Celastrol is a type of quinone methyl triterpene isolated from traditional Chinese medicine Tripterygium wilfordii, with pharmacological activities, like anti-inflammatory, immunosuppression and anti-tumor. This study focused on the effects of celastrol on adhesion, migration and invasion of lung cancer cells. The migration inhibition of lung cancer cells induced by celastrol was detected by the scratch test. The invasion inhibition of lung cancer cells induced by celastrol was measured by the transwell experiment. RT-PCR and Western blot were used to determine the effect of different concentrations of celastrol in integrin family and Akt signaling pathway in lung cancer cells. The results showed that celastrol inhibited adhesion, migration and invasion of lung cancer cells and expressions of integrins β3, β4, αv and phosphorylated Akt, GSK-3β, c-Raf, PDK1 in Akt signal pathway in a dose-dependent manner. Therefore, the study implies that Celastrol could inhibit the metastasis of lung cancer cells by suppressing Akt signaling pathway and expression of integrins.
Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Integrins ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; pathology ; physiopathology ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Signal Transduction ; drug effects ; Triterpenes ; pharmacology

Objective To assess the value of hemofiltration in the prevention of contrast induced nephropathy(CIN) post percutaneous coronary intervention(PCI) in severe chronic kidney disease stages(CKD) patients. Methods We evaluated 30 CKD patients who underwent PCI followed by bedside hemofiltration. We measured serum creatinine levels before PCI, 24 hours, 72 hours, and one week after PCI, and calculated creatinine clearance(CrCl) according to Cockcroft and Gault equation.We observed the incidence of CIN, and the short term clinical efficacy of hemofiltralion. Results The average age of the 30 patients was (72.87 ± 8.71) years old, with 21 (70%) male patients. The stages of CKD among the patients included CKD 3 (3 patients, 10%), CKD 4 (20 patients, 66.7%) and CKD 5 (7 patients, 23.3%). The average duration of hemofiltration was (7.5±4.1) hours. Serum creatinine before PCI, 24 hours, 72 hours and 1 week after PCI was (498.7±143.7)μmol/L, (353.2±128.0)μmol/L, (450.0±132.2)μmol/L, (488.0±145.7)μmol/L respectively,and CrCl was (20.3±10.2) ml/min, (36.5±14.3) ml/min, (28.3±10.4) ml/min, (21.0±10.3) ml/min respectively. There was no CIN. Mean follow-up was (3.1 ± 2.6) months. There was no new cardiovascular events, and no new patients need to rely on long term hemodialysis. Conclusions For patients with severe renal insufficiency, hemofiltration may reduce the incidence of CIN, It is an alternative preventive measures to prevent CIN.

Epigenetics comprises the modifications made in gene expressions without changing the DNA sequence itself. Significant epigenetic changes take place during spermatogenesis and fertilization and exert direct influences on embryogenesis. This article provides an overview of the latest researches on epigenetics of male germ cells and a brief discussion on the correlation of sperm with embryogenesis in four aspects: DNA methylation, histone modification, regulation of non-coding RNAs, and genomic imprinting.
Animals ; DNA Methylation ; Embryonic Development ; Epigenesis, Genetic ; Genomic Imprinting ; Histones ; metabolism ; Humans ; Male ; Spermatozoa

Objective:To compare two flexible embryo catheters and determine whether clinical out-come differs in the in vitro fertilization-embryo transfer (IVF-ET)cycles.Methods:This prospective control study was conducted by one doctor between July 2012 and November 2013.In the study,2 064 patients undergoing fresh embryo transfer by using IVF-ET/intracytoplasmic sperm injection (ICSI)-ET in Reproductive Medical Center of Peking University Third Hospital were recruited.The subjects were di-vided into two groups.Cook Sydney IVF embryo transfer catheters (product model:K-JETS-7019-SIVF) were used for embryo transfer in group 1 (n =949),and FrydmanCCD catheters (product model:131230301)were used in group 2 (n =1 115).Pregnancy outcomes were compared between these two groups.Results:There was no significant difference in age,diagnosis for infertility and stimulation proto-col used between the two groups.In addition,there was no difference in the number of oocytes collected and in the number and score of embryos transferred.The significantly higher implantation rate,clinical pregnancy rate,and live birth rate (34.40% vs.26.92%,51.21% vs.41.52%,42.57% vs. 33.09%,P <0.05)were observed in group 1 compared with group 2.The abortion rate was not signifi-cantly different between the two groups (11.93% vs.15.98%,P >0.05).The proportion of difficult transfer was higher in group 1 than that in group 2 (5.27% vs.3.41%,P <0.05 ).There was no difference in the clinical pregnancy rate and live birth rate between the two difficult transfer cycles.Con-clusion:The type of embryo transfer catheter affects the clinical outcome in IVF.Good clinical outcome can be obtained by using Cook Sydney IVF catheter,which is worthy of clinical promotion.

Objective To analyze the value of plane QRS-T angle on prediction of malignant ventricular arrhythmia (MVA) occurred after emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods The clinical data of 418 patients with STEMI who underwent PCI within 12 h of symptom onset were retrospectively analyzed, and the patients were divided into plane QRS-T angle ≤ 90° group (324 cases) and plane QRS-T angle>90° group (94 cases) according to the plane QRS-T angle after PCI. The clinical data were compared between 2 groups. Results Compared with patients in plane QRS-T angle ≤ 90° group, patients in plane QRS-T angle > 90° group was older: (67.4 ± 11.8) years vs. (63.6 ± 12.0) years, QTc interval was longer: (438.60 ± 34.97) ms vs. (425.24 ± 25.49) ms, rate of left ventricular ejection fraction (LVEF) <45% was higher: 57.4% (54/94) vs. 35.8% (116/324), rate of using of beta-blockers was less: 74.5% (70/94) vs. 84.9% (275/324), but the incidences of hypertension and MVA were higher:79.8%(75/94) vs. 64.5%(209/324) and 10.6%(10/94) vs. 1.2%(4/324), and there were statistical differences (P<0.01 or<0.05). Logistic regression analysis showed that plane QRS-T angle >90° was an independent risk factor of MVA after PCI in STEMI patients (OR = 9.640, P =0.001), and using of beta-blockers was a protective factor (OR = 0.266, P = 0.028). Conclusions Plane QRS-T angle>90° is an independent risk factor of MVA after PCI in STEMI patients, while the use of beta-blockers is a protective factor. Paients with STEMI after PCI should be alert to the occurrence of MVA in the condition of plane QRS-T angle>90° and not taking beta-blockers.

Objective To evaluate the efficiency of rotational atherectomy (RA) with drug-eluting stents (DES) by intravascular ultrasound (IVUS) for elderly patients with heavily calcified lesions. Methods Thirteen patients aged above 70 years with heavily calcified coronary artery having underwent the treatment of RA and DES by IVUS were enrolled. The levels of troponin T, creatine kinase isozyme-MB and creatinine were detected before and after operation.The levels of minimus lumen diameter, diameter stenosis rate, effective area of the lumen before and after operation were compared. The immediate success rate was evaluated and the follow-up results were recorded. Results Thirteen patients in accordance with angiography and IVUS examination were confirmed as severe calcification. The levels of troponin T, creatine kinase isozyme-MB and creatinine detected before and after operation had no significantly differences (P>0.05). The levels of minimus lumen diameter, diameter stenosis rate and effective area of the lumen before and after operation had significant differences:(2.06 ± 0.38) mm vs. (3.98 ± 0.76) mm, (73.26 ± 7.02)%vs. (17.00 ± 3.34)%, (4.53 ± 1.50) mm2 vs. (12.54 ± 6.19) mm2, P<0.01. The rate of left anterior descending artery, circumflex artery and right coronary artery calcification was 10/13, 0 and 1/13. All patients′operation was successful. Followed up for (14.6 ± 3.4) months, no patients had angina and myocardial infarction, or required target vessel revascularization. Conclusions RA with DES by IVUS can be safely used in elderly patients with severely calcified coronary artery disease, and can improve the success rate of intervention operation.

Objective To explore human umbilical cord blood mesenchymal stem cells(MSCs)colonization in hypoxic-ischemic encephalopathy(HIE)rats brain.Methods Models of 7-day-old newborn rats with HIE brain injury were established.Meanwhile,on the same day,MSCs were transplanted with Hoechst 33258 for 24 hours into rats models marked by flurescent nucleotide dye injected through caudal vein or with stereotactic instrument.After 15-30 days,then MSCs were detected with fluorescene microscope.Results With the improved rice methods,HIE animal model was successfully attained.Majority of MSCs were distributed in the cortex,hippocampus of the lesioned hemisphere,especially in the forehead.And abtained a good fusion with HIE rats brain tissue.Conclusion Human umbilical cord blood MSCs can be cultured,when transplanted into the HIE rats model,they can move into intracranial,and integer with rats brain tissue.

OBJECTIVETo sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.

METHODSRapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.

RESULTSBiodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.

CONCLUSIONSPLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.

Animals ; Aorta, Abdominal ; drug effects ; Coronary Vessels ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Infusions, Intra-Arterial ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Polyglycolic Acid ; chemistry ; Rabbits ; Sirolimus ; administration & dosage ; pharmacokinetics ; Swine ; Swine, Miniature

OBJECTIVETo observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness-heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them.

METHODSUrine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis.

RESULTSPLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, α-oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, β-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid.

CONCLUSIONThe metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing.

Biomarkers ; urine ; Discriminant Analysis ; Gastritis ; urine ; Hot Temperature ; Humans ; Hydroxybutyrates ; Ketoglutaric Acids ; Least-Squares Analysis ; Medicine, Chinese Traditional ; Metabolome ; physiology ; Metabolomics ; Principal Component Analysis ; Proton Magnetic Resonance Spectroscopy ; Qi ; Syndrome

OBJECTIVETo investigate the effect of the overexpression of the ERbeta gene on the penile vascular endothelium of ERbeta knockout (ERbetaKO) mice and its molecular mechanisms.

METHODSWe randomly divided 12 ERbetaKO male mice into groups A (ERbetaKO + TNFalpha + pAdxsi-ERbeta) and B (ERbetaKO + TNFalpha + empty virus), the former treated by pAdxsi-ERbeta adenovirus transfection, the latter with empty virus, and meanwhile both injected intraperitoneally with TNFalpha at 6 microg per kg body weight per d for 14 days. Then we observed the erectile function of the mice by APO, determined the changes of the endothelial markers CD34 and vWF by immunohistochemical staining, and detected the expressions of the relevant molecules in the eNOS-NO pathway by RT-PCR, Western blot and immunohistochemistry.

RESULTSCompared with group B, group A showed a significantly increased number of penile erections (0.50 +/- 0.55 vs 2.17 +/- 0.41, P < 0.05), shortened erectile latency ([28.83 +/- 1.33] min vs [24.00 +/- 1.27] min, P < 0.05), enriched CD34 and vWF markers (0.67 +/- 0.52 vs 1.50 +/- 0.55 and 0.50 +/- 0.55 vs 1.33 +/- 0.52, both P < 0.05), elevated expressions of eNOS and Cam (RT-PCR: 1.38 +/- 0.03 vs 1.62 +/- 0.05 and 1.02 +/- 0.09 vs 1.42 +/- 0.05, both P < 0.05; Western blot: 1.27 +/- 0.04 vs 1.55 +/- 0.07 and 0.76 +/- 0.05 vs 0.95 +/- 0.08, both P < 0.05), and reduced expression of caveolin-1 (RT-PCR: 2.13 +/- 0.13 vs 1.72 +/- 0.08, P < 0.05; Western blot: 3.99 +/- 0.16 vs 3.40 +/- 0.14, P < 0.05). The results of RT-PCR were consistent with those of Western blot.

CONCLUSIONThe ERbeta gene protects the penile vascular endothelium via the eNOS-NO pathway.

Adenoviridae ; genetics ; Animals ; Endothelium, Vascular ; metabolism ; Estrogen Receptor beta ; genetics ; Male ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Penis ; blood supply ; metabolism ; Transfection