1.Hypoxia stimulates vascular endothelial growth factor production in human renal flbroblasts
Heng LI ; Zhihong LIU ; Dong LIU
Chinese Journal of Nephrology 1997;0(03):-
Objective To investigate the effect of hypoxia on vascular endothelial growth factor (VEGF) expression and secretion in human renal fibroblasts. Methods Human renal fibroblasts were primary cultured from donor kidney, and cells in passage 3 were used in this experiment. Hypoxia was induced by incubation in a gas-tight box gassed with 10% CO2/10% H2/80% N2 for 24 hours. VEGF mRNA levels were measured by semi-quantitative RT-PCR method. VEGF proteins expressed on cell surface were measured by flow cytometry. VEGF proteins secreted into supernatants were measured by ELISA method. Results Hypoxia caused a 2. 5-fold increase of VEGF mRNA level in human renal fibroblasts. Hypoxia also induced significant increases of VEGF proteins on cell surfaces (mean fluorescence intensities: 1. 053?0. 055 vs 0.763?0.057, n=4,P
4.Effect of administration of transient receptor potential vanilloid 1 antagonist capsazepine into the nucleus accumbens on central modulations of body weight and fat accumulation in rats
Bo HUANG ; Li-Jun HENG ; Heng GUO ; Dong JIA ; Xue-Lian WANG ; Wei-Xin LI ; Guo-Dong GAO
Chinese Journal of Neuromedicine 2012;11(2):129-133
Objective To study the effect of administration of transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ) into the nucleus accumbens (NAc) on the regulation of body weight and fat accumulation in rats, and evaluate the therapeutic effect of CPZ on neuropathic obesity. Methods Forty rats were randomly divided into 5 groups (n=8), namely, control group (without giving any treatment),group A (performed intra-NAc injection of 1 nmol/mL CPZ),group B (performed intra-NAc injection of 10 nmol/mL CPZ),group C (performed injection of 10 nmol/mL CPZ via the areas adjacent to NAc) and group D (performed injection of 10 nmol/mL CPZ via the dorsal striatum); rats of the later 4 groups were given 1 μL CPZ daily for a consecutive 3 d.The body weight of rats from different treatment groups 1 and 3 weeks after the injection was measured and compared them to that of the control group.Then,the animals were sacrificed,the body fat content of each group was evaluated. Results The body weight in rats of group A 1 week after the injection increased (126.31± 10.25)% as compared with their original weight, and that in rats of control group increased (148.78±6.98)% as compared with their original weight, which showed significant difference between the 2 increment (P<0.05); the body weight in rats of group B 1 week after the injection increased (115.87± 13.90)% as compared with their original weight, which showed significant decrease as compared with that in the control group (P<0.05); The body weight in rats of group B 3 week after the injection increased (132.82±15.8)% as compared with their original weight, and that in rats of control group increased (164.86±6.34)% as compared with their original weight,which showed significant difference between the 2 increment (P<0.05).Furthermore,the body fat content in group B was significantly lower than that of other groups (P<0.05). Conclusion Blockade of NAc TRPV1 receptor by CPZ has significant inhibitory central adjusting effect on body weight and fat content in rats; and TRPV1 antagonist may potentially serve as a specific drug for neuropathic obesity.
5.Clinical value of serum CA19-9,CA125 and CP2 in mucinous ovarian tumor:a retrospective study of 273 patients
Li DONG ; Heng CUI ; Xiaoping LI ; Lifang SUN ; Xiaohong CHANG ; Xudong HANG ; Honglan ZHU
Chinese Journal of Obstetrics and Gynecology 2008;43(1):5-8
Objective To evaluate the diagnostic and prognostic value of serum CA19-9,CA125 and CP2 in mucinous ovarian tumors.Methods In this retrospective study,the serum CA19-9,CA125 and CP2 levels of 273 hospitalized patients with ovarian tumors of either mucinous or non-mucinous type were analyzed.Results(1)CA19-9 had the biggest area under chive(AUC)in mucinous tumors followed with CA125 while CA125 and CP2 had bigger AUC in non-mucinous tumor.(2)For the diagnosis of mucinous tumors,CA19-9 and CA125 combination showed a greatly increased sensitivity compared with CA19-9 or CA125 alone(93.8%versus 75.0%and 66.7%,P<0.05)with no significant improvement of the specificity(P>0.05).For the diagnosis of non-mucinous tumors,CA125 and CP2 combination showed an increased sensitivity compared with CA125 or CP2 alone(85.0%versus 80.7%,P>0.05,85.0%versus 70.6%,P<0.05)with no significant improvement of the specificity(P>0.05).(3)Seventy percent of tumor marker-positive patients could undergo cytoreductive surgery.Compared with those who could not undergo cytoreductive surgery,they were more likely to have normal tumor marker two months after surgery (P<0.05)and longer interval to re-elevation of tumor markers(P>0.05),with lower reeurrence and death rate (P<0.05).All of the 20 tumor marker-negative patients could have eytoreduetive surgery with only 10%recurrence.(4)CA19-9 inereased mainly in recurrent mucinous tumor,while CA125 increased dominantly in recurrent non-mueinous tumor.(5)The survival rate of CA125 and CP2 positive patients was much lower than CA125 and CP2 negative patients(P<0.05),while the survival rate was similar between CA19-9 positive and CA19-9 negative patients.Conclusions CA19-9 is a sensitive index for diagnosis of mucinous ovarian tumors.Combination of CA19-9 with CA125 can improve the sensitivity of diagnosis and postoperative monitoring of mucinous ovarian tumors.Combination of CA125 with CP2 is more valuable in the diagnosis of non-mucinous ovarian tumors.
6.Expression,roles and therapy target values of CD24 in oral squamous cell carcinoma
Heng MO ; Chengzhi GAO ; Shaojie WANG ; Mei LI ; Jianqiang DONG ; Weidong YU
Journal of Peking University(Health Sciences) 2016;48(1):16-22
Objective:To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy.Me-thods:Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues.Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells,oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA)and CD24 antibody on CD24 expression,and the proliferation and tumorsphere formation capacity of these two cell lines.Results:CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05),as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05).CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05 ).Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05).Among them ATRA at least involved partially in the proliferation by down-regulating the CD24 expression (P<0.05 ),while CD24 antibody blocking had no effect on the CD24 expression.Conclusion:CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells.Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target.
7.Effects of volatile anesthetics on rat heart ischemia-reperfusion injury in vitro
Heng LI ; Chengxiang YANG ; Kai SUN ; Xianhui MENG ; Xiaoli DONG ; Yinming ZENG ; Jun WANG
Chinese Journal of Pathophysiology 2000;0(10):-
AIM: To investigate the effect of volatile anesthetics on function,metabolism,ATPase activity and free radicals in isolated ischemia /reperfusion(I/R) rat hearts.METHODS: 136 SD rats were anesthetized with pentobarbital and randomly divided into six groups and 17 sub-groups(n=8),according to the given drug.In a normal thermal isolated Langendorff rat heart model,four volatile anesthetics in 1.5 MAC concentration were given before global ischemia 25 min and during reperfusion 30 min.Coronary flow(CF),LVEDP,left ventricular developed pressure(LVDP),?dp/dt were monitored at 15 min of equilibrium,15 min of drug treatment,the end of reperfusion.Myocardial adenosine triphosphate(ATP),malodialdehyde(MDA),activity of Ca2+-ATPase and Na+-K+-ATPase,and superoxide dismutase(SOD) were determined at 15 min of equilibrium,15 min of drug treatment or absence,10 min global ischemia and the end of reperfusion.RESULTS: CF and LVEDP were iocreased significantly after exposured to volatile anesthetics 15 min,and LVDP,+dp/dtmax were significantly decreased.However,LVDP and +dp/dtmax were increased at the end of reperfusion in the treated groups.HR in halothane and isoflurane groups was decreased before ischemia and after reperfusion.The myocardial ATP content was significantly increased before and after ischemia in the treated groups.At the end of reperfusion,the activity of SOD was significantly higher and myocardial MDA content was significantly lower in the treated groups than those in control group.The activity of Ca2+-ATPase,compared with the control group,was markedly decreased before ischemia in halothane,enflurane and isoflurane group.Nonetheless,the activity of Ca2+-ATPase was clearly increased in the treated groups during ischemia and at the end of reperfusion.The activity of Na+-K+-ATPase was only enhanced in halothane group at the end of reperfusion among groups.CONCLUSION: The volatile anesthetics depress myocardial systolic function.There are markedly protective effects against myocardial I/R injury.Meanwhile,the volatile anesthetics improve the recovery of function and metabolism,and increase CF and the activity of Ca2+-ATPase and Na+-K+-ATPase in rats.
8.Correlation Analysis of Subclinical Hypothyroidism With its Treatment in Patients After Coronary Artery Bypass Grafting
Heng WANG ; Lihuan LI ; Yuntai YAO ; Chenghui ZHOU ; Nengxin FANG ; Dong CHEN
Chinese Circulation Journal 2016;31(9):870-873
Objective: To study subclinical hypothyroidism (SCH) with its treatment in patients after coronary artery bypass grafting (CABG). Methods: A total of 1500 patients received CABG by the same surgical team in our hospital from 2010-06 to 2014-03 were retrospectively studied. According to thyroid function, the patients were divided into 2 groups: SCH group,n=107 and Normal group, n=1393. With 1:4 propensity score matching, there were 104 patients in SCH group and 416 patients in Normal group enrolled in our research. The rates of intra-aortic balloom pumping (IABP) implantation and peri-operational blood transfusion, mechanical ventilation time, new onsets of stroke, myocardial infarction and atrial ifbrillation, malignant arrhythmia, acute kidney injury and in-hospital mortality were observed. The outcome of treatment was assessed by single- and multi-factor analysis. Results: Compared with Normal group, SCH group showed increased mechanical ventilation time (23.3±47.9) h vs (15.0±5.5) h, P<0.05; more patients had mechanical ventilation time>12 h (89.4% vs 78.8%),P<0.05 and more patients had IABP implantation (3.8% vs 0.72%),P<0.05. SCH was related to mechanical ventilation time>12 h (OR=2.363, 95% CI 1.183-4.516) and IABP implantation (OR=6.126, 95% CI 1.190-31.537). The in-hospital death and other events were similar between 2 groups,P>0.05. Conclusion: Our research indicated that SCH was related to mechanical ventilation time and IABP implantation in patients after CABG.
9.Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose.
Li LIAO ; Hua HUA ; Jun-Ning ZHAO ; Heng LUO ; An-Dong YANG
China Journal of Chinese Materia Medica 2014;39(6):1101-1106
To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD < 15%). The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies. Pharmacokinetic parameters of THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.
Administration, Oral
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Dronabinol
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chemistry
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pharmacokinetics
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