1.Inhibitory of Dexamethasone on podocytes apoptosis induced by Puromycin via stabilizing phosphatidylinositol 3 kinase/protein kinase B signaling pathway
Shaoping HE ; Li YU ; Shengyou YU ; Zhihong HAO ; Yao ZHANG
Chinese Journal of Applied Clinical Pediatrics 2017;32(9):677-681
Objective To investigate the role of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway in Dexamethasone (DEX) inhibiting podocytes apoptosis which was induced by Puromycin (PAN).Methods Mouse glomerular podocytes were cultured in vitro,and were divided into control group,dimethyl sulfoxide (DMSO) group,PAN group,DEX group,and LY294002 (inhibitor of PI3 K) group.The mRNA expression of CD2-associated protein (CD2AP) was measured by using real time fluorescent quantitative polymerase chain reaction,and intracellular distribution was detected by using indirect immunofluorescence staining.Co localization of CD2AP and p85 was detected by using confocal fluorescence microscopy.The expressions of Akt,phosphorylated (p)-Akt,glycogen synthase kinase-3β (GSK3 β) and phosphorylated (p)-GSK3β were evaluated by using Western blot.Results The expressions of CD2AP mRNA in PAN group at each time point (8 h,24 h,48 h) (1.11 ± 0.16,0.78 ±0.09,0.56 ± 0.43) were significantly lower than those in the control group (1.90 ± 0.26,2.09 ± 0.12,2.28 ±0.95),and the differences were statistically significant (all P < 0.05);CD2AP distributed in foot process with uniform filament and discontinuous coarse particle around perinuclear;CD2AP and p85 distributed in cell membrane and cytoplasm evenly in control group,but accumulated in nuclei in the PAN group.The expressions of CD2AP mRNA in DEX group at each time point (8 h,24 h,48 h) (1.53 ± 0.14,2.15 ± 0.27,2.13 ± 0.15) were significantly higher than those in the PAN group,and the differences were also statistically significant (all P < 0.05);the distribution density and range of CD2AP were greater than those in the PAN group,and the accumulation with p85 in nuclei decreased obviously.The expressions of p-Akt and p-GSK3β were inhibited by PAN in a dose-dependent manner (P <0.05).The expressions of p-Akt and p-GSK3 β were lowest after PAN stimulated at 15 min and 30 min respectively.However,the expressions of p-Akt and p-GSK3 β increased depending on the concentration of DEX (P < 0.05).In addition,the expressions of p-Akt and p-GSK3 β could be blocked by LY294002 (P < 0.01).Conclusion DEX can protect podocytes and inhibit podocytes apoptosis through stabilizing the expression and distribution of CD2AP.The stale expression of PI3K/Akt signaling pathway is the key factor in DEX protecting podocytes.
2.Research in the treatment of hilar cholangiocarcinoma with hemihepatectomy in 50 cases
Weiyong YU ; Yao ZHAO ; Jingdong HE ; Xiaofei CHEN ; Xiaojuan YU
Chongqing Medicine 2013;(31):3773-3775
Objective To compare the clinical and follow-up results of different ways of operation for the treatment of patients with hilar cholangiocarcinoma ,and to explore its e key technology and related prognosis .Methods 31 out of 50 patients with biliary and partial liver resection(control group) ,19 patients with hemihepatectomy (observation group) .Radical resection rate and surviv-al rate were compared in the two groups .Results radical resection rate control group and observation group was 35 .48% (11/31) and 68 .42% (13/19) ,the difference was statistically significant (P=0 .014);the difference of 1 ,3 ,5 year survival rates between the two groups were statistically significant (P= 0 .03) ,observation group :85 .4% ,58 .6% ,32 .2% ,control group:86 .1% ,65 .2% , 20 .0% .Conclusion Radical resection is still the most important measures the patients for cure and long-term survival ,radical re-section rate ,survival rate ,and prognosis could be improved greatly by improving operation skills and experience accumulation ,com-bined with hepatectomy .
3.Effects and mechanism of visfatin on MMP-9 in macrophages
yu-qi, FAN ; ben, HE ; bin-yao, WANG
Journal of Shanghai Jiaotong University(Medical Science) 2006;0(09):-
Objective To investigate the effects and mechanism of visfatin on matrix metalloproteinases-9(MMP-9)expression and invasive activity in macrophages.Methods THP-1 monocytes were induced into macrophages.To investigate the effects of visfatin on MMP-9,cells were divided into 2 groups:①macrophages+visfatin 12 h;②macrophages+visfatin 24 h.The concentrations of visfatin in each group were:0(control),50,100,200,400 ng/mL.MMP-9 mRNA and protein expression were analysed by RT-PCR and Western blotting,and MMP-9 invasive activity was assayed by gelatin zymography.To investigate the mechanism of visfatin on MMP-9,cells were divided into 5 groups:①macrophages without stimulation(control);②macrophages pretreated with MAPK p38,ERK1/2,JNK pathway inhibitor for 1 h,then stimulated with visfatin(200 ng/mL)for 24 h;③macrophages pretreated with retinoid X receptors(RXR)nature ligand or peroxisome proliferators-activated receptor ?(PPAR?)natural/synthetic ligand for 1 h,then stimulated with visfatin(200 ng/mL)for 24 h;④macrophages stimulated with visfatin(200 ng/mL)for 24 h;⑤macophages+visfatin(200 ng/mL)for different time(5,10,15,30,60 min).MMP-9 expression,PPAR? expression,and the effect of visfatin on MAPK phosphorylation were analysed by Western blotting.Results Visfatin not only significantly enhanced MMP-9 mRNA and protein expression in macrophages(P
4.Efficacy comparison between gemcitabine combined with nedaplatin and paclitaxel combined with nedaplatin in treatment of locally advanced nasopharyngeal carcinoma
Xuebing PAN ; Yu HE ; Junwei SHAO ; Mantian YAO ; Jun JIA
Cancer Research and Clinic 2017;29(6):394-397
Objective To investigate the effect of gemcitabine, paclitaxel combined with nedaplatin in treatment of locally advanced nasopharyngeal carcinoma. Methods 40 patients diagnosed as locally advanced nasopharyngeal carcinoma from May 2012 to August 2014 were randomly divided into observation group and control group. Patients in the observation group received gemcitabine plus nedaplatin chemotherapy, while those in the control group received paclitaxel plus nedaplatin chemotherapy. Then chemotherapy effect, adverse reactions, survival time and tumor marker contents were compared. Results The effective rate of the observation group was 65 % (13/20), which was higher than that (30 %, 6/20) of the control group (χ2 = 4.912, P< 0.05), however, there were no statistically differences in gastrointestinal reactions, bone marrow suppression, liver damage, kidney damage between groups (P> 0.05). Before chemotherapy, the SCCAg and CYFRA21-1 content of the control group were (2.30 ±0.31) ng/L and (18.27±2.19)μg/L, and the observation group were (2.34±0.27) ng/L and (18.48±2.25)μg/L, and there was no significant difference between the groups (P>0.05). After chemotherapy, the SCCAg and CYFRA21-1 content of the control group were (1.92±0.22) ng/L and (13.72±1.74) μg/L, and the observation group were (1.20 ±0.15) ng/L and (8.49 ±0.91) μg/L (P= 0.000). Conclusion Gemcitabine combined with nedaplatin chemotherapy can improve the chemotherapy effect and reduce tumor marker content, without increasing more adverse reactions, which is an ideal chemotherapy regimen for advanced nasopharyngeal carcinoma.
5.Effect of Alkanes on the Production of a Solvent-stable Extracellular Protease by the Organic Solvent Tolerant Bacterium Bacillus licheniformis YP1
Shuang LI ; Xiao-Yu TANG ; Yao PAN ; Bing-Fang HE ;
Microbiology 1992;0(03):-
In this paper, the effect of 5% (V/V) n-alkanes (e.g, n-Heptane, n-Octane, n-Decane, n-Dodecanen-Tetradecane and n-Hexadecane) on the growth and protease production of organic-solvent-tolerant- bacte-rium Bacillus licheniformis YP1 was studied. 5%(V/V) n-alkanes had no effect on the stability of YP1 prote-ase. 5% (V/V) n-alkanes had no notable influence on the yield of strain YP1 but dramatically affected theprotease production. The presence of n-Heptane, n-Octane and n-Decane deeply repressed the protease pro-duction; however n-Dodecane, n-Tetradecane and n-Hexadecane enhanced the protease production promi-nencely. The concentration of n-Tetradecane (1%-8%, V/V) had a direct ration with the protease production.The detailed experiments showed that the notable increase of protease activity appeared at the late logarithmof cultivation compared with the blank. The cell shape of YP1 strain remarkably decreased when grown inthe presence of n-Tetradecane. This is the first report about the effect of n-alkanes on the protease productionby the solvent tolerant bacterium.
6.Effects of different anti-rejection drugs and projects on dyslipidemia after organ transplantation
Mengjuan XUE ; Chaoyang LYU ; Yao ZHANG ; Shunmei HE ; Mingxiang YU
Chinese Journal of Endocrinology and Metabolism 2015;(9):816-818
[Summary] Dyslipidemia after organ transplantation is one of the important risk factors of postoperative cardiovascular disease and graft dysfunction. There are many factors that result in postoperative dyslipidemia. However, the factors influencing serum lipid levels are changing with the development of organ transplantation. In this article the effects of different anti-rejection drugs such as cyclosporine, azathioprine, mycophenolate mofetil, tacrolimus, rapamycin ( sirolimus ) , corticosteroids, and monoclonal antibody on dyslipidemia after organ transplantation were summarized in different eras.
7.The influence of interleukin-2 receptor antagonists exerted on organ transplant recipients
Shunmei HE ; Yao ZHANG ; Xianying CHEN ; Zhaoyang Lü ; Mingxiang YU
Chinese Journal of Endocrinology and Metabolism 2013;(6):540-543
[Summary] Interleukin-2 receptor antagonist (IL-2Ra,ie,basiliximab and daclizumab),a new antibody agent,is widely employed in lowering the risk of acute rejection after organ transplantation,but it meanwhile causes increasing concerns on the effect it exerts on glucose metabolism in transplant recipients,and so far the exact effect still remains controversial.New onset diabetes after transplantation (NODAT) is one of the most influential metabolic complications affecting graft survival and patients' long-term outcomes.Some of the current researches indicate that IL2Ra may improve glucose metabolism in the transplant recipients,some show just the opposite,yet others show no effects.Hence further investigations focusing this aspect are needed.
8.Research strategies and applications of functional metabolomics in anti-depressive mechanisms of traditional Chinese medicine
Meng-yu ZHANG ; Lin XIAO ; Yao-yao REN ; Rui TAN ; He-zhong JIANG ; Xiao-qing WU
Acta Pharmaceutica Sinica 2023;57(7):1732-1741
Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.
9.Study on the intervention effect of Qileng decoction (芪棱汤) on mitochondria mediated and caspase-9 dependent apoptopic pathway
Qinhua YU ; Hongyu JIANG ; Siwei ZHANG ; Gang HE ; Yao TAN ; Hailan TANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2006;0(01):-
Objective: To evaluate the effects and partly mechanism of Qileng decoction(QLD,芪棱汤) resisting focal cerebral ischemia/reperfusion(I/R) injury in rats by apoptosis and signal transduction pathway.Methods: The rats were randomly divided into three groups including sham operation group,normal saline(NS) control group and QLD group.The model of focal cerebral I/R injury was induced by using modified thread embolizing in rats.Rats were evaluated by neurologic function score at 2 hours after ischemia and 2,4,6,12,24 and 48 hours after cerebral reperfusion,and the pathological changes of nerve cells and mitochondria ultrastructure at pallium and hippocampus CA1 region were observed at 24 hours after reperfusion.Immunohistochemical method was performed to examine the expression of cytochrome C(cyt C) and caspase-9 at different time points after reperfusion.Apoptosis of nerve cells in ischemic penumbra(IP) was also characterized by terminal deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling(TUNEL) method.Results: Compared with NS control group,neurologic function scores at different reperfusion time points were improved and the pathological changes were ameliorated at 24 hours after cerebral I/R in QLD group.Mitochondria hydropsia was alleviated,mitochondrial cristae fragmentation and granulum basale shedding were diminished,and mitochondrial basical morphology was retained.Meanwhile,apoptosis index(AI) was decreased and the expressions of cyt C and caspase-9 were reduced in IP in QLD group.Conclusion: QLD intervenes in mitochondria mediated and caspase-9 dependent apoptopic pathway.QLD lowers AI and plays a role of protecting nerve by maintaining mitochondrial basical form,stabilizing mitochondrial membrane and inhibiting the release of cyt C and activation of caspase-9.The above actions are possibly some parts of mechanisms of QLD resisting focal cerebral I/R injury.
10.Clinical Effect of Ubenimex Capsules Combined with SOX Chemotherapy on Treatment of Advanced Gastric Cancer
Wei LI ; Zhongqiang YAO ; Zhongqiu LIU ; Qihua HE ; Xiaojing YU ; Zhigang FAN
Progress in Modern Biomedicine 2017;17(23):4495-4497,4470
Objective:To study the clinical effect and safety of ubenimex capsules and SOX chemotherapy on the advanced gastric cancer.Methods:90 patients with advanced gastric cancer who were treated in our hospital from September 2013 to September 2015 were selected and randomly divided into the observation group (n=45) and the control group (n=45).The patients in the control group were treated with SOX chemotherapy,while the patients in the observation group were treated with ubenimex capsules on the basis of control group.Then the serum levels of MMP-2 and MMP-9,the immune functions,the clinical efficacy,the adverse reactions and survival rate of two groups were observed and compared before and after the treatment.Results:After treatment,the CD4+,CD4+/CD8+ in the observation group were higher than those of the control group (P<0.05);The levels of MMP2 and MMP-9 in the observation group were lower than those of the control group (P<0.05);The total effective rate of the observation group was higher than that of the control group [68.89%(31/45) vs 48.89%(22/45)] (P<0.05);The incidence of thrombocytopenia,leukopenia,nausea and vomiting and abnormal liver functions in the observation group was lower than that of the control group (P<0.05);The survival rate of the observation group was higher than that of the control group at 6 months and 12 months [93.33% (42/45) vs 77.78% (35/45),82.22% (37/45) vs 57.78% (26/45)](P<0.05).Conclusion:Compared with SOX chemotherapy alone,ubenimex capsules and SOX chemotherapy could effectively improve the immune function,enhance the long-term survival rate with high safety of patients with advanced gastric cancer.