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Objective To investigate the effect of CYP46A1 on the pathogenesis of Alzheimer's disease.Methods Recombinant lentiviral vectors which including anthropogenic CYP46A1 were injected into bilateral hippocampus of 3-monthold male 5XFAD transgenic mice,while empty vectors were injected into the corresponding position of the control group.After two months,the ability of learning and memory were tested by Morris water maze and T maze experiments,and amyloid plaque and inflammatory infiltration in the brain were detected by immunohistochemical staining and ELISA respectively.Results Compared with the control group,CYP46A1 virus injection significantly increased the CYP46A1 mRNA and protein expression in hippocampus.In addition,CYP46A1 overexpression significantly decreased the latency to find the platform in Morris water maze test and increased the correct rate to choose in T maze test.Aβ immunohistochemical staining and plaques area statistics demonstrated that the amyloid plaque area of hippocampus in CYP46A1 overexpression mice was significantly reduced,and there was a significantly decrease of hippocampal astrocytes expression by means of GFAP staining.Furthermore,hippocampal CYP46A1 overexpression significantly decreased the expression level of Aβ40,Aβ42,IL-1β and TNF-α,while compare with the control group.Conclusion CYP46A1 overexpression in hippocampus can promote the cognitive impairment,as well as ameliorate the brain inflammatory infiltration in 5XFAD transgenic mice,suggesting that CYP46A1 has anti-Alzheimer's disease like effects.
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Aim To investigate the influence of inhibi-tory nanocomposite on EC-9706 cells and the effect of nanocomposite on ESCCAL _ 1 LncRNA expression, siRNA-loaded nanocomposite being prepared as non-vi-rus delivery system Methods Mesoporous silica nano-particles were prepared by sol-gel method under room temperature and coated by cationic polymerpolyethylen-imine (PEI)on the surface to stay positive charge, which could facilitate its combination with negatively charged ESCCAL _ 1 siRNA. The size and surface charge of nanocomposite were determined by laser par-ticle analyzer and TEM. The inhibitory rate of nanopar-ticles on EC-9706 cells was detected by MTT methods. Entrapment efficiency was determined by agarose gel e-lectrophoresis. The uptake-siRNA was detected by flu-orescence microscope. The expression of ESCCAL _1 LncRNA was detected by RT-PCR. Results The MSNP appeared to have a high dispensability and hom-ogeneous size by particle size analyzer and transmission electron microscopy(TEM). The formed nanoparticles had a surface mesoporous diameter of 3 ~ 5 nm. The proliferation of ESCCAL_1 was inhibited significantlly (P < 0. 05),and the 72h inhibitory rate was (54. 93 ± 2. 6)%;the siRNA loading could be effectively up-taken by EC-9706 cells;ESCCAL_1 silencing efficien-cy was 69. 5% . Conclusions The tumor targeting nanocomposite with high encapsulation efficiency is prepared. The proliferation of esophageal cancer EC-9706 cells can be effectively inhibited by anocompos-ite-mediated siRNA,and the expression of ESCCAL_1 is effectively silenced in EC-9706 cells. The nanocom-posite is an efficient gene delivery system and may have potential application in gene therapy.
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<p><b>OBJECTIVE</b>To observe the effect of rhynchophylline on methamphetamine-dependent zebrafish and explore the possible mechanism.</p><p><b>METHODS</b>Zebrafish were divided into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place preference (CPP) was induced in zebrafish with methamphetamine, and the staying time in the drug box and the tracking map of the zebrafish were observed with Noldus Ethovision XT system. The protein expressions of TH, NR2B and GLUR2 in the brain of zebrafish with CPP were detected with Western blotting.</p><p><b>RESULTS</b>Compared with the control group, zebrafish in methamphetamine group showed significant variations in the staying time and swimming distance in the drug box after conditioning (P<0.05) with obvious alterations of NR2B, TH and GLUR2 expressions in the brain (P<0.05). Treatment of methamphetamine-dependent zebrafish with high-dose rhynchophylline significantly reduced the variations in the staying time and swimming distance in the drug box (P<0.05) and in the expressions of NR2B, TH and GLUR2 in the brain (P<0.05).</p><p><b>CONCLUSION</b>Rhynchophylline can inhibit methamphetamine dependence in zebrafish, the mechanism of which may involve the expressions of TH, NR2B and GLUR2 proteins in the brain.</p>
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<p><b>OBJECTIVE</b>To evaluate the feasibility of cone beam computed tomography (CBCT) for the evaluation of trabecular bone structure in mandibular condyle and to investigate the distribution of the trabecular bone structure within mandibular condyle.</p><p><b>METHODS</b>Eighty condyles from 40 healthy young volunteers (aged 20-32) were scanned by CBCT. A coronoid image was acquired of each condyle and divided into 8 regions where regions of interest were specified. After CBCT images were binarized, four morphological parameters including bone volume fraction, trabecular thickness, trabecular number and trabecular separation were computed.</p><p><b>RESULTS</b>All parameters were significantly different between the superior zone and middle/inferior zone of the condyle (P < 0.05). Superior zone showed the largest bone volume fraction (52.2%), the highest trabecular number (1.33 mm(-1)), the thinnest trabecular thickness (393.48 microm), and the smallest trabecular separation (361.59 microm). Inferior zone showed the smallest bone volume fraction (49.64%). These results were not significantly different between bilateral sides of the condyles (P > 0.05).</p><p><b>CONCLUSIONS</b>Trabecular bone structure was inhomogeneous within the condyle, but symmetrical between bilateral sides of the condyles. CBCT combined with image processing is a feasible tool in evaluating trabecular bone structure of human mandibular condyle.</p>
Subject(s)
Adult , Female , Humans , Male , Young Adult , Cone-Beam Computed Tomography , Image Processing, Computer-Assisted , Mandibular Condyle , Diagnostic ImagingABSTRACT
The aim was to explore the modulating and inhibiting effects of arsenic trioxide, ginseng saponin and beta-elemene on telomere length and telomerase activity in K562 cell line, and to study their anti-tumor mechanism and seek new method of therapy for acute leukemia. Human erythroleukemia cell line K562 was co-cultured with arsenic trioxide, ginseng saponin, beta-elemene separately, cells were collected after 24, 48 and 72 hours for further detecting. Telomere length and telomerase activity were detected by the methods of Southern-blot and PCR-ELISA respectively. The effects of these drugs on telomere length and telomerase activity were observed at different concentrations and length of time. The results showed that (1) telomerase activity of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene. The inhibiting effects depended on drug concentrations and length of time. When co-cultured at proper concentration and period of time, telomerase activity could be inhibited; (2) viability of K562 cells decreased after co-cultured with arsenic trioxide, ginseng saponin and beta-elemene, the inhibiting effect depends on drug concentrations and length of time; (3) after co-cultured with arsenic trioxide, ginseng saponin, and beta-elemene for 72 hours, telomere length of K562 cell line prolonged a little. It is concluded that (1) arsenic trioxide, ginseng saponin and beta-elemene can inhibit telomerase activity in K562 cell line, the suppression of telomerase activity may be one of the mechanisms of anti-tumor effect; (2) arsenic trioxide, ginseng saponin and beta-elemene can inhibit the growth of K562 cell line, the inhibiting effect depends on concentration and time; (3) when telomerase activity was suppressed, the telomere length prolonged a little, indicating that in K562 cell line may exist another mechanism to regulate telomere length, except telomerase activation.
Subject(s)
Humans , Arsenicals , Pharmacology , Cell Survival , K562 Cells , Oxides , Pharmacology , Panax , Saponins , Pharmacology , Sesquiterpenes , Pharmacology , Telomerase , Metabolism , TelomereABSTRACT
To explore the change of telomerase activity in acute leukemia (AL) cells and its relationship with cell cycle, PCR-ELISA was used to detect telomerase activity of bone marrow cells from 148 AL patients, including 92 cases with acute non-lymphocytic leukemia (ANLL) and 56 cases with acute lymphocytic leukemia (ALL). Thirty-six patients without bone marrow disorders were detected as normal control. The cell cycle of 16 patients and 4 controls was detected with flow cytometry. The results showed that the positive rate of telomerase was 71.6% (106/148) in the cells from AL patients, which was higher than that in the control group 5.6% (2/36). It was 88.9% (32/36) in the relapse group and 81.3% (61/75) in the untreated group. Both rates were higher than that in the CR group (35.1%, 13/37). There was no significant difference in the ALL and ANLL groups. The cell number in various phases of cell cycle had no significant difference between telomerase positive and negative groups. It was concluded that the activation of telomerase was very common in acute leukemia cells. Telomerase positive rate was closely associated with the different stages and progress of acute leukemia, and it might be a molecular marker for increased proliferation of leukemic cells during the process of the disease. Activation of telomeras had no correlation with cell number in different phases of cell cycle, while telomerase activity is modulated by other biological factors in addition to cell cycle.