1.Effects of TSG on H2O2-induced Apoptosis and Expressions of XIAP and p53 in HUVECs
Ying YANG ; Xiqiang GAO ; Shiyin LONG
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2015;(6):629-633
Objective To study the effects of tetrahydroxy stilbene glucoside(TSG)on H2O2‐induced apoptosis of human umbilical vein endothelial cells (HUVECs)and on the expressions of X‐linked inhibitor of apoptosis protein (XIAP)and p53.Methods HUVECs were cultured in vitro and divided into 6 groups:control group ,300 μmol/L H2O2 group ,1 μmol/L TSG+ 300 μmol/L H2O2 group ,10 μmol/L TSG+300 μmol/L H2O2 group ,100 μmol/L TSG+ 300 μmol/L H2O2 group ,30μmol/L Embelin+ 10 μmol/L TSG+ 300 μmol/L H2O2 group.The morphology of apoptotic cells was observed by Hoechst 33258 staining.The mRNA and protein expressions of XIAP ,p53 ,Caspase‐3 were detected by RT‐PCR and Western blotting , respectively.Results The number of apoptotic cells and the expression level of p53 were significantly increased while the ex‐pression level of XIAP was dramatically decreased in H2O2 group as compared with control group.The expression level of p53 and the number of apoptotic cells were down‐regulated while the expression level of XIAP was up‐regulated after treatment with 10 or 100 μmol/L TSG when compared with H2O2group.Moreover ,compared with those in 10 μmol/L TSGgroup ,the number of apoptotic cells and the expression of Caspase‐3 were significantly enhanced after pretreatment with 30 μmol/L Embelin for 6 h.Conclusion TSG can inhibit H2O2‐induced apoptosis of HUVECs by down‐regulating the expression level of p53 and up‐reg‐ulating the expression level of XIAP.
2.Toxic Reactions of Memantine in Acute Toxicologic Experiment in Neonatal Rats
ying, GAO ; hui-jin, CHEN ; long-hua, QIAN
Journal of Applied Clinical Pediatrics 2004;0(08):-
Objective To explore the acute toxic reactions of memantine in neonatal rats. Methods Based on Completely Lethal dose(LD_(100)) and median lethal dose (LD_(50))of memantine in SD neonatal rats acquired in a preliminary test of death dose, 60 neonatal rats were randomly divided into normal group which were given water injection intraperitoneally and 5 study groups which were given different doses of memantine intraperitoneally.LD_(50) was calculated with Bliss method and the toxic reactions of memantine were observed in all neonatal rats of 6 groups after administration of memantine. Results LD_(50) of memantine in SD neonatal rats was((74.386?2.811)) mg/kg with 95% confidence at the range of 59.334-93.257 mg/kg.Side effects occurred at 1-4 minutes after administration. Excitatory jitteriness,ataxia,decreased respiratory rate and passivity were usually observed in groups with a lower dosage (52.0 mg/kg,61.2 mg/kg,72.0 mg/kg);some of them also manifested side lying, cyanosis and respiratory failure.While neonatal rats with a higher dosage (85 mg/kg,100 mg/kg)mainly manifested visible symptoms of inhibition, respiratory failure,side (lying) and cyanosis.However,no jitteriness and ataxia were observed in them.The neonatal rats usually died around 1 hour after memantine administration;survival rats usually returned to normal 4-5 hours after administration.Conclusion There is a positive correlation between toxic reactions and the mortality with memantine dosage in neonatal rats.
4.Lornoxicam,clinical observation and peptide drugs in the treatment of osteoarthritis
Long GAO ; Ying CHEN ; Huan LIU ; Zhao YANG ; Huhu ZHANG
Chinese Journal of Biochemical Pharmaceutics 2017;37(9):308-309,311
Objective To investigate the combined use of osteoarthritis treatment effect of lornoxicam and peptide drugs.Methods 260 patients with osteoarthritis treated in our hospital from May 2014 to June 2016 were selected, were randomly divided into study group and control group, each group of 130 cases.The patients in the control group were treated with sodium hyaluronate and lornoxicam, the study group was given bone peptide on the basis of the control group. The pain scores, knee function and adverse reactions were compared between the two groups.Results There was no significant difference in VAS and WOMAC scores between the two groups before treatment; after treatment, the improvement of VAS and WOMAC score in the study group was better than that in the control group (P<0.05). There was no significant difference in the incidence of adverse drug reactions between the two groups. Conclusion Sodium hyaluronate, bone peptide, lornoxicam and other drugs in the treatment of patients with osteoarthritis clinical efficacy is obvious, and fewer adverse reactions.
5.A Low Noise Amplifier System for Nanopore-based Single Molecule Analysis
Bingyong YAN ; Zhen GU ; Rui GAO ; Chan CAO ; Yilun YING ; Wei MA ; Yitao LONG
Chinese Journal of Analytical Chemistry 2015;(7):971-976
A novel amplifier system was proposed for low-noise recording of pico-ampere current in nanopore experiment (<100 pA). As an example, the amplifier system was applied in α-hemolysin based nanopore detection of DNA-PEG-DNA conjugate to record the signals of translocation and bumping events in buffer solution (1 mol/L KCl, 10 mmol/L Tris--HCl, 1 mmol/L EDTA and pH=8. 0). The amplified current signal was filtered by a 3 kHz Bessel filter and sampled by a 100 kHz analog-digital convertor. As a result, the presented amplifier system could lower the noise in recording the current. The current blockages (<10 pA) of single molecules with low amplitude were recovered due to the high signal-to-noise ratio.
6.Pathological Changes of Memantine in Neonatal Rats in Acute Toxicologic Experiment
ying, GAO ; hui-jin, CHEN ; long-hua, QIAN ; ming-hua, JIANG
Journal of Applied Clinical Pediatrics 1992;0(06):-
Objective To investigate the pathomorphology effects of memantine on organs in neonatal rats.Methods Sixty-eight neonatal rats were randomly divided into 7 groups:5 groups by different doses memantine intraperitoneally and the controls by water intraperitoneally.The pathomorphology changes of organs were observed in all dead neonatal rats promptly after administration of memantine and in all survived rats after 7 days recover.Results 1.The ratio of organ weight and body weight in dead neonatal rats were higher than those of controls.2.The result of pathomorphology indicated that neurodegeneration and necrosis in the brain,the liver congestion and cell degeneration.The other organs had not distinct changes.3.The pathologic changes and mortality rate of neonatal rats were positively correlated with the dosage of memantine.Conclusion Memantine will affect liver and brain of neonatal rats.
7.Long-term outcome of 160 patients with stage Ⅱb cervical carcinoma treated with pre-operative and intra-operative radiotherapy
Ying GAO ; Zi LIU ; Xi CHEN ; Hongbing MA ; Wei LUO ; Long ZHANG
Chinese Journal of Radiation Oncology 2010;19(4):321-323
Objective To investigate the 5-and 10-year survival and complications of patients with stage Ⅱb cervical carcinoma treated by pre-operative photon radiotherapy (POPRT) plus brachytherapy (192Ir) and selective lymphadenectomy hysterectomy (SLH) plus intra-operative electron radiotherapy (IOERT). Methods From February 1997 to May 2007, 160 patients with stage Ⅱb cervical carcinoma were treated by POPRT of 20 Gy in 10 fractions to the whole pelvis, 192Ir brachytherapy of 14 Gy in 2fractions, followed by IOERT of 18 -20 Gy to the whole pelvis during SLH one week after. Results The follow-up rate was 98.1%. The number of patients followed-up for 5 and 10 years was 143 and 135,respectively. The 5-year overall survival rate, disease-free survival rate and local control rate of all patients were 89.4%, 86. 3% and 96. 3%, with the corresponding 10-year rates of 84.4%, 81.0% and 95.0%,respectively. The radiation-induced rectitis and cystitis were 5.0% and 0. 6%, respectivly. The rate of hydronephrosis and lower extremity edema was 6. 3% and 1.3%, respectively. Conclusions Combination of EBRT plus 192Ir brachytherapy and SLH plus IOERT could improve the survival and local control of patiens with cervical carcinoma, with only a few side effects.
8.Liguzinediol exerts positive inotropic effect by enhancing Ca 2+release from sarcoplasmic reticulum mediated by sarcoplasmic reticulum Ca2+ATPase
Wei WANG ; Sha LI ; Mengdan ZHANG ; Ying GAO ; Shuyin XUE ; Kesu CHEN ; Zhongyue WANG ; Long CHEN
Chinese Journal of Pharmacology and Toxicology 2016;30(3):197-202
OBJECTIVE To explore kinetic features and its underlying mechanism of the positive inotropic effect of liguzinediol(LZDO)in rats. METHODS ①An In vivo study was made to record the effect of LZDO 20 mg · kg-1 injected for 30 consecutive min from the left external jugular vein on pressure-volume relationships. ②Ex vivo study was used to record the antagonistic effect of LZDO on reduced contractility induced by caffeine. Caffeine and LZDO were perfused as follows:normal perfusion solution, caffeine 0.5 mmol · L-1,and then caffeine 0.5 mmol · L-1+LZDO 100 μmol · L-1. ③ Ca2+ transient from cardiomyocyte sarcoplasmic reticulum (SR) was measured to analyze the effect of LZDO on Ca2 +release blocked by thapsigargin. Thapsigargin and LZDO were perfused as follows:normal perfusion solution,thapsigargin 2 μmol · L-1,and then thapsigargin 2 μmol · L-1+LZDO 100 μmol · L-1.④The SR vesicles were prepared and the effect of LZDO(1,10 and 100μmol·L-1)on sarcoplasmic reticulum Ca2+ATPase(SERCA2a)activity was determined according to the ultramicro-Ca2+-ATP enzyme kit. RESULTS ① LZDO 20 mg · kg- 1 significantly reduced the end-systolic volume (Ves) and enhanced the end-systolic pressure (Pes),stroke volume (SV),ejection fraction (EF),cardiac output(CO),peak rate of rise of left ventricular pressure(+dp/dtmax)and stroke work(SW)(P<0.05). However,LZDO 20 mg · kg-1 did not significantly change the heart rate(HR )or the end-diastolic volume (Ved). ② Caffeine 0.5 mmol · L- 1 significantly enhanced HR,left ventricular developed pressure (LVDP ),and+dp∶dtmax at 5 min after caffeine and decreased at 30 min. However,LZDO 100μmol·L-1 restored the reduced HR,LVDP,and+dp/dtmax induced by caffeine at 30 min(P<0.05).③Thapsigargin 2μmol·L-1 significantly reduced the SR Ca2+transient from perfusion solution group(100±5)%to(51± 5)%(P<0.05) and LZDO 100 μmol · L-1 failed to restore the decreased Ca2+ transient〔(49 ± 4)%〕. Normalized Ca2+transients were reduced by thapsigargin 2μmol·L-1 and thapsigargin 2μmol·L-1+LZDO 100 μmol · L-1. ④ LZDO(10 and 100 μmol · L-1)significantly increased the activities of SERCA2a in perfusion solution group 0.98±0.10 to 1.17±0.20 and (1.43±0.09)μmol Pi·g-1·h-1,respectively(P<0.05). CONCLUSION LZDO can enhance SR Ca2+ gradient by activating the SERCA2a and might be developed to serve as a potential positive inotropic agent in clinical settings.
9.The Establishment of an Anti-Trypanosoma Drug Screening System with Leucyl-tRNA Synthetase as an Inhibition Target
Guang-Wei GAO ; Ying YAO ; Da-Zhong DING ; Long YE ; Hu-Chen ZHOU ; Da-Wei LI ;
China Biotechnology 2006;0(12):-
Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.
10.Action of NO and TNF-alpha release of rats with cadmium loading in malfunctiion of multiple system organ.
Long CHEN ; Juan ZHOU ; Wei GAO ; Ying-Zi JIANG
Acta Physiologica Sinica 2003;55(5):535-540
Thirty-six healthy Sprague-Dawley male rats were used and divided randomly into a control group (group C), a medium-dose cadmium loading group (group M) and a high-dose cadmium loading group (group H). Cadmium chloride was diluted with saline to contain 0.4 mg/ml of autoclaved cadmium solution. Groups M and H were injected in the abdominal cavity with 0.5 and 1.0 mg of cadmium per kg body weight respectively, and group C with saline of the same dosage as in group H over 7 d. Six rats of each group were killed on the 4th day and 7th day after cadmium loading, respectively, and blood, testis, liver and heart were collected. Cadmium content, changes in nitric oxide and tumor necrosis factor-alpha were studied in blood and the tissues of testis, liver and heart. Results showed that during the entire experimental period, body weight in groups M and H decreased significantly as compared with that in group C; cadmium concentration increased significantly in testis, heart and liver of groups M and H, and rose with increased dosage and time of cadmium loading; there was no obvious difference in plasma nitric oxide between groups M and C, though nitric oxide was higher in group M than in group C. Nitric oxide in group H was significantly superior to that in group C. Plasma tumor necrosis factor-alpha was markedly higher in groups M and H than in group C. Nitric oxide contents in the rat s testis, liver and heart homogenates with cadmium loading were higher than those in group C or significantly superior to group C. The same changes in tumor necrosis factor-alpha in the tissue homogenates of the testis and heart were found, but no obvious difference in tumor necrosis factor-alpha in the liver between the three groups was observed. It is suggested that the massive release of nitric oxide and tumor necrosis factor-alpha induced by cadmium loading may play an important role in the induction of malfunction of multiple systems or organs in rats.
Animals
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Cadmium Chloride
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pharmacokinetics
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toxicity
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Liver
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metabolism
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Male
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Multiple Organ Failure
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metabolism
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Myocardium
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metabolism
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Nitric Oxide
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metabolism
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Rats
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Rats, Sprague-Dawley
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Testis
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metabolism
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Tumor Necrosis Factor-alpha
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metabolism