Objective To evaluate the effects of two different chronic glaucoma models on intraocular pressure elevation and retinal structure changes in rat.Methods Two different chronic ocular hypertension (COH) models were made by three episcleral vein cauterization or latex microspheres injection into anterior chamber,6 cases of each model.IOP measurements of right eyes (COH eye) and left eye (control eye) were taken weekly by TonoPen (an applanation tonometer).Retinal ganglion cells (RGCs) were retrogradely labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) seven weeks later.Retina structure was observed by immunofluorescence.Results IOP was elevated at postoperative 1-8 weeks,and the mean IOP in the episcleral vein cauterization group was (27.20 ± 1.83) mmHg (1 kPa =7.5 mmHg),whereas the control group was (19.80 ± 1.35) mmHg (P =0.001,n =6).The mean IOP in the latex microspheres injection group was (27.40 ± 1.88) mmHg,whereas the control group was (19.40 ± 1.00) mmHg (P =0.000,n =6).Compared with control rat at postoperative 8 weeks,RGCs loss in episcleral vein cauterization group were 37.9％,39.6 and 33.5％ (all P =0.000,n =6),latex microspheres injection group were 37.3％,39.4％ and 33.5％ (all P =0.000,n =6).There was no statistical difference between episcleral vein cauterization group and latex microspheres injection group (P =0.855,0.949,0.634,n =6).Compared with control rat at postoperative 8 weeks,GCL thickness in both COH models were also significant reduced,but there was no statistical difference in GCL thickness among control group (7.32 ± 0.39) μm,episcleral vein cauterization group (4.97 ±0.33) μm,latex microspheres injection group (5.00 ±0.31) μm.Misoperation or careless operation may lead to microspheres particle residual on flat-mounted rat retina.Conclusion The episcleral vein cauterization or latex microspheres injection into anterior chamber can all increase the IOP.However,there are some advantages in episcleral vein cauterization such as few costs than latex microspheres injection and no microsphere contamination.

0.05).Conclusion The implanted radioactive 125I seeds can damage all kinds of tissues at different degrees,but this kind of damage is reversible,the dog may repair the damage through its own repair ability,its clinical application is safe.

Objective To study the best titer of recombinant adeno-associated virus serotype 2 (rAAV2) delivered to myocardium by targeted ultrasound microbubbles. Methods Twenty one adult SD rats were divided into seven groups. SonoVue attached with different titer [1.5 × 109~ 3.0 × 1011 vg/ml (virus genome/ml)] of rAAV2-EGFP was infused into the tail vein of rats, following ultrasound mediated microbubbles destruction,as experiment groups. Normal saline was infused into the tail vein of rats as the control group (without rAAV2). Rats were killed after 14 days and hearts were harvested. GFP protein expression which showed rAAV2 transfer was observed under fluorescence microscope in frozen section and integrate optical density(IOD) was measured by Image Pro Plus software. Results When the titer of rAAV2 was 1.5 × 1011 vg/ml infused into the tail vein of rats there was much more GFP expression in myocardium than lower titers (P <0.01). Conclusions The best titer of rAAV2 delivered to myocardium by targeted ultrasound microbubbles is 1.5 × 1011 vg/ml in the tail vein infusion of rats.

Objective To investigate the relationship between the content of stromal cell-derived factor-1 (SDF-1) in myocardium in different period of myocardial infarction and left ventricular function.Methods Twenty three Chinese miniature pigs were randomly divided into the experimental group and the control group.The swines in experimental group were prepared as acute myocardial infarction model by ligating anterior descending coronary artery and were randomly divided into 6 subgroups according to the different time points after infarction.The left ventricular end-diastolic diameter (LVDd),left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were measured respectively.Global circumferential strain (GCS) and global radial strain (GRS) of left ventricle were measured.The content of SDF-1 were also measured by real-time quantitative PCR.Results Compared with the control group,SDF-1 levels were significantly elevated,and LVEF,LVFS,GCS and GRS were reduced.However,LVDd were significantly increased.The content of SDF-1 and GCS has a negative correlation (r =-0.580,P =0.000).Conclusions The content of SDF-1 in myocardial tissue have a certain relationship with GCS of left ventricular myocardium.

Objective To investigate the safety and efficacy of protective measures(hydration treatment)during perioperative period of interventional therapy for renal function of gerontic patients with coronary artery disease(CAD)complicated by chronic renal insufficiency(CRI).Methods The relation between hydration therapies and the renal function of 168 CAD patients(≥60 years old)complicated by CRI were analyzed.These patients were divided into three groups:in the group A,patients underwent selective coronary angiography(SCA)with conventional treatment during interventional perioperative period(IPP);in the group B,patients underwent SCA and treated with the NaCl plus low dose NaHCO3 during IPP;in the group C,patients underwent percutaneous coronary intervention(PCI),and meanwhile treated with the same dose NaCl and NaHCO3 as the group B during IPP.Results Coronary interventions were successful in all 168 patients.Contrast medium associated nephropathy(CAN)was found in 30 patients,and incidences of the CAN were 17(27.4%)in the group A,3(7.5%)in the group B and 10(15.2%)in the group C,respectively.The accompanying diseases and characteristics of the patients also effected the incidence of CAN:the CAN incidence of patients with hyperlipidemia was significantly higher than that with normal cholesterol(P<0.001);patients with diabetes was significantly higher than that with normal serum glucose(P<0.001);patients with stenosis of renal artery was significantly higher than that with normal renal artery(P<0.001);patients with heart failure(grade Ⅲ～Ⅳ)was significantly higher than that with the grade Ⅰ～Ⅱ(P<0.001).Conclusion The hydration treatment with the NaCl plus low dose NaHCO3 during IPP can protect renal function and increase tolerance for gernotic CAD patients complicated by CRI during IPP,and improve prognosis.

Aim To investigate the influence of down-regulating adenosine A1 receptor and adenosine A2 A receptor gene expression on proliferation and activation of acetaldehyde-induced hepatic stellate cell-T6 cells through siRNA. Methods Alcoholic liver fibrosis in vitro model was constructed by inducing HSC-T6 cells with acetaldehyde. siRNA targeting A1R and A2AR were designed and synthesized according to its mRNA. The siRNA was transfected into rat HSC-T6 cells by li-posome LipofectamineTM 2000. HSC cell proliferation was measured by MTT. The mRNA levels of A1R, A2AR, α-SMA, Collagen I in the supernatant of the cell culture were measured by Quantitative Real-Time PCR. The protein levels of A1R, A2AR, α-SMA, Collagen I were measured by Western blot. Results A1 R and A2 AR siRNA effectively inhibited the cell proliferation, and they also significantly decreased the levels of A1R, A2AR,α-SMA, Collagen I, suggesting that A1 R and A2 AR might be potential target genes in the alcoholic liver fibrosis. Conclusions Silencing A1 R or A2 AR by RNAi can significantly inhibit the HSC proliferation, A1R and A2AR may be potential therapeutic target genes for alcoholic liver fibrosis.

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

Objective:To establish the HPLC fingerprint of dry ginger to provide experimental evidence for the quality control. Methods:An Agilent TC-C18 column (250 mm × 4. 6 mm,5 μm) was used, the flow phase was acetonitrile-water with gradient elu-tion, the flow rate was 1. 0 ml·min-1 , the column temperature was 30℃, and the detection wavelength was 240 nm. The data were e-valuated by the similarity evaluation software for TCM fingerprint. Results:There were 10 common peaks in HPLC chromatogram of 10 batches of dry ginger at 240 nm, and the chemical similar coefficient was 99%. Conclusion: The fingerprint of ginger at 240 nm is highly specific and typical with a rich fund of information, which can provide useful references for the quality control and evaluation of dry ginger.