ling YAN ; Chan-juan CUI ; Lei HUANG ; Zhen-ru FENG

Chinese Medical Sciences Journal.2015;30(3):199-202.

Adult ; Female ; Humans ; Lupus Erythematosus, Systemic ; enzymology ; Male ; Middle Aged ; Peroxidase ; blood

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