1.Ultrasonic microbubbles for glioma-targeted drug delivery.
Li-juan CHEN ; Cui-tao LU ; Ying-zheng ZHAO ; Li-na DU ; Yi-guang JIN
Acta Pharmaceutica Sinica 2015;50(1):99-103
Ultrasonic microbubbles were used to open blood-brain barriers (BBB) with a reversed and limited behavior feature in the study, which could improve the brain-targeted delivery of anti-tumor drugs. The glioma rat model was prepared. Low-frequency ultrasound was combined with microbubbles to affect the permeability of BBB compared with the permeability of independently administered Evans blue (EB) crossing BBB. Time point and length of ultrasound were investigated whether they affect the permeability of BBB and the damage of brain tissue. The effect of the growth time of glioma on BBB permeability was explored. Only glioma had a very little impact on BBB permeability. However, ultrasonic microbubbles opened the BBB with the features of temporary, limited and reversed behavior and improved EB and magnetic resonance imaging contrast agent penetrating BBB. A length of 30 s ultrasound is appropriate for opening BBB and no damage of brain tissue. Drugs should be injected before ultrasound so that they enter into brain as BBB opening. Ultrasonic microbubbles can open BBB effectively and safely, which improve drugs penetrating BBB under proper time point and length.
Animals
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Blood-Brain Barrier
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Contrast Media
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Drug Delivery Systems
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Glioma
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drug therapy
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Magnetic Resonance Imaging
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Microbubbles
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Permeability
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Rats
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Ultrasonics
2.Effects of interleukin-1α on the expression of matrix metalloproteinases and tissue matrix metalloproteinase inhibitors in swine trabecular meshwork cells
Jie, WANG ; Yu-guang, ZHU ; Xi-juan, WANG ; Yan, ZHU ; Li-hua, ZHANG ; Ying-ying, ZHONG ; Xiao-nan, DU
Chinese Journal of Experimental Ophthalmology 2011;29(9):800-803
BackgroundObstruction of aqueous humor out flow pathway or abnormality of the extracellular matrix( ECM ) of trabecular meshwork cells causes high intraocular pressure. The balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases(TIMPs) is critical for the metabolism of ECM. Interleukin1α(IL-1α) can influence outflow of aqueous humor by regulating MMPs level. Objective This study was to investigate the effect of interleukin-1α on the expression of MMP-2,MMP-3 and TIMP-I in cultured swine trabecular meshwork cells.Methods Swine sclera with trabecular meshwork tissue was isolated from 20 swine eyes and cultured with explant cultured method. Cultured cells were passaged and third generation cells were identified by fibronectin ( FN ) and laminin ( LN ) staining. After 24 hours of serum starvation, trabecular meshwork cells treated with IL-1α at the concentration of 10 mg/L were regarded as the IL group,and serum-free culture medium used to treat trabecular meshwork cells was regarded as the control group. The expression of MMP-2, MMP-3 and TIMP-1 proteins in trabecular meshwork cells were detected by immunohistochemistry,and the expression of MMP-2 mRNA, MMP-3 mRNA and TIMP-1 mRNA were detected by RT-PCR. The examination results were compared between the two groups. ResultsThe third generation of cells were positive for FN and LM. Compared with the control group, the expression levels of MMP-3 and TIMP-1 proteins(A value) in trabecular meshwork cells were significantly higher in the IL group than the control group(t=-7. 694,t =-5. 199,P<0. 05) ,but no obvious difference was found in the expression of MMP-2 between the two groups( t=-2. 365, P>0.05 ). The higher expression levels in MMP-3 mRNA and TIMP-1 mRNA (A value) in trabecular meshwork cells were seen in comparison with the control group (t =-3. 025,t=-1. 921 ,P<0. 05). However,similar results were found in the expression of MMP-2 mRNA between the two groups(t =- 1. 173, P>0.05 ). ConclusionsThe overexpression of MMP-3 and TIMP-1 proteins and their mRNA leads to the imbalance of MMP-3/TIMP-1 and promotes the decomposition of ECM in the trabecular meshwork, and therefore increases aqueous outflow.
3.Imbalance of endogenous homocysteine and hydrogen sulfide metabolic pathway in essential hypertensive children.
Li CHEN ; Sumou INGRID ; Ya-guang DING ; Ying LIU ; Jian-guang QI ; Chao-shu TANG ; Jun-bao DU
Chinese Medical Journal 2007;120(5):389-393
BACKGROUNDHypertension is a common disease of the cardiovascular system. So far, the pathogenesis of primary hypertension remains unclear. The elaboration of its pathogenesis is an important topic in the field which calls for urgent resolution. The aim of this study was to probe into the metabolic imbalance of homocysteine (Hcy) and hydrogen sulfide (H(2)S) in children with essential hypertension, and its significance in the pathogenesis of essential hypertension.
METHODSTwenty-five children with essential hypertension and 30 healthy children with normal blood pressure were enrolled in the study. The medical history was investigated and a physical examination was conducted on the subjects. Plasma Hcy content was examined by fluorescence polarization immunoassay (FPIA). The plasma H(2)S level was detected by a modified method with a sulfide electrode. Data were presented as mean +/- standard deviation. The t test was applied to the mean values of both groups. Pearson linear correlation analysis was applied to the plasma Hcy and H(2)S as well as to the systolic pressure against the plasma H(2)S/Hcy ratio.
RESULTSPlasma Hcy, an intermittent metabolite of the endogenous methionine pathway, was markedly increased but plasma H(2)S, a final product of this pathway was significantly decreased in hypertensive cases when compared with normal subjects ((Hcy: (12.68 +/- 9.69) micromol/L vs (6.62 +/- 4.79) micromol/L (t = 2.996, P < 0.01); H(2)S: (51.93 +/- 6.01) micromol/L vs (65.70 +/- 5.50) micromol/L) (t = -8.670, P < 0.01)). The ratio of plasma H(2)S/Hcy in children with hypertension was 5.83 +/- 2.91, while that of the control group was 11.60 +/- 3.30, and the difference is significant with a t = -6.610 and P < 0.01. A negative correlation existed between plasma Hcy and H(2)S concentrations, r = -0.379, P < 0.05. And a negative correlation was found between systolic blood pressure and the plasma H(2)S/Hcy ratio, r = -0.687, P < 0.05.
CONCLUSIONThere was a metabolic imbalance of homocysteine and hydrogen sulfide in essential hypertensive children.
Adolescent ; Child ; Female ; Homocysteine ; metabolism ; Humans ; Hydrogen Sulfide ; metabolism ; Hypertension ; etiology ; metabolism ; physiopathology ; Male ; Systole
4.Observation of Dynamic Changes in Ultra-Micro-Structure of Pulmonary Arteries and Endogenous Hydrogen Sulfide in Rats with Left-Right Shunt
xiao-hui, LI ; jun-bao, DU ; xiu-ying, TANG ; hong-fang, JIN ; ya-guang, DING ; jian, LI ; chao-shu, TANG
Journal of Applied Clinical Pediatrics 2004;0(07):-
Objective To explore the relationship between dynamic changes in ultra-micro-structural of pulmonary arteries and endogenous hydrogen sulfide in rats with left-right shunt.Methods Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of pulmonary artery structural remodeling. After 1 day, 3 days, 1 week, 4 weeks and 8 weeks of experiment, the ultra-micro-morphologic changes of pulmonary arteries of rats were observed under electronic microscope and H_2S concentration in serum was evaluated by modified sulfide electrode method.Results The changes of ultra-micro-structure of pulmonary arteries were progressively exacerbated, endothelial cells became swollen and large in size on 3 days, smooth muscular cells increased in size as well as the change of endothelial cells in 1 week, and they changed from contractile phenotype to synthetic phenotype in 4 weeks.Conclusions Shunt exhibited changes of ultra-micro-structure of pulmonary arteries are accompanied by the changes of endogenous H_2S. It is suggested that endogenous H_2S might play a protective role in changes of ultra-micro-structure of pulmonary artery.
5.Clinical Analysis of Cardiac Involvement in Children with Mitochondriopathies
jian-guang, QI ; ying, ZHANG ; yu, QI ; yan-ling, YANG ; ye, WU ; yu-wu, JIANG ; jiong, QIN ; jun-bao, DU
Journal of Applied Clinical Pediatrics 1986;0(01):-
Objective To explore the clinical characteristics of cardiac involvement in children with mitochondriopathies.Methods The clinical data of 23 children with mitochondriopathies were reviewed.The changes of electrocardiography,echocardiography and heart enzymes were analyzed.Results In 15 cases of mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episode(MELAS syndrome),electrocardiography was performed on 9 cases,6 of them showed abnormal electrocardiographic findings,including right bundle branch block,ST-T change,Wolff-Parkinson-White syndrome,et al.On echocardiographic examination in 9 MELAS syndrome ca-ses,only 1 case showed hypertrophy cardiomyopathy.Six cases had increased plasma creatine kinaseMB(CK-MB) mass and only one of 12 MELAS syndrome cases had increased cardiac troponin I(cTnI) level.In 8 cases of subacute necrotizing encephalomyopathy(Leigh syndrome),electrocardiography was performed on 5 cases,4 of them showed abnormal electrocardiographic findings,including sinus tachycardia,ST-T change and low voltage.Two cases showed normal electrocardiography.Three out of 6 cases with Leigh syndrome showed increased plasma CK-MB mass.The molecular genetic examinations were performed in 13 cases of MELAS syndrome and 6 cases of Leigh syndrome.The mitochondrial DNA nt 3243 A→G mutation was found in white blood cells of 9 MELAS syndrome cases,the mutation rate being 37%-60%.The mitochondrial DNA nt 8993 T→C mutation was found in white blood cells of 2 Leigh syndrome cases.Conclusion In children with mitochondriopathies,myocardiac involvement is comparatively common,and even cardiomyopathy can occur.
6.Effects of transforming growth factor-beta1 gene therapy on bone rarefaction around endosseous implant.
Ying-guang CAO ; Rong WANG ; Ke SONG ; Zong-qiang XIONG ; Jian-ming DU ; Hua-jun WANG
West China Journal of Stomatology 2007;25(4):335-338
OBJECTIVETo investigate the effects of transforming growth factor-beta1 (TGF-beta1) gene therapy on bone defect and bone rarefaction around endosseous implant.
METHODSThe primary cultured bone marrow derived stroma cells (BMSCs) was transfected by plasmid pCDNA3.1(+) -TGF-beta1, and was adhered with polylactic-co-glycolic acid (PLGA) for constructing TGF-beta1 gene-modified artificial bone. The model of rats with placed titanium implants in the proximal metaphyses of the tibiae after ovariectomy was made. The TGF-beta1 gene-modified artificial bone (experimental group), BMSCs-PLGA compound artificial bone (control group) and nothing (blank control group) were placed in the bone defect around implant. The tibiae were examined by decalcified sections with immunohistochemical method and histological analysis methods at intervals of 4 and 8 weeks after implant surgery in order to detect the expression of TGF-beta1 in new bone adjacent to the implant and the healing of the bone defect around the implant.
RESULTSThe expression level of TGF-beta1 of experimental group was higher than that of control group and blank control group at the 4th week. The histological analysis indicated that the gene-modified artificial bone had stronger osetogenic potential than others.
CONCLUSIONTGF-beta1 gene-modified artificial bone promotes the repair of the bone defect around titanium implants in osteoporotic rats.
Animals ; Bone and Bones ; Cells, Cultured ; Dental Implantation, Endosseous ; Dental Implants ; Female ; Genetic Therapy ; Prostheses and Implants ; Rats ; Stromal Cells ; Titanium ; Transfection ; Transforming Growth Factor beta1
7.Range of plasma hydrogen sulfide in children.
Ya-guang DING ; Jie MI ; Ying LIU ; Hong-fang JIN ; Chao-shu TANG ; Jun-bao DU
Acta Academiae Medicinae Sinicae 2006;28(5):714-716
OBJECTIVETo measure the range of plasma hydrogen sulfide (H2S) in children.
METHODSTotally 200 healthy children were classified into 4 groups based on age and sex: 7-14 years old group (n = 75, 43 boys and 32 girls), 15-19 years old group (n = 125, 64 boys and 61 girls). Plasma H2S level was detected by a modified sulfide electrode-based method.
RESULTSPlasma H2 S levels were (52.2181 +/- 17.9400) micromol/L in 7-14 years old boys, (51.9441 +/- 16.5448) micromol/L in 7-14 years old girls, (52.8771 +/- 14.1444) micromol/L in 15-19 years old boys, and (53.6551 +/- 14.5563) micromol/L in 15-19 years old girls (P > 0.05). In summary, the range of plasma H2S in children was about (52.8234 +/- 15.4339) micromol/L.
CONCLUSIONThe range of plasma H2S in children is about (52.8234 +/- 15.4339) micromol/L.
Adolescent ; Age Factors ; Blood Gas Analysis ; methods ; Child ; Female ; Humans ; Hydrogen Sulfide ; blood ; Male ; Reference Values ; Sex Factors
8.Effect of Bio-Oss loading with rAAV-BMP7 on regeneration of bone defects around dental implant.
Ke SONG ; Jian-ming DU ; Ren-hui LUO ; Ying-guang CAO
West China Journal of Stomatology 2008;26(4):421-429
OBJECTIVETo evaluate in vivo gene delivery of Bio-Oss coated with adeno-associated virus-mediated human bone morphogenetic protein 7 (rAAV-BMP7/Bio-Oss) for bone regeneration around dental implants.
METHODSIn vitro rAAV-BMP7 were constructed and compounded with Bio-Oss. In 6 male New Zealand rabbits, two hydroxyapatite (HA) coated titanium dental implants were placed respectively to each animal in the bilateral tibia metaphysis. Before implantation, a standardized gap (8 mm in width, 4 mm in depth) was created between the implant surface and the surrounding bone walls. Rabbits were randomly divided into three groups (group A, B, C). Gaps of group A were filled with rAAV-BMP7/Bio-Oss (n = 4), gaps of group B were filled with Bio-Oss alone (n = 4), and gaps of group C were filled with nothing (n = 4). The rabbits were sacrificed at 4 and 8 weeks respectively, and the sclerous tissue slices obtained, then histology and histomorphometric analysis were conducted.
RESULTSHistological and histomorphometric analysis revealed an enlarged bone-forming area in the bone defects of group A and B at 4 and 8 weeks after implantation. Greater bone-implant contact was achieved with rAAV-BMP7/Bio-Oss than with Bio-Oss alone and this difference was statistically significant (P < 0.05).
CONCLUSIONrAAV-BMP7/Bio-Oss can induce a stronger peri-implant bone reaction and larger new bone formation than Bio-Oss alone in the treatment of bone defects adjacent to titanium dental implants.
Animals ; Bone Morphogenetic Protein 7 ; Bone Regeneration ; Bone Substitutes ; Bone and Bones ; Dental Implantation, Endosseous ; Dental Implants ; Durapatite ; Humans ; Male ; Minerals ; Rabbits ; Titanium
9.Identification of the regions of copy number amplification associated with hepatocellular carcinoma.
Shi-guang ZHANG ; Ying-tang GAO ; Wen-qin SONG ; Zhi DU ; Bin YANG ; Yi-Jun WANG ; Zheng-yan ZHU
Chinese Journal of Oncology 2009;31(8):566-570
OBJECTIVETo screen and determine the regions of copy number variation (CNV) associated with hepatocellular carcinoma (HCC) using SNP array and fluorescence quantitative PCR.
METHODSThe CNV from HCC cell line TJ3ZX-01 was analyzed using GeneChip Human Mapping 500K SNP array. According to the data obtained by SNP array analysis, four candidate amplification regions were verified in 41 primary HCC samples by fluorescence quantitative PCR.
RESULTSFour regions of copy number amplification at 1q21.2, 1q22 approximately 23.1, 7p22.1 and 22q13.1 were detected by SNP array analysis. The four candidate amplicons occurred in 56.1% (23/41) of HCC samples at 1q21.2; 80.5% (33/41) at 1q22 approximately 23.1; 75.6% (31/41) at 7p22.1 and 31.7% (13/41) at 22q13.1 analyzed with sequence tagged site (STS) markers by quantitative PCR.
CONCLUSIONIn four candidate amplification regions selected by SNP array analysis and detected by fluorescence quantitative PCR, three amplification regions show increased copy number in more than 50.0% HCC tissues. This result indicates that these amplification regions are associated with pathogenesis of hepatocellular carcinoma.
Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; DNA Copy Number Variations ; genetics ; Female ; Humans ; Liver Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide ; Sequence Tagged Sites
10.Changes of prostaglandin D2 receptor on T cells in peripheral blood of children with asthma.
Yan-Feng YING ; Ye HU ; Xiao-Yun SHAN ; Juan DU ; Ping-Guang TU
Chinese Journal of Contemporary Pediatrics 2009;11(3):199-202
OBJECTIVEChronic airway inflammation is associated with the polarization of TH2 cells in asthma. Prostaglandin D2 (PGD2) plays an important role in the polarization of TH2 cells. This study aimed to investigate the changes of PGD2 receptors (DP1/CRTH2) on T lymphocytes and their significance in asthma.
METHODSSeventy-two children with asthma were assigned to two groups: acute attack (n=42) and remission (n=30). Thirty-five healthy children were used as the control group. Plasma levels of TH2 cytokines IL-4 and IL-5, and TH1 cytokine INF-gamma were detected using ELISA. Radiological binding assay (RBA) was used to measure the contents of DP1/CRTH2 receptors on T cells in peripheral blood (PPB).
RESULTSThe total combining contents of DP and CRTH2 on T cells in PPB in the acute attack and the remission groups were significantly higher than those in the control group (p<0.01). There was no significant difference in the DP1 content among the three groups. Serum levels of IL-4 and IL-5 significantly increased (p<0.01), in contrast, serum levels of TH1 cytokine IFN-gamma were significantly reduced in the acute attack and the remission groups compared with those in the control group (p<0.01).
CONCLUSIONSThe total combining contents of DP and CRTH2 on T cells increased, serum levels of TH2 cytokines also increased, but serum levels of TH1 cytokine decreased significantly in the acute attack and the remission phases in children with asthma. This showed that a polarization of TH2 cells occurred in children with asthma and suggested that CRTH2 antagonism may be a new target for the treatment of asthma.
Asthma ; etiology ; immunology ; therapy ; Child ; Child, Preschool ; Chromosome Mapping ; Cytokines ; blood ; Female ; Humans ; Male ; Receptors, Immunologic ; blood ; Receptors, Prostaglandin ; blood ; T-Lymphocytes ; chemistry ; Th2 Cells ; immunology