The effects of anti-sense interleukin-5 gene transferred by recombinant adeno-associated virus in allergic rats

The accumulation and infiltration of eosinophils in airways is one of the most important characteristics of asthma, and is mediated partly by secretion of IL-5 from Th2 lymphocytes. It is well known that interleukin-5 (IL-5) played an important role in the regulation of eosinophils. In this study, an anti-sense IL-5 gene transferred by recombinant adeno-associated virus (rAAV-ASIL-5) was prepared to transfect allergic rats. It was found that the expression of IL-5 protein in plasma and BALF were inhibited significantly. The rAAV-ASIL-5-mediated suppression of total cell counts in peripheral blood and BALF were also observed. Moreover, rAAV-ASIL-5 remarkably reduced the eosinophil counts in peripheral blood and BALF, as well as the expression of ECP protein in plasma and BALF. The inflammation in lungs of rAAV-ASIL-5 pretreated rats also became slighter when compared with allergic rats. Otherwise, no apparent pathological damage to vital organs of rats was found. In conclusion, recombinant adeno-associated virus-mediated delivery of anti-sense IL-5 gene inhibited the accumulation of eosinophils and the airways inflammation in rat model of allergic asthma via suppressing IL-5 expression. It suggested the feasibility of rAAV-ASIL-5 in the gene therapy for allergic asthma and other eosinophilic diseases

circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promotes hypoxic pulmonary arterial smooth muscle cell proliferation in COPD

Hypoxia plays a crucial role in pulmonary vascular remodelling at the early stage of chronic obstructive pulmonary disease (COPD). Circle RNA (circRNA) has been identified to play a critical role in multiple diseases. However, the role of circRNAs in pulmonary vascular remodelling in COPD remains unclear. In this study, we aim to investigate the role of circRNAs in pulmonary arterial smooth muscle cell proliferation and pulmonary vascular remodelling in COPD. COPD patients show lower partial pressure of arterial oxygen and pulmonary arterial remodeling as compared with controls. circRNA microarray and real-time PCR analyses show significantly higher level of circ-BPTF and lower miR-486-5p level in the pulmonary arteries of COPD patients as compared with controls. Hypoxia suppresses miR-486-5p expression but promotes expressions of circ-BPTF and cell migration inducing protein (CEMIP) in human pulmonary arterial smooth muscle cells (PASMCs) in vitro. Loss- and gain-of-function experiments show that circ-BPTF promotes PASMC proliferation in vitro. Moreover, luciferase reporter assay results indicate that circ-BPTF regulates PASMC proliferation by acting as an miR-486-5p sponge. CEMIP is identified as a candidate target gene of miR-486-5p by luciferase reporter assay. Overall, our study shows that circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promote hypoxic PASMC proliferation in pulmonary vascular remodelling in COPD

A Single Nucleotide Polymorphism in 3' Untranslated Region of Epithelial Growth Factor Receptor Confers Risk for Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease

Objective: Polymorphisms located at microRNA (miRNA) binding sites may interfere with the miRNA/mRNA interaction. The objective of this study was to identify the association between a single nucleotide polymorphism (774 T>C) in 3'-untranslated region (3'-UTR) of Epithelial Growth Factor Receptor (EGFR) and development of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) as well as to explore the molecular mechanism. Methods and Results: In this study, we validated EGFR as a target of miR-214 in pulmonary artery smooth muscle cell (PASMC), which was further confirmed by the observation that exogenous overexpression of miR-214 significantly downregulated the expression of EGFR in the PASMCs genotyped as TT or TC, but not in CC group. Meanwhile, we found COPD patients with CC genotype had significantly higher risk for PH (OR = 1.965, p = 0.0095), compared with TT and TC genotypes,. Additionally, the PASMCs were isolated from 72 COPD patients, with which miR-214 and EGFR expression levels were determined, and we found that miR-214 level was comparable between each genotype group, the concentration of EGFR in CC genotype group was significantly higher than in TT or TC genotype group. Conclusion: Our study confirmed that EGFR 3'UTR 774 T>C polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of PH in COPD

Remote substituent effects on gas-phase homolytic Fe-O and Fe-S bond energies of p-G-C6H4OFe(CO)2(5-C5H5) and p-G-C6H4SFe(CO)2(5-C5H5) studied using Hartree-Fock and density functional theory methods

Major State Basic Research Development Program [G2000078100]; Ministry of Science and Technology of China; State Key Laboratory of Elemento-organic Chemistry, Nankai University [201007]; Natural Science Foundation of China [51072093, 91022010]Metal-ligand bond enthalpy data can afford invaluable insights into important reaction patterns in organometallic chemistry and catalysis. In this paper, the Fe-O and Fe-S homolytic bond dissociation energies [Hhomo(Fe-O)'s and Hhomo(Fe-S)'s] of two series of para-substituted phenoxydicarbonyl(5-cyclopentadienyl) iron [p-G-C6H4OFp (1)] and (para-substituted benzenethiolato)dicarbonyl(5-cyclopentadienyl) iron [p-G-C6H4SFp (2)] were studied using Hartree-Fock and density functional theory (DFT) methods with large basis sets. In this study, Fp is (5-C5H5)Fe(CO)2, and G are NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2. The results show that DFT methods can provide the best price/performance ratio and accurate predictions of Hhomo(Fe-O)'s and Hhomo(Fe-S)'s. The remote substituent effects on Hhomo(Fe-O)'s and Hhomo(Fe-S)'s [Hhomo(Fe-O)'s and Hhomo(Fe-S)'s] can also be satisfactorily predicted. The good correlations [r=0.98 (g, 1), 0.98 (g, 2)] of Hhomo(Fe-O)'s and Hhomo(Fe-S)'s in series 1 and 2 with the substituent sigma p+ constants imply that the para-substituent effects on Hhomo(Fe-O)'s and Hhomo(Fe-S)'s originate mainly from polar effects, but those on radical stability originate from both spin delocalization and polar effects. Hhomo(Fe-O)'s (1) and Hhomo(Fe-S)'s (2) conform to the captodative principle. Insight from this work may help the design of more effective catalytic processes. Copyright (c) 2013 John Wiley & Sons, Ltd

Remote substituent effects on gas-phase homolytic Fe-O and Fe-S bond energies of p-G-C6H4OFe(CO)2(η5- C5H5) and p-G-C6H4SFe(CO) 2(η5-C5H5) studied using Hartree-Fock and density functional theory methods

Metal-ligand bond enthalpy data can afford invaluable insights into important reaction patterns in organometallic chemistry and catalysis. In this paper, the Fe-O and Fe-S homolytic bond dissociation energies [ΔH homo(Fe-O)'s and ΔHhomo(Fe-S)'s] of two series of para-substituted phenoxydicarbonyl(η5-cyclopentadienyl) iron [p-G-C6H4OFp (1)] and (para-substituted benzenethiolato)dicarbonyl(η5-cyclopentadienyl) iron [p-G-C 6H4SFp (2)] were studied using Hartree-Fock and density functional theory (DFT) methods with large basis sets. In this study, Fp is (η5-C5H5)Fe(CO)2, and G are NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2. The results show that DFT methods can provide the best price/performance ratio and accurate predictions of ΔH homo(Fe-O)'s and ΔHhomo(Fe-S)'s. The remote substituent effects on ΔHhomo(Fe-O)'s and ΔH homo(Fe-S)'s [ΔΔHhomo(Fe-O)'s and ΔΔHhomo(Fe-S)'s] can also be satisfactorily predicted. The good correlations [r = 0.98 (g, 1), 0.98 (g, 2)] of ΔΔH homo(Fe-O)'s and ΔΔHhomo(Fe-S)'s in series 1 and 2 with the substituent σp+ constants imply that the para-substituent effects on ΔHhomo(Fe-O)'s and ΔHhomo(Fe-S)'s originate mainly from polar effects, but those on radical stability originate from both spin delocalization and polar effects. ΔΔHhomo(Fe-O)'s (1) and ΔΔH homo(Fe-S)'s (2) conform to the captodative principle. Insight from this work may help the design of more effective catalytic processes. Copyright ? 2013 John Wiley & Sons, Ltd

Hartree-Fock and density functional theory study of remote substituent effects on gas-phase heterolytic Fe-O and Fe-S bond energies of p-G-C6H4OFe(CO)(2)(eta(5)-C5H5) and p-G-C6H4SFe(CO)(2)(eta(5)-C5H5)

Major State Basic Research Development Program [G2000078100]; Ministry of Science and Technology of China, State Key Laboratory of Elemento-organic Chemistry [201007]; Nankai University; Natural Science Foundation of China [51072093, 91022010]The knowledge of accurate bond strengths is a fundamental basis for a proper analysis of chemical reaction mechanisms. Quantum chemical calculations at different levels of theory have been used to investigate heterolytic FeaEuro'O and FeaEuro'S bond energies of paraaEurosubstituted phenoxydicarbonyl(i(5)aEurocyclopentadienyl) iron [paEuroGaEuroC(6)H(4)O(i(5)aEuroC(5)H(5))Fe(CO)(2), abbreviated as paEuroGaEuroC(6)H(4)OFp (1), where GaEuro?=aEuro?NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2] and paraaEurosubstituted benzenethiolatodicarbonyl(i(5)aEurocyclopentadienyl) iron [paEuroGaEuroC(6)H(4)S(i(5)aEuroC(5)H(5))Fe(CO)(2), abbreviated as paEuroGaEuroC(6)H(4)SFp (2)] complexes. The results show that BP86 and TPSSTPSS can provide the best price/performance ratio and more accurate predictions in the study of i"H-het(FeaEuro'O)'s and i"H-het(FeaEuro'S)'s. The excellent linear freeaEuroenergy relations [raEuro?=aEuro?0.99 (g, 1a), 1.00 (g, 2b)] among the i"i"H-het (FeaEuro'O)'s and i"pk(a)'s of OaEuro'H bonds of paEuroGaEuroC(6)H(4)OH or i"i"H-het(FeaEuroS)'s and i"pk(a)'s of SaEuro'H bonds of paEuroGaEuroC(6)H(4)SH imply that the governing structural factors for these bond scissions are similar. And the linear correlations [raEuro?=aEuro?a?'0.99 (g, 1g), a?'0.98 (g, 2h)] among the i"i"H-het (FeaEuroO)'s or i"i"H-het(FeaEuroS)'s and the substituent i integral(a?')(p) constants show that these correlations are in accordance with Hammett linear freeaEuroenergy relationships. The polar effects of these substituents and the basis set effects influence the accuracy of i"H-het(FeaEuro'O)'s or i"H-het(FeaEuro'S)'s. i"i"H-het(FeaEuro'O)'s(g) (1) and i"i"H-het(FeaEuro'S)'s(g)(2) follow the CaptoaEurodative principle. The substituent effects on the FeaEuro'O bonds are much stronger than those on the less polar FeaEuro'S bonds. Insight from this work may help the design of more effective catalytic processes. Copyright a (c) 2013 John Wiley & Sons, Ltd

Hartree-Fock and density functional theory study of remote substituent effects on gas-phase heterolytic Fe-O and Fe-S bond energies of p-G-C 6H4OFe(CO)2(η5-C 5H5) and p-G-C6H4SFe(CO) 2(η5-C5H5)

The knowledge of accurate bond strengths is a fundamental basis for a proper analysis of chemical reaction mechanisms. Quantum chemical calculations at different levels of theory have been used to investigate heterolytic Fe-O and Fe-S bond energies of para-substituted phenoxydicarbonyl(η5- cyclopentadienyl) iron [p-G-C6H4O(η5-C 5H5)Fe(CO)2, abbreviated as p-G-C 6H4OFp (1), where G-=-NO2, CN, COMe, CO 2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2] and para-substituted benzenethiolatodicarbonyl(η5-cyclopentadienyl) iron [p-G-C6H4S(η5-C5H 5)Fe(CO)2, abbreviated as p-G-C6H 4SFp (2)] complexes. The results show that BP86 and TPSSTPSS can provide the best price/performance ratio and more accurate predictions in the study of I?Hhet(Fe-O)'s and I?Hhet(Fe-S)'s. The excellent linear free-energy relations [r-=-0.99 (g, 1a), 1.00 (g, 2b)] among the I?I?Hhet (Fe-O)'s and I?pka's of O-H bonds of p-G-C6H4OH or I?I?Hhet(Fe-S) 's and I?pka's of S-H bonds of p-G-C6H4SH imply that the governing structural factors for these bond scissions are similar. And the linear correlations [r-=-0.99 (g, 1g),-0.98 (g, 2h)] among the I?I?Hhet (Fe-O)'s or I?I?Hhet(Fe-S)'s and the substituent Ip- constants show that these correlations are in accordance with Hammett linear free-energy relationships. The polar effects of these substituents and the basis set effects influence the accuracy of I?Hhet(Fe-O)'s or I?Hhet(Fe-S)'s. I?I?Hhet(Fe-O)'s(g) (1) and I?I?H het(Fe-S)'s(g)(2) follow the Capto-dative principle. The substituent effects on the Fe-O bonds are much stronger than those on the less polar Fe-S bonds. Insight from this work may help the design of more effective catalytic processes. Copyright ? 2013 John Wiley & Sons, Ltd