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Aim: To investigate whether VGX-1027 could prevent PM2.5-induced mouse lung inflammation and airway hyperresponsiveness. Methods: Fortyeight C57BL/6 mice were randomly divided into control group, VGX-1027(50 mg · kg-1) + PBS group, PM2.5 group, VGX-1027 (12. 5 mg · kg-1) + PM2.5 group, VGX-1027(25 mg · kg-1) + PM2.5 group, and VGX-1027(50 mg · kg-1) + PM2.5 group. Mice were injected intraperitoneally with PBS or corresponding doses of VGX-1027 one hour before intranasal instillation of PBS or PM2.5(7. 8 mg · kg-1) for two consecutive days. 24 hours after last intranasal instillation, airway hyperresponsiveness and bronchoalveolar lavage fluid (BALF) cell numbers were measured. Lung inflammation scores were evaluated by HE staining and the levels of inflammatory cytokines in BALF were detected by ELISA, and the expressed levels of NLRP3 and caspase-1, as well as the phosphorylation levels of NF-kB protein were determined using Western blotting. Results: PM2.5 intranasal instillation induced significant lung inflammation and airway hyperresponsiveness. In the PM2.5 group, VGX-1027 at 12. 5 mg · kg-1 did not inhibit PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration compared to PM2.5-instilled mice; however, VGX-1027 at 25 and 50 mg · kg-1 inhibited PM2.5-induced airway hyperresponsiveness and lung inflammatory infiltration, decreased the number of inflammatory cells and the levels of inflammatory factors in BALF, and down-regulated NLRP3 and caspase-1 expression, as well as the phosphorylation levels of NF-κB. Conclusion: VGX-1027 could inhibit PM2.5-induced lung inflammation and airway hyperresponsiveness in mice.
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<p><b>OBJECTIVE</b>To analyze the promoter methylation status, mRNA expression and clinical significance of DKK-3 and WIF-1 genes in patients with acute myeloid leukemia(AML).</p><p><b>METHODS</b>Methylation specific polymerase chain reaction (MS-PCR) mothod was carried out to detect DKK-3 and WIF-1 gene promoter methylation status in bone marrow specimen from 56 patients with AML and 20 patients with iron deficiency anaemia(IDA) as control; then the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNA expression of DKK-3, WIF-1 gene and β -catenin in the above-mentioned specinens, and their relationship with the clinical features and survival time was analyzed.</p><p><b>RESULTS</b>The promoter methylation rate of DKK-3 and WIF-1 gene in AML patients were significantly higher than that in control group(χ=15.330,P<0.001; χ=17.371,P<0.001). There was no relationship between DKK-3 and WIF-1 gene promoter methylation rate and AML patient's sex, age, clinical typing. The relative expression of DKK-3 and WIF-1 gene mRNA in AML group were 0.840±0.320 and 0.792±0.313, which were lower than those in control group (1.134±0.392 and 1.047±0.334) respectively, the difference was statistically significant (t=3.415,P=0.000; t=3.070, P=0.003). The relative expression of β-catenin mRNA in AML bone marrow specimens in AML group was 0.756±0.304, which was higher than that in control group(0.342±0.105), the difference was statistically significant (t=5.943, P=0.001). The expression of DKK-3 and WIF-1 gene mRNA negatively correlated with β-catenin mRNA(r=-0.543; r=-0.562). Kaplan Meier survival curve analysis showed that overall survival time in AML patients with DKK-3 gene methylation was shorter than that in the AML patients with DKK-3 gene unmethylation(χ=3.957, P=0.042). Futhermore, the orerall survival time in AML patients with WIF-1 gene methylation was also shorter than that in AML patients with WIF-1 gene unmethylation (χ=4.520, P=0.029).</p><p><b>CONCLUSION</b>Wnt/β-catenin signaling pathway is abnormally activated in AML patients, the DKK-3 and WIF-1 gene promoter methylation may be involved in Wnt pathways activation and the pathogenesis of AML.</p>
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The present study aims to investigate the lignan constituents from Sambucus williamsii and their proliferation effects on osteoblast-like UMR106 cells. Seven compounds were isolated and purified by macroporous resin D101, silica gel, Sephadex LH-20, Toyopearl HW-40, ODS column chromatographies and Preparative HPLC(C-18). Their structures were elucidated by spectroscopic methods as threo-guaiacylglycerol-beta-0-4'-conifery ether (1), lirioresinol A (2), 1-hydroxypinoresinol (3), 5-methoxybalanophonin (4), balanophonin (5), 5-methoxy-trans-dihydrodehydrodiconiferyl alcohol (6), and p-hydroxybenzaldehyde (7). Compounds 3-7 were obtained from this genus for the first time. The proliferation effects of all isolated compounds on osteoblast-like UMR106 cells were determined. Compounds 1-7 (1 x 10(-12)-1 x 10(-7) mol x L(-1)) increased UMR106 cell proliferation to some extent.
Subject(s)
Cell Line , Cell Proliferation , Lignans , Pharmacology , Osteoblasts , Cell Biology , Plant Stems , Chemistry , Sambucus , ChemistryABSTRACT
Objective: To study the chemical constituents in 60% ethanol extract from the stems of Sambucus williamsii. Methods: Six compounds were isolated and purified by macroporous resin D-101, silica gel, Sephadex LH-20, Toyopearl HW-40, ODS column chromatographies, and RP-HPLC. Results: Their structures were elucidated by spectroscopic methods and identified as 23-hydroxy-3-oxo-28-nor-12, 16-dien oleanane (1), 3-oxo-oleanolic acid (2), oleanolic acid (3), betulinic acid (4), palmitic acid (5), and 1-octacosanol (6). Conclusion: Compound 1 is a new nortriterpenoid named sambucusan A. Compounds 2 and 6 are isolated from this plant for the first time.