1.Recent advance in the regulation of PTEN's function
Chinese Pharmacological Bulletin 2003;0(07):-
The tumor suppressor PTEN is a dual-specificity phosphatase possessing both protein phosphatase and lipid phosphatase activity. PTEN inhibits phosphatidylinositol-3-kinase (PI3-K)/ Akt signaling pathway by dephosphorylating phosphatidylinositol-(3,4,5)-triphosphate at the 3 site. PTEN plays a pivotal role in cell growth, proliferation, migration, and apoptosis. The deregulation of PTEN has been implicated in a variety of human cancers such as prostate, endometrial, and breast cancers. Cellular PTEN's function appears to be regulated by its expression, phosphorylation, oxidation, and membrane binding. This review summarized the current progress in the molecular mechanism of PTEN's function.
2.Serine/threonine protein kinase Akt and Akt targeting anticancer drug development
Chinese Pharmacological Bulletin 1987;0(01):-
Dyregulation of serine/threonine protein kinase Akt/PKB activity is a prominent feature of many human cancers.A large number of studies have demonstrated that Akt plays a key role in mediating cell growth and proliferation,promoting cell migration and invasion,stimulating neoangiogenesis,and protecting from pro-apoptotic stimuli.In view of the highly pleiotropic biologic effects of Akt signaling in multiple aspects of tumor pathophysiology,development of clinically applicable drugs specifically targeting Akt has been the subject of intense research.Up to now,a number of Akt specific inhibitors such as API2,Akt-I-1,Akt-I-2 and DCIEL have been developed and investigated in pre-clinical studies.These compounds have been shown to potently inhibit growth of tumors with aberrantly expressed or activated Akt,therefore,are likely to be developed as promising targeted anticancer drugs.
3.Infection Control During Gastroscopy
Yuehua LIU ; Jinghua ZHENG ; Lunhua ZHAO
Chinese Journal of Nosocomiology 2006;0(05):-
OBJECTIVE To reduce the cross infection during gastroscopy and probe into the(administrative) measures in preventing infection.METHODS The hidden infection of sterilizing gastroscope was analyzed in order to work out the measures to prevent infection.RESULTS Choosing the correct methods of sterilizing gastroscope could(avoid the) incomplete sterilization and reduce the cross infection.CONCLUSIONS Be strict in sterilizing(procedure)s and protecting measures,and prevent the interactive infection in the hospital during gastroscopy.
4.Differential roles of phosphatidylinositol 3-kinase in mitogen-activated prote in kinase activation by insulin and epidermal growth factor
Lunhua LIU ; Yili XIE ; Liguang LOU
Chinese Pharmacological Bulletin 1987;0(01):-
Aim To investigate the roles of phosphatidylinositol 3 -kinase (PI3K) in the mitogen-activated protein kinase (MAPK) activation by in sulin and epidermal growth factor (EGF). Methods Phosphorylated MAPK, Akt (also termed protein kinase B) and total protein level of MAPK were d etermined by Western blotting using phospho- or non-phospho-state specific an tibodies;the roles of PI3K in these signaling transduction pathways were assess ed by use of PI3K specific inhibitor wortmannin.Results Both in sulin and EGF rapidly stimulated MAPK phosphorylation; wortmannin totally blocke d the MAPK phosphorylation stimulated by insulin, but not by EGF.By contrast, wo rtmannin equally inhibited Akt phosphorylation stimulated by both insulin and EG F. Moreover, wortmannin inhibited insulin-stimulated MAPK phosphorylation in a concentration-dependent manner,and the inability of wortmannin to inhibit EGF -stimulated MAPK phosphorylation was not changed with the use of low concentrat ions of EGF.Conclusion PI3K plays different roles in the MAPK a ctivation induced by insulin and EGF.
5.Effect of hydroxysafflor yellow A on apoptosis of human renal tubular epithelial cells under cold hypoxia and reoxygenation
Jie WANG ; Weipeng LIN ; Hanqiao LI ; Lunhua CHEN ; Zhengyuan YAO ; Min LIU ; Zhanqing LI ; Xue YI
Clinical Medicine of China 2021;37(5):400-405
Objective:To investigate the effect of hydroxysafflor yellow A(HSYA) preconditioning group on apoptosis induced by cold hypoxia/reoxygenation (cold H/R) injury in human renal tubular epithelial cells (HK2 cells).Methods:After digestion and passage, HK2 cell lines were divided into Sham group (control group), cold hypoxia and reoxygenation group (cold H/R group, cells cold hypoxia for 4 h, reoxygenation for 4 h), and HSYA preconditioning group (each HSYA subgroup was given different doses of HSYA 0.5 h before hypoxia, and the other operations were the same as the cold H/R group). The cell survival rate was measured by CCK-8 method.The expression of Bcl-2, Bax and Caspase-3 proteins in HK-2 cells were detected by immunocytochemistry and Western blotting.Results:(1) Compared with cold H/R group, different doses of HSYA could improve cell survival rate in different degrees, but only HSYA25 μmol/L group had the most significant effect (74.000±5.500 vs.59.000±3.800, P<0.05). (2) Immunocytochemistry semi-quantitative score: Compared with cold H/R group, the expression of Bax and Caspase-3 in HK2 cells of HSYA25 μmol/L group was significantly decreased(0(0, 1) vs. 8(6, 8), Z=2.041, P<0.05 and (3.400±0.548) vs.(7.800±1.095), t=11.000, P<0.01). The expression of Bcl-2 protein was increased significantly ((6.800±1.095) vs.(1.400±0.548), t=10.590, P<0.01). The ratio of Bcl-2/Bax increased significantly.(3)Western blot was used to detect protein: Compared with the cold H/R group, the protein levels of Bax, Cleaved-Caspase-3 and Pro-caspase-3 of HK2 cells in the HSYA25 μmol/L group were significantly decreased ((0.707±0.012) vs.(0.968±0.117), (0.480±0.009)vs.(0.735±0.005), (0.992±0.008)vs.(1.197±0.005), all P<0.01). The expression of Bcl-2 protein was significantly increased, and the ratio of Bcl-2/Bax was significantly increased ((0.410±0.009) vs.(0.273±0.008), (0.582±0.016) vs (0.282±0.080), all P<0.01). The experimental results were consistent with the immunocytochemistry. Conclusion:HSYA can effectively reduce the damage of HK2 cells after cold hypoxia and reoxygenation.
6.Protective effects of N-acetylcysteine regulating HIF-1a / iNOS signal pathway on ischemic-reperfusion injury in rat heart transplantation
Xue YI ; Yongqian LIU ; Hanqiao LI ; Lunhua CHEN ; Hongyuan ZHONG ; Yigen WU ; Lixian CHENG ; Ying SHI ; Zhanqing LI
Clinical Medicine of China 2018;34(3):249-252
Objective To observe the effect of HIF-1a/iNOS signaling pathway on myocardial ischemia-reperfusion injury in rat heart transplantation and the protective mechanism of N-acetylcysteine (NAC) on donor heart after cardiac transplantation in rats.Methods Eighty healthy male Lewis rats were randomly divided into 3 groups,the control group (0.3 ml saline was infused via inferior vena cava 30 min before donor harvest or implantation),NAC donor pretreatment group [NAC (30 mg/kg.w) was injected into the vena cava of donor rat 30 min defore donor harvest],and the NAC receptor pretreatment group (NAC 300 mg/kg.w was injected into the vena cava of the recipient rats 30 min before transplantation.The 30 min was injected into the vena cava of the recipient rats).A transplant model was established and the graft was obtained after 24 h transplantation.The expression of iNOS,HIF-1a and mRNA in cardiac muscle tissue was detected by immunohistochemistry and Real time-PCR.Results HIF-1a protein expression in graft myocardial tissue was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group (P <0.05),the differences were statistically significant (2.72±0.17 vs.2.24±0.23 vs.3.14.±0.16,F=56.26,P =0.000).The iNOS protein expression in NAC donor pretreatment group,and NAC recipient pretreatment group were lower than that in the control group (1.52±0.18 vs.1.61±0.19 vs.3.30±0.18,F=232.345,P =0.000),the differences were statistically significant (P < 0.05).24 h after transplantation,the differences in graft myocardial tissue HIF-1a and iNOS mRNA among the three groups were statistically significant (F=7.467,16.490,P=0.003,0.000).The expression of iNOS mRNA in the NAC receptor pretreatment group was significantly lower than that in the control group (P<0.05).Conclusion HIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation,and the protective effect of NAC on donor heart maybe mediated via this pathway.