1.Efficacy of locally administered dexamethasone for prevention of low back pain after labor epidural analgesia
Si ZENG ; Tao FENG ; Wenjie SU ; Liu LIU ; Xue YANG ; Zhixun LAN
Chinese Journal of Anesthesiology 2015;35(6):711-713
Objective To evaluate the efficacy of locally administered dexamethasone for prevention of low back pain after labor epidural analgesia.Methods Two hundred nulliparous parturients who required labor epidural analgesia,of ASA physical status Ⅰ or Ⅱ,were randomly divided into 2 groups (n =100 each) using a random number table:control group (group C) and dexamethasone group (group D)).In group D,lidocaine 4 ml and dexamethasone 1 ml (5 mg) were injected around the puncture site.In group C,lidocaine 4 ml and normal saline 1 ml were injected around the puncture site.Epidural puncture was performed after local administration.According to the results of epidural puncture,each group was further divided into two subgroups:single puncture group (Cs subgroup,Ds subgroup) and repetitive puncture group (Cr subgroup,Dr subgroup).The patients were followed up for 72 h,and the development of low back pain was recorded.Results Compared to group C,the incidence of low back pain was significantly decreased,and pain was reduced in group D.The incidence of low back pain was significantly lower in Ds group than in Cs group,and in Dr group than in Cr group.Conclusion Locally administered dexamethasone 5 mg is helpful in reducing low back pain after labor epidural anesthesia.
2.Discovery of natural BH3 mimetics and research on related mechanism
Si-Meng GU ; Shuai-Shuai LIU ; Yue ZHANG ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):281-282
In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.
3.Inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism
Shuai-Shuai LIU ; Si-Meng GU ; Jian-Hui DUAN ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):295-296
Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.
4.Cisplatin inhibites HeLa cell proliferation by suppressing activation of metastasis suppressor gene 1-extracellular signal-regulated kinase/serine-threonine kinase
Si ZHANG ; Yuanlin LIU ; Xue LI ; Xiangdong ZHOU ; Yue ZHAO ; Pingping ZHANG ; Ying TONG ; Yi ZHANG
Chinese Journal of Pharmacology and Toxicology 2016;30(4):350-355
OBJECTIVE To study the molecular mechanism of cisplatin(DDP)by which HeLa cell growth and proliferation are inhibited. METHODS Cultured HeLa cells were treated with DDP 0.02-75 μmol · L-1 for 24 or 48 h. CCK-8 assay was used to determine the cell proliferation. The wound scratch assay was used to detect the cell migration and invasion. Flow cytometry was used to detect the cell cycle arresting. q-PCR was used to test the expression of metastasis suppressor gene 1 (MTSS1)mRNA. Western blot was used to determine protein levels of MTSS1,phosphorylated-extra?cellular signal-regulated kinase(p-ERK) and phosphorylated-serine-threonine kinase(p-AKT). RESULTS Following the treatment with DDP for 24 or 48 h,the proliferation of HeLa cells was inhibited significantly (P<0.05),the value of the half inhibitory concentration (IC50) of cells was 4.14 and 11.82 μmol · L-1. Migration and invasion activity of HeLa cells were reduced according to the wound scratch assay(P<0.05). Flow cytometry results showed that the cell cycle was arrested at S phase. q-PCR results showed that MTSS1 mRNA expression changed with DDP in a concentration-dependent manner (r24 h=-0.965,P<0.01;r48 h=-0.953,P<0.01). Western blot showed that the protein levels of MTSS1,p-ERK and p-AKT expression declined significantly with the increase in DDP concentrations(p-ERK:r24 h=-0.875,P<0.01;r48 h=-0.966,P<0.01. p-AKT:r24 h=-0.831,P<0.01;r48 h=-0.863,P<0.01. MTSS1:r24 h=-0.969,P<0.01;r48 h=-0.988,P<0.01). CONCLUSION DDP treatment inhibits HeLa growth and proliferation by interfering with the MTSS1 expression and disturbing the activation of ERK and AKT signaling pathways.
5.Role of amplified in breast cancer 1 in expression of epithelium mesenchymal transition related markers in hepatocellular carcinoma
Jingjing XU ; Si GUO ; Haibo YU ; Yuqiong LIU ; Jianping CAI ; Rui XUE
Chinese Journal of Hepatobiliary Surgery 2015;21(2):122-127
Objective To investigate the expression and clinical features of amplified in breast cancer 1 (AIB1) and epithelial mesenchymal transition (EMT) markers in human hepatocellular carcinoma and to observe the effect of AIB1 silencing by RNA interference (RNAi) on expression of EMT markers and invasiveness of HepG2 cells.Methods In this study,expression of AIB1,E-cadherin,Vimentin,ZO-1,and N-cadherin protein in 81 hepatocellular carcinomas were assessed through immunohistochemistry and clinicopathological significance was analyzed.After the lentiviral vector of AIB1 RNA interference was transfected into HepG2 cells,the expression of AIB1 and EMT markers was detected by real-time PCR and Western blot.The invasion and metastasis was evaluated by Transwell analysis.Results The expression of AIB1 protein was significantly up-regulated in the hepatocellular carcinoma tissue compared to the normal tumor adjacent tissue.The frequency of AIB1 overexpression in hepatocellular carcinomas with lymph node metastasis is 63% (P < 0.05).Correlation analysis demonstrated that the AIB1 protein expression was inversely correlated with E-cadherin,and positively correlated with Vimentin in hepatocellular carcinomas.After transfection with AIB1 targeting siRNA,the expression of AIB1 mRNA and protein decreased significantly (P < 0.05).Knockdown of AIB1 expression increased the expression of E-cadherin and inhibited the expression of Vimentin.In addition,the invasion of HepG2 cells silenced AIB1 were significantly descented.Conclusion Above data suggests that overexpression of AIB1 might promote invasiveness and metastasis of cancer cells through regulation of E-cadherin and Vimentin expression in hepatocellular carcinomas.
6.Effect of Qingguang'an on elastic fiber, MMP- 7, TlMP - 1 in scarring area of filtration canal after glaucoma surgery
Yuan-Bi, LI ; Qing-Hua, PENG ; Xue-Si, HUANG ; Xiao-Liu, CHEN ; Han-Yu, TAN
International Eye Science 2015;(1):20-25
?AlM: To observe the effect of Qingguang'an on elastic fiber, MMP-7, TlMP-1 in scarring area of filtration canal after glaucoma surgery through the four Qingguang'an effective groups and Qingguang'an granules, to discuss and compare their mechanism of action on scarring area of filtration canal.?METHODS:Four effective components of Qingguang'an were used in groups D, E, F, G and H after glaucoma surgery, compared with group A ( blank ) , group B (model) and group C ( MMC) to observe the effect of elastic fiber, MMP-7, TlMP-1 in scarring filtration canal.?RESULTS:Compared with the preoperative basic lOP and 2d , 1, 2, 4wk postoperative lOP of groups C, E and H, the lOP of three group rose up slower than other groups, and kept the lowest data at 28d. There was significant difference compared with the rest of A, B, D, F, G groups (P<0. 05). The area and density of elastic fiber in surgery group were significantly different with that of black control group ( P<0. 05 ), but there were no statistical differences between groups C and H, groups C and F, groups H and E (P>0. 05). The difference was statistically significant among other groups (P<0. 01).?CONCLUSlON:The scarring area of filtration canal after glaucoma surgery is the major reason which lead to the failure of surgery. Qingguang'an effective group 2, Qingguang'an granules and MMC could reduced the scar tissue by restrained the elastic fiber, TlMP - 1 and increased the MMP-7. By observing the experimental results that both Qingguang'an effective group 2 and Qingguang'an granules could restrained the scarring area of filtration canal, the effects were unbiased, Qingguang'an granules group is better than effective group 2.
7.Apoptosis and proliferation of peripheral blood lymphocytes from primary nephrotic syndrome children and effects of dexamethasone on them
xiao-ming, LIU ; si-guang, LU ; ling-yu, XUE ; ping, JI
Journal of Applied Clinical Pediatrics 2004;0(09):-
Objective To explore the apoptosis and proliferation of peripheral blood lymphocytes(PBLs) from primary nephrotic syndrome(PNS) and effects of dexamethasone(Dex) on them.Methods Minimal change NS(MCNS), non-minimal change NS(NMCNS) and healthy children were involved in this study. PBLs were cultured in vitro with Dex or PHA+Dex or without PHA and Dex. Apoptosis of PBLs was measured by propidium iodide(PI) staining; The effects of Dex at different concentrons on PBLs′proliferation were investigated by 3H-TdR incorporation.Results The apoptotic rate of vacuity group in MCNS was lower compared with NMCNS and healthy controls(P
8.Relationship of Membrane Glucocorticoid Receptors in Peripheral Blood Lymphocytes from Minimal Change Nephrotic Children and Influence of Glucocorticoid on Apoptosis and Proliferation
xiao-ming, LIU ; si-guang, LU ; zheng, WANG ; ling-yu, XUE
Journal of Applied Clinical Pediatrics 2004;0(11):-
Objective To study the expression of membrane glucocorticoid receptors(mGR), the correlation between mGR and glucocorticoid(GC)'s effects on apoptosis and proliferation of peripheral blood lymphocytes(PBLs) in minimal change nephrotic syn-drome(MCNS)and the influence of GC on mGR. Methods MCNS, nonminimal change NS(NMCNS) and healthy children were involved in this study. Indirect immune fluorescence and flow cytometry were used to examine the percentages of positive mGR lymphocytes; the apoptosis of PBLs was measured by propidium iodide(PI) staining and the proliferation of PBLs was investigated by fa -TdR incorporation. Results 1.mGR expression in MCNS was higher than that in NMCNS and healthy control,but it was reduced after clinical GC therapy(P
9.Meconium Ileus Combined with Pseudohypoaldosteronism Type Ⅰ in 1 Child
mu-xue, YU ; wei-qi, CHEN ; si-qi, ZHUANG ; jun-cheng, LIU
Journal of Applied Clinical Pediatrics 2004;0(07):-
Objective To improve the recognition of meconium ileus and pseudohypoaldosteronism type Ⅰ and to explore the relationship between neonatal meconium ileus and cystic fibrosis.Methods The clinical and follow-up data of a premature infant with meconium ileus and pseudohypoaldosteronism type Ⅰ was analyzed.Relevant literature was reviewed.Results The child was a very low-birth weight premature infant who didn′t pass meconuim within 24 hours of birth and persistent abdominal distention was noted.Laparotomy was performed on day 4.Thick and inspissated meconium was found in the ileum with perforation.The atretic intestine was resected,and a double-barreled enterostomies was performed.On day 30,the child presented hyponatremia,hyperkalemia,high levels of plasma renin and aldosterone and was given 9 g/L salt supplementation.At 6-month age,9 g/L salt supplementation was discontinued.Anastomosis was performed at 8-month age.The child recovered with a good prognosis whose catch-up growth was obtained at 18-month age and didn′t pre-sent manifestations of cystic fibrosis.Conclusions This case could be diagnosed as meconium ileus and pseudohypoaldosteronism type Ⅰ.The relationship between neonatal meconium ileus and cystic fibrosis is different in China and the regions of Caucasian.
10.Effects of cyclopamine on endometrial carcinoma (HEC-1 A) and apoptosis
Pingping ZHANG ; Xue LI ; Yuanlin LIU ; Si ZHANG ; Xiangdong ZHOU ; Ying TONG ; Yi ZHANG
Military Medical Sciences 2017;41(1):48-52
Objective To investigate the effects of cyclopamine (CYP) on endometrial carcinoma (HEC-1A) cell survival and on induction of cell apoptosis .Methods HEC-1A cells were treated with various doses of CYP (0, 5,10, 20 and 40 μmol/L) for 24 h respectively .Then,the inverted microscope was used to observe cell morphology .Cell proliferation and apoptosis were tested by CCK-8 assay and AO/EB bi-labelling assay.The apoptosis rate of HEC-1A was analyzed using flow cytometric analysis , and the key gene expression of Bax and Bcl-2 was detected by quantitative PCR .Results The HEC-1A cells exhibited dramatic morphological changes after treatment with CYP and in a dose-dependent manner .CYP significantly inhibited HEC-1A cell proliferation using CCK8 assays(P<0.05), and induced cell death by AO/EB bi-labelling assay.Moreover,flow cytometry analysis showed that CYP treatment resulted in HEC-1A cell apoptosis, and that a higher concentration of CYP induced severer cell apoptosis (P<0.05).Meanwhile, CYP treated HEC-1A cells exhibited up-regulated expression of Bax and down-regulated expression of Bcl-2 according to Q-PCR.Conclusion Our findings indicatee that CYP can inhibit HEC-1A cell proliferation and induce cell apoptosis .