Betulinic acid prevents high glucose­induced expression of extracellular matrix protein in cardiac fibroblasts by inhibiting the TGF­ß1/Smad signaling pathway.

The proliferation and differentiation of cardiac fibroblasts (CFs) is central to cardiac fibrosis. Betulinic acid (BA) is an active compound isolated from the bark of the birch tree Betula spp. (Betulaceae) and has been shown to attenuate hepatic fibrosis. However, the effect of BA on the high glucose­induced fibrosis response in CFs remains to be elucidated, therefore, the present study investigated the effect of BA on high glucose­induced CFs and examined the possible mechanism underlying the effect of BA on CF transdifferentiation. CFs were pre­incubated with various concentrations of BA for 24 h and then stimulated with high glucose (25 mM) for various times. Cell proliferation was evaluated using an MTT assay. The mRNA expression levels of α­smooth muscle actin (SMA) and transforming growth factor (TGF)­ß1 were determined using reverse transcription­quantitative polymerase chain reaction analysis. The protein expression levels of α­SMA, collagen I, collagen III, fibronectin, TGF­ß1, small mothers against decapentaplegic (Smad)2/3, phosphorylated (p)­Smad2 and p­Smad3 and were detected using western blot analysis. The data revealed that BA attenuated the CF proliferation and myofibroblast differentiation induced by high glucose. In addition, BA inhibited the expression of extracellular matrix (ECM) in the CFs induced by high glucose. It was also found that BA inhibited the high glucose­induced phosphorylation of Smad2/3 in the CFs. Taken together, BA suppressed the high glucose­induced increase in the proliferation of CFs and expression of ECM via inhibition of the TGF­ß1/Smad signaling pathway. Thus, BA may offer therapeutic potential towards the treatment of cardiac fibrosis.

Cyano-bridged FeIII2CuII3 and FeIII4NiII4 complexes: syntheses, structures, and magnetic properties.

Two tricyanometallate precursors, (Bu4N)[(Tp4Bo)Fe(CN)3].H2O.2MeCN (1) and (Bu4N)[(pzTp)Fe(CN)3] (2) [Bu4N+ = tetrabutylammonium cation; Tp4Bo = tris(indazolyl)hydroborate; pzTp = tetrakis(pyrazolyl)borate], with a low-spin FeIII center have been synthesized and characterized. The reactions of 1 or 2 with [Cu(Me3tacn)(H2O)2](ClO4)2 (Me3tacn = N,N',N' '-trimethyl-1,4,7-triazacyclononane) afford two pentanuclear cyano-bridged clusters, [(Tp4Bo)2(Me3tacn)3Cu3Fe2(CN)6](ClO4)4.5H2O (3) and [(pzTp)2(Me3tacn)3Cu3Fe2(CN)6](ClO4)4.4H2O (4), respectively. Assembly reactions between 2 and [Ni(phen)(CH3OH)4](ClO4)2 (phen = 1,10-phenanthroline) or Zn(OAc)2.2H2O afford a molecular box [(pzTp)4(phen)4Ni4Fe4(CH3OH)4(CN)12](ClO4)4.4H2O (5) and a rectangular cluster [(pzTp)2Zn2Fe2(OAc)2(H2O)2(CN)6] (6). Their molecular structures were determined by single-crystal X-ray diffraction. In complexes 1 and 2, the central FeIII ions are coordinated by three cyanide carbon atoms and three nitrogen atoms of Tp4Bo- or pzTp-. Both complexes 3 and 4 show a trigonal-bipyramidal geometry, in which [(L)Fe(CN)3]- units occupy the apical positions and are linked through cyanide to [Cu(Me3tacn)]2+ units situated in the equatorial plane. Complex 5 possesses a cubic arrangement of eight metal irons linked through edge-spanning cyanide bridges, while complex 6 shows Zn2Fe2(CN)4 rectangular structure, in which FeIII and ZnII ions are alternately bridged by the cyanide groups. Intramolecular ferromagnetic couplings are observed for complexes 3-5, and they have S = 5/2, 5/2, and 6 ground states and appreciable magnetic anisotropies with negative D values equal to -0.49, -2.39, and -0.39 cm-1, respectively.

Cyano-bridged pentanuclear Fe(III)3M(II)2 (M = Ni, Co, Fe) clusters: synthesis, structures, and magnetic properties.

The reactions of [M(II)(Tpm(Me))(H2O)3]2+ (M = Ni, Co, Fe; Tpm(Me) = tris(3,5-dimethyl-1-pyrazoyl)methane) with [Bu4N][(Tp)Fe(III)(CN)3] (Bu4N+ = tetrabutylammonium cation; Tp = tris(pyrazolyl)hydroborate) in MeCN-Et2O afford three pentanuclear cyano-bridged clusters, [(Tp)3(Tpm(Me))2Fe(III)3M(II)2(CN)9]ClO4.15H2O (M = Ni, 1; M = Co, 2) and [(Tp)3(Tpm(Me))2Fe(III)3Fe(II)2(CN)9]BF4.15H2O (3). Single-crystal X-ray analyses reveal that they show the same trigonal bipyramidal structure featuring a D3h-symmetry core, in which two opposing Tpm(Me)-ligated M(II) ions situated in the two apical positions are linked through cyanide bridges to an equatorial triangle of three Tp-ligated Fe(III) (S = 1/2) centers. Magnetic studies for complex 1 show ferromagnetic coupling giving an S = 7/2 ground state and an appreciable magnetic anisotropy with a negative D(7/2) value equal to -0.79 cm(-1). Complex 2 shows zero-field splitting parameters deducted from the magnetization data with D = -1.33 cm(-1) and g = 2.81. Antiferromagnetic interaction was observed in complex 3.