ObjectiveTo observe the inhibition effect of docetaxel-loaded lipid microbubbles (DLLM) combined with ultrasound targeted microbubbles destruction (UTMD) on microvessel in rabbit VX2 liver tumor models.MethodsSixty rabbits were randomly divided into 6 groups (n= 10),i.e.Doc group (used docetaxel only),DLLM group (used docetaxel-loaded lipid microbubbles),Doc+US group (used docetaxel combined with ultrasound positioning irradiation),PLM+US group (used microbubbles combined with ultrasound positioning irradiation),DLLM+US group (used docetaxel-loaded lipid microbubbles combined with ultrasound positioning irradiation) and control group.The expression of CD34 and VEGF and microvessel density (MVD) were compared among different groups.ResultsAfter treatment,the expression of CD34 in DLLM+US group was lower,the MVD of DLLM+US group was markedly lower than that of the other groups (P＜0.01),while the expression of VEGF in this group was the lowest among all 6 groups (P＜ 0.01).ConclusionDLLM combined with UTMD can inhibit the generation of microvessels in rabbit VX2 liver tumor,thus inhibit the growth of the tumor.

OBJECTIVETo investigate the role of methylation on E-cadherin inactivation in nasopharyngeal carcinoma (NPC) cell line HNE1 and CNE2, as well as evaluate the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-dC) on cell abilities of proliferation and invasion.

METHODSThe expression level of E-cadherin was measured by RT-PCR, Western blot and immunohistochemistry (polymer method), the methyaltion status was analyzed by methylation-specific PCR (MSP), and cell proliferation and invasion were examined by MTT and invasion assay, separately before and after treatment with demethylating agent 5-Aza-dC.

RESULTSThe expression level of E-cadherin was down-regulated compared with the normal tissue, simultaneously partially methylated in gene promoter. Treatment with 20 µmol/L 5-Aza-dC increased the expression of E-cadherin and reduced the methylation degree. Moreover, it also significantly suppressed cell growth (27.6% for HNE1 cells and 34.3% for CNE2 cells, P < 0.05) and invasiveness (37.2% for HNE1 cells and 29.7% for CNE2 cells, P < 0.05).

CONCLUSIONSAberrant methylation around gene promoter region may play an important part in down regulation of E-cadherin in NPC, suggesting a potential therapeutic strategy for demethylating agents such as 5-Aza-dC.

Antimetabolites, Antineoplastic ; pharmacology ; Azacitidine ; analogs & derivatives ; pharmacology ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; DNA Methylation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Promoter Regions, Genetic

OBJECTIVETo investigate the effect of survivin antisense oligodeoxynucleotide (ASODN) on proliferation and apoptosis of human malignant melanoma cells.

METHODShMMC A375 colonies in log growth phase were collected and divided into control group (C, without transfection), sense chain group [SC, transfected with 600 nmol/L survivin sense oligodeoxynucleotide (ODN)], mismatch chain group (MC, transfected with 600 nmol/L survivin mismatch sense ODN), liposome group (L, treated with liposome), antisense chain group (AC, transfected with survivin ASODN, and subdivided into AC 200, 400, 600 nmol/L subgroups) according to the random number table. Transfection result was observed under inverted fluorescence microscope. Inhibition rate of cell proliferation was calculated after determination of cell viability with MTT method. Cell cycle and apoptosis rate were detected with bi-variable flow cytometry. Expression of survivin protein was determined with Western blot. Activity of caspase-3 was assessed with kinase method. Data were processed with analysis of variance.

RESULTS(1) Cell transfection rates in SC, MC, AC 600 nmol/L groups were all above 80%. (2) Compared with those in SC group [(5.23 +/- 0.25)%], MC group [(5.09 +/- 0.13)%] and L group [(4.70 +/- 0.45)%], inhibition rates of cell proliferation in AC 200, 400, 600 nmol/L groups 24 hours after transfection [(10.30 +/- 0.56)%, (16.69 +/- 0.58)%, (24.67 +/- 0.67)%] were significantly increased (F = 746.91, and P values all below 0.05). As time after transfection went on, proliferation inhibition rate was increased obviously. (3) Apoptosis rate in AC 200, 400, 600 nmol/L groups 24 hours after transfection was respectively (13.5 +/- 1.9)%, (20.1 +/- 1.5)%, (32.1 +/- 2.9)%, which were significantly higher than those in C, SC, MC, and L groups [(6.5 +/- 0.6)%, (5.6 +/- 0.7)%, (6.4 +/- 1.0)%, (6.5 +/- 1.3)%, F = 139.9, P values all below 0.05]. Cells in AC group were blocked in G2/M stage. (4) Compared with those in C group, expression amount of survivin protein decreased, and caspase-3 activity obviously increased (F = 63.1, P values all below 0.05) in AC group. No significant difference in caspase-3 activity between SC, MC, L groups and C group was observed (F = 0.512, P values all above 0.05).

CONCLUSIONSSurvivin ASODN can inhibit the proliferation of hMMC A375 in a concentration-time dependent manner, and it induces G2/M stage block and promotes its apoptosis.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitor of Apoptosis Proteins ; Melanoma ; metabolism ; pathology ; Microtubule-Associated Proteins ; genetics ; pharmacology ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; Transfection

OBJECTIVETo investigate the effect of apelin on vasodilatation of isolated pulmonary arterial rings in rats and its relationship to the nitric oxide (NO) pathway, and to observe the difference of vasodilatation between hypoxic rats and normoxic rats.

METHODSThirty-six male Sprague-Dawley (SD) rats were randomly divided into hypoxic group and normoxic group. The effects of accumulated apelin on pulmonary arterial rings preconstricted with norepinephrine (NE) were observed by using tissue organ bath system. After pulmonary arterial rings were pretreated with three methods: removing the endothelium, pretreating with nitric oxide synthase inhibitor L-NAME or soluble guanylatecyclase inhibitor ODQ, the different effect of apelin was observed. In addition, the difference of vasodilatation between hypoxic rats and normal rats were observed.

RESULTS(1) Exposure of intact endothelium pulmonary arterial rings preconstricted by NE to apelin at concentration (0.01 - 100 nmol/L) induced a significant concentration dependent relaxation. The maximal vasorelaxant effect of apelin was 10.62% +/- 2.60%, which was inhibited by removal of the endothelium (P < 0.01), pretreatment with L-NAME (P < 0.01) or ODQ (P < 0.01). (2) Response of pulmonary arterial rings from hypoxic pulmonary hypertension rats was decreased (P < 0.05). Compared to normal rats, at a concentration of 100 nmol/L, the response to apelin on arteries from hypoxic rats decreased 60.45% (P < 0.01). But the values of EC50 were not significantly different (P > 0.05).

CONCLUSIONThese results indicate that apelin relaxes the pulmonary arterial rings of rats in an endothelium dependent manner, which may have a relationship to NO signaling pathway. The response of vasodilatation is decreased in the pulmonary arterial rings from the hypoxic rats.

Animals ; Apelin ; Hypoxia ; physiopathology ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; pharmacology ; Male ; Nitric Oxide ; metabolism ; Pulmonary Artery ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vasodilation ; drug effects

OBJECTIVETo investigate the expression and distribution of mast cell tryptase (MCT) in scar, and to discuss the different MCT gene expression in keloid, hypertrophic scar and normal skin.

METHODS20 samples of keloid, 20 samples of hypertrophic scar and 20 samples of normal skin were collected. The distribution of MCT was investigated by immunofluorescence histochemistry, and the MCT mRNA expression was detected by Relative Quantification real-time fluorescent PCR.

RESULTSMCT gene was mainly located in the collagen fiber bundles of the scar, especially in the superficial layer of scar. MCT mRNA expression was significantly higher in keloid than that in hypertrophic scar and normal skin (P < 0.01). Averagely, the MCT gene expression in keloid was 2.5 times and 5.4 times of that in hypertrophic scar and normal skin.

CONCLUSIONSMCT gene may play a role in the pathogenesis of scar.

Adolescent ; Adult ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Humans ; Keloid ; metabolism ; pathology ; RNA, Messenger ; genetics ; Skin ; metabolism ; pathology ; Tryptases ; genetics ; metabolism ; Young Adult

PURPOSE: In recent years, the incidence of early-stage colorectal cancer (CRC) has markedly increased in the population within the Republic of Korea. The aim of this study was to evaluate the clinicopathologic features of adenomatous polyps in TNM stage I CRC patients and in the general population. METHODS: Between March 2003 and September 2009, 168 patients with stage I CRC were enrolled in this study. In addition, the records of 4,315 members of the general population without CRC, as determined by colonoscopy during a health check-up, were reviewed. RESULTS: Of the 168 patients with stage I CRC, 68 (40.5%) had coexisting colorectal adenomatous polyps and of the 4,315 members of the general population, 1,112 (26.0%) had coexisting adenomatous polyps (P = 0.006). The prevalences of adenomatous polyp multiplicity in early CRC and in the general population were 32% and 15%, respectively (P = 0.023). Patients with coexisting adenomatous polyps had a higher frequency of tubulovillous or villous adenomas than members of the general population with polyps (7.5% vs. 2.0%, P = 0.037). Furthermore, a subgroup analysis showed that the occurrence (44% vs. 34%, P = 0.006) and the multiplicity (32% vs. 15%, P = 0.023) of adenomatous polyps were greater for T2 than T1 cancer. CONCLUSION: The prevalence and the multiplicity of adenomatous polyps in TNM stage I CRC is higher than it is in the general population. The findings of this study suggest that depth of invasion of early stage CRC affects the prevalence and the number of adenomatous polyps in the remaining colon and rectum.
Adenoma, Villous ; Adenomatous Polyps ; Colon ; Colonoscopy ; Colorectal Neoplasms ; Humans ; Incidence ; Korea ; Polyps ; Prevalence ; Rectum ; Republic of Korea

OBJECTIVE To investigate the effect of LW- AFC, a new formula of the main active components extracted from Liuwei Dihuang decoction, on treatment of Alzheimer disease (AD) in mouse models. METHODS After treatment LW- AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β(Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels. Lymphocyte subsets were detected using flow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice, including the impairment of object recognition memory, spatial learning and memory, and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed Αβ deposition in the brain, and reduced the concentration of Aβ1- 42 in the hippocampus and plasma of APP/PS1 mice. LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone, luteinizing hormone, and follicle- stimulating hormone in the pituitary. Moreover, LW-AFC increased CD8+CD28+T cells, and reduced CD4+CD25+Foxp3+T cells in the spleen lymphocytes, down- regulated interleukin(IL)- 1β, IL- 2, IL- 6, IL- 23, granulocyte- macrophage colony stimulating factor, and tumor necrosis factor-α and -β, and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil, which supports the use of LW-AFC as a potential agent for AD therapy.

OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang (LW) possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW.In the present study,we investigated the effect of LW-AFC on AD mouse models. METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain (SAMP8), classic AD animal models, were employed. After the treatment of LW-AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1and SAMP8 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed amyloid-β(Αβ)deposition in the brain,and reduced the concentration of Aβ1-42in the hippo-campus and plasma of APP/PS1 mice. LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman-tine and donepezil. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network, which supports the use of LW-AFC as a potential agent for AD therapy.

Objective To investigate the interaction between vessel and vena cava filter (VCF) with different numbers of support poles and the influence on blood flow during its implantation by using finite element method and computational fluid dynamics method, so as to provide more scientific guidance for intervention treatment and design & development of the filter. Methods Three kinds of VCF models with 4, 6, 8 support poles were established by using Solidworks, respectively. The stress distribution and radial support stiffness of the vessel and filter under working condition were then simulated and analyzed by using ABAQUS. The distributions of blood flow velocity, pressure and shear stress after VCF implantation were simulated by using Fluent. Results All the mechanical and fluid properties of the three kinds of VCFs were within the scope of security. The comprehensive mechanical performance of the 6-pole filter was better, while for the 8 pole-filter, it showed larger stress under working condition, larger support intensity, higher exit velocity, larger shear stress on the filter mesh, and the trail of the flow was changed from laminar to transition flow, which might cause some damage to the vessel wall. The 4 pole-filter under working condition had a larger stress on the vessel, while its exit velocity was lower, which could be likely to cause local damage on the vessel wall, and disadvantageous to accurately positioning the filter in diseased region of the vessel. Conclusions The 6 pole-filter has a superior hemodynamic effect and comprehensive mechanical properties, which reduces the potential possibility of damage to the vessel wall caused by implantation of the filter. The simulation analysis on VCF provides a good reference for design of the filter and its intervention treatment in clinic.