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.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
7.A case of deep mycosis caused by Rhizomucor chlamydosporus
Yu-Chun CAO ; Xing-Ping CHEN ; Xue-Si ZENG ; Hui CHEN ; Mu-Fen WAN ; Shou-Xin LI
Chinese Journal of Dermatology 2003;0(11):-
Objective To report a case of deep mycosis caused by Rhizomucor chlamydosporus. Methods Medical history,histopathology and laboratory examination were investigated,and fungal identifi- cation by microscopy and culture as well in the patient.Results The patient,a 41-year-old male,initially presented with mild-tender and progressively aggravating masses on the right glutea,both groins,and back of the head of pancreas.Later,ulcer,necrosis,and black crusts developed at the primary lesions accompanied with nausea,vomitting and dysfunction of liver.Pathological examination revealed a chronic granuloma- tous inflammation in the dermis and subcutaneous tissue;and branching,nonseptate and broad hyphae in multinuclear giant cells,tissue spaces and blood vessel lumens,and,few PAS-positive septate hyphae as well as basophilic chlamydospores located in multinuclear giant cells.The isolate was identified as R. chlamydosporus.Conclusions The case of deep mycosis caused by R.chlamydosporus began with invasive granuloma,followed by necrotic ulcer,with condition aggravating rapidly,and the patient finally died of se- rious cachexia.
8.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.
9.Danshen Modulates Nrf2-mediated Signaling Pathway in Cisplatin-induced Renal Injury
CAO SI-SI ; YAN MIAO ; HOU ZHEN-YAN ; CHEN YING ; JIANG YUN-SHENG ; FAN XIN-RONG ; FANG PING-FEI ; ZHANG BI-KUI
Journal of Huazhong University of Science and Technology (Medical Sciences) 2017;37(5):761-765
Danshen,an efficacious agent for cardiovascular diseases,has been found to play an essential role in kidney injury.In the present study,the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model.Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment.A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity.The mice were sacrificed 72 h after cisplatin intoxication.Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed.Histopathological changes of kidney tissues were detected using HE staining.Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected.Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting.The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice.Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin.Moreover,Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues.Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice.It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice,which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.
10.Correlation between Fractional Anisotropy and Amyotrophic Lateral Sclerosis, and Effect of Inte- grative Medical Treatment on ALS.
Mei-li TANG ; Bao-xin DU ; Zhi-yuan CHEN ; Xin CHEN ; Si-run LIU ; Yu-pin LIU ; Ru-hang HUANG ; Bo LIU
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(4):421-424
OBJECTIVETo explore whether fractional anisotropy (FA) value could be taken as a quantitative indicator for tracing and reexamining amyotrophic lateral sclerosis (ALS), and to analyze the correlation between FA value and integrative medical treatment.
METHODSTotally 18 ALS patients were recruited in this study. All patients received diffusion tensor imaging (DTI) using 3. OT (Propeller HD) MRI twice. Six regions of interest (ROI) were selected to measure FA values. Survival analyses were performed in 11 cases of end point events.
RESULTS(1) Three ROI (cerebral peduncle, posterior limb of internal capsule, and corona radiata) all indicated that FA value was the highest in patients with mild health status scale of amyotrophic lateral sclerosis (ALS/HSS). (2) There was statistical difference in the means of FA values in cerebral peduncle, posterior limb of internal capsule, and corona radiata of 18 cases between initial examination and reexamination (P < 0.01). (3) Kaplan-Meier survival curve showed the survival rate of ALS patients decreased as time went by, with the median survival time of 48 months.
CONCLUSIONSFA value was inversely proportional to the severity of ALS, the more severe, the lower FA values. FA value was an objective indicator for assessing the severity of ALS. ALS is an incurable disease till now. Integrative medical treatment might become one direction for ALS patients.
Amyotrophic Lateral Sclerosis ; diagnosis ; therapy ; Anisotropy ; Diffusion Tensor Imaging ; Humans ; Integrative Medicine