[The effect of miR-124 on homocysteine-induced atherosclerosis via promoter region DNA methylation in ApoE(-/-) mice].

The aim of the present study is to explore the role of miR-124 and its promoter region DNA methylation in homocysteine (Hcy)-induced atherosclerosis. ApoE(-/-) mice were fed with hypermethionine diet for 16 weeks to duplicate hyperhomocysteinemia model. Meanwhile, a normal control group (C57BL/6J mice fed with normal diet, N-control) and a model control group (ApoE(-/-) mice fed with normal diet, A-control) were set. The degree of atherosclerosis was observed by HE and oil red O staining. Automatic biochemical analyzer was used to detect the serum levels of Hcy. Foam cell model was duplicated and oil red O staining was used to confirm whether the model was successfully established. And foam cells were stimulated with 0, 50, 100, 200, 500 µmol/L Hcy and 50 µmol/L Hcy + 10 µmol/L AZC respectively. Real-time quantitative PCR (RT-qPCR) was used to detect the expressions of miR-124 in mice aorta and foam cells; Nested landing methylation specific PCR (nMS-PCR) was used to detect the levels of miR-124 promoter DNA methylation in mice aorta and foam cells. Meanwhile, the effects of DNA methylation inhibitor AZC on miR-124 expression were observed at the cellular level. The effect of miR-124 promoter DNA methylation status on lipid accumulation in foam cells was observed by oil red O staining. The results showed that compared with model control group, the serum levels of Hcy in high methionine group were significantly increased (P < 0.01) and developed aortic atherosclerotic plaque, the expression of miR-124 was markedly decreased (P < 0.01), while the levels of miR-124 promoter DNA methylation were significantly increased (P < 0.01). Given different levels of Hcy, the expression of miR-124 in foam cells was decreased, while the levels of miR-124 promoter DNA methylation were increased in a dose-dependent manner (P < 0.05, P < 0.01). AZC reversed the results of mentioned indices as above markedly (P < 0.05). Downregulation of miR-124 may play a role in Hcy-induced atherosclerosis and its promoter DNA methylation status may be an important mechanism in this process.

The impact of high-altitude migration on cardiac structure and function: a 1-year prospective study.

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

The diversity of difluoroacetylene coordination modes obtained by coupling fluorocarbyne ligands on binuclear manganese carbonyl sites.

Recent work has shown that the fluorocarbyne ligand CF, isoelectronic with the NO ligand, can be generated by the defluorination of CF(3) metal complexes, as illustrated by the 2006 synthesis by Hughes et al. of [C(5)H(5)Mo(CF)(CO)(2)] in good yield by the defluorination of [C(5)H(5)Mo(CF(3))(CO)(3)]. The fluorocarbyne ligand has now been investigated as a ligand in the manganese carbonyl complexes [Mn(CF)(CO)(n)] (n = 3, 4) and [Mn(2)(CF)(2)(CO)(n)] (n = 4-7) by using density functional theory. In mononuclear complexes, such as [Mn(CF)(CO)(4)], the CF ligand behaves very much like the NO ligand in terms of pi-acceptor strength. However, in the binuclear complexes the two CF ligands couple in many of the low-energy structures to form a bridging C(2)F(2) ligand derived, at least formally, from difluoroacetylene, FC[triple bond]CF. The geometries of such [Mn(2)(C(2)F(2))(CO)(n)] complexes suggest several different bonding modes of the bridging C(2)F(2) unit. These include bonding through the orthogonal pi bonds of FC[triple bond]CF, similar to the well-known [R(2)C(2)Co(2)(CO)(6)] complexes, or bonding of the C(2)F(2) unit as a symmetrical or unsymmetrical biscarbene. This research suggests that fluorocarbyne metal chemistry can serve as a means for obtaining a variety of difluoroacetylene metal complexes, thereby avoiding the need for synthesizing and handling the very unstable difluoroacetylene.

Effect of hydrogen atoms on the structures of trinuclear metal carbonyl clusters: trinuclear manganese carbonyl hydrides.

The structures of the trinuclear manganese carbonyl hydrides H(3)Mn(3)(CO)(n) (n = 12, 11, 10, 9) have been investigated by density functional theory (DFT). Optimization of H(3)Mn(3)(CO)(12) gives the experimentally known structure in which all carbonyl groups are terminal and each edge of a central Mn(3) equilateral triangle is bridged by a single hydrogen atom. This structure establishes the canonical distance 3.11 A for the Mn-Mn single bond satisfying the 18-electron rule. The central triangular (mu-H)(3)Mn(3) unit is retained in the lowest energy structure of H(3)Mn(3)(CO)(11), which may thus be derived from the H(3)Mn(3)(CO)(12) structure by removal of a carbonyl group with concurrent conversion of one of the remaining carbonyl groups into a semibridging carbonyl group to fill the resulting hole. The potential energy surface of H(3)Mn(3)(CO)(10) is relatively complicated with six singlet and five triplet structures. One of the lower energy H(3)Mn(3)(CO)(10) structures has one of the hydrogen atoms bridging the entire Mn(3) triangle and the other two hydrogen atoms bridging Mn-Mn edges. This H(3)Mn(3)(CO)(10) structure achieves the favored 18-electron configuration with a very short MnMn triple bond of 2.36 A. The other low energy H(3)Mn(3)(CO)(10) structure retains the (mu-H)(3)Mn(3) core of H(3)Mn(3)(CO)(12) but has a unique six-electron donor eta(2)-mu(3) carbonyl group bridging the entire Mn(3) triangle similar to the unique carbonyl group in the known compound Cp(3)Nb(3)(CO)(6)(eta(2)-mu(3)-CO). For H(3)Mn(3)(CO)(9) a structure with a central (mu(3)-H)(2)Mn(3) trigonal bipyramid lies >20 kcal/mol below any of the other structures. Triplet structures were found for the unsaturated H(3)Mn(3)(CO)(n) (n = 11, 10, 9) systems but at significantly higher energies than the lowest lying singlet structures.

Mononuclear and binuclear manganese carbonyl hydrides: the preference for bridging hydrogens over bridging carbonyls.

The structures of the mononuclear derivatives HMn(CO)n (n=4 and 3) are shown by density functional theory (B3LYP and PB86) to derive from octahedral HMn(CO)5 by losses of various combinations of carbonyl groups with relatively little change in the C-Mn-C angles involving the remaining carbonyl groups. The binuclear H2Mn2(CO)n structures are predicted to have bridging hydrogen atoms in preference to bridging carbonyl groups. Thus, two structures are found for the binuclear H2Mn2(CO)9, isoelectronic with Fe2(CO)9, in which all nine of the carbonyl groups are terminal carbonyl groups. The lowest lying H2Mn2(CO)9 structure is the dihydrogen complex (OC)5Mn-Mn(CO)4(eta2-H2), in which one of the equatorial CO groups of Mn2(CO)10 is replaced by a dihydrogen ligand. A slightly higher energy H2Mn2(CO)9 structure by approximately 6 kcal mol(-1) has an Mn-Mn bond bridged by a single hydrogen and all terminal carbonyl groups as well as a single terminal hydrogen. The H2Mn2(CO)8 molecule is predicted to have a structure with a central Mn(micro-H)2Mn core related to diborane. In this structure the manganese-manganese bond of length 2.703 A (BP86) can be considered the diprotonated formal double bond required to give both manganese atoms the favoured 18-electron configuration. The more highly unsaturated H2Mn2(CO)n (n=7, 6) derivatives have similar structures derived from the H2Mn2(CO)8 structure by loss of one or two carbonyl groups. In many cases the Mn[triple bond, length as m-dash]Mn distance in the central Mn(micro-H)2Mn unit shortens to approximately 2.4 A suggesting a diprotonated triple bond.