1.Research progress of small molecule inhibitors targeting PI3K-Akt-mTOR pathway
Qiaojun HE ; Xiaowu DONG ; Hong ZHU ; Yongzhou HU ; Bo YANG
Chinese Journal of Biochemical Pharmaceutics 2016;36(8):6-15
Aberrant activation of the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB,Akt)-mammalian target of rapamycin(mTOR) pathway is commonly observed in human cancer and is critical for cell survival, proliferation and differentiation.A variety of small molecule inhibitors targeting PI3K-Akt-mTOR pathway are under clinical studies.This review will summarize the recent studies in terms of the PI3K-Akt-mTOR signaling pathway and cancer,research progress of the antitumor activity possessed by PI3K-Akt-mTOR inhibitors,as well as the recent research in the related field conducted by our group.
2.Effects of suppression hypoxia-inducible factor-1α expression by small interfering RNA on glycolysis in esophageal carcinoma
Nana TANG ; Hong ZHU ; Guijun HE ; Bo HAO ; Ruihua SHI
Chinese Journal of Digestion 2013;(2):115-118
Objective To investigate the effects of hypoxia-inducible factor (HIF)-1α on glycolysis of human esophageal squamous carcinoma cells and the possible mechanism.Methods TE13 and Eca109 cells were cultured under normal oxygen (20%O2) and hypoxia (1%O2) conditions.The hypoxia was duration 6 hours,12 hours,24 hours and 48 hours.HIF-1α gene was stable silented by RNA interference method and TE13/small interfering HIF cells and Eca109/siHIF cells were obtained.The cell culture condition and time was same as TE13 and Eca109 cells.The changes of HIF-1α expression were detected by Western-blot.The changes of lactic acid concentration in cell culture supernatant were determined by Spectrophotometry.The changes of glucose transporter-1 (GLUT-1) and lactic dehydrogenase A (LDHA) expression at mRNA level were examined by realtime polymerase chain reaction.The changes of GLUT-1 and LDHA expression at protein level were tested by Western blot.Using t or t' test to analyze the effects of hypoxia duration on HIF-1αexpression at protein level.One-way ANOVA was applied for the difference analysis between the groups.Results In TE13 and Eca109 cells,the HIF-1α expression significantly increased under hypoxia condition and reached the peak at 12 hour (t=6.11,8.31; both P<0.05).The lactic acid secretion of TE13/siHIF cells and Eca109/siHIF cells was (1.24±0.33) and (1.28±0.37) mmol/L,which significantly decreased when compared with TE13 and Eca109 cells [(3.25±1.34) and (4.91±1.69) mmol/L,t=2.53,3.59,both P<0.05].The lactic acid secretion of TE13 and Eca109 cells significantly increased after hypoxia [(6.48±1.73) and (8.02± 1.95) mmol/L,t=2.715,2.050,both P<0.05].There was no significant lactic acid secretion in TE13/siHIF cells and Eca109/siHIF cells after hypoxia (P > 0.05).The expressions of GLUT-1 and LDHA at mRNA level were significantly suppressed in TE13/siHIF cells and Eca109/siHIF cells (normal oxygen:t=6.98,3.92,7.25,3.67,all P<0.05).The expression of GLUT-1 at protein level remarkably weaked (normal oxygen:t=4.57、16.56,hypoxia:t=6.19、6.09,all P<0.05),while the expression of LDHA at protein level slightly decreased (P>0.05).Conclusions The level of glycolysis can be lowered by suppression HIF-1α expression in human esophageal squamous carcinoma cells.The pathway may be involved in the suppression of GLUT-1 and LDHA expression.Except for HIF-1α,there may be other regulating factors in LDHA protein expression at same time.
3.Changes of Serum Growth Hormone,Insulin-Like Growth Factor-Ⅰ and Insulin-Like Growth Factor Binding Portein-3 Levels in Children with Hypothyroidism
xu, XU ; yong, HE ; hong, SHA ; bo-ru, MEI
Journal of Applied Clinical Pediatrics 2004;0(08):-
Objective To detect the serum growth hormone(GH),insulin-like growth factor-I(IGF-Ⅰ),insulin-like growth factor binging protein-3(IGFBP-3) levels in children with hypothyroidism and explore the change regulation of GH-IGF axis and thyroxine.Methods Fifty-six hypothyroidism children were divided into congonital hypothyroidism(CH)(14 cases) and Hashimoto's thyroiditis(32 cases).Serum GH,IGF-Ⅰ,IGFBP-3 levels of 56 hypothyroidism children before and after luothyroxine sodium L-T4 treatment and 50 normal children were detected with radioimmunoassay or enzyme-linked immunosorbent assay methods.Results Serum IGF-I,IGFBP-3 levels in 9 CH newborn group were lower,and they were normal after thyroxine substitute therapy.But those of 5 children with CH and 32 cases with Hashimoto's thyroiditis were not significantly changed.Conclusions The GH-IGF axis is inordinate in the CH children,which is an important reason of stature short.Early thyroxine substitute therapy is very helpful to maintain normal growth and development of children with CH.
4.To Strengthen Information Analysis and Evaluation Competency——On the Education of Information Literacy of Medical Students
Hong HU ; Wenlong ZHAO ; Chunli LI ; Bo LV ; Yan HE
Chinese Journal of Medical Education Research 2005;0(05):-
As society develops,it has become one of the important goals of higher medical personnel training to cultivate medical students' information literacy.After explaining the definition of information literacy,this paper discussed the importance of information analysis and evaluation in information literacy education.
5.The volume of residual urine correlates with bladder outlet obstruction and detrusor contractility in patients with benign prostatic hyperplasia.
Wei-li WU ; Hua SHEN ; Kai LIAO ; Hong-bo YU ; He-tong ZHOU ; Hong-fei WU
National Journal of Andrology 2015;21(8):729-732
OBJECTIVETo identify the correlation of the volume of residual urine (VRU) with the severity of bladder outlet obstruction (BOO) and detrusor contractility in patients with benign prostatic hyperplasia (BPH).
METHODSA total of 152 patients with clinically diagnosed BPH underwent ultrasonography for measurement of the prostate volume and RVU, free uroflowmetry, and urodynamic examination for the severity of BOO and detrusor contractility. Using the software SPSS20. 0, we analyzed the correlation between the ultrasonographic results and urodynamic parameters and compared the two sample means by the t-test.
RESULTSThe prostate volume was correlated positively with BOO severity (r = 0.432, P < 0.01) and detrusor contractility (r = 0.343 , P < 0.01) while Qmax negatively with BOO severity (r = 0.327, P < 0.01) but not significantly with detrusor contractility (r = 0.123, P > 0.05). VRU showed a significantly negative correlation with detrusor contractility when > 150 ml (r = -0.490, P < 0.01), even more significantly when > 300 ml (r = -0.717, P < 0.01), but exhibited no significant correlation with it when ≤ 150 ml (r = 0.041, P > 0.05).
CONCLUSIONVRU can somehow predict the detrusor function. For patients with VRU > 150 ml, especially for those with VRU > 300 ml, the detrusor function should be evaluated and urodynamic examination is recommended for exact assessment of BOO severity and detrusor contractility.
Aged ; Humans ; Male ; Muscle Contraction ; Muscle Hypertonia ; diagnostic imaging ; physiopathology ; Organ Size ; Prostate ; diagnostic imaging ; Prostatic Hyperplasia ; diagnostic imaging ; physiopathology ; Severity of Illness Index ; Ultrasonography ; Urinary Bladder Neck Obstruction ; diagnostic imaging ; physiopathology ; Urine ; Urodynamics
6.Nursing care of patients in checking of adenosine infusion 99mTC-MIBI myocardial perfusion imaging
Jing HE ; Bo HONG ; Xiao-Hong SHAO
Chinese Journal of Modern Nursing 2012;18(15):1766-1768
Objective To explore the clinical observation experience and nursing care for patients in checking of adenosine infusion 99mTc-MIBI myocardial perfusion imaging.Methods Fifty cases performed check of adenosine infusion 99mTc-MIBI myocardial perfusion imaging following strict indications and contraindication and strengthened mental health education.Patients' electrocardiogram,blood pressure and adverse reaction were closely monitored after adenosine was injected.Meanwhile,patients' complaints were highly concerned and first aid or prevention for complication were prepared.Results Among 50 cases,9 cases had no adverse reaction,39 cases had mild adverse reactions,2 cases had obvious adverse reaction,and no patients had serious adverse reaction such as arrhythmia,acute myocardial infarction,bronchial asthma and so on.Fifty cases went through the check without unexpected event.Conclusions It is important to strengthen patients' observation and nursing care in the checking of adenosine infusion 99mTc-MIBI myocardial perfusion imaging,so that we can help patients complete the check successfully and ensure their security.
7.The Dynamic Changes of Soil Beneficial Bacteria in Cotton Continuous Cropping Soil South Xinjiang
Ming-Fu GONG ; Xia-Bo ZHAO ; He-Yun ZHENG ; Hong-Zhuan SUN ; Jiang-Zhou HE ; Li-Li ZHANG ;
Microbiology 1992;0(04):-
To research the effect of continuous cropping on cotton soil microorganisms and soil microorgan-isms on grow of cotton,we studied the total numbers of aerobic self-nitrogen-fixing bacteria,potassium bacteria,cellulose decomposing bacteria,phosphate solubilizing bacteria,organic-phosphorus-dissolving bacteria distributed in continuous cropping cotton fields of regimental farm 2 and 3 of the first agricultural division through dilution spread plate method.Results showed that the total numbers of five kinds of bacte-ria was highest in blooming and bolling periods,lowest in seeding periods and higher in before sowing pe-riods.The total numbers of five kinds of bacteria was no notable regular changes with continuous cropping year.The numbers of aerobic self-nitrogen-fixing bacteria at different cotton growth stages in regimental farm 2 was higher than in regimental farm 3 and the numbers change of other bacteria was varied in different cotton growth stages in regimental farm 2 and 3.Soil beneficial bacteria were negatively correlated with a variety of soil nutrient ion and free-living nitrogen fixing bacteria were significantly positive correlated with soil total nitrogen.
8.The expression of hypoxia-inducible factor-1α and HK-Ⅱ in esophageal squamous cell carcinoma and its effect in glycolysis
Nana TANG ; Hong ZHU ; Hailin JIN ; Weifeng ZHANG ; Guijun HE ; Bo HAO ; Ruihua SHI
Chinese Journal of Digestion 2012;32(2):108-112
Objective To investigate the changes of hypoxia-inducible factor(HIF)-1α and hexokinase-Ⅱ(HK-Ⅱ)expression in human esophageal squamous cell carcinoma and its effect in glycolysis.Methods TE13 cells and Eca109 cells were cultured under hypoxic condition(1 %O2)for different hypoxic time(6,12,24 and 48 hours).Cells cultured under normal oxygen condition(20%O2)were set as control.The changes of HIF-1α and HK-Ⅱ expressions at protein level were detected by Western blot.HIF-1α genes were specifically silenced with RNA interference technology(RNAi),and then the changes of HIF-1α and HK-Ⅱ expression were determined by realtime PCR and Western blot.Under normal oxygen and hypoxic condition,the changes of lactic acid concentration in cell culture medium were detected by spectrophotometric method.Results Under hypoxic condition,the expression of HIF-1α and HK-Ⅱ gradually increased as hypoxic time extended(P<0.05),reached a peak at 12h and then gradually decreased as time extended.Compared with that under normal oxygen condition,the expression of HK-Ⅱ in TE13 cells and Eca109 cells significantly increased under hypoxic condition(P<0.05),which was more significant after 12 hours hypoxia.The result of realtime PCR indicated that under normal oxygen condition the expression of HIF-1α at RNA level in TE13/shRNA cells and Eca109/shRNA cells significantly decreased compared with TE13 cells and Eca109 cells without interference(P<0.05).The expression of HK-Ⅱ at RNA level was consistent with the result of HIF-1α.Under normal and hypoxia condition,the expression of HK-Ⅱ at protein level in TE13/shRNA cells and Eca109/shRNA cells significantly decreased compared with TE13 cells and Eca109 cells without interference,and the difference was statistic significant(P<0.05).The lactic acid secretion of TE13 cells and Eca109 cells under hypoxia condition(14.707 ± 3.594 and 15.062 ±3.901)was higher than that under normal oxygen condition(6.070±1.839 and 6.891±1.592,P<0.05).The lactic acid secretion of TE13/shRNA cells and Eca109/shRNA cells significantly decreased compared with TE13 cells and Eca109 cells without interference,and the difference was statistic significant(P<0.05).Conclusion The expressions of HIF-1α and HK-Ⅱ in human esophageal squamous cell carcinoma significantly increased under hypoxia conditions.The expression of HK-Ⅱ is closely correlated with lactic acid concentration and HIF-1α expression.HIF-1α may affect cell glycolysis through HK-Ⅱ.
9.Expression and clinical significance of hypoxia inducible factor-1alpha, survivin and vascular endothelial growth factor in esophageal squamous cell carcinoma.
Hong-zhen ZHANG ; Jing ZHANG ; Ning XU ; Xin-bo DUAN ; Chun-nian HE
Chinese Journal of Pathology 2007;36(10):689-690
Adult
;
Aged
;
Aged, 80 and over
;
Carcinoma, Squamous Cell
;
metabolism
;
pathology
;
radiotherapy
;
Esophageal Neoplasms
;
metabolism
;
pathology
;
radiotherapy
;
Female
;
Follow-Up Studies
;
Gene Expression Regulation, Neoplastic
;
Humans
;
Hypoxia-Inducible Factor 1, alpha Subunit
;
metabolism
;
Inhibitor of Apoptosis Proteins
;
Lymphatic Metastasis
;
Male
;
Microtubule-Associated Proteins
;
metabolism
;
Middle Aged
;
Neoplasm Staging
;
Paraffin Embedding
;
Survival Rate
;
Vascular Endothelial Growth Factor A
;
metabolism
10.Pineal mechanism of danggui shaoyao powder on anti-aging.
Chinese Journal of Integrated Traditional and Western Medicine 2008;28(5):444-447
OBJECTIVETo study whether Danggui Shaoyao Powder (DSP) is by way of improving pineal function to realize its anti-aging effects.
METHODSForty aged rats were randomly divided into the sham operated group (A), the pinealectomized group (B), the sham medicated group (C), the pinealectomized and medicated group (D). The medication given was gastric perfusion of DSP for 3 weeks. Learning and memory ability of rats was observed using Morris water maze and the serum melatonin (MLT) concentration of the rats was measured by radio-immunoassay.
RESULTSThe average escape latency in Group B was significantly longer than that in other groups (P <0.05). The times of passing through the platform and the percentage of swimming distance in Group C were significantly higher than those in other groups (P <0.05). The serum MLT was higher at daytime than at night in Group C and D (P <0.05); that at daytime in Group C was higher than Group A (P <0.05) and also higher in Group D than Group B; that at daytime was higher in Group C than Group D; that at night markedly decreased in Group D as compared with Group B (P <0.05).
CONCLUSIONDSP could increase the melatonin secretion and improve learning and memory ability. Since its effects reduced after pinealectomy, it could be deduced that improving pineal function should be one of the action mechanisms for anti-aging.
Aging ; drug effects ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Learning ; drug effects ; Melatonin ; blood ; Memory ; drug effects ; Pineal Gland ; drug effects ; secretion ; Powders ; Rats