Metabolic and molecular effects of dietary extra virgin olive oil in blood and placenta of women with GDM.

Gestational diabetes mellitus (GDM) increases the risks of maternal, placental, and neonatal complications. Previously, we found that a diet enriched in extra virgin olive oil (EVOO) prevents increased maternal triglyceridemia and placental proinflammatory markers in a cohort of GDM patients. The aim of this work was to evaluate maternal circulating markers of insulin resistance, placental collagen, glycogen and lipid levels, and placental levels of proteins, mRNAs, and a microRNA involved in the endocytic pathway in the same cohort of control women and women with GDM who received or did not receive a diet enriched in EVOO (36 g/day) from weeks 24 to 28 of pregnancy until term. Results: At term, the TG/HDL cholesterol ratio, fatty acid binding protein 4 circulating levels, and maternal BMI were increased in the GDM patients, alterations prevented by the maternal diet enriched in EVOO. Although there were no changes in placental lipid levels and lipid profile, GDM placentas were thicker than controls and showed increased glycogen and collagen content, alterations prevented by the EVOO enriched diet. GDM placentas showed increases in megalin levels, in the expression of several genes involved in the endocytic pathway, and in miR-199, which targets these genes, alterations prevented by the maternal diet enriched in EVOO. Conclusions: We identified novel beneficial effects of an EVOO-enriched diet in GDM women, a diet capable of regulating maternal insulin resistance, the structure and metabolism of the placenta, and the placental endocytic pathway, suggesting effects that may be beneficial for fetal development.

Lupane Triterpenoids and New Derivatives as Antiproliferative Agents Against Prostate Cancer Cells.

BACKGROUND/AIM: This study examined the potential role of natural triterpenoids lupeol, calenduladiol and heliantriol B2, and a set of 19 derivatives, as antiproliferative and antimetastatic agents against prostate cancer cells. MATERIALS AND METHODS: Natural triterpenoids were isolated from Chuqiraga erinaceae. Analogs were obtained by transformations of lupeol and calenduladiol. The effects of compounds on PC-3 and LNCaP cells were determined using the MTT assay. Compounds with half-maximal inhibitory concentration <70 µM were evaluated as antimetastatic agents by a wound-healing assay. RESULTS: Lupeol-3ß-sulfate, a new semisynthetic lupane, was the most active compound. In general, sulfated derivatives displayed higher activity than the lead against both cell lines. A new analog, calenduladiol-3ß-monosulfate, inhibited the migration of PC-3 cells; heliantriol B2 and 3ß-aminolupane inhibited the migration of LNCaP cells in a concentration-dependent manner. CONCLUSION: Our study provides novel agents with cytotoxic effects on prostate cancer cells, which may represent a potential new therapeutic approach for prostate cancer.

Liver X receptor-α activation enhances cholesterol secretion in lactating mammary epithelium.

Liver X receptors (LXRs) are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms, LXRα and LXRß, have been well characterized in liver, adipocytes, macrophages, and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared with midpregnancy. LXRα is the primary isoform, and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced sterol regulatory element-binding protein 1c (Srebp1c) and ATP-binding cassette transporter a7 (Abca7) expression in MECs. Cumulatively, our findings identify LXRα as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.

Phytochemical Study of the Genus Salpichroa (Solanaceae), Chemotaxonomic Considerations, and Biological Evaluation in Prostate and Breast Cancer Cells.

Twelve Salpichroa taxa have been phytochemically analyzed. From the aerial parts of S. scandens, four known salpichrolides A, C, I, S, and an unreported withanolide named salpichrolide V (1), were isolated. In S. dependens, S. gayi, S. glandulosa subsp. glandulosa, S. glandulosa subps. weddellii, S. leucantha, S. micrantha, S. microloba, S. proboscidea, S. ramosissima, S. tristis var. tristis, and S. weberbauerii, no withanolides were found. The chemical content of ca. 85% of the Salpichroa taxa is in agreement with molecular studies, which suggest that Salpichroa and Jaborosa, a genus considered morphologically close to Salpichroa, are distant in the systematic of the Solanoideae subfamily. Moreover, the in vitro cytotoxic activity of a set of natural salpichrolides and derivatives was examined against two prostate carcinoma cell lines (PC3 and LNCaP) and two human breast cancer cell lines (MCF-7 and T47D). Several compounds showed moderate activity (IC50  = 64.91 - 29.97 µm).

A definitive analytical spectroscopic study of Indian yellow, an ancient pigment used for dating purposes.

The Raman spectrum of tartrazine has been mistakenly reported as being that of Indian yellow in the literature, which has serious consequences for the identification of this pigment in art works regarding their authentication. Unlike tartrazine, Indian yellow (a natural mixture of the magnesium and calcium salts of euxanthic acid) exhibits in its Raman spectrum a strong fluorescent background when visible excitation is used, however, excitation in the near infrared (1064nm) permitted the observation of the Raman bands from the raw pigment with the main features placed at 1346, 1368, 1425, 1441 and 1626cm-1. Indian yellow identification was assured by 1H and 13C Nuclear Magnetic Resonance characterization and the complete assignment of the proton and carbon resonances was accomplished using heteronuclear single quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), nuclear overhauser effect spectroscopy (NOESY) and 1H-1H correlation spectroscopy (COSY). Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and X-ray fluorescence (XRF) analyzes were also conducted on a genuine sample of this historical pigment.

Virtuous colours for Mary. Identification of lapis lazuli, smalt and cochineal in the Andean colonial image of Our Lady of Copacabana (Bolivia).

The image of Our Lady of Copacabana, a gilded polychrome sculpture carved in maguey wood in 1583, is one of the most important devotions in the Americas. In former research, we have identified the use of gypsum, Armenian bole, cerussite and atacamite in its polychromy. In this study, a red sample taken from the Virgin's tunic and a blue sample extracted from the cloak have been analysed with the aim to identify both pigments and offer insights into the painting technique. Analysis by micro-Raman spectroscopy complemented with scanning electron microscopy-energy dispersive spectroscopy and high-performance liquid chromatography allowed the identification of carmine lake in the red sample. Analysis by micro-Raman spectroscopy of the surface of the blue sample and its cross section showed the presence of smalt-the blue-glass pigment-over a cerussite layer, bathed by a very thin ultramarine layer-from a probable native origin-following a pictorial tradition that would last even until the eighteenth century. This is the first time that lapis lazuli has been scientifically identified in a Spanish American colonial painted layer.This article is part of the themed issue 'Raman spectroscopy in art and archaeology'.

Two Catechol Siderophores, Acinetobactin and Amonabactin, Are Simultaneously Produced by Aeromonas salmonicida subsp. salmonicida Sharing Part of the Biosynthetic Pathway.

The iron uptake mechanisms based on siderophore synthesis used by the fish pathogen Aeromonas salmonicida subsp. salmonicida are still not completely understood, and the precise structure of the siderophore(s) is unknown. The analysis of genome sequences revealed that this bacterium possesses two gene clusters putatively involved in the synthesis of siderophores. One cluster is a candidate to encode the synthesis of acinetobactin, the siderophore of the human pathogen Acinetobacter baumannii, while the second cluster shows high similarity to the genes encoding amonabactin synthesis in Aeromonas hydrophila. Using a combination of genomic analysis, mutagenesis, biological assays, chemical purification, and structural determination procedures, here we demonstrate that most A. salmonicida subsp. salmonicida strains produce simultaneously the two siderophores, acinetobactin and amonabactin. Interestingly, the synthesis of both siderophores relies on a single copy of the genes encoding the synthesis of the catechol moiety (2,3-dihydroxybenzoic acid) and on one encoding a phosphopantetheinyl transferase. These genes are present only in the amonabactin cluster, and a single mutation in any of them abolishes production of both siderophores. We could also demonstrate that some strains, isolated from fish raised in seawater, produce only acinetobactin since they present a deletion in the amonabactin biosynthesis gene amoG. Our study represents the first evidence of simultaneous production of acinetobactin and amonabactin by a bacterial pathogen and reveals the plasticity of bacterial genomes and biosynthetic pathways. The fact that the same siderophore is produced by unrelated pathogens highlights the importance of these systems and their interchangeability between different bacteria.

Intrauterine programming of lipid metabolic alterations in the heart of the offspring of diabetic rats is prevented by maternal diets enriched in olive oil.

SCOPE: Maternal diabetes can program metabolic and cardiovascular diseases in the offspring. The aim of this work was to address whether an olive oil supplemented diet during pregnancy can prevent lipid metabolic alterations in the heart of the offspring of mild diabetic rats. METHODS AND RESULTS: Control and diabetic Wistar rats were fed during pregnancy with either a standard diet or a 6% olive oil supplemented diet. The heart of adult offspring from diabetic rats showed increases in lipid concentrations (triglycerides in males and phospholipids, cholesterol, and free fatty acids in females), which were prevented with the maternal diets enriched in olive oil. Maternal olive oil supplementation increased the content of unsaturated fatty acids in the hearts of both female and male offspring from diabetic rats (possibly due to a reduction in lipoperoxidation), increased the expression of Δ6 desaturase in the heart of male offspring from diabetic rats, and increased the expression of peroxisome proliferator activated receptor α in the hearts of both female and male offspring from diabetic rats. CONCLUSION: Relevant alterations in cardiac lipid metabolism were evident in the adult offspring of a mild diabetic rat model, and regulated by maternal diets enriched in olive oil.

Synthesis and cytotoxic evaluation of four new 6E-hydroximinosteroids.

Four new 6E-hydroximinosteroids (1, 2a, 3 and 4) have been synthesized from the corresponding ketones, 2ß,3ß-dihydroxy-5α-cholestan-6-one (5), 2α,3α-dihydroxy-5α-cholestan-6-one (6), 2ß,3α-dihydroxy-5α-cholestan-6-one (7) and 2ß,3α-dihydroxy-5α-cholestan-6-one-disulfate (8). The cytotoxic activity of the steroidal oximes was evaluated against two prostate carcinoma cell lines (PC-3 and LNCaP) and compared with that of five polyhydroxylated sulfated analogs (8-12). Oxime 3 and trisulfated analog 11 were the most active compounds with IC50 values of 10.8µM (PC-3) and 7.9µM (LNCaP), respectively.

Pseudocnoside A, a new cytotoxic and antiproliferative triterpene glycoside from the sea cucumber Pseudocnus dubiosus leoninus.

A new triterpene glycoside, pseudocnoside A (1), was isolated from the sea cucumber Pseudocnus dubiosus leoninus. The structure of the new compound was established on the basis of extensive NMR spectroscopic analysis ((1)H and (13)C NMR, (1)H,(1)H-COSY, HMBC, HSQC, TOCSY and NOESY), HR-ESI-MS data and chemical transformations. In addition, the cytotoxicity and antiproliferative activities of 1 and structurally related triterpene glycosides isolated from the sea cucumbers Psolus patagonicus and Hemioedema spectabilis were evaluated against cancer cell lines A-549 and HeLa.

Fatty acid composition of the edible sea cucumber Athyonidium chilensis.

The edible sea cucumber Athyonidium chilensis is a fishery resource of high commercial value in Chile, but no information on its lipid and fatty acid composition has been previously reported. Phospholipids were the major lipid contents of the ethanolic extracts of tubules, internal organs and body wall of A. chilensis. Saturated fatty acids predominated in tubule phospholipids (40.69%), while in internal organs and body wall phospholipids, the monounsaturated fatty acids were in higher amounts (41.99% and 37.94%, respectively). The main polyunsaturated fatty acids in phospholipids were C20 : 2ω-6, arachidonic (C20 : 4ω-6) and eicosapentaenoic (C20 : 5ω-3) acids. These results demonstrate for the first time that A. chilensis is a valuable food for human consumption in terms of fatty acids.

Patagonicosides B and C, two antifungal sulfated triterpene glycosides from the sea cucumber Psolus patagonicus.

Two new triterpene glycosides, patagonicosides B and C (2 and 3, resp.), together with the known patagonicoside A (1), have been isolated from the EtOH extract of the sea cucumber Psolus patagonicus. The structures of the new compounds were established on the basis of extensive NMR spectroscopic analysis ((1)H- and (13)C-NMR, (1)H,(1)H-COSY, HMBC, HSQC, TOCSY, and NOESY), HR-ESI-MS data, and chemical transformations. Compounds 1-3 and their desulfated analogs showed antifungal activities against the phytopathogenic fungus Cladosporium cladosporoides in a dose-dependent fashion.

Antiproliferative, cytotoxic and hemolytic activities of a triterpene glycoside from Psolus patagonicus and its desulfated analog.

BACKGROUND: The major triterpene glycoside of the sea cucumber Psolus patagonicus and its desulfated analog were tested for their antiproliferative, cytotoxic and hemolytic activities, and their effect on NF-kappaB activation. METHODS: The antiproliferative action of glycosides 1 and 2 were determined on 3 tumor cell lines. Their effect on the activation of NF-kappaB was evaluated by indirect immunofluorescence assay staining and the concomitant IkappaBalpha degradation was studied by Western blot. RESULTS: Both compounds were able to suppress the growth of 3 tumor cell lines (Hep3B, MDA-MB231 and A549) and induced the activation of NF-kappaB, a key player linking chronic inflammation and cancer, concomitant with IkappaBalpha degradation in the A549 tumor cell line. Compounds 1 and 2 showed hemolytic activity with half maximal inhibitory concentration (IC(50)) values around 80 microM. CONCLUSIONS: Both glycosides showed low cytotoxic activity in A549 tumor cells in comparison with sea cucumber triterpene glycosides containing a linear tetrasaccharide chain. This could be a result of the uncommon presence of two 12alpha- and 17alpha-hydroxyl groups and a Delta(7) double bond in the aglycone moiety. This aglycone functionalization may be related to their low membranolytic activity. Although glycosides 1 and 2 exert an antiproliferative effect, their mechanisms of action do not involve inhibition of NF-kappaB. Recently, it has been shown that diverse and new mechanisms of action are responsible for the antitumor and cytotoxic activities of marine compounds. Therefore, more extensive studies are needed to establish a mechanism of action and to deduce a clear structure-activity relationship of sea cucumber triterpene glycosides.