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OBJECTIVE To study the neuroprotective effects of Shenzao jianna o oral liquid （SZJN）on Alzheimer ’s disease （AD）model mice and its mechanism. METHODS The mice were randomly divided into sham operation group ，model group ， Donepezil hydrochloride tablet group （0.65 mg/kg），SZJN low-dose ，medium-dose and high-dose groups （0.3，1.5 and 7.5 g/kg， calculated by crude drug quantity ），with 12 mice in each group ，half male and half female. Each group was given relevant medicine（intragastric administration of water at constant volume in sham operation group and model group ），twice a day ，for consecutive 28 d. On the 15th day of administration ，intracerebroventricular injection of β-amyloid 1-42（Aβ1-42）combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein （CREB） and expression of brain-derived neurotrophic factor （BDNF） in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group ，the escape latency of the model group was significantly prolonged ，and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced （P＜0.01）. The level of SOD in brain tissue ，the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly （P＜0.01），while the level of MDA increased significantly （P＜ 0.01）. In hippocampal CA 1 area and cortical tissue ，nerve cells showed significantly decreased number ，the disordered arrangement and large gap ；the shape of nucleus was irregular and deeply stained ，and Nissl body was blurred ，loosely arranged and the number decreased. Compared with model group ，the escape latency of mice in each dose group of SZJN was significantly shortened ，and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly jing- increased（P＜0.01）. Above indexes of brain tissue in mice were reversed sig nificantly in SZJN high-dose group （P＜0.01），and pathological damage of brain tiss ue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice ，and alleviate the pathological injury and oxidative stress of brain tissue ，which may be related to the activation of CREB/BDNF signaling pathway.
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Objective:To propose a markless patient setup workflow based on the optical surface monitoring system (AlignRT) and open-face mask immobilization for whole-course head tumor radiotherapy, assess the setup time and repositioning frequency of the proposed workflow, and conduct a comparative analysis of the differences, correlation, and consistency of the setup errors of the AlignRT and cone beam CT (CBCT) systems.Methods:A retrospective analysis was conducted for the data on the errors of 132 fractionated setup based on open-face mask immobilization of 33 head tumor patients. AlignRT-guided markless patient setup workflow was applied throughout the radiotherapy. Meanwhile, the body structures automatically generated by the treatment planning system were used as body references. The 6-degree-of-freedom (6DoF) setup errors (lateral, vertical, longitudinal, rotation, pitch, roll, and yaw directions), setup time, and repositioning frequency of the AlignRT and CBCT systems were recorded and analyzed. The Wilcoxon and Spearman analyses were used to statistically assess the differences and correlation of the setup errors of the two systems. Moreover, the Bland-Altman analysis was employed to evaluate the consistency of the two systems.Results:The 6DoF setup errors of CBCT were within the clinical tolerance (linear motions: -0.30 to 0.30 cm; rotational motions: -2.0° to 2.0°). The setup time and repositioning frequency of CBCT were (98 ± 31) s and 1.51% (2/132), respectively. There was no significant difference in setup errors between the two systems except those in x-axis ( Z = -3.11, P= 0.002), y-axis ( Z = -7.40, P<0.001), and Pitch ( Z= -4.48, P<0.001). There was a significant positive correlation between the setup errors along lateral ( rs = 0.47, P<0.001) and vertical ( rs = 0.29, P = 0.001) directions, rotation (Rtn; rs = 0.47, P<0.001), pitch (Pitch; rs = 0.28, P = 0.001) and roll (Roll; rs = 0.45, P<0.001) of the two systems. The 95% limits of agreement (95% LoA) of 6DoF setup errors were -0.12 to 0.09 cm, -0.07 to 0.17 cm, -0.19 to 0.20 cm, -1.0° to 0.9 °, -1.0° to 1.5°, and -0.9° to 1.0°, respectively. The 95% confidence interval (95% CI) of 95% LoA was -0.14 to 0.11 cm, -0.09 to 0.19 cm, -0.23 to 0.23 cm, -1.2° to 1.1°, -1.2° to 1.7°, and-1.0° to 1.1°, respectively, all of which were within the permissible error ranges. The 6DoF setup error difference of 3.41% (27/792< 5%) was beyond the 95% LoA. The maximum absolute differences of 6DoF setup errors within the 95% LoA were 0.12, 0.16, 0.19 cm, 0.9°, 1.5°, and 1.0°, respectively. Conclusions:The proposed markless setup workflow based on AlignRT combined with open-face mask immobilization for whole-course head tumor radiotherapy exhibits reasonable agreement and consistency with the patient setup using CBCT, with acceptable clinical efficiency. It can be applied to the first radiotherapy and the real-time monitoring of therapy to improve the safety and thus is of value in clinical applications.
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OBJECTIVE：To study the effects and mechanism of panaxadiol （PD） on Tau protein phosphorylation in the SH-SY5Y cells transfected with APP gene（APP-SH-SY5Y）. METHODS ：The target of PD and non-receptor tyrosine kinases Fyn was verified by molecular docking. SH-SY 5Y cells were cultured in vitro ，and the APP-SH-SY 5Y cell models and green fluorescent （GFP）-SH-SY5Y cell model （control cell ）was constructed. The expression of Aβ1-42 was detected so as to verify the success of APP-SH-SY5Y cell model. Taking GFP-SH-SY 5Y cells as control ，the effects of 5，10，20，30，40 μmol/L PD and 125，250， 500，1 000，2 000 nmol/L PP 2（Fyn inhibitor ，positive control ）on the survival rate of APP-SH-SY 5Y cells were detected by CCK-8 assay after treated for 24 h，so as to confirm the optimal concentration. The concentration of Ca 2 + ，the ratio fophosphorylated Tau protein （p-Tau）/Tau，phosphorylatedn Src（p-Src）/Fyn and phosphorylated glutamate receptor 2B（p-GluN2B）/ GluN2B were detected in APP-SH-SY 5Y cells after trated with the optimal concentration of PD and PP 2 for 24 h. RESULTS ：The results of molecular simulation docking showed that PD could target Fyn protein. Compared with GFP-SH-SY 5Y cells ，the protein expression of Aβ1-42 in APP-SH-SY 5Y cell were increased significantly （P＜0.01）. The optimal concentration of PD and PP 2 were 20 μmol/L and 500 nmol/L. The 20 μmol/L PD and 500 nmol/L PP 2 could increase the survival rate of the cells and reduced the concentration of Ca 2+，the ratio of p-Tau/Tau ，p-Src/Fyn，and p-GluN 2B/GluN2B. CONCLUSIONS：PD can reduce the the phosphorylation of Tau protein through inhibiting Fyn/GluN 2B signaling pathway.
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Objective:To analyze and compare the radiation dose and image quality of kilo-voltage cone beam CT systems on different Varian accelerator platforms, providing data to support clinical decisions on selecting optimal protocols for image-guided radiotherapy based on cost-effective ratio (image quality / radiation dose).Methods:The radiation dose and image quality of various CBCT systems and scanning protocols on Varian Edge, Truebeam and ix (new and old) LINACs were obtained using a CT dose index (CTDI) phantom combined with a CT ionization chamber and a Catphan604 phantom, respectively. Figure of merit (FOM) was used to evaluate the cost-effective ratio of the image guidance schemes.Results:Considerable inter-system varieties of FOMs were observed, varying from 0.65 (Image Gently-full trajectory) to 48.46 (Image Gently-half trajectory). The inter-protocol varieties were also large, where the mean±SD was 22.14±13.47.Conclusions:Considering the explicit inter-system and inter-protocol varieties, it is clinically favorable to evaluate the image guidance schemes based on machine-specific measurement. For instance, parameters and equipment with low CTDI w can be beneficial for dose-sensitive patients. High CNR regimen favors patients with high image quality requirements. For ordinary patients, cost-effective ratio in terms of FOM can be very helpful to guide the decision-making of clinical image-guided radiotherapy.
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Objective:To build patient setup workflow based on the optical surface monitoring system (OSMS) in postoperative radiotherapy for breast cancer, and compare the setup accuracy and PTV margin between OSMS based setup and conventional skin marker based method.Methods:The setup data of 20 cases of postoperative radiotherapy for breast cancer were retrospectively analyzed and divided into two groups: OSMS setup group and conventional skin marker setup group with 10 patients in each group. All CBCT rigid registration values in six dimensions ( x, y, z, Rtn, Pitch, Roll) were obtained, and the absolute value and distribution of errors were statistically analyzed by single sample t-test and χ2-test respectively. Finally, the CTV-PTV margins were compared using the extension formula. Results:The mean values in OSMS setup group and conventional skin marker setup group in sixdirections were 0.18 and 0.18 cm, 0.12 and 0.13 cm, 0.13 and 0.23 cm, 0.55° and 0.74°, 0.63° and 0.99°, 0.67° and 0.68°, respectively, while the standard deviations were 0.13 and 0.12 cm, 0.09 and 0.09 cm, 0.11 and 0.16 cm, 0.37° and 0.55°, 0.53° and 0.65°, 0.42° and 0.55°, respectively. The setup error differed in both z and Pitch directions( t=3.53, 2.98, P<0.05), while the error distribution rate difference was statistically significant between two groups in z direction( χ2=11.090, P<0.05). The CTV-PTV margins in OSMS setup group and conventional skin marker setup group were 0.28 and 0.26 cm, 0.21 and 0.20 cm, 0.24 and 0.35 cm, respectively. Conclusions:The proposed OSMS-based patient setup work flow is better than the conventional skin marker based method in setup accuracy, with significant setup error differences in z and Pitch directions. The proposed OSMS workflow is of potential clinical benefit.
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OBJECTIVE@#To investigate the effect of osthole on the expression of amyloid precursor protein (APP) in Alzheimer's disease (AD) cell model and its mechanism.@*METHODS@#The SH-SY5Y cell with over expression of APP was established by transfection by liposome 2000. The cells were treated with different concentrations of osthole, and the cell viability was determined by MTT and lactate dehydrogenase (LDH) assay. The differentially expressed miRNAs with and without osthole treatment were detected by miRNA array, and the target genes binding to the differentially expressed miRNAs were identified and verified by databases and Cytoscape. After the inhibitor of the differentially expressed miRNA was transduced into cells, the changes of APP and amyloid β (Aβ) protein were determined by immunofluorescence cytochemistry, and the mRNA expression of APP was determined by RT-PCR.@*RESULTS@#The AD cell model with over expression of APP was established successfully. The results of MTT and LDH assay showed that osthole had a protective effect on cells and alleviated cell damage. miR-101a-3p was identified as the differentially expressed miRNA, which was binding to the 3'-UTR of APP. Compared with APP group, the expression of APP and Aβ protein and APP mRNA increased in the miR-101a-3p inhibitor group (all <0.01), while the expression of APP and Aβ protein and APP mRNA decreased in the cells with osthole treatment (all <0.01).@*CONCLUSIONS@#Osthole inhibits the expression of APP by up-regulating miR-101a-3p in AD cell model.
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Humans , Alzheimer Disease , Amyloid beta-Peptides , Amyloid beta-Protein Precursor , Genetics , Cell Line , Coumarins , Pharmacology , Gene Expression Regulation , Genetics , MicroRNAs , Genetics , MetabolismABSTRACT
Aim To observate the effect of chemokine receptor(CXCR4) gene transfection on biological behavior of bone marrow mesenchymal stem cells in vitro.Methods Firstly, bone marrow mesenchymal stem cells were divided into three groups:GFP(transfected GFP into MSCs), CXCR4+(transfected CXCR4+ into MSCs) and CXCR4-(transfected CXCR4-into MSCs) group.Then, their capacity of proliferation, differentiation and migration ability (in vitro) was assessed with immunofluorescence cytochemistry method, flow cytometry assay and Transwell cell chemotaxis test.Results The high or low expression of CXCR4 had no effect on their ability of proliferation and differentiation into lung tissue.Compared with GFP group, however, CXCR4+-MSCs group significantly increased the number of migrating cells, while CXCR4——MSCs group showed no change in the number of migrating cells.Conclusions The proliferation and differentiation capacities are not affected by the high or low expression of CXCR4.The high expression of CXCR4 can significantly enhance the migration ability of MSCs to inflammatory lesions, and the low one has no effect on the migration of the cells.After the transplantation of MSCs, CXCR4′s high expression will access to the lesion area to participate in tissue repairing rapidly and largely, significantly enhancing the therapeutic efficacy.
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Aim To investigate the neuroprotective effects of osthole(Ost)on the primary cultured cortical neurons transfected with APP595/596 gene and its underlying mechanism.Methods Neonatal mouse cortical neurons were transfected with APP595/596 gene to establish AD cell models for the further study.Then,the cell viability was detected by CCK-8 assay,and the leakage of lactate dehydrogenase(LDH)was assayed by LDH kit to evaluate the injury degree.Transferase-mediated nick end labeling(TUNEL)was used to evaluate the cell apoptosis.The expression of β-amyloid peptide(Aβ)and β-site APP cleaving enzyme 1(BACE1)was measured by immunofluorescence,while the miRNA-107 was measured by RT-PCR.Results Compared to model group,Ost could significantly improve the neurons viability,decrease the LDH release and prevent the apoptosis.Ost also inhibited the expression of Aβ and BACE1 at protein level,while enhanced the expression of miRNA-107 at gene level.Conclusion Ost plays a neuroprotective role in neurons transfected with APP595/596 gene in part through up-regulating miRNA-107.
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Aim To investigate the effects of neurotro-phin-3 ( NT-3 ) gene overexpression on the differentia-tion into cholinergic neuron of neural stem cells ( NSCs) in vitro and its underlying mechanism. Meth-ods Brain-derived NSCs from newborn mice were iso-lated and cultured in vitro and determined by immuno-fluorescence. The NSCs were divided into three groups: NSCs, GFP-NSCs and NT-3-NSCs groups. The expression of NT-3 was detected by immunofluo-rescence and ELISA. Then, the ability of NSCs on dif-ferentiation into cholinergic neuron was detected by im-munofluorescence and RT-PCR, and the Acetylcholine Assay Kit was used for acetylcholine ( ACh) , and the expression of Hes1 , Mash1 and Ngn1 mRNA was de-termined by RT-PCR. Results The neurosphere dis-played Nestin and Sox 2-postive by immunofluores-cence, suggesting that the cultured cells were NSCs. The proportion of ChAT immunopositive cells was sig-nificantly higher in the NT-3-NSCs group than that in the other two groups ( P <0. 01 ) . Ach secretion in NT-3-NSCs was significantly elevated compared with the other two groups ( P <0. 01 ) . NSCs transfected with NT-3 increased the levels of Mash1 and Ngn1 mR-NA, and decreased the level of Hes1 mRNA ( P <0. 05 ) . Conclusion NT-3 can significantly promote the in vitro differentiation of NSCs into cholinergic neu-rons via probablly inhibiting Notch signaling pathway.
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OBJECTIVE:To investigate the protective effects of osthole on the nerves in model mice with craniocerebral injury. METHODS:Mice models of craniocerebral injury were established by craniotomy drill. There was a sham-operation group(isomet-ric normal saline),a model group (isometric normal saline) and osthole high,mediu,low dose groups (30,20,10 mg/kg). The drugs were given to the mice 1 h after successful establishment of the models,ip,once a day,for consecutive 14 d. Neurological severity score was conducted for the mice 12 h,3 d,7 d,14 d and 21 d after the establishment of models;HE stain was conduct-ed 7 d and 14 d thereafter and the wounds areas of brain were observed by microscope;the activity of myeloperoxidase(MPO)in the homogenate of mice’s brain tissues were determined 1 d and 3 d after the establishment of models;immunohistochemical meth-od was adopted to determine the expressions of the brain-derived neurotrophic factors (BDNF) and neurotrophic factor (NT) 3 in the mice’s brain tissues 7 d after the establishment of models. RESULTS:Compared with model group,the neurological severity scores of the mice in osthole high dose group and medium dose group were decreased 3 d,14 d and 21 d after the establishment of models;that in osthole high dose group were decreased 7 d after the establishment of models. The wounds areas of brain in osthole high dose group were smaller 7 d after the establishment of models;those in osthole high dose group and medium dose group were smaller 14 d after the establishment of models. The activity of MPO in the brain tissue in osthole high dose group was decreased 24 h and 72 h after the establishment of models.The expressions of the BDNF and NT-3 in the brain tissue homogenate in osthole high dose group and medium dose group were increased 7 d after the establishment of models,with significant differences(P<0.01 or P<0.05). CONCLUSIONS:Osthole has certain protective effects on the nerves in mice with craniocerebral injury. The mechanism may be related to improving the mice’s neurological functions,promoting wound healing,inhibiting the production of inflammato-ry factors,increasing the expression of neurotrophic factors.
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Aim To investigate the effect of osthole on neuron synapses infected APP gene and its underlying mechanism. Methods The neurons were divided into three groups:GFP, APP, APP+Ost groups. The neu-rons were infected APP gene with containing mutational site in vitro for mimicking the characterstics of Alzhei-mer’ s disease ( AD) . The cell viability was assessed by CCK-8 , the expression of synapsin-1 was deter-mined by immunofluorescence, and the concentration of PSD-95 and SYP were detected by ELISA. The ex-pressions of Aβ1-42 , CAMKK2 , phoshorylated AMPKα1 , AMPKα1 protein were determined by West-ern blot. Results Strong APP staining was visible in neurons infected with APP and abundant expression of Aβ1-42 , a neurotoxic oligomer. Compared with APP group, APP+Ost group significantly increased cell vi-ability, promoted the expression of synapsin-1, up-reg-ulated the concentration of PSD-95 and SYP, and de-creased the expressions of CAMKK2 and p-AMPKα1 . Conclusions Ost can protect the neuron synapses a-gainst infected with APP gene. Its neuroprotective effect may be related to inhibiting the CAMKK2/AMPK signal pathway.
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Aim To investigate the effects of osthol on cell apoptosis and inflammatory cell infiltration after brain stab wound injury in mice. Methods The mice underwent the stab wound injury by a needle, then were randomly divided into sham operation group, model group, osthol 10, 20, 30 mg · kg-1 treatment group. The main examinations included mice brain wa-ter content; the apoptotic cytokines Bax, Bcl-2, Caspase-3 mRNA expression were assessed by PT-PCR; immunohistochemistry staining was used to de-tect neutrophils (MPO) and microglia (Iba-1) infiltra-tion and Caspase-3 positive cell expression around in-jured lesions. Results Treatment with osthole 20, 30 mg·kg-1 group significantly reduced the water content in injured brain, improved the ratio of Bax/Bcl-2, and reduced the expression of apoptosis cytokine Caspase-3 mRNA. Osthole 30 mg·kg-1 treatment group obvious-ly reduced the infiltration of neutrophils and microglial cells and significantly reduced the number of apoptotic cells around the injured cerebral cortex. Conclusion Osthole has therapeutic effect on stab wound injury in mice, and the possible mechanism may be by reducing the infiltration of inflammatory cells and reducing apop-totic cells.
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Objective To investigate the effects of osthole on neural stem cells ( NSCs) differentiation and explore the potential mechanism. Methods Brain-derived NSCs from newborn mice were isolated and cultured in vitro and determined by immunofluorescence. The P5 generations of NSCs were placed in culture solution with osthole at concentrations of (0,10,50, 100 μmol·L-1 ) . The neuron, astrocyte and oligodendroglia cell differentiation were determined by immunofluorescence. The mRNA expression of Notch 1 and its target genes Mash 1 and Neurogenin 2 were assessed by RT-PCR. Results The neurosphere displayed Nestin and Sox 2-postive by immunofluorescence, suggesting that the cultured cells were NSCs. Osthole promoted NSCs differentiating into more neuron(P<0. 01) and oligodendrocyte(P<0. 05), but not astrocyte. Meanwhile, osthole significantly reduced the mRNA expression of Notch 1(P<0. 01) and increased Ngn 2(P<0. 01)at the dose of 100 μmol·L-1. Conclusion Osthole enhances NSCs differentiating into more neuron and oligodendrocyte via probablly inhibiting Notch signal pathway.
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Aim To investigate the effects of osthole ( Ost) on the ability of proliferation and differentiation in APP transduced neural stem cells( NSCs) , and neu-ronal apoptosis, in order to find related mechanism. Methods A model of Alzheimer′s disease( AD) cells was successfully established by transducing APP gene into NSCs in vitro. The ability of proliferation and dif-ferentiation was tested by staining. The viability of NSCs was determined by using CCK-8 assay. The cell apoptosis was tested by Hoechst 33258 staining. The expression of GSK-3β and β-catenin mRNA was deter-mined by RT-PCR. The expression of GSK-3β and β-catenin protein was determined by Western blot. Re-sults The ability of proliferation had increased by 10 . 24% with Ost treatment, compared with APP group. The ability of differentiation had increased by 6 . 74%with Ost treatment, compared with APP group. The vi-ability of NSCs had increased and cell apoptotic rate had decreased significantly. From the results of RT-PCR and Western blot, we could find the expression of GSK-3βmRNA and protein had decreased, and the ex-pression of β-catenin mRNA and protein had increased significantly, compared with APP group. Conclusion Ost could enhance the ability of proliferation and dif-ferentiation into more neurons of NSCs transducing APP gene, and reduce neuronal apoptosis. It might be relat-ed with activiting Wnt/β-catenin signaling pathway.
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AIM:To explore the protective effect of osthole on the SH-SY5Y cells transfected with APP595/596 gene, and to investigate the molecular mechanism.METHODS:The SH-SY5Y cells were transfected with APP595/596 gene in vitro for establishing a cell model to study the pathogenic role of amyloid β-protein ( Aβ) .The cell viability was detected by CCK-8 assay.The release of lactate dehydrogenase ( LDH) was determined by the colour reaction of dia-phorase-INT.The cell apoptotic rate was analyzed by flow cytometry.The expression of β-site APP cleaving enzyme 1 ( BACE1) at mRNA and protein levels was detected by RT-PCR and Western blot.The expression of Aβwas measured by the technique of immunofluorescence cytochemistry and Western blot.RESULTS: Treatment with osthole inhibited the LDH release, and increased the viability of the cells.The percentage of apoptotic cells was also significantly decreased. Osthole also inhibited the expression of BACE1 at mRNA and protein levels and the protein expression of Aβ.CONCLU-SION:Osthole has protective effect on SH-SY5Y cells transfected with APP595/596 gene.The mechanism may be associ-ation with inhibiting the mRNA and protein expression of BACE1.
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BACKGROUND:Neural stem cells have self-renewal and multidirectional differentiation potential, but under normal circumstances, the number of neural stem cells is less, and most cells are in the resting state. Thus, to promote the proliferation of neural stem cells is the key to the treatment of neurodegenerative diseases. OBJECTIVE:To investigate the effects of osthole on the proliferation of neural stem cells cultured in vitro, and to analyze its mechanism underlying promoting the proliferation. METHODS:Neural stem cells were cultured in vitro, and passage 3 cells were cultured with different concentrations of osthole(10, 50 and 100μmol/L). After 24 hours, cellvitality was determined by cellcounting kit-8. After 3, 5, 7 days of further culture, the radius of neurospheres was measured, and Ki67-positive cells were counted by immunofluorescence staining. Meanwhile, after 3 days of further culture, the gene expression of Notch 1, Hes 1 and Mash 1 in neural stem cells was detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the control group, 50, 100μmol/L osthole could obviously promote the proliferation ability of neural stem cells. 100μmol/L osthole had the most significant effect and increased the expression of Notch 1 gene, Hes 1 gene, but it had no effect on Mash 1 gene. These results suggest that osthole can promote proliferation of neural stem cells cultured in vitro and its mechanism may be associated with activation of Notch 1 gene and Hes 1 gene in Notch signaling pathway.
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OBJECTIVE:To retrospect the experiments and clinical research on tropomyosin(TM) and make sure the 4 genes of TM in mammals and the relationship between its gene mutation and weakness of skeletal muscle as well as hypertrophic cardiomyopathy in order to provide support for preventative measures and rehabilitation interventions. DATA SOURCES:Conducting computerized search on experiments and clinical reports from January 1987 to Augsut 2004 regarding TM to Medline and Wanfang Database.The key searching words of " tropomyosin, gene, mutation" both in English and Chinese were used with the restricted language of English and Chinese respectively. DATA SELECTION:The fiirst trial was conducted to the found literatures while the articles with " single case,experience" in title and non-research ones were excluded. Then full text of the rest reports was searched.Randomized control clinical trial(RCT) was used as the selective standard. DATA EXTRACTION:There were 30 articles found regarding the randomized and non-randomized trials on the research and advance of molecular biology of TM with 21 of them met the selective standard and 9 articles were excluded. DATA SYNTHESIS:The study showed that TM was an important regulatory protein for muscle contraction,which existed widely in various kinds of eukaryotes in the way of isomers. Four TM genes of mammals had been confirmed by which 20 TM isomers could be expressed.Different TM gene could induce different diseases respectively. CONCLUSION:At present,research of TM is not just limited to the process of muscle contraction,study on its effects on the conversion of vascular smooth muscle cell has been attached much attention.The application of gene engineering will essentially diagnose and cure the disease therefore medical behaviors and quality of life will be consequently changed.
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Objective:To investigate the effects of Adp53 and F56 on the growth and lung metastasis of breast cancer.Methods:The BICR-H1 cells were inoculated into the mammary fatty pad of BALB/C nude mice and NOD/SCID mice to establish breast cancer model.Then the nude mice with xenograft tumor were randomized into group Adp53+F56,Adp53,F56 and control.The NOD/SCID mice with xenograft tumor were randomized into group Adp53+F56,Adp53,F56,Adlacz and control.They were theated for 3 weeks according to the plan,diversity of the volume and histopathology of xenograft tumor of nude mice was observed and the expressions of p53 and VEGF gene,and microvessel density(MVD)were detected by immunohistochemistry.Lung metastasis of breast cancer in NOD/SCID mice was observed.Results:(1)Intratumoral injections of Adp53,F56,and their combination resulted in an inhibition on the growth of xenograft tumor of BICR-H1 cells.The ultimate relative growth volumes of groups Adp53+F56,Adp53,F56 and control were 2.47,4.37,4.69 and 12.49 respectively.(2)After treatment,P53 positive rate of group Adp53+F56,Adp53 increased 9.4%,6.3% than before respectively,but compared with control group,the difference is not significant(P=0.693);VEGF protein of group Adp53+F56,Adp53 and F56 decreased 21.9%,9.4% and 3.1% than before respectively,but compared with control group,the difference was not significant(P=0.284).Necrosis and decrease of vessel in the tumor and morphological change of endothelium were observed under light microscope in the groups Adp53+F56,Adp53 and F56.MVD estimated by FⅧ-RA staining of group Adp53+F56,Adp53 and F56 were 14.50?2.54,16.28?3.44 and 18.06?7.66,compared with control group(24.93?6.53),the difference is significant(P=0.000).(3)The average number of lung metastasis of NOD/SCID mice in group Adp53+F56,Adp53 and F56 were 1.143?0.378,2.750?0.886 and 3.375?0.518 respectively,lower than Adlacz group(5.000?0.816)and control group(5.670?0.817)obviously(P=0.000).Conclusion:Adp53 combined with F56 can greatly inhibit growth and matastasis of breast cancer in vivo.The mechanism of anti-tumor effects of Adp53 and F56 may be related to the anti-angiogenesis effect on malignant tumor through inhibiting the expression and activity of VEGF.
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Inverse agonist is a new type of classification.Different form antagonist that blocks the effect of agonist,inverse agonist produces opposite effect to that of agonist.The characteristics of inverse agonists acting on different receptors including H_2,H_3,? opioid,adrenergic ?, and 5-HT_((1B)) receptors are discussed in this paper.Recent investigation suggested that inverse agonist has potential clinical application.
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Object To study the effects of WUZI SIWU GUASHITANG (WT) against multi glycosides of Tripterygium wilfordii Hook. f. (GTW) induced genital system toxicity in male rats and its mechanism. Methods Male rats in treatment groups were treated respectively with a 80 days oral administration of large , middle and small doses of WT plus a fixed dose of GTW. The rats as control were treated with GTW alone or saline. Thereafter, the changes in testis organ index, the number of spermatozoa, the rate of movable spermatozoa and the structure of spermatogenic cell epithlium were observed and the serum testosterone level was determined by IRMA. Then the comparison was made between treatment and control groups as to above variables. Results As compared with GTW group, large or middle dose of WT significantly increased the weight of testis, the number of spermatozoa and the rate of movable spermatozoa. Large dose of WT could relieve the damage of GTW to the spermatogenic cell epithelium completely and keep the serum testosterone at normal level. Conclusion The combined use of GTW with WT is very useful in relief of GTW induced adverse reactions of genital system in male rats. The mechanism by which WT exerts the counteractive effects is related to protecting the spermatogenic cell epithelium from being damaged by GTW, and keeping the serum testosterone at normal level.