1.The effect of P-glycoprotein on 18F-FDG uptake in vitro
Chunjing YU ; Bin ZHANG ; Shengming DENG ; Weixing WAN ; Yiwei WU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2013;(3):213-216
Objective To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18F-FDG uptake in Bcap37 and Bcap37/multidrug resistancce (MDR)1 cell lines in vitro,and to explore the relationship between 18F-FDG uptake and P-gp expression at cellular level.Methods Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 106 per well.Three days later,37 kBq/ml 18F-FDG,or 37 kBq/ml 18F-FDG + 100 μmoL/L VER,or 37 kBq/ml 18F-FDG + 50 μmol/L GF120918 were added into each well.Mter incubated for 10,30,60 and 120 min at 37 ℃ and in 5% CO2,the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately.The radioactivity of 18 F-FDG was measured using a gamma counter.The uptake of 18F-FDG was expressed as the ratio of 18F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis.Results 18F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min.The uptake rate was (1.88 ±0.19) % in Bcap37/MDR1 cells and (1.37 ± 0.18) % in Bcap37 cells (t =7.832,P < 0.05).On the contrary,18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min.The uptake rates were (2.29 ±0.23)% and (2.34 ±0.15)% in Bcap37 cells,(1.47 ±0.14)% and (1.53 ±0.22)% in Bcap37/MDR1 cells (t =8.437,8.283,both P < 0.05).18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t =9.032,9.243 and 8.765,8.803,all P < 0.05).The uptake rates with VER or GF120918 were (2.45 ±0.21)% and (2.46 ±0.25)%,(2.50 ±0.24)% and (2.48 ±0.27)%.There was no significant difference of 18F-FDG uptake in Bcap37 cells with or without VER or GF120918.Conclusions 18F-FDG is a substrate of P-gp at cellular level.P-gp may act as an efflux pump to reduce 18F-FDG uptake in Bcap37/MDR1 cells.The uptake of 18F-FDG can be used to evaluate the function of P-gp in tumor cells.
2.The effect of P-glycoprotein on 18F-FDG uptake in tumor-bearing nude mice
Chunjing YU ; Bin ZHANG ; Shengming DENG ; Weixing WAN ; Yiwei WU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2015;35(3):208-211
Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P>0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P<0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P<0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P>0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.
3.Role of p38 mitogen activated protein kinase signaling pathway in lung ischemia-reperfusion protection offered by HOE642
Jia DENG ; Yu SHI ; Xiyang ZHANG ; Yabing ZHANG ; Bin LIU
Journal of Central South University(Medical Sciences) 2017;42(7):749-754
Objective:To explore the protective effect of sodium channels antagonists HOE642 on lung ischemia reperfusion and the role of the p38 mitogen activated protein kinase (p38MAPK) signaling pathway in this process.Methods:A total of 36 mice were randomly divided into a sham operation group (SHAM group),a lung ischemia reperfusion group (I/R group) and a lung ischemia reperfusion+HOE642 group (HOE group).The water content was detected by electronic scales,and the lung tissue pathological changes were observed under optical microscope.The inflammatory cytokines including IL-6 and TNF-α were examined by ELISA.The intracellular calcium fluorescence intensity was examined and observed under fluorescence microscope,and the protein expression of p38MAPK was detected by Western blot.Results:Lung water content in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P<0.05).Lung interstitial edema,hemorrhage,lung tissue inflammatory cells infiltration were significantly alleviated in the HOE group than those in the I/R group,while the injury in the HOE group was aggravated than those in the SHAM group (both P<0.05).T he IL-6 and TNF-α in lung tissues in the HOE group were lower than those in the I/R group,but higher than those in the SHAM group (both P<0.05).Intracellular calcium fluorescence intensity in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P<0.05).The protein expression of p38MAPK in lung tissues in the HOE group was lower than that in the I/R group,but higher than that in the SHAM group (both P<0.05).Conclusion:HOE642 may exert protective effect on pulmonary I/R injury through regulation of the p38MAPK signaling pathway,resulting in reduction of intracellular calcium ion concentration and calcium overload,and decrease of inflammatory response.
4.Clinical analysis of the correlation between hyperlipidemia and colorectal polyps
Bin LIN ; Zhouxiong XING ; Lu YU ; Liang DENG ; Xuebin ZHOU ; Keshu XU
Chinese Journal of Digestion 2014;34(1):37-40
Objective To explore the correlation between hyperlipidemia and colorectal polyps by compare the level of serum lipids in patients with colorectal polyps.Methods The levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) of 159 patients with colorectal polyps and 138 controls were tested.The serum lipids between colorectal polyps group and control group,of colorectal polyps with different pathological type,of adenomatous polyps with different pathological type,of adenomatous polyps with different location,colorectal polyps of different gender were compared.Chi square test or t test were performed for data analysis.Results The incidence of hyperlipidemia of colorectal polyps group was 41.5% (66/159),which was higher than that of control group (16.7%,23/138) and the difference was statistically significant (x2 =36.56,P<0.01),its levels of TG,TC and LDL-C were all higher than those of the latter ((1.52±0.56) mmol/L vs (1.06 ± 0.42) mmol/L,(5.22±0.86) mmol/L vs (4.52±0.96) mmol/L,(2.85±0.66) mmol/L vs (2.52± 0.35) mmol/L; t=4.23,4.02,3.72,all P<0.01).There were no significant differences in the levels of TC,TG and LDL-C between colorectal polyps with different pathological type (all P> 0.05).The incidence of hyperlipidemia of tubular villous adenoma and villous adenoma (progressive adenomas) was 60.0% (15/25),which was higher than that of tubular adenoma group (33.3%,20/60) and the difference was statistically significant (x2=5.18,P<0.05).The incidence of hyperlipidemia of left colon and rectal polyps group was 46.2% (49/106),which was higher than that of right colon polyps group (28.6 %,12/42) and the difference was statistically significant (x2 =3.87,P<0.05).The incidence of hyperlipidemia of male colorectal polyps group was 47.2% (51/108),which was higher than that of female group (29.4%,15/51) and the difference was statistically significant (x2 =4.53,P<0.05).The level of TG of male colorectal polyps group was higher than that of female group ((1.84 ± 0.73) mmol/L vs (1.55±0.65) mmol/L) and the difference was statistically significant (t=3.98,P<0.05).Age (r=0.766,P=0.009),TG level (r=0.535,P=0.012) and TClevel (r=0.688,P=0.025) were positively correlated with genesis of colorectal polyps.Conclusion There is a significant correlation between hypertriglyceride,hypercholesteremia and colorectal polyps.
5.Endovascular aortic repair for acute thoracic aortic rupture
Fan YANG ; Jian YANG ; Fengxu YU ; Bin LIAO ; Mingbin DENG ; Hui KANG ; Yibing FANG
Chinese Journal of Trauma 2013;(3):211-215
Objective To investigate feasibility and validity of endovascular aortic repair (EVAR) of traumatic thoracic aortic injuries (TTAI).Methods A retrospective analysis was conducted on data of 13 patients with TTAI.Pathological changes were evaluated by spinal CT angiography (CTA) preoperatively and re-evaluated by digital subtraction angiography (DSA) in EVAR.CTA was performed again to confirm therapeutic effects at postoperative 3,6,12 months and annually thereafter.Results All patients had successful EVAR.Complete or partial cover of left subclavian artery was observed in four patients.Endoleak in angiography shortly after stent delivery was noticed in three patients.However,endoleak disappeared in one patient after short stent placement for twice; endoleak was evidently decreased in one patient after balloon dilation.Follow-up was performed for another patient with slight endoleak.A total of 12 patients were followed up,which showed no complications,such as endoleak,ischemia of left upper extremity,paralysis or stent-graft migration.Conclusion EVR is safe and effective in treatment of TTAI.
6.Effects of butylphthalide post-processing on the XIAP and BNIP3 expressions in the hippocampus CA1 of focal cerebral ischemia reperfusion rats
Zhenfang QIU ; Chunying DENG ; Shiying LI ; Jinxia ZHANG ; Yonggui HE ; Hong YU ; Bin LIU
Journal of Medical Postgraduates 2015;(12):1257-1261
[Abstract ] Objective The purpose of this study was to observe the effects of dl-3n-butylphthalide (NBP) sodium chloride injection post-processing on the expressions of X-inhibitor of apoptosis (XIAP) and Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in the hippocampus CA1 neurons of focal cerebral ischemia reperfusion (IR) rats, and to investigate the brain-protection mechanisms of NBP. Methods A total of65 adult male Sprague-Dawley rats were divided into five groups of equal number, sham op-eration, IR, and low-,medium -and high-dose NBP, according to the random number table. The IR models were established by modified ligation of the middle cerebral artery.The animals in the NBP groups received intra-abdominal injection of NBP at 2, 4, and 6 mg/kg, re-spectively.All the rats were sacrificed at 24 hours after modeling,neurological scores obtained by Zea Longa, the volume of infarction measured by TTC staining, the number of apoptotic cells counted by TUNEL, and the expressions of XIAP and BNIP3 detected by immunohistochemistry and real-time PCR. Results The neural function defect scores were markedly lower in low-, medium-and high-dose NBP groups than in IR model rats (P<0.05), with statis-tically significant differences among the three dose groups (P<0.05).The volume of infarction was remarkably higher in the low-dose than in the medium-and high-dose NBP groups (P<0.05).The number of apoptotic cells in the hippocampus CA1 neurons was de-creased in the NBP groups as compared with the IR models (P<0.05).The XIAP-and BNIP3-positive cells were significantly in-creased in the IR model rats as compared with the sham operation group ([22.31 ±0.94] and [60.13 ±2.59]/HP vs [3.07 ±1.43] and [5.78 ±0.44]/HP, P<0.05).In comparison with the IR models, the NBP-treated rats showed a progressively increased number of XIAP-positive cells in low-, medium-, and high-dose groups ([28.70 ±1.18], [32.79 ±0.88], and [37.01 ±1.24]/HP) (P<0.05) but a decreased number of BNIP3-positive cells in the three dose groups ([52.07 ±1.02], [40.30 ±2.00], and [31.04 ± 0.43]/HP) (P<0.05).Similarly, the expression of XIAP mRNA was up-regulated while that of BNIP3 mRNA down-regulated in the NBP treatment groups as compared with the IR model rats, both in a dose-dependent manner (P<0.05). Conclusion NBP post-processing has a neuroprotective effect on IR rats, which is associated with its impact on the expressions of XIAP and BNIP3.
7.Pathogenesis of influenza A (H5N1) virus-induced viral pneumonia in the rhesus macaque
Dongming LI ; Tianwen LAI ; Shaochang DENG ; Dong WU ; Yu ZHANG ; Min CHEN ; Yingying LV ; Bin WU
Chinese Journal of Zoonoses 2014;(8):806-811
At present ,the mechanism of highly pathogenic avian influenza H5N1 virus causing human infection or death is still not fully clear .In order to better understand the pathogenesis of the disease ,the rhesus macaques were infected with H5N1 virus (AF148678/ACGoose/Guangdong/11961H5N1) .We analyzed the clinical symptoms ,characteristics of the virus invades body ,pathological changes ,and immune response to discuss the pathogenesis of viral pneumonia induced by H 5N1 virus infection from the early time to the recovery time .The rhesus macaques were infected with H5N1 virus through nasal .Clinical signs were assessed daily ,and major organs and blood were collected for detection of blood routine analysis ,viruses were isola-ted and titrated from organs ,and pathologic and immunohistochemical were also conducted .As a result ,the rhesus macaques in-fected with H5N1 virus experienced fever ,dyspnea ,and anorexia .The respiratory tract was the major target of the virus and the virus could not replicate in organs outside the respiratory tract .Positive staining cells by immunohistochemistry were bronchial epithelial cells and alveolar macrophages .Rhesus macaques experienced temporary severe pneumonia after 1-3 days ,mainly be-cause of neutrophils infiltration ;gradual recovery 6 days later ,mainly with macrophage infiltration ;lung tissue presented recov-ery state after 14 days ,mainly with T lymphocytes infiltration .Finally ,we concluded that the predilection of the H 5N1 virus to infect the lower airway suggests that it may be a limiting factor in human-to-human transmissibility of the H5N1 virus .The pathogenesis may include virus invasion ,replication and immune injury .
8.Normal development of Cajal-Retzius cells in mouse hippocampus and their changes in APPswe transgenic mice
Wenjuan FAN ; Weijie CHENG ; Yanli NIU ; Mingshan LI ; Dongming YU ; Guotao SUN ; Bin LIU ; Jinbo DENG
Acta Anatomica Sinica 2010;41(2):211-218
ObjectiveIn order to compare the alteration of reelin-immunoreactive Cajal-Retzius cells (CR cells) in molecular layer of dentate gyrus of APPswe transgenic mice with wild type, the histochemical and developmental characteristics of CR cells were studied, therefore, the roles of CR cells in Alzheimer's disease would be revealed further.Methods The Thioflavine S staining, reelin immunofluorescence with or without reelin/glutamate and reelin/GABA immuno-double staining were carried out in the study. In the meantime, Western blotting was used to study the expression of reelin in hippocampi of the both wild type and transgenic mice. Results Reelin positive CR cells could be double-labeled with either glutamate or GABA immunostaining. Caspase-3 immunofluorescence demonstrated that some CR cells went through apoptosis during their development. Compared with wild type, CR cells in APPswe transgenic mice had significantly decreased in the molecular layer of the dentate gyrus. The result was supported with Western blotting analysis of reelin expression in hippocampus. Conclusion Reelin could be co-expressed with either glutamate or GABA, suggesting CR cells would be glutamatergic exciting neurons and GABAergic interneurons. The loss of CR cells during development probably was caused by the neuroapoptosis. Significant decrease of CR cells in hippocampus of APPswe transgenic mice indicated reelin may play an important role in AD pathological alterations.
9.Effects on activation of protein kinase C and phosphorylation of glutamate receptor 2 by electromagnetic irradiation in rat cerebellum
Yong LIU ; Deng-Gao WANG ; Zheng-Ping YU ; Guang-Bin ZHANG ;
Chinese Journal of Physical Medicine and Rehabilitation 2003;0(08):-
Objective To investigate the effects of electromagnetic irradiation on activation of protein kinase C(PKC)and phosphorylation of glutamate receptor 2(GluR2)in rat cerebellum.Methods Sixty male Wistar rats were divided randomly into a control group and an electromagnetic exposure group(including 5 subgroups ob- served at different time points after the irradiation,eg.0 hour,3 hours,12 hours,24 hours and 72 hours after irradi- ation),with 10 rats in each group.All the rats in the exposure group were exposed to 90 mW/cm2 electromagnetic ir- radiation for 20 minutes,their rectal temperature was detected immediately after irradiation and the specific absorption rate(SAR)value was calculated,activation of PKC was detected with improved TaKai method,the level of cerebellar GluR2 expression and phosphorylation(ser880)was detected by using Western blot.Results Immediately(0 hour)after exposure,the rectal temperature of rats increased 2.99℃,SAR value was 8.66 W/kg.When compared to the control group,it was found that there was no significant difference between the exposure group and the control group with regard to all the parameters at 3,12,24 and 72 hours after exposure,except that the cerebellar PKC acti- vation and GluR2(ser 880)phosphorylation decreased significantly immediately after irradiation.Conclusion The electromagnetic irradiation has injurious effects on cerebellar signal pathway of for motor learning.
10.Clinical evaluation of ureteroscopic endo-incision and drainage in the treatment of renal cysts
Xiaoping WANG ; Zhixiang LAN ; Chengyang LI ; Yaoliang DENG ; Hai YU ; Yanwei HUANG ; Bin HU ; Jinyu YANG
Chinese Journal of Urology 2009;30(3):195-197
Objective To evaluate the efficacy and safety of ureteroscopic endo-incision and drainage in the treatment of renal cysts.Methods Thirty cases(19 females and 11 males)of renal cysts(1 1 parapelvie cysts,15 simple cysts.and 4 multiple cysts)were treated with ureteroscopic endo-incision and drainage.The renal cysts were located in renal pelvis,and opened and decompressed by electrotme with ureteroscope.Double J stent was placed afterwards.Urinary and blood biochemistry were tested post-operatively.Results All the operations were successfully completed with no severe complication.The cyst managing time ranged from 15 tO 45 min.Urinary biochemistry(urinary protein and glucose)turned normal 1 2 days after the surgery.Patients were followed up for 3 to 9 months.Renal cysts disappeared in 24 cases,diminished in 4 cases,and recurred in 2 cases.Conclusion Application of ureteroscopic technique in the treatment of renal cyst is safe,effective and minimally invasive.