Aim To introduce a high throughput screen model for PTK inhibitors. Methods With tyrosine containing polypeptides as substrate, in reaction buffer PTK extracts catalyzed the phosphorylation of tyrosine residues. ELISA method was used to measure the activity of protein tyrosine kinase. Resutls The IC_ 50 of genistein was 110 ?mol?L -1. From more than 7000 samples, 16 were found to possess some degree of PTK inhibiting activity. Conclusion This HTS model for screening PTK inhibitors was stable and sensitive.

Aim To investigate the rationality and the dose of TSD combined with TSA on reducing serum uric acid and anti-inflammatory.Methods Mice hyperuricemic models were made by uric acid intraperitoneal injection or yeast extract paste intragastric administration.Mice ear swelling model was induced by locally painting dimethylbenzene.Optimized combination dosage of TSD and TSA was obtained using the Codrug software.Results In the mice hyperuricemic models,the serum uric acid in TSD group,TSD plus TSA group and positive control groups was significantly reduced compared with the model group(P

Aim To discover lead compound whose function is similar to EPO.Methods A high-throughput Fluorescent Polarization(FP) assay was established for screening ligand of EPO receptor from small molescules and natural products.In the FP assay,EPO receptor was abstracted from FVA cell.EPO was labeled with FITC.Results The optimized concentration of FITC-EPO was 10~(-9) mol?L~(-1).Different concentrations of DMSO(VDMSO/Vtotal: 0%,0.5%,1%,2.5%,5%) didn′t affect the FP assay.The value of Z′ in the FP assay was 0.78.Conclusion The assay was robust and of high sensitivity.

OBJECTIVE To study the changes in matrix metalloproteinase-9 (MMP-9) mRNA, tissue-inhibitor of metalloproteinase-1 (TIMP-1) mRNA and the ratio of MMP-9 mRNA/TIMP-1 mRNA in the lungs of paraquate poisoning rats, and to investigate the protective effects of sodium dimercaptopropane sulfonate (DMPS, Unithiol). METHODS One hundred and twenty male SD rats were divided into 12 groups (n=10) randomly: normal control, DMPS control, PQ poisoning 1, 3, 7, 14 and 28 d model groups, (DMPS+PQ) 1, 3, 7, 14 and 28 d groups. PQ poisoning model was established by intraperitoneal injecting paraquate. The expression of MMP-9 mRNA and TIMP-1 mRNA in lung tissues was detected by RT-PCR. RESULTS ①By observing the changes of action and observing the lung tissues sections, the rats' PQ poisoning models was successfully established. ②The histopathology of lung showed infiltration of inflammatory cell in acute phase(within 2 weeks), the inflammation decreased gradually after 2 weeks, hyperplasia of collagen and pulmonary fibrosis were instead. Howerer, the pathological changes were alleviated obviously in the (DMPS+PQ) groups. ③Compared with the PQ groups, the expression of MMP-9 mRNA and TIMP-1 mRNA in lungs diminished greatly in the DMPS+PQ groups after rats injected DMPS(P<0.05); the ratio of MMP-9/TIMP-1 mRNA was bigger at 7, 14 and 28 d in the DMPS+PQ groups after rats injected DMPS. CONCLUSION Down-regulation of the expression of MMP-9 mRNA and TIMP-1 mRNA and up-regulation ratio of MMP-9 mRNA/TIMP-1 mRNA by DMPS may be one of mechanisms by which pulmonary injury and pulmonary fibrosis are prevented in the acute paraquate poisoning.

Objective To systematically review the effect of traditional Chinese medicine (TCM) in an animal model of lung injury induced by paraquat (PQ),and to provide a theoretical basis for future clinical trials.Methods The Wanfang,CNKI,VIP,PubMed/MEDLINE,EMBASE database (from January 1979 to September 2012) were searched.All papers concerning TCM in animal model of lung injury induced by PQ were retrieved.Study selection and data extraction were performed on the basis of Cochrane systematic review methods.Weighted mean difference (WMD) and 95％ confidence interval (95％CI) with random effects model was adopted to investigate the effect of TCM on lung injury induced by PQ.Results Eighteen papers involving 1 188 rats met our criteria.Meta-analysis showed that TCM could improve the lung coefficiency (WMD-0.07,95％ CI-0.14 to-0.01,P=0.03),reduce lung wet/dry weight ratio (WMD-1.15,95％CI-2.03 to-0.27,P=0.01),increase the serum superoxide dismutase (SOD) activity (WMD 56.08,95％CI 23.46 to 88.70,P=0.000 8),improve plasma glutathione peroxidase (GSH-Px) level (WMD 26.64,95％CI 18.95 to 34.33,P＜0.000 01),and lower serum malondialdehyde(MDA) level (WMD-0.65,95％CI-1.00 to-0.30,P=0.000 2),however there was no significant difference in the level of serum tumor necrosis factor-α (TNF-α) and hydroxyproline (HYP) level between TCM and controls (TNF-α:WMD-25.15,95％CI-54.87 to 4.57,P=0.10; HYP:WMD-0.11,95％CI-2.71 to 0.48,P=0.17).Conclusions These findings demonstrate the efficacy of TCM in animal models of lung injury induced by PQ.However taking account of heterogeneity,the efficacy should be interpreted with caution.

Accidents ; Acute Lung Injury ; chemically induced ; Administration, Oral ; Humans ; Mediastinal Emphysema ; complications ; Potassium Permanganate ; toxicity

ObjectiveTo investigate the effects of an intelligent aerobic bicycle training on lower limb motor function, cardiopulmonary function and activities of daily living (ADL) in patients with ischemic stroke at different courses. MethodsFrom November, 2019 to November, 2021, 138 ischemic stroke patients were stratified-randomly divided into control group (n = 69) and experimental group (n = 69). All the patients received medication and routine rehabilitation training, and the experimental group additionally received intelligent aerobic bicycle training, for eight weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremities (FMA-LE), peak oxygen uptake (VO₂peak), Six-minute Walk Test (6MWT) and modified Barthel Index (MBI) before, and four weeks and eight weeks after treatment. ResultsThe performances of FMA-LE, VO₂peak, 6MWT and MBI improved in both groups after treatment (|t| > 6.763, P < 0.001), and improved more in the experimental group than in the control group (|t| > 2.439, P < 0.05). For the patients beginning training less than one month after stroke, the performances of FMA-LE, VO₂peak and 6MWT improved more in the experimental group than in the control group (|t| > 2.036, P < 0.05); for those during one to three months, the performances of 6MWT and MBI improved more (|t| > 2.005, P < 0.05); for those during three to six months, the performances of all the tests were not significantly different (|t| < 1.303, P > 0.05). ConclusionIntelligent aerobic bicycle training may improve the lower limb motor function, cardiopulmonary function and ADL for patients with ischemic stroke, especially intervening earlier.

Objective: To investigate the effects of zirconia micro coating on the proliferation and differentiation of osteoblasts on the surface of zirconia ceramic, and to provide a strategy for zirconia implant surface treatment. Methods: Forty tablets of zirconia ceramic, with the diameter of 15 mm and the thickness of 1.5 mm, were prepared. Then, twenty tablets polished by water sandpaper were taken as the control group, and 20 pieces of the zirconia coating after sintering micron were taken as the experimental group. The micromorphology of the surface of the two groups were observed by scanning electron microscope. The cell morphology after inoculation with MC3T3-E1 of osteoblasts on the surface of the material was investigated for 1, 3, and 5 days by scanning electron microscope. The cell proliferation was detected at 1 and 3 days by methyl thiazolyl tetrazolium. The cell differentiation ability was detected at 3 and 7 days by real-time quantitative PCR. Statistical analysis was conducted by independent sample t test. Results: After coating with zirconia micron particles, pores with the diameter of 1-20 μm could be observed on the surface of the test group of tiles through high temperature sintering. The growth of osteoblasts on the surface of the ceramic chip in the test group and control group exhibited the similar cell morphology. As they were cultured for 1 day, the experimental group exhibited a similar quality of cells as those in the test group (P>0.05). After 3 days' incubation, comparing with the cell quality of the test group (1.067 ± 0.077) (P<0.05), the quality of osteoblasts on the surface of zirconia ceramics coating increased to 1.763±0.165, and the expression of mRNA in alkaline phosphatase (ALP), osteopotin (OPN) and osteocalcin (OCN) also increased with the amount of 1.63±0.28, 1.99±0.41 and 1.60±0.30, respectively, compared with the test group (1.00± 0.00) (P<0.05). Seven days later, the expression of mRNA in Runt-related transcription factor-2 (RNUX2) (1.33±0.19), special AT-rich sequence binding protein-2 (SATB2) (1.64 ± 0.36), as well as alkaline phosphatase (ALP) (1.78±0.40), OPN (2.25±0.36), and OCN (1.88±0.21), showed a remarkably increase compared with the test group (1.00±0.00) (P<0.05). Conclusions Zirconia micro coating on the surface of zirconia ceramics promoted the proliferation and differentiation of osteoblasts adhered.

OBJECTIVETo investigate the effect of curcumin on liver injury in rats induced by paraquat-mediated oxidative stress and the mechanism underlying its effect.

METHODSSixty rats were randomly divided into 4 groups: control group, curcumin control group (curcumin 50 mg/kg), paraquat group (2% paraquat solution 100 mg/kg), and curcumin intervention group (curcumin 50 mg/kg at 15 min, 24 h, or 48 h after paraquat exposure). On days 1, 3, or 7 after paraquat administration, and liver tissue was collected thereafter. The content of malonaldehyde (MDA) and the activities of superoxide dismutase activity (SOD) and catalase (CAT) in the liver tissue were determined by chemical colorimetry. The activities of heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) in the liver tissue were determined by ELISA. The mRNA and protein levels of NF-E2-related factor 2 (Nrf2) were determined by RT-PCR and Western blot, respectively. The pathological changes of liver tissue were examined by optical microscopy.

RESULTSNo significant change was observed between the control group and the curcumin control group in any examination of this study (P > 0.05). Both paraquat group and curcumin intervention group showed increase in MDA content, decreases in SOD and CAT activities, increases in HO-1 and NQO-1 activities, and increases in the protein and mRNA levels of Nrf2, in comparison with the control group (P < 0.05 for all except HO-1 activity in paraquat group on day 7). In comparison with the parquet group on the same day, the curcumin intervention group showed decrease in MDA content, increases in the activities of SOD, CAT, HO-1, and NQO-1, and increases in the mRNA and protein levels of Nrf2 on days 1, 3, and 7 (P < 0.05). The pathological examination revealed that the damage of liver tissue in the paraquat group was the most serious on the 3rd day after paraquat exposure, and the damage was consistently alleviated by curcumin intervention on days 1, 3, and 7, as compared with the paraquat group.

CONCLUSIONOxidative stress plays an important role in paraquat-induced acute liver damage in rats, and curcumin can exert a hepatoprotective effect against oxidative stress by increasing the expression of Nrf2 and the activities of HO-1, NQO-1, SOD, and CAT and reducing the content of MDA.

Animals ; Catalase ; metabolism ; Curcumin ; pharmacology ; Disease Models, Animal ; Heme Oxygenase (Decyclizing) ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; NAD(P)H Dehydrogenase (Quinone) ; metabolism ; Oxidative Stress ; drug effects ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism