AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgo...AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.展开更多
Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bi...Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.展开更多
AIM:To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS:Kupffer cells, isolated from the livers of control an...AIM:To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS:Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS:A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis.展开更多
Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site...Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha(PDGFR a) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFR a in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.展开更多
AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of c...AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.展开更多
To investigate the role of platelet membrane glycoprotein (GP) Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mea...To investigate the role of platelet membrane glycoprotein (GP) Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity (MFI), were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.展开更多
AIM: To investigate whether the expression of plateletderived growth factor receptor-α-positive(PDGFRα^+)-cells is altered in Hirschsprung's disease(HD).METHODS: HD tissue specimens(n = 10) were collected at the...AIM: To investigate whether the expression of plateletderived growth factor receptor-α-positive(PDGFRα^+)-cells is altered in Hirschsprung's disease(HD).METHODS: HD tissue specimens(n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus(n = 10). Immunolabelling of PDGFRα^+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα^+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα^+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.展开更多
BACKGROUND:Vascular endothelial growth factor(VEGF) induces bone marrow-derived mesenchymal stem cell(BMSC) differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas.However,the m...BACKGROUND:Vascular endothelial growth factor(VEGF) induces bone marrow-derived mesenchymal stem cell(BMSC) differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas.However,the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood.OBJECTIVE:To investigate the role of platelet-derived growth factor(PDGF) receptor(PDGFR) in BMSC differentiation and migration induced by VEGF.DESIGN,TIME AND SETTING:A parallel,controlled,in vitro experiment was performed at the Molecular Neurobiology & Neural Regeneration and Repairing Laboratory,Anhui Provincial Hospital of Anhui Medical University,China from June 2008 to March 2009.MATERIALS:U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences;mouse anti-human PDGFR and VEGF receptor(VEGFR) monoclonal antibodies were purchased from Peprotech,USA.METHODS:Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1,VEGFR-2,PDGFR-α,and PDGFR-β to block biological activity of related receptors,followed by induced differentiation with 50 μg/L VEGF.BMSCs induced with 50 μg/L VEGF alone served as the VEGF-induced group.The control group remained untreated.MAIN OUTCOME MEASURES:Cell surface markers were identified by flow cytometry;BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction;the Transwell model was used to observe cell migration.RESULTS:After blocking the PDGFR,VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor(vWF) expression.However,inhibition with VEGF receptor blocking agents,VEGF induced BMSCs to express CD-31 and vWF.Following inhibition of the PDGFR,the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased,as well as the number of BMSCs migrating to glioma cells.However,through the use of VEGF receptor blocking agents,the number of migrating cells remained unchanged.VEGF preculture increased the number of BMSCs migrating to gliomas.CONCLUSION:VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation.The VEGF/PDGFR pathway participates in BMSC directional migration to glioma.VEGF pretreatment increased efficiency of BMSC migration to glioma.展开更多
Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-...Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott's method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.展开更多
Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop new generative,potent and safe agents for inhibiting platelet aggregation and preventing abo...Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop new generative,potent and safe agents for inhibiting platelet aggregation and preventing above diseases are urgently required.Some traditional Chinese medicines of″Houxue Huayu″have been shown to inhibit platelet aggregation potently.In the present study the mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated and compared with ticlopidine.Four platelet aggregation inducers,ADP,arachidonic acid,collagen and thrombin were used in the study.It was found that puerarin and dl-PHPB specifically inhibited ADP induced platelet aggregation like ticlopidine did.However,salvianolic acid B inhibited both ADP and collagen induced platelet aggregations with similar potency.Due to existing two ADP receptor subtypes on platelets,P2Y1 and P2Y12,we studied the action of above compounds on the receptors and the signaling pathways.It was found that dl-PHPB decreased IP1 accumulation produced by ADP,but had no effect on IP1 level induced by m-3M3 FBS,an activator of PLC.M-3M3 FBS might attenuate the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation.In addition,dl-PHPB did not affect cyclic AMP formation in platelets by ADP,which is different from P2Y12 antagonist ticlopidine.Puerarin showed the similar effects of dl-PHPB.Therefore,the actions of dl-PHPB and puerarin might be through P2Y1receptor-PLC-βpathway.Salvianolic acid B did not reduce the IP1 accumulation stimulated by ADP.It might act on the receptor subtype P2Y12.Our results suggest that components of Chinese herb medicine might be a resource for development of novel anti-platelet drugs.展开更多
In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on...In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on platelets as the rhodocytin receptor.Thereafter,several studies have showed that platelet CLEC-2 isinvolved in lymphatic/blood vessel separation,tumormetastasis and thrombus formation.展开更多
BACKGROUND:The pharmacological action of traditional Chinese medicine compound is the comprehensive effect of the various ingredients,and the interactions of various ingredients are closely correlated with the final e...BACKGROUND:The pharmacological action of traditional Chinese medicine compound is the comprehensive effect of the various ingredients,and the interactions of various ingredients are closely correlated with the final effect.In order to reveal the compatibility mechanism of BHD's prescription in treating and preventing ischemic cerebrovascular disease,we needed explore the effect and relation of ingredients in the prescription.OBJECTIVE:To observe the effect of Buyang Huanwu decoction(BHD)and Astragalus mongholicus on the activity of platelet activating factor receptor(PAFR)in the platelet of rabbits in vitro,and investigate the mechanism of Astragalus mongholicus.DESIGN:A decomposed recipes study.SETTING:Guangzhou University of Traditional Chinese Medicine.MATERIALS:Five New Zealand rabbits,weighing 2-3 kg,both sexes,were used.BHD was composed of Sheng Huang Qi 120 g,Dang Gui Wei 6 g,Chi Shao 4.5 g,Chuan Xiong 3 g,Di Long 3 g,Tao Ren 3 g,Hong Hua 3 g.The prescription for activating blood circulation consisted of Dang Gui Wei 6 g,Chi Shao 4.5 g,Chuan Xiong 3 g,Di Long 3 g,Tao Ren 3 g and Hong Hua 3 g.The prescription for invigorating qi consisted of 120 g Sheng Huang Qi.The prepared herbal pieces were purchased from the traditional Chinese medicine Dispensary of Foshan Second People's Hospital,and appraised by Professor Xu from Science of Chinese Materia Medica College,Guangzhou University of Traditional Chinese Medicine.3H-PAF was supplied by Amersham Co.,Ltd.(specific activity:6.475 TBq/mmol;batch number:200402);PAF standard by Biomol Co.,Ltd.(batch number:P1318V).METHODS:The experiments were carried out in the Laboratory of Nuclear Medicine,Guangzhou University of Traditional Chinese Medicine from September to December 2004.①Injections of BHD,prescriptions for activating blood circulation and invigorating qi were prepared by the decoction and alcohol sedimentation technique.Rabbit common carotid artery blood(40 mL)was drawn via intubation to prepare platelet suspension of (0.8-1.0) ×1010L-1.②Determination of 3H-PAF and washed PAFR binding:The general combination tube(T) contained washed platelet-rich plasma(WPRP)380μL +3H-PAF(0.35 nmol/L)10μL+distilled water 5μL:The nonspecific binding tube(P)contained WPRP 380μL+3H-PAF(0.35 nmol/L)10μL+cold PAF(1μmol/L)5μL:The sample tube(Y)contained WPRP 380μL+3H-PAF(0.35 nmol/L)10μL+experimental medicine(injection of BHD,prescriptions for activating blood circulation or invigorating qi)5μL.The test was conducted for three times for each sample in the same way as mentioned above.The samples were shaken on the oscillator for 30 s,then bathed at 25℃ for 40 minutes,and the reaction was terminated with cold Tris buffer containing 0.1% BSA.multichannel cell detachment separator was used for vacuum suction to filter the separated free 3H-PAF,and the filter paper was washed with cold Tris buffer for four times,then dried in the baking oven(80℃)for 1 hour,and placed in xylol liquid scintillator,and the radioactivity was determined automatically by the liquid scintillation detector.The mean of the three parallel tubes was calculated.The specific binging inhibition rate was calculated:SBIR=[(T-Y)/(T-P)]×100%].③Univariate analysis of variance was conducted.And for comparison of each paired groups,the q test was adopted.MAIN OUTCOME MEASURES:Effect of BHD whole prescription,prescriptions for activating blood circulation and invigorating qi on the specific binding inhibition rate of 3H-PAF and PAFR.RESULTS: BHD,prescriptions for activating blood circulation and invigorating qi were all able to inhibit the specific binding of 3H-PAF to PAFR,the specific blinding inhibition rates were(45.90±7.50)%.(97.90±1.84)% and(26.75±2.48)%,respectively,and there were significant differences between every two groups(P＜0.01).CONCLUSION:Single Astragalus mongholicus(120 g)can inhibit the specific blinding of PAFR in the platelet of the rabbit with 3H-PAF,but the combination of Astragalus mongholicus with the drugs for activating blood circulation in BHD can significantly decrease the inhibiting action of the latter on PAFR activity of the platelet,reflecting the combined mechanism of "removing blood stasis without injuring the vital qi"in BHD.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of ...BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.展开更多
BACKGROUND: Studies have demonstrated that NG2-positive glial cells in the adult rats arepredominantly located in the gray and white matter of the cerebral cortex and hippocampus.Platelet-derived growth factor-α rece...BACKGROUND: Studies have demonstrated that NG2-positive glial cells in the adult rats arepredominantly located in the gray and white matter of the cerebral cortex and hippocampus.Platelet-derived growth factor-α receptor (PDGF-αR) cells are a subset of oligodendrocytes, whichare not as mature as NG2-positive cells. Distribution and migration of PDGF-αR-positive cells in therat brain remain poorly understood.OBJECTIVE: Using immunohistochemical methods, the distribution of oligodendrocyte precursorcells (PDGF-αR-positive) was analyzed in the adult rat brain.DESIGN, TIME AND SETTING: Immunohistochemical study was performed at the Department ofHistology and Embryology of the Third Military Medical University from September 2007 toSeptember 2008.MATERIALS: Rabbit anti-PDGF-αR polyclonal antibody was purchased from Santa CruzBiotechnology, USA. Streptomycin-avidin-biotin complex immunohistochemistry kit was purchasedfrom Zhongshan Goldenbridge Biotechnology, China.METHODS: Whole brains from 5 healthy, adult, Wistar rats were collected for immunohistochemistryand the mean value of PDGF-αR-expressing cells was quantified. The absolute values weretranslated to ranked data of high, moderate, and low grades (high grade: 10 positive cells; moderategrade: 5-9 cells; low grade: < 5 cells in a 400 x visual field). Based on the number of cell processesand branches, as well as the number of PDGF-αR-positive cells, in different regions, the cells wereclassified into three categories, i.e., type Ⅰ-Ⅲ. From type Ⅰ to type Ⅲ, the number of processesgradually increased.MAIN OUTCOME MEARSURES: The number and distribution of PDGF-αR-positive cells in differentbrain regions of adult rats.RESULTS: PDGF-αR-positive cells were located in the forebrain and midbrain, but not in thecerebellum or brainstem. In the olfactory bulb and hippocampus, a total of 60% PDGF-αR-positivecells were type I and these cells were not mature as others. In the cerebral cortex, olfactory system,hippocampus, and optic chiasma, where neuronal bodies aggregated, approximately 40% of thePDGF-αR-positive cells were type Ⅱ, with few type Ⅲ cells. In the white matter, corpus callosum,basal nucleus, and thalamus, PDGF-αR-positive cell density was moderate. In the olfactory bulb andhippocampus, PDGF-αR-positive cell density was high. PDGF-αR-positive cells were not observedin the cerebellum or brainstemCONCLUSION: PDGF-αR-positive cells were aggregated in the olfactory bulb and hippocampus inthe adult, rat brain, but few cells were detected in the cerebellum and brainstem.展开更多
Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived ...Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.展开更多
AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathologica...AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.展开更多
Thrombosis formation on disrupted atherosclerotic plaque is the most common acuse of cardiovascular diseases, in the pathophysiology, increased platelet reactivity is a descriptor of the risk of cardiovascular events ...Thrombosis formation on disrupted atherosclerotic plaque is the most common acuse of cardiovascular diseases, in the pathophysiology, increased platelet reactivity is a descriptor of the risk of cardiovascular events in healthy persons and in patients with overt coronary artery disease. Regardless of the stimulus for activation platelet-platelet interation and thrombus formation is ultimately regulated through the GP Ⅱ b/Ⅲ a receptor展开更多
Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether...Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphology of oligodendrocyte precursor cells labeled by NG2 or PDGFRα in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive(NG2^+) cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2^+ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRα positive(PDGFRα^+) cells were coincident with NG2^+ cells. The colocalization of NG2 and PDGFRα in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRα were predominantly in the early postnatal stage of development. The numbers of NG2^+/PDGFRα^+ cells and PDGFRα^+ cells decreased, but the number of NG2^+ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRα, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRα are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.展开更多
基金the National Natural Science Foundation of China, No. 30300465
文摘AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.
基金The National Natural Science Foundation of China, No. 30772883
文摘Acute pancreatitis (AP) causes release of platelet- activating factor (PAF), which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF is a cell surface secretion of bioactive lipid, which could produce physiological and pathological effects by binding to its cell surface receptor called platelet-activating factor receptor (PAF-R). Studies showed that PAF participates in the occurrence and development of AP and administration of platelet-activating factor receptor antagonists (PAF-RAs) could significantly reduce local and systemic events after AP. PAF has also been implicated as a key mediator in the progression of severe AP, which can lead to complications and unacceptably high mortality rates. Several classes of PAF-RA show PAF- RAs significant local and systemic effects on reducing inflammatory changes. As a preventive treatment, PAF-RA could block a series of PAF-mediated inflammatory injury and thus improve the prognosis of AP. This review introduces the important role of PAF-RA in the treatment of AP.
基金Supported by the Key Scientific and Technological Research Foundation of the National 863 Program,No.2003AA208106Medical Outstandard Foundation of Army,No.04J020
基金the Major Science and Technology Research Fund of the National 863 Program, No. 2003AA208106the Fund for Outstanding Medical Scientists of PLA, No. 04J020
文摘AIM:To determine the platelet-activating factor (PAF) synthesis and its receptor expression in Kupffer cells in rat carbon tetrachloride-induced cirrhosis. METHODS:Kupffer cells, isolated from the livers of control and CCl4-induced cirrhotic rats, were placed in serum-free medium overnight. PAF saturation binding, ET-1 saturation and competition binding were assayed. ET-1 induced PAF synthesis, mRNA expression of PAF, preproendothelin-1, endothelin A (ETA) and endothelin B (ETB) receptors were also determined. RESULTS:A two-fold increase of PAF synthesis (1.42 ± 0.14 vs 0.66 ± 0.04 pg/μg DNA) and a 1.48-fold increase of membrane-bound PAF (1.02 ± 0.06 vs 0.69 ± 0.07 pg/μg DNA) were observed in activated Kupffer cells of cirrhotic rats. The application of ET-1 to Kupffer cells induced PAF synthesis in a concentration-dependent manner in both cirrhotic and normal rats via ETB receptor, but PAF synthesis in the activated Kupffer cells was more effective than that in the normal Kupffer cells. In activated Kupffer cells, PAF receptor expression and PAF binding capacity were markedly enhanced. Activated Kupffer cells raised the [125I]-ET-1 binding capacity, but changed neither the affinity of the receptors, nor the expression of ETA receptor. CONCLUSION:Kupffer cells in the course of CCl4-induced cirrhosis are the main source of increased PAF. ET-1 is involved endogenously in stimulating the PAF synthesis in activated Kupffer cells via ETB receptor by paracrine. ETA receptor did not appear in activated Kupffer cells, which may exacerbate the hepatic and extrahepatic complications of cirrhosis.
基金supported by the W.W. Smith Charitable Trust and Department of Defense (CDMRP) grants W81XWH-09-1-0593 and W81XWH-09-1-0724
文摘Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha(PDGFR a) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFR a in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.
基金Supported by The National Natural Science Foundation of China,No.31671192 and No.31571180Foundation of Xin Hua Hospital,No.JZPI201708
文摘AIM To investigate the distribution and function of interstitialcells of Cajal(ICCs) and platelet-derived growth factor receptor-α positive(PDGFRα+) cells in the proximal and distal colon.METHODS The comparison of colonic transit in the proximal and distal ends was performed by colonic migrating motor complexes(CMMCs). The tension of the colonic smooth muscle was examined by smooth muscle spontaneous contractile experiments with both ends of the smooth muscle strip tied with a silk thread. Intracellular recordings were used to assess electrical field stimulation(EFS)-induced inhibitory junction potentials(IJP) on the colonic smooth muscle. Western blot analysis was used to examine the expression levels of ICCs and PDGFRα in the colonic smooth muscle.RESULTS Treatment with NG-nitro-L-arginine methyl ester hydrochloride(L-NAME) significantly increased the CMMC frequency and spontaneous contractions, especially in the proximal colon, while treatment with MRS2500 increased only distal CMMC activity and smooth muscle contractions. Both CMMCs and spontaneous contractions were markedly inhibited by NPPB, especially in the proximal colon. Accordingly, CyPPA sharply inhibited the distal contraction of both CMMCs and spontaneous contractions. Additionally, the amplitude of stimulationinduced nitric oxide(NO)/ICC-dependent slow IJPs(sIJPs) by intracellular recordings from the smooth muscles in the proximal colon was larger than that in the distal colon, while the amplitude of electric field stimulationinduced purinergic/PDGFRα-dependent fast IJPs(fIJPs) in the distal colon was larger than that in the proximal colon. Consistently, protein expression levels of c-Kit and anoctamin-1(ANO1) in the proximal colon were much higher, while protein expression levels of PDGFRα and small conductance calcium-activated potassium channel 3(SK3) in the distal colon were much higher.CONCLUSION The ICCs are mainly distributed in the proximal colon and there are more PDGFRα+ cells are in the distal colon, which generates a pressure gradient between the two ends of the colon to propel the feces to the anus.
基金supported by a grant from the National Natural Science Foundation of China (No. 30572441).
文摘To investigate the role of platelet membrane glycoprotein (GP) Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy (HT), the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity (MFI), were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant (P<0.05). There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects (P>0.05). It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.
基金Supported by National Children’s Research Centre/Children’s Medical Research Foundation,Ireland
文摘AIM: To investigate whether the expression of plateletderived growth factor receptor-α-positive(PDGFRα^+)-cells is altered in Hirschsprung's disease(HD).METHODS: HD tissue specimens(n = 10) were collected at the time of pull-through surgery, while colonic control samples were obtained at the time of colostomy closure in patients with imperforate anus(n = 10). Immunolabelling of PDGFRα^+-cells was visualized using confocal microscopy to assess the distribution of these cells, while Western blot analysis was undertaken to quantify PDGFRα protein expression.RESULTS: Confocal microscopy revealed PDGFRα+-cells within the mucosa, myenteric plexus and smooth muscle in normal controls, with a marked reduction in PDGFRα^+-cells in the HD specimens. Western blotting revealed high levels of PDGFRα protein expression in normal controls, while there was a striking decrease in PDGFRα protein expression in the HD colon.CONCLUSION: These findings suggest that the altered distribution of PDGFRα^+-cells in both the aganglionic and ganglionic HD bowel may contribute to the motility dysfunction in HD.
基金the National Natural Science Foundation of China,No.30672166
文摘BACKGROUND:Vascular endothelial growth factor(VEGF) induces bone marrow-derived mesenchymal stem cell(BMSC) differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas.However,the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood.OBJECTIVE:To investigate the role of platelet-derived growth factor(PDGF) receptor(PDGFR) in BMSC differentiation and migration induced by VEGF.DESIGN,TIME AND SETTING:A parallel,controlled,in vitro experiment was performed at the Molecular Neurobiology & Neural Regeneration and Repairing Laboratory,Anhui Provincial Hospital of Anhui Medical University,China from June 2008 to March 2009.MATERIALS:U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences;mouse anti-human PDGFR and VEGF receptor(VEGFR) monoclonal antibodies were purchased from Peprotech,USA.METHODS:Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1,VEGFR-2,PDGFR-α,and PDGFR-β to block biological activity of related receptors,followed by induced differentiation with 50 μg/L VEGF.BMSCs induced with 50 μg/L VEGF alone served as the VEGF-induced group.The control group remained untreated.MAIN OUTCOME MEASURES:Cell surface markers were identified by flow cytometry;BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction;the Transwell model was used to observe cell migration.RESULTS:After blocking the PDGFR,VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor(vWF) expression.However,inhibition with VEGF receptor blocking agents,VEGF induced BMSCs to express CD-31 and vWF.Following inhibition of the PDGFR,the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased,as well as the number of BMSCs migrating to glioma cells.However,through the use of VEGF receptor blocking agents,the number of migrating cells remained unchanged.VEGF preculture increased the number of BMSCs migrating to gliomas.CONCLUSION:VEGF interacts with PDGFRs on the BMSC surface to attract BMSC directional migration and induce BMSC differentiation.The VEGF/PDGFR pathway participates in BMSC directional migration to glioma.VEGF pretreatment increased efficiency of BMSC migration to glioma.
基金supported by the National Natural Science Foundation of China,No.30471934
文摘Traumatic brain injury causes gene expression changes in different brain regions. Occurrence and development of traumatic brain injury are closely related, involving expression of three factors, namely cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. However, little is known about the correlation of these three factors and brain neuronal injury. In this study, primary cultured rat hippocampal neurons were subjected to fluid percussion injury according to Scott's method, with some modifications. RT-PCR and semi-quantitative immunocytochemical staining was used to measure the expression levels of cyclooxygenase-2, glutamate receptor-2, and platelet activating factor receptor. Our results found that cyclooxygenase-2 expression were firstly increased post-injury, and then decreased. Both mRNA and protein expression levels reached peaks at 8 and 12 hours post-injury, respectively. Similar sequential changes in glutamate receptor 2 were observed, with highest levels mRNA and protein expression at 8 and 12 hours post-injury respectively. On the contrary, the expressions of platelet activating factor receptor were firstly decreased post-injury, and then increased. Both mRNA and protein expression levels reached the lowest levels at 8 and 12 hours post-injury, respectively. Totally, our findings suggest that these three factors are involved in occurrence and development of hippocampal neuronal injury.
文摘Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop new generative,potent and safe agents for inhibiting platelet aggregation and preventing above diseases are urgently required.Some traditional Chinese medicines of″Houxue Huayu″have been shown to inhibit platelet aggregation potently.In the present study the mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated and compared with ticlopidine.Four platelet aggregation inducers,ADP,arachidonic acid,collagen and thrombin were used in the study.It was found that puerarin and dl-PHPB specifically inhibited ADP induced platelet aggregation like ticlopidine did.However,salvianolic acid B inhibited both ADP and collagen induced platelet aggregations with similar potency.Due to existing two ADP receptor subtypes on platelets,P2Y1 and P2Y12,we studied the action of above compounds on the receptors and the signaling pathways.It was found that dl-PHPB decreased IP1 accumulation produced by ADP,but had no effect on IP1 level induced by m-3M3 FBS,an activator of PLC.M-3M3 FBS might attenuate the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation.In addition,dl-PHPB did not affect cyclic AMP formation in platelets by ADP,which is different from P2Y12 antagonist ticlopidine.Puerarin showed the similar effects of dl-PHPB.Therefore,the actions of dl-PHPB and puerarin might be through P2Y1receptor-PLC-βpathway.Salvianolic acid B did not reduce the IP1 accumulation stimulated by ADP.It might act on the receptor subtype P2Y12.Our results suggest that components of Chinese herb medicine might be a resource for development of novel anti-platelet drugs.
文摘In 1995,Huang et al.reported that rhodocytin,asnake toxin purified from callosdasma rhodostoma venomstimulates platelet aggregation.Ten years later,Suzuki-Inoue et al.identified C-type lectin-like receptor 2(CLEC-2)on platelets as the rhodocytin receptor.Thereafter,several studies have showed that platelet CLEC-2 isinvolved in lymphatic/blood vessel separation,tumormetastasis and thrombus formation.
基金grants from Scientific Planning Program of Guangdong Province, No. 2004B36001009Scientific Research Funds of Guangdong Bureau of Traditional Chinese Medicine, No. 30002+1 种基金 Scientific Development Special Planning Funds of Foshan City, No. 200124Medical Scientific Research Program of Foshan City, No. 2000096
文摘BACKGROUND:The pharmacological action of traditional Chinese medicine compound is the comprehensive effect of the various ingredients,and the interactions of various ingredients are closely correlated with the final effect.In order to reveal the compatibility mechanism of BHD's prescription in treating and preventing ischemic cerebrovascular disease,we needed explore the effect and relation of ingredients in the prescription.OBJECTIVE:To observe the effect of Buyang Huanwu decoction(BHD)and Astragalus mongholicus on the activity of platelet activating factor receptor(PAFR)in the platelet of rabbits in vitro,and investigate the mechanism of Astragalus mongholicus.DESIGN:A decomposed recipes study.SETTING:Guangzhou University of Traditional Chinese Medicine.MATERIALS:Five New Zealand rabbits,weighing 2-3 kg,both sexes,were used.BHD was composed of Sheng Huang Qi 120 g,Dang Gui Wei 6 g,Chi Shao 4.5 g,Chuan Xiong 3 g,Di Long 3 g,Tao Ren 3 g,Hong Hua 3 g.The prescription for activating blood circulation consisted of Dang Gui Wei 6 g,Chi Shao 4.5 g,Chuan Xiong 3 g,Di Long 3 g,Tao Ren 3 g and Hong Hua 3 g.The prescription for invigorating qi consisted of 120 g Sheng Huang Qi.The prepared herbal pieces were purchased from the traditional Chinese medicine Dispensary of Foshan Second People's Hospital,and appraised by Professor Xu from Science of Chinese Materia Medica College,Guangzhou University of Traditional Chinese Medicine.3H-PAF was supplied by Amersham Co.,Ltd.(specific activity:6.475 TBq/mmol;batch number:200402);PAF standard by Biomol Co.,Ltd.(batch number:P1318V).METHODS:The experiments were carried out in the Laboratory of Nuclear Medicine,Guangzhou University of Traditional Chinese Medicine from September to December 2004.①Injections of BHD,prescriptions for activating blood circulation and invigorating qi were prepared by the decoction and alcohol sedimentation technique.Rabbit common carotid artery blood(40 mL)was drawn via intubation to prepare platelet suspension of (0.8-1.0) ×1010L-1.②Determination of 3H-PAF and washed PAFR binding:The general combination tube(T) contained washed platelet-rich plasma(WPRP)380μL +3H-PAF(0.35 nmol/L)10μL+distilled water 5μL:The nonspecific binding tube(P)contained WPRP 380μL+3H-PAF(0.35 nmol/L)10μL+cold PAF(1μmol/L)5μL:The sample tube(Y)contained WPRP 380μL+3H-PAF(0.35 nmol/L)10μL+experimental medicine(injection of BHD,prescriptions for activating blood circulation or invigorating qi)5μL.The test was conducted for three times for each sample in the same way as mentioned above.The samples were shaken on the oscillator for 30 s,then bathed at 25℃ for 40 minutes,and the reaction was terminated with cold Tris buffer containing 0.1% BSA.multichannel cell detachment separator was used for vacuum suction to filter the separated free 3H-PAF,and the filter paper was washed with cold Tris buffer for four times,then dried in the baking oven(80℃)for 1 hour,and placed in xylol liquid scintillator,and the radioactivity was determined automatically by the liquid scintillation detector.The mean of the three parallel tubes was calculated.The specific binging inhibition rate was calculated:SBIR=[(T-Y)/(T-P)]×100%].③Univariate analysis of variance was conducted.And for comparison of each paired groups,the q test was adopted.MAIN OUTCOME MEASURES:Effect of BHD whole prescription,prescriptions for activating blood circulation and invigorating qi on the specific binding inhibition rate of 3H-PAF and PAFR.RESULTS: BHD,prescriptions for activating blood circulation and invigorating qi were all able to inhibit the specific binding of 3H-PAF to PAFR,the specific blinding inhibition rates were(45.90±7.50)%.(97.90±1.84)% and(26.75±2.48)%,respectively,and there were significant differences between every two groups(P＜0.01).CONCLUSION:Single Astragalus mongholicus(120 g)can inhibit the specific blinding of PAFR in the platelet of the rabbit with 3H-PAF,but the combination of Astragalus mongholicus with the drugs for activating blood circulation in BHD can significantly decrease the inhibiting action of the latter on PAFR activity of the platelet,reflecting the combined mechanism of "removing blood stasis without injuring the vital qi"in BHD.
基金Supported by National Natural Science Foundation of China,No.81601692Program of Liaoning Province Department of Education,No.LK2016002
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs) associated with neurofibromatosis are uncommon compared to their gastrointestinal counterparts. Patients with neurofibromatosis type 1(NF-1) have an increased risk of developing gastrointestinal tumors, including rare types such as GIST.CASE SUMMARY A 60-year-old male Chinese patient was diagnosed with NF-1 10 years ago and presented with upper abdominal discomfort and black stools. Endoscopic ultrasonography and an enhanced abdominal computed tomography scan revealed a mass located 4 cm from the muscular layer of the descending duodenum. A 59-year-old Chinese woman who was diagnosed with NF-1 25 years ago presented with sudden unconsciousness and black stools. Multiple masses in the duodenum were noted by echogastroscopy and an enhanced abdominal computed tomography scan. Both patients presented with cutaneous neurofibromas. The histologic examination of tumors from both patients revealed spindle cells and low mitotic activity. Immunohistochemically, the tumor cells showed strong positivity for KIT(CD117), DOG-1, CD34, and Dehydrogenase Complex Subunit B, and negativity for SMA, desmin, S-100, and β-catenin. None of the six tumors from two patients had KIT exon 9, 11, 13, or 17 or platelet-derived growth factor receptor α exon 12 or 18 mutation, which is a typical finding for sporadic GISTs. None of the six tumors from the two patients had a BRAFV600 E mutation. The patients were alive and well during the follow-up period(range:0.6-5 yr).CONCLUSION There have been only a few previous reports of GISTs associated with NF-1.Although GISTs associated with NF-1 have morphologic and immunohistochemical similarities with GISTs, the pathogenesis, incidence,genetic background, and prognosis are not completely known. A medical history of NF-1 in a patient who has gastrointestinal bleeding or anemia and an intraabdominal mass with nonspecific computed tomography features may help in diagnosing GIST by virtue of the well-known association of these two entities.Molecular genetic studies of cases indicated that GISTs in NF-1 patients have a different pathogenesis than sporadic GISTs.
基金Supported by: the National Natural Science Foundation of China, No. 30572364the Natural Science Foundation of Chongqing, No. 2007BB5008
文摘BACKGROUND: Studies have demonstrated that NG2-positive glial cells in the adult rats arepredominantly located in the gray and white matter of the cerebral cortex and hippocampus.Platelet-derived growth factor-α receptor (PDGF-αR) cells are a subset of oligodendrocytes, whichare not as mature as NG2-positive cells. Distribution and migration of PDGF-αR-positive cells in therat brain remain poorly understood.OBJECTIVE: Using immunohistochemical methods, the distribution of oligodendrocyte precursorcells (PDGF-αR-positive) was analyzed in the adult rat brain.DESIGN, TIME AND SETTING: Immunohistochemical study was performed at the Department ofHistology and Embryology of the Third Military Medical University from September 2007 toSeptember 2008.MATERIALS: Rabbit anti-PDGF-αR polyclonal antibody was purchased from Santa CruzBiotechnology, USA. Streptomycin-avidin-biotin complex immunohistochemistry kit was purchasedfrom Zhongshan Goldenbridge Biotechnology, China.METHODS: Whole brains from 5 healthy, adult, Wistar rats were collected for immunohistochemistryand the mean value of PDGF-αR-expressing cells was quantified. The absolute values weretranslated to ranked data of high, moderate, and low grades (high grade: 10 positive cells; moderategrade: 5-9 cells; low grade: < 5 cells in a 400 x visual field). Based on the number of cell processesand branches, as well as the number of PDGF-αR-positive cells, in different regions, the cells wereclassified into three categories, i.e., type Ⅰ-Ⅲ. From type Ⅰ to type Ⅲ, the number of processesgradually increased.MAIN OUTCOME MEARSURES: The number and distribution of PDGF-αR-positive cells in differentbrain regions of adult rats.RESULTS: PDGF-αR-positive cells were located in the forebrain and midbrain, but not in thecerebellum or brainstem. In the olfactory bulb and hippocampus, a total of 60% PDGF-αR-positivecells were type I and these cells were not mature as others. In the cerebral cortex, olfactory system,hippocampus, and optic chiasma, where neuronal bodies aggregated, approximately 40% of thePDGF-αR-positive cells were type Ⅱ, with few type Ⅲ cells. In the white matter, corpus callosum,basal nucleus, and thalamus, PDGF-αR-positive cell density was moderate. In the olfactory bulb andhippocampus, PDGF-αR-positive cell density was high. PDGF-αR-positive cells were not observedin the cerebellum or brainstemCONCLUSION: PDGF-αR-positive cells were aggregated in the olfactory bulb and hippocampus inthe adult, rat brain, but few cells were detected in the cerebellum and brainstem.
文摘Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.
基金Supported by the Scientific research Fund of Peking University Cancer Hospital,No.2013 zizhu-8
文摘AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.
文摘Thrombosis formation on disrupted atherosclerotic plaque is the most common acuse of cardiovascular diseases, in the pathophysiology, increased platelet reactivity is a descriptor of the risk of cardiovascular events in healthy persons and in patients with overt coronary artery disease. Regardless of the stimulus for activation platelet-platelet interation and thrombus formation is ultimately regulated through the GP Ⅱ b/Ⅲ a receptor
基金supported by grants from the National Natural Science Foundation of China,No.31100769
文摘Platelet-derived growth factor receptor alpha(PDGFRα) is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphology of oligodendrocyte precursor cells labeled by NG2 or PDGFRα in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive(NG2^+) cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2^+ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRα positive(PDGFRα^+) cells were coincident with NG2^+ cells. The colocalization of NG2 and PDGFRα in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRα were predominantly in the early postnatal stage of development. The numbers of NG2^+/PDGFRα^+ cells and PDGFRα^+ cells decreased, but the number of NG2^+ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRα, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRα are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.
