4.Aspirin inhibits tumor cell metastasis mediated by HGF/c-Met
Xiao-yang DAI ; Si-kang CHEN ; Jin-xin CHE
Acta Pharmaceutica Sinica 2022;57(10):2985-2994
In this study, we investigated the effect of aspirin on tumor biological effects mediated by hepatocyte growth factor/cellular-mesenchymal-epithelial transition factor (HGF/c-Met) axis, and preliminarily explored the molecular mechanism of inhibiting tumor metastasis by aspirin. The binding of aspirin to c-Met was predicted by molecular docking; cellular thermal shift assay (CETSA) was used to verify the binding of aspirin to c-Met at the cellular level. The inhibitory effect of aspirin on c-Met kinase was detected by kinase activity; Western blot, cell scattering test, cell branching morphogenesis and Transwell test were used to evaluate the cell signal transduction, morphological changes and migration and invasion ability. The results showed that aspirin could effectively inhibit the kinase activity of c-Met with a half inhibitory concentration of 0.95 mmol·L-1. The results of docking showed that aspirin could bind to the ATP pocket of c-Met protein, and the main binding sites were Tyr1230, Tyr1159 and Met1229. The CETSA test also showed that aspirin could form binding complex with c-Met protein. Western blot results showed that aspirin could inhibit the up-regulation of phosphorylated Met stimulated by HGF in a concentration-dependent manner. The results of cell scattering test showed that aspirin could block HGF/c-Met promoted cell scattering in a concentration dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L-1, and this effect was independent of HGF. Similarly, the results of MDCK cell branching morphogenesis experiment showed that aspirin could inhibit HGF/c-Met mediated invasive growth in a concentration dependent manner. The results of Transwell test showed that aspirin could block HGF/c-Met mediated cell migration and invasion in a concentration-dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L-1, and this effect was independent of HGF. The above results indicate that aspirin can bind to c-Met, thereby blocking the biological effects mediated by HGF/c-Met, and inhibiting tumor metastasis. This study revealed the new biological function of aspirin, and provided a new theoretical basis for a comprehensive understanding of the anti-metastatic effect of aspirin.
5.A minipig based experimental teaching model for slippery pulse
Dongzhi CHEN ; Xin NIU ; Xuezhi YANG ; Xiaoying DONG ; Zhiguo ZHANG ; Wei GAO ; Yinchu SI
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(12):-
Objective:To establish experimental teaching model for slippery pulse by mini-pig.Methods:The model of slippery pulse was established by driping low molecule dextran in vein.The normal and slippery pulse were extracted from axil artery of mini-pig by two experienced traditional Chinese physician through double blind method.Meanwile,the correlative parameters of pulse graph of axil artery such as MSAB,MSBC,HFF,HE/HB and TW were extracted through optimizational extraction method by using NX-8 multifunctional sphygmograph.Results:The pulse rate of slippery pulse of mini-pig was slightly fast than that of normal pulse.The rhythm of slippery pulse was regularity,the nger sensation was powerful,and the pulse syate was smooth.Compared with the normal pluse,the pulse graph of slippery pluse displayed a steep ascend ramus,high and narrow B wave,tiny D wave,lower E valley and obvious F wave.HB,MSAB and MSBC increased(P
6.Protective effect of CBD and nimodipine against rat cortical neuronal injury in vitro
Ke-Wan WANG ; Xin-Min BAO ; Si-Yun SHU ; Chang-Cai CHEN
Journal of Southern Medical University 2000;20(6):523-526
Objective To investigate the protective effects of CBD and Nimodipine against injuries secondary to glutamate-inuced or traumatic injury in rat cortical neurons in vitro. Methods Mix-cultured cortical neurons of SD rat were subjected to either glutamate injury or mechanical damage. The degree of injury were detected by cell count of trypan blue staining and measurement of lactate dehydrogenase (LDH) activity in the culture medium. Results When combined treatment with CBD and Nimodipine was used separately, moderate protective effects against the injury of cultured cortical neurons induced by glutamate or trauma were observed, which was obvious when compared with the injured group without treatment (P<0.01). When combined treatment with CBD and Nimodipine was administered, strong protective effect were observed than that with treatment using CBD or Nimodipine alone (P<0.01). Conclusion It is suggested that CBD combined with Nimodipine are synergetic. Combined use of different excitotoxic antagonists can be fruitful in the therapeutic intervention of secondary traumatic damage.
7.Protective effect of CBD and nimodipine against rat cortical neuronal injury in vitro
Ke-Wan WANG ; Xin-Min BAO ; Si-Yun SHU ; Chang-Cai CHEN
Journal of Southern Medical University 2000;20(6):523-526
Objective To investigate the protective effects of CBD and Nimodipine against injuries secondary to glutamate-inuced or traumatic injury in rat cortical neurons in vitro. Methods Mix-cultured cortical neurons of SD rat were subjected to either glutamate injury or mechanical damage. The degree of injury were detected by cell count of trypan blue staining and measurement of lactate dehydrogenase (LDH) activity in the culture medium. Results When combined treatment with CBD and Nimodipine was used separately, moderate protective effects against the injury of cultured cortical neurons induced by glutamate or trauma were observed, which was obvious when compared with the injured group without treatment (P<0.01). When combined treatment with CBD and Nimodipine was administered, strong protective effect were observed than that with treatment using CBD or Nimodipine alone (P<0.01). Conclusion It is suggested that CBD combined with Nimodipine are synergetic. Combined use of different excitotoxic antagonists can be fruitful in the therapeutic intervention of secondary traumatic damage.
8.A randomized,double-blind,multicenter study of adefovir dipivoxii in treating patients with HBeAg-positive chronic hepatitis B
Hong ZHAO ; Chong-Wen SI ; Yue-Xin ZHANG ; Xin-Yue CHEN ; Lei WANG ; Xiao-Ping TANG ; Chunliang LEI ;
Chinese Journal of Infectious Diseases 2000;0(02):-
Objective To evaluate the efficacy and safety of adefovir dipivoxil(ADV)in treating patients with hepatitis B e antigen(HBeAg)positive chronic hepatitis B.Methods In this randomized,double blind,placebo-controlled,multicenter trial,210 eligible patients with HBeAg positive chronic hepatitis B were recruited and randomized(randomization ratio was 2:1)receiving ADV 10 mg/d for 48 weeks(ADV+ADV group,n=142)or placebo for 24 weeks followed by ADV 10 mg/d for 24 weeks(PLB+ADV group,n=68).The primary endpoint was virological response. The secondary endpoint was serologic response(HBeAg loss rate and HBeAg seroconversion rate) and alanine aminotransferase normalization rate.Results After 24 weeks therapy,mean reduction of hepatitis B virus(HBV)DNA level comparing with that of baseline was 3.12 log_(10)copy/mL in ADV +ADV group while it was 0.95 log_(10)copy/mL in PLB+ADV group.The percentages of patients with HBV DNA clearance(HBV DNA level
9.Diagnosis and treatment of congenital fourth branchial anomaly
Liang-Si CHEN ; Si-Yi ZHANG ; Xiao-Ning LUO ; Xin-Han SONG ; Jian-Dong ZHAN ; Shao-Hua CHEN ; Zhong-Ming LU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2010;45(10):835-838
Objective To discuss the anatomic features, clinical presentations, diagnosis,differentiations and treatments of congenital fourth branchial anomaly(CFBA). Methods The clinical data of 8 patients with CFBA were retrospectively analyzed. Results Of the 8 patients aging from 27 to 300 months(median age: 114 months), 4 male and 4 female; 3 untreated previously and 5 recurrent. All lesions, including 1 cyst, 3 sinus (with internal opening) and 4 fistula, located in the left necks. Three patients presented acute suppurative thyroiditis, 4 deep neck abscesses, and 1 neck lump. Preoperative examinations included barium esophagogram, direct laryngoscopy, ultrasonography, CT, MRI, and so on.The principles of managements were adequate drainage, infection control during acute period and radical surgery during quiescent period. Classic surgical approach consisted of complete excision of branchial lesions, dissection of recurrent laryngeal nerve and partial thyroidectomy. Selective neck dissection was applied in recurrent cases to extirpate branchial lesions, scarrings and inflammatory granuloma.Postoperatively, 1 case was with local incision infection which healed by wound care; 1 case was with temporary vocal cord paralysis which completely recovered 1 month after operation. No recurrence was found in all of 8 cases with follow-up of 13 to 42 months (median: 21 months). Conclusions CFBA relates closely anatomically with recurrent laryngeal nerve and thyroid grand. The barium esophagogram and direct laryngoscopy are the most useful diagnostic tools. CT and MRI are all beneficial to the diagnosis of CFBA.The treatment key to CFBA is the complete excision of lesion during a quiescent period after inflammatory control, together with the dissection of recurrent laryngeal nerve ,partial thyroidectomy and partial resection of lamina of thyroid cartilage (if necessary), which all can decrease the risk of complications and recurrence.For recurrent cases, selective neck dissection is a safe and effective surgical procedure.
10.Evaluation of bFGF effect on corneal collagen and nerve recovery following LASIK with confocal microscopy
Liu-xue-ying, ZHONG ; Ying, LI ; Xiao, ZHANG ; Si-yang, CHEN ; Xin, DING ; Feng-rong, AI ; Bing-jun, CHEN
Chinese Journal of Experimental Ophthalmology 2011;29(6):525-529
Background Basic fibroblast growth factor(bFGF)secreted by cornea after injury is important to cytothesis,collagen fibers reconstruction and axons recovery.However,the local bFGF is not enough for the reparation process.Objective This study aimed to observe the findings of corneal collagen and nerve recovery under the confocal microscopy through focusing(CMTF) in the eyes with intervene of exogenous recombinant bFGF(rbFGF) after excimer laser in situ keratomileusis(LASIK).Methods LASIK rabbit models were binocularly created in 34 clean New Zealand white rabbits.The tobramycin combined with dexamethasone were dropped after operation for 10 days in bilateral eyes.rbFGF was topically administered in the right eyes of rabbits from 1 day through 3 months after LASIK,and lubricant was used in the left eyes at the same way.The corneal collagen and nerve recovery,keratocyte and endothelial cell counting were observed with CMTF at the 1st week,2nd week,2nd month,3rd month and 5th month after LASIK.Results Total 19 rabbits were meted the request of LASIK models.The keratocyte densities in anterior stroma of both groups reached the lowest level at the 2nd week and the highest level at the 3rd month.Otherwise,haze changed on the contrary.No statistically significant differences were found in anterior stroma keratocyte densities,haze grade,grey value between rbFGF group and lubricant group at various time points after operation(P>0.05).The nerve cord densities of both groups were increased gradually,and those under the epithelial basement membrane were more dominant.The nerve density of the anterior stroma of rbFGF group was significant higher than the lubricant one in the 2nd group(P=0.038).The considerably elevated the subepithelial nerve density value was also seen in rbFGF group compared with lubricant at 5 months after operation(Z=-2.060,P=0.039).No any corneal neovascularization occurred in both groups through experiment duration.The positive correlation was found between grey value with haze grade in rbFGF group(b=22.687,F=37.975,P=0.000) and lubricant group(b=20.410,F=18.516,P=0.000).However,haze grade was not significant correlated with stromal keratocyte density(rbFGF group:b=0.001,F=0.164,P=0.668;lubricant group:b=-0.002,F=1.896,P=0.178).Conclusion Exogenous bFGF can improve the recovery of corneal nerve and regeneration of keratocyte after LASIK.No evidence of bFGF promoting corneal neovascularization is found in this experiment.