High fat diet significantly changed the global gene expression profile involved in hepatic drug metabolism and pharmacokinetic system in mice.

BACKGROUND: High fat diet impact transcription of hepatic genes responsible for drug metabolism and pharmacokinetics. Until now, researches just focused on a couple specific genes without a global profile showing. Age-dependent manner was also not noted well. This study aims to investigate the high fat diet effect on transcriptome of drug metabolism and pharmacokinetic system in mouse livers and show the age-dependent evidence. METHODS: C57BL/6 male mice were used in this experiment. High fat diet was used to treat mice for 16 and 38 weeks. Serum total cholesterol, low density lipoprotein cholesterol, aspartate transaminase, and alanine transaminaselevels were measured. Meanwhile, Histology, RNA-Seq, RT-PCR analysis and fourteen major hepatic bile acids quantification were performed for the liver tissues. Data was mined at levels of genes, drug metabolism and pharmacokinetic sysem, and genome wide. RESULTS: Treatment with high fat diet for 38 weeks significantly increased levels of serum lipids as well as aspartate transaminase, and alanine transaminase. Meanwhile, lipid accumulation in livers was observed. At week 38 of the experiment, the profile of 612 genes involved in drug metabolism and pharmacokinetics was significantly changed, indicated by a heatmap visulization and a principal component analysis. In total 210 genes were significantly regulated. Cyp3a11, Cyp4a10, and Cyp4a14 were down-regulated by 10-35 folds, while these three genes also were highly expressed in the liver. High fat diet regulated 11% of genome-wide gene while 30% of genes involved in the hepatic drug metabolism and pharmacokinetic system. Genes, including Adh4, Aldh1b1, Cyp3a11, Cyp4a10, Cyp8b1, Fmo2, Gsta3, Nat8f1, Slc22a7, Slco1a4, Sult5a1, and Ugt1a9, were regulated by high fat diet as an aging-dependent manner. Bile acids homeostasis, in which many genes related to metabolism and transportation were enriched, was also changed by high fat diet with an aging-dependet manner. Expression of genes in drug metabolism and disposition system significantly correlated to serum lipid profiles, and frequently correlated with each other. CONCLUSIONS: High fat diet changed the global transcription profile of hepatic drug metabolism and pharmacokinetic system with a age-dependent manner.

Coordination and Supramolecular Assemblies of Fully Substituted Cyclopentanocucurbit[6]uril with Lanthanide Cations in the Presence of Tetrachlorozincate Anions, and Their Potential Applications.

Coordination and supramolecular assemblies of a fully substituted cyclopentanocucurbit[6]uril (CyP6Q[6]) with a series of lanthanide cations (Ln3+) have been investigated in the presence of tetrachlorozincate anion ([ZnCl4]2-). X-ray single-crystal diffraction analysis has revealed that the interaction of CyP6Q[6] and a series of Ln3+cations unexpectedly results in the formation of at least seven different CyP6Q[6]-based coordination complex adduct and supramolecular assemblies groups, including with (1) La3+, Ce3+cations; (2) Pr3+, Nd3+cations; (3) Eu3+, Gd3+, Tb3+, Dy3+ with P1̅ or P1 space group, in which CyP6Q[6] molecules coordinate alternatively with Ln3+cations and form linear coordination polymers; (4) CyP6Q[6] molecules interact alternatively with [Ho(H2O)8]3+ aqueous complexes and form linear supramolecular chains; CyP6Q[6] molecules can assemble two different Ln3+ free porous supramolecular assemblies from CyP6Q[6]-Ln(NO3)3-ZnCl2-HCl systems, Ln = Tm, Yb, and Lu; however, no solid crystals were obtained from system containing Er3+cation. Thus, these differences could lead CyP6Q[6] to be useful in not only the isolation of lighter lanthanides from their heavier lanthanides but also special selectivity for different volatile organic compounds.

A turn-on supramolecular fluorescent probe for sensing benzimidazole fungicides and its application in living cell imaging.

A cucurbit[8]uril-based turn-on supramolecular fluorescent probe between cucurbit[8]uril (Q[8]) and pyronine Y (PyY) (designated 2PyY@Q[8]) in acidic aqueous solution showed a remarkable fluorescence 'turn-on' response to benzimidazole fungicides such as thiabendazole, fuberidazole and carbendazim. The 2PyY@Q[8] fluorescent probe can be used to detect benzimidazole fungicides with high sensitivity and selectivity with a detection limit of ~10-8mol/L. A good linear relationship of emission intensity at ~580nm for benzimidazole fungicides at concentrations of 0.4-5.0µmol/L was observed. The proposed sensing mechanism was investigated using 1H NMR spectroscopy combined with density functional theory calculations at the B3LYP/6-31G(d) level. The cell imaging study showed that the 2PyY@Q[8] complex could be used to image benzimidazole fungicide in prostate cancer (PC3) cells, which may help to elucidate relevant biological processes at the molecular level.

Tuning the giant magnetoelastic transition in Ba3BiIr2O9 and Ba3BiRu2O9.

We have experimentally investigated the effects of pressure on the magnetoelastic transitions associated with the opening of spin-gaps in Ba3BiIr2O9 and Ba3BiRu2O9. For both compounds, reducing the unit cell volume by either external physical and internal chemical pressure was found to reduce the temperature T(*) of the transition and, to a lesser extent, the magnitude of the associated negative thermal volume expansion. The results yield the latent heat associated with the transitions, -3.34(3) × 10(2) J mol(-1) for Ba3BiIr2O9 and -7.1(5) × 10(2) J mol(-1) for Ba3BiRu2O9. The transition in Ba3BiRu2O9 is significantly more robust than in Ba3BiIr2O9, requiring an order of magnitude higher pressures to achieve the same reduction in T(*). The differing responses of the two compounds points to differences between the 4d and 5d metals and hence to the importance of spin-orbit coupling, which is expected to be much stronger in the Ir compound.

Pressure-induced intersite Bi-M (M=Ru, Ir) valence transitions in hexagonal perovskites.

Pressure-induced charge transfer from Bi to Ir/Ru is observed in the hexagonal perovskites Ba(3+n)BiM(2+n)O(9+3n) (n=0,1; M=Ir,Ru). These compounds show first-order, circa 1% volume contractions at room temperature above 5 GPa, which are due to the large reduction in the effective ionic radius of Bi when the 6s shell is emptied on oxidation, compared to the relatively negligible effect of reduction on the radii of Ir or Ru. They are the first such transitions involving 4d and 5d compounds, and they double the total number of cases known. Ab initio calculations suggest that magnetic interactions through very short (ca. 2.6 Å) M-M bonds contribute to the finely balanced nature of their electronic states.

[Preparation of new solid-phase microextraction fiber based on cucurbit[7] uril coordination polymers and its application in determination of polycyclic aromatic hydrocarbons from environmental water samples].

A novel solid-phase microextraction fiber was prepared via simple adhesion process. Fused-silica fiber was used as supporting substrate and the cucurbit[7] uril/Eu coordination polymers induced by [CdCl4]2- anion was affixed onto the surface of fused-silica fiber with high-temperature epoxy resin as a sorbent coating. The SPME coating was characterized by scanning electron microscopy and thermal analysis. Coupled to gas chromatography, the fiber was used to extract polycyclic aromatic hydrocarbons (PAHs) in aqueous samples. Analytical performances of the proposed method were investigated under the optimum extraction conditions (extraction temperature, 75 °C; mass concentration of NaCl, 200 g/L; extraction time, 40 min; desorption time, 2 min; desorption temperature, 250 °C) compared with commercial fibers for the same analytes. For the seven PAHs (naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene and pyrene), good linearity was obtained ranging from 1 µg/L to 1000 µg/L. Limits of detection were 0.29-2.09 µg/L with the RSDs no more than 8.6%. The established SPME-GC method was applied to determine the spiked PAHs in real river water samples and satisfactory results were obtained with recoveries between 97. 2% and 109. 0%. Under the optimal conditions, the extraction effect of home-made coating was similar to the commercial PDMS (polydimethylsiloxane) coating, which further confirmed its potential in the solid-phase microextraction.

Key role of bismuth in the magnetoelastic transitions of Ba3BiIr2O9 and Ba3BiRu2O9 as revealed by chemical doping.

The key role played by bismuth in an average intermediate oxidation state in the magnetoelastic spin-gap compounds Ba3BiRu2O9 and Ba3BiIr2O9 has been confirmed by systematically replacing bismuth with La(3+) and Ce(4+). Through a combination of powder diffraction (neutron and synchrotron), X-ray absorption spectroscopy, and magnetic properties measurements, we show that Ru/Ir cations in Ba3BiRu2O9 and Ba3BiIr2O9 have oxidation states between +4 and +4.5, suggesting that Bi cations exist in an unusual average oxidation state intermediate between the conventional +3 and +5 states (which is confirmed by the Bi L3-edge spectrum of Ba3BiRu2O9). Precise measurements of lattice parameters from synchrotron diffraction are consistent with the presence of intermediate oxidation state bismuth cations throughout the doping ranges. We find that relatively small amounts of doping (∼10 at%) on the bismuth site suppress and then completely eliminate the sharp structural and magnetic transitions observed in pure Ba3BiRu2O9 and Ba3BiIr2O9, strongly suggesting that the unstable electronic state of bismuth plays a critical role in the behavior of these materials.

Structural and magnetic studies of the electron doped manganites Sr0.65Pr0.35-xCexMnO3 (0.00 ≤ x ≤ 0.35).

The nuclear and magnetic structures and properties of Sr0.65Pr0.35-xCexMnO3 (0.00 ≤ x ≤ 0.35) were investigated using a combination of synchrotron x-ray and neutron powder diffraction, along with magnetic and x-ray absorption near edge structure measurements. At room temperature, doping with Ce results in a transition from a tetragonal structure in I4/mcm to an orthorhombic one in Imma associated with the loss of long range orbital ordering. At low temperatures, we observe the formation of an orthorhombic Fmmm phase. XANES measurements demonstrate that the Ce exists as a mixture of Ce(3+) and Ce(4+).

N-(7-Methyl-1,8-naphthyridin-2-yl)acetamide-acetic acid (1/1).

In the title adduct, C11H11N3O·C2H4O2, all non-H atoms of the acetamide mol-ecule are roughly coplanar, with an r.m.s. deviation of 0.0720 Å. The dihedral angle between the ring plane and the acetamide group is 8.5 (2)°. In the crystal, O-H⋯N and N-H⋯O hydrogen bonds link the acetamide and acetic acid mol-ecules.

N-(7-Dibromo-methyl-5-methyl-1,8-naphthyridin-2-yl)acetamide-pyrrolidine-2,5-dione (1/1).

In the title co-crystal, C(12)H(11)Br(2)N(3)O·C(4)H(5)NO(2), the naphthyridine derivative and the pyrrolidine-2,5-dione mol-ecules have crystallographic mirror-plane symmetry with all non-H atoms, except the Br atom, located on the mirror plane. In the crystal, N-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into heterodimers. These dimers are further linked into a one-dimensional structure along [010] by weak C-Br⋯O inter-actions [Br⋯O = 3.028 (5) Šand C-Br⋯O = 158.52 (4)°].

[Advances in studies on chemical constituents and biological activities of Desmodium species].

The chemical constituents isolated from Desmodium species (Leguminosae) included terpenoids, flavonoids, steroids, alkaloids compounds. Modem pharmacological studies have showed that the Desmodium species have antioxidant, antibacterial, anti-inflammatory, hepatoprotective, diuretic, antipyretic, analgesic and choleretic activity. This article mainly has reviewed the research advances of chemical constituents and biological activities of Desmodium species since 2003.

Giant magnetoelastic effect at the opening of a spin-gap in Ba3BiIr2O9.

As compared to 3d (first-row) transition metals, the 4d and 5d transition metals have much more diffuse valence orbitals. Quantum cooperative phenomena that arise due to changes in the way these orbitals overlap and interact, such as magnetoelasticity, are correspondingly rare in 4d and 5d compounds. Here, we show that the 6H-perovskite Ba(3)BiIr(2)O(9), which contains 5d Ir(4+) (S = 1/2) dimerized into isolated face-sharing Ir(2)O(9) bioctahedra, exhibits a giant magnetoelastic effect, the largest of any known 5d compound, associated with the opening of a spin-gap at T* = 74 K. The resulting first-order transition is characterized by a remarkable 4% increase in Ir-Ir distance and 1% negative thermal volume expansion. The transition is driven by a dramatic change in the interactions among Ir 5d orbitals, and represents a crossover between two very different, competing, ground states: one that optimizes direct Ir-Ir bonding (at high temperature), and one that optimizes Ir-O-Ir magnetic superexchange (at low temperature).

Structures and phase transitions in the ordered double perovskites Ba2BiIIIBiVO6 and Ba2BiIIISbVO6.

High-resolution neutron powder diffraction has been used to investigate the structures and phase transitions in the double perovskites Ba(2)Bi(3+)Bi(5+)O(6) (dibarium dibismuth hexaoxide) and Ba(2)BiSbO(6) (dibarium bismuth antimony hexaoxide) in the temperature ranges 4.2-973 and 4.2-625 K, respectively. The charge-ordered bismuthate adopts four structures in the temperature range - monoclinic in P2(1)/n, monoclinic in I2/m, rhombohedral in R3, and finally cubic in Fm3m. The low-temperature monoclinic structure has been determined for the first time. The transitions from P2(1)/n to I2/m, at 132 K, and R3 to Fm3m, at 820 K, are tricritical in nature; the transition from I2/m to R3 at ca 430 K is discontinuous. The behaviour of Ba(2)BiSbO(6) is very similar, except that the transition temperatures are lower - 250 K for I2/m to R3 and 515 K for R3 to Fm3m - and the low-temperature structure is not formed at all. The R3 to Fm3m transition in this compound is closer to second order in nature, although there is evidence for some contribution from higher-order terms.

XAFS studies of anti-inflammatory dinuclear and mononuclear Zn(II) complexes of indomethacin.

Zinc K-edge X-ray absorption fine structure (XAFS) experiments were performed in the solid and solution states at low temperature (10 K), on dimeric and monomeric anti-inflammatory Zn(II) complexes of indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid=IndoH] of the formula [Zn2(Indo)4L2] [L=pyridine (Py), N,N-dimethylacetamide (DMA)], [Zn(Indo)2L2] [L=ethanol (EtOH), methanol (MeOH)], and Zn(II) acetate dihydrate [Zn(OAc)2(OH2)2]. The bond distances and angles obtained from multiple-scattering fits to the XAFS data of the Zn(II) dimeric complexes in the solid and solution states exhibit excellent correspondence with those obtained from single crystal diffraction studies. The Zn...Zn separations of 2.97 and 2.96 A and carboxylate group O-C-O angles of 125 degrees for powdered [Zn2(Indo)4(Py)2] and [Zn2(Indo)4(DMA)2] agree well with the XRD values of 2.969(1) and 2.9686(6) A and 125.8(4) degrees and 126.1(2) degrees, respectively. The calculated Zn-O(RCOO) and Zn-L bond distances of 2.03 and 2.04 A, or 2.02 and 1.98 A for Py or DMA complexes, respectively, also agree well with crystallographic data. The X-ray powder diffraction data on samples of the monomers exhibited additional reflections apart from those due to the crystallographically characterized cis-[Zn(eta2-O,O'-Indo)2L2], but microanalyses were consistent with this formulation. Therefore, mixed models that contained the cis complex and a second component consisting of a trans-six-coordinate complex, a five-coordinate complex, or a four-coordinate complex were used to model the XAFS. The best fits to the XAFS data were obtained with a mixture of the cis-six-coordinate complex and a four-coordinate complex containing two monodentate Indo ligands. The bond lengths for the six-coordinate structure were consistent with those determined on a single crystal, and those for the four-coordinate complexes were consistent with related four-coordinate structures with two monodentate carboxylate ligands. Dissolution of the dimer (DMA adduct) in DMF resulted in a mixture of dimer and monomer species as shown by MS XAFS fitting. This is the first time that solution structures have been determined for anti-inflammatory Zn(II) complexes, and this is an important first step in understanding the pharmacology of the complexes.

Gastrointestinal toxicity, antiinflammatory activity, and superoxide dismutase activity of copper and zinc complexes of the antiinflammatory drug indomethacin.

Gastrointestinal (GI) toxicity is one of the major problems associated with antiinflammatory drugs. The complexation of the powerful antiinflammatory drug (IndoH) by metal ions, as a means of reducing GI toxicity, has been studied. The in vitro superoxide dismutase (SOD) activity, in vivo antiinflammatory activity, and gastrointestinal ulcerogenic properties of IndoH, [Cu2(Indo)4(DMF)2], and [Zn2(Indo)4(DMA)2] are reported. No SOD activity was observed for IndoH or [Zn2(Indo)4(DMA)2], but [Cu2(Indo)4(DMF)2] inhibited the reduction of nitroblue tetrazolium (NBT) at an IC50 value of 0.23 microM. All three compounds exhibited antiinflammatory activity in male Sprague-Dawley rats at an equivalent Indo dose of 10 mg/kg following oral administration of the drugs in 2% CMC solution. The severity of the toxicity (macroscopic ulcerations) in the stomach following oral dosing with [Zn2(Indo)4(DMF)2] was not significantly lower than that induced by IndoH (P = 0.78). Gastric ulcerations induced by [Cu2(Indo)4(DMF)2] were significantly lower than those induced by IndoH or [Zn2(Indo)4(DMA)2] (P = 0.0012 and P = 0.0175, respectively) but significantly greater than the control (P = 0.0013). The intestinal ulcerations induced by [Cu2(Indo)4(DMF)2] or [Zn2(Indo)4(DMA)2] were approximately 15 times lower than those of IndoH. A further indicator of gastrointestinal toxicity, caecal haemoglobin, increased in the following order: control < [Cu2(Indo)4(DMF)2] < [Zn2(Indo)4(DMA)2] < IndoH.[Cu2(Indo)4(DMF)2] exhibited the most promising results of the Indo complexes assayed, in that it exhibited SOD activity and the lowest gastrointestinal damage while also exhibiting antiinflammatory activity that was comparable to that for IndoH. Low-temperature EPR analyses also showed that the formulation used for [Cu2(Indo)4(DMF)2] administration was crucial to the integrity of the complex.