1.Eukaryotic elongation factor 2 kinase and cancer.
Gen-zhu WANG ; Xin QI ; Jing LI
Acta Pharmaceutica Sinica 2015;50(7):808-813
Eukaryotic elongation factor 2 kinase (eEF2K) is well known as a Ca2+/calmodulin (CaM)-dependent kinase. eEF2K catalyzes the phosphorylation of eEF2 and subsequently inactivates eEF2 by impairing its ability to bind to the ribosome, thereby negatively modulates protein synthesis. The high expression of eEF2K has been found recently in several types of malignancies. As participating in the progress of tumor, eEF2K emerges a potential target for future cancer therapy. The relationship between eEF2K and tumor, and the latest progress of eEF2K inhibitors were summarized in this article.
Elongation Factor 2 Kinase
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antagonists & inhibitors
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metabolism
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Humans
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Neoplasms
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metabolism
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Peptide Elongation Factor 2
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metabolism
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Phosphorylation
2.Eukaryotic elongation factor 2 kinase and cancer.
Genzhu WANG ; Xin QI ; Jing LI
Acta Pharmaceutica Sinica 2015;50(7):808-13
Eukaryotic elongation factor 2 kinase (eEF2K) is well known as a Ca2+/calmodulin (CaM)-dependent kinase. eEF2K catalyzes the phosphorylation of eEF2 and subsequently inactivates eEF2 by impairing its ability to bind to the ribosome, thereby negatively modulates protein synthesis. The high expression of eEF2K has been found recently in several types of malignancies. As participating in the progress of tumor, eEF2K emerges a potential target for future cancer therapy. The relationship between eEF2K and tumor, and the latest progress of eEF2K inhibitors were summarized in this article.
3.Research of serotonin transporter in the mechanism of abdominal pain in irritable bowel syndrome
Chinese Journal of Digestion 2010;30(6):398-401
Objective To investigate the role of serotonin transporter (SERT) in pathogenesis of abdominal pain in irritable bowel syndrome (IBS). Methods Neonatal SD rats were divided into control group and IBS abdominal pain model group which was established by colorectal distension.The colon, nucleus raphes dorsalis (NRD) and prefrontal cortex (FC) tissues were harvested when all rats grew into adults. Expressions of SERT and 5-HT were determined by real-time PCR and immunohistochemistry. Results The expression of SERT mRNA in colon, NRD and FC tissues in model and control group were 13.95±2.05 vs 8.65±1.33, 52.69±22.59 vs 13.82±5.71 and0.48±0.17 vs 0.17±0.14, respectively, with significant differences (all P values <0.05). The protein expression of SERT in colon and NRD,but not FC tissues,decreased in model group compared with control group (13.19±3.82 vs 21.35±4.49,2.47±0.44 vs 4.55±0.92, respectively, P<0.05).Meanwhile, in comparison with control group, the expression of 5-HT in colon was significantly increased in model group (5.56±0.48 vs 2.68±0.22), but decreased in NRD and FC tissues (3.75±0.43 vs 7.46±0.72, 5.07 ± 0.80 vs 7.97 ±1.10, respectively, P<0.05). Conclusions Low expression of SERT in brain and colon may attribute to the pathogenesis of abdominal pain in IBS.
4.Study on the Energy Metabolism of Skeletal Muscle of Healthy People in Different Age Group using Phosphorus MR Spectroscopy
Jing QI ; Dehang WANG ; Xiaomei ZHU
Journal of Practical Radiology 2001;0(10):-
Objective To evaluate the energy metabolism of normal muscle in different age group.Methods Noninvasive 31P-MRS was acquired from quadriceps muscles in healthy people including 10 adults and 6 juvenile.Peak areas were standardized for longitudinal saturation and coil inhomogeneity.The concentration of phosphomonoesterase(PME),inorganic phosphate(Pi),phosphodiesterase(PDE),phosphocreatine(CrP)and adenosine triphosphate(ATP)was determined from spectra.Concentrations of adenosine diphosphate(ADP)and phosphorylation potential(PP)were calculated from the biochemistry reaction equilibrium.Enzymatically active magnesium ATP complex Mg-ATP and pH value were determined from relative chemical shift.Results Normal muscle had prominent high energy phosphate peaks,the mean concentration of CP and ATP was 24.76 and 18.38 mmol/kg in adults,25.52 and 21.36 mmol/kg in young subject.In comparison with adult group,young subjects had lower PDE and higher ATP values.pH value,magnesium ATP and total magnesium were higher in young subjects too.Pi,CP,ADP,PP,free Mg2+ and free ATP concentration were similar in both group.Conclusion High energy compounds were slightly higher in juvenile subjects.31P-MRS is a noninvasive technique to evaluate energy metabolism in different age group.
5.A Research on Risk Factors of Complicated Hypertension in Type 2 Diabetic Patients
Jing WANG ; Xiuying QI ; Xiaoying LI
Chinese Journal of Prevention and Control of Chronic Diseases 2006;0(02):-
Objective To explore the risk factors for complicated hypertension in type 2 diabetic patients. Methods A community-based case-control study was conducted and some risk factors of complicated hypertension in type 2 diabetic patients were analyzed.126 cases and 273 controls were type 2 diabetic patients with and without hypertension respectively.Results The results from univariate logistic regression analysis showed that the occurrence of complicated hypertension in type 2 diabetic patients was statistically related to the body mass index(BMI),waist hip ratio(WHR) and the intake of grain crop.The corresponding OR with 95% CI were 1.474(1.101~1.973),1.478(1.180~1.852) and 1.349(1.098~1.657),respectively.After adjusted for confounding factors,the associations mentioned above were still statistically significant.No associations were observed between complicated hypertension in type 2 diabetes and diabetes duration,glycemia control,exercise,smoking and alcohol drinking,serum total cholesterol,triglycerides,high density lipoprotein,low density lipoprotein and very low density lipoprotein cholesterol levels.Conclusion The high body mass index(BMI),high waist hip ratio(WHR) and high intake of grain crop may increase the risk for the complicated hypertension in type 2 diabetic patients.
6.Study on feasible prophylactic proposal for the periventricular-intraventricular hemorrhage in preterm infants
Jing LIU ; Qi WANG ; Yanhua CHEN
Chinese Journal of Perinatal Medicine 2003;0(06):-
Objective To study the feasible prophylactic proposal for the periventricular-intraventricular hemorrhage(PIVH)in preterm infants with the aim to reduce the mortality and improve the prognosis.Methods From January 2004 to June 2005,pregnant women at high risk for preterm delivery and with gestational age of less than 35 weeks and their infants were enrolled and divided into five groups randomly.Pregnant women received antenatal intramuscular or intravenously injection of vitamin K_1 10 mg per day for 2 to 7 days were Group A.Group B received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 1 day.Group C received antenatal intramuscular or intravenously injection of dexamethasone 10 mg per day for 2 days.Group D received dexamethasone 10 mg per day for 1 or 2 days and vitamin K_1 10 mg per day for 2 to 7 days.Infants in the phenobarbital group received intravenous injection of phenobarbital within 3 hours after birth for 3 to 5 days.Infants in the control group received neither phenobarbital after birth nor dexamethasone or vitamin K_1 injection antenatally.Results PIVH was diagnosed in 17 of 40(42.5%)in Group A,34 of 63(54.0%)in Group B,36 of 70(51.4%)in Group C,14 of 44(31.8%)in Group D,they all higher than control group(?2=15.10,P=0.004).More infants in the control group had severe PIVH(Grade Ⅲ and Ⅳ)than other groups(?2=9.527,P=0.049).The incidence of PIVH and severe PIVH in Group B and Group C were no significant difference.Furthermore,the incidence of PIVH was no difference in phenobarbital group(60.0%)and control group(65.2%)(?2=0.361,P=0.548).But the incidence of severe PIVH in phenobarbital group(5.0%)was less than control group(18.4%)(?2=4.04,P=0.044).Conclusions The combined antenatal administration of dexamethasone and vitamin K_1 can reduce the incidence of PIVH in preterm infants.Postnatal administration of phenobarbital can not decrease the incidence of PIVH,but decrease the frequency of severe PIVH.
7.Hypoglycemic Activity of Polysaccharide of Roots of Common Anemarrhena(Anemarrhena asphodeloides)
Jing WANG ; Shengfang GE ; Qi CHEN
Chinese Traditional and Herbal Drugs 1994;0(10):-
Root stem of Anemarrhena asPhodeloides was extracted with hot water,treated with ethanol and dilutealkali to temove protein. The polysaccharide thus obtained was given to mice by gastric gavage. Result showedthat the polysaccharide can marked1y lower the blood sugar and liver glycogen of mice without affecting bloodlipid level. When given intraperitoneally, it also showed hypoglycemic activity- For alloxan diabetic mice, thepolysaccharide can also markedly lower its b1ood sugar by gastric gavage.
9.Effect of propofol on autophagy in rat heart during ischemia-reperfusion injury
Xiuru QI ; Chunliang WANG ; Ying WANG ; Jing CHEN ; Hongjie WANG
The Journal of Practical Medicine 2016;32(10):1580-1583
Objective To investigate the effect of propofol on autophagy in SD rat heart during myocar-dial ischemia-reperfusion (I/R) injury. Methods Twenty-one male SD rats were randomly divided into three groups as follows (n = 7): the sham operation group, in which rats underwent sham operation without tightening of the coronary artery sutures; the myocardial ischemia-reperfusion group , in which rats were induced by occlud-ing the left anterior descending coronary artery for 30 min , followed by 120 min reperfusion and 0.9% NaCl in-fusion at 3 mL/(kg·h) at 10 min before occluding the left anterior descending coronary artery; the myocardial ischemia- reperfusion- propofol group, in which rats underwent I/R and propofol infusion at 6 mg/(kg·h) at 10 min before occluding the left anterior descending coronary artery. Before tightening of the coronary artery, at 30 min post-tightening of the coronary artery and at 120 min post-reperfusion, HR、 LVSP and ± dp/dtmax of rats were recordedin each group. Atter 120 min post-reperfusion, the serum concentrations of cTnT was measured. The in-jured cardiac tissue was collected to investigate the ultrastructure change under the TEM and to determine the levels of mTOR and p-mTOR. Results No signifcant differences in HR, LVSP and ± dp/dtmax before tighten-ing of the coronary artery. But, at 30 min post- tightening of the coronary artery, compared with groupⅠ, the HR, LVSP and ±dp/dtmax were significantly decresed in groupⅡ and Ⅲ(P < 0.05). Then, at 2 h post-reper-fusion, compared with groupⅠ, the HR, LVSP, ±dp/dtmax and the level of p-mTOR were significantly de-creased, but the serum concentration of cTnT was significantly increased in groupⅡ(P < 0.05); but, compared with groupⅡ, the HR, LVSP, ± dp/dtmax and the level of p-mTOR were significantly increased, the serum concentration of cTnT and the level of mTOR were significantly decreased in group Ⅲ(P < 0.05). Conclusions These data suggest that propofol could heighten the level of p-mTOR, and attenuate the expression of mTOR dur-ing the myocardial ischemia-reperfusion injury in SD rats.
10.Establishment of the method to evaluate cardiac toxicity by real-time cell analysis system on human embryonic stem cells
Qi ZHAO ; Xijie WANG ; Shuyan WANG ; Jing MA
Chinese Pharmacological Bulletin 2016;(1):138-143
Aim To establish an in vitro early drug cardiac tox-icity evaluation method by human embryonic stem cells derived cardiomyocytes ( hESC-CM) and real-time cell analysis Cardio (RTCA Cardio) system. Method The hESC-CM were cultured at RTCA Cardio E-Plate 96. Impedance signals from hESC-CM were analyzed for beating rate, contraction amplitude and beating rhythm irregularity to determine the optimum inoculation density and detection duration. Based on this, we used 0. 1 % DMSO to be the solvent and quinidine (0. 2, 0. 78, 3. 13, 12. 5, 50 and 100 μmol·L - 1 ) known as affecting cardiac activity to validate this method. Result The results revealed no significant changes in the cell index (CI), transient pulse patterns, beating rate and amplitude of hESC-CM. Quinidine will affect the CI and transi-ent pulse patterns of hESC-CM and decrease the beating rate and amplitude of hESC-CM when its concentration ≥3. 13 μmol · L - 1 . And this effect is concentration-dependent, the higher the concentration,the more time they need to recover beating and the more significant the beating rate and amplitude inhibition of quinidine on hESC-CM. Conclusion The method established by hESC-CM and RTCA Cardio system can detect the effect of quinidine on the contraction of hESC-CM, and this indicates that this method has the potential to be an attractive high-throughput tool for screening potential drugs in early evaluation of drug car-diotoxicity.