The role of proliferator-activated receptor gamma coactivator-1 alpha in the fatty-acid -dependent transcriptional control of interleukin-10 in hepatic cells of rodents

Interleukin-10 (IL-10) is an endogenous factor that restrains hepatic insulin resistance in diet-induced steatosis Reducing IL-10 expression increases proinflammatory activity in the steatotic liver and worsens insulin resistance As the transcriptional coactivator proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) plays a central role in dysfunctional hepatocytic activity in diet-induced steatosis, we hypothesized that at least part of the action of PGC-1 alpha could be mediated by reducing the transcription of the IL-10 gene Here, we used immunoblotting, real-time polymerase chain reaction, immunocytochemistry, and chromatin immunoprecipitation assay to investigate the role of PGC-1 alpha in the control of IL-10 expression in hepatic cells First, we show that, in the intact steatotic liver, the expressions of IL-10 and PGC-1 alpha are increased Inhibiting PGC-1 alpha expression by antisense oligonucleotide increases IL-10 expression and reduces the steatotic phenotype. In cultured hepatocytes, the treatment with saturated and unsaturated fatty acids increased IL-10 expression. This was accompanied by increased association of PGC-1 alpha with c-Maf and p50-nuclear factor (NF) kappa B, 2 transcription factors known to modulate IL-10 expression In addition, after fatty acid treatment. PGC-1 alpha, c-Maf, and p50-NF kappa B migrate from the cytosol to the nuclei of hepatocytes and bind to the IL-10 promoter region Inhibiting NF kappa B activation with salicylate reduces IL-10 expression and the association of PGC-1 alpha with p50-NF kappa B Thus, PGC-1 alpha emerges as a potential transcriptional regulator of the inflammatory phenomenon taking place in the steatotic liver (C) 2010 Elsevier Inc All rights reserved

Adsorption of Pb(2+), Cu(2+) and Cd(2+) in FDU-1 silica and FDU-1 silica modified with humic acid

Ordered mesoporous silica with cubic structure, type FDU-1, was synthesized under strong acid media using B-50-6600 poly(ethylene oxide)-poly(butilene oxide)-poly(ethylene oxide) triblock copolymer (EO(39)BO(47)EO(39)) and tetraethyl orthosilicate (TEOS). Humic acid (HA) was modified to the synthesis process at a concentration of 1.5 mmol per gram of SiO(2). Thermogravimetry, small angle X-ray diffraction, nitrogen adsorption and high resolution transmission electron microscopy were used to characterize the samples. The pristine FDU-1 and FDU-1 with incorporated 1.5 mmol of HA were tested for adsorption of Pb(2+), Cu(2+) and Cd(2+) in aqueous solution. Incorporation of humic acid into the FDU-1 silica afforded an adsorbent with strong affinity for Cd(2+), Cu(2+) and Pb(2+) from single ion solutions. Adsorption of Cu(2+) was significantly enhanced after incorporation of humic acid, a fact that can be explained by the formation of complexes with carboxylic and phenolic groups at low concentrations of the metal cation. The results demonstrated the potential applicability of FDU-1 with incorporated HA in the removal of low concentrations of heavy metal cations from aqueous solution, such as wastewaters, after usual precipitation of metal hydroxides in alkaline medium and proper pH conditioning in the range between 6 and 7. (C) 2007 Elsevier Inc. All rights reserved.

Lead(II)-induced formation and coordination of 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one

Cyclization of (n)butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)(2) led to tile formation of the complex [Pb(HTz)(2)] (H(2)Tz = 3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)](n), the first example of a Tz(2-) metal complex. (C) 2008 Elsevier B.V. All rights reserved.

New insights on surface-enhanced Raman scattering based on controlled aggregation and spectroscopic studies, DFT calculations and symmetry analysis for 3,6-bi-2-pyridyl-1,2,4,5-tetrazine adsorbed onto citrate-stabilized gold nanoparticles

Asystematic study on the surface-enhanced Raman scattering (SERS) for 3,6-bi-2-pyridyl-1,2,4,5-tetrazine (bptz) adsorbed onto citrate-modified gold nanoparticles (cit-AuNps) was carried out based on electronic and vibrational spectroscopy and density functional methods. The citrate/bptz exchange was carefully controlled by the stepwise addition of bptz to the cit-AuNps, inducing flocculation and leading to the rise of a characteristic plasmon coupling band in the visible region. Such stepwise procedure led to a uniform decrease of the citrate SERS signals and to the rise of characteristic peaks of bptz, consistent with surface binding via the N heterocyclic atoms. In contrast, single addition of a large amount of bptz promoted complete aggregation of the nanoparticles, leading to a strong enhancement of the SERS signals. In this case, from the distinct Raman profiles involved, the formation of a new SERS environment became apparent, conjugating the influence of the local hot spots and charge-transfer (CT) effects. The most strongly enhanced vibrations belong to a(1) and b(2) representations, and were interpreted in terms of the electromagnetic and the CT mechanisms: the latter involving significant contribution of vibronic coupling in the system. Copyright (C) 2010 John Wiley & Sons, Ltd.

Ultrasound promoted greener synthesis of 2-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles

A rapid and cleaner procedure for the synthesis of a series of 2-(3,5-diaryl-45-dihydro-1H-pyrazol-1-yl)-4-phenylthiazoles under ultrasonic irradiation in ethanol is described. (C) 2010 Elsevier B.V. All rights reserved.

Aflatoxins and cyclopiazonic acid in feed and milk from dairy farms in Sao Paulo, Brazil

The occurrence of aflatoxins (AF) B(1), B(2), G(1), G(2) and cyclopiazonic acid (CPA) in feeds, and AFM(1) and CPA in milk was determined in dairy farms located in the northeastern region of Sao Paulo state, Brazil, between October 2005 and February 2006. AF and CPA determinations were performed by HPLC. AFB(1) was found in 42% of feed at levels or 1.0-26.4 mu g kg(-1) (mean: 7.1 +/- 7.2 mu g kg(-1)). The concentrations of AFM(1) in raw milk varied between 0.010 and 0.645 mu g l(-1) (mean: 0.104 +/- 0.138 mu g l(-1)). Only one sample was above the tolerance limit adopted in Brazil (0.50 mu g l(-1)) for AFM(1) in milk. Regarding CPA in feed, six (12%) samples showed concentrations of 12.5-1533 mu g kg(-1) (mean: 57.6 +/- 48.7 mu g kg(-1)). CPA was detected in only three milk samples (6%) at levels of 6.4, 8.8 and 9.1 mu g l(-1). Concentrations of aflatoxins and CPA in feed and milk were relatively low, although the high frequency of both mycotoxins indicates the necessity to continuously monitor dairy farms to prevent contamination of feed ingredients.

Abscisic acid and auxin accumulation in Catasetum fimbriatum roots growing in vitro with high sucrose and mannitol content

Endogenous contents of indolyl-3-acetic acid (IAA) and abscisic acid (ABA) were quantified in excised roots of Catasetum fimbriatum (Orchidaceae) cultured in vitro on solidified Vacin and Went medium with 1, 2, 4, 6, 8 and 10 % sucrose, as well as 2 % sucrose plus mannitol. Maximum root growth was observed in media with 4 % sucrose and 2 % sucrose plus 2.2 % mannitol, suggesting that a moderate water or osmotic stress promotes orchid root growth. Contents of both ABA and IAA increased in parallel to increasing sucrose concentration and a correlation between root elongation and the ABA/IAA ratio was observed. Incubating isolated C. fimbriatum roots with radiolabeled tryptophan, we showed an accumulation of IAA and its conjugates.

Lipid, fatty acid, protein, amino acid and ash contents in four Brazilian red algae species

Four species of marine benthic algae (Laurencia filiformis, L. intricata, Gracilaria domingensis and G. birdiae) that belong to the phylum Rhodophyta were collected in Espirito Santo State, Brazil and investigated concerning their biochemical composition (fatty acid, total lipid, soluble proteins, amino acid and ash). The total content of lipid (% dry weight) ranged from 1.1% to 6.2%: fatty acid from 0.7% to 1.0%: soluble protein from 4.6% to 18.3%, amino acid from 6.7% to 11.3% and ash from 22.5% to 38.4%. judging from their composition, the four species of algae appear to be potential sources of dietary proteins, amino acids, lipids and essential fatty acids for humans and animals. (C) 2009 Elsevier Ltd. All rights reserved.

Caldensinic acid, a prenylated benzoic acid from Piper caldense

The CH(2)Cl(2) and MeOH extracts from leaves of Piper caldense were subjected to chromatographic separation procedures to afford the new prenylated benzoic acid, caldensinic acid (3-[(2`E,6`E,10`E)-11`-carboxy-3`,7`,15`-trimethylhexadeca-2`,6`,10`,14`-tetraenyl]-4,5-dihydroxybenzoic acid) whose structure was determined by spectral analysis, mainly NMR ((1)H, (13)C, HSQC, HMBC) and ESI-MS. The natural compound and derivatives displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum by direct bioautography. (C) 2009 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.

Modulation of rat neutrophil function in vitro by cis- and trans-MUFA

In the present study, the effects of trans-MUFA, elaidic acid (EA; 18 : 1-9t) and vaccenic acid (VA; 18 : 1-11t) on rat neutrophil functions were compared with those of cis-monounsaturated oleic acid (OA) (18 : 1-9c) and saturated stearic acid (SA; 18 : 0) (10-150 mu M). Trans-fatty acids enhanced neutrophil phagocytic capacity, superoxide (O(2)(center dot-)) and hydrogen peroxide production, and candidacidal activity. The same effects were observed for OA. Cells treated with trans-MUFA showed reduced production of NO(center dot), whereas those treated with OA showed an increase in production. Treatment with SA did not provoke significant effect on the parameters investigated. The increase in O(2)(center dot-) production induced by MUFA was not observed when diphenyleneiodonium, an NADPH oxidase inhibitor, was added to the medium. This finding suggests that MUFA stimulate neutrophil NADPH oxidase activity. The addition of 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4-(1H-inclol-3-yl)-1H-pyrrole-2,5-dione, a protein kinase C (PKC) inhibitor, and wortmannin, a phosphatidylinositol-3 kinase (PI3K) inhibitor, did not affect O(2)(center dot-) production induced by MUFA. Therefore, the mechanisms by which MUFA stimulate NADPH oxidase are not dependent on PKC and do not seem to involve PI3K. Experiments using Zn(2+), an inhibitor of NADPH oxidase H(+) channel, indicated that MUFA activate the NADPH oxidase complex in rat neutrophil due to opening of H(+) channel.

L-Proline uptake in Crithidia deanei is influenced by its endosymbiont bacterium

Crithidia deanei, a monoxenic trypanosomatid, presents an endosymbiotic bacterium in its cytoplasm. Both the protozoan and the bacterium maintain intensive metabolic exchange, resulting in an interesting model to study the coevolution of metabolisms. The relevance of L-proline for the growth of C. deanei and its transport into these cells was studied. Both the endosymbiont-containing (wild) and the endosymbiont-free protozoa (aposymbiont or cured) strains, when grown in medium supplemented with L-proline, reached higher cell densities than those grown in unsupplemented media. We biochemically characterized the uptake of L-proline in both the wild (K(m)=0.153 +/- 0.022 mM, V(max)=0.239 +/- 0.011 nmol min(-1) per 4 x 10(7) cells) and the aposymbiont strains (K(m)=0.177 +/- 0.049 mM, V(max)=0.132 +/- 0.012 nmol min(-1) per 4 x 10(7) cells). These data suggest a single type of proline transporter whose activity is upregulated by the presence of the symbiotic bacterium. Proline transport was further characterized and was found to be insensitive to the extracellular concentration of Na(+), but sensitive to K(+) and pH. The abolition of proline uptake by respiratory chain inhibitors and valinomycin indicates that the proline transport in C. deanei is dependent on the plasma membrane K(+) gradient.

Preparation of Achiral and Chiral (E)-Enaminopyran-2,4-diones and Their Phytotoxic Activity

A short and efficient approach to a range of new chiral and achiral functionalized (E)-enaminopyran-2,4-diones starting with commercially available dehydroacetic acid is described. The phytotoxic properties of these (E)-enaminopyran-2,4-diones were evaluated by their ability to interfere with the growth of Sorghum bicolor and Cucumis sativus seedlings. A different sensitivity of the two crops was evident with the (E)-enaminopyran-2,4-diones. The most active compounds were also tested against two weeds, Ipomoea grandifolia and Brachiaria decumbens. To the best of our knowledge, this is the first report describing enaminopyran-2,4-diones as potential plant growth regulators.

Ruthenium(II) complexes containing N(4)-tolyl-2-acetylpyridine thiosemicarbazones and phosphine ligands: NMR and electrochemical studies of cis-trans isomerization

[Ru(HL)(PPh3)(2)Cl]Cl complexes have been obtained in which HL = N(4)-ortho (complex 1), N(4)-meta (complex 2) and N(4) pctratolyl 2-acetylpyridine thiosemicarbazone (complex 3). NMR and electrochemical studies indicate that both cis and trans isomers exist in solution, and that the cis isomers are converted into the trans isomers with time. Crystal structure determination of (1) reveals that the traps isomer is formed in the solid state. (c) 2007 Elsevier B.V. All rights reserved.

Novel Zn(2+)-binding Sites in Human Transthyretin IMPLICATIONS FOR AMYLOIDOGENESIS AND RETINOL-BINDING PROTEIN RECOGNITION

Human transthyretin (TTR) is a homotetrameric protein involved in several amyloidoses. Zn(2+) enhances TTR aggregation in vitro, and is a component of ex vivo TTR amyloid fibrils. We report the first crystal structure of human TTR in complex with Zn(2+) at pH 4.6-7.5. All four structures reveal three tetra-coordinated Zn(2+)-binding sites (ZBS 1-3) per monomer, plus a fourth site (ZBS 4) involving amino acid residues from a symmetry-related tetramer that is not visible in solution by NMR.Zn(2+) binding perturbs loop E-alpha-helix-loop F, the region involved in holo-retinol-binding protein (holo-RBP) recognition, mainly at acidic pH; TTR affinity for holo-RBP decreases similar to 5-fold in the presence of Zn(2+). Interestingly, this same region is disrupted in the crystal structure of the amyloidogenic intermediate of TTR formed at acidic pH in the absence of Zn(2+). HNCO and HNCA experiments performed in solution at pH 7.5 revealed that upon Zn(2+) binding, although the alpha-helix persists, there are perturbations in the resonances of the residues that flank this region, suggesting an increase in structural flexibility. While stability of the monomer of TTR decreases in the presence of Zn(2+), which is consistent with the tertiary structural perturbation provoked by Zn(2+) binding, tetramer stability is only marginally affected by Zn(2+). These data highlight structural and functional roles of Zn(2+) in TTR-related amyloidoses, as well as in holo-RBP recognition and vitamin A homeostasis.

Total phenolic content and free radical scavenging activities of methanolic extract powders of tropical fruit residues

Methanolic extract powders of acerola, passion fruit and pineapple industrial residues, including pulp, seeds and peel, altogether (except for acerola) devoid of seeds, were screened for antioxidant capacity. The total phenolic contents (TPCs) of the extract powders were compared with their radical-scavenging activities (RSA) against both DPPH(center dot) and superoxide anion (O(2)(center dot-)) radicals, and their protective effect against liposome peroxidation, triggered by peroxyl radical. Lipid peroxidation was followed by the fluorescence decay of the probe, 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C(11)-BODIPY(581/591)). The TPCs of acerola, passion fruit and pineapple extract powders were (94.6 +/- 7.4); (41.2 +/- 4.2) and (9.1 +/- 1.3) mg of gallic acid equivalents g(-1) of dry extract, respectively. Acerola showed the best RSA-DPPH(center dot) scores, whereas passion fruit was more protective on the RSA-O(2)(center dot-) system. Together with the protective effects against lipid peroxidation (rate of BODIPY decay) which, were similar for acerola and passion fruit extracts, these data suggest that the methanolic extracts of acerola and passion fruit residues may be useful as antioxidant supplements, particularly the acerola extract, due to its high phenolic content. (C) 2008 Elsevier Ltd. All rights reserved